Human brain atlas-based multimodal MRI analysis of volumetry, diffusimetry, relaxometry and lesion distribution in multiple sclerosis patients and healthy adult controls: Implications for understanding the pathogenesis of multiple sclerosis and consolidation of quantitative MRI results in MS (original) (raw)
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Multi-modal quantitative MRI investigation of brain tissue neurodegeneration in multiple sclerosis
Journal of Magnetic Resonance Imaging, 2012
Purpose-To investigate the utility of multimodal quantitative magnetic resonance imaging (qMRI) and atlas-based methods to identify characteristics of lesion-driven injury and neurodegeneration in relapsing remitting multiple sclerosis (RRMS) Materials and Methods-This work is health insurance portability and accountability act compliant. High resolution T1-weighted, dual echo and fluid-attenuated inversion recovery and diffusion tensor MRI images were prospectively acquired on 68 RRMS patients (range 25-58 years) and 68 age-matched controls. The data were analyzed using standardized human brain atlasbased tissue segmentation procedures to obtain regional volumes and their corresponding T2 relaxation times and DTI maps. Results-Group-averaged brain atlas-based qMRI maps of T2, fractional anisotropy and diffusivities are visually presented and compared between controls and RRMS. The analysis shows a widespread injury in RRMS. Atrophy of the CC was substantial in RRMS. The qMRI attributes of the neocortex in combination with the CC such as T2 and diffusivities were elevated and correlated with disability. Conclusion-Using a standardized multimodal qMRI acquistion and analyses that accounted for lesion distribution we demonstrate that cerebral pathology is widespread in RRMS. Our analysis of CC and neocortex qMRI metrics in relation to disability points to a neurodegenerative injury component that is independent from lesions.
Archives of Neurology, 2005
Background: Diffusion-tensor (DT) magnetic resonance imaging (MRI) has the potential to elucidate some characteristics of tissue microstructure inaccessible to other MRI techniques. Objective: To investigate whether normal-appearing brain tissue abnormalities occur in patients with multiple sclerosis at the earliest clinical stage and whether their severity is predictive of a short-term disease evolution by using DT MRI. Design: Forty-five patients and 22 healthy control subjects were studied. All patients had had a clinically isolated syndrome within the 3 months preceding study enrollment and paraclinical evidence of disease dissemination in space. During a single session, dualecho, pulsed-gradient spin-echo echo-planar, and postgadolinium T1-weighted images of the brain were obtained from each subject. In patients, dual-echo and enhanced images were obtained after 3 and 12 months, to detect MRI signs of disease dissemination in time. An on-study neurological examination was also conducted to ascertain the occurrence of clinical relapses. Mean diffusivity and fractional anisotropy maps were derived from DT images. Normal-appearing white matter (NAWM) and normal-appearing gray matter mean diffusivity and fractional anisotropy histograms were produced and analyzed. Results: During the study period, 29 patients showed MRI evidence of disease dissemination in time. When compared with healthy controls, patients showed higher average NAWM mean diffusivity (P = .01), lower average NAWM mean diffusivity peak height (PϽ.001), and fractional anisotropy (PϽ.001). The DT MRI characteristics of patients did not differ between those with and those without disease dissemination in time at follow-up. Conclusions: In patients with multiple sclerosis at the earliest clinical stage, the severity of NAWM damage does not predict new lesion formation in the short term, suggesting that the "diffuse" component of tissue damage is, at least partially, independent of the "discrete," predominantly inflammatory aspects of the disease since its clinical onset.
Diffusion tensor imaging for characterizing white matter changes in multiple sclerosis
The Egyptian Journal of Radiology and Nuclear Medicine, 2014
To investigate the diagnostic values of quantitative diffusion tensor imaging parameters in detecting abnormalities in white matter of MS patients and correlate this with lesion load and clinical disability as prognostic factors. Patients and methods: Diffusion tensor imaging (DTI) was performed in 45 consecutive MS patients and 20 age-matched healthy control volunteers from March 2011 to November 2013. Mean diffusivity (MD), volume ratio (VR) and the fractional anisotropy (FA) were measured in normal appearing white matter (NAWM) and in different types of focal MS lesions during both activity and remission and compared with normal white matter (NWM) of the control group. Evaluation of lesion load was done by the semiautomated method. Clinical assessment of MS was established using the Kurtzke expanded disability status scale (EDSS) and the Kurtzke functional system score. Results: Significant increase of MD and decrease of FA and VR from normal appearing white matter of the patients to MRI detected active lesions and the least is inactive plaques comparing with NWM of the control group (P value 0.003 for MD, 0.013 for FA, and 0.014 for VR). Correlation and significant difference between {(increase in MD) and (decrease in FA and VR)} and lesion load (strongest in parietal lobes) and also Kurtzke expanded disability status scale (EDSS) and Kurtzke functional system score (KFS-p).
Multiparameter MRI quantification of microstructural tissue alterations in multiple sclerosis
NeuroImage: Clinical
Conventional MRI is not sensitive to many pathological processes underpinning multiple sclerosis (MS) ongoing in normal appearing brain tissue (NABT). Quantitative MRI (qMRI) and a multiparameter mapping (MPM) protocol are used to simultaneously quantify magnetization transfer (MT) saturation, transverse relaxation rate R2* (1/T2*) and longitudinal relaxation rate R1 (1/T1), and assess differences in NABT microstructure between MS patients and healthy controls (HC). Methods: This prospective cross-sectional study involves 36 MS patients (20 females, 16 males; age range 22-63 years; 15 relapsing-remitting MS-RRMS; 21 primary or secondary progressive MS-PMS) and 36 agematched HC (20 females, 16 males); age range 21-61 years). The qMRI maps are computed and segmented in lesions and 3 normal appearing cerebral tissue classes: normal appearing cortical grey matter (NACGM), normal appearing deep grey matter (NADGM), normal appearing white matter (NAWM). Individual median values are extracted for each tissue class and MR parameter. MANOVAs and stepwise regressions assess differences between patients and HC. Results: MS patients are characterized by a decrease in MT, R2* and R1 within NACGM (p < .0001) and NAWM (p < .0001). In NADGM, MT decreases (p < .0001) but R2* and R1 remain normal. These observations tend to be more pronounced in PMS. Quantitative MRI parameters are independent predictors of clinical status: EDSS is significantly related to R1 in NACGM and R2* in NADGM; the latter also predicts motor score. Cognitive score is best predicted by MT parameter within lesions. Conclusions: Multiparametric data of brain microstructure concord with the literature, predict clinical performance and suggest a diffuse reduction in myelin and/or iron content within NABT of MS patients.
Benha Medical Journal
Background: Magnetic resonance imaging (MRI) is a very vital tool to diagnose and monitor multiple sclerosis (MS). Standard MRI measures lack of pathological specificity and are weakly correlated with MS clinical manifestations. Advanced MRI techniques together with diffusion studies square measure up the understanding of the mechanisms underlying tissue injury, repair and functional adaptation in MS but, they need careful standardization. It doesn't only enhance the understanding of the pathophysiology and evolution of disease, but also to generate research hypotheses, monitor treatment, increase costeffectiveness and power of clinical trials. Aim of the Work: The aim of this study is to evaluate the role of DTI in assessment of MS versus the normally-appearing white matter (NAWM). Patients and Methods: The study included 50 patients, 42 females and 8 males having MS (between 20 and 40 years of age) referred from Neurologists to Radio-diagnosis Department at Benha University hospitals with 5 age-matched control subjects (during the period between Aug. 2018 and Jan. 2020). Each patient included in the study was subjected to full history taking, reviewing medical sheet and MR examination including: Conventional MR examination and Diffusion Tensor imaging. Technique was performed using a standard 1.5 Tesla unit. Results: The study showed that DTI can reveal changes in NAWM in MS cases before visible sizable plaques can be detected by conventional MRI.
Diffusion tensor imaging of post mortem multiple sclerosis brain
NeuroImage, 2007
Magnetic resonance imaging (MRI) is being used to probe the central nervous system (CNS) of patients with multiple sclerosis (MS), a chronic demyelinating disease. Conventional T 2 -weighted MRI (cMRI) largely fails to predict the degree of patients' disability. This shortcoming may be due to poor specificity of cMRI for clinically relevant pathology. Diffusion tensor imaging (DTI) has shown promise to be more specific for MS pathology. In this study we investigated the association between histological indices of myelin content, axonal count and gliosis, and two measures of DTI (mean diffusivity [MD] and fractional anisotropy [FA]), in unfixed post mortem MS brain using a 1.5-T MR system. Both MD and FA were significantly lower in post mortem MS brain compared to published data acquired in vivo. However, the differences of MD and FA described in vivo between white matter lesions (WMLs) and normal-appearing white matter (NAWM) were retained in this study of post mortem brain: average MD in WMLs was 0.35 × 10 − 3 mm 2 /s (SD, 0.09) versus 0.22 (0.04) in NAWM; FA was 0.22 (0.06) in WMLs versus 0.38 (0.13) in NAWM. Correlations were detected between myelin content (Tr myelin ) and (i) FA (r = − 0.79, p < 0.001), (ii) MD (r = 0.68, p < 0.001), and (iii) axonal count (r = − 0.81, p < 0.001). Multiple regression suggested that these correlations largely explain the apparent association of axonal count with (i) FA (r = 0.70, p < 0.001) and (ii) MD (r = − 0.66, p < 0.001). In conclusion, this study suggests that FA and MD are affected by myelin content and -to a lesser degree -axonal count in post mortem MS brain.
Journal of Magnetic Resonance Imaging, 2009
Purpose-To investigate the utility of caudate nuceli macro-and microstructural metrics as markers of gray matter degeneration in healthy adults and relapsing-remitting multiple sclerosis patients. Materials and Methods-The normal age and pathology-related changes in caudate nuclei volume (CNV), the corresponding diffusion tensor metrics and the T 2 relaxation times were measured in a cohort of 32 healthy adults (12 men / 20 women; age range 21-59 years) and 32 age-matched relapsing-remitting multiple sclerosis (RRMS) patients (8 men / 34 women; age range 21-57 years). Results-Smaller values in both the absolute CNV and the caudate volume ratio relative to the total intracranial volume (CNVp), were observed in the RRMS group relative to healthy controls. The fractional anisotropy (FA), based on the diffusion tensor imaging (DTI) of the caudate nuclei increased with age in healthy adults (r = 0.52; p = 0.003), but not in patients (r = 0.28; p = 0.12). The caudate FA value was approximately 9% larger in RRMS patients relative to controls (p = 0.001). The mean diffusivity of CN was greater in the RRMS group compared to controls (p=0.02). The caudate T 2 relaxation times were smaller in the RRMS group relative to the control group (3% reduction, p = 0.05). T2 relaxation times did not exhibit age-related changes (p > 0.35) in either cohort. Strong and significant correlations between CNVp and whole brain lesion load (r = −0.48; p = 0.005) and whole brain CSF fraction (r = −0.46; p = 0.01) were also noted. Conclusion-These preliminary findings indicate that caudate DTI-derived metrics can serve as potential quantitative radiological markers of MS pathology.
Neural Regeneration Research, 2019
Multiple sclerosis is a neurodegenerative and inflammatory disease, a hallmark of which is demyelinating lesions in the white matter. We hypothesized that alterations in white matter microstructures can be noninvasively characterized by advanced diffusion magnetic resonance imaging. Seven diffusion metrics were extracted from hybrid diffusion imaging acquisitions via classic diffusion tensor imaging, neurite orientation dispersion and density imaging, and q-space imaging. We investigated the sensitivity of the diffusion metrics in 36 sets of regions of interest in the brain white matter of six female patients (age 52.8 ± 4.3 years) with multiple sclerosis. Each region of interest set included a conventional T2-defined lesion, a matched perilesion area, and normal-appearing white matter. Six patients with multiple sclerosis (n = 5) or clinically isolated syndrome (n = 1) at a mild to moderate disability level were recruited. The patients exhibited microstructural alterations from normal-appearing white matter transitioning to perilesion areas and lesions, consistent with decreased tissue restriction, decreased axonal density, and increased classic diffusion tensor imaging diffusivity. The findings suggest that diffusion compartment modeling and q-space analysis appeared to be sensitive for detecting subtle microstructural alterations between perilesion areas and
Journal of Neurology, 2018
Objective Both normal gray matter atrophy and brain tissue relaxation rates, in addition to total lesion volume, have shown significant correlations with cognitive test scores in multiple sclerosis (MS). Aim of the study was to assess the relative contributions of macro-and microstructural changes of both normal and abnormal brain tissues, probed, respectively, by their volumes and relaxation rates, to the cognitive status and physical disability of MS patients. Methods MRI studies from 241 patients with relapsing-remitting MS were retrospectively analyzed by fully automated multiparametric relaxometric segmentation. Ordinal backward regression analysis was applied to the resulting volumes and relaxation rates of both normal (gray matter, normal-appearing white matter and CSF) and abnormal (T2-weighted lesions) brain tissues, controlling for age, sex and disease duration, to identify the main independent contributors to the cognitive status, as measured by the percentage of failed tests at a cognitive test battery (Rao's Brief Repeatable Battery and Stroop test, available in 186 patients), and to the physical disability, as assessed by the Expanded Disability Status Scale (EDSS). Results The R1 relaxation rate (a putative marker of tissue disruption) of the MS lesions appeared the single most significant contributor to cognitive impairment (p < 0.001). On the contrary, the EDSS appeared mainly affected by the decrease in R2 of the gray matter (p < 0.0001), (possibly influenced by cortical plaques, edema and inflammation). Conclusions In RR-MS the tissue damage in white matter lesions appears the single main determinant of the cognitive status of patients, likely through disconnection phenomena, while the physical disability appears related to the involvement of gray matter.
American Journal of Neuroradiology, 2012
BACKGROUND AND PURPOSE: MRI markers of neuroaxonal damage in MS have emerged as critical long-term predictors of MS-related disability. Here we investigated the potential of whole-brain diffusivity and brain volume for the prediction of cross-sectional disability and short-to medium-term clinical evolution. MATERIALS AND METHODS: In this multimodal prospective longitudinal MRI study of 54 patients with MS (87% under immunomodulatory therapy, baseline and follow-up at a median of 12 months), ADC histogram analysis, WM lesion load, BPF, whole-brain atrophy rate, MSFC score, and EDSS score were obtained. A total of 44 patients with no relapse at both time points were included. RESULTS: At both time points, ADC histogram analysis provided robust predictors of the MSFC scores (maximal R 2 ϭ 0.576, P Ͻ .001), incorporated cognition and fine-motor skill subscores, and EDSS scores. Significant changes beyond physiologic age-related changes at follow-up were noted for ADC histogram markers and BPF. Stronger diffusivity alterations and brain volume at baseline predicted MSFC decline, as demonstrated by multiple linear regression analysis (mean ADC, R 2 ϭ 0.203; P ϭ .003) and lower baseline BPF in patients with declined compared with stable MSFC scores (P ϭ .001). Results were independent of intercurrent relapses. CONCLUSIONS: Diffusion histogram analysis provided stable surrogates of disability in MS and proved sensitive for monitoring disease progression during a median of 12 months. Advanced neuroaxonal pathology at baseline was indicative of an increased risk for sustained progression during a median of 12 months, independent of intercurrent relapses. ABBREVIATIONS: BPF ϭ brain parenchyma fraction; CI ϭ confidence interval; EDSS ϭ Expanded Disability Status Scale; GM ϭ gray matter; MSFC ϭ MS Functional Composite; 9-HPT ϭ 9-Hole Peg Test; PASAT ϭ Paced Auditory Serial Addition Test; PBVC ϭ percentage brain volume change; TWT ϭ timed walk test; WMLL perc ϭ WM lesion load volume as percentage of total WM volume