Spatial Distribution and Long-Term Alterations of Peripheral Nerve Lesions in Schwannomatosis.

Purpose To examine the spatial distribution and long-term alterations of peripheral nerve lesions in patients with schwannomatosis by in vivo high-resolution magnetic resonance neurography (MRN). Methods In this prospective study, the lumbosacral plexus as well as the right sciatic, tibial, and peroneal nerves were examined in 15 patients diagnosed with schwannomatosis by a standardized MRN protocol at 3 Tesla. Micro-, intermediate- and macrolesions were assessed according to their number, diameter and spatial distribution. Moreover, in nine patients, peripheral nerve lesions were compared to follow-up examinations after 39 to 71 months. Results In comparison to intermediate and macrolesions, microlesions were the predominant lesion entity at the level of the proximal (p < 0.001), mid- (p < 0.001), and distal thigh (p < 0.01). Compared to the proximal calf level, the lesion number was increased at the proximal (p < 0.05), mid- (p < 0.01), and distal thigh level (p < 0.01), while between the different thigh levels, no differences in lesion numbers were found. In the follow-up examinations, the lesion number was unchanged for micro-, intermediate and macrolesions. The diameter of lesions in the follow-up examination was decreased for microlesions (p < 0.01), not different for intermediate lesions, and increased for macrolesions (p < 0.01). Conclusion Microlesions represent the predominant type of peripheral nerve lesion in schwannomatosis and show a rather consistent distribution pattern in long-term follow-up. In contrast to the accumulation of nerve lesions, primarily in the distal nerve segments in NF2, the lesion numbers in schwannomatosis peak at the mid-thigh level. Towards more distal portions, the lesion number markedly decreases, which is considered as a general feature of other types of small fiber neuropathy.

Dorsal Root Ganglion Morphometric Changes Under Oxaliplatin Treatment : Longitudinal Assessment by Computed Tomography.

PURPOSE: Magnetic resonance neurography (MRN) can detect dorsal root ganglia (DRG) hypertrophy in patients with oxaliplatin-induced peripheral neuropathy (OXIPN) but is difficult to apply in clinical daily practice. Aims of this study were (i) to assess whether DRG volume is reliably measurable by routine computed tomography (CT) scans, (ii) to measure longitudinal changes in DRG during and after oxaliplatin administration and (iii) to assess correlation between DRG morphometry and individual oxaliplatin dose. METHODS: For comparison of MRN and CT measurements, CT scans of 18 patients from a previous MRN study were analyzed. For longitudinal assessment of DRG size under treatment, 96 patients treated with oxaliplatin between January and December 2014 were enrolled retrospectively. DRG volumetry was performed by analyzing routine CT scans, starting with the last scan before oxaliplatin exposure (t0) and up to four consecutive timepoints after initiation of oxaliplatin therapy (t1-t4) with the following median and ranges in months: 3.1 (0.4-4.9), 6.2 (5.3-7.8), 10.4 (8.2-11.9), and 18.4 (12.8-49.8). RESULTS: DRG volume measured in CT showed a moderately strong correlation with MRN (r = 0.51, p < 0.001) and a strong correlation between two consecutive CTs (r = 0.77, p < 0.001). DRG volume increased after oxaliplatin administration with a maximum at timepoint t2. Higher cumulative oxaliplatin exposure was associated with significantly higher absolute DRG volumes (p = 0.005). Treatment discontinuation was associated with a nonsignificant trend towards lower relative DRG volume changes (p = 0.08). CONCLUSION: CT is a reliable method for continuous DRG morphometry; however, since no standardized assessment of OXIPN was performed in this retrospective study, correlations between DRG size, cumulative oxaliplatin dose and clinical symptoms in future prospective studies are needed to establish DRG size as a potential OXIPN biomarker.

Long-term Follow-up and Histological Correlation of Peripheral Nervous System Alterations in Neurofibromatosis Type 2.

PURPOSE: To examine long-term alterations of the dorsal root ganglia (DRG) and the peripheral nerve in patients with neurofibromatosis type 2 (NF2) by in vivo high-resolution magnetic resonance neurography (MRN) and their correlation to histology. METHODS: In this prospective study the lumbosacral DRG, the right sciatic, tibial, and peroneal nerves were examined in 6 patients diagnosed with NF2 and associated polyneuropathy (PNP) by a standardized MRN protocol at 3 T. Volumes of DRG L3-S2 as well as peripheral nerve lesions were assessed and compared to follow-up examinations after 14-100 months. In one patient, imaging findings were further correlated to histology. RESULTS: Follow-up MRN examination showed a non-significant increase of volume for the DRG L3: +0.41% (p = 0.10), L4: +22.41% (p = 0.23), L5: +3.38% (p = 0.09), S1: +10.63% (p = 0.05) and S2: +1.17% (p = 0.57). Likewise, peripheral nerve lesions were not significantly increased regarding size (2.18 mm2 vs. 2.15 mm2, p = 0.89) and number (9.00 vs. 9.33, p = 0.36). Histological analyses identified schwannomas as the major correlate of both DRG hyperplasia and peripheral nerve lesions. For peripheral nerve microlesions additionally clusters of onion-bulb formations were identified. CONCLUSION: Peripheral nervous system alterations seem to be constant or show only a minor increase in adult NF2. Thus, symptoms of PNP may not primarily attributed to the initial schwannoma growth but to secondary long-term processes, with symptoms only occurring if a certain threshold is exceeded. Histology identified grouped areas of Schwann cell proliferations as the correlate of DRG hyperplasia, while for peripheral nerve lesions different patterns could be found.

Pre-examinations Improve Automated Metastases Detection on Cranial MRI.

MATERIALS AND METHODS: Our local ethics committee approved this retrospective monocenter study.First, a dual-time approach was assessed, for which the CNN was provided sequences of the MRI that initially depicted new MM (diagnosis MRI) as well as of a prediagnosis MRI: inclusion of only contrast-enhanced T1-weighted images (CNNdual_ce) was compared with inclusion of also the native T1-weighted images, T2-weighted images, and FLAIR sequences of both time points (CNNdual_all).Second, results were compared with the corresponding single time approaches, in which the CNN was provided exclusively the respective sequences of the diagnosis MRI.Casewise diagnostic performance parameters were calculated from 5-fold cross-validation. RESULTS: In total, 94 cases with 494 MMs were included. Overall, the highest diagnostic performance was achieved by inclusion of only the contrast-enhanced T1-weighted images of the diagnosis and of a prediagnosis MRI (CNNdual_ce, sensitivity = 73%, PPV = 25%, F1-score = 36%). Using exclusively contrast-enhanced T1-weighted images as input resulted in significantly less false-positives (FPs) compared with inclusion of further sequences beyond contrast-enhanced T1-weighted images (FPs = 5/7 for CNNdual_ce/CNNdual_all, P < 1e-5). Comparison of contrast-enhanced dual and mono time approaches revealed that exclusion of prediagnosis MRI significantly increased FPs (FPs = 5/10 for CNNdual_ce/CNNce, P < 1e-9).Approaches with only native sequences were clearly inferior to CNNs that were provided contrast-enhanced sequences. CONCLUSIONS: Automated MM detection on contrast-enhanced T1-weighted images performed with high sensitivity. Frequent FPs due to artifacts and vessels were significantly reduced by additional inclusion of prediagnosis MRI, but not by inclusion of further sequences beyond contrast-enhanced T1-weighted images. Future studies might investigate different change detection architectures for computer-aided detection.

C-Fiber Loss as a Possible Cause of Neuropathic Pain in Schwannomatosis.

Schwannomatosis is the third form of neurofibromatosis and characterized by the occurrence of multiple schwannomas. The most prominent symptom is chronic pain. We aimed to test whether pain in schwannomatosis might be caused by small-fiber neuropathy. Twenty patients with schwannomatosis underwent neurological examination and nerve conduction studies. Levels of pain perception as well as anxiety and depression were assessed by established questionnaires. Quantitative sensory testing (QST) and laser-evoked potentials (LEP) were performed on patients and controls. Whole-body magnetic resonance imaging (wbMRI) and magnetic resonance neurography (MRN) were performed to quantify tumors and fascicular nerve lesions; skin biopsies were performed to determine intra-epidermal nerve fiber density (IENFD). All patients suffered from chronic pain without further neurological deficits. The questionnaires indicated neuropathic symptoms with significant impact on quality of life. Peripheral nerve tumors were detected in all patients by wbMRI. MRN showed additional multiple fascicular nerve lesions in 16/18 patients. LEP showed significant faster latencies compared to normal controls. Finally, IENFD was significantly reduced in 13/14 patients. Our study therefore indicates the presence of small-fiber neuropathy, predominantly of unmyelinated C-fibers. Fascicular nerve lesions are characteristic disease features that are associated with faster LEP latencies and decreased IENFD. Together these methods may facilitate differential diagnosis of schwannomatosis.

Macroangiopathy is a positive predictive factor for response to immunotherapy.

Immunotherapies demand for predictive biomarkers to avoid unnecessary adverse effects and costs. Analytic morphomics is the technique to use body composition measures as imaging biomarkers for underlying pathophysiology to predict prognosis or outcome to therapy. We investigated different body composition measures to predict response to immunotherapy. This IRB approved retrospective analysis encompassed 147 patients with ipilimumab therapy. Degree of macroangiopathy was quantified with the newly defined total plaque index (TPI), i.e. the body height corrected sum of the soft and hard plaque volume of the infrarenal aorta on portalvenous CT scans. Furthermore, mean psoas density (MPD), different adipose tissue parameters as well as degree of cerebral microangiopathy were extracted from the imaging data. Subsequent multivariate Cox regression analysis encompassed TPI, MPD, serum LDH, S100B, age, gender, number of immunotherapy cycles as well as extent of distant metastases. TPI and MPD correlated positively with PFS in multivariate analysis (p = 0.03 and p = 0.001, respectively). Furthermore, single visceral organ and/or soft tissue involvement significantly decreased progression risk (p = 0.01), whereas increased S100B level showed a trend towards PFS shortening (p = 0.05). In conclusion, degree of macroangiopathy and sarcopenia were independent predictors for outcome to immunotherapy and of equivalent significance compared to other clinical biomarkers.

Peripheral nervous system alterations in infant and adult neurofibromatosis type 2.

OBJECTIVE: To examine the involvement of dorsal root ganglia and peripheral nerves in children with neurofibromatosis type 2 compared to healthy controls and symptomatic adults by in vivo high-resolution magnetic resonance neurography. METHODS: In this prospective multicenter study, the lumbosacral dorsal root ganglia and sciatic, tibial, and peroneal nerves were examined in 9 polyneuropathy-negative children diagnosed with neurofibromatosis type 2 by a standardized magnetic resonance neurography protocol at 3T. Volumes of dorsal root ganglia L3 to S2 and peripheral nerve lesions were assessed and compared to those of 29 healthy children. Moreover, dorsal root ganglia volumes and peripheral nerve lesions were compared to those of 14 adults with neurofibromatosis type 2. RESULTS: Compared to healthy controls, dorsal root ganglia hypertrophy was a consistent finding in children with neurofibromatosis type 2 (L3 +255%, L4 +289%, L5 +250%, S1 +257%, and S2 +218%, p < 0.001) with an excellent diagnostic accuracy. Moreover, peripheral nerve lesions occurred with a high frequency in those children compared to healthy controls (18.89 ± 11.11 vs 0.90 ± 1.08, p < 0.001). Children and adults with neurofibromatosis type 2 showed nonsignificant differences in relative dorsal root ganglia hypertrophy rates (p = 0.85) and peripheral nerve lesions (p = 0.28). CONCLUSIONS: Alterations of peripheral nerve segments occur early in the course of neurofibromatosis type 2 and are evident even in children not clinically affected by peripheral polyneuropathy. While those early alterations show similar characteristics compared to adults with neurofibromatosis type 2, the findings of this study suggest that secondary processes might be responsible for the development and severity of associated polyneuropathy.

Dorsal root ganglia volume is increased in patients with the Fabry-related GLA variant p.D313Y.

PURPOSE: To examine dorsal root ganglia and proximal nerve segments in patients carrying the Fabry-related GLA-gene variant p.D313Y in comparison to patients with classical Fabry mutations and healthy controls by morphometric and functional magnetic resonance neurography. METHODS: This prospective multicenter study examines the lumbosacral dorsal root ganglia and sciatic nerve in 11 female p.D313Y patients by a standardized magnetic resonance neurography protocol at 3 T. Volumes of dorsal root ganglia L3 to S2, permeability of dorsal root ganglia L5 and S1, and spinal nerve L5 as well as cross-sectional area of the sciatic nerve were assessed and compared to 10 females carrying a classical Fabry mutation and 16 healthy female controls. RESULTS: Compared to healthy controls, dorsal root ganglia volumes of p.D313Y females were enlarged by 53% (L3), 48% (L4), 43% (L5), 57% (S1) (p < 0.001), and 55% (S2) (p < 0.05), but less pronounced compared to females carrying a classical Fabry mutation. Compared to healthy controls, p.D313Y patients showed no changes of dorsal root ganglia vascular permeability, while patients with a classical Fabry mutation showed a distinct decrease (p < 0.05). Sciatic nerve cross-sectional area was mildly increased by 6% in p.D313Y as well as in classical Fabry patients (p < 0.05). CONCLUSIONS: Patients carrying the GLA-gene variant p.D313Y show distinctly enlarged dorsal root ganglia, while vascular permeability remains within normal limits. Overall, these alterations partially share characteristics commonly seen in patients with a mutation causing classical FD. This suggests that p.D313Y causes a potentially treatable condition resembling an early stage of Fabry disease.

Susceptibility-weighted imaging in malignant melanoma brain metastasis.

BACKGROUND: The value of cerebral susceptibility-weighted imaging (SWI) in malignant melanoma (MM) patients remains controversial and the effect of melanin on SWI is not well understood. PURPOSE: To systematically analyze the spectrum of intracerebral findings in MM brain metastases (BM) on SWI and to determine the diagnostic value of SWI. STUDY TYPE: Retrospective. POPULATION/SUBJECTS: In all, 100 patients with melanoma BM (69 having received radiotherapy [RT] and 31 RT-naïve) and a control group of 100 melanoma patients without BM were included. For detailed analysis of signal characteristics, 175 metastases were studied. FIELD STRENGTH/SEQUENCE: Gradient echo SWI sequence at 1.5, 3.0, and 9.4 T. ASSESSMENT: Signal characteristics from melanotic and amelanotic BMs on SWI with a focus on blooming artifacts were analyzed, as well as the presence and longitudinal dynamics of isolated SWI blooming artifacts in patients with and without BM. STATISTICAL TESTS: Chi-squared and Student's t-test were used for contingency table measures and group data of signal and clinical characteristics, respectively. RESULTS: Melanotic and amelanotic metastases did not show significant differences of SWI blooming artifacts (38% vs. 43%, P = 0.61). Most metastases without an initial SWI artifact developed a signal dropout during follow-up (80%; 65/81). Isolated SWI artifacts were detected more frequently in patients with BM (20 vs. 9, P = 0.03), of which the majority were found in patients who had received RT (17 vs. 3, P = 0.08). None of these isolated SWI blooming artifacts turned into overt metastases over time (median follow-up: 8.5 months). Similar findings persisted as remnants of successfully treated metastases (88%; 7/8). DATA CONCLUSION: We conclude that SWI provides little additional diagnostic benefit over standard T1 -weighted imaging, as melanin content alone does not cause diagnostically relevant SWI blooming. Signal transition of SWI may rather indicate secondary phenomena like microbleeding and/or metal scavenging. Our results suggest that isolated SWI artifacts do not constitute vital tumor tissue but represent unspecific microbleedings, RT-related parenchymal changes or posttherapeutic remnants of former metastatic lesions. LEVEL OF EVIDENCE: 3 Technical Efficacy Stage: 5 J. Magn. Reson. Imaging 2019;50:1251-1259.

Dorsal root ganglia in vivo morphometry and perfusion in female patients with Fabry disease.

PURPOSE: To examine dorsal root ganglia and the proximal nerve segments in female patients with Fabry disease by functional and morphometric magnetic resonance neurography. METHODS: In this prospective multicenter study the lumbosacral dorsal root ganglia and proximal sciatic nerve were examined in ten female patients with Fabry disease by a standardized magnetic resonance neurography protocol at 3 T. Volumes of dorsal root ganglia L3-S2, permeability of dorsal root ganglia L5 and S1 and the spinal nerve L5 as well as the cross-sectional area of the proximal sciatic nerve were compared to 16 gender-matched healthy controls. RESULTS: Dorsal root ganglia were symmetrically enlarged by 54% (L3), 79% (L4), 60% (L5), 94% (S1), and 106% (S2) (p < 0.001). Additionally, permeability of the blood-tissue interface was decreased by 47% (p < 0.001). This finding was most pronounced in the peripheral zone of the dorsal root ganglia, where the cell bodies of the primary sensory neurons are located (p < 0.001). While spinal nerve permeability showed no differences compared to healthy controls, proximal sciatic nerve cross-sectional area was mildly increased by 6% (p < 0.01). CONCLUSION: Although heterozygous, Fabry females show severe enlarged dorsal root ganglia with a concomitant dysfunctional perfusion, even in patients with minor disease progression and in patients who are not considered for enzyme replacement therapy yet. Alterations in dorsal root ganglia volume and perfusion might serve as a very early in vivo marker for involvement of the peripheral nervous system in Fabry disease, even in patients with residual enzyme activity.

Assessing the predictability of IDH mutation and MGMT methylation status in glioma patients using relaxation-compensated multipool CEST MRI at 7.0 T.

Background: Early identification of prognostic superior characteristics in glioma patients such as isocitrate dehydrogenase (IDH) mutation and O6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation status is of great clinical importance. The study purpose was to investigate the non-invasive predictability of IDH mutation status, MGMT promoter methylation, and differentiation of low-grade versus high-grade glioma (LGG vs HGG) in newly diagnosed patients employing relaxation-compensated multipool chemical exchange saturation transfer (CEST) MRI at 7.0 Tesla. Methods: Thirty-one patients with newly diagnosed glioma were included in this prospective study. CEST MRI was performed at a 7T whole-body scanner. Nuclear Overhauser effect (NOE) and isolated amide proton transfer (APT; downfield NOE-suppressed APT = dns-APT) CEST signals (mean value and 90th signal percentile) were quantitatively investigated in the whole tumor area with regard to predictability of IDH mutation, MGMT promoter methylation status, and differentiation of LGG versus HGG. Statistics were performed using receiver operating characteristic (ROC) and area under the curve (AUC) analysis. Results were compared with advanced MRI methods (apparent diffusion coefficient and relative cerebral blood volume ROC/AUC analysis) obtained at 3T. Results: dns-APT CEST yielded highest AUCs in IDH mutation status prediction (dns-APTmean = 91.84%, P < 0.01; dns-APT90 = 97.96%, P < 0.001). Furthermore, dns-APT metrics enabled significant differentiation of LGG versus HGG (AUC: dns-APTmean = 0.78, P < 0.05; dns-APT90 = 0.83, P < 0.05). There was no significant difference regarding MGMT promoter methylation status at any contrast (P > 0.05). Conclusions: Relaxation-compensated multipool CEST MRI, particularly dns-APT imaging, enabled prediction of IDH mutation status and differentiation of LGG versus HGG and should therefore be considered as a non-invasive MR biomarker in the diagnostic workup.

Sensitivity of different MRI sequences in the early detection of melanoma brain metastases.

BACKGROUND: After the emergence of new MRI techniques such as susceptibility- and diffusion-weighted imaging (SWI and DWI) and because of specific imaging characteristics of melanoma brain metastases (MBM), it is unclear which MRI sequences are most beneficial for detection of MBM. This study was performed to investigate the sensitivity of six clinical MRI sequences in the early detection of MBM. METHODS: Medical records of all melanoma patients referred to our center between November 2005 and December 2016 were reviewed for presence of MBM. Analysis encompassed six MRI sequences at the time of initial diagnosis of first or new MBM, including non-enhanced T1-weighted (T1w), contrast-enhanced T1w (ceT1w), T2-weighted (T2w), T2w-FLAIR, susceptibility-weighted (SWI) and diffusion-weighted (DWI) MRI. Each lesion was rated with respect to its conspicuity (score from 0-not detectable to 3-clearly visible). RESULTS: Of 1210 patients, 217 with MBM were included in the analysis and up to 5 lesions per patient were evaluated. A total of 720 metastases were assessed and all six sequences were available for 425 MBM. Sensitivity (conspicuity ≥2) was 99.7% for ceT1w, 77.0% for FLAIR, 64.7% for SWI, 61.0% for T2w, 56.7% for T1w, and 48.4% for DWI. Thirty-one (7.3%) of 425 lesions were only detectable by ceT1w but no other sequence. CONCLUSIONS: Contrast-enhanced T1-weighting is more sensitive than all other sequences for detection of MBM. Disruption of the blood-brain-barrier is consistently an earlier sign in MBM than perifocal edema, signal loss on SWI or diffusion restriction.

Dorsal root ganglia volume differentiates schwannomatosis and neurofibromatosis 2.

Schwannomatosis and neurofibromatosis type 2 are hereditary tumor syndromes, and peripheral neuropathy has been reported in both. We prospectively applied in vivo morphometric measurement of dorsal root ganglia volume in 16 schwannomatosis patients, 14 neurofibromatosis type 2 patients, and 26 healthy controls by magnetic resonance neurography. Compared to healthy controls, dorsal root ganglia hypertrophy was a consistent finding in neurofibromatosis type 2 (L3, + 267%; L4, + 235%; L5, + 241%; S1, + 300%; S2, + 242%; Bonferroni-adjusted p < 0.001) but not in schwannomatosis. Dorsal root ganglia may be a vulnerable site in origination of areflexia and sensory loss and a useful diagnostic marker in neurofibromatosis type 2. Ann Neurol 2018;83:854-857.

Neuropathies in the setting of Neurofibromatosis tumor syndromes: Complexities and opportunities.

The term 'Neurofibromatosis' (NF) comprises a group of rare diseases with related clinical presentations but distinct genetic conditions. All currently known types - NF1, NF2 and Schwannomatosis - predispose afflicted individuals to the development of glial cell-derived (gliogenic) tumors. Furthermore, the occurrence of neuropathic symptoms, which add to the overall neurologic disability of patients, has been described in all disease entities. We show that neuropathic symptoms are a common and clinically important, yet infrequently studied feature in the NF spectrum. However, the clinical relevance and respective underlying pathogenesis, varies greatly among the different NF types. In this review, we summarize and interpret the latest basic research findings, as well as clinical observations, in respect of Neurofibromatosis-associated neuropathies.

Human dorsal root ganglion in vivo morphometry and perfusion in Fabry painful neuropathy.

OBJECTIVE: To evaluate functional and morphometric magnetic resonance neurography of the dorsal root ganglion and peripheral nerve segments in patients with Fabry painful neuropathy. METHODS: In this prospective study, the lumbosacral dorsal root ganglia and proximal peripheral nerve segments of the lower extremity were examined in 11 male patients with Fabry disease by a standardized 3T magnetic resonance neurography protocol. Volumes of L3 to S2 dorsal root ganglia, perfusion parameters of L5-S1 dorsal root ganglia and the spinal nerve L5, and the cross-sectional area of the proximal sciatic nerve were compared to healthy controls. RESULTS: Dorsal root ganglia of patients with Fabry disease were symmetrically enlarged by 78% (L3), 94% (L4), 122% (L5), 115% (S1), and 119% (S2) (p < 0.001). In addition, permeability of the blood-tissue interface was decreased by 53% (p < 0.001). This finding was most pronounced in the peripheral zone of the dorsal root ganglion containing the cell bodies of the primary sensory neurons (p < 0.001). Spinal nerve permeability showed no difference between patients with Fabry disease and controls (p = 0.7). The sciatic nerve of patients with Fabry disease at the thigh level showed an increase in cross-sectional area by 48% (p < 0.001). CONCLUSIONS: Patients with Fabry disease have severely enlarged dorsal root ganglia with dysfunctional perfusion. This may be due to glycolipid accumulation in the dorsal root ganglia mediating direct neurotoxic effects and decreased neuronal blood supply. These alterations were less pronounced in peripheral nerve segments. Thus, the dorsal root ganglion might play a key pathophysiologic role in the development of neuropathy and pain in Fabry disease.

T1ρ-weighted Dynamic Glucose-enhanced MR Imaging in the Human Brain.

Purpose To evaluate the ability to detect intracerebral regions of increased glucose concentration at T1ρ-weighted dynamic glucose-enhanced (DGE) magnetic resonance (MR) imaging at 7.0 T. Materials and Methods This prospective study was approved by the institutional review board. Nine patients with newly diagnosed glioblastoma and four healthy volunteers were included in this study from October 2015 to July 2016. Adiabatically prepared chemical exchange-sensitive spin-lock imaging was performed with a 7.0-T whole-body unit with a temporal resolution of approximately 7 seconds, yielding the time-resolved DGE contrast. T1ρ-weighted DGE MR imaging was performed with injection of 100 mL of 20% d-glucose via the cubital vein. Glucose enhancement, given by the relative signal intensity change at T1ρ-weighted MR imaging (DGEρ), was quantitatively investigated in brain gray matter versus white matter of healthy volunteers and in tumor tissue versus normal-appearing white matter of patients with glioblastoma. The median signal intensities of the assessed brain regions were compared by using the Wilcoxon rank-sum test. Results In healthy volunteers, the median signal intensity in basal ganglia gray matter (DGEρ = 4.59%) was significantly increased compared with that in white matter tissue (DGEρ = 0.65%) (P = .028). In patients, the median signal intensity in the glucose-enhanced tumor region as displayed on T1ρ-weighted DGE images (DGEρ = 2.02%) was significantly higher than that in contralateral normal-appearing white matter (DGEρ = 0.08%) (P < .0001). Conclusion T1ρ-weighted DGE MR imaging in healthy volunteers and patients with newly diagnosed, untreated glioblastoma enabled visualization of brain glucose physiology and pathophysiologically increased glucose uptake and may have the potential to provide information about glucose metabolism in tumor tissue. © RSNA, 2017 Online supplemental material is available for this article.

Tumor Infiltration in Enhancing and Non-Enhancing Parts of Glioblastoma: A Correlation with Histopathology.

PURPOSE: To correlate histopathologic findings from biopsy specimens with their corresponding location within enhancing areas, non-enhancing areas and necrotic areas on contrast enhanced T1-weighted MRI scans (cT1). MATERIALS AND METHODS: In 37 patients with newly diagnosed glioblastoma who underwent stereotactic biopsy, we obtained a correlation of 561 1mm3 biopsy specimens with their corresponding position on the intraoperative cT1 image at 1.5 Tesla. Biopsy points were categorized as enhancing (CE), non-enhancing (NE) or necrotic (NEC) on cT1 and tissue samples were categorized as "viable tumor cells", "blood" or "necrotic tissue (with or without cellular component)". Cell counting was done semi-automatically. RESULTS: NE had the highest content of tissue categorized as viable tumor cells (89% vs. 60% in CE and 30% NEC, respectively). Besides, the average cell density for NE (3764 ± 2893 cells/mm2) was comparable to CE (3506 ± 3116 cells/mm2), while NEC had a lower cell density with 2713 ± 3239 cells/mm2. If necrotic parts and bleeds were excluded, cell density in biopsies categorized as "viable tumor tissue" decreased from the center of the tumor (NEC, 5804 ± 3480 cells/mm2) to CE (4495 ± 3209 cells/mm2) and NE (4130 ± 2817 cells/mm2). DISCUSSION: The appearance of a glioblastoma on a cT1 image (circular enhancement, central necrosis, peritumoral edema) does not correspond to its diffuse histopathological composition. Cell density is elevated in both CE and NE parts. Hence, our study suggests that NE contains considerable amounts of infiltrative tumor with a high cellularity which might be considered in resection planning.

Multifocal nerve lesions and LZTR1 germline mutations in segmental schwannomatosis.

Schwannomatosis is a genetic disorder characterized by the occurrence of multiple peripheral schwannomas. Segmental schwannomatosis is diagnosed when schwannomas are restricted to 1 extremity and is thought to be caused by genetic mosaicism. We studied 5 patients with segmental schwannomatosis through microstructural magnetic resonance neurography and mutation analysis of NF2, SMARCB1, and LZTR1. In 4 of 5 patients, subtle fascicular nerve lesions were detected in clinically unaffected extremities. Two patients exhibited LZTR1 germline mutations. This appears contrary to a simple concept of genetic mosaicism and suggests more complex and heterogeneous mechanisms underlying the phenotype of segmental schwannomatosis than previously thought. Ann Neurol 2016;80:625-628.

Prognostic value of combined visualization of MR diffusion and perfusion maps in glioblastoma.

We analyzed whether the combined visualization of decreased apparent diffusion coefficient (ADC) values and increased cerebral blood volume (CBV) in perfusion imaging can identify prognosis-related growth patterns in patients with newly diagnosed glioblastoma. Sixty-five consecutive patients were examined with diffusion and dynamic susceptibility-weighted contrast-enhanced perfusion weighted MRI. ADC and CBV maps were co-registered on the T1-w image and a region of interest (ROI) was manually delineated encompassing the enhancing lesion. Within this ROI pixels with ADC values the 70th percentile (CBVmax) and the intersection of pixels with ADCmin and CBVmax were automatically calculated and visualized. Initially, all tumors with a mean intersection greater than the upper quartile of the normally distributed mean intersection of all patients were subsumed to the first growth pattern termed big intersection (BI). Subsequently, the remaining tumors' growth patterns were categorized depending on the qualitative representation of ADCmin, CBVmax and their intersection. Log-rank test exposed a significantly longer overall survival of BI (n = 16) compared to non-BI group (n = 49) (p = 0.0057). Thirty-one, four and 14 patients of the non-BI group were classified as predominant ADC-, CBV- and mixed growth group, respectively. In a multivariate Cox regression model, the BI-, CBV- and mixed groups had significantly lower adjusted hazard ratios (p-value, α(Bonferroni) < 0.006) when compared to the reference group ADC: 0.29 (0.0027), 0.11 (0.038) and 0.33 (0.0059). Our study provides evidence that the combination of diffusion and perfusion imaging allows visualization of different glioblastoma growth patterns that are associated with prognosis. A possible biological hypothesis for this finding could be the interpretation of the ADCmin fraction as the invasion-front of tumor cells while the CBVmax fraction might represent the vascular rich tumor border that is "trailing behind" the invasion-front in the ADC group.