Michael Forsting

<b><i>Background:</i></b> Intracranial aneurysm with and without subarachnoid haemorrhage (SAH) is a relevant health problem: The overall incidence is about 9 per 100,000 with a wide range, in some countries up to 20 per 100,000. Mortality rate with conservative treatment within the first months is 50–60%. About one third of patients left with an untreated aneurysm will die from recurrent bleeding within 6 months after recovering from the first bleeding. The prognosis is further influenced by vasospasm, hydrocephalus, delayed ischaemic deficit and other complications. The aim of these guidelines is to provide comprehensive recommendations on the management of SAH with and without aneurysm as well as on unruptured intracranial aneurysm. <b><i>Methods:</i></b> We performed an extensive literature search from 1960 to 2011 using Medline and Embase. Members of the writing group met in person and by teleconferences to discuss recommendations. Search results were graded according to the criteria of the European Federation of Neurological Societies. Members of the Guidelines Committee of the European Stroke Organization reviewed the guidelines. <b><i>Results:</i></b> These guidelines provide evidence-based information on epidemiology, risk factors and prognosis of SAH and recommendations on diagnostic and therapeutic methods of both ruptured and unruptured intracranial aneurysms. Several risk factors of aneurysm growth and rupture have been identified. We provide recommendations on diagnostic work up, monitoring and general management (blood pressure, blood glucose, temperature, thromboprophylaxis, antiepileptic treatment, use of steroids). Specific therapeutic interventions consider timing of procedures, clipping and coiling. Complications such as hydrocephalus, vasospasm and delayed ischaemic deficit were covered. We also thought to add recommendations on SAH without aneurysm and on unruptured aneurysms. <b><i>Conclusion:</i></b> Ruptured intracranial aneurysm with a high rate of subsequent complications is a serious disease needing prompt treatment in centres having high quality of experience of treatment for these patients. These guidelines provide practical, evidence-based advice for the management of patients with intracranial aneurysm with or without rupture. Applying these measures can improve the prognosis of SAH.

Intracerebral hemorrhage (ICH) accounted for 9% to 27% of all strokes worldwide in the last decade, with high early case fatality and poor functional outcome. In view of recent randomized controlled trials (RCTs) of the management of ICH, the European Stroke Organisation (ESO) has updated its evidence-based guidelines for the management of ICH.A multidisciplinary writing committee of 24 researchers from 11 European countries identified 20 questions relating to ICH management and created recommendations based on the evidence in RCTs using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.We found moderate- to high-quality evidence to support strong recommendations for managing patients with acute ICH on an acute stroke unit, avoiding hemostatic therapy for acute ICH not associated with antithrombotic drug use, avoiding graduated compression stockings, using intermittent pneumatic compression in immobile patients, and using blood pressure lowering for secondary prevention. We found moderate-quality evidence to support weak recommendations for intensive lowering of systolic blood pressure to <140 mmHg within six-hours of ICH onset, early surgery for patients with a Glasgow Coma Scale score 9-12, and avoidance of corticosteroids.These guidelines inform the management of ICH based on evidence for the effects of treatments in RCTs. Outcome after ICH remains poor, prioritizing further RCTs of interventions to improve outcome.

The risk of stroke after transfemoral aortic valve implantation (TAVI) due to dislodgement and subsequent embolization of debris from aortic arch atheroma or from the calcified valve itself ranges between 2% and 10%. The rate of clinically silent cerebral ischemia is unknown but may be even higher.Thirty-two patients who underwent TAVI with the use of a balloon-expandable (n=22) or self-expandable (n=10) stent valve prosthesis were included in this descriptive study and compared with a historical control group of 21 patients undergoing open surgical aortic valve replacement. Periprocedural apparent and silent cerebral ischemia was assessed by neurological testing and serial cerebral diffusion-weighted magnetic resonance imaging at baseline, at 3.4 (2.5 to 4.4) days after the procedure, and at 3 months. TAVI was successful in all patients. After the procedure, new foci of restricted diffusion on cerebral diffusion-weighted magnetic resonance imaging were found in 27 of 32 TAVI patients (84%) and were more frequent than after open surgery (10 of 21 patients [48%]; P=0.011). These lesions were usually multiple (1 to 19 per patient) and dispersed in both hemispheres in a pattern suggesting cerebral embolization. Volumes of these lesions were significantly smaller after TAVI than after surgery (77 [59 to 94] versus 224 [111 to 338] mm(3); P<0.001). There were neither measurable impairments of neurocognitive function nor apparent neurological events during the in-hospital period among TAVI patients, but there was 1 stroke (5%) in the surgical patient group. On 3-month follow-up diffusion-weighted magnetic resonance imaging, there were no new foci of restricted diffusion, and there was no residual signal change associated with the majority (80%) of the foci detected in the periprocedural period.Clinically silent new foci of restricted diffusion on cerebral magnetic resonance imaging were detected in almost all patients (84%) undergoing TAVI. Although typically multiple, these foci were not associated with apparent neurological events or measurable deterioration of neurocognitive function during 3-month follow-up. Further work needs to be directed to determine the clinical significance of these findings in a larger patient population.

This article represents the recommendations for the management of spontaneous intracerebral haemorrhage of the European Stroke Initiative (EUSI). These recommendations are endorsed by the 3 European societies which are represented in the EUSI: the European Stroke Council, the European Neurological Society and the European Federation of Neurological Societies.

The purpose of this study was to assess the safety and performance of the Wingspan stent system and Gateway percutaneous transluminal angioplasty balloon catheter in the treatment of high-grade, intracranial atherosclerotic lesions in patients who had failed medical therapy.In this prospective, multicenter, single-arm study, medically refractory patients with a modified Rankin score < or =3 and recurrent symptoms attributable to angiographically demonstrated intracranial stenosis > or =50% in a vessel 2.5 to 4.5 mm in diameter were enrolled. Intracranial lesions were predilated with an undersized Gateway balloon catheter to 80% of the native vessel diameter, followed by deployment of the self-expanding Wingspan stent to facilitate further remodeling of the atherosclerotic plaque and to maintain vessel patency. Neurologic examinations and angiograms were performed at 6 months after the procedure.Among the 45 patients enrolled, the degree of stenosis was reduced from a baseline of 74.9+/-9.8% to 31.9+/-13.6% after stenting and 28+/-23.2% at the 6-month follow-up. The 30-day composite ipsilateral stroke/death rate was 4.5% (2/44); at the 6-month follow-up, the ipsilateral stroke/death rate was 7.0%, the rate for all strokes was 9.7%, and all-cause mortality was 2.3%. Physician-reported follow-up in 43 patients (average of 13 months) conducted outside the study protocol (not adjudicated by the clinical event committee) reported 1 additional ipsilateral stroke.In medically refractory patients with high-grade intracranial atherosclerotic stenoses, a new treatment paradigm involving predilation with an undersized Gateway percutaneous transluminal angioplasty balloon catheter and placement of a self-expanding Wingspan stent system appears to be safe, may facilitate remodeling, and may contribute to favorable angiographic outcomes.

Nusinersen is approved for the treatment of 5q spinal muscular atrophy of all types and stages in patients of all ages. Although clinical trials have shown improvements in motor function in infants and children treated with the drug, data for adults are scarce. We aimed to assess the safety and efficacy of nusinersen in adults with 5q spinal muscular atrophy.We did an observational cohort study at ten academic clinical sites in Germany. Patients with genetically confirmed 5q spinal muscular atrophy (age 16-65 years) with a homozygous deletion of exons 7, 8, or both, or with compound heterozygous mutations were eligible for inclusion and received nusinersen treatment in accordance with the label for a minimum treatment time of 6 months to a follow-up of up to 14 months. The primary outcome was the change in the total Hammersmith Functional Motor Scale Expanded (HFMSE) score, assessed at months 6, 10, and 14, and based on pre-post comparisons. This study is registered with the German Clinical Trials Register (number DRKS00015702).Between July 13, 2017, and May 1, 2019, 173 patients were screened, of whom 139 (80%) were eligible for data analysis. Of these, 124 (89%) were included in the 6-month analysis, 92 (66%) in the 10-month analysis, and 57 (41%) in the 14-month analysis; patients with missing baseline HFMSE scores were excluded from these analyses. Mean HFMSE scores were significantly increased compared with baseline at 6 months (mean difference 1·73 [95% CI 1·05-2·41], p<0·0001), 10 months (2·58 [1·76-3·39], p<0·0001), and 14 months (3·12 [2·06-4·19], p<0·0001). Clinically meaningful improvements (≥3 points increase) in HFMSE scores were seen in 35 (28%) of 124 patients at 6 months, 33 (35%) of 92 at 10 months, and 23 (40%) of 57 at 14 months. To 14-month follow-up, the most frequent adverse effects among 173 patients were headache (61 [35%] patients), back pain (38 [22%]), and nausea (19 [11%]). No serious adverse events were reported.Despite the limitations of the observational study design and a slow functional decline throughout the natural disease course, our data provide evidence for the safety and efficacy of nusinersen in the treatment of adults with 5q spinal muscular atrophy, with clinically meaningful improvements in motor function in a real-world cohort.None.

Computed tomography (CT) studies are requested by specialists from most medical disciplines and play a vital role in the diagnosis and treatment of patients. It follows that physicians of all specialties should possess basic knowledge of computed tomography, its proper use, and the radiation exposure associated with it.This review is based on publications retrieved by a selective search of the literature.Approximately 12 million CT studies are carried out in Germany each year, and the trend is rising. Approximately 9% of all diagnostic studies involving ionizing radiation are CT studies. On average, more than 60% of the collective effective dose due to medical radiation exposure is attributable to CT. There are two types of radiation effects caused by ionizing radiation: sto - chastic and deterministic. The additional, individual relative lifetime cancer mortality risk due to ionizing radiation with wholebody exposure at a low single dose is estimated at 5% per sievert. Radiation exposure from CT studies of the head and trunk, e.g. of a patient with polytrauma, corresponds to an additional lifetime cancer mortality risk of approximately 0.1% at an effective dose of approximately 20 millisievert.The radiation exposure due to CT, and the risks to which patients are subjected by it, have become more important with greater use of CT. Technical advances, targeted dose monitoring, and analyses of dose data can help identify areas where improvement is necessary, in furtherance of the overriding goal of lowering patients' radiation exposure while preserving adequate image quality.

PURPOSE To investigate the incidence and prognostic value of local brain swelling, the extent of parenchymal hypodensity, and the hyperdense middle cerebral artery sign as shown by CT within the first 5 hours after the onset of symptoms in patients with angiographically proved middle cerebral artery trunk occlusions. METHODS Fifty-three patients were studied prospectively with CT 46 to 292 minutes (median, 120; mean, 134 +/- 59) after symptom onset and scored clinically at admission and 4 weeks later. All patients were treated with recombinant tissue plasminogen activator (30 to 100 mg). RESULTS Early CT showed parenchymal hypodensity in 43 patients (81%), local brain swelling in 20 patients (38%), and hyperdensity of the middle cerebral artery trunk in 25 patients (47%). Hypodensity covering more than 50% of the middle cerebral artery territory had an 85%, local brain swelling a 70%, and the hyperdense middle cerebral artery sign a 32% positive predictive value for fatal clinical outcome. Specificity of these findings for fatal outcome was 94%, 83%, and 51%, respectively, and sensitivity was 61%, 78% and 44%, respectively. CONCLUSIONS Early CT in acute middle cerebral artery trunk occlusion is highly predictive for fatal clinical outcome if there is extended hypodensity or local brain swelling despite aggressive therapeutic attempts such as thrombolysis or decompressive surgery.

<h3>Objective</h3> To address the role of anxiety and depression symptoms in altered pain processing in irritable bowel syndrome (IBS). <h3>Design</h3> In this functional magnetic resonance imaging study, the blood oxygen level-dependent (BOLD) response to rectal distensions delivered at previously determined individual discomfort thresholds was assessed. <h3>Patients</h3> 15 female patients with irritable bowel syndrome (IBS) and with normal rectal pain thresholds, and 12 healthy women. <h3>Measures</h3> The correlation of anxiety and depression symptoms, measured with the Hospital Anxiety and Depression Scale (HADS), with subjective pain ratings and the BOLD response during distension-induced brain activation were analysed within IBS. Group differences in pain-induced brain activation with and without controlling for HADS scores were evaluated. <h3>Results</h3> Patients with IBS experienced significantly more pain and discomfort upon rectal distensions in the scanner, despite unaltered rectal sensory thresholds. Anxiety and depression scores were associated with these subjective stimulus ratings, but not with rectal sensory thresholds. Anxiety symptoms in IBS were significantly associated with pain-induced activation of the anterior midcingulate cortex and pregenual anterior cingulate cortex. Depression scores correlated with activation of the prefrontal cortex (PFC) and cerebellar areas within IBS. Group comparisons with the two-sample t test revealed significant activation in the IBS versus controls contrast in the anterior insular cortex and PFC. Inclusion of anxiety and depression scores, respectively, as confounding variables led to a loss of significant group differences. <h3>Conclusions</h3> Altered central processing of visceral stimuli in IBS is at least in part mediated by symptoms of anxiety and depression, which may modulate the affective–motivational aspects of the pain response.

To investigate the role of a patient foramen ovale in the pathogenesis of multiple brain lesions acquired by sport divers in the absence of reported decompression symptoms.Prospective double blind cohort study.Diving clubs around Heidelberg and departments of neuroradiology and neurology.87 sport divers with a minimum of 160 scuba dives (dives with self contained underwater breathing apparatus).Presence of multiple brain lesions visualised by cranial magnetic resonance imaging and presence and size of patent foramen ovale as documented by echocontrast transcranial Doppler ultrasonography.25 subjects were found to have a right-to-left shunt, 13 with a patent foramen ovale of high haemodynamic relevance. A total of 41 brain lesions were detected in 11 divers. There were seven brain lesions in seven divers without a right-to-left shunt and 34 lesions in four divers with a right-to-left shunt. Multiple brain lesions occurred exclusively in three divers with a large patent foramen ovale (P = 0.004).Multiple brain lesions in sport divers were associated with presence of a large patent foramen ovale. This association suggests paradoxical gas embolism as the pathological mechanism. A patent foramen ovale of high haemodynamic relevance seems to be an important risk factor for developing multiple brain lesions in sport divers.

The introduction of flow diverters (FDs) has expanded the possibilities for reconstructive treatment of difficult intracranial aneurysms. Concern remains as to the long-term patency of the perforating arteries and side branches covered during stent placement. Our purpose was to evaluate the performance of and early effect on covered branches after implantation of the Silk FD in the treatment of basilar artery aneurysms.Twelve patients with an aneurysm of the basilar artery that was treated by implantation of the Silk FD were included in our retrospective study. Both unruptured and previously ruptured, formerly untreated, and recurrent aneurysms were treated. During follow-up, patients were monitored for clinical evolution, patency of the covered vessels, and aneurysmal obliteration.Of the 2 ruptured aneurysms, 1 was initially treated by FD implantation. The FD covered the basilar bifurcation and the origin of a P1 segment of the posterior cerebral artery in 9 cases, the origin of the superior cerebellar artery in 9, and of the anterior inferior cerebellar artery in 3. There was 1 acute basilar artery occlusion a few hours after FD implantation. During a mean follow-up of 16 weeks, 3 patients experienced a symptomatic neurologic event.Implantation of the Silk FD in the basilar artery was feasible and well tolerated in most cases to date. However, late ischemic events affecting perforating arteries may occur after FD implantation, suggesting that the indication should be restricted to otherwise untreatable aneurysms in this location.

Abstract The objective of our study was to determine the frequency of EGF‐receptor‐gene rearrangement in relation to tumour‐growth behaviour in an unselected group of glioma patients. We investigated 73 glial tumours with different grades of malignancy (17 low‐grade gliomas, 14 anaplastic variants, and 42 GBM) by Southern analysis, reverse transcriptase PCR (RT‐PCR) amplification of mRNA, and Western analysis. An amplification of the EGF‐receptor gene was present in 19/42 GBM but in only I anaplastic astrocytoma. By RT‐PCR, 4/19 GBM with gene amplification showed a specific amino‐terminal aberrant splice mutation of 801 bp in addition to undeleted mRNA. By Western analysis, 27/42 GBM showed expression of the EGF‐receptor protein. Protein levels, however, varied among individual tumours. Four GBM containing an aberrant splice mutation exhibited an immunoreactive protein of 130 kDa MW in addition to the normal EGF‐receptor protein p170. All GBM patients underwent surgery followed by a standard course of radiotherapy. Neuroradiological follow‐up in 31/42 GBM patients consisted of bimonthly MRJ examinations. There was a statistically significant difference in the mean latency period until tumour regrowth of patients suffering from GBM with and without EGF‐receptor‐gene amplification (9 weeks vs. 32 weeks). Our data indicate more rapid tumour regrowth kinetics of GBM with amplified EGF receptor genes in vivo . © 1994 Wiley‐Liss, Inc.

Higher magnetic field strengths and continuous improvement of high-resolution imaging in multiple sclerosis (MS) are expected to provide unique in-vivo and non-invasive insights in pathogenesis and clinical monitoring. The purpose of this study was to investigate the potential of high-resolution imaging of MS lesions in vivo comparing 7T with conventional 1.5T.Twelve consecutive patients with clinically definite MS were scanned on a 7T whole-body scanner and on a 1.5T Avanto. The 1.5T and 7T imaging protocol consisted of high-resolution axial proton density (PD) + T2-weighted turbo spin-echo and T2*-weighted gradient-echo (GRE), and sagittal T1-weighted 3D magnetization-prepared rapid acquisition of gradient echo.The sequence parameters at 7T had to be modified because of specific absorption rate (SAR) restrictions while keeping contrast parameters equivalent to 1.5T. White matter lesions were better detected and delineated from adjacent structures at 7T compared with 1.5T. There were 42% of the patients who showed additional lesions at 7T: there were 97 white matter lesions detected on 1.5T versus 126 lesions at 7T, an increase of 23%. The perivascular migration of MS lesions was well visualized on T2*-weighted GRE sequences. In larger lesions (10 mm), a multilayer structure was revealed on T2*-weighted GRE not seen at 1.5T. Because of the higher resolution, it was possible to differentiate between juxtacortical white matter lesions and cortical lesions. There were 44% of the subcortical lesions depicted at 7T that showed cortical involvement.Ultra-high-field imaging of patients with MS at 7T was well tolerated and provided better visualization of MS lesions in the gray matter and demonstrated structural abnormalities within the MS lesions themselves more effectively.

Acute ischemia in the complete territory of the carotid artery may lead to massive cerebral edema with raised intracranial pressure and progression to coma and death due to uncal, cingulate, or tonsillar herniation. Although clinical data suggest that patients benefit from undergoing decompressive surgery for acute ischemia, little data about the effect of this procedure on experimental ischemia are available. In this article the authors present results of an experimental study on the effects of decompressive craniectomy performed at various time points after endovascular middle cerebral artery (MCA) occlusion in rats. Focal cerebral ischemia was induced in 68 rats using an endovascular occlusion technique focused on the MCA. Decompressive craniectomy was performed in 48 animals (in groups of 12 rats each) 4, 12, 24, or 36 hours after vessel occlusion. Twenty animals (control group) were not treated by decompressive craniectomy. The authors used the infarct volume and neurological performance at Day 7 as study endpoints. Although the mortality rate in the untreated group was 35%, none of the animals treated by decompressive craniectomy died (mortality 0%). Neurological behavior was significantly better in all animals treated by decompressive craniectomy, regardless of whether they were treated early or late. Neurological behavior and infarction size were significantly better in animals treated very early by decompressive craniectomy (4 hours) after endovascular MCA occlusion (p < 0.01); surgery performed at later time points did not significantly reduce infarction size. The results suggest that use of decompressive craniectomy in treating cerebral ischemia reduces mortality and significantly improves outcome. If performed early after vessel occlusion, it also significantly reduces infarction size. By performing decompressive craniectomy neurosurgeons will play a major role in the management of stroke patients.

In patients with irritable bowel syndrome (IBS), pain amplification and hypervigilance might result from altered affective-motivational modulation of the pain response. We investigated the effects of emotional context on the behavioral and neural response to visceral stimuli in IBS patients.We used functional magnetic resonance imaging (fMRI) to assess the blood oxygen level-dependent response to nonpainful and painful rectal distensions in 15 female IBS patients and 12 healthy women. Distensions were delivered during psychologic stress or relaxation; data were compared with those in a neutral condition (control). Group and context-dependent differences in the processing of visceral stimulation were assessed at behavioral and the neuronal levels. Secondary analyses of group differences were performed using anxiety scores as a covariate because of higher anxiety symptoms among patients with IBS.During rectal stimulation, IBS patients demonstrated more pronounced stress-induced modulation of neural activation in multiple brain regions, including the insula, midcingulate cortex, and ventrolateral prefrontal cortex. In response to relaxation, IBS patients demonstrated reduced modulation of distension-induced activation in the insula. During relaxation, the difference observed between groups could be accounted for by higher anxiety symptoms in patients with IBS; differential effects of stress in the insula and prefrontal regions were not attributable to anxiety.IBS patients appear to have disrupted emotional modulation of neural responses to visceral stimuli, possibly reflecting the neural basis for altered visceral interoception by stress and negative emotions.

Background and Purpose We sought to determine whether early (&lt;8 hours) or delayed (8 to 24 hours) recanalization after stroke may be an independent variable in the improvement of clinical outcome in patients with occlusion of the middle cerebral artery. Methods We prospectively studied 77 patients by combined Scandinavian Stroke Scale score at admission, repeated computed tomography and angiography before and after thrombolytic treatment at &lt;8 hours after stroke onset, and transcranial Doppler ultrasound 24 hours later. We tested an association between clinical and neuroradiological baseline characteristics, recanalization, and outcome as assessed by the modified Rankin Scale 4 weeks after stroke and determined the effect of recanalization on mortality and good outcome (Rankin Scale grades 0 to 3) by multiple logistic regression analyses. Results Recanalization rates at 8 and 24 hours after stroke correlated with sites of occlusion (middle cerebral artery branch, 73% and 73%; trunk, 27% and 38%, respectively; intracranial internal carotid artery bifurcation, 14% and 14%; P =.002), collaterals (good, 43% and 51%, respectively; scarce, 17% and 19%, respectively; P =.01), and Scandinavian Stroke Scale score at admission ( P =.002). Six of 7 patients with delayed recanalization had good outcomes. Recanalization at &lt;8 hours after symptom onset had no independent predictive value for good outcome ( P =.69). Recanalization at 24 hours increased the proportion of good outcomes from 23% to 75% in a subgroup of patients. Recanalization did not independently affect mortality ( P &gt;.15). Conclusions Even if delayed, arterial recanalization may improve clinical outcome in a subgroup of patients with middle cerebral artery occlusion.

Even though previous neuropsychological studies and clinical case reports have suggested an association between pedophilia and frontocortical dysfunction, our knowledge about the neurobiological mechanisms underlying pedophilia is still fragmentary. Specifically, the brain morphology of such disorders has not yet been investigated using MR imaging techniques. Whole brain structural T1-weighted MR images from 18 pedophile patients (9 attracted to males, 9 attracted to females) and 24 healthy age-matched control subjects (12 hetero- and 12 homosexual) from a comparable socioeconomic stratum were processed by using optimized automated voxel-based morphometry within multiple linear regression analyses. Compared to the homosexual and heterosexual control subjects, pedophiles showed decreased gray matter volume in the ventral striatum (also extending into the nucl. accumbens), the orbitofrontal cortex and the cerebellum. These observations further indicate an association between frontostriatal morphometric abnormalities and pedophilia. In this respect these findings may support the hypothesis that there is a shared etiopathological mechanism in all obsessive–compulsive spectrum disorders.

To detail the rationale, design, and future perspective of implementing whole-body magnetic resonance (MR) imaging in the German National Cohort, a large multicentric population-based study.All institutional review boards approved the study, and informed consent is obtained before study enrollment. Participants are enrolled from a random sample of the general population at five dedicated imaging sites among 18 recruitment centers. MR imaging facilities are equipped with identical 3.0-T imager technology and use uniform MR protocols. Imager-specific hardware and software settings remained constant over the study period. On-site and centralized measures of image quality enable monitoring of completeness of the acquisitions and quality of each of the MR sequences. Certified radiologists read all MR imaging studies for presence of incidental findings according to predefined algorithms.Over a 4-year period, six participants per day are examined at each center, totaling a final imaging cohort of approximately 30 000 participants. The MR imaging protocol is identical for each site and comprises a set of 12 native series to cover neurologic, cardiovascular, thoracoabdominal, and musculoskeletal imaging phenotypes totaling approximately 1 hour of imaging time. A dedicated analysis platform as part of a central imaging core incorporates a thin client-based integrative and modular data handling platform to enable multicentric off-site image reading for incidental findings. Scientific analysis will be pursued on a per-project hypothesis-driven basis.Population-based whole-body MR imaging as part of the German National Cohort will serve to compile a comprehensive image repository, will provide insight into physiologic variants and subclinical disease burden, and has the potential to enable identification of novel imaging biomarkers of risk.

To assess the feasibility of hybrid imaging of the heart with fluorine 18 fluorodeoxyglucose (FDG) on an integrated 3-T positron emission tomography (PET)/magnetic resonance (MR) imaging system.The present study was approved by the local institutional review board. Written informed consent was obtained from all patients before imaging. Twenty consecutive patients with myocardial infarction (n = 20) underwent cardiac PET/MR imaging examination. Ten patients underwent additional cardiac PET/computed tomography (CT) before PET/MR. Two-dimensional half-Fourier acquisition single-shot turbo spin-echo sequences, balanced steady-state free precession cine sequences, two-dimensional turbo inversion-recovery magnitude T2-weighted sequences, and late gadolinium-enhanced (LGE) segmented two-dimensional inversion-recovery turbo fast low-angle shot sequences were performed. According to the 17-segment model, PET tracer uptake, wall motion, and late gadolinium enhancement were visually assessed for each segment on a binary scale, and categorical intermethod agreement was calculated by using the Cohen κ. The maximum standardized uptake value was measured in corresponding myocardial locations on PET/CT and PET/MR images.Agreement was substantial over all patients and segments between PET and LGE images (κ = 0.76) and between PET and cine images (κ = 0.78). In 306 segments, 97 (32%) were rated as infarcted on PET images, compared with 93 (30%) rated as infarcted on LGE images and with 90 (29%) rated as infarcted on cine images. In a subgroup of patients (n = 10) with an additional PET/CT scan, no significant difference in myocardial tracer uptake between PET/CT and PET/MR images was found (paired t test, P = .95).Cardiac PET/MR imaging with FDG is feasible and may add complementary information in patients with ischemic heart disease.

Studies aimed at identifying structural brain alterations associated with persistent violent behavior or psychopathy have not adequately accounted for a lifetime history of substance misuse. Thus, alterations in gray matter (GM) volume that have been reported to be correlates of violent behavior and/or psychopathy may instead be related to lifelong substance use disorders (SUDs).To identify alterations in GM volume associated with violent behavior and those associated with lifelong SUDs.Cross-sectional study.Participants were recruited from penitentiaries, forensic hospitals, psychiatric outpatient services, and communities in Germany. Structural magnetic resonance imaging was performed at a university hospital.Four groups of men were compared: 12 men with SUDs who exhibited violent behavior (hereafter referred to as violent offenders), 12 violent offenders without SUDs, 13 men with SUDs who did not exhibit violent behavior (hereafter referred to as nonoffenders), and 14 nonoffenders without SUDs.Voxel-based morphometry was used to analyze high-resolution magnetic resonance imaging scans. Assessments of mental disorders, psychopathy (using the Psychopathy Checklist-Screening Version), aggressive behavior, and impulsivity were conducted by trained clinicians.Compared with nonoffenders, violent offenders presented with a larger GM volume in the amygdala bilaterally, the left nucleus accumbens, and the right caudate head and with less GM volume in the left insula. Men with SUDs exhibited a smaller GM volume in the orbitofrontal cortex, ventromedial prefrontal cortex, and premotor cortex than did men without SUDs. Regression analyses indicated that the alterations in GM volume that distinguished the violent offenders from nonoffenders were associated with psychopathy scores and scores for lifelong aggressive behavior. The GM volumes of the orbitofrontal cortex and prefrontal cortex that distinguished the men with SUDs from the men without SUDs were correlated with scores for response inhibition.These findings suggest that a greater GM volume in the mesolimbic reward system may be associated with violent behavior and that reduced GM volumes in the prefrontal cortex, orbitofrontal cortex, and premotor area characterize men with SUDs.

Objectives Gadolinium-based contrast agents (GBCAs) have become an integral part in daily clinical decision making in the last 3 decades. However, there is a broad consensus that GBCAs should be exclusively used if no contrast-free magnetic resonance imaging (MRI) technique is available to reduce the amount of applied GBCAs in patients. In the current study, we investigate the possibility of predicting contrast enhancement from noncontrast multiparametric brain MRI scans using a deep-learning (DL) architecture. Materials and Methods A Bayesian DL architecture for the prediction of virtual contrast enhancement was developed using 10-channel multiparametric MRI data acquired before GBCA application. The model was quantitatively and qualitatively evaluated on 116 data sets from glioma patients and healthy subjects by comparing the virtual contrast enhancement maps to the ground truth contrast-enhanced T1-weighted imaging. Subjects were split in 3 different groups: enhancing tumors (n = 47), nonenhancing tumors (n = 39), and patients without pathologic changes (n = 30). The tumor regions were segmented for a detailed analysis of subregions. The influence of the different MRI sequences was determined. Results Quantitative results of the virtual contrast enhancement yielded a sensitivity of 91.8% and a specificity of 91.2%. T2-weighted imaging, followed by diffusion-weighted imaging, was the most influential sequence for the prediction of virtual contrast enhancement. Analysis of the whole brain showed a mean area under the curve of 0.969 ± 0.019, a peak signal-to-noise ratio of 22.967 ± 1.162 dB, and a structural similarity index of 0.872 ± 0.031. Enhancing and nonenhancing tumor subregions performed worse (except for the peak signal-to-noise ratio of the nonenhancing tumors). The qualitative evaluation by 2 raters using a 4-point Likert scale showed good to excellent (3–4) results for 91.5% of the enhancing and 92.3% of the nonenhancing gliomas. However, despite the good scores and ratings, there were visual deviations between the virtual contrast maps and the ground truth, including a more blurry, less nodular-like ring enhancement, few low-contrast false-positive enhancements of nonenhancing gliomas, and a tendency to omit smaller vessels. These “features” were also exploited by 2 trained radiologists when performing a Turing test, allowing them to discriminate between real and virtual contrast-enhanced images in 80% and 90% of the cases, respectively. Conclusions The introduced model for virtual gadolinium enhancement demonstrates a very good quantitative and qualitative performance. Future systematic studies in larger patient collectives with varying neurological disorders need to evaluate if the introduced virtual contrast enhancement might reduce GBCA exposure in clinical practice.

Altered pain anticipation likely contributes to disturbed central pain processing in chronic pain conditions like irritable bowel syndrome (IBS), but the learning processes shaping the expectation of pain remain poorly understood. We assessed the neural circuitry mediating the formation, extinction, and reactivation of abdominal pain-related memories in IBS patients compared to healthy controls (HC) in a differential fear conditioning paradigm.During fear acquisition, predictive visual cues (CS(+)) were paired with rectal distensions (US), while control cues (CS(-)) were presented unpaired. During extinction, only CSs were presented. Subsequently, memory reactivation was assessed with a reinstatement procedure involving unexpected USs. Using functional magnetic resonance imaging, group differences in neural activation to CS(+) vs CS(-) were analyzed, along with skin conductance responses (SCR), CS valence, CS-US contingency, state anxiety, salivary cortisol, and alpha-amylase activity. The contribution of anxiety symptoms was addressed in covariance analyses.Fear acquisition was altered in IBS, as indicated by more accurate contingency awareness, greater CS-related valence change, and enhanced CS(+)-induced differential activation of prefrontal cortex and amygdala. IBS patients further revealed enhanced differential cingulate activation during extinction and greater differential hippocampal activation during reinstatement. Anxiety affected neural responses during memory formation and reinstatement.Abdominal pain-related fear learning and memory processes are altered in IBS, mediated by amygdala, cingulate cortex, prefrontal areas, and hippocampus. Enhanced reinstatement may contribute to hypervigilance and central pain amplification, especially in anxious patients. Preventing a 'relapse' of learned fear utilizing extinction-based interventions may be a promising treatment goal in IBS.

Background The “glymphatic system” (GS), a brain-wide network of cerebrospinal fluid microcirculation, supplies a pathway through and out of the central nervous system (CNS); malfunction of the system is implicated in a variety of neurological disorders. In this exploratory study, we analyzed the potential of a new imaging approach that we coined delayed T2-weighted gadolinium-enhanced imaging to visualize the GS in vivo. Methods Heavily T2-weighted fluid-attenuated inversion recovery (hT2w-FLAIR) magnetic resonance imaging was obtained before, and 3 hours and 24 hours after intravenous gadolinium-based contrast agent (GBCA) application in 33 neurologically healthy patients and 7 patients with an impaired blood-brain barrier (BBB) due to cerebral metastases. Signal intensity (SI) was determined in various cerebral fluid spaces, and white matter hyperintensities were quantified by applying the Fazekas scoring system. Findings Delayed hT2w-FLAIR showed GBCA entry into the CNS via the choroid plexus and the ciliary body, with GBCA drainage along perineural sheaths of cranial nerves and along perivascular spaces of penetrating cortical arteries. In all patients and all sites, a significant SI increase was found for the 3 hours and 24 hours time points compared with baseline. Although no significant difference in SI was found between neurologically healthy patients and patients with an impaired BBB, a significant positive correlation between Fazekas scoring system and SI increase in the perivascular spaces 3 hours post injection was shown. Interpretation Delayed T2-weighted gadolinium-enhanced imaging can visualize the GBCA pathway into and through the GS. Presence of GBCAs within the GS might be regarded as part of the natural excretion process and should not be mixed up with gadolinium deposition. Rather, the correlation found between deep white matter hyperintensities, an imaging sign of vascular dementia, and GS functioning demonstrated feasibility to exploit the pathway of GBCAs through the GS for diagnostic purposes.

This study aimed to assess the diagnostic performance of integrated positron emission tomography (PET)/magnetic resonance imaging (MRI) of the breast for lesion detection and local tumor staging of patients with primary breast cancer in comparison to PET/computed tomography (CT) and MRI.The study was approved by the local institutional review board. Forty-nine patients with biopsy-proven invasive breast cancer were prospectively enrolled in our study. All patients underwent a PET/CT, and subsequently, a contrast-enhanced PET/MRI of the breast after written informed consent was obtained before each examination. Two radiologists independently evaluated the corresponding data sets (PET/CT, PET/MRI, and MRI) and were instructed to identify primary tumors lesions as well as multifocal/multicentric and bilateral disease. Furthermore, the occurrence of lymph node metastases was assessed, and the T-stage for each patient was determined. Histopathological verification of the local tumor extent and the axillary lymph node status was available for 30 of 49 and 48 of 49 patients, respectively. For the remaining patients, a consensus characterization was performed for the determination of the T-stage and nodal status, taking into account the results of clinical staging, PET/CT, and PET/MRI examinations. Statistical analysis was performed to test for differences in diagnostic performance between the different imaging procedures. P values less than 0.05 were considered to be statistically significant.Positron emission tomography/MRI and MRI correctly identified 47 (96%) of the 49 patients with primary breast cancer, whereas PET/CT enabled detection of 46 (94%) of 49 breast cancer patients and missed a synchronous carcinoma in the contralateral breast in 1 patient. In a lesion-by-lesion analysis, no significant differences could be obtained between the 3 imaging procedures for the identification of primary breast cancer lesions (P > 0.05). Positron emission tomography/MRI and MRI allowed for a correct identification of multifocal/multicentric disease in 3 additional patients if compared with PET/CT. For the definition of the correct T-stage, PET/MRI and MRI showed identical results and were correct in significantly more cases than PET/CT (PET/MRI and MRI, 82%; PET/CT, 68%; P < 0.05). Furthermore, the calculated sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy for the detection of nodal positive patients (n = 18) were 78%, 94%, 88%, 88%, and 88% for PET/CT; 67%, 87%, 75%, 82%, and 80% for MRI; and 78%, 90%, 82%, 88%, and 86% for PET/MRI, respectively. Differences between the imaging modalities were not statistically significant (P > 0.05).Integrated PET/MRI does not provide diagnostic advantages for local tumor staging of breast cancer patients in comparison to MRI alone. Positron emission tomography/MRI and MRI enable an improved determination of the local tumor extent in comparison to PET/CT, whereas all 3 imaging modalities offer a comparable diagnostic performance for the identification of axillary disease.

<h3>Objective</h3> Understanding the neural circuitry of placebo analgesia in the context of visceral pain is increasingly important given evidence of clinical benefit of placebo treatment in IBS. This functional MRI study addressed placebo analgesia in IBS, UC and healthy control (HC) volunteers. <h3>Design</h3> Painful rectal distensions were delivered in N=17 patients with IBS , N=15 patients with UC in remission, and sex-matched and age-matched HCs in an adaptation phase followed by intravenous application of saline combined with either positive instructions of pain relief (placebo) or neutral instructions (control). Neural activation during cued-pain anticipation and pain was analysed along with ratings of expected and perceived pain and measures of negative affectivity and salivary cortisol concentrations. Correlational analyses between placebo analgesia responses and negative affect were accomplished. <h3>Results</h3> HC and UC revealed significant pain inhibition during placebo analgesia, as evidenced by reduced neural activation in pain-related brain areas. In contrast, patients with IBS failed to effectively engage neural downregulation of pain, as evidenced by the absence of placebo-induced changes in distension-induced brain activation, resulting in a significant group difference in the cingulate cortex compared with HC. Depression scores correlated with weaker placebo analgesia, whereas state and trait anxiety were not associated. <h3>Conclusions</h3> Patients with IBS failed to effectively engage neural downregulation of rectal distension-induced pain during placebo analgesia, indicating a specific deficit in cognitive pain inhibition, which may in part be mediated by depression.

Systemic inflammation impairs mood and cognitive functions, and seems to be involved in the pathophysiology of psychiatric disorders. Functional magnetic resonance imaging (fMRI) studies revealed altered task-related blood-oxygen-level-dependent (BOLD) responses during experimental endotoxemia, but little is known about effects of systemic inflammation on resting-state activity of the brain. Thus, we conducted a randomized, placebo-controlled study in healthy men receiving an intravenous injection of either low-dose (0.4 ng/kg) lipopolysaccharide (LPS) (N=20) or placebo (N=25). Resting state activity was measured at baseline and 3.5h post-injection. Based on a two (condition) × two (group) design, we used multi-subject independent component analysis (ICA) to decompose and estimate functional connectivity within resting-state networks (RSNs). Seed-based analyses were applied to investigate the effect of LPS on the functional coupling for a priori-defined regions-of-interest (ROIs). ICA analyses identified 13 out of 35 components displaying common RSNs. Seed based analysis revealed greater functional connectivity between the left thalamus and the cerebellum after LPS compared to placebo administration, while the functional coupling between seeds within the amygdala, insula, and cingulate cortex and various brain regions including parieto-frontal networks was significantly reduced. Within the LPS group, endotoxin-induced increases in Interleukin (IL)-6 were significantly associated with resting-state connectivity between the left thalamus and left precuneus as well as the right posterior cingulate cortex. In summary, this exploratory study provides first evidence that systemic inflammation affects the coupling and regulation of multiple networks within the human brain at rest.

<h3>Objective</h3> Delayed cerebral ischemia (DCI) is strongly associated with poor outcome after subarachnoid hemorrhage (SAH). Cerebral vasospasm is a major contributor to DCI and requires special attention. To evaluate the effect of vasospasm management on SAH outcome, we performed a pooled analysis of 2 observational SAH cohorts. <h3>Materials</h3> Data from 2 institutional databases with consecutive patients with SAH treated between 2005 and 2012 were pooled. The effect of 2 institutional standards of conservative and endovascular vasospasm treatment (EVT) on the rates of DCI (new cerebral infarcts not visible on the post-treatment imaging) and unfavorable outcome (modified Rankin Scale score &gt;2) at 6 months follow-up was analyzed. <h3>Results</h3> The final analysis included 1,057 patients with SAH. There was no difference regarding demographic (age and sex), clinical (Hunt &amp; Hess grades, acute hydrocephalus, treatment modality, and infections), and radiographic (Fisher grades and aneurysm location) characteristics of the populations. However, there was a significant difference in the rate (24.4% [121/495] vs 14.4% [81/562], <i>p</i> &lt; 0.0001) and timing (first treatment on day 6 vs 8.9 after SAH, <i>p</i> &lt; 0.0001) of EVT. The rates of DCI (20.8% vs 29%, <i>p</i> = 0.0001) and unfavorable outcome (44% vs 50.6%, <i>p</i> = 0.04) were lower in the cohort with more frequent and early EVT. Multivariate analysis confirmed independent effect of EVT standard on DCI risk and outcome. <h3>Conclusions</h3> A preventive strategy utilizing frequent and early EVT seems to reduce the risk of DCI in patients with SAH and improve their functional outcome. We recommend prospective evaluation of the value of preventive EVT strategy on SAH. <h3>Classification of evidence</h3> This study provides Class III evidence that for patients with SAH, a frequent and early EVT to treat vasospasm reduces the risk of DCI and improves functional outcome.

Our purpose was to investigate differences between PET/MRI and PET/CT in lesion detection and classification in oncologic whole-body examinations and to investigate radiation exposure differences between the 2 modalities. <b>Methods:</b> In this observational single-center study, 1,003 oncologic examinations (918 patients; mean age, 57.8 ± 14.4 y) were included. Patients underwent PET/CT and subsequent PET/MRI (149.8 ± 49.7 min after tracer administration). Examinations were reviewed by radiologists and nuclear medicine physicians in consensus. Additional findings, characterization of indeterminate findings on PET/CT, and missed findings on PET/MRI, including their clinical relevance and effective dose of both modalities, were investigated. The McNemar test was used to compare lesion detection between the 2 hybrid imaging modalities (<i>P</i> &lt; 0.001, indicating statistical significance). <b>Results:</b> Additional information on PET/MRI was reported for 26.3% (264/1,003) of examinations, compared with PET/CT (<i>P</i> &lt; 0.001). Of these, additional malignant findings were detected in 5.3% (53/1,003), leading to a change in TNM staging in 2.9% (29/1,003) due to PET/MRI. Definite lesion classification of indeterminate PET/CT findings was possible in 11.1% (111/1,003) with PET/MRI. In 2.9% (29/1,003), lesions detected on PET/CT were not visible on PET/MRI. Malignant lesions were missed in 1.2% (12/1,003) on PET/MRI, leading to a change in TNM staging in 0.5% (5/1,003). The estimated mean effective dose for whole-body PET/CT amounted to 17.6 ± 8.7 mSv, in comparison to 3.6 ± 1.4 mSv for PET/MRI, resulting in a potential dose reduction of 79.6% (<i>P</i> &lt; 0.001). <b>Conclusion:</b> PET/MRI facilitates staging comparable to that of PET/CT and improves lesion detectability in selected cancers, potentially helping to promote fast, efficient local and whole-body staging in 1 step, when additional MRI is recommended. Furthermore, younger patients may benefit from the reduced radiation exposure of PET/MRI.

Multiparametric magnetic resonance imaging (mpMRI) and targeted biopsies (TBs) facilitate accurate detection of significant prostate cancer (sPC). However, it remains unclear how many cores should be applied per target.To assess sPC detection rates of two different target-dependent magnetic resonance imaging (MRI)/transrectal ultrasonography (TRUS)-fusion biopsy approaches (TB and target saturation [TS]) compared with extended systematic biopsies (SBs).Retrospective single-centre outcome of transperineal MRI/TRUS-fusion biopsies of 213 men was evaluated. All men underwent TB with a median of four cores per MRI lesion, followed by a median of 24 SBs, performed by experienced urologists. Cancer and sPC (International Society of Urological Pathology grade group ≥2) detection rates were analysed. TB was compared with SB and TS, with nine cores per target, calculated by the Ginsburg scheme and using individual cores of the lesion and its "penumbra".Cancer detection rates were calculated for TS, TB, and SB at both lesion and patient level. Combination of SB + TB served as a reference. Statistical differences in prostate cancer (PC) detection between groups were calculated using McNemar's tests with confidence intervals.TS detected 99% of 134 sPC lesions, which was significantly higher than the detection by TB (87%, p = 0.001) and SB (82%, p < 0.001). SB detected significantly more of the 72 low-risk PC lesions than TB (99% vs 68%, p < 0.001) and 10% (p = 0.15) more than that detected by TS. At a per-patient level, 99% of men harbouring sPC were detected by TS. This was significantly higher than that by TB and SB (89%, p = 0.03 and 81%, p = 0.001, respectively). Limitations include limited generalisability, as a transperineal biopsy route was used.TS detected significantly more cases of sPC than TB and extended SB. Given that both 99% of sPC lesions and men harbouring sPC were identified by TS, the results suggest that this approach allows to omit SB cores without compromising sPC detection.Target saturation of magnetic resonance imaging-suspicious prostate lesions provides excellent cancer detection and finds fewer low-risk tumours than the current gold standard combination of targeted and systematic biopsies.

Acute ischemia in the territory of the carotid artery can lead to massive cerebral edema with raised intracranial pressure and progression to coma and death due to uncal, cingulate, or tonsillar herniation. Thus far, only anecdotal experience with supratentorial ischemia treated by decompressive craniectomy has been reported; and there are no published experimental data dealing with this kind of therapy in acute supratentorial stroke. In this study, we present our results on the effect of decompressive craniectomy in an endovascular model of cerebral infarction in rats.Focal cerebral ischemia was induced in 50 rats using an endovascular occlusion technique of the middle cerebral artery. Decompressive craniectomy was performed in 30 animals: in 15 animals after 1 hour and in the remaining 15 animals 24 hours after vessel occlusion. Twenty animals were not treated by decompressive craniectomy (control group).Mortality in the nontreated group was 35%, whereas none of the animals treated by decompressive craniectomy died. Neurological behavior, weight loss, and infarction size were all significantly better in the animals treated by decompressive craniectomy, regardless of whether they had been treated after 1 or 24 hours (P < .01).Our results suggest that decompressive craniectomy for cerebral ischemia not only reduces mortality but also significantly improves outcome and reduces infarction size, probably because of increased perfusion pressure through leptomeningeal collaterals. This experimental study suggests that a controlled study of decompressive craniectomy in patients with acute internal carotid or middle cerebral artery occlusion would be worthwhile. By performing decompressive craniectomy in a small, selected group of patients, neurosurgeons may play an important role in the management of these patients.

Objective: Neurocognitive dysfunction is a common complication after cardiac surgery with cardiopulmonary bypass (CPB). Studies using magnetic resonance imaging (MRI) have demonstrated that new focal brain lesions can occur after coronary artery bypass grafting (CABG), even in patients without apparent neurological deficits. Diffusion-weighted MRI is superior to conventional MRI and allows for sensitive and early detection of ischemic brain lesions. We prospectively investigated cerebral injury early and 3 months after CABG using diffusion-weighted MRI and related the findings to clinical data and neurocognitive functions. Methods: Twenty-nine patients [67.6±8.6 (52–85) years, 5 females] undergoing elective CABG with CPB were examined before surgery, at discharge and 3 months after surgery. A battery of standardized neuropsychological tests and questionnaires on depression and mood were administered. Conventional and diffusion-weighted MRI of the brain was performed and new lesions were analyzed. Clinical characteristics, neuropsychological test performance and radiographic data were collected and compared. Results: There was no major neurological complication after CABG. Thirteen patients (45%) exhibited 32 new ischemic lesions on postoperative diffusion-weighted MRI. The lesions were small, rounded and equally dispersed in both hemispheres. Eight patients had at least two lesions. At discharge, significant deterioration of neuropsychological performance was observed in 6 of the 13 tests compared to baseline assessment. By 3 months postoperatively, 5 of the 6 tests returned to preoperative levels. Verbal learning ability, however, remained impaired. The presence of new focal brain lesions was not associated with impaired neuropsychological performance. There was also no correlation between clinical variables, intraoperative parameters and postoperative complications and MRI findings. Conclusions: Although neurocognitive decline after CABG is mostly transient, memory impairment can persist for months. New ischemic brain lesions on postoperative diffusion-weighted MRI do not appear to account for the persistent neurocognitive decline.

Experimental data on cortical reorganization in blind subjects using H(2)(15)O positron emission tomography and functional magnetic resonance imaging (fMRI) showed activation of the visual cortex related to Braille reading and tactile discrimination tasks in congenitally and early blind subjects. The purpose of our study was to differentiate whether occipital activation of blind subjects during Braille reading is task specific or only triggered by sensory or motor area activation. Twelve congenitally and early-onset blind subjects were studied with fMRI during Braille reading, discriminating nonsense dots, sensory stimulation with electromagnetic pulses, and finger tapping. All experiments were performed utilizing a block design with 6 active epochs alternating with 6 rest conditions lasting 34 s each. Echo-planar imaging sequences with 34 transversal slices were performed on a 1.5-T MR scanner. All blind individuals reading Braille and discriminating nonsense dots showed robust activation of the primary, secondary, and higher visual cortex. Application of peripheral electrical stimuli to the reading hand revealed expected sensory activation of the primary somatosensory cortex, but no activation in the visual cortex. Pure motor activation during finger tapping with the reading hand showed expected precentral activation and no activation of visual cortex. In conclusion, occipital activation during Braille reading and discrimination tasks is not due to plasticity of sensory or motor function; pure motor or sensory tasks do not lead to an activation of striate cortex. The brain learns to differentiate between "finger touching" and "finger reading." Our results suggest that activation of the visual cortex in blind subjects is related to higher and more complex brain functions.

The aim of the present study was to compare eyeblink conditioning in cerebellar patients with lesions including the territory of the superior cerebellar artery (SCA) and in patients with lesions restricted to the territory of the posterior inferior cerebellar artery (PICA). The cerebellar areas known to be most critical in eyeblink conditioning based on animal data (i.e. Larsell lobule H VI and interposed nucleus) are commonly supplied by the SCA. Eyeblink conditioning was expected to be impaired in SCA, but not in PICA patients. A total of 27 cerebellar patients and 25 age‐matched controls were tested. Cerebellar lesions were primarily unilateral (n = 20). Most patients suffered from ischaemic infarctions of the SCA (n = 11) or the PICA (n = 13). The other patients presented with cerebellar tumours (n = 2) and cerebellar agenesis (n = 1). The extent of the cortical lesion (i.e. which lobuli were affected) and possible involvement of the cerebellar nuclei was determined by 3D‐MRI. As expected, the ability to acquire classically conditioned eyeblink responses was significantly reduced in the group of all cerebellar patients compared with the controls. In the patients with unilateral cerebellar lesions, conditioning deficits were present ipsilaterally. In SCA patients with lesions including hemispheral lobules VI and Crus I, eyeblink conditioning was significantly reduced on the affected side compared with the unaffected side. No significant difference between the affected and unaffected sides was present in patients with lesions restricted to the common PICA territory (i.e. Crus II and below). Conditioning deficits were neither significantly different in SCA patients with pure cortical lesions compared with SCA patients with additional nuclear impairment nor in SCA patients with unilateral lesions compared with SCA patients with bilateral lesions. To summarize, unilateral cortical lesions of the superior cerebellum appear to be sufficient to reduce eyeblink conditioning in humans significantly.

Following coronary artery bypass graft surgery, some studies using magnetic resonance imaging (MRI) have demonstrated new small ischemic brain lesions in patients without apparent neurological deficits. We aimed to prospectively evaluate brain injury after cardiac valve replacement using MRI and to determine the relationship to neurocognitive function.Thirty patients with a mean age of 64.9+/-9.8 years (range, 32-82, 12 female) receiving cardiac valve replacement (aortic valve replacement [AVR], n = 24; mitral valve replacement [MVR], n = 2; AVR and MVR, n = 2; AVR and mitral valve repair, n = 2) were investigated. Study protocol included neurological examination, comprehensive neuropsychological assessment and diffusion-weighted (DW) MRI. The investigations were performed before surgery and 5 days and 4 months after surgery.Postoperative DW MRI detected new focal brain lesions in 14 patients (47%). No patient revealed a focal neurological deficit. Six patients (43%) had multiple (> or = 3) lesions (range, 1-7). Lesion volume ranged from 50-500 mm3 except 1 territorial infarct of 1900 mm3. Of a total of 41 lesions, 27 (66%) were located in the right hemisphere and 32 in a subcortical location. By 5 days postoperatively, significant neurocognitive decline was observed in 5 of 13 tests affecting memory, attention and rate of information processing. By 4 months, dysfunction had recovered in all cognitive areas. The presence of new ischemic lesions was not associated with neurocognitive decline at discharge. There was also no significant correlation between clinical and operative variables and the presence of new DW lesions or neuropsychological outcome.Following cardiac valve replacement, new small ischemic brain lesions were detected by diffusion-weighted MRI. Neurocognitive decline was present early after operation, but resolved within 4 months. A correlation of new ischemic lesions to postoperative cognitive dysfunction or clinical variables was not found.

In the present study, timing of conditioned eyeblink responses (CRs) was investigated in cerebellar patients and age-matched controls using a standard delay paradigm. Findings were compared with previously published data of CR incidences in the same patient population (Gerwig et al., 2003; Timmann et al., 2005). Sixteen patients with pure cortical cerebellar degeneration (spinocerebellar ataxia type 6 and idiopathic cerebellar ataxia), 14 patients with lesions within the territory of the superior cerebellar artery, and 13 patients with infarctions within the territory of the posterior inferior cerebellar artery were included. The affected cerebellar lobules and possible involvement of cerebellar nuclei were determined by three-dimensional magnetic resonance imaging (MRI) in patients with focal lesions ( n = 27). Based on a voxel-by-voxel analysis, MRI lesion data were related to eyeblink conditioning data. CR incidence was significantly reduced, and CRs occurred significantly earlier in patients with cortical cerebellar degeneration and lesions of the superior cerebellum compared with controls. Incidence and timing of CRs was not impaired in patients with lesions restricted to the posterior and inferior cerebellum. Voxel-based MRI analysis revealed that cortical areas within the anterior lobe (Larsell lobule HV) were most significantly related to timing deficits, whereas reduced CR incidences were related to more caudal parts (lobule HVI) of the superior cerebellar cortex. The present data suggest that different parts of the superior cerebellar cortex may be involved in the formation of the stimulus association and appropriate timing of conditioned eyeblink responses in humans. Extracerebellar premotoneuronal disinhibition, however, is another possible explanation for changes in CR timing.

IN THE VAST majority of studies that address the role of surgery in the management of high-grade gliomas, the degree of tumor removal accomplished is solely based on the intraoperative perception of the neurosurgeon. Despite its fundamental importance for a comparison of different treatment modalities, little systematic effort has been made to evaluate the residual gross tumor by neuroimaging methods immediately after surgery. We report the results of a prospective study using contrast-enhanced computed tomography and magnetic resonance imaging (MRI) to monitor 60 patients after the resection of a high-grade glioma. In each case, the first scans were obtained between Days 1 and 5 after surgery, followed by serial imaging every 2 to 3 months, usually until the condition of the patient deteriorated severely or the patient died. Gadolinium-enhanced MRI proved to be extremely valuable for assessing gross residual tumor when performed during Days 1 to 3 after the resection of a preoperatively enhancing high-grade glioma. This timing avoided surgically induced contrast enhancement and minimized interpretative difficulties. In delineating residual tumor, MRI was vastly superior to computed tomography. About 80% of tumor “recurrences” emerged from definitely enhancing remnants, as revealed by early postoperative MRI. The neurosurgeon's estimation of gross tumor burden reduction could be shown to be much less accurate (by a factor of 3) than the postoperative assessment by modern neuroimaging. In our series, residual tumor enhancement was the most predictive prognostic factor of survival in patients with glioblastoma, followed by radiotherapy. Patients with a residual tumor postoperatively had a 6.595-times higher risk of death in comparison to patients without a residual tumor. Patients undergoing radiotherapy had a 0.258-times lower risk of death in comparison to patients who were not treated with radiation. Concerning survival, the prognostic significance of both variables surpassed age and performance.

PURPOSE To evaluate efficacy and clinical benefit of early thrombolytic therapy in intracranial internal carotid artery occlusion. METHODS Thirty-two patients (mean age, 56 years) with acute intracranial internal carotid artery occlusion were studied clinically and with CT and angiography before and after thrombolytic therapy with intravenous alteplase (n = 16), superselective intraarterial alteplase (n = 8), and superselective intraarterial urokinase (n = 8). RESULTS Initial CT showed a large parenchymal hypodensity in 11 (34%) patients, a small hypodensity in 15 (47%) patients, and no hypodensity in 6 (19%) patients. Recanalization after thrombolytic therapy was observed in 4 patients (12.5% in each treatment group). Follow-up CT showed six hemorrhagic infarcts and four parenchymal hematomas unrelated to recanalization, alteplase, or urokinase administration, but commonly associated with intraarterial treatment. Clinical outcome was fatal in 53%, poor in 31%, and moderate or good in 16% of the patients. Outcome was equal in different treatment groups and closely linked to both the quality of leptomeningeal collaterals and the extent of parenchymal hypodensity on the first CT. CONCLUSION Because intravenous or intraarterial treatment with alteplase or urokinase fails to recanalize the vascular obstruction, it does not improve the prognosis of intracranial internal carotid artery occlusion over that of the natural course. Improved results may be possible with novel recanalization techniques.

Although heterosexual and homosexual individuals clearly show differences in subjective response to heterosexual and homosexual sexual stimuli, the neurobiological processes underlying sexual orientation are largely unknown. We addressed the question whether the expected differences in subjective response to visual heterosexual and homosexual stimuli may be reflected in differences in brain activation pattern. Twenty-four healthy male volunteers, 12 heterosexuals and 12 homosexuals, were included in the study. BOLD signal was measured while subjects were viewing erotic videos of heterosexual and homosexual content. SPM02 was used for data analysis. Individual sexual arousal was assessed by subjective rating. As compared to viewing sexually neutral videos, viewing erotic videos led to a brain activation pattern characteristic for sexual arousal in both groups only when subjects were viewing videos of their respective sexual orientation. Particularly, activation in the hypothalamus, a key brain area in sexual function, was correlated with sexual arousal. Conversely, when viewing videos opposite to their sexual orientation both groups showed absent hypothalamic activation. Moreover, the activation pattern found in both groups suggests that stimuli of opposite sexual orientation triggered intense autonomic response and may be perceived, at least to some extent, as aversive.

Our objective was to compare the diagnostic accuracy of an all-in-one protocol of whole-body 18F-FDG PET/CT and integrated 18F-FDG PET/CT mammography with the diagnostic accuracy of a multimodality algorithm for initial breast cancer staging.Forty women (mean age, 58.3 y; range, 30.8-78.4 y; SD, 12 y) with suspected breast cancer were included. For the primary tumor, we compared 18F-FDG PET/CT mammography versus MRI mammography; for axillary lymph node status, 18F-FDG PET/CT versus clinical investigation and ultrasound; and for distant metastases, 18F-FDG PET/CT versus a multimodality staging algorithm. Histopathology and clinical follow-up served as the standard of reference. The Fisher exact test evaluated the significance of differences (P < 0.05). Alterations in patient management caused by 18F-FDG PET/CT were documented.No significant differences were found in the detection rate of breast cancer lesions (18F-FDG PET/CT, 95%; MRI, 100%; P = 1). 18F-FDG PET/CT correctly classified lesion focality significantly more often than did MRI (18F-FDG PET/CT, 79%; MRI, 73%; P < 0.001). MRI correctly defined the T stage significantly more often than did 18F-FDG PET/CT (MRI, 77%; 18F-FDG PET/CT, 54%; P = 0.001). 18F-FDG PET/CT detected axillary lymph node metastases in 80% of cases; clinical investigation/ultrasound, in 70%. This difference was not statistically significant (P = 0.067). Distant metastases were detected with 18F-FDG PET/CT in 100% of cases, and the multimodality algorithm identified distant metastases in 70%. This difference was not statistically significant (P = 1). Three patients had extraaxillary lymph node metastases that were detected only by PET/CT (cervical, retroperitoneal, mediastinal/internal mammary group). 18F-FDG PET/CT changed patient management in 12.5% of cases.Our data suggest that a whole-body 18F-FDG PET/CT mammography protocol may be used for staging breast cancer in a single session. This initial assessment of the 18F-FDG PET/CT protocol indicates similar accuracy to MRI for the detection of breast cancer lesions. Although MRI seems to be more accurate when assessing the T stage of the tumor, 18F-FDG PET/CT seems able to more accurately define lesion focality. Although 18F-FDG PET/CT mammography was able to detect axillary lymph node metastases with a high sensitivity, this method cannot soon be expected to replace the combination of clinical examination, ultrasound, and sentinel lymph node biopsy for axillary assessment.

Although the neuronal mechanisms underlying normal sexual motivation and function have recently been examined, the alterations in brain function in deviant sexual behaviours such as paedophilia are largely unknown. The objective of this study was to identify paedophilia-specific functional networks implicated in sexual arousal. Therefore a consecutive sample of eight paedophile forensic inpatients, exclusively attracted to females, and 12 healthy age-matched heterosexual control participants from a comparable socioeconomic stratum participated in a visual sexual stimulation procedure during functional magnetic resonance imaging. The visual stimuli were sexually stimulating photographs and emotionally neutral photographs. Immediately after the imaging session subjective responses pertaining to sexual desire were recorded. Principally, the brain response of heterosexual paedophiles to heteropaedophilic stimuli was comparable to that of heterosexual males to heterosexual stimuli, including different limbic structures (amygdala, cingulate gyrus, and hippocampus), the substantia nigra, caudate nucleus, as well as the anterior cingulate cortex, different thalamic nuclei, and associative cortices. However, responses to visual sexual stimulation were found in the orbitofrontal cortex in healthy heterosexual males, but not in paedophiles, in whom abnormal activity in the dorsolateral prefrontal cortex was observed. Thus, in line with clinical observations and neuropsychological studies, it seems that central processing of sexual stimuli in heterosexual paedophiles may be altered by a disturbance in the prefrontal networks, which, as has already been hypothesized, may be associated with stimulus-controlled behaviours, such as sexual compulsive behaviours. Moreover, these findings may suggest a dysfunction (in the functional and effective connectivity) at the cognitive stage of sexual arousal processing.

Transsexuals harbor the strong feeling of having been born to the wrong sex. There is a continuing controversial discussion of whether or not transsexualism has a biological representation. Differences between males and females in terms of functional imaging during erotic stimuli have been previously described, revealing gender-specific results.Therefore, we postulated that male-to-female (MTF) transsexuals may show specific cerebral activation differing from their biological gender.Cerebral activation patterns during viewing of erotic film excerpts in functional magnetic resonance imaging (fMRI).Twelve male and 12 female heterosexual volunteers and 12 MTF transsexuals before any treatment viewed erotic film excerpts during fMRI. Additionally, subjective rating of sexual arousal was assessed. Statistics were performed using the Statistical Parametric Mapping software.Significantly enhanced activation for men compared with women was revealed in brain areas involved in erotic processing, i.e., the thalamus, the amygdala, and the orbitofrontal and insular cortex, whereas no specific activation for women was found. When comparing MTF transsexuals with male volunteers, activation patterns similar to female volunteers being compared with male volunteers were revealed. Sexual arousal was assessed using standard rating scales and did not differ significantly for the three groups.We revealed a cerebral activation pattern in MTF transsexuals compared with male controls similar to female controls compared with male controls during viewing of erotic stimuli, indicating a tendency of female-like cerebral processing in transsexualism.

Summary In this placebo analgesia study, the expectation of pain relief reduced perceived painfulness of visceral stimuli, which was associated with activity changes in thalamus, and prefrontal and somatosensory cortices. This functional magnetic resonance imaging study analysed the behavioural and neural responses during expectation-mediated placebo analgesia in a rectal pain model in healthy subjects. In N = 36 healthy subjects, the blood oxygen level–dependent (BOLD) response during cued anticipation and painful rectal stimulation was measured. Using a within-subject design, placebo analgesia was induced by changing expectations regarding the probability of receiving an analgesic drug to 0%, 50%, and 100%. Placebo responders were identified by median split based on pain reduction (0% to 100% conditions), and changes in neural activation correlating with pain reduction in the 0% and 100% conditions were assessed in a regions-of-interest analysis. Expectation of pain relief resulted in overall reductions in pain and urge to defecate, and this response was significantly more pronounced in responders. Within responders, pain reduction correlated with reduced activation of dorsolateral and ventrolateral prefrontal cortices, somatosensory cortex, and thalamus during cued anticipation (paired t tests on the contrast 0% > 100%); during painful stimulation, pain reduction correlated with reduced activation of the thalamus. Compared with nonresponders, responders demonstrated greater placebo-induced decreases in activation of dorsolateral prefrontal cortex during anticipation and in somatosensory cortex, posterior cingulate cortex, and thalamus during pain. In conclusion, the expectation of pain relief can substantially change perceived painfulness of visceral stimuli, which is associated with activity changes in the thalamus, prefrontal, and somatosensory cortices. Placebo analgesia constitutes a paradigm to elucidate psychological components of the pain response relevant to the pathophysiology and treatment of chronic abdominal pain.

To compare maximum and mean standardized uptake values (SUVmax/mean) of normal organ tissues derived from [(18)F]-fluoro-desoxyglucose (FDG) positron emission tomography/magnetic resonance imaging (PET/MRI) using MR attenuation correction (MRAC) (DIXON-based 4-segment μ-map) with [(18)F]-FDG positron emission tomography/computed tomography (PET/CT) using CT-based attenuation correction (CTAC).In 25 oncologic patients (15 men, 10 women; age 57 ± 13 years) after routine whole-body FDG-PET/CT (60 min after injection of 290 ± 40 MBq [(18)F]-FDG) a whole-body PET/MRI was performed (Magnetom Biograph mMR, Siemens Healthcare, Erlangen, Germany). Volumes of interest of 1.0 cm(3) were drawn in 7 physiological organ sites in MRAC-PET and the corresponding CTAC-PET images manually. Spearman correlation coefficients were calculated to compare MRAC- and CTAC based SUV values; Wilcoxon-Matched-Pairs signed ranks test was performed to test for potential differences.The mean delay between FDG-PET/CT and PET/MRI was 92 ± 18 min. Excellent correlations of SUV values were found for the heart muscle (SUVmax/mean: R=0.97/0.97); reasonably good correlations were found for the liver (R=0.65/0.72), bone marrow (R=0.42/0.41) and the SUVmax of the psoas muscle (R=0.41). For subcutaneous fat, the correlation coefficient was 0.66 for SUVmean (p<0.05). Correlations between MRAC and CTAC were non-significant for SUVmean of the psoas muscle, SUVmax of subcutaneous fat, SUVmax and SUVmean of the lungs, SUVmax and SUVmean of the blood-pool. The median SUVmax and SUVmean in MRAC-PET were lower than the respective CTAC values in all organs (p<0.05) but heart (SUVmax) and the bone marrow (SUVmean).In conclusion, in oncologic patients examined with PET/CT and PET/MRI SUVmax and SUVmean values generally correlate well in normal organ tissues, except the lung, subcutaneous fat and the blood pool. SUVmax and SUVmean derived from PET/MRI can be used reliably in clinical routine.

Fear conditioning is relevant for elucidating the pathophysiology of anxiety, but may also be useful in the context of chronic pain syndromes which often overlap with anxiety. Thus far, no fear conditioning studies have employed aversive visceral stimuli from the lower gastrointestinal tract. Therefore, we implemented a fear conditioning paradigm to analyze the conditioned response to rectal pain stimuli using fMRI during associative learning, extinction and reinstatement. In N = 21 healthy humans, visual conditioned stimuli (CS(+)) were paired with painful rectal distensions as unconditioned stimuli (US), while different visual stimuli (CS(-)) were presented without US. During extinction, all CSs were presented without US, whereas during reinstatement, a single, unpaired US was presented. In region-of-interest analyses, conditioned anticipatory neural activation was assessed along with perceived CS-US contingency and CS unpleasantness. Fear conditioning resulted in significant contingency awareness and valence change, i.e., learned unpleasantness of a previously neutral stimulus. This was paralleled by anticipatory activation of the anterior cingulate cortex, the somatosensory cortex and precuneus (all during early acquisition) and the amygdala (late acquisition) in response to the CS(+). During extinction, anticipatory activation of the dorsolateral prefrontal cortex to the CS(-) was observed. In the reinstatement phase, a tendency for parahippocampal activation was found. Fear conditioning with rectal pain stimuli is feasible and leads to learned unpleasantness of previously neutral stimuli. Within the brain, conditioned anticipatory activations are seen in core areas of the central fear network including the amygdala and the anterior cingulate cortex. During extinction, conditioned responses quickly disappear, and learning of new predictive cue properties is paralleled by prefrontal activation. A tendency for parahippocampal activation during reinstatement could indicate a reactivation of the old memory trace. Together, these findings contribute to our understanding of aversive visceral learning and memory processes relevant to the pathophysiology of chronic abdominal pain.

Summary The experience and neural processing of visceral pain can be increased or decreased using nocebo or placebo suggestions. To elucidate placebo and nocebo effects in visceral pain, we conducted a functional magnetic resonance imaging (fMRI) study to analyze effects of positive and negative treatment expectations in a rectal pain model. In 36 healthy volunteers, painful rectal distensions were delivered after intravenous application of an inert substance combined with either positive instructions of pain relief (placebo group) or negative instructions of pain increase (nocebo group), each compared to neutral instructions. Neural activation during cued-pain anticipation and pain was analyzed along with expected and perceived pain intensity. Expected and perceived pain intensity were significantly increased in the nocebo group and significantly decreased in the placebo group. In the placebo group, positive expectations significantly reduced activation of the somatosensory cortex during anticipation and of the insula, somatosensory cortex, and amygdala during pain delivery when compared to neutral expectations. Within the nocebo group, negative expectations led to significantly increased insula activation during painful stimulation. Direct group contrasts during expectation modulation revealed significantly increased distension-induced activation within the somatosensory cortex in the nocebo group. In conclusion, the experience and neural processing of visceral pain can be increased or decreased by drug-specific expectations. This first brain imaging study on nocebo effects in visceral pain has implications for the pathophysiology and treatment of patients with chronic abdominal complaints such as irritable bowel syndrome.

Clinical and biochemical remission in acromegaly can frequently be achieved with the recombinant GH receptor antagonist pegvisomant, even when other treatments fail. However, increases in tumor volume have been reported.Because previous studies suffer from inhomogenous magnetic resonance imaging (MRI) protocols, this prospective study examined the long-term course of adenoma volume during pegvisomant therapy by standardized MRI.Five centers in Germany participated. High-resolution MRI was performed at baseline and 6, 12, and 24 months after enrollment.Patients were outpatients, and pegvisomant is third-line therapy in most of the cases.The primary end point was tumor volume at 24 month follow-up, measured by a single, double-blinded rater.Forty-five of 61 patients completed 24 months' follow-up (73.8%). Tumor volume increase greater than 25% during the study was observed in three of 61 patients (4.9%), all during the first year of enrollment. All three patients had had octreotide treatment before initiation of pegvisomant; none of them had had radiotherapy. All volumetric findings were comparable with clinical radiological interpretations. ANOVA revealed no significant change in tumor volume after 24 months (n = 45).This study shows that pegvisomant therapy infrequently coincides with tumor growth during long-term treatment of acromegaly. Because all significant tumor volume increases occurred during the first year, these changes might correlate to the change of medication and thus be the result of a rebound from somatostatin-induced shrinkage.

Background Bone scintigraphy is the standard procedure for the detection of bone metastases in breast cancer patients. FDG-PET/CT has been reported to be a sensitive tool for tumor staging in different malignant diseases. However, its accuracy for the detection of bone metastases has not been compared to bone scintigraphy. Purpose To compare whole-body FDG-PET/CT and bone scintigraphy for the detection of bone metastases on a lesion basis in breast cancer patients. Material and Methods Twenty-nine consecutive women (mean age 58 years, range 35-78 years) with histologically proven breast cancer were assessed with bone scintigraphy and whole-body FDG-PET/CT. Twenty-one patients (72%) were suffering from primary breast cancer and eight patients (28%) were in aftercare with a history of advanced breast cancer. Both imaging procedures were assessed for bone metastases by a radiologist and a nuclear medicine physician. Concordant readings between bone scintigraphy and FDG-PET/CT were taken as true. Discordant readings were verified with additional MRI imaging in all patients and follow-up studies in most patients. Results A total of 132 lesions were detected on bone scintigraphy, FDG-PET/CT or both. According to the reference standard, 70/132 lesions (53%) were bone metastases, 59/132 lesions (45%) were benign, and three lesions (2%) remained unclear. The sensitivity of bone scintigraphy was 76% (53/70) compared to 96% (67/70) for FDG-PET/CT. The specificity of bone scintigraphy and FDG-PET/CT was 95% (56/59) and 92% (54/59), respectively. According to the reference standard bone metastases were present in eight out of the 29 patients (28%), whereas 20 patients (69%) were free of bone metastases. One (3%) patient had inconclusive readings on both modalities as well as on MRI and follow-up studies. Bone scintigraphy and FDG-PET/CT correctly identified seven out of eight patients with bone metastases and 20 out of 20 patients free of metastases. Conclusion On a lesion-basis whole-body FDG-PET/CT is more sensitive and equally specific for the detection of bone metastases compared with bone scintigraphy.

To evaluate 7T MRI in the assessment of cerebrovascular alterations as seen in vascular dementia by means of detection of cerebral microbleeds (CMB) and depiction of white matter lesions (WML). 7T imaging was evaluated with respect to 1.5T.Ten healthy volunteers and 10 patients with CMBs and/or WMLs were examined at 1.5T and 7T using gradient-echo (T2*, SWI) and turbo-spin-echo sequences (FLAIR). Comparisons of image quality, CMB and WML detection rates between sequences and field strengths were performed.Using high-resolution SWI at 7T 129 CMBs were detected compared to 75 at 1.5T using clinical SWI. With T2* at 7T 101 CMBs could be detected (33 CMBs at 1.5T). Lesion sizes were significantly larger for higher field strength. FLAIR images at 7T highlighted WMLs known from 1.5T with comparable extent. Gray and white matter contrast in FLAIR was slightly better at 1.5T, whereas image resolution and contrast of the WMLs to surrounding tissue was higher at 7T.By means of higher sensitivity for CMBs, 7T (SWI, T2*) might have significant impact on the early detection, diagnosis, and optimized antithrombotic therapy of cerebrovascular patients (eg, vascular dementia) in the future. Given the current state of technical development, 7T is approximately on par with 1.5T in the depiction of WMLs and their distribution, but holds the potential for future improvements.

Increases in peripheral cytokines during acute inflammation may affect various neuropsychological functions.The aim of this functional magnetic resonance imaging (fMRI) study was to investigate the effects of acute endotoxemia on mood and the neural response to emotionally aversive visual stimuli in healthy human subjects.In a double-blind, randomized crossover study, 18 healthy males received a bolus injection of bacterial lipopolysaccharide (LPS; 0.4 ng/kg) or saline.Plasma levels of pro-and anti-inflammatory cytokines and cortisol as well as mood ratings were analyzed together with the blood-oxygen-level dependent (BOLD) response during the presentation of aversive versus neutral pictures.Endotoxin administration induced pronounced transient increases in plasma levels of TNF-a, IL-1ra, IL-6, IL-10, and cortisol.Positive mood was decreased and state anxiety increased.In addition, activation of right inferior orbitofrontal cortex (OFC) in response to emotional visual stimuli was significantly increased in the LPS condition.Increased prefrontal activation during the presentation of emotional material may reflect enhanced cognitive regulation of emotions as an adaptive response during an acute inflammation.These findings may have implications for the putative role of inflammatory processes in the pathophysiology of depression.

To compare the diagnostic competence of FAST-PET/MRI and PET/CT for whole-body staging of female patients suspect for a recurrence of a pelvic malignancy.24 female patients with a suspected tumor recurrence underwent a PET/CT and subsequent PET/MRI examination. For PET/MRI readings a whole-body FAST-protocol was implemented. Two readers separately evaluated the PET/CT and FAST PET/MRI datasets regarding identification of all tumor lesions and qualitative assessment of visual lesion-to-background contrast (4-point ordinal scale).Tumor relapse was present in 21 of the 24 patients. Both, PET/CT and PET/MRI allowed for correct identification of tumor recurrence in 20 of 21 cases. Lesion-based sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy for the detection of malignant lesions were 82%, 91%, 97%, 58% and 84% for PET/CT and 85%, 87%, 96%, 63% and 86% for PET/MRI, lacking significant differences. Furthermore, no significant difference for lesion-to-background contrast of malignant and benign lesions was found.FAST-PET/MRI provides a comparably high diagnostic performance for restaging gynecological cancer patients compared to PET/CT with slightly prolonged scan duration, yet enabling a markedly reduced radiation exposure.

Transcatheter aortic valve implantation (TAVI) results in the dislodgement of debris with risk of cerebral lesions or stroke. The EMBOL-X protection device (Edwards Lifesciences, Irvine, CA) is positioned within the ascending aorta to capture such debris.Between July 2012 and April 2014 we randomly assigned 30 high-risk patients to undergo transaortic TAVI with the SAPIEN XT prosthesis (Edwards Lifesciences) combined with either the EMBOL-X device (group-1, n = 14) or without (group-2, n = 16). Periprocedural cerebral lesions were assessed by diffusion-weighted magnetic resonance imaging (DW-MRI) at baseline and within 7 days post-procedurally.New foci of restricted diffusion on cerebral DW-MRI were found in 69% in group-2 and 50% in group-1. Lesion size was smaller in patients treated with the EMBOL-X device than in those without (88 ± 60 vs 168 ± 217 mm(3), p = 0.27, t = 1.2, degrees of freedom = 10). Transaortic TAVI patients treated with the EMBOL-X device had significantly smaller lesion volumes in the supply region of the middle cerebral artery (33 ± 29 vs 76 ± 67 mm(3), p = 0.04). There were no neurologic events after transaortic TAVI.The intraaortic protection device seems to reduce both the incidence and the volume of new cerebral lesions (ClinicalTrials.gov number, NCT01735513).

High blood pressure is one of the main risk factors for cerebral white matter lesions (WMLs). There is limited evidence from one randomized trial that blood pressure-lowering is able to slow WML progression. We investigated whether telmisartan prevents WML progression in the imaging substudy of the Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) trial.This predefined substudy comprised 771 patients (mean age, 65 years) with recent ischemic stroke of noncardioembolic origin who received telmisartan or placebo during a mean follow-up of 27.9 (SD, 7.6) months and had 2 evaluable MRI examinations after index stroke and at study closeout. All MRI scans were centrally adjudicated for progression of periventricular and subcortical WML by 2 neuroradiologists blinded to treatment allocation.Mean blood pressure was 3.0/1.3 mm Hg lower with telmisartan compared with placebo at follow-up MRI. There was no statistically significant difference in progression of the mean periventricular WML score (least squares mean difference, 0.14; 95% CI, -0.12 to 0.39; P=0.29) and mean subcortical WML diameter (least squares mean difference, -0.35 mm; 95% CI, -1.00 to 0.31 mm; P=0.30) during follow-up between patients on telmisartan and placebo.Treatment with telmisartan on top of existing antihypertensive medication did not result in significant blood pressure-lowering and did not prevent the progression of WML in patients with a recent ischemic stroke in this patient cohort. Our analysis is limited by the relatively short follow-up period. Clinical Trial Registration- URL: http://clinicaltrials.gov. Unique Identifier: NCT00153062.

Epicardial adipose tissue (EAT) volume is associated with coronary plaque burden and adverse events. We aimed to determine, whether CT-derived EAT attenuation in addition to EAT volume distinguishes patients with and without myocardial infarction.In 94 patients with confirmed or suspected coronary artery disease (aged 66.9±14.7years, 61%male) undergoing cardiac CT imaging as part of clinical workup, EAT volume was retrospectively quantified from non-contrast cardiac CT by delineation of the pericardium in axial images. Mean attenuation of all pixels from EAT volume was calculated. Patients with type-I myocardial infarction (n = 28) had higher EAT volume (132.9 ± 111.9ml vs. 109.7 ± 94.6ml, p = 0.07) and CT-attenuation (-86.8 ± 5.8HU vs. -89.0 ± 3.7HU, p = 0.03) than patients without type-I myocardial infarction, while EAT volume and attenuation were only modestly inversely correlated (r = -0.24, p = 0.02). EAT volume increased per standard deviation of age (18.2 [6.2-30.2] ml, p = 0.003), BMI (29.3 [18.4-40.2] ml, p<0.0001), and with presence of diabetes (44.5 [16.7-72.3] ml, p = 0.0002), while attenuation was higher in patients with lipid-lowering therapy (2.34 [0.08-4.61] HU, p = 0.04). In a model containing volume and attenuation, both measures of EAT were independently associated with the occurrence of type-I myocardial infarction (OR [95% CI]: 1.79 [1.10-2.94], p = 0.02 for volume, 2.04 [1.18-3.53], p = 0.01 for attenuation). Effect sizes remained stable for EAT attenuation after adjustment for risk factors (1.44 [0.77-2.68], p = 0.26 for volume; 1.93 [1.11-3.39], p = 0.02 for attenuation).CT-derived EAT attenuation, in addition to volume, distinguishes patients with vs. without myocardial infarction and is increased in patients with lipid-lowering therapy. Our results suggest that assessment of EAT attenuation could render complementary information to EAT volume regarding coronary risk burden.

The aim of this cohort study was to assess the risk of developing cancer, specifically leukaemia, tumours of the central nervous system and lymphoma, before the age of 15 years in children previously exposed to computed tomography (CT) in Germany. Data for children with at least one CT between 1980 and 2010 were abstracted from 20 hospitals. Cancer cases occurring between 1980 and 2010 were identified by stochastic linkage with the German Childhood Cancer Registry (GCCR). For all cases and a sample of non-cases, radiology reports were reviewed to assess the underlying medical conditions at time of the CT. Cases were only included if diagnosis occurred at least 2 years after the first CT and no signs of cancer were recorded in the radiology reports. Standardised incidence ratios (SIR) using incidence rates from the general population were estimated. The cohort included information on 71,073 CT examinations in 44,584 children contributing 161,407 person-years at risk with 46 cases initially identified through linkage with the GCCR. Seven cases had to be excluded due to signs possibly suggestive of cancer at the time of first CT. Overall, more cancer cases were observed (O) than expected (E), but this was mainly driven by unexpected and possibly biased results for lymphomas. For leukaemia, the SIR (SIR = O/E) was 1.72 (95 % CI 0.89–3.01, O = 12), and for CNS tumours, the SIR was 1.35 (95 % CI 0.54–2.78, O = 7). Despite careful examination of the medical information, confounding by indication or reverse causation cannot be ruled out completely and may explain parts of the excess. Furthermore, the CT exposure may have been underestimated as only data from the participating clinics were available. This should be taken into account when interpreting risk estimates.

Multiple intracranial aneurysms (MIAs) are common findings of cerebral angiographies; however, MIA prevalence varies in different patient cohorts. We sought to elucidate risk factors influencing MIA prevalence and the clinical consequences.We systematically searched PubMed, Scopus, Embase, and Cochrane Library databases for publications before January 15, 2017, reporting MIA prevalence and risk factors. We used random-effects meta-analysis and multivariate regression analysis to assess the impacts of individual, study, and population characteristics.We included 174 studies reporting on MIA (mean overall prevalence, 20.1%; range, 2%-44.9%) in 134 study populations with 86 989 intracranial aneurysm (IA) patients enrolled between 1950 and 2015. Studies from Europe and North America (P<0.001) and more recent enrolment years (P=0.046) were independently associated with higher MIA prevalence. In meta-analysis, MIA correlated with female sex (odds ratio [OR], 1.59; 95% confidence interval [CI], 1.4-1.8), higher patient age (>40 years; OR, 1.6; 95% CI, 1.14-2.25), arterial hypertension (OR, 1.51; 95% CI, 1.17-1.94), smoking (OR, 1.89; 95% CI, 1.37-2.6) and familial IA (OR, 2.02; 95% CI, 1.47-2.77), and formation of de novo (OR, 3.92; 95% CI, 1.95-7.87) and growth of initial IA (OR, 3.47; 95% CI, 1.87-6.45). Risk of subarachnoid hemorrhage in MIA patients was higher only in longitudinal studies from Japan and Korea (OR, 2.08; 95% CI, 1.46-2.96).Female sex, higher age, arterial hypertension, smoking, and familial IA are major risk factors for MIA. In addition, MIA patients are at risk for enhanced IA formation. Further studies are needed to evaluate rupture risk and the role of ethnicity, especially in the context of increased MIA identification with improved neurovascular imaging.

Objectives The objective of this study was to assess the diagnostic value of integrated positron emission tomography/magnetic resonance imaging (PET/MRI) for whole-body staging of patients with recurrent gynecological pelvic malignancies, in comparison to whole-body MRI alone. Materials and Methods The study was approved by the local institutional ethics committee. Written informed consent was obtained before each examination. Thirty-four consecutive patients with a suspected recurrence of cervical (n = 18) or ovarian (n = 16) cancer were prospectively enrolled for an integrated PET/MRI examination, which comprised a diagnostic, contrast-enhanced whole-body MRI protocol including dedicated sagittal dynamic imaging of the pelvis. Two radiologists separately evaluated the data sets regarding lesion count, lesion detection, lesion characterization, and diagnostic confidence. Mean and median values were calculated for each rating. Statistical analyses were performed both per-patient and per-lesion bases using a Wilcoxon signed-rank test to indicate potential significant differences among PET/MRI and MRI (alone) data sets. Results Malignant lesions were present in 25 of the 34 patients. Positron emission tomography/magnetic resonance imaging offered correct and superior identification of all 25 patients with cancer recurrence, compared with MRI alone (23/25). A total of 118 lesions (malignant, 89; benign, 29) were detected. Positron emission tomography/magnetic resonance imaging correctly identified 88 (98.9%) of 89 malignant lesions, whereas MRI alone allowed for correct identification of 79 (88.8%) of the 89 malignant lesions. In addition, PET/MRI provided significantly higher lesion contrast and diagnostic confidence in the detection of malignant lesions (P < 0.001) compared with MRI alone. Conclusions These first results demonstrate the high diagnostic potential of integrated PET/MRI for the assessment of recurrence of female pelvic malignancies compared with MRI alone.

There exists converging evidence to support a role of pain-related fear in the pathophysiology and treatment of chronic pain conditions. Pain-related fear is shaped by associative learning and memory processes, which remain poorly characterized especially in the context of abdominal pain such as in irritable bowel syndrome (IBS). Therefore, using event-related functional magnetic resonance imaging (fMRI), we assessed the neural mechanisms mediating the formation, extinction and reinstatement of abdominal pain-related fear in healthy humans. Employing painful rectal distensions as clinically-relevant unconditioned stimuli (US), in this fear conditioning study we tested if differential excitatory and inhibitory learning is evocable after very few CS-US learning trials ("rapid conditioning"), and explored the underlying neural substrates of these learning and memory processes.In N=24 healthy men and women, "rapid" fear acquisition was accomplished by pairing visual conditioned stimuli (CS(+)) with painful rectal distensions as unconditioned stimuli (US), while different visual stimuli (CS(-)) were presented without US (differential delay conditioning with five CS(+) and five CS(-) presentations and a 80% reinforcement ratio). During extinction, all CS were presented without US. Subsequently, a reinstatement procedure was implemented, defined as the retrieval of an extinguished memory after unexpected and unpaired exposure to the US, followed by CS presentations. For each phase, changes in perceived CS-US contingency and CS unpleasantness were assessed with visual analogue scales and compared with analyses of variance. fMRI data were analyzed using whole-brain analyses (at p<.001 uncorrected) and in regions-of-interest analyses with familywise error correction of alpha (pFWE<.05). Differential neural activation in response to the CS during each experimental phase (i.e., CS(+)>CS(-); CS(+)<CS(-)) was analyzed without and subsequently also with a linear parametric modulation including trial number as a regressor.A significant valence change (i.e. increased CS(+) unpleasantness) was observed following acquisition, indicating successful differential aversive learning. On the other hand, CS-US contingency awareness was not fully established. These behavioral results were paralleled by differential activation of the putamen (pFWE<.05), insula (pFWE<.05) and secondary somatosensory cortex (S2, p<.001 uncorrected) in response to the CS(+) during acquisition. The same analysis with a linear parametric modulation confirmed but also strengthened the resulting activations, which were all highly significant in ROI analyses at pFWE<.05. Extinction and reinstatement involved differential activation in response to the CS(-), involving the cingulate cortex and primary motor cortex (M1) during extinction and the posterior cingulate cortex (PCC) during reinstatement (all p<.001 uncorrected), without obvious effects upon linear parametric modulation analysis.Abdominal pain stimuli are effective US that elicit conditioned pain-related fear even after very few learning experiences without full contingency awareness. These findings extend similar evidence of "rapid learning" in response to interoceptive US (e.g., conditioned taste aversion, conditioned nausea), and have implications for the pathophysiology and treatment of chronic abdominal pain such as in IBS.

Nusinersen is an intrathecally administered antisense oligonucleotide (ASO) and the first approved drug for the treatment of spinal muscular atrophy (SMA). However, progressive neuromyopathic scoliosis and the presence of spondylodesis can impede lumbar punctures in SMA patients. Our aim was to assess the feasibility and safety of the treatment in adults with SMA.For the intrathecal administration of nusinersen, we performed conventional, fluoroscopy-assisted and computer tomography (CT)-guided lumbar punctures in adult patients with type 2 and type 3 SMA. We documented any reported adverse events and performed blood tests.We treated a total of 28 adult SMA patients (9 patients with SMA type 2 and 19 patients with SMA type 3) aged between 18-61 years with nusinersen. The mean Revised Upper Limb Module (RULM) score at baseline in SMA type 2 and SMA type 3 patients was 9.9 ± 4.6 and 29.5 ± 8.5, respectively. The mean Hammersmith Functional Motor Scale Expanded (HFMSE) score at baseline was 3.1 ± 2.5 and 31.2 ± 18.1, respectively. Half of the SMA type 3 patients were ambulatory at treatment onset. In total, we performed 122 lumbar punctures with 120 successful intrathecal administrations of nusinersen. Lumbar punctures were well tolerated, and no serious adverse events occurred.Our data demonstrate the feasibility and tolerability of intrathecal treatment with nusinersen in adults with SMA type 2 and type 3. However, treatment can be medically and logistically challenging, particularly in patients with SMA type 2 and in patients with spondylodesis.

Abstract This functional magnetic resonance imaging study addressed similarities and differences in behavioral and neural responses to experimental visceral compared with somatic pain stimuli and explored the contribution of fear of pain to differences between pain modalities. In N = 22 healthy women, we assessed blood oxygen level–dependent responses to rectal distensions and cutaneous heat stimuli matched for perceived pain intensity. Fear of pain and pain unpleasantness were assessed before and after scanning. Visceral pain was more fear evoking and more unpleasant, and trial-by-trial intensity ratings failed to habituate across trials (all interactions modality × time: P &lt; 0.01). Differences in fear of pain and pain intensity independently contributed to greater visceral pain unpleasantness (combined regression model: R 2 = 0.59). We observed joint neural activations in somatosensory cortex and frontoparietal attention network (conjunction analysis: all p FWE &lt;0.05), but distensions induced greater activation in somatosensory cortex, dorsal and ventral anterior insula, dorsal anterior and midcingulate cortices, and brainstem, whereas cutaneous heat pain led to enhanced activation in posterior insula and hippocampus (all p FWE &lt;0.05). Fear of visceral pain correlated with prefrontal activation, but did not consistently contribute to neural differences between modalities. These findings in healthy women support marked differences between phasic pain induced by rectal distensions vs cutaneous heat, likely reflecting the higher salience of visceral pain. More studies with clinically relevant pain models are needed to discern the role of fear in normal interindividual differences in the response to different types of pain and as a putative risk factor in the transition from acute to chronic pain.

The aim of this study is to evaluate and compare the diagnostic potential of integrated whole-body [18F]FDG-PET/MRI to [18F]FDG-PET/CT for detection of a potential primary cancer and metastases in patients suspected for cancer of unknown primary (CUP).A total of 20 patients (15 male, 5 female, age 53±13 years) suspect for CUP underwent a dedicated head and neck & whole-body [18F]FDG-PET/CT (Biograph mCT 128, Siemens Healthcare) and a subsequent simultaneous [18F]FDG-PET/MRI examination (Biograph mMR, Siemens Healthcare). Two readers rated the datasets (PET/CT; PET/MRI) regarding the detection of the primary cancer and metastases, lesion conspicuity (4-point ordinal scale) and diagnostic confidence (3-point ordinal scale). PET analysis comprised the assessment of maximum standardized uptake values (SUVmax) of all PET-positive lesions using volume of interest (VOI) analysis derived from the PET/CT and PET/MR datasets. All available data considering histology and imaging including prior and clinical follow-up examinations served as reference standard. Statistical analysis included comparison of mean values using Mann-Whitney U test and correlation of SUVmax using Pearson's correlation.In 14 out of 20 patients 49 malignant lesions were present. The primary cancer could be correctly identified in 11/20 patients with both PET/CT and PET/MRI. PET/CT enabled the detection of a total 38 metastases, PET/MR respectively of 37 metastases (one lung metastasis <5mm was missed). PET/CT and PET/MRI showed comparably high lesion conspicuity (2.6±0.6 each), with superior assessment of cervical lesions in PET/MRI and an indicated superior assessment of pulmonary lesions in PET/CT. Diagnostic confidence was rated comparably high in PET/CT and PET/MRI (2.7±0.5 each). The mean values of SUVmax of all PET-positive lesions (PET/MRT 7.9±4.2 vs. PET/CT 7.2±3.5) showed a strong positive correlation between the SUVs derived from both hybrid imaging systems (Pearson's correlation r=0.927).Both hybrid imaging techniques provide a comparable diagnostic ability for detection of primary cancer and metastases in patients with CUP, with comparably high lesion conspicuity and diagnostic confidence, offering superior assessment of cervical lesions in PET/MRI and potentially of pulmonary lesions in PET/CT. Furthermore, due to the significantly lower dose of ionizing radiation, PET/MRI may serve as a powerful alternative to PET/CT, particularly for therapy monitoring and/or surveillance considering the long-term cumulative dose.

OBJECTIVE The complete clipping of a cerebral aneurysm usually warrants its sustained occlusion, while clip remnants may have far-reaching consequences. The aim of this study is to identify the risk factors for clip remnants requiring retreatment and/or exhibiting growth. METHODS All consecutive patients with primary aneurysm clipping performed at University Hospital of Essen between January 1, 2003, and December 31, 2013, were eligible for this study. Aneurysm occlusion was judged on obligatory postoperative digital subtraction angiography and the need for repeated vascular control. The identified clip remnants were correlated with various demographic and clinical characteristics of the patients, aneurysm features, and surgery-related aspects. RESULTS Of 616 primarily clipped aneurysms, postoperative angiography revealed 112 aneurysms (18%) with clip remnants requiring further control (n = 91) or direct retreatment (n = 21). Seven remnants exhibited growth during follow-up, whereas 2 cases were associated with aneurysmal bleeding. Therefore, a total of 28 aneurysms (4.5%) were retreated as clip remnants (range 1 day to 67 months after clipping). In the multivariate analysis, the need for retreatment of clip remnant was correlated with the aneurysm's initial size (&gt; 12 mm; OR 3.22; p = 0.035) and location (anterior cerebral artery &gt; internal carotid artery &gt; posterior circulation &gt; middle cerebral artery; OR 1.85; p = 0.003). Younger age with a cutoff at 45 years (OR 33.31; p = 0.004) was the only independent predictor for remnant growth. CONCLUSIONS The size and location of the aneurysm are the main risk factors for clip remnants requiring retreatment. Because of the risk for growth, younger individuals (&lt; 45 years old) with clip remnants require a long-term (&gt; 5 years) vascular follow-up. Clinical trial registration no: DRKS00008749 (Deutsches Register Klinischer Studien)

We aimed to determine the association of pericoronary adipose tissue (PCAT) volume and attenuation with culprit lesions in the underlying coronary segment in patients with acute myocardial infarction.In patients with myocardial infarction, PCAT volume and attenuation surrounding the following segments were manually traced from non-contrast CT imaging: LM, proximal and mid-segment of LAD, RCA, and LCX. PCAT volume and attenuation surrounding culprit and non-culprit lesions were compared. Odds ratios (OR) and 95% confidence intervals (CI) were calculated per 1 standard deviation increase in PCAT volume/attenuation.We included 46 subjects (mean age 64.4 ± 16.4 years, 71% male) with acute myocardial infarction. PCAT volume around the right coronary artery was higher compared to left coronary segments, while PCAT attenuation decreased from proximal to distal segments. PCAT volume surrounding culprit lesions was higher compared to segments without culprit lesion (4.90 ± 3.07 ml vs. 2.33 ± 2.63 ml, p < 0.0001), whereas the attenuation was not different (-84.8 ± 9.4 HU vs. -84.2 ± 9.9 HU, p = 0.77). In univariate regression analysis, PCAT volume was significantly associated with the probability of presence of culprit lesions (OR [95% CI]: 3.10 [1.84-5.22], p < 0.0001). Associations remained stable upon adjustment for risk factors (3.34 [1.81-6.15], p < 0.0001). PCAT attenuation was not relevantly different around culprit lesions (unadjusted: 0.94 [0.63-1.40], p = 0.77, risk factor adjusted: 1.00 [0.61-1.64], p = 0.996).In patients with acute myocardial infarction, PCAT volume is strongly and independently associated with culprit lesions in the underlying coronary segments, whereas PCAT attenuation does not relevantly differentiate surrounding coronary segments with and without culprit lesions.

Delayed cerebral ischemia (DCI) has a strong impact on outcome of patients with aneurysmal subarachnoid hemorrhage (SAH). Positive effect of antiplatelet therapy on DCI rates has been supposed upon smaller SAH series.To analyze the benefit/risk profile of antiplatelet use in SAH patients.This retrospective case-control study was based on institutional observational cohort with 994 SAH patients treated between January 2003 and June 2016. The individuals with postcoiling antiplatelet therapy (aspirin with/without clopidogrel) were compared to a control group without antiplatelet therapy. Occurrence of DCI, major/minor bleeding events in the follow-up computed tomography scans, and favorable outcome at 6 mo after SAH (modified Rankin scale < 3) were compared in both groups.Of 580 patients in the final analysis, 329 patients received post-treatment antiplatelet medication. There were no significant differences between the compared groups with regard to basic outcome confounders. Aspirin use was independently associated with reduced DCI risk (P < .001, adjusted odds ratio = 0.41, 95% confidence interval 0.24-0.65) and favorable outcome (P = .02, adjusted odds ratio = 1.78, 95% confidence interval 1.06-2.98). Regarding bleeding complications, aspirin was associated only with minor bleeding events (P = .02 vs P = .51 for major bleeding events).Regular administration of aspirin might have a positive impact on DCI risk and outcome of SAH patients, without increasing the risk for clinically relevant bleeding events. In our SAH cohort, dual antiplatelet therapy showed no additional benefit on DCI risk, but increased the likelihood of major bleeding events.

PURPOSE Image analysis is one of the most promising applications of artificial intelligence (AI) in health care, potentially improving prediction, diagnosis, and treatment of diseases. Although scientific advances in this area critically depend on the accessibility of large-volume and high-quality data, sharing data between institutions faces various ethical and legal constraints as well as organizational and technical obstacles. METHODS The Joint Imaging Platform (JIP) of the German Cancer Consortium (DKTK) addresses these issues by providing federated data analysis technology in a secure and compliant way. Using the JIP, medical image data remain in the originator institutions, but analysis and AI algorithms are shared and jointly used. Common standards and interfaces to local systems ensure permanent data sovereignty of participating institutions. RESULTS The JIP is established in the radiology and nuclear medicine departments of 10 university hospitals in Germany (DKTK partner sites). In multiple complementary use cases, we show that the platform fulfills all relevant requirements to serve as a foundation for multicenter medical imaging trials and research on large cohorts, including the harmonization and integration of data, interactive analysis, automatic analysis, federated machine learning, and extensibility and maintenance processes, which are elementary for the sustainability of such a platform. CONCLUSION The results demonstrate the feasibility of using the JIP as a federated data analytics platform in heterogeneous clinical information technology and software landscapes, solving an important bottleneck for the application of AI to large-scale clinical imaging data.

Background Recently, radiomics has emerged as a non-invasive, imaging-based tissue characterization method in multiple cancer types. One limitation for robust and reproducible analysis lies in the inter-reader variability of the tumor annotations, which can potentially cause differences in the extracted feature sets and results. In this study, the diagnostic potential of a rapid and clinically feasible VOI (Volume of Interest)-based approach to radiomics is investigated to assess MR-derived parameters for predicting molecular subtype, hormonal receptor status, Ki67- and HER2-Expression, metastasis of lymph nodes and lymph vessel involvement as well as grading in patients with breast cancer. Methods A total of 98 treatment-naïve patients (mean 59.7 years, range 28.0–89.4) with BI-RADS 5 and 6 lesions who underwent a dedicated breast MRI prior to therapy were retrospectively included in this study. The imaging protocol comprised dynamic contrast-enhanced T1-weighted imaging and T2-weighted imaging. Tumor annotations were obtained by drawing VOIs around the primary tumor lesions followed by thresholding. From each segmentation, 13.118 quantitative imaging features were extracted and analyzed with machine learning methods. Validation was performed by 5-fold cross-validation with 25 repeats. Results Predictions for molecular subtypes obtained AUCs of 0.75 (HER2-enriched), 0.73 (triple-negative), 0.65 (luminal A) and 0.69 (luminal B). Differentiating subtypes from one another was highest for HER2-enriched vs triple-negative (AUC 0.97), followed by luminal B vs triple-negative (0.86). Receptor status predictions for Estrogen Receptor (ER), Progesterone Receptor (PR) and Hormone receptor positivity yielded AUCs of 0.67, 0.69 and 0.69, while Ki67 and HER2 Expressions achieved 0.81 and 0.62. Involvement of the lymph vessels could be predicted with an AUC of 0.8, while lymph node metastasis yielded an AUC of 0.71. Models for grading performed similar with an AUC of 0.71 for Elston-Ellis grading and 0.74 for the histological grading. Conclusion Our preliminary results of a rapid approach to VOI-based tumor-annotations for radiomics provides comparable results to current publications with the perks of clinical suitability, enabling a comprehensive non-invasive platform for breast tumor decoding and phenotyping.

Background: A growing number of reports suggest that infection with SARS-CoV-2 often leads to neurological involvement; however, data on the incidence and severity are limited to mainly case reports and retrospective studies. Methods: This prospective, cross-sectional study of 102 SARS-CoV-2 PCR positive patients investigated the frequency, type, severity and risk factors as well as underlying pathophysiological mechanisms of neurological involvement (NIV) in COVID-19 patients. Results: Across the cohort, 59.8% of patients had NIV. Unspecific NIV was suffered by 24.5%, mainly general weakness and cognitive decline or delirium. Mild NIV was found in 9.8%; most commonly, impaired taste or smell. Severe NIV was present in 23.5%; half of these suffered cerebral ischaemia. Incidence of NIV increased with respiratory symptoms of COVID-19. Mortality was higher with increasing NIV severity. Notably, 83.3% with severe NIV had a pre-existing neurological co-morbidity. All cerebrospinal fluid (CSF) samples were negative for SARS-CoV-2 RNA, and SARS-CoV-2 antibody quotient did not suggest intrathecal antibody synthesis. Of the patients with severe NIV, 50% had blood–brain barrier (BBB) disruption and showed a trend of elevated interleukin levels in CSF. Antibodies against neuronal and glial epitopes were detected in 35% of the patients tested. Conclusion: Cerebrovascular events were the most frequent severe NIV and severe NIV was associated with high mortality. Incidence of NIV increased with respiratory symptoms and NIV and pre-existing neurological morbidities were independent risk factors for fatality. Inflammatory involvement due to BBB disruption and cytokine release drives NIV, rather than direct viral invasion. These findings might help physicians define a further patient group requiring particular attention during the pandemic.

Bone-tracer scintigraphy has an established role in diagnosis of cardiac amyloidosis (CA) as it detects transthyretin amyloidosis (ATTR). Positron emission tomography (PET) with amyloid tracers has shown high sensitivity for detection of both ATTR and light-chain (AL) CA. We aimed to investigate the accuracy of 18F-flutemetamol in CA.We enrolled patients with CA or non-amyloid heart failure (NA-HF), who underwent cardiac 18F-flutemetamol PET/MRI or PET/CT. Myocardial and blood pool standardized tracer uptake values (SUV) were estimated. Late gadolinium enhancement (LGE) and T1 mapping/ extracellular volume (ECV) estimation were performed.We included 17 patients (12 with CA, 5 with NA-HF). PET/MRI was conducted in 13 patients, while PET/CT was conducted in 4. LGE was detected in 8 of 9 CA patients. Global relaxation time and ECV were higher in CA (1448 vs. 1326, P = 0.02 and 58.9 vs. 33.7%, P = 0.006, respectively). Positive PET studies were demonstrated in 2 of 12 patients with CA (AL and ATTR). Maximal and mean SUV did not differ between groups (2.21 vs. 1.69, P = 0.18 and 1.73 vs. 1.30, P = 0.13).Although protein-independent binding is supported by our results, the diagnostic yield of PET was low. We demonstrate here for the first time the low sensitivity of PET for CA.

Concentration-time curves derived from dynamic susceptibility-contrast enhanced magnetic resonance imaging are widely used to calculate cerebrovascular parameters. To exclude effects of recirculation, a non-linear regression method is used to fit a gamma-variate function to the concentration-time course. In previous studies the errors arising from the fitting procedure have not been quantified. In a computer simulation we investigate the uncertainties of parameters calculated from the fitted gamma-variate function, exploring the dependencies on signal-to-noise (SNR), time resolution (delta t), and maximal signal drop (MSD). Our study was performed to give a framework on how to design MR-sequences and choose contrast media and their application in order to yield concentration-time curves which allow a reliable performance of the gamma-variate fitting procedure. We recorded 396 concentration-time curves from regions of interest of 40 patients. The gamma-variate fitting procedure was applied to these curves resulting in 396 parameter sets. Ideal concentration-time curves as gamma-variate functions were generated from these sets with a given delta t, MSD, and SNR. Recirculation effect was simulated. Then the gamma-variate fitting was performed again. From ideal and simulated gamma-variate function the area and the normalized first moment were calculated. The uncertainties of the values calculated from the simulated curve relating to the values of the original one were determined. Increase of SNR decreases the involved errors. With SNR values of 100 and more there is only minor influence of delta t and MSD and the fitted curve approximates the original data very well. Smaller values of SNR lead to a stronger influence of delta t and MSD and a higher number of fitting failures. With increasing delta t the uncertainties also increase. Intermediate values of MSD (30% to 70%) yield the smallest errors while increasing or decreasing MSD yields an increase of uncertainty. To achieve low uncertainties in the calculation of cerebrovascular parameters from gamma-variate fits, delta t of the imaging sequence and MSD must be considered. This is more important the lower SNR is. The shown dependencies should be taken into account when choosing MR sequence parameters and application of contrast media.

✓ The authors present two cases of patients with small, acutely ruptured, wide-necked aneurysms of the distal vertebral artery that were not amenable to conventional coil embolization and were instead treated by means of a double-stent method in which one stent was placed inside another. Angiography performed immediately after the procedure revealed a significant reduction in aneurysm filling; total occlusion of the lesion was observed after 7 days and confirmed 6 months later in both aneurysms. By placing one stent inside the other, stent permeability can be reduced, which may result in significant hemodynamic changes with accelerated aneurysm thrombosis. This double-stent method may represent a therapeutic alternative, especially in cases of small, wide-necked aneurysms in which conventional endovascular techniques or stent-supported coil embolization is not considered feasible or is believed to be too dangerous, and surgical treatment is contraindicated.

ABSTRACT Background and Purpose . To study whether computed tomography (CT) can measure the water content of early ischemic edema. Methods . The authors obtained cranial CT in 5 groups of rats subjected to 1 hour (n = 8),2 hours (n = 11),3 hours (n = 13),4 hours (n = 13), or 6 hours (n = 14) of right middle cerebral artery (MCA) occlusion. Immediately after CT, the authors removed the rats’ brains and determined tissue water content by the dry‐wet weight method. They correlated brain x‐ray attenuation with brain tissue water content. Results . Mean brain tissue water content remained constant in the nonischemic left hemispheres at 77.9%± 0.6% and increased up to 79.3%± 1.0% in the right hemispheres after 6 hours of permanent right MCA occlusion. X‐ray attenuation remained constant in the left hemispheres at 75.6 ± 2.2 Hounsfield units (HU) and decreased to 71.7 ± 3.4 HU in the right hemispheres after 6 hours of right MCA occlusion. The decrease in x‐ray attenuation correlated significantly with the increase in ischemic brain tissue water content ( y = 217.3 – 1.8 × x ; r = .55, P &lt; .0001). That means that a 1% increase in hemispheric tissue water content causes a decrease in x‐ray attenuation of 1.8 HU. Conclusions . After MCA occlusion, immediate brain tissue net water uptake is associated with a decrease in x‐ray attenuation. CT can monitor ischemic edema in an acute stroke.

The goal of the present study was to test the impact of administration time of the angiotensin II type 1–receptor blocker candesartan on cerebral blood flow (CBF), infarct size, and neuroscore in transient cerebral ischemia. Therefore, 1-hour middle cerebral artery occlusion (MCAO) was followed by reperfusion. Rats received 0.5-mg/kg candesartan intravenously 2 hours before MCAO (pretreatment), 24 hours after MCAO, every 24 hours after MCAO, or 2 hours before and every 24 hours after MCAO. Infarct size (mm 3 ) and a neuroscore at day 7 were compared with controls. CBF was quantified by radiolabeled microspheres and laser-Doppler flowmetry. Compared with controls (95 ± 8), infarct size in candesartan-treated groups was smaller (59 ± 5, 68 ± 10, 28 ± 3, and 15 ± 3, respectively; P &lt; 0.05). Although there was no difference in neuroscore between pretreatment and controls (1.55 ± 0.18, 1.80 ± 0.13), other treatment regimens resulted in improved neuroscores (1.33 ± 0.16, 1.11 ± 0.11, 0.73 ± 0.15; P &lt; 0.05). CBF in pretreated animals at 0.5 hours after MCAO was significantly higher than in controls (0.58 ± 0.09 mL · g −1 ·· min −1 and 44% ± 7% of baseline compared with 0.49 ± 0.06 mL · g −1 ·· min −1 and 37% ± 6%, microspheres and laser-Doppler flowmetry; P &lt; 0.05). Thus, candesartan reduces infarct size even if administered only during reperfusion. Apart from pretreatment, other treatment regimens result in significantly improved neuroscores. In the acute phase of cerebral ischemia, candesartan increases CBF.

Neuroimaging constitutes an important component in the diagnosis of the underlying infectious agents in central nervous system infection. This review summarizes progress in the neuroimaging of infectious central nervous system disease since January 2003. It focuses on imaging of viral encephalitis, including that caused by exotic and emerging viruses, and on imaging in immunodeficient patients.Diffusion-weighted imaging has been shown to be superior to conventional magnetic resonance imaging for the detection of early signal abnormalities in herpes simplex virus encephalitis but also in enterovirus 71 encephalitis and in West Nile encephalitis. Several studies defined the pattern of magnetic resonance imaging signal changes in endemic diseases such as West Nile encephalitis, Murray Valley encephalitis, enterovirus 71 encephalitis and Japanese encephalitis, but also in encephalitides due to ubiquitous viruses such as measles virus and Lyssavirus (rabies). In patients with HIV infection, apparent diffusion coefficient ratios obtained by diffusion-weighted imaging were significantly greater in lesions due to Toxoplasma encephalitis than in primary central nervous system lymphomas.The diagnosis of unclear infectious central nervous system diseases remains a challenge. More recent magnetic resonance imaging techniques, such as diffusion-weighted imaging and magnetic resonance spectroscopy, provide additional helpful information. However, the mainstay of diagnosis remains the detection of viral DNA or serological markers of specific infectious agents within the cerebrospinal fluid.

Summary: Purpose: Diffusion‐weighted magnetic resonance imaging (DWI) after focal status epilepticus has demonstrated focal alterations of the apparent diffusion coefficient (ADC) in the epileptogenic zone. We hypothesized that localized dynamic alterations of brain diffusion during the immediate postictal state will be detectable by serial DWI and correlate with the epileptogenic zone. Methods: Nine adult patients (four men, five women) with medically intractable epilepsy were prospectively examined with a total of 25 DWI scans taken 2–210 min after a seizure. Results: The interictal ADC was significantly (p &lt; 0.05) elevated in the ictogenic hippocampus in all patients with temporal lobe epilepsy. The following postictal changes of the ADC were seen: (a) decreases by maximally 25–31%, which were most pronounced in the epileptogenic zone (n = 2); (b) generalized ADC changes after generalized seizures (n = 1) or prolonged complex partial seizures (n = 2); (c) no major changes after short‐lived seizures or if the time to first DWI scan was &gt;15 min or both (n = 3); and (d) widespread bilateral ADC increases after a flumazenil‐induced seizure (n = 1). Conclusions: ADC changes seen during serial postictal DWI are complex and appear to reflect origin and spread of the preceding seizure. A delineation of the epileptogenic zone appears to be possible only in complex‐partial seizures of &gt;60 s duration that do not secondarily generalize.

The differential role of the cerebellar cortex and nuclei has rarely been addressed in human lesion and functional brain imaging studies. One important reason is the difficulty of defining the localization of the cerebellar nuclei and extent of possible lesions based on CT or MR scans. The present MRI investigation was specifically designed to study the anatomy of the deep cerebellar nuclei. In both basal ganglia and cerebellar nuclei of healthy human subjects the amount of iron is high compared to the rest of the brain. Clusters of iron are paramagnetic and, therefore, tend to cause local inhomogenities in a magnetic field. The iron-induced susceptibility artefacts were used to visualize the cerebellar nuclei as hypointensities on MR images. A three-dimensional atlas of the dentate (D), interposed (I), and fastigial (F) nuclei is presented in standard proportional stereotaxic space coordinates based on findings in a healthy 26-year-old female. A three-dimensional axial volume of the cerebellum was acquired using a T1-weighted fast low-angle shot (FLASH) sequence on a Siemens Sonata 1.5 Tesla MR. To increase the signal to noise ratio the sequence was acquired 5 times and averaged. Each volume was registered, resampled to 1.00 × 1.00 × 1.00-mm3 voxel size and spatially normalized into a standard proportional stereotaxic space (the MNI-space) using SPM99. Localization of cerebellar nuclei were confirmed by comparison with postmortem MRI and histological microsections of another brain.

Cross-modal plasticity in deaf subjects is still discussed controversial. We tried to figure out whether the plasticity is dependent on the extent of hearing loss. Three groups of volunteers, comprising twelve individuals each, were investigated. They were characterized by three distinctive features, one had normal hearing, the other one lost hearing and the third had only minimal residual hearing ability. All participants, except those of group one, were capable of using German Sign Language (GSL). The groups were studied with functional MRI in a standard block design during individuals' watching sign language videos alternating with black frame. During sign language conditions, deaf subjects revealed a significant activation of the auditory cortex in both hemispheres comprising Brodmann areas (BA) 42 and 22 corresponding to the secondary associative auditory areas. Additionally, activation of the angular and supramarginal gyrus was seen. Activation of the primary auditory cortex was revealed in deaf subjects with total hearing loss during sign language tasks but not in subjects with residual hearing ability. In conclusion our results indicate a cortical reorganization of the auditory cortex comprising primary auditory fields only present in subjects with total hearing loss.

In a previous study, a three-dimensional (3D) MRI atlas of the human cerebellar nuclei was introduced based on findings in one healthy human subject [Dimitrova, A., Weber, J., Redies, C., Kindsvater, K., Maschke, M., Kolb, F.P., Forsting, M., Diener, H.C., Timmann, D., 2002. MRI atlas of the human cerebellar nuclei. NeuroImage 17, 240-255]. The present MRI investigation was designed to study variability of the anatomy of the dentate/interposed nuclei in a larger group of healthy subjects. Similar to our previous study, iron-induced susceptibility artifacts were used to visualize the cerebellar nuclei as hypointensities on MR images. Data of 63 healthy subjects (27 female, 36 male; mean age 45.3+/-13.4 years, age range 22--71 years) were included. A 3D axial volume of the cerebellum was acquired using a T2*-weighted FLASH sequence on a Siemens Sonata 1.5 T MR scanner. Each volume was registered, re-sampled to 1.00 x 1.00 x 1.00 mm(3) voxel size and spatially normalized into a standard proportional stereotaxic space using SPM99. Dentate/interposed nuclei were traced on axial images and saved as regions of interest using MRIcro-software by two independent examiners. A probabilistic 3D MRI atlas of the cerebellar dentate/interposed nuclei is presented based on findings in all subjects.

High diagnostic accuracy, emerging whole-body concepts, and lack of side effects combine to render MRI a natural candidate for screening purposes. The aim of this study was to evaluate the technical feasibility of a comprehensive multiorgan-targeting MRI examination and determine the frequency of findings in subjects without a history of serious disease.The study group was composed of 331 subjects. The MRI protocol (mean examination time, 63 min) encompassed the target organs: the brain, arterial system, heart, and colon. Diagnoses were deemed relevant if the physician had to inform the subject about the findings. Subjects with a history of serious illnesses were excluded from subsequent analysis (n=33). All analyses were performed for the resulting subgroup of 298 subjects (247 men, 51 women; mean age, 49.7 years).All 298 examinations were diagnostic excluding eight MR colonography components in which remaining stool hampered reliable diagnosis. Follow-up or radiologic confirmation could be obtained in 75% of all cases with relevant findings (128/169); only one false-positive result was encountered. Of the study group, 21% exhibited signs of atherosclerotic disease. Two cerebral infarctions and one myocardial infarction, previously unknown, were encountered; 12% had peripheral vascular disease. Twelve colonic polyps and nine pulmonary lesions were correctly detected. Of all MRI examinations, 29% revealed relevant additional findings in nontargeted organs. Only one minor allergoid reaction was encountered.The presented data point toward an increased use of MRI for screening in the future, but to date screening MRI should not be performed outside a research setting because the cost-benefit relation is unclear.

Abstract The human hippocampus plays a central role in various neuropsychiatric disorders, such as temporal lobe epilepsy (TLE), Alzheimer's dementia, mild cognitive impairment, and schizophrenia. Its volume, morphology, inner structure, and function are of scientific and clinical interest. Magnetic resonance (MR) imaging is a widely employed tool in neuroradiological workup regarding changes in brain anatomy, (sub‐) volumes, and cerebral function including the hippocampus. Gain in intrinsic MR signal provided by higher field strength scanners and concomitant improvements in spatial resolution seem highly valuable. An examination protocol permitting complete, high‐resolution imaging of the human hippocampus at 7 T was implemented. Coronal proton density, T2, T2*, and fluid‐attenuated inversion recovery contrasts were acquired as well as an isotropic 3D magnetization‐prepared rapid acquisition gradient‐echo (500 μm isotropic voxel dimension, noninterpolated). Observance of energy deposition restrictions within acceptable scan times remained challenging in the acquisition of thin, spin‐echo‐based sections. At the higher resolution enabled by 7 T, demarcation of the hippocampus and some internal features including gray/white matter differentiation and depiction of the hippocampal mantle becomes much more viable when compared with 1.5 T; thus, in the future, this imaging technology might help in the diagnosis of subtle hippocampal changes. © 2008 Wiley‐Liss, Inc.

Objective To determine the safety and tolerability of gadobutrol in a large number of non-selected patients from routine clinical radiology practices. Materials and methods Six prospectively planned, observational surveillance studies were conducted at more than 300 institutions in Europe and Canada from 2000 to 2007. Demographic and medical status data, details of the diagnostic procedure, contrast agent administration and adverse drug reaction (ADR) data were collected using a standardized questionnaire. Results A total of 14,299 patients were enrolled. The mean age of the patients was 53.7 years; 1.3% of the patients were <18 years old and 40.8% were 60 years or older. The body regions most frequently examined were head/neck/brain (54.3%), followed by spine (7.2%), pelvis/joints/limbs (6.7%) and multiple body regions (6.4%). Gadobutrol-enhanced magnetic resonance angiography (MRA) was performed in 14.7% of patients. Overall, the mean volume of gadobutrol administered for contrast-enhanced magnetic resonance imaging was 12 mL (0.16 mmol gadolinium [Gd]/kg body weight [BW]; mean BW: 75.5 kg), whereas for contrast-enhanced MRA the mean volume was 15.7 mL (0.21 mmol Gd/kg BW). Seventy-eight of the 14,299 patients (0.55%) reported at least one ADR. Two (0.01%) serious ADRs were reported. The most frequently reported ADR was nausea, which occurred in 36 patients (0.25%). Conclusion Gadobutrol 1.0 M is very well tolerated and has a good safety profile. The occurrence of ADRs observed following the intravenous injection of gadobutrol is comparable with the published data of other Gd-based contrast agents.

Conduct disorder (CD) prior to age 15 is a precursor of schizophrenia in a minority of cases and is associated with violent behavior through adulthood, after taking account of substance misuse. The present study used structural magnetic imaging to examine gray matter (GM) volumes among 27 men with schizophrenia preceded by CD (SZ+CD), 23 men with schizophrenia but without CD (SZ–CD), 27 men with CD only (CD), and 25 healthy (H) men. The groups with schizophrenia were similar in terms of age of onset and duration of illness, levels of psychotic symptoms, and medication. The 2 groups with CD were similar as to number of CD symptoms, lifelong aggressive behavior, and number of criminal convictions. Men with SZ+CD, relative to those with SZ–CD, displayed (1) increased GM volumes in the hypothalamus, the left putamen, the right cuneus/precuneus, and the right inferior parietal cortex after controlling for age, alcohol, and drug misuse and (2) decreased GM volumes in the inferior frontal region. Men with SZ+CD (relative to the SZ–CD group) and CD (relative to the H group) displayed increased GM volumes of the hypothalamus and the inferior and superior parietal lobes, which were not associated with substance misuse. Aggressive behavior, both prior to age 15 and lifetime tendency, was positively correlated with the GM volume of the hypothalamus. Thus, among males, SZ+CD represents a distinct subtype of schizophrenia. Although differences in behavior emerge in childhood and remain stable through adulthood, further research is needed to determine whether the differences in GM volumes result from abnormal neural development distinct from that of other males developing schizophrenia.

The aim of this study was to assess the diagnostic benefit of diffusion-weighted imaging (DWI) in an (18)F-FDG PET/MR imaging protocol for whole-body staging of women with primary or recurrent malignancies of the pelvis.Forty-eight patients with a primary pelvic malignancy or suspected recurrence of a pelvic malignancy were included in our study. All patients underwent a whole-body (18)F-FDG PET/MR imaging examination that included DWI. Two radiologists separately evaluated the PET/MR imaging datasets without DWI followed by a second interpretation with DWI. First, both readers identified all primary tumors, as well as lymph node and distant metastases. In a second session, PET and DWI data were assessed qualitatively. Image interpretation comprised lesion conspicuity defined as visual lesion-to-background contrast (4-point ordinal scale) and diagnostic confidence (3-point ordinal scale) for all tumors. The results from histopathologic examination and cross-sectional imaging follow-up (≥6 mo) were used as the reference standard. Statistical analysis was performed to assess the significance of differences between obtained values.Among the 122 suspected lesions seen, 98 (80.3%) were considered malignant. PET/MR imaging without DWI had a sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of 92.9%, 87.5%, 96.8%, 75.0%, and 91.8%, respectively, for the detection of malignant lesions. PET/MR imaging with DWI had slightly higher values (94.9%, 83.3%, 95.9%, 80.0%, and 92.6%, respectively), but the difference was not significant (P > 0.05). In the qualitative assessment of lesion-to-background contrast, PET had significantly (P < 0.05) higher values (3.79 ± 0.58) than DWI (3.63 ± 0.77). Furthermore, significantly (P < 0.05) higher scores were found for diagnostic confidence using PET (2.68 ± 0.64) for the determination of malignant lesions, when compared with DWI (2.53 ± 0.69).DWI in PET/MR imaging has no diagnostic benefit for whole-body staging of women with pelvic malignancies. The omission of DWI for staging or restaging gynecologic cancer may significantly reduce examination times, thus increasing patient comfort without a relevant decrease in diagnostic competence.

Background To evaluate a potential correlation of the maximum standard uptake value (SUVmax) and the minimum apparent diffusion coefficient (ADCmin) in primary and recurrent cervical cancer based on integrated PET/MRI examinations. Methods 19 consecutive patients (mean age 51.6 years; range 30–72 years) with histopathologically confirmed primary cervical cancer (n = 9) or suspected tumor recurrence (n = 10) were prospectively enrolled for an integrated PET/MRI examination. Two radiologists performed a consensus reading in random order, using a dedicated post-processing software. Polygonal regions of interest (ROI) covering the entire tumor lesions were drawn into PET/MR images to assess SUVmax and into ADC parameter maps to determine ADCmin values. Pearson’s correlation coefficients were calculated to assess a potential correlation between the mean values of ADCmin and SUVmax. Results In 15 out of 19 patients cervical cancer lesions (n = 12) or lymph node metastases (n = 42) were detected. Mean SUVmax (12.5±6.5) and ADCmin (644.5±179.7×10−5 mm2/s) values for all assessed tumor lesions showed a significant but weak inverse correlation (R = −0.342, p<0.05). When subdivided in primary and recurrent tumors, primary tumors and associated primary lymph node metastases revealed a significant and strong inverse correlation between SUVmax and ADCmin (R = −0.692, p<0.001), whereas recurrent cancer lesions did not show a significant correlation. Conclusions These initial results of this emerging hybrid imaging technique demonstrate the high diagnostic potential of simultaneous PET/MR imaging for the assessment of functional biomarkers, revealing a significant and strong correlation of tumor metabolism and higher cellularity in cervical cancer lesions.

Positron emission tomography/magnetic resonance imaging (PET/MRI) requires efficient scan protocols for whole-body cancer staging. The aim of this study was to evaluate if the application of diffusion-weighted MR imaging (DWI) results in a diagnostic benefit for lesion detection in oncologic patients if added to a whole-body [18F]-fluorodesoxyglucose ([18F]-FDG) PET/MRI protocol.25 consecutive oncologic patients (16 men, 9 women; age 57 ± 12 years) prospectively underwent whole-body [18F]-FDG-PET/MRI including DWI on a hybrid PET/MRI scanner. A team of two readers assessed [18F]-FDG PET/MRI without DWI for primary tumors and metastases. In a second session, now considering DWI, readers reassessed [18F]-FDG PET/MRI accordingly. Additionally, the lesion-to-background contrast on [18F]-FDG PET and DWI was rated qualitatively (0, invisible; 1, low; 2, intermediate; 3, high). Wilcoxon's signed-rank test was performed to test for differences in the lesion-to-background contrast.49 lesions were detected in 16 patients (5 primaries, 44 metastases). All 49 lesions were concordantly detected by [18F]-FDG PET/MRI alone and [18F]-FDG PET/MRI with DWI. The lesion-to-background contrast on DWI compared to [18F]-FDG PET was rated lower in 22 (44.9%) of 49 detected lesions resulting in a significantly higher lesion-to-background contrast on [18F]-FDG PET compared to DWI (P=0.001).DWI as part of whole-body [18F]-FDG PET/MRI does not benefit lesion detection. Given the necessity to optimize imaging protocols with regard to patient comfort and efficacy, DWI has to be questioned as a standard tool for whole-body staging in oncologic PET/MRI.