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.

Simultaneous perfusion, diffusion, T2 *, and T1 mapping with MR fingerprinting.

PURPOSE: Quantitative mapping of brain perfusion, diffusion, T2 *, and T1 has important applications in cerebrovascular diseases. At present, these sequences are performed separately. This study aims to develop a novel MRI technique to simultaneously estimate these parameters. METHODS: This sequence to measure perfusion, diffusion, T2 *, and T1 mapping with magnetic resonance fingerprinting (MRF) was based on a previously reported MRF-arterial spin labeling (ASL) sequence, but the acquisition module was modified to include different TEs and presence/absence of bipolar diffusion-weighting gradients. We compared parameters derived from the proposed method to those derived from reference methods (i.e., separate sequences of MRF-ASL, conventional spin-echo DWI, and T2 * mapping). Test-retest repeatability and initial clinical application in two patients with stroke were evaluated. RESULTS: The scan time of our proposed method was 24% shorter than the sum of the reference methods. Parametric maps obtained from the proposed method revealed excellent image quality. Their quantitative values were strongly correlated with those from reference methods and were generally in agreement with values reported in the literature. Repeatability assessment revealed that ADC, T2 *, T1 , and B1 + estimation was highly reliable, with voxelwise coefficient of variation (CoV) <5%. The CoV for arterial transit time and cerebral blood flow was 16% ± 3% and 25% ± 9%, respectively. The results from the two patients with stroke demonstrated that parametric maps derived from the proposed method can detect both ischemic and hemorrhagic stroke. CONCLUSION: The proposed method is a promising technique for multi-parametric mapping and has potential use in patients with stroke.

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.

Tinnitus sound amplification and masking therapy: Treatment and outcomes at the University of North Carolina at Chapel Hill.

BACKGROUND: Tinnitus is burdensome to many patients. Sound amplification and masking therapy has been useful for some patients. METHOD: Retrospective chart review of patients treated for tinnitus at a single academic medical center over a 12-month period. Information on treatment course and outcomes was collected and analyzed. Statistical comparisons were made using a t-test for paired means. RESULTS: In 2021, 141 patients were evaluated for tinnitus sound amplification and masking therapy at our medical center. Average age at presentation was 55.2. Average onset was 6-7 years before presentation. Tinnitus perception was decreased in patients who received a trial of amplification and masking therapy, from 9.2 out of 20 at baseline to 6.1 with amplification and 3.2 with amplification and masking at the initial visit. The difference in each of these values is statistically significant. Nine patients recorded a Tinnitus Handicap Index (THI), which measures tinnitus burden, before and after being treated with amplification and masking therapy. These nine patients saw a decrease in THI from 39.6/100 to 19.1/100, which was also statistically significant. LIMITATIONS: This study has several limitations. Our data are from a single clinic over one year with limited follow up information, and it is a retrospective study. CONCLUSION: Our data showed benefit in sound amplification and masking therapy for the treatment of tinnitus. Patients treated with amplification and masking therapy showed a statistically significant decrease in perception of their tinnitus during their in-office demonstration. Long term data are still needed. Our data contribute to the broader discussion on the proper treatment course of tinnitus and the most effective measures.

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.

Evaluation of 3D stack-of-spiral turbo FLASH acquisitions for pseudo-continuous and velocity-selective ASL-derived brain perfusion mapping.

PURPOSE: The most-used 3D acquisitions for ASL are gradient and spin echo (GRASE)- and stack-of-spiral (SOS)-based fast spin echo, which require multiple shots. Alternatively, turbo FLASH (TFL) allows longer echo trains, and SOS-TFL has the potential to reduce the number of shots to even single-shot, thus improving the temporal resolution. Here we compare the performance of 3D SOS-TFL and 3D GRASE for ASL at 3T. METHODS: The 3D SOS-TFL readout was optimized with respect to fat suppression and excitation flip angles for pseudo-continuous ASL- and velocity-selective (VS)ASL-derived cerebral blood flow (CBF) mapping as well as for VSASL-derived cerebral blood volume (CBV) mapping. Results were compared with 3D GRASE readout on healthy volunteers in terms of perfusion quantification and temporal SNR (tSNR) efficiency. CBF and CBV mapping derived from 3D SOS-TFL-based ASL was demonstrated on one stroke patient, and the potential for single-shot acquisitions was exemplified. RESULTS: SOS-TFL with a 15° flip angle resulted in adequate tSNR efficiency with negligible image blurring. Selective water excitation was necessary to eliminate fat-induced artifacts. For pseudo-continuous ASL- and VSASL-based CBF and CBV mapping, compared to the employed four-shot 3D GRASE with an acceleration factor of 2, the fully sampled 3D SOS-TFL delivered comparable performance (with a similar scan time) using three shots, which could be further undersampled to achieve single-shot acquisition with higher tSNR efficiency. SOS-TFL had reduced CSF contamination for VSASL-CBF. CONCLUSION: 3D SOS-TFL acquisition was found to be a viable substitute for 3D GRASE for ASL with sufficient tSNR efficiency, minimal relaxation-induced blurring, reduced CSF contamination, and the potential of single-shot, especially for VSASL.

Clinical and radiologic characteristics associated with multiple sclerosis misdiagnosis at a tertiary referral center in the United States.

BACKGROUND: Misdiagnosis of multiple sclerosis (MS) is common and can have harmful effects on patients and healthcare systems. Identification of factors associated with misdiagnosis may aid development of prevention strategies. OBJECTIVE: To identify clinical and radiological predictors of MS misdiagnosis. METHODS: We retrospectively reviewed medical records of all patients who were referred to Johns Hopkins MS Center from January 2018 to June 2019. Patients who carried a diagnosis of MS were classified as correctly diagnosed or misdiagnosed with MS by the Johns Hopkins clinician. Demographics, clinical, laboratory, and radiologic data were collected. Differences between the two groups were evaluated, and a regression model was constructed to identify predictors of misdiagnosis. RESULTS: Out of 338 patients who were previously diagnosed with MS, 41 (12%) had been misdiagnosed. An alternative diagnosis was confirmed in 28 (68%) of the misdiagnosed patients; cerebrovascular disease was the most common alternate diagnosis. Characteristics associated with misdiagnosis were female sex (odds ratio (OR): 5.81 (95% confidence interval (CI): 1.60, 21.05)) and non-specific brain magnetic resonance imaging (MRI) lesions (OR: 7.66 (3.42, 17.16)). CONCLUSION: Misdiagnosis is a frequent problem in MS care. Non-specific brain lesions were the most significant predictor of misdiagnosis. Interventions aimed to reduce over-reliance on imaging findings and misapplication of the McDonald criteria may prevent MS misdiagnosis.

Tinnitus cases after COVID-19 vaccine administration, one institution's observations.

OBJECTIVE: After the role out of the COVID-19 vaccine in the United States, there has been increase in case reports of tinnitus attributed to the vaccine reported. We present our institution's experience over the initial 13 month period the vaccines were available. STUDY DESIGN: Retrospective chart review. SETTING: Tertiary academic otology and general otolaryngology practice. PATIENTS: Patients who received a COVID-19 vaccine and a tinnitus diagnosis code. INTERVENTIONS: Observation, steroids (oral and intratympanic), diagnostic imaging and audiometry. MAIN OUTCOME MEASURES: Patients who received a COVID-19 vaccine in the time frame of 12/1/2020-12/31/21 with a diagnosis of tinnitus, an audiogram, and at least one visit with one of our Otolaryngologists were included in the study. Twenty-seven of the 1254 patients identified met these criteria. The patients ranged in age from 41 to 84 years old including seven male and twenty female patients. Sixteen received the Pfizer vaccine, seven received the Moderna vaccine and four patients received the Janssen vaccine. CONCLUSIONS: No definite correlation could be established between COVID-19 vaccine and tinnitus. Any concurrent sudden hearing loss should be treated as usual with oral or intratympanic steroids. Health care providers should be aware of the tinnitus onset and if new or recent onset, to refer for prompt audiogram and Otolaryngology evaluation.

Retinal Findings in Haemorrhagic Destruction of the Brain, Subependymal Calcification, and Congenital Cataracts (HDBSCC): Case Report and Review.

We describe a child from a consanguineous family born with a rare autosomal recessive disorder affecting junctional adhesion molecule 3 (JAM3) causing profound neurological and ophthalmological injury known as haemorrhagic brain destruction, subependymal calcifications, and congenital cataracts (HDBSCC; MIM# 613730). She was the product of an unremarkable pregnancy and was born near to term but was noted shortly after birth to have congenital cataracts, poor vision, increased muscle tone, seizures, and developmental delay. Her older sister had an identical syndrome and had previously been documented to have homozygous mutations in JAM3. Examination in our patient, although difficult because of bilateral central cataracts, revealed very poor vision, attenuated retinal vessels, optic atrophy, and a retinal haemorrhage in the right eye, implying that abnormal development of the retinas and/or optic nerves may at times play a significant role in the poor vision noted in children with HDBSCC.

Simultaneous Hemodynamic and Structural Imaging of Ischemic Stroke With Magnetic Resonance Fingerprinting Arterial Spin Labeling.

BACKGROUND: Perfusion and structural imaging play an important role in ischemic stroke. Magnetic resonance fingerprinting (MRF) arterial spin labeling (ASL) is a novel noninvasive method of ASL perfusion that allows simultaneous estimation of cerebral blood flow (CBF), bolus arrival time (BAT), and tissue T1 map in a single scan of <4 minutes. Here, we evaluated the utility of MRF-ASL in patients with ischemic stroke in terms of detecting hemodynamic and structural damage and predicting neurological deficits and disability. METHODS: A total of 34 patients were scanned on 3T magnetic resonance imaging. MRF-ASL, standard single-delay pseudo-continuous ASL, T2-weighted, and diffusion magnetic resonance imaging were performed. Regions of interest of lesion and contralateral normal tissues were manually delineated. CBF (with 2 different compartmental models), BAT, and tissue T1 parameters were quantified. Cross-sectional linear regression analyses were performed to examine the relationship between MRF-ASL parameters and National Institutes of Health Stroke Scale (NIHSS) and modified Rankin Scale. Receiver operating characteristic analyses were performed to determine the utility of MRF-ASL in the classification of stroke lesion voxels. RESULTS: MRF-ASL derived parameters revealed a significant difference between stroke lesion and contralateral normal regions of interest, in that lesion regions manifested a lower CBF1-compartment (P<0.001), lower CBF2-compartment (P<0.001), longer BAT (P=0.002), and longer T1 (P<0.001) compared with normal regions of interest. NIHSS scores at acute stage revealed a strong association with lesion-normal differences in CBF1-compartment,diff (ß=-0.11, P=0.008), CBF2-compartment,diff (ß=-0.16, P=0.003), and T1,diff (ß=0.008, P=0.001). MRF-ASL parameters were also predictive of NIHSS score and modified Rankin Scale scale measured at a later stage, although the degree of the associations was weaker. These associations tended to be even stronger when the MRF-ASL data were acquired at the acute/subacute stage. Compared with standard pseudo-continuous ASL, the multiparametric capability of MRF-ASL yielded higher area under curve values in the receiver operating characteristic analyses of stroke voxel classifications. CONCLUSIONS: MRF-ASL may provide a new approach for quantitative hemodynamic and structural imaging in ischemic stroke.

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.

MR fingerprinting ASL: Sequence characterization and comparison with dynamic susceptibility contrast (DSC) MRI.

MR Fingerprinting (MRF)-based Arterial-Spin-Labeling (ASL) has the potential to measure multiple parameters such as cerebral blood flow (CBF), bolus arrival time (BAT), and tissue T1 in a single scan. However, the previous reports have only demonstrated a proof-of-principle of the technique but have not examined the performance of the sequence in the context of key imaging parameters. Furthermore, there has not been a study to directly compare the technique to clinically used perfusion method of dynamic-susceptibility-contrast (DSC) MRI. The present report consists of two studies. In the first study (N = 8), we examined the dependence of MRF-ASL sequence on TR time pattern. Ten different TR patterns with a range of temporal characteristics were examined by both simulations and experiments. The results revealed that there was a significance dependence of the sequence performance on TR pattern (p < 0.001), although there was not a single pattern that provided dramatically improvements. Among the TR patterns tested, a sinusoidal pattern with a period of 125 TRs provided an overall best estimation in terms of spatial consistency. These experimental observations were consistent with those of numerical simulations. In the second study (N = 8), we compared MRF-ASL results with those of DSC MRI. It was found that MRF-ASL and DSC MRI provided highly comparable maps of cerebral blood flow (CBF) and bolus-arrival-time (BAT), with spatial correlation coefficients of 0.79 and 0.91, respectively. However, in terms of quantitative values, BAT obtained with MRF-ASL was considerably lower than that from DSC (p < 0.001), presumably because of the differences in tracer characteristics in terms of diffusible versus intravascular tracers. Test-retest assessment of MRF-ASL MRI revealed that the spatial correlations of parametric maps were 0.997, 0.962, 0.746 and 0.863 for B1+ , T1 , CBF, and BAT, respectively. MRF-ASL is a promising technique for assessing multiple perfusion parameters simultaneously without contrast agent.

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.

Subependymal giant cell astrocytoma-like astrocytoma: a neoplasm with a distinct phenotype and frequent neurofibromatosis type-1-association.

Neurofibromatosis type-1 is a familial genetic syndrome associated with a predisposition to develop peripheral and central nervous system neoplasms. We have previously reported on a subset of gliomas developing in these patients with morphologic features resembling subependymal giant cell astrocytoma, but the molecular features of these tumors remain undefined. A total of 14 tumors were studied and all available slides were reviewed. Immunohistochemical stains and telomere-specific FISH were performed on all cases. In addition, next-generation sequencing was performed on 11 cases using a platform targeting 644 cancer-related genes. The average age at diagnosis was 28 years (range: 4-60, 9F/5M). All tumors involved the supratentorial compartment. Tumors were predominantly low grade (n = 12), with two high-grade tumors, and displayed consistent expression of glial markers. Next-generation sequencing demonstrated inactivating NF1 mutations in 10 (of 11) cases. Concurrent TSC2 and RPTOR mutations were present in two cases (1 sporadic and 1 neurofibromatosis type-1-associated). Interestingly, alternative lengthening of telomeres was present in 4 (of 14) (29%) cases. However, an ATRX mutation associated with aberrant nuclear ATRX expression was identified in only one (of four) cases with alternative lenghtening of telomeres. Gene variants in the DNA helicase RECQL4 (n = 2) and components of the Fanconi anemia complementation group (FANCD2, FANCF, FANCG) (n = 1) were identified in two alternative lenghtening of telomere-positive/ATRX-intact cases. Other variants involved genes related to NOTCH signaling, DNA maintenance/repair pathways, and epigenetic modulators. There were no mutations identified in DAXX, PTEN, PIK3C genes, TP53, H3F3A, HIST1H3B, or in canonical hotspots of IDH1, IDH2, or BRAF. A subset of subependymal giant cell astrocytoma-like astrocytomas are alternative lenghtening of telomere-positive and occur in the absence of ATRX alterations, thereby suggesting mutations in other DNA repair/maintenance genes may also facilitate alternative lenghtening of telomeres. These findings suggest that subependymal giant cell astrocytoma-like astrocytoma represents a biologically distinct group that merits further investigation.