Joonmi Oh

Survival analysis in patients with glioblastoma multiforme: Predictive value of choline-to-n-acetylaspartate index, apparent diffusion coefficient, and relative cerebral blood volume

To investigate the potential value of pre‐external‐beam radiation therapy (XRT) choline‐to‐NAA (N‐acetylaspartate) index (CNI), apparent diffusion coefficient (ADC), and relative cerebral blood volume (rCBV) for predicting survival in newly diagnosed patients with glioblastoma multiforme (GBM).

Quantitative apparent diffusion coefficients and T2 relaxation times in characterizing contrast enhancing brain tumors and regions of peritumoral edema

To investigate the potential value and relationship of in vivo quantification of apparent diffusion coefficients (ADCs) and T2 relaxation times for characterizing brain tumor cellularity and tumor‐related edema.

Directional diffusion in relapsing-remitting multiple sclerosis: A possible in vivo signature of Wallerian degeneration

To examine the role of directional dependence of the apparent diffusion coefficients in the evaluation of normal‐appearing brain regions of patients with relapsing‐remitting multiple sclerosis.

Mechanisms of normal appearing corpus callosum injury related to pericallosal T1 lesions in multiple sclerosis using directional diffusion tensor and 1H MRS imaging

Objectives: To investigate the extent of tissue damage in a region of normal appearing corpus callosum (NACC) for different forms of multiple sclerosis (MS) using diffusion tensor and proton magnetic resonance (MR) spectroscopic imaging. Methods: A total of 47 patients with MS and 15 controls were included. Regions of interest from the NACC were manually segmented using high resolution anatomical images. Diffusion tensor eigenvalues and metabolite ratio of N-acetyl-aspartate (NAA) to creatine/phosphocreatine (Cr) were calculated in the NACC region. Results: Increased apparent diffusion coefficients (ADCs) and decreased anisotropy were observed in the NACC for patients with MS relative to the control subjects. These resulted from increased diffusion tensor eigenvalues perpendicular to the maximum diffusion direction. The NAA:Cr ratio was decreased in the NACC for patients with MS relative to the control subjects. Significant correlations between pericallosal T1 lesion load and MR modalities in the NACC were observed for patients with relapsing remitting/secondary progressive MS (RR/SPMS), but not for patients with primary progressive MS (PPMS). Conclusion: This study provides further insight into changes in the ADC and diffusion anisotropy based on the diffusion tensor eigenvalues for patients with MS. The changes in the diffusion tensor eigenvalues and NAA:Cr ratio in the NACC for patients with RR/SPMS suggest axonal injury and/or dysfunction induced by wallerian degeneration. The lack of correlation between these variables in the NACC and focal MS lesions for patients with PPMS further supports intrinsic differences related to tissue injury between these subtypes of MS.

Multislice brain myelin water fractions at 3T in multiple sclerosis

Purpose. To evaluate a multislice nonlinearly‐spaced 12‐echo imaging sequence at 3T covering the supratentorial brain for the quantification of myelin water fraction (MWF) in multiple sclerosis (MS) patients. Methods. Eighty‐nine patients with, or at risk of, MS (69 relapsing remitting MS [RRMS], 7 secondary progressive MS [SPMS], 13 clinically isolated syndrome [CIS]) and 28 controls were studied. Twelve‐echo datasets were acquired using a multislice T2 prep spiral imaging sequence and were fitted using a nonnegative least squares algorithm. The mean MWF within normal appearing white matter (NAWM), contrast‐enhancing (CE), and nonenhancing T2 lesions were calculated. Results. Mean MWF in white matter for controls was 11.3%. Mean MWF was significantly reduced in NAWM of MS patients (10.6%, P= .004) relative to controls. SPMS/RRMS patients with disease duration >5 years (10.3%) had lower MWF compared to CIS/RRMS with disease duration ≤5 years (10.8%, P= .03). Mean MWF was reduced by 26% and 29% within both CE (P < .0001) and nonenhancing T2 lesions (P < .0001) relative to controls. Conclusions. Using a multicomponent T2 sequence at 3T, a significant decrease in the supratentorial MWF was observed in MS NAWM and lesions relative to controls. The method was sensitive to detect white matter changes early in the disease process.

MRI lesion volume heterogeneity in primary progressive MS in relation with axonal damage and brain atrophy

Objectives: To investigate whether axonal damage in primary progressive (PP) multiple sclerosis (MS), as measured by proton magnetic resonance spectroscopy (HMRS) imaging and brain atrophy, is a function of T2 weighted brain lesion volume. Methods: 34 PP MS patients were divided into two categories: low (<3 cm3, n = 18) or high (≥3 cm3, n = 16) T2 lesion load (LL). An Index of Brain Atrophy (IBA) was calculated and HMRS metabolite ratios were derived from a central brain area centred at the corpus callosum. Results: Patient groups did not differ with regard to clinical characteristics and showed lower mean IBA and mean N-acetylaspartate:creatinine (NAA:Cr) ratios compared to healthy controls. Conclusion: PP patients with low and high brain T2LL have detectable brain atrophy and NAA:Cr reduction compared to healthy controls. In PP MS, T2 lesions alone are insufficient to explain the presence of brain atrophy and decrease in NAA:Cr.

Magnetic Resonance Spectroscopy Markers of Disease Progression in Multiple Sclerosis

IMPORTANCE Predicting disease evolution is becoming essential for optimizing treatment decision making in multiple sclerosis (MS). Multiple sclerosis pathologic damage typically includes demyelination, neuro-axonal loss, and astrogliosis. OBJECTIVE To evaluate the potential of magnetic resonance markers of central nervous system injury to predict brain-volume loss and clinical disability in multiple sclerosis. DESIGN, SETTING, AND PARTICIPANTS Participants were selected from the Multiple Sclerosis Center at the University of California-San Francisco. The preliminary data set included 59 patients with MS and 43 healthy control individuals. The confirmatory data set included 220 patients from an independent, large genotype-phenotype research project. MAIN OUTCOMES AND MEASURES Baseline N-acetylaspartate (NAA) level, myo-inositol (mI) in normal-appearing white and gray matter, myelin water fraction in normal-appearing white matter, markers of axonal damage, astrogliosis, and demyelination were evaluated as predictors in a preliminary data set. Potential predictors were subsequently tested for replication in a confirmatory data set. Clinical scores and percentage of brain-volume change were obtained annually over 4 years as outcomes. Predictors of outcomes were assessed using linear models, linear mixed-effects models, and logistic regression. RESULTS N-acetylaspartate and mI both had statistically significant effects on brain volume, prompting the use of the mI:NAA ratio in normal-appearing white matter as a predictor. The ratio was a predictor of brain-volume change in both cohorts (annual slope in the percentage of brain-volume change/unit of increase in the ratio: -1.68; 95% CI, -3.05 to -0.30; P = .02 in the preliminary study cohort and -1.08; 95% CI, -1.95 to -0.20; P = .02 in the confirmatory study cohort). Furthermore, the mI:NAA ratio predicted clinical disability (Multiple Sclerosis Functional Composite evolution: -0.52 points annually, P < .001; Multiple Sclerosis Functional Composite sustained progression: odds ratio, 2.76/SD increase in the ratio; 95% CI, 1.32 to 6.47; P = .01) in the preliminary data set and predicted Multiple Sclerosis Functional Composite evolution (-0.23 points annually; P = .01), Expanded Disability Status Scale evolution (0.57 points annually; P = .04), and Expanded Disability Status Scale sustained progression (odds ratio, 1.46; 95% CI, 1.10 to 1.94; P = .009) in the confirmatory data set. Myelin water fraction did not show predictive value. CONCLUSIONS AND RELEVANCE The mI:NAA ratio in normal-appearing white matter has consistent predictive power on brain atrophy and neurological disability evolution. The combined presence of astrogliosis and axonal damage in white matter has cardinal importance in disease severity.

Dissociating perceptual and conceptual implicit memory in multiple sclerosis patients

Previous studies indicate that Multiple Sclerosis (MS) patients exhibit deficits in tests of explicit memory such as free recall, but show normal priming on implicit tests of memory such as word stem completion. However, the memory performance of patients with different MS disease subtypes has not been fully examined. In the current study, memory was assessed in Primary Progressive (PPMS), Relapsing Remitting (RRMS), and Secondary Progressive (SPMS) MS subgroups. Explicit memory as well as perceptual and conceptual implicit memory were examined using free recall, word fragment completion, and exemplar generation tests, respectively. All three groups of MS patients exhibited free recall deficits and normal priming on the exemplar generation test. However, the PPMS group exhibited a deficit in word fragment completion priming, whereas the RRMS and SPMS groups exhibited normal levels of priming on this task. Lesion load was assessed using magnetic resonance imaging and was negatively correlated with explicit memory performance, but it did not account for the observed deficits in perceptual implicit memory. The results indicate that PPMS patients exhibit a pattern of memory impairment that is distinct from that of the RRMS and SPMS groups. Moreover, the results indicate that perceptual implicit memory can be neurologically dissociated from conceptual implicit memory.

Amyloid PET Screening for Enrichment of Early-Stage Alzheimer Disease Clinical Trials: Experience in a Phase 1b Clinical Trial.

Amyloid positron emission tomography (PET) imaging is being investigated as a screening tool to identify amyloid-positive patients as an enrichment strategy for Alzheimer disease (AD) clinical trial enrollment. In a multicenter, phase 1b trial, patients meeting clinical criteria for prodromal or mild AD underwent florbetapir PET scanning at screening. PET, magnetic resonance imaging, and coregistered PET/magnetic resonance imaging scans were reviewed by 2 independent readers and binary visual readings tabulated. Semiquantitative values of cortical to whole cerebellar standard uptake value ratios were computed (threshold 1.10). Of 278 patients with an evaluable PET scan, 170 (61%) and 185 (67%) were amyloid-positive by visual reading and quantitative analysis, respectively; 39% were excluded from the study due to an amyloid-negative scan based on visual readings. More ApoE &egr;4 carriers than noncarriers were amyloid-positive (80% vs. 43%). Comparison of visual readings with quantitative results identified 21 discordant cases (92% agreement). Interreader and intrareader agreements from visual readings were 98% and 100%, respectively. Amyloid PET imaging is an effective and feasible screening tool for enrollment of amyloid-positive patients with early stages of AD into clinical trials.

COMPARISON OF BASELINE ARIA-H PREVALENCE AT 1.5T AND 3T MRI FIELD STRENGTHS IN A MULTI-SITE GLOBAL CLINICAL TRIAL WITH A COHORT OF 2,137 AD SUBJECTS

Abbreviations: ARIA-H 1⁄4 amyloid-related imaging abnormality hemorrhage/hemosiderin deposition, T 1⁄4 Tesla, N 1⁄4 Subject numbers in each MRI Scanner Strength 1.5T or 3.0T, n 1⁄4 number of subjects in each ARIA-H category. Twelve randomized subjects scanned on 1.5T scanners and 5 randomized subjects scanned on 3T scanners had MRIs that were not assessable for ARIA-H and were not included in this analysis. Poster Presentations: Saturday, July 15, 2017 P37