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(18)F-FDG PET/MRI might be the diagnostic method of choice for Hodgkin lymphoma patients, as it combines significant metabolic information from PET with excellent soft-tissue contrast from MRI and avoids radiation exposure from CT. However, a major issue is longer examination times than for PET/CT, especially for younger children needing anesthesia. Thus, a targeted selection of suitable whole-body MRI sequences is important to optimize the PET/MRI workflow. Methods: The initial PET/MRI scans of 84 EuroNet-PHL-C2 study patients from 13 international PET centers were evaluated. In each available MRI sequence, 5 PET-positive lymph nodes were assessed. If extranodal involvement occurred, 2 splenic lesions, 2 skeletal lesions, and 2 lung lesions were also assessed. A detection rate was calculated dividing the number of visible, anatomically assignable, and measurable lesions in the respective MRI sequence by the total number of lesions. Results: Relaxation time–weighted (T2w) transverse sequences with fat saturation (fs) yielded the best result, with detection rates of 95% for nodal lesions, 62% for splenic lesions, 94% for skeletal lesions, and 83% for lung lesions, followed by T2w transverse sequences without fs (86%, 49%, 16%, and 59%, respectively) and longitudinal relaxation time–weighted contrast-enhanced transverse sequences with fs (74%, 35%, 57%, and 55%, respectively). Conclusion: T2w transverse sequences with fs yielded the highest detection rates and are well suited for accurate whole-body PET/MRI in lymphoma patients. There is no evidence to recommend the use of contrast agents.

Purpose To assess the additional value of quantitative tCho evaluation to diagnose malignancy and lymph node metastases in suspicious lesions on multiparametric breast MRI (mpMRI, BI-RADS 4, and BI-RADS 5). Methods One hundred twenty-one patients that demonstrated suspicious multiparametric breast MRI lesions using DCE, T2w, and diffusion-weighted (DW) images were prospectively enrolled in this IRB-approved study. All underwent single-voxel proton MR spectroscopy (1H-MRS, point-resolved spectroscopy sequence, TR 2000 ms, TE 272 ms) with and without water suppression. The total choline (tCho) amplitude was measured and normalized to millimoles/liter according to established methodology by two independent readers (R1, R2). ROC-analysis was employed to predict malignancy and lymph node status by tCho results. Results One hundred three patients with 74 malignant and 29 benign lesions had full 1H-MRS data. The area under the ROC curve (AUC) for prediction of malignancy was 0.816 (R1) and 0.809 (R2). A cutoff of 0.8 mmol/l tCho could diagnose malignancy with a sensitivity of > 95%. For prediction of lymph node metastases, tCho measurements achieved an AUC of 0.760 (R1) and 0.788 (R2). At tCho levels Conclusion Quantitative tCho evaluation from 1H-MRS allowed diagnose malignancy and lymph node status in breast lesions suspicious on multiparametric breast MRI. tCho therefore demonstrated the potential to downgrade suspicious mpMRI lesions and stratify the risk of lymph node metastases for improved patient management. Key Points • Quantitative tCho evaluation can distinguish benign from malignant breast lesions suspicious after multiparametric MRI assessment. • Quantitative tCho levels are associated with lymph node status in breast cancer. • Quantitative tCho levels are higher in hormonal receptor positive compared to hormonal receptor negative lesions.

Machine learning classifications of first-episode psychosis (FEP) using neuroimaging have predominantly analyzed brain volumes. Some studies examined cortical thickness, but most of them have used parcellation approaches with data from single sites, which limits claims of generalizability. To address these limitations, we conducted a large-scale, multi-site analysis of cortical thickness comparing parcellations and vertex-wise approaches. By leveraging the multi-site nature of the study, we further investigated how different demographical and site-dependent variables affected predictions. Finally, we assessed relationships between predictions and clinical variables. 428 subjects (147 females, mean age 27.14) with FEP and 448 (230 females, mean age 27.06) healthy controls were enrolled in 8 centers by the ClassiFEP group. All subjects underwent a structural MRI and were clinically assessed. Cortical thickness parcellation (68 areas) and full cortical maps (20,484 vertices) were extracted. Linear Support Vector Machine was used for classification within a repeated nested cross-validation framework. Vertex-wise thickness maps outperformed parcellation-based methods with a balanced accuracy of 66.2% and an Area Under the Curve of 72%. By stratifying our sample for MRI scanner, we increased generalizability across sites. Temporal brain areas resulted as the most influential in the classification. The predictive decision scores significantly correlated with age at onset, duration of treatment, and positive symptoms. In conclusion, although far from the threshold of clinical relevance, temporal cortical thickness proved to classify between FEP subjects and healthy individuals. The assessment of site-dependent variables permitted an increase in the across-site generalizability, thus attempting to address an important machine learning limitation.

The aim of this retrospective cross-sectional study was to provide an MRI-based examination framework of venous malformations (VMs) infiltrating the sciatic nerve and determine the frequency of nerve infiltration patterns and muscle involvement in correlation to the patients’ quality of life. Pelvic and lower limb MR images of 378 patients with vascular malformations were examined retrospectively. Pain levels and restriction of motion were evaluated with a questionnaire. Cross-sectional areas of affected nerves were compared at standardized anatomical landmarks. Intraneural infiltration patterns and involvement of muscles surrounding the sciatic nerve were documented. Sciatic nerve infiltration occurred in 23/299 patients (7.7%) with VM. In all cases (23/23; 100%), gluteal or hamstring muscles surrounding the nerve were affected by the VM. Infiltrated nerves were enlarged and showed signal alterations (T2-hyperintensity) compared to the unaffected side. Enlarged nerve cross-sectional areas were associated with elevated pain levels. Three nerve infiltration patterns were observed: subepineurial (12/23; 52.2%), subparaneurial (6/23; 26.1%) and combined (5/23; 21.7%) infiltration. This study provides a clinically relevant assessment for sciatic nerve infiltration patterns and muscle involvement of VMs, while suggesting that VMs in gluteal and hamstring muscles require closer investigation of the sciatic nerve by the radiologist.

Objective The aim of this study was to evaluate the safety and clinical outcomes of percutaneous sclerotherapy of venous disorders of the labia majora in patients with vascular malformations of the lower limbs. Methods Thirty percutaneous sclerotherapy treatments were performed over a 6-year period among 17 female patients with symptomatic venous malformation (VM) or secondary varicosis of the labia majora. Four patients were treated with sclerotherapy alone, 13 patients had additional procedures to control the VM before sclerotherapy. Polidocanol was used as sclerosant. Indications for sclerotherapy included pain, bleeding, thrombophlebitis, and swelling. Genitourinary symptoms were recorded. The number of treatments and procedure-related complications were registered. Complications were classified according to the Society of Interventional Radiology (SIR) classification system (grade A-E). The 3-month postintervention follow-up included magnetic resonance imaging, clinical examination, and a symptom-related questionnaire. If no reintervention was necessary, consultation was scheduled biannually. Results All patients had local swelling and pain; only a fraction of the patients had further symptoms with bleeding or thrombophlebitis (47% each). Eight patients required reintervention. No major complications were observed; minor complications such as postprocedural swelling occurred in 29% (SIR grade A), pain occurred in 17% (SIR grade B), and skin blistering developed in 5% (SIR grade B). Upon follow-up examination after a median of 40 months, 76% showed complete relief of symptoms, and 23% reported partial relief. All patients reported a substantial reduction in pain (75% >5 points in visual analogue scale) and swelling (88% complete cessation). Conclusions Percutaneous sclerotherapy is a safe and effective treatment option of VM and secondary varicosis of the labia majora.

Background The manifestation of chronic pain and psychological impairments are related to alterations of neurotransmitter metabolism in cerebral pain processing regions, e.g., anterior cingular cortex (ACC), insula. Magnetic resonance spectroscopy ((1)H-MRS) enables in vivo quantification of neurotransmitters in the brain and was applied in this study to examine the hypothesized chronic pain-related imbalance between excitatory (glutamatergic) and inhibitory (GABA-ergic) neurotransmitter turnovers in the brain of patients with nonspecific chronic pain. Materials and methods A total of 19 patients with nonspecific chronic (> 3 months) back pain and 19 age- and gender-matched healthy subjects participated in this study. Glutamate and GABA as well as glutamate/GABA ratios were determined in the ACC and insula using (1)H-MRS. Sociodemographic, psychological, and pain-related features were measured with standardized questionnaires. Results There was a strong variance of glutamate/GABA ratios for both patients and healthy subjects with no significant difference between the two groups. Regression analysis revealed certain significant predictors, such as anxiety as causal variable for reduced glutamate and depression and age as predictors for reduced GABA in ACC. In the patient group, intensity of pain was a significant predictor for glutamate and GABA levels in the insula. Conclusions Despite the uniform diagnosis of nonspecific chronic back pain, we observed a strong variance of neurotransmitters in cerebral pain processing regions. It is necessary to include psychological as well as clinical parameters (e.g., intensity of pain or depression) for a proper interpretation of neurotransmitter turnovers.

Interventional studies suggest that changes in physical fitness affect brain function and structure. We studied the influence of high intensity physical exercise on hippocampal volume and metabolism in 17 young healthy male adults during a 6-week exercise program compared with matched controls. We further aimed to relate these changes to hypothesized changes in exercised-induced brain-derived neurotrophic factor (BDNF), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α). We show profound improvement of physical fitness in most subjects and a positive correlation between the degree of fitness improvement and increased BDNF levels. We unexpectedly observed an average volume decrease of about 2%, which was restricted to right hippocampal subfields CA2/3, subiculum, and dentate gyrus and which correlated with fitness improvement and increased BDNF levels negatively. This result indicates that mainly those subjects who did not benefit from the exercise program show decreased hippocampal volume, reduced BDNF levels, and increased TNF-α concentrations. While spectroscopy results do not indicate any neuronal loss (unchanged N-acetylaspartate levels) decreased glutamate-glutamine levels were observed in the right anterior hippocampus in the exercise group only. Responder characteristics need to be studied in more detail. Our results point to an important role of the inflammatory response after exercise on changes in hippocampal structure.

Background Glutamatergic dysfunction, deregulated mitochondrial metabolism and alterations of membrane phospholipids are considered as core pathology of psychosis, and have been studied in schizophrenic illness using magnetic resonance spectroscopy (MRS). Combining 1H- and 31P-MRS, this study investigates these aspects in Ultra-high risk (UHR-T) patients right after transition to psychosis (T0) and after a two years interval (T1) in a naturalistic longitudinal design, including treatment as usual by cognitive-behavioral therapy (CBT) and pharmacotherapy with second generation antipsychotics. Methods We applied 3 T chemical shift imaging (3D 31P-MRS, 2D 1H-MRS) and hippocampal single-voxel 1H-MRS in 29 neuroleptic-naïve UHR-T patients and 27 healthy controls matched for age and gender. Glutamate (Glu) and N-acetyl-aspartate (NAA) reflect neuronal functioning, phosphocreatine (PCr), adenosine triphosphate (ATP) and NAA indicate mitochondrial function and energy metabolism, and phosphomono- and diester indicate the balance of phospholipid synthesis (PME) and -breakdown (PDE). Psychopathology was assessed using the CAARMS, BPRS-E and SCL-90-R. Generalized linear mixed models were used to examine case-control differences in metabolite changes over time, and associations with clinical improvement. Results At T0, cross-sectional analysis revealed decreased NAA, Glu and PME levels in the left dorsolateral prefrontal cortex (DLPFC) and thalamus of UHR-T patients as well as higher PCr and lower PDE levels in the right hippocampus. (ii) Follow-up analysis (T1) showed in patients a significant increase of Glu in the bilateral DLPFC and the right thalamus, while a decrease of PCr was observed in the right hippocampus. Discussion The observed metabolite pattern at T0 likely reflects a hypofunction of glutamatergic neurons and a disturbance of membrane phospholipid turnover in fronto-thalamo-hippocampal networks during the first acute onset phase of psychotic illness. The pattern of changes at T1 is suggestive for an improvement of neuronal functioning in these networks that is caused by therapy, and presumably underlies the observed clinical improvement in terms of negative symptoms and cognitive impairment.

Background Glutamatergic dysfunction, deregulated mitochondrial metabolism and alterations of membrane phospholipids have been extensively investigated in schizophrenic illness by using in vivo magnetic resonance spectroscopy (MRS). Findings in the ultra-high risk (UHR) phase of psychotic illness, however, are still rare and inconsistent. Combining both 1H- and 31P-MRS, this study investigates these aspects in the different UHR patient subgroups as defined by PACE (Personal Assessment and Crisis Evaluation) criteria. Methods We applied 3 T chemical shift imaging (3D 31P-MRS, 2D 1H-MRS) and hippocampal single-voxel MRS in 69 neuroleptic-naïve UHR patients (age: 26.2 ± 6.2y; males 59.4% 41/69, attenuated symptoms (AS) n=50, BLIPS n=5, genetic risk (GR) n=8, AS+GR n=6; transition rate 17.2%, all transitions in the AS or BLIPS group) and 61 healthy controls (age: 25.2 ± 4.8y; males 54.1% 33/61). 11 metabolite markers were investigated (neuronal/mitochondrial metabolism: glutamate (Glu), N-acetyl-aspartate (NAA), phosphocreatine (PCr), and adenosine triphosphate (ATP); phospholipid synthesis: phosphomonoester/-metabolites (PME, Peth, Pch); phospholipids breakdown: phosphodiester/-metabolites (PDE, Gpeth, Gpch); astrocyte activation: myo-Inositol (mI)) in 5 brain regions (dorsolateral prefrontal cortex, DLPFC; dorsomedial prefrontal cortex, DMPFC; dorsal anterior cingulate cortex, dACC; mediodorsal thalamus, Th; and hipoocampus, Hip). Psychopathology was assessed using the CAARMS-Interview as well as PANSS, BPRS-E and SCL-90-R ratings. Statistical analysis included multi-and univariate ANOVA, Kruskal-Wallis-tests and correlation analysis. Results (i) In all UHR individuals (and also in the AS and BLIPS subgroup), NAA was reduced in the left Th. There was no alteration of Glu. While PCr was increased in the left DLPFC, left dACC (right trend) and in the right Hip, ATP was not different from controls. PME were decreased in the right Hip, PDE did not differ from controls. mI was found increased in the left Hip. (ii) In the GR subgroup PCr was increased in the bilateral Th. The PME metabolite Peth was decreased in the right Th. PDE were increased in the left dACC. mI was increased in the left Th. Discussion While the observed pattern of metabolite abnormalities in the AS and BLIPS risk group suggests a pathology that affects the left thalamus (NAA decrease), left DLPFC, dACC and bilateral Hip (left: PCr increase, PME decrease; right mI increase), the pathology of the GR group appears more focussed on the bilateral Th (bil. PCr increase, right PME decrease, left mI increase) and left dACC (PDE increase). The results suggest a functional disturbance of networks including the left DLPFC, dACC, bilateral Hip and Th, whereby the latter might be more an expression of a genetic risk profile.

In vivo(1)H MR spectroscopic detection of pain associated metabolic changes in the human brain may allow for an objective evaluation of the perceived pain intensity and assessment of the involved neurotransmitters. Ultimately, it may lead to a deeper understanding of the mechanisms that underlie neuronal pain processing. The present study reports results of time-resolved measurements of acute heat pain induced changes of the excitatory (Glx) and inhibitory (GABA+) neurotransmitter turnover in the anterior cingulate cortex (ACC) and occipital cortex (OC) by using (1)H MEGA-PRESS spectroscopy. In ACC and OC, the ratio Glx/tCr increased by median values of 21.5% (p < 0.001) and 15.7% (p < 0.001), respectively. At the same time, GABA+/tCr decreased by median values of 15.1% (p = 0.114) in ACC and 12.7% (p < 0.001) in OC. To our knowledge, this study demonstrates for the first time the possibility of quantifying pain-induced neurotransmitter changes in the brain by using functional (1)H MEGA-PRESS. The increase of Glx/tCr may be ascribed to an elevated glutamatergic turnover, while the decrease of GABA+/tCr may reflect reduced activity of the inhibitory system in ACC and OC during pain processing.

The Publisher regrets that this article is an accidental duplication of an article that has already been published, http://dx.doi.org/10.1016/j.neuroimage.2010.11.069. The duplicate article has therefore been withdrawn.

Reliable detection of metabolic changes in the brain in vivo induced by chronic low back pain may provide improved understanding of neurophysiological mechanisms underlying the manifestation of chronic pain. In the present study, absolute concentrations of N-acetyl-aspartate (NAA), creatine (Cr), total choline (tCho), myo-inositol (mI), glutamate (Glu) and glutamine (Gln) were measured in three different pain processing cortical regions (anterior insula, anterior cingulate cortex, and thalamus) of ten patients with non-specific chronic low back pain by means of proton MR spectroscopy ((1)H-MRS) and compared to matched healthy controls. Significant decrease of Glu was observed in the anterior cingulate cortex of patients. Patients also revealed a trend of decreasing Gln concentrations in all investigated brain areas. Reductions of NAA were observed in the patient group in anterior insula and in anterior cingulated cortex, whereas mI was reduced in anterior cingulated cortex and in thalamus of patients. Reduced concentrations of Glu and Gln may indicate disordered glutamatergic neurotransmission due to prolonged pain perception, whereas decrease of NAA and mI may be ascribed to neuron and glial cell loss. No significant changes were found for Cr. The morphological evaluation of anatomic brain data revealed a significantly decreased WM volume of 17% (p

Non-invasive in vivo detection of cortical neurotransmitter concentrations and their changes in the presence of pain may help to better understand the biochemical principles of pain processing in the brain. In the present study acute heat pain related changes of the excitatory neurotransmitter glutamate were investigated in the anterior insular cortex of healthy volunteers by means of time-resolved functional proton magnetic resonance spectroscopy (1H-MRS). Dynamic metabolite changes were estimated with a temporal resolution of five seconds by triggering data acquisition to the time course of the cyclic stimulus application. An overall increase of glutamate concentration up to 18% relative to the reference non-stimulus condition was observed during the application of short pain stimuli.

IntroductionMagnetic resonance spectroscopy (MRS) using 2D-chemical shift imaging (CSI) allows the quantification of brain metabolites in vivo across several brain regions. Previous studies using 31Phosphorus MRS have shown alterations of phospholipid compounds and high-energy phosphates like ATP in prefrontal and temporal regions in schizophrenia.AimWe used a monozygotic (MZ) co-twin study design to examine whether metabolic alterations are due to genetic effects or the expression of disease phenotype.Methods31P-MRS with 2D-CSI was applied at 1.5 T in 8 MZ twin pairs (3 male, 5 female; mean age 33.8, SD 13.1) discordant for a DSM-IV and ICD-10 diagnosis of either schizophrenia (4 pairs), acute schizophreniform psychosis (1 pair), or schizoaffective disorder (3 pairs)) and 8 age- and gender-matched healthy control MZ twins (mean age: 32.9, SD 14.3). Metabolic profiles were compared using oneway ANOVAs.ResultsVoxel-wise comparisons between affected twins and healthy control twins revealed increased PDE concentrations in right cerebellum and increased ATP concentrations in right frontal cortex, insular cortex and bilateral cerebellum. Alterations in energy metabolism were shown in healthy co-twins compared to healthy control twins with an increase in PDE concentrations in right posterior lateral cerebellum, an increase in ATP concentration in left lateral prefrontal cortex as well as left anterior/ lateral temporal cortex and an increase in PCr in left lateral prefrontal cortex.ConclusionsOur findings suggest that metabolic alterations in schizophrenia result from a combination of both genetic effects and disease manifestation, which can be further explored in larger twin samples.