Person:
Bakshi, Rohit

Profile Picture

Email Address

AA Acceptance Date

Birth Date

Research Projects

Organizational Units

Job Title

Last Name

Bakshi

First Name

Rohit

Name

Bakshi, Rohit
Author's Publications: search.filters.isAuthorOfPublication.d3011377-e386-4a19-8aec-e28be9e82c18

Search Results

Now showing 1 - 10 of 30
  • No Thumbnail Available
    Publication
    3 T MRI relaxometry detects T2 prolongation in the cerebral normal-appearing white matter in multiple sclerosis
    (Elsevier BV, 2009-07-01) Neema, Mohit; Goldberg-Zimring, Daniel; Guss, Zachary D.; Healy, Brian; Guttmann, Charles; Houtchens, Maria; Weiner, Howard; Horsfield, Mark A.; Hackney, David; Alsop, David; Bakshi, Rohit
    MRI at 3 T has increased sensitivity in detecting overt multiple sclerosis (MS) brain lesions; a growing body of data suggests clinically relevant damage occurs in the normal-appearing white matter (NAWM). We tested a novel pulse sequence to determine whether 3 T MRI spin–spin relaxometry detected damage in NAWM of MS patients (n = 13) vs. age-matched normal controls [(NL) (n = 11)]. Baseline characteristics of the MS group were: age (mean ± SD) 42.5 ± 5.4 (range 33–51 years), disease duration 9.0 ± 6.4 (range 1–22 years), Expanded Disability Status Scale score 2.5 ± 1.7 (range 1–6.5). Brain MRI measures, obtained at 3 T, included global and regional NAWM transverse relaxation rate [R2 (= 1/T2)], derived from 3D fast spin-echo T2 prepared images, and global white matter volume fraction derived from SPGR images. The regional NAWM areas investigated were the frontal lobe, parietal lobe, and the genu and splenium of the corpus callosum. Mean NAWM R2 was lower (indicating T2 prolongation) in MS than NL in the whole brain (p = 0.00047), frontal NAWM (p = 0.00015), parietal NAWM (p = 0.0069) and callosal genu (p = 0.0019). Similarly, R2 histogram peak position was lower in NAWM in MS than NL in the whole brain (p = 0.019). However, the normalized WM volume fractions were similar in both MS and NL (p > 0.1). This pilot study suggests that a novel 3D fast spin-echo pulse sequence at 3 T, used to derive R2 relaxation maps, can detect tissue damage in the global and regional cerebral NAWM of MS patients that is missed by conventional lesion and atrophy measures. Such findings may represent demyelination, inflammation, glial proliferation and axonal loss.
  • No Thumbnail Available
    Publication
    The Relationships among MRI-Defined Spinal Cord Involvement, Brain Involvement, and Disability in Multiple Sclerosis
    (Wiley, 2012-04) Cohen, Adam B.; Neema, Mohit; Arora, Ashish; Dell’Oglio, Elisa; Benedict, Ralph H. B.; Tauhid, Shahamat; Goldberg-Zimring, Daniel; Chavarro-Nieto, Christian; Ceccarelli, Antonella; Klein, Joshua; Stankiewicz, James M.; Houtchens, Maria; Buckle, Guy J.; Alsop, David; Guttmann, Charles; Bakshi, Rohit
    Objective To determine the inter-relationships between MRI-defined lesion and atrophy measures of spinal cord involvement and brain involvement and their relationships to disability in a small cohort of patients with multiple sclerosis (MS). Background Although it is known that cervical spinal cord atrophy correlates with disability in MS, it is unknown whether it is the most important determinant when compared to other regions of the CNS. Furthermore, it is not clear to what extent brain and cord lesions and atrophy are related. Design/methods 3T MRI of the whole brain and whole spinal cord was obtained in 21 patients with MS, including 18 with relapsing-remitting, one with secondary progressive, one with primary progressive, and one with a clinically isolated syndrome. Brain global gray and white matter volumes were segmented with SPM8. Spinal cord contour volume was segmented in whole by a semi-automated method with bins assigned to either the cervical or thoracic regions. All CNS volumes were normalized by the intracranial volume. Brain and cord T2 hyperintense lesions were segmented using a semi-automated edge finding tool. Results Among all MRI measures, only upper cervical spinal cord volume significantly correlated with Expanded Disability Status Scale score (r=−0.515, p=0.020). The brain-cord relationships between whole or regional spinal cord volume or lesions and gray matter, white matter, or whole brain volume or whole brain lesions were generally weak and all non-significant. Conclusions/relevance In this preliminary study of mildly disabled, treated MS patients, cervical spinal cord atrophy most strongly correlates with physical disability in MS when accounting for a wide range of other CNS measures of lesions and atrophy, including thoracic or whole spinal cord volume, and cerebral gray, white or whole brain volume. The weak relationship between spinal cord and brain lesions and atrophy may suggest that they progress rather independently in patients with MS.
  • Thumbnail Image
    Publication
    Automated segmentation of cerebral deep gray matter from MRI scans: effect of field strength on sensitivity and reliability
    (BioMed Central, 2017) Chu, Renxin; Hurwitz, Shelley; Tauhid, Shahamat; Bakshi, Rohit
    Background: The cerebral subcortical deep gray matter nuclei (DGM) are a common, early, and clinically-relevant site of atrophy in multiple sclerosis (MS). Robust and reliable DGM segmentation could prove useful to evaluate putative neuroprotective MS therapies. The objective of the study was to compare the sensitivity and reliability of DGM volumes obtained from 1.5T vs. 3T MRI. Methods: Fourteen patients with MS [age (mean, range) 50.2 (32.0–60.8) years, disease duration 18.4 (8.2–35.5) years, Expanded Disability Status Scale score 3.1 (0–6), median 3.0] and 15 normal controls (NC) underwent brain 3D T1-weighted paired scan-rescans at 1.5T and 3T. DGM (caudate, thalamus, globus pallidus, and putamen) segmentation was obtained by the fully automated FSL-FIRST pipeline. Both raw and normalized volumes were derived. Results: DGM volumes were generally higher at 3T vs. 1.5T in both groups. For raw volumes, 3T showed slightly better sensitivity (thalamus: p = 0.02; caudate: p = 0.10; putamen: p = 0.02; globus pallidus: p = 0.0004; total DGM: p = 0.01) than 1.5T (thalamus: p = 0.05; caudate: p = 0.09; putamen: p = 0.03; globus pallidus: p = 0.0006; total DGM: p = 0.02) for detecting DGM atrophy in MS vs. NC. For normalized volumes, 3T but not 1.5T detected atrophy in the globus pallidus in the MS group. Across all subjects, scan-rescan reliability was generally very high for both platforms, showing slightly higher reliability for some DGM volumes at 3T. Raw volumes showed higher reliability than normalized volumes. Raw DGM volume showed higher reliability than the individual structures. Conclusions: These results suggest somewhat higher sensitivity and reliability of DGM volumes obtained from 3T vs. 1.5T MRI. Further studies should assess the role of this 3T pipeline in tracking potential MS neurotherapeutic effects.
  • Thumbnail Image
    Publication
    Detection of aryl hydrocarbon receptor agonists in human samples
    (Nature Publishing Group UK, 2018) Rothhammer, Veit; Borucki, Davis M.; Kenison, Jessica E.; Hewson, Patrick; Wang, Zhongyan; Bakshi, Rohit; Sherr, David H.; Quintana, Francisco
    The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor with important functions in the immune response and cancer. AHR agonists are provided by the environment, the commensal flora and the metabolism. Considering AHR physiological functions, AHR agonists may have important effects on health and disease. Thus, the quantification of AHR agonists in biological samples is of scientific and clinical relevance. We compared different reporter systems for the detection of AHR agonists in serum samples of Multiple Sclerosis (MS) patients, and assessed the influence of transfection methods and cell lines in a reporter-based in vitro assay. While the use of stable or transient reporters did not influence the measurement of AHR agonistic activity, the species of the cell lines used in these reporter assays had important effects on the reporter readings. These observations suggest that cell-specific factors influence AHR activation and signaling. Thus, based on the reported species selectivity of AHR ligands and the cell species-of-origin effects that we describe in this manuscript, the use of human cell lines is encouraged for the analysis of AHR agonistic activity in human samples. These findings may be relevant for the analysis of AHR agonists in human samples in the context of inflammatory and neoplastic disorders.
  • Thumbnail Image
    Publication
    Dual‐Sensitivity Multiple Sclerosis Lesion and CSF Segmentation for Multichannel 3T Brain MRI
    (John Wiley and Sons Inc., 2017) Meier, Dominik S.; Guttmann, Charles; Tummala, Subhash; Moscufo, Nicola; Cavallari, Michele; Tauhid, Shahamat; Bakshi, Rohit; Weiner, Howard
    ABSTRACT BACKGROUND AND PURPOSE A pipeline for fully automated segmentation of 3T brain MRI scans in multiple sclerosis (MS) is presented. This 3T morphometry (3TM) pipeline provides indicators of MS disease progression from multichannel datasets with high‐resolution 3‐dimensional T1‐weighted, T2‐weighted, and fluid‐attenuated inversion‐recovery (FLAIR) contrast. 3TM segments white (WM) and gray matter (GM) and cerebrospinal fluid (CSF) to assess atrophy and provides WM lesion (WML) volume. METHODS To address nonuniform distribution of noise/contrast (eg, posterior fossa in 3D‐FLAIR) of 3T magnetic resonance imaging, the method employs dual sensitivity (different sensitivities for lesion detection in predefined regions). We tested this approach by assigning different sensitivities to supratentorial and infratentorial regions, and validated the segmentation for accuracy against manual delineation, and for precision in scan‐rescans. RESULTS Intraclass correlation coefficients of .95, .91, and .86 were observed for WML and CSF segmentation accuracy and brain parenchymal fraction (BPF). Dual sensitivity significantly reduced infratentorial false‐positive WMLs, affording increases in global sensitivity without decreasing specificity. Scan‐rescan yielded coefficients of variation (COVs) of 8% and .4% for WMLs and BPF and COVs of .8%, 1%, and 2% for GM, WM, and CSF volumes. WML volume difference/precision was .49 ± .72 mL over a range of 0–24 mL. Correlation between BPF and age was r = .62 (P = .0004), and effect size for detecting brain atrophy was Cohen's d = 1.26 (standardized mean difference vs. healthy controls). CONCLUSIONS This pipeline produces probability maps for brain lesions and tissue classes, facilitating expert review/correction and may provide high throughput, efficient characterization of MS in large datasets.
  • Thumbnail Image
    Publication
    Microstructural Changes in the Striatum and Their Impact on Motor and Neuropsychological Performance in Patients with Multiple Sclerosis
    (Public Library of Science, 2014) Cavallari, Michele; Ceccarelli, Antonia; Wang, Guang-Yi; Moscufo, Nicola; Hannoun, Salem; Matulis, Christina R.; Jackson, Jonathan S.; Glanz, Bonnie; Bakshi, Rohit; Neema, M; Guttmann, Charles
    Grey matter (GM) damage is a clinically relevant feature of multiple sclerosis (MS) that has been previously assessed with diffusion tensor imaging (DTI). Fractional anisotropy (FA) of the basal ganglia and thalamus might be increased in MS patients, and correlates with disability scores. Despite the established role of the striatum and thalamus in motor control, mood and cognition, the impact of DTI changes within these structures on motor and neuropsychological performance has not yet been specifically addressed in MS. We investigated DTI metrics of deep GM nuclei and their potential association with mobility and neuropsychological function. DTI metrics from 3T MRI were assessed in the caudate, putamen, and thalamus of 30 MS patients and 10 controls. Sixteen of the patients underwent neuropsychological testing. FA of the caudate and putamen was higher in MS patients compared to controls. Caudate FA correlated with Expanded Disability Status Scale score, Ambulation Index, and severity of depressive symptomatology. Putamen and thalamus FA correlated with deficits in memory tests. In contrast, cerebral white matter (WM) lesion burden showed no significant correlation with any of the disability, mobility and psychometric parameters. Our findings support evidence of FA changes in the basal ganglia in MS patients, as well as deep GM involvement in disabling features of MS, including mobility and cognitive impairment. Deep GM FA appears to be a more sensitive correlate of disability than WM lesion burden.
  • Thumbnail Image
    Publication
    T1- vs. T2-based MRI measures of spinal cord volume in healthy subjects and patients with multiple sclerosis
    (BioMed Central, 2015) Kim, Gloria; Khalid, Fariha; Oommen, Vinit V.; Tauhid, Shahamat; Chu, Renxin; Horsfield, Mark A.; Healy, Brian; Bakshi, Rohit
    Background: The reliable and efficient measurement of spinal cord atrophy is of growing interest in monitoring disease progression in multiple sclerosis (MS). Methods: We compared T1- and T2-weighted MRI for measuring cervical spinal cord volume in 31 patients with MS and 18 age-matched controls (NC) from T1-weighted gradient recalled echo and T2-weighted fast spin-echo 1.5 T axial acquisitions. The two sequences were matched on slice thickness, signal averages and voxel size. An active surface software tool determined the normalized mean cervical cord cross-sectional area. Results: T1-derived cord areas were higher than T2 areas in the whole cohort (estimated mean difference = 7.03 mm2 (8.89 %); 95 % Confidence Interval (CI): 5.91, 8.14; p < 0.0001) and in both groups separately. There were trends for lower spinal cord areas in MS vs. NC with both sequences. For the T1 cord area, the mean difference was 3.7 mm2 (4.55 %) (95 % CI: −1.36, 8.78; p = 0.15). For the T2 cord area, the difference was larger [mean difference 4.9 mm2 (6.52 %) (95 % CI: −0.83, 10.67); p = 0.091]. The T1 and T2 cord areas showed similar weak to moderate correlations with measures of clinical status and T2 spinal cord lesion volume in the MS group. Superficial spinal cord T2 lesions had no apparent confounding effect on the outlining tool. The mean intra-rater and inter-rater coefficients of variation ranged from 0.27 to 0.91 % for T1- and 0.66 to 0.99 % for T2-derived cord areas. Conclusion: T2-weighted images may prove efficient for measuring cervical spinal cord atrophy in MS, with the added advantage of lesion detectability.
  • Thumbnail Image
    Publication
    Handling changes in MRI acquisition parameters in modeling whole brain lesion volume and atrophy data in multiple sclerosis subjects: Comparison of linear mixed-effect models
    (Elsevier, 2015) Chua, Alicia S.; Egorova, Svetlana; Anderson, Mark C.; Polgar-Turcsanyi, Mariann; Chitnis, Tanuja; Weiner, Howard; Guttmann, Charles R.G.; Bakshi, Rohit; Healy, Brian
    Magnetic resonance imaging (MRI) of the brain provides important outcome measures in the longitudinal evaluation of disease activity and progression in MS subjects. Two common measures derived from brain MRI scans are the brain parenchymal fraction (BPF) and T2 hyperintense lesion volume (T2LV), and these measures are routinely assessed longitudinally in clinical trials and observational studies. When measuring each outcome longitudinally, observed changes may be potentially confounded by variability in MRI acquisition parameters between scans. In order to accurately model longitudinal change, the acquisition parameters should thus be considered in statistical models. In this paper, several models for including protocol as well as individual MRI acquisition parameters in linear mixed models were compared using a large dataset of 3453 longitudinal MRI scans from 1341 subjects enrolled in the CLIMB study, and model fit indices were compared across the models. The model that best explained the variance in BPF data was a random intercept and random slope with protocol specific residual variance along with the following fixed-effects: baseline age, baseline disease duration, protocol and study time. The model that best explained the variance in T2LV was a random intercept and random slope along with the following fixed-effects: baseline age, baseline disease duration, protocol and study time. In light of these findings, future studies pertaining to BPF and T2LV outcomes should carefully account for the protocol factors within longitudinal models to ensure that the disease trajectory of MS subjects can be assessed more accurately.
  • Thumbnail Image
    Publication
    An expanded composite scale of MRI-defined disease severity in multiple sclerosis: MRDSS2
    (Lippincott Williams & Wilkins, 2014) Bakshi, Rohit; Neema, M; Tauhid, Shahamat; Healy, Brian C.; Glanz, Bonnie; Kim, Gloria; Miller, Jennifer; Berkowitz, Julia L.; Bove, Riley; Houtchens, Maria; Severson, Christopher; Stankiewicz, James; Stazzone, Lynn; Chitnis, Tanuja; Guttmann, Charles R.G.; Weiner, Howard; Ceccarelli, Antonia
    The objective of this study was to test a new version of the Magnetic Resonance Disease Severity Scale (MRDSS2), incorporating cerebral gray matter (GM) and spinal cord involvement from 3 T MRI, in modeling the relationship between MRI and physical disability or cognitive status in multiple sclerosis (MS). Fifty-five MS patients and 30 normal controls underwent high-resolution 3 T MRI. The patients had an Expanded Disability Status Scale score of 1.6±1.7 (mean±SD). The cerebral normalized GM fraction (GMF), the T2 lesion volume (T2LV), and the ratio of T1 hypointense LV to T2LV (T1/T2) were derived from brain images. Upper cervical spinal cord area (UCCA) was obtained from spinal cord images. A within-subject d-score (difference of MS from normal control) for each MRI component was calculated, equally weighted, and summed to form MRDSS2. With regard to the relationship between physical disability and MRDSS2 or its individual components, MRI–Expanded Disability Status Scale correlations were significant for MRDSS2 (r=0.33, P=0.013) and UCCA (r=−0.33, P=0.015), but not for GMF (P=0.198), T2LV (P=0.707), and T1/T2 (P=0.240). The inclusion of UCCA appeared to drive this MRI–disability relationship in MRDSS2. With regard to cognition, MRDSS2 showed a larger effect size (P=0.035) than its individual components [GMF (P=0.081), T2LV (P=0. 179), T1/T2 (P=0.043), and UCCA (P=0.818)] in comparing cognitively impaired with cognitively preserved patients (defined by the Minimal Assessment of Cognitive Function in MS). Both cerebral lesions (T1/T2) and atrophy (GMF) appeared to drive this relationship. We describe a new version of the MRDSS, which has been expanded to include cerebral GM and spinal cord involvement. MRDSS2 has concurrent validity with clinical status.
  • Thumbnail Image
    Publication
    The Effect of Dimethyl Fumarate on Cerebral Gray Matter Atrophy in Multiple Sclerosis
    (Springer Healthcare, 2016) Dupuy, Sheena L.; Tauhid, Shahamat; Hurwitz, Shelley; Chu, Renxin; Yousuf, Fawad; Bakshi, Rohit
    Introduction: The objective of this pilot study was to compare cerebral gray matter (GM) atrophy over 1 year in patients starting dimethyl fumarate (DMF) for multiple sclerosis (MS) to that of patients on no disease-modifying treatment (noDMT). DMF is an established therapy for relapsing–remitting (RR) MS. Methods: We retrospectively analyzed 20 patients with RRMS at the start of DMF [age (mean ± SD) 46.1 ± 10.2 years, Expanded Disability Status Scale (EDSS) score 1.1 ± 1.2, timed 25-foot walk (T25FW) 4.6 ± 0.8 s] and eight patients on noDMT (age 42.5 ± 6.6 years, EDSS 1.7 ± 1.1, T25FW 4.4 ± 0.6 s). Baseline and 1-year 3D T1-weighted 3T MRI was processed with automated pipelines (SIENA, FSL-FIRST) to assess percentage whole brain volume change (PBVC) and deep GM (DGM) atrophy. Group differences were assessed by analysis of covariance, with time between MRI scans as a covariate. Results: Over 1 year, the DMF group showed a lower rate of whole brain atrophy than the noDMT group (PBVC: −0.37 ± 0.49% vs. −1.04 ± 0.67%, p = 0.005). The DMF group also had less change in putamen volume (−0.06 ± 0.22 vs. −0.32 ± 0.28 ml, p = 0.02). There were no significant on-study differences between groups in caudate, globus pallidus, thalamus, total DGM volume, T2 lesion volume, EDSS, or T25FW (all p > 0.20). Conclusions: These results suggest a treatment effect of DMF on GM atrophy appearing at 1 year after starting therapy. However, due to the retrospective study design and sample size, these findings should be considered preliminary, and require confirmation in future investigations. Funding Biogen.