MRI-pathology correlations in fixed brain autopsy tissue were conducted in 3 subjects with confirmed PML. Results: With PML (n=26 total, n = 5 multiple sclerosis natalizumab-associated), juxtacortical changes on susceptibility weighted imaging (SWI) or gradient echo (GRE) sequences were noted in 3/3 cases on 7 tesla (T) MRI and 14/22 cases (63.6%) on 1.5T or 8/22 (36.4%) 3T MRI. 7 (87.5%) had changes Rabbit Polyclonal to PKR present on average 2.7 1.8 months (mean SD) prior to diagnosis. Postmortem 7T MRI showed SWI changes corresponded to areas of increased iron density along the grey-white matter (GM-WM) junction predominantly in macrophages. Conclusions: Susceptibility changes in PML along the GM-WM junction can precede noticeable FLAIR changes and correlates with iron accumulation in macrophages. clinical scans, Students two-sided t-test was performed to compare continuous variables and chi-squared statistic was used to analyze categorical variables; significance p 0.05. Susceptibility changes were between patients with PML and PCNSL and ORs with BJE6-106 95% CI were derived. Inter-rater agreement and Cohens kappa () are reported where applicable. An in-house script (ImageJ version 1.52e, NIH, USA) was used to calculate BJE6-106 the percentage area occupied by iron staining, immunohistochemistry (MHCII, GFAP), and immunofluorescence (MHCII and ferritin-L). Pairwise comparisons of different regions (GM, GM-WM junction, and WM) were done using t-tests with pooled SD and Bonferroni correction. R Studio/R was used for statistical analysis.28 Results I. Retrospective case control study In vivo disease characteristics of patients with PML Twenty-six PML and an equal number of PCNSL cases were identified with demographic data and lesion distribution summarized (Table 1). PML etiologies included HIV (34.6%), lymphoproliferative disorders (26.9%; leukemia, lymphoma, and idiopathic lymphopenia), MS on natalizumab (19.2%), organ transplant (11.5%), and chronic inflammatory disorders (7.7%; polymyositis and dermatomyositis). Table 1. Demographics characteristics and MRI features of included patients with PML and PCNSL. non-MS patients in either pre- or post-PML MRIs. Of note, 5/8 subjects with seizures had juxtacortical susceptibility changes (1 did not have a GRE/SWI available). Open in a separate window Physique 1. 7T SWI sequence with arrow indicating linear hypointense band along WM-cortical boundary. Red asterisks (*) denote WM FLAIR hyperintensities and green plus-signs (+) normal appearing WM. Abbreviations: SWI C susceptibility-weighted imaging. T C tesla, WM C white BJE6-106 matter. Open in a separate window Physique 2. Progression of PML lesions (each colored arrow represents a unique lesion) on 1.5T brain MRI from left to right through time (months 0C4). Highlighted panel in yellow marking 7T SWI with a hypointense band along the cortical-WM boundary corresponding to FLAIR hyperintensity. FLAIR hyperintensities are subtle and months 0C2 preceding acquisition of the SWI sequence. The FLAIR hyperintensities associated with the SWI changes continue to evolve and become more confluent from months 3 to 4 4. Open in a separate window Physique 3. Variability of SWI hypointensity and FLAIR hyperitensity in 3 PML regions on 3T and 7T MRI. Panel A: 7T GRE sequence, Panel B: 3T FLAIR sequence, and Panel C: 3 T SWI sequence. Variability of the SWI hypointensity and FLAIR hyperintensity are apparent in comparing 3 cortical regions. Region 1 has minimal SWI changes (C) but with marked FLAIR changes (B). Region 2 has marked SWI changed with FLAIR hyperintesity predominantly along the cortex with relatively normal appearing WM. Region 3 demonstrates both cortical SWI changes with associated WM FLAIR hyperintensity. Abbreviations: FLAIR – fluid attenuated inversion recovery, GRE C gradient echo, PML C progressive multifocal leukoencephalopathy, SWI C susceptibility weighted imaging, T C telsa, WM C white matter. In the PCNSL cohort, 25 patients had SWI or GRE sequence available. Similar changes had been only observed in 3 (12.0%) individuals with PCNSL. Two had been recognized in 1.5T SWI and something in 3.0T SWI sequences (100% contract, 1.00). Susceptibility adjustments across the cortex had been more prevalent in PML than PCNSL (OR 12.83, 95%.
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