Silent cerebral infarction during immune TTP remission: prevalence, predictors, and impact on cognition.

Immune thrombotic thrombocytopenic purpura (iTTP) survivors have increased risk of cardiovascular disease, including strokes, and report persistent cognitive difficulties during remission. We conducted this prospective study involving iTTP survivors during clinical remission to determine the prevalence of silent cerebral infarction (SCI), defined as magnetic resonance imaging (MRI) evidence of brain infarction without corresponding overt neurodeficits. We also tested the hypothesis that SCI is associated with cognitive impairment, assessed using the National Institutes of Health ToolBox Cognition Battery. For cognitive assessments, we used fully corrected T scores adjusted for age, sex, race, and education. Based on the diagnostic and statistical manual 5 criteria, we defined mild and major cognitive impairment as T scores with a 1 or 2 standard deviation (SD) and >2 SD below the mean on at least 1 test, respectively. Forty-two patients were enrolled, with 36 completing MRIs. SCI was present in 50% of the patients (18), of which 8 (44.4%) had prior overt stroke including during acute iTTP. Patients with SCI had higher rates of cognitive impairment (66.7% vs 27.7%; P = .026), including major cognitive impairment (50% vs 5.6%; P = .010). In separate logistic regression models, SCI was associated with any (mild or major) cognitive impairment (odds ratio [OR] 10.5 [95% confidence interval (95% CI), 1.45-76.63]; P = .020) and major cognitive impairment (OR 7.98 [95% CI, 1.11-57.27]; P = .039) after adjusting for history of stroke and Beck depression inventory scores. MRI evidence of brain infarction is common in iTTP survivors; the strong association of SCI with impaired cognition suggests that these silent infarcts are neither silent nor innocuous.

Brain AVM compactness score in children with hereditary hemorrhagic telangiectasia.

OBJECTIVE: The brain arteriovenous malformation (BAVM) nidus compactness score (CS), determined on angiography, predicts BAVM recurrence after surgical resection among children with sporadic BAVMs. We measured the angiographic CS for BAVMs among children with hereditary hemorrhagic telangiectasia (HHT) to determine CS characteristics in this population. METHODS: A pediatric interventional neuroradiologist reviewed angiograms to determine the CS of BAVMs in children with HHT recruited to the BVMC. CS is based on overall nidus and perinidal anomalous vessel compactness. CS categories included 1 = diffuse nidus, 2 = intermediate nidus, and 3 = compact nidus. RESULTS: Forty-eight of 78 children (61.5%) with HHT and brain vascular malformations had a conventional angiogram; 47 (97.9%) angiograms were available. Fifty-four BAVMs were identified in 40 of these 47 children (85.1%). Of 54 BAVMs in children with HHT, CS was 1 in 7 (13%), 2 in 29 (53.7%), and 3 in 18 BAVMs (33.3%) compared with CS of 1 in six (26.1%), 2 in 15 (65.2%), and 3 in 2 BAVMs (8.7%) among 23 previously reported children with sporadic BAVMs, p = 0.045 (Fisher's exact). Seven children with HHT had intracranial hemorrhage: 4 had CS = 3, 1 had CS = 2, and 2 had CS = 1. CONCLUSIONS: A range of CSs exists across HHT BAVMs, suggesting it may be an angiographic measure of interest for future studies of BAVM recurrence and hemorrhage risk. Children with HHT may have more compact niduses compared to children with sporadic BAVMs. Additional research should determine whether CS affects hemorrhage risk or post-surgical recurrence risk in HHT-associated BAVMs, which could be used to direct BAVM treatment.

Test-retest reliability of 3D velocity-selective arterial spin labeling for detecting normal variations of cerebral blood flow.

Velocity-selective inversion (VSI) based velocity-selective arterial spin labeling (VSASL) has been developed to measure cerebral blood flow (CBF) with low susceptibility to the prolonged arterial transit time and high sensitivity to brain perfusion signal. The purpose of this magnetic resonance imaging study is to evaluate the test-retest reliability of a VSI-prepared 3D VSASL protocol with whole-brain coverage to detect baseline CBF variations among cognitively normal participants in different brain regions. Coefficients of variation (CoV) of both absolute and relative CBF across scans or sessions, subjects, and gray matter regions were calculated, and corresponding intraclass correlation coefficients (ICC) were computed. The higher between-subject CoV of absolute CBF (13.4 ± 2.0%) over within-subject CoV (within-session: 3.8 ± 1.1%; between-session: 4.9 ± 0.9%) yielded moderate to excellent ICC (within-session: 0.88±0.08; between-session: 0.77±0.14) to detect normal variations of individual CBF. The higher between-region CoV of relative CBF (11.4 ± 3.0%) over within-region CoV (within-session: 2.3 ± 0.9%; between-session: 3.3 ± 1.0%) yielded excellent ICC (within-session: 0.92±0.06; between-session: 0.85±0.12) to detect normal variations of regional CBF. Age, blood pressure, end-tidal CO2, and hematocrit partially explained the variability of CBF across subjects. Together these results show excellent test-retest reliability of VSASL to detect both between-subject and between-region variations supporting its clinical utility.

Perfusion measurement in brain gliomas using velocity-selective arterial spin labeling: comparison with pseudo-continuous arterial spin labeling and dynamic susceptibility contrast MRI.

OBJECTIVES: To evaluate the performance of velocity-selective (VS) ASL among patients with untreated gliomas by comparing with both pseudo-continuous (PC) ASL and dynamic susceptibility contrast-enhanced perfusion-weighted imaging (DSC-PWI). METHODS: Forty-four consecutive patients with newly diagnosed glioma who underwent preoperative perfusion MRI including VSASL, PCASL, and DSC-PWI between 2017 and 2019 were retrospectively evaluated. Visual inspection was performed to evaluate the tumor signal intensity relative to gray matter based on 1-5 score criteria and weighted kappa was used to evaluate the pair-wise concordance between VSASL or PCASL and DSC-PWI. The relative tumor blood flow (rTBF) was measured from sampling intra-tumoral areas of hot-spot on the blood flow map and normalized against the contralateral normal gray matter blood flow. Linear regression and Bland-Altman analyses were performed to evaluate the correlation and agreement of rTBF measurements between ASL methods and DSC-PWI. The ROC analysis was constructed to determine the diagnostic performance of three perfusion methods for grading gliomas. RESULTS: TBF maps derived from VSASL were more comparable with DSC-PWI than PCASL on visual inspection (weighted kappa of 0.90 vs 0.68). In quantitative analysis, VSASL-rTBF yielded higher correlation with the values from DSC-PWI than PCASL-rTBF (R2 = 80% vs 47%, p < 0.001 for both). Both ASL and DSC-derived rTBF showed good distinction between low-grade and high-grade gliomas (p < 0.001). Compared to PCASL, VSASL yielded superior diagnostic sensitivity, specificity, and accuracy in glioma grading. CONCLUSIONS: VSASL showed great promise for accurate quantification of TBF and could potentially improve the diagnostic performance of ASL in preoperative grading of gliomas. KEY POINTS: • VSASL demonstrated a greater agreement with DSC-PWI than with PCASL on visual inspection and perfusion quantification. • VSASL showed a higher diagnostic sensitivity, negative predictive value, and accuracy than PCASL for glioma grading. • With the advantages of insensitivity to transit delay and no need of prescribing a labeling plane, VSASL could potentially improve the diagnostic performance of ASL for a more accurate, noninvasive quantification of TBF in patients with glioma.

Dose-Lowering in Contrast-Enhanced MRI of the Central Nervous System: A Retrospective, Parallel-Group Comparison Using Gadobenate Dimeglumine.

BACKGROUND: Concerns over gadolinium (Gd) retention encourage the use of lower Gd doses. However, lower Gd doses may compromise imaging performance. Higher relaxivity gadobenate may be suited to reduced dose protocols. PURPOSE: To compare 0.05 mmol/kg and 0.1 mmol/kg gadobenate in patients undergoing enhanced MRI of the central nervous system (CNS). STUDY TYPE: Retrospective, multicenter. POPULATION: Three hundred and fifty-two patients receiving 0.05 (n = 181) or 0.1 (n = 171) mmol/kg gadobenate. FIELD STRENGTH/SEQUENCES: 1.5 T and 3.0 T/precontrast and postcontrast T1-weighted spin echo/fast spin echo (SE/FSE) and/or gradient echo/fast field echo (GRE/FFE); precontrast T2-weighted FSE and T2-FLAIR. ASSESSMENT: Images of patients with extra-axial lesions at 1.5 T or any CNS lesion at 3.0 T were reviewed by three blinded, independent neuroradiologists for qualitative (lesion border delineation, internal morphology visualization, contrast enhancement; scores from 1 = poor to 4 = excellent) and quantitative (lesion-to-brain ratio [LBR], contrast-to-noise ratio [CNR]; SI measurements at regions-of-interest on lesion and normal parenchyma) enhancement measures. Noninferiority of 0.05 mmol/kg gadobenate was determined for each qualitative endpoint if the lower limit of the 95% confidence interval (CI) for the difference in precontrast + postcontrast means was above a noninferiority margin of -0.4. STATISTICAL TESTS: Student's t-test for comparison of mean qualitative endpoint scores, Wilcoxon signed rank test for comparison of LBR and CNR values; Wilcoxon rank sum test for comparison of SI changes. Tests were significant for P < 0.05. RESULTS: The mean change from precontrast to precontrast + postcontrast was significant for all endpoints. Readers 1, 2, and 3 evaluated 304, 225, and 249 lesions for 0.05 mmol/kg gadobenate, and 382, 309, and 298 lesions for 0.1 mmol/kg gadobenate. The lower limit of the 95% CI was above -0.4 for all comparisons. Significantly, higher LBR and CNR was observed with the higher dose. DATA CONCLUSION: 0.05 mmol/kg gadobenate was noninferior to 0.1 mmol/kg gadobenate for lesion visualization. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 3.

Safety and diagnostic efficacy of gadoteridol for magnetic resonance imaging of the brain and spine in children 2 years of age and younger.

BACKGROUND: Neonates and young children require efficacious magnetic resonance imaging (MRI) examinations but are potentially more susceptible to the short- and long-term adverse effects of gadolinium-based contrast agents due to the immaturity of their body functions. OBJECTIVE: To evaluate the acute safety and diagnostic efficacy of gadoteridol (ProHance) for contrast-enhanced MRI of the central nervous system (CNS) in children ≤2 years of age. MATERIALS AND METHODS: One hundred twenty-five children ≤2 years old (including 57 children <6 months old) who underwent contrast-enhanced MRI of the CNS with gadoteridol at 0.1 mmol/kg body weight were retrospectively enrolled at five imaging centers. Safety data were assessed for acute/subacute adverse events in the 48 h following gadoteridol administration and, when available, vital signs, electrocardiogram (ECG) and clinical laboratory values obtained from blood samples taken from 48 h before until 48 h following the MRI exam. The efficacy of gadoteridol-enhanced MRI compared to unenhanced MRI for disease diagnosis was evaluated prospectively by three blinded, unaffiliated readers. RESULTS: Thirteen changes of laboratory values (11 mild, 1 moderate, 1 unspecified) were reported as adverse events in 7 (5.6%) patients. A relationship to gadoteridol was deemed possible though doubtful for two of these adverse events in two patients (1.6%). There were no clinical adverse events, no serious adverse events and no clinically meaningful changes in vital signs or ECG recordings. Accurate differentiation of tumor from non-neoplastic disease, and exact matching of specific MRI-determined diagnoses with on-site final diagnoses, was achieved in significantly more patients by each reader following the evaluation of combined pre- and post-contrast images compared to pre-contrast images alone (84.6-88.0% vs. 70.9-76.9%; P≤0.006 and 67.5-79.5% vs. 47.0-66.7%; P≤0.011, respectively). CONCLUSION: Gadoteridol at 0.1 mmol/kg body weight is safe, well tolerated and effective for contrast-enhanced MRI of the CNS in children ≤2 years of age.

Improved velocity-selective-inversion arterial spin labeling for cerebral blood flow mapping with 3D acquisition.

PURPOSE: To further optimize the velocity-selective arterial spin labeling (VSASL) sequence utilizing a Fourier-transform based velocity-selective inversion (FT-VSI) pulse train, and to evaluate its utility for 3D mapping of cerebral blood flow (CBF) with a gradient- and spin-echo (GRASE) readout. METHODS: First, numerical simulations and phantom experiments were done to test the susceptibility to eddy currents and B1 field inhomogeneities for FT-VSI pulse trains with block and composite refocusing pulses. Second, the choices of the post-labeling delay (PLD) for FT-VSI prepared 3D VSASL were evaluated for the sensitivity to perfusion signal. The study was conducted among a young-age and a middle-age group at 3T. Both signal-to-noise ratio (SNR) and CBF were quantitatively compared with pseudo-continuous ASL (PCASL). The optimized 3D VSI-ASL was also qualitatively compared with PCASL in a whole-brain coverage among two healthy volunteers and a brain tumor patient. RESULTS: The simulations and phantom test showed that composite refocusing pulses are more robust to both eddy-currents and B1 field inhomogeneities than block pulses. 3D VSASL images with FT-VSI preparation were acquired over a range of PLDs and PLD = 1.2 s was selected for its higher perfusion signal. FT-VSI labeling produced quantitative CBF maps with 27% higher SNR in gray matter compared to PCASL. 3D whole-brain CBF mapping using VSI-ASL were comparable to the corresponding PCASL results. CONCLUSION: FT-VSI with 3D-GRASE readout was successfully implemented and showed higher sensitivity to perfusion signal than PCASL for both young and middle-aged healthy volunteers.

Cerebral blood volume mapping using Fourier-transform-based velocity-selective saturation pulse trains.

PURPOSE: Velocity-selective saturation (VSS) pulse trains provide a viable alternative to the spatially selective methods for measuring cerebral blood volume (CBV) by reducing the sensitivity to arterial transit time. This study is to compare the Fourier-transform-based velocity-selective saturation (FT-VSS) pulse trains with the conventional flow-dephasing VSS techniques for CBV quantification. METHODS: The proposed FT-VSS label and control modules were compared with VSS pulse trains utilizing double refocused hyperbolic tangent (DRHT) and 8-segment B1-insensitive rotation (BIR-8). This was done using both numerical simulations and phantom studies to evaluate their sensitivities to gradient imperfections such as eddy currents. DRHT, BIR-8, and FT-VSS prepared CBV mapping was further compared for velocity-encoding gradients along 3 orthogonal directions in healthy subjects at 3T. RESULTS: The phantom studies exhibited more consistent immunity to gradient imperfections for the utilized FT-VSS pulse trains. Compared to DRHT and BIR-8, FT-VSS delivered more robust CBV results across the 3 VS encoding directions with significantly reduced artifacts along the superior-inferior direction and improved temporal signal-to-noise ratio (SNR) values. Average CBV values obtained from FT-VSS based sequences were 5.3 mL/100 g for gray matter and 2.3 mL/100 g for white matter, comparable to literature expectations. CONCLUSION: Absolute CBV quantification utilizing advanced FT-VSS pulse trains had several advantages over the existing approaches using flow-dephasing VSS modules. A greater immunity to gradient imperfections and the concurrent tissue background suppression of FT-VSS pulse trains enabled more robust CBV measurements and higher SNR than the conventional VSS pulse trains.

Correction to: White matter changes in primary central nervous system lymphoma patients treated with high-dose methotrexate with or without rituximab.

The following discrepancies and errors were found in the original publication.

White matter changes in primary central nervous system lymphoma patients treated with high-dose methotrexate with or without rituximab.

PURPOSE: White matter changes (WMCs) can develop following systemic chemotherapy in patients with primary central nervous system lymphomas (PCNSLs), but the frequency and extent of these changes is not well characterized. This single center retrospective semi-quantitative study was performed to determine the rate, timing and grade of WMC on MRI in adult patients with newly-diagnosed radiotherapy-naïve PCNSL undergoing treatment with high-dose methotrexate (HD-MTX) with or without the addition of rituximab (-R). METHODS: Serial MRI scans of consecutive adult PCNSL patients treated with HD-MTX ± R were assessed for WMC comparing the pre-treatment to post-treatment scans utilizing a 0-to-8-point severity scoring system. RESULTS: Forty-seven PCNSL patients treated with either HD-MTX-R (n = 34; median age 66, 50% male) or HD-MTX (n = 13; median age 53, 54% male) were included in the analysis. WMC were detected in 62% (95% CI 46-76%) overall, in 68% of the HD-MTX-R, and in 46% of the HD-MTX group. Among patients with WMC (n = 29), WMC were first detected at an average of 2.8 months from beginning of therapy in the HD-MTX-R versus at 10.7 months in the HD-MTX group. Average WMC non-zero scores when first detected following the start of treatment were 2.5 (± 1.1) in HD-MTX-R and 1.5 (± 0.6) in HD-MTX. CONCLUSIONS: Development of WMC in PCNSL patients treated with MTX and MTX-R is common. WMC changes appear to be more frequent, occur earlier and are more extensive in patients treated with HD-MTX-R compared to HD-MTX. Prospective studies are required to determine whether WMC correlate with survival or neurocognitive outcomes.

Concurrent BRAF/MEK Inhibitors in BRAF V600-Mutant High-Grade Primary Brain Tumors.

BRAF V600 mutations are being identified in patients with primary brain tumors more often as molecular testing becomes widely available. Targeted treatment with BRAF inhibitors has been attempted in individual cases with some responses, whereas others showed no response or developed resistance. Preclinical work suggests that gliomas could be more responsive to the concurrent use of BRAF and MEK inhibition for MAP kinase pathway suppression. This report presents 2 cases of malignant brain tumors with BRAF V600E mutations that were resistant to radiation and temozolomide, and reports on their response to targeted treatment with the BRAF and MEK inhibitors dabrafenib and trametinib. One patient with an anaplastic pleomorphic xanthoastrocytoma experienced a partial response for 14 months, demonstrated by progressive tumor shrinkage and clinical improvement; however, this was followed by clinical and radiographic progression. The patient with glioblastoma continued to have stable disease after 16 months of treatment. These cases are encouraging in a disease that urgently needs new treatments. Further work is necessary to understand response rates, duration, and survival in primary brain tumors.

Quantitative measurement of cerebral blood volume using velocity-selective pulse trains.

PURPOSE: To develop a non-contrast-enhanced MRI method for cerebral blood volume (CBV) mapping using velocity-selective (VS) pulse trains. METHODS: The new pulse sequence applied velocity-sensitive gradient waveforms in the VS label modules and velocity-compensated ones in the control scans. Sensitivities to the gradient imperfections (e.g., eddy currents) were evaluated through phantom studies. CBV quantification procedures based on simulated labeling efficiencies for arteriolar, capillary, and venular blood as a function of cutoff velocity (Vc) are presented. Experiments were conducted on healthy volunteers at 3T to examine the effects of unbalanced diffusion weighting, cerebrospinal (CSF) contamination and variation of Vc. RESULTS: Phantom results of the used VS pulse trains demonstrated robustness to eddy currents. The mean CBV values of gray matter and white matter for the experiments using Vc = 3.5 mm/s and velocity-compensated control with CSF-nulling were 5.1 ± 0.6 mL/100 g and 2.4 ± 0.2 mL/100 g, respectively, which were 23% and 32% lower than results from the experiment with velocity-insensitive control, corresponding to 29% and 25% lower in averaged temporal signal-to-noise ratio values. CONCLUSION: A novel technique using VS pulse trains was demonstrated for CBV mapping. The results were both qualitatively and quantitatively close to those from existing methods. Magn Reson Med 77:92-101, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Size of Facial Port-Wine Birthmark May Predict Neurologic Outcome in Sturge-Weber Syndrome.

OBJECTIVE: To determine whether the size of the birthmark in patients with Sturge-Weber syndrome (SWS) who have brain involvement can help predict neurologic disability. STUDY DESIGN: Fifty-one patients with SWS with facial birthmarks and brain involvement documented on magnetic resonance imaging were included in this retrospective chart review. A neuroradiologist, blinded to all clinical information, assigned a previously validated SWS neuroimaging score. A pediatric neurologist prospectively assigned previously validated neurologic severity scores, based on seizures, hemiparesis, visual field cut, and cognitive impairments. Three raters, blinded to clinical scores, independently graded the size of facial birthmark in each patient based on photographs. Their scores were averaged. Birthmark scores were compared with the imaging and neurologic severity results using nonparametric correlation analysis. RESULTS: Size of facial port-wine birthmark correlates with magnetic resonance imaging scores on the left and right sides (ρ = 0.57 and 0.66 [P < .001], respectively). Size is also positively associated with the neurologic severity rating for patients age 6 years and above (1-sided Fisher exact, P = .032). CONCLUSIONS: The size of facial port-wine birthmark in SWS brain involvement can be developed as a tool to predict neurologic severity of the disease.

A case of acute onset succinic semialdehyde dehydrogenase deficiency: neuroimaging findings and literature review.

BACKGROUND: Succinic semialdehyde dehydrogenase (SSADH) deficiency is a rare autosomal recessive disorder of γ-aminobutyric acid metabolism, leading to elevated levels of γ-aminobutyric acid and γ-hydroxybutyric acid in cerebrospinal fluid. PATIENT: We describe the neuroimaging findings of a previously healthy 6-month-old girl with acute onset of lethargy, hypotonia, and choreiform movements, and a subsequent diagnosis of SSADH deficiency. Magnetic resonance (MR) imaging of the brain revealed symmetric T2 hyperintense signal abnormalities and reduced diffusivity of the globus pallidi bilaterally. Arterial spin-labeling perfusion MR imaging suggested bilateral hyperperfusion of the globus pallidi. MR spectroscopy of the thalamus and frontal lobe white matter revealed increased signal intensity in the glutamate and glutamine region of the spectra between 2.1 and 2.4 ppm. CONCLUSION: The unique early imaging findings described here may be attributable to bioenergetic failure and deficiency in mitochondrial energy metabolism and are consistent with SSADH-knockout mice studies.

Severe auditory processing disorder secondary to viral meningoencephalitis.

OBJECTIVE: To describe auditory function in an individual with bilateral damage to the temporal and parietal cortex. DESIGN: Case report. STUDY SAMPLE: A previously healthy 17-year old male is described who sustained extensive cortical injury following an episode of viral meningoencephalitis. He developed status epilepticus and required intubation and multiple anticonvulsants. RESULTS: Serial brain MRIs showed bilateral temporoparietal signal changes reflecting extensive damage to language areas and the first transverse gyrus of Heschl on both sides. The patient was referred for assessment of auditory processing but was so severely impaired in speech processing that he was unable to complete any formal tests of his speech processing abilities. Audiological assessment utilizing objective measures of auditory function established the presence of normal peripheral auditory function and illustrates the importance of the use of objective measures of auditory function in patients with injuries to the auditory cortex. CONCLUSIONS: Use of objective measures of auditory function is essential in establishing the presence of normal peripheral auditory function in individuals with cortical damage who may not be able to cooperate sufficiently for assessment utilizing behavioral measures of auditory function.

Infectious Diseases of the Brain and Spine: Parasitic and Other Atypical Transmissible Diseases.

Atypical infections of the brain and spine caused by parasites occur in immunocompetent and immunosuppressed hosts, related to exposure and more prevalently in endemic regions. In the United States, the most common parasitic infections that lead to central nervous system manifestations include cysticercosis, echinococcosis, and toxoplasmosis, with toxoplasmosis being the most common opportunistic infection affecting patients with advanced HIV/AIDS. Another rare but devastating transmittable disease is prion disease, which causes rapidly progressive spongiform encephalopathies. Familiarity and understanding of various infectious agents are a crucial aspect of diagnostic neuroradiology, and recognition of unique features can aid timely diagnosis and treatment.

Infectious Diseases of the Brain and Spine: Fungal Diseases.

Advances in treatments of autoimmune diseases, acquired immunodeficiency syndrome, organ transplantation, and the use of long-term devices have increased the rates of atypical infections due to prolonged immune suppression. There is a significant overlap in imaging findings of various fungal infections affecting the central nervous system (CNS), often mimicking those seen in neoplastic and noninfectious inflammatory conditions. Nonetheless, there are imaging characteristics that can aid in distinguishing certain atypical infections. Hence, familiarity with a wide range of infectious agents is an important part of diagnostic neuroradiology. In this article, an in-depth review of fungal diseases of the CNS is provided.

Velocity-Selective Arterial Spin Labeling Perfusion in Monitoring High Grade Gliomas Following Therapy: Clinical Feasibility at 1.5T and Comparison with Dynamic Susceptibility Contrast Perfusion.

MR perfusion imaging is important in the clinical evaluation of primary brain tumors, particularly in differentiating between true progression and treatment-induced change. The utility of velocity-selective ASL (VSASL) compared to the more commonly utilized DSC perfusion technique was assessed in routine clinical surveillance MR exams of 28 patients with high-grade gliomas at 1.5T. Using RANO criteria, patients were assigned to two groups, one with detectable residual/recurrent tumor ("RT", n = 9), and the other with no detectable residual/recurrent tumor ("NRT", n = 19). An ROI was drawn to encompass the largest dimension of the lesion with measures normalized against normal gray matter to yield rCBF and tSNR from VSASL, as well as rCBF and leakage-corrected relative CBV (lc-rCBV) from DSC. VSASL (rCBF and tSNR) and DSC (rCBF and lc-rCBV) metrics were significantly higher in the RT group than the NRT group allowing adequate discrimination (p < 0.05, Mann-Whitney test). Lin's concordance analyses showed moderate to excellent concordance between the two methods, with a stronger, moderate correlation between VSASL rCBF and DSC lc-rCBV (r = 0.57, p = 0.002; Pearson's correlation). These results suggest that VSASL is clinically feasible at 1.5T and has the potential to offer a noninvasive alternative to DSC perfusion in monitoring high-grade gliomas following therapy.

Novel proton MR spectroscopy findings in adenylosuccinate lyase deficiency.

Adenylosuccinate lyase (ADSL) deficiency is a rare inborn error of metabolism resulting in accumulation of metabolites including succinylaminoimidazole carboxamide riboside (SAICAr) and succinyladenosine (S-Ado) in the brain and other tissues. Patients with ADSL have progressive psychomotor retardation, neonatal seizures, global developmental delay, hypotonia, and autistic features, although variable clinical manifestations may make the initial diagnosis challenging. Two cases of the severe form of the disease are reported here: an 18-month-old boy with global developmental delay, intractable neonatal seizures, progressive cerebral atrophy, and marked hypomyelination, and a 3-month-old girl presenting with microcephaly, neonatal seizures, and marked psychomotor retardation. In both patients in vivo proton magnetic resonance spectroscopy (MRS) showed the presence of S-Ado signal at 8.3 ppm, consistent with a prior report. Interestingly, SAICAr signal was also detectable at 7.5 ppm in affected white matter, which has not been reported in vivo before. A novel splice-site mutation, c.IVS12 + 1/G > C, in the ADSL gene was identified in the second patient. Our findings confirm the utility of in vivo proton MRS in suggesting a specific diagnosis of ADSL deficiency, and also demonstrate an additional in vivo resonance (7.5 ppm) of SAICAr in the cases of severe disease.

Downfield Proton MRSI at 3 Tesla: A Pilot Study in Human Brain Tumors.

PURPOSE: To investigate the use of 3D downfield proton magnetic resonance spectroscopic imaging (DF-MRSI) for evaluation of tumor recurrence in patients with glioblastoma (GBM). METHODS: Seven patients (4F, age range 44-65 and mean ± standard deviation 59.3 ± 7.5 years) with previously treated GBM were scanned using a recently developed 3D DF-MRSI sequence at 3T. Short TE 3D DF-MRSI and water reference 3D-MRSI scans were collected with a nominal spatial resolution of 0.7 cm3. DF volume data in eight slices covered 12 cm of brain in the cranio-caudal axis. Data were analyzed using the 'LCModel' program and a basis set containing nine peaks ranging in frequency between 6.83 to 8.49 ppm. The DF8.18 (assigned to amides) and DF7.90 peaks were selected for the creation of metabolic images and statistical analysis. Longitudinal MR images and clinical history were used to classify brain lesions as either recurrent tumor or treatment effect, which may include necrosis. DF-MRSI data were compared between lesion groups (recurrent tumor, treatment effect) and normal-appearing brain. RESULTS: Of the seven brain tumor patients, two were classified as having recurrent tumor and the rest were classified as treatment effect. Amide metabolite levels from recurrent tumor regions were significantly (p < 0.05) higher compared to both normal-appearing brain and treatment effect regions. Amide levels in lesion voxels classified as treatment effect were significantly lower than normal brain. CONCLUSIONS: 3D DF-MRSI in human brain tumors at 3T is feasible and was well tolerated by all patients enrolled in this preliminary study. Amide levels measured by 3D DF-MRSI were significantly different between treatment effect and tumor regrowth.