Doris Da May Lin

Background and ObjectivesSpinal cord stroke (SCS) is an underrecognized cause of severe acute myelopathy in children that can be misdiagnosed as an infectious or inflammatory process. Limited chara...

Purpose: Magnetic resonance spectroscopic imaging (MRSI) is a versatile technique to investigate the spatial distribution of in vivo metabolism. However, processing MRSI data is demanding, and only a few software packages support end-to-end analysis. The goal of this study was to implement fully automated, end-to-end MRSI analysis into the open-source ‘Osprey-MRSI’ software package. Methods: MRSI-specific analysis and visualization capabilities were implemented, building on the existing Osprey workflow. Modifications included spatial transformation and filtering operations, automated brain masking and tissue segmentation of the MRSI data, improved lipid filtering, rapid integral maps, linear-combination modeling with explicit B ₀ frequency-shift correction, and generation of quality-control maps and metabolic images. A fully interactive GUI and semi-interactive HTML reports provide a user-friendly way to inspect each step of the analysis. All analysis derivatives are also exported in NIfTI and NIfTI-MRS format for easy visualization and synergies with other toolboxes and modalities. Results: The automated MRSI workflow was successfully used to analyze short- and medium-TE 3T in vivo MRSI datasets from all major vendors (Philips, GE, Siemens) across multiple sites. Correct coregistration of MRSI data and MR images was validated using phantom data from each vendor and existing MRSI processing tools. Conclusion: Osprey-MRSI offers state-of-the-art methods with minimal user interaction available for non-expert users. The modularity of the workflow and the modeling algorithm will foster innovation and development of novel MRSI-specific analysis methods.

Purpose:Isocitrate dehydrogenase (IDH)-mutant (mIDH) gliomas are slow-growing infiltrating tumors of astrocytic or oligodendroglial origin. Mutated metabolic enzymes IDH1 or IDH2 lead to the production of 2-hydroxyglutarate (2HG) that can be measured with optimized in vivo magnetic resonance spectroscopy (MRS). As the 2HG oncometabolite plays a key role in the molecular pathogenesis of mIDH tumor, direct suppression of 2HG production has proven to be a viable intervention strategy, for example, with the small-molecule inhibitors ivosidenib (mIDH1) and vorasidenib (mIDH1/mIDH2). The aim of this study was to explore whether MRS measurements of 2HG can be used to noninvasively monitor response to treatment with mIDH inhibitors and to relate this response to changes in MRI-assessed tumor volume. Experimental Design:Eighteen patients with diagnosed IDH-mutated glioma were enrolled and received ivosidenib or vorasidenib therapy. MRI/MRS scans with 2HG-optimized single-voxel PRESS were performed before treatment and repeated (follow-up) with a median on-drug follow-up of 4.3 months. Results:In the 14 patients that passed spectroscopy quality control (median follow-up 3.9 months), we observed a substantial and significant decrease in 2HG levels (P < 0.001) regardless of tumor and treatment type (astrocytoma/oligodendroglioma and ivosidenib/vorasidenib), whereas total choline (tCho) and glutamine, metabolites characteristically increased in glioma, also showed a significant decrease (P < 0.01). Volumetric assessment revealed a modest decrease on average, indicating tumor growth arrest. Conclusion:The striking reductions in tumor 2HG and tCho levels early following initiation of targeted therapy using an IDH inhibitor suggest that MRS may provide an important tool for monitoring treatment response of lower-grade gliomas.

Supplementary tables and figures for manuscript “Ivosidenib and Vorasidenib decrease intratumoral 2-hydroxyglutarate and total choline levels in lower-grade glioma: an in vivo MR Spectroscopy study”.

Purpose: Isocitrate dehydrogenase (IDH)-mutant (mIDH) gliomas are slow-growing infiltrating tumors of astrocytic or oligodendroglial origin. Mutated metabolic enzymes IDH1 or IDH2 lead to the production of 2-hydroxyglutarate (2HG) that can be measured with optimized in vivo magnetic resonance spectroscopy (MRS). As the 2HG oncometabolite plays a key role in the molecular pathogenesis of mIDH tumor, direct suppression of 2HG production has proven to be a viable intervention strategy, for example, with the small-molecule inhibitors ivosidenib (mIDH1) and vorasidenib (mIDH1/mIDH2). The aim of this study was to explore whether MRS measurements of 2HG can be used to noninvasively monitor response to treatment with mIDH inhibitors and to relate this response to changes in MRI-assessed tumor volume. Experimental Design: Eighteen patients with diagnosed IDH-mutated glioma were enrolled and received ivosidenib or vorasidenib therapy. MRI/MRS scans with 2HG-optimized single-voxel PRESS were performed before treatment and repeated (follow-up) with a median on-drug follow-up of 4.3 months. Results: In the 14 patients that passed spectroscopy quality control (median follow-up 3.9 months), we observed a substantial and significant decrease in 2HG levels (P < 0.001) regardless of tumor and treatment type (astrocytoma/oligodendroglioma and ivosidenib/vorasidenib), whereas total choline (tCho) and glutamine, metabolites characteristically increased in glioma, also showed a significant decrease (P < 0.01). Volumetric assessment revealed a modest decrease on average, indicating tumor growth arrest. Conclusion: The striking reductions in tumor 2HG and tCho levels early following initiation of targeted therapy using an IDH inhibitor suggest that MRS may provide an important tool for monitoring treatment response of lower-grade gliomas.

Tuberous sclerosis complex (TSC) is a genetic disorder that affects multiple organs, particularly the brain, and is associated with neurologic impairments such as cognitive deficits and seizures. There are relatively few prior studies investigating brain metabolites in TSC. The aim of this study was to investigate neurochemical alterations in TSC, focusing on cortical/subcortical glioneuronal tubers as well as normal-appearing regions, and comparing them with matched healthy control subjects. The study included 19 subjects with TSC (mean, 15.9 [SD, 9.5] years), and 33 age- and sex-matched healthy controls (mean, 19.7 [SD, 8.2] years). Multislice 2D-MR spectroscopic imaging was used for quantification of metabolites, including total N-acetylaspartate (tNAA), choline (tCho), creatine (tCr), glutamate and glutamine (Glx) and myo-inositol (mI) in both tubers and normal-appearing brain regions in individuals with TSC and comparing them with those in control subjects. Metabolite ratios were also examined for correlation with age. mI/tCr was significantly elevated in TSC compared with controls in WM, GM, and tubers (P < .05 or better). In addition, both tNAA/tCr and tCho/tCr were decreased in tubers and in normal-appearing WM compared with controls (P < .001). Finally, Glx/tCr was elevated in tubers compared with controls (P < .05), and individuals with TSC did not exhibit age-related Glx/tCr decreases that were observed in controls in both GM and WM. Subtle, but significant metabolic abnormalities were found for subjects with TSC compared with healthy controls, both in tubers and in normal-appearing brain regions. The variation of metabolite levels as a function of age also differed between TSC and controls. These findings may provide information on the underlying pathophysiology of TSC, and future work is needed to investigate the relationships of these findings to neurologic symptoms, including seizures and cognitive impairment.

Background: Spinal cord stroke (SCS) is rare and frequently misdiagnosed. This study describes the clinical and radiological characteristics of vertebral body infarction (VBI) associated with SCS. Methods: To assess VBI in patients with SCS, we retrospectively examined clinical data and magnetic resonance imaging from patients diagnosed at a specialized referral center. VBI was defined as a T2-weighted hyperintensity within a vertebral body near ischemic cord lesions. Additional features, such as gadolinium enhancement, lesion distribution, and the exclusion of other explanations, were also analyzed. Each vertebra was evaluated for its level, pattern of signal changes, and enhancement, then correlated with the lesion distribution and related arterial spinal supply. Results: Among 126 patients with SCS, 15 (12%) showed MRI evidence of VBI. Thirteen patients (87%) had multiple vertebrae affected, with 80% of cases involving two adjacent vertebral bodies. Of the 35 vertebrae displaying signs of VBI, 20 (57%) were thoracic, 9 (25%) were cervical, and 6 (17%) were lumbar. In 80% of SCS cases, VBI MRI abnormalities were found at the same or lower vertebral levels corresponding to the cord lesions; these were typically hyperintense on T2-weighted and STIR sequences, with 92% showing contrast enhancement. The location of the ischemic lesions in the vertebral bodies was anterolateral (47%), posteramedial (23%), hemivertebral (17%), or posterolateral (9%), with two vertebrae showing diffuse involvement. The spinal vascular territories included the artery of Adamkiewicz (n=9, 60%), the upper artery of the cervical enlargement (n=6, 40%), the artery of von Haller (n=5, 33%), and the lower artery of the cervical enlargement in two cases (13%). Conclusion: The co-occurrence of VBI and SCS is attributable to their shared arterial supply, as the MRI findings in VBI generally mirror the spinal vascular anatomy. VBI serves as a key indicator of vascular injury and an important diagnostic marker for SCS.

Survivors of immune thrombotic thrombocytopenic purpura (iTTP) face an increased risk of cerebrovascular disease, including silent cerebral infarction (SCI), cognitive impairment, and stroke. The prospective Neurologic Sequelae of iTTP study evaluated the natural history of SCI (by brain magnetic resonance imaging) during clinical remission and its association with stroke risk and cognitive impairment, measured by the National Institutes of Health Toolbox cognition battery. SCI burden was quantified using the modified age-related white matter changes (ARWMC) score. Among 42 patients who completed the baseline study visit, 28 completed a second assessment at a median interval of 12.5 months. New or progressive SCI were observed in 8 of 28 patients (28.6%), with the median ARWMC score increasing from 4 to 5 (P = .002). SCI progression was associated with a higher baseline ARWMC score (median, 7 vs 1; P = .011) but not with age, hypertension, diabetes, or average remission ADAMTS13 activity. Over a median follow-up of 32 months, 6 of 42 participants (14.3%) developed stroke, with significantly higher stroke risk among those with a higher baseline ARWMC score (hazard ratio, 1.36; 95% confidence interval, 1.01-1.83; P = .043). Cognitive function significantly improved in patients without SCI progression but not in those with progressive SCI. In summary, SCI is progressive during clinical remission in iTTP and associated with an increased risk of stroke and persistent cognitive impairment. SCI burden and progression may serve as shorter-term end points for clinical trials aimed at mitigating stroke risk and improving cognitive outcomes after iTTP.