Comparison of Neurite Orientation Dispersion and Density Imaging and Two-Compartment Spherical Mean Technique Parameter Maps in Multiple Sclerosis

Background: Neurite orientation dispersion and density imaging (NODDI) and the spherical mean technique (SMT) are diffusion MRI methods providing metrics with sensitivity to similar characteristics of white matter microstructure. There has been limited comparison of changes in NODDI and SMT parameters due to multiple sclerosis (MS) pathology in clinical settings.Purpose: To compare group-wise differences between healthy controls and MS patients in NODDI and SMT metrics, investigating associations with disability and correlations with diffusion tensor imaging (DTI) metrics.Methods: Sixty three relapsing-remitting MS patients were compared to 28 healthy controls. NODDI and SMT metrics corresponding to intracellular volume fraction (vin), orientation dispersion (ODI and ODE), diffusivity (D) (SMT only) and isotropic volume fraction (viso) (NODDI only) were calculated from diffusion MRI data, alongside DTI metrics (fractional anisotropy, FA; axial/mean/radial diffusivity, AD/MD/RD). Correlations between all pairs of MRI metrics were calculated in normal-appearing white matter (NAWM). Associations with expanded disability status scale (EDSS), controlling for age and gender, were evaluated. Patient-control differences were assessed voxel-by-voxel in MNI space controlling for age and gender at the 5% significance level, correcting for multiple comparisons. Spatial overlap of areas showing significant differences were compared using Dice coefficients.Results: NODDI and SMT show significant associations with EDSS (standardised beta coefficient −0.34 in NAWM and −0.37 in lesions for NODDI vin; 0.38 and −0.31 for SMT ODE and vin in lesions; p < 0.05). Significant correlations in NAWM are observed between DTI and NODDI/SMT metrics. NODDI vin and SMT vin strongly correlated (r = 0.72, p < 0.05), likewise NODDI ODI and SMT ODE (r = −0.80, p < 0.05). All DTI, NODDI and SMT metrics detect widespread differences between patients and controls in NAWM (12.57% and 11.90% of MNI brain mask for SMT and NODDI vin, Dice overlap of 0.42).Data Conclusion: SMT and NODDI detect significant differences in white matter microstructure between MS patients and controls, concurring on the direction of these changes, providing consistent descriptors of tissue microstructure that correlate with disability and show alterations beyond focal damage. Our study suggests that NODDI and SMT may play a role in monitoring MS in clinical trials and practice.

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Multiple sclerosis pathology in the normal and abnormal appearing white matter of the corpus callosum by diffusion tensor imaging

Multiple Sclerosis Journal ◽

10.1191/1352458504ms1053oa ◽

2004 ◽

Vol 10 (4) ◽

pp. 392-397 ◽

Cited By ~ 40

Author(s):

Bernard D Coombs ◽

Alan Best ◽

Mark S Brown ◽

David E Miller ◽

John Corboy ◽

...

Keyword(s):

Multiple Sclerosis ◽

Diffusion Coefficient ◽

White Matter ◽

Corpus Callosum ◽

Diffusion Tensor ◽

Age And Gender ◽

Secondary Degeneration ◽

Quantitative Mr ◽

Normal Appearing White Matter ◽

And Gender

Lesions in the corpus callosum in multiple sclerosis (MS) include those that are hyperintense on T2-weighted images, which can be either focal (isolated) or connected, but there is evidence that the corpus callosum, similar to other white matter regions, contains normal appearing white matter (NAWM) which is abnormal based on quantitative MR methodologies. In this pilot study, diffusion tensor based measures were determined in corpus callosum from 10 patients with MS and 12 age and gender matched controls. T2-hyperintense lesions were carefully segmented out from normal appearing corpus callosum to minimize contamination of the NAWM fraction with these lesions. The orientationally averaged diffusion coefficient was increased and the fractional anisotropy reduced in the NAWM fraction of the MS patients. These results confirm prior studies which suggest that pathology in the NAWM occurs independent of focal MS lesions, and are not likely the result of sample contamination through or across slices. This injury to the NAWM may be the result of focal, microscopic T2-invisible lesions and/or secondary degeneration related to distant lesions whose related fibres cross the corpus callosum.

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Dysmature superficial white matter microstructure in developmental focal epilepsy

Brain Communications ◽

10.1093/braincomms/fcz002 ◽

2019 ◽

Vol 1 (1) ◽

Cited By ~ 3

Author(s):

Lauren M Ostrowski ◽

Daniel Y Song ◽

Emily L Thorn ◽

Erin E Ross ◽

Sally M Stoyell ◽

...

Keyword(s):

White Matter ◽

Fractional Anisotropy ◽

Diffusion Tensor ◽

Mean Diffusivity ◽

Fine Motor ◽

Epilepsy Syndrome ◽

Healthy Controls ◽

Deep White Matter ◽

White Matter Microstructure ◽

Benign Epilepsy

Abstract Benign epilepsy with centrotemporal spikes is a common childhood epilepsy syndrome that predominantly affects boys, characterized by self-limited focal seizures arising from the perirolandic cortex and fine motor abnormalities. Concurrent with the age-specific presentation of this syndrome, the brain undergoes a developmentally choreographed sequence of white matter microstructural changes, including maturation of association u-fibres abutting the cortex. These short fibres mediate local cortico-cortical communication and provide an age-sensitive structural substrate that could support a focal disease process. To test this hypothesis, we evaluated the microstructural properties of superficial white matter in regions corresponding to u-fibres underlying the perirolandic seizure onset zone in children with this epilepsy syndrome compared with healthy controls. To verify the spatial specificity of these features, we characterized global superficial and deep white matter properties. We further evaluated the characteristics of the perirolandic white matter in relation to performance on a fine motor task, gender and abnormalities observed on EEG. Children with benign epilepsy with centrotemporal spikes (n = 20) and healthy controls (n = 14) underwent multimodal testing with high-resolution MRI including diffusion tensor imaging sequences, sleep EEG recordings and fine motor assessment. We compared white matter microstructural characteristics (axial, radial and mean diffusivity, and fractional anisotropy) between groups in each region. We found distinct abnormalities corresponding to the perirolandic u-fibre region, with increased axial, radial and mean diffusivity and fractional anisotropy values in children with epilepsy (P = 0.039, P = 0.035, P = 0.042 and P = 0.017, respectively). Increased fractional anisotropy in this region, consistent with decreased integrity of crossing sensorimotor u-fibres, correlated with inferior fine motor performance (P = 0.029). There were gender-specific differences in white matter microstructure in the perirolandic region; males and females with epilepsy and healthy males had higher diffusion and fractional anisotropy values than healthy females (P ≤ 0.035 for all measures), suggesting that typical patterns of white matter development disproportionately predispose boys to this developmental epilepsy syndrome. Perirolandic white matter microstructure showed no relationship to epilepsy duration, duration seizure free, or epileptiform burden. There were no group differences in diffusivity or fractional anisotropy in superficial white matter outside of the perirolandic region. Children with epilepsy had increased radial diffusivity (P = 0.022) and decreased fractional anisotropy (P = 0.027) in deep white matter, consistent with a global delay in white matter maturation. These data provide evidence that atypical maturation of white matter microstructure is a basic feature in benign epilepsy with centrotemporal spikes and may contribute to the epilepsy, male predisposition and clinical comorbidities observed in this disorder.

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White matter and nigral alterations in multiple system atrophy-parkinsonian type

npj Parkinson s Disease ◽

10.1038/s41531-021-00236-0 ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Takashi Ogawa ◽

Taku Hatano ◽

Koji Kamagata ◽

Christina Andica ◽

Haruka Takeshige-Amano ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

White Matter ◽

Multiple System Atrophy ◽

Volume Fraction ◽

Diffusion Tensor ◽

Free Water ◽

Substantia Nigra Pars Compacta ◽

Healthy Controls ◽

Cerebellar Peduncle

AbstractMultiple system atrophy (MSA) is classified into two main types: parkinsonian and cerebellar ataxia with oligodendrogliopathy. We examined microstructural alterations in the white matter and the substantia nigra pars compacta (SNc) of patients with MSA of parkinsonian type (MSA-P) using multishell diffusion magnetic resonance imaging (dMRI) and myelin sensitive imaging techniques. Age- and sex-matched patients with MSA-P (n = 21, n = 10 first and second cohorts, respectively), Parkinson’s disease patients (n = 19, 17), and healthy controls (n = 20, 24) were enrolled. Magnetization transfer saturation imaging (MT-sat) and dMRI were obtained using 3-T MRI. Measurements obtained from diffusion tensor imaging (DTI), free-water elimination DTI, neurite orientation dispersion and density imaging (NODDI), and MT-sat were compared between groups. Tract-based spatial statistics analysis revealed differences in diffuse white matter alterations in the free-water fractional volume, myelin volume fraction, and intracellular volume fraction between the patients with MSA-P and healthy controls, whereas free-water and MT-sat differences were limited to the middle cerebellar peduncle in comparison with those with Parkinson’s disease. Region-of-interest analysis of white matter and SNc revealed significant differences in the middle and inferior cerebellar peduncle, pontine crossing tract, corticospinal tract, and SNc between the MSA-P and healthy controls and/or Parkinson’s disease patients. Our results shed light on alterations to brain microstructure in MSA.

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Diffusion Tensor Imaging Before and 3 Months After Concentrated Exposure Response Prevention in Obsessive-Compulsive Disorder

Frontiers in Psychiatry ◽

10.3389/fpsyt.2021.674020 ◽

2021 ◽

Vol 12 ◽

Author(s):

Vilde Brecke ◽

Anders Lillevik Thorsen ◽

Olga Therese Ousdal ◽

Chris Vriend ◽

Dag Alnæs ◽

...

Keyword(s):

Treatment Outcome ◽

Diffusion Tensor Imaging ◽

White Matter ◽

Obsessive Compulsive Disorder ◽

Diffusion Tensor ◽

Healthy Controls ◽

Obsessive Compulsive ◽

Illness Onset ◽

Compulsive Disorder ◽

White Matter Microstructure

Background: Subtle differences in white matter microstructure have been found in obsessive-compulsive disorder (OCD) compared to controls using diffusion tensor imaging (DTI), but it is unclear if and how this change after treatment. The primary aim of this pre-registered study was to investigate white matter integrity between OCD patients and controls and changes after concentrated exposure and response prevention (ERP).Methods: Fractional anisotropy (FA), radial diffusivity (RD), axial diffusivity (AD) and mean diffusivity (MD) were estimated using FMRIB Software Library (FSL). The images were registered to a study-specific template using a longitudinal pipeline based on full tensor information in DTI-TK. Voxel-based analysis was performed using tract-based spatial statistics (TBSS). Using SPSS, we compared the integrity in three bilateral regions of interest (ROI), the sagittal stratum, posterior thalamic radiation and cingulum, in 32 OCD patients and 30 matched healthy controls at baseline. Patients received a four-day concentrated ERP format. We investigated longitudinal changes in 26 OCD patients and 22 healthy controls at 3months follow-up using repeated-measures ANOVA. Exploratory t-tests were conducted for AD and MD. Secondary hypothesis used linear regression to investigate if baseline FA predict treatment outcome 3 months later, and if patients with illness onset before 18 years of age would show lower FA in sagittal stratum. Finally, we performed sensitivity analysis on medication and comorbidity influences on FA.Results: Three months after treatment, 77% of the patients were in remission. Contrary to our hypotheses, we did not find any significant differences in FA, RD, AD or MD between the groups before treatment, nor significant group by time effects in any of the ROI. None of the baseline FA measures significantly predicted treatment outcome. Illness onset before 18 years of age did not significantly predict FA in the sagittal stratum. Adjusting for medication or comorbid anxiety or mood disorder did not influence the results.Conclusions: Although concentrated ERP in OCD lead to high remission, we did not find significant long-term changes by DTI. Future studies will benefit from using larger sample sizes and multi-shell diffusion-weighted imaging when investigating white matter microstructure in OCD and underlying neurobiological mechanisms of treatment.

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Childhood adversity, depression, age and gender effects on white matter microstructure: a DTI study

Brain Structure and Function ◽

10.1007/s00429-014-0769-x ◽

2014 ◽

Vol 220 (4) ◽

pp. 1997-2009 ◽

Cited By ~ 30

Author(s):

Izuchukwu D. Ugwu ◽

Francesco Amico ◽

Angela Carballedo ◽

Andrew J. Fagan ◽

Thomas Frodl

Keyword(s):

White Matter ◽

Childhood Adversity ◽

Gender Effects ◽

Age And Gender ◽

White Matter Microstructure ◽

And Gender

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Disentangling white-matter damage from physiological fibre orientation dispersion in multiple sclerosis

Brain Communications ◽

10.1093/braincomms/fcaa077 ◽

2020 ◽

Vol 2 (2) ◽

Cited By ~ 6

Author(s):

Kasper Winther Andersen ◽

Samo Lasič ◽

Henrik Lundell ◽

Markus Nilsson ◽

Daniel Topgaard ◽

...

Keyword(s):

Multiple Sclerosis ◽

White Matter ◽

Fractional Anisotropy ◽

Diffusion Mri ◽

Fibre Orientation ◽

Cerebral White Matter ◽

Healthy Controls ◽

Lesion Load ◽

Normal Appearing White Matter ◽

Relapsing Remitting

Abstract Multiple sclerosis leads to diffuse damage of the central nervous system, affecting also the normal-appearing white matter. Demyelination and axonal degeneration reduce regional fractional anisotropy in normal-appearing white matter, which can be routinely mapped with diffusion tensor imaging. However, the standard fractional anisotropy metric is also sensitive to physiological variations in orientation dispersion of white matter fibres. This complicates the detection of disease-related damage in large parts of cerebral white matter where microstructure physiologically displays a high degree of fibre dispersion. To resolve this ambiguity, we employed a novel tensor-valued encoding method for diffusion MRI, which yields a microscopic fractional anisotropy metric that is unaffected by regional variations in orientation dispersion. In 26 patients with relapsing-remitting multiple sclerosis, 14 patients with primary-progressive multiple sclerosis and 27 age-matched healthy controls, we compared standard fractional anisotropy mapping with the novel microscopic fractional anisotropy mapping method, focusing on normal-appearing white matter. Mean microscopic fractional anisotropy and standard fractional anisotropy of normal-appearing white matter were significantly reduced in both patient groups relative to healthy controls, but microscopic fractional anisotropy yielded a better reflection of disease-related white-matter alterations. The reduction in mean microscopic fractional anisotropy showed a significant positive linear relationship with physical disability, as reflected by the expanded disability status scale. Mean reduction of microscopic fractional anisotropy in normal-appearing white matter also scaled positively with individual cognitive dysfunction, as measured with the symbol digit modality test. Mean microscopic fractional anisotropy reduction in normal-appearing white matter also showed a positive relationship with total white-matter lesion load as well as lesion load in specific tract systems. None of these relationships between normal-appearing white-matter microstructure and clinical, cognitive or structural measures emerged when using mean fractional anisotropy. Together, the results provide converging evidence that microscopic fractional anisotropy mapping substantially advances the assessment of cerebral white matter in multiple sclerosis by disentangling microstructure damage from variations in physiological fibre orientation dispersion at the stage of data acquisition. Since tensor-valued encoding can be implemented in routine diffusion MRI, microscopic fractional anisotropy mapping bears considerable potential for the future assessment of disease progression in normal-appearing white matter in both relapsing-remitting and progressive forms of multiple sclerosis as well as other white-matter-related brain diseases.

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[18F]Florbetapir PET/MR imaging to assess demyelination in multiple sclerosis

European Journal of Nuclear Medicine and Molecular Imaging ◽

10.1007/s00259-019-04533-y ◽

2019 ◽

Vol 47 (2) ◽

pp. 366-378 ◽

Cited By ~ 1

Author(s):

Antonio Carotenuto ◽

Beniamino Giordano ◽

George Dervenoulas ◽

Heather Wilson ◽

Mattia Veronese ◽

...

Keyword(s):

Multiple Sclerosis ◽

White Matter ◽

Mr Imaging ◽

Pet Imaging ◽

Diffusion Tensor ◽

Volume Ratio ◽

Reference Method ◽

Healthy Controls ◽

Normal Appearing White Matter

Abstract Purpose We evaluated myelin changes throughout the central nervous system in Multiple Sclerosis (MS) patients by using hybrid [18F]florbetapir PET-MR imaging. Methods We included 18 relapsing-remitting MS patients and 12 healthy controls. Each subject performed a hybrid [18F]florbetapir PET-MR and both a clinical and cognitive assessment. [18F]florbetapir binding was measured as distribution volume ratio (DVR), through the Logan graphical reference method and the supervised cluster analysis to extract a reference region, and standard uptake value (SUV) in the 70–90 min interval after injection. The two quantification approaches were compared. We also evaluated changes in the measures derived from diffusion tensor imaging and arterial spin labeling. Results [18F]florbetapir DVRs decreased from normal-appearing white matter to the centre of T2 lesion (P < 0.001), correlated with fractional anisotropy and with mean, axial and radial diffusivity within T2 lesions (coeff. = −0.15, P < 0.001, coeff. = −0.12, P < 0.001 and coeff. = −0.16, P < 0.001, respectively). Cerebral blood flow was reduced in white matter damaged areas compared to white matter in healthy controls (−10.9%, P = 0.005). SUV70–90 and DVR are equally able to discriminate between intact and damaged myelin (area under the curve 0.76 and 0.66, respectively; P = 0.26). Conclusion Our findings demonstrate that [18F]florbetapir PET imaging can measure in-vivo myelin damage in patients with MS. Demyelination in MS is not restricted to lesions detected through conventional MRI but also involves the normal appearing white matter. Although longitudinal studies are needed, [18F]florbetapir PET imaging may have a role in clinical settings in the management of MS patients.

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Association Study Between White Matter Microstructure and Intelligence Decline in Schizophrenia

Clinical EEG and Neuroscience ◽

10.1177/15500594211063314 ◽

2021 ◽

pp. 155005942110633

Author(s):

Junya Matsumoto ◽

Kenichiro Miura ◽

Masaki Fukunaga ◽

Kiyotaka Nemoto ◽

Daisuke Koshiyama ◽

...

Keyword(s):

White Matter ◽

Functional Connectivity ◽

Gray Matter ◽

Diffusion Tensor ◽

Region Of Interest ◽

Healthy Controls ◽

Resonance Imaging ◽

White Matter Microstructure ◽

Magnetic Resonance Imaging Mri ◽

Diffusion Tensor Imaging Dti

Patients with schizophrenia can exhibit intelligence decline, which is an important element of cognitive impairment. Previous magnetic resonance imaging (MRI) studies have demonstrated that patients with schizophrenia have altered gray matter structures and functional connectivity associated with intelligence decline defined by a difference between premorbid and current intelligence quotients (IQs). However, it has remained unclear whether white matter microstructures are related to intelligence decline. In the present study, the indices of diffusion tensor imaging (DTI) obtained from 138 patients with schizophrenia and 554 healthy controls were analyzed. The patients were classified into three subgroups based on intelligence decline: deteriorated (94 patients), preserved (42 patients), and compromised IQ (2 patients) groups. Given that the DTI of each subject was acquired using either one of two different MRI scanners, we analyzed DTI indices separately for each scanner group. In the comparison between the deteriorated IQ group and the healthy controls, differences in some DTI indices were noted in three regions of interest irrespective of the MRI scanners, whereas differences in only one region of interest were noted between the preserved IQ group and the healthy controls. However, the comparisons between the deteriorated and preserved IQ groups did not show any reproducible differences. Together with the previous findings, it is thought that gray matter structures and functional connectivity are more promising as markers of intelligence decline in schizophrenia than white matter microstructures.

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Chronic Cocaine Use and White Matter Integrity: A Diffusion Tensor Imaging Study

10.31234/osf.io/cb4tr ◽

2021 ◽

Author(s):

Cooper Benton Hodges ◽

Joel Steinberg ◽

Edward Zuniga ◽

Liangsuo Ma ◽

James Matthew Bjork ◽

...

Keyword(s):

Substance Use ◽

Diffusion Tensor Imaging ◽

White Matter ◽

Alcohol Consumption ◽

Diffusion Tensor ◽

White Matter Integrity ◽

Healthy Controls ◽

Cocaine Use ◽

White Matter Microstructure ◽

Chronic Cocaine

Chronic substance use and its effects on brain function and structure has long been of interest to clinicians and researchers. Prior cross-sectional comparisons of diffusion tensor imaging (DTI) metrics have suggested deleterious effects of chronic substance use (i.e., cocaine use) on white matter integrity. However, it is unclear whether these effects would persist when accounting for confounding factors, such as chronic alcohol use, and how improving DTI technologies may enhance detection of substance use-related pathology. In this study, we sought to conduct a replication of previous work in this area and determine whether there are any patterns of persistent differences in white matter microstructure between individuals with a history of Cocaine Use Disorder (CocUD, according to DSM-IV) and healthy controls. 46 participants (21 healthy controls, 25 chronic cocaine users) were recruited from the Richmond, Virginia metropolitan area. Information regarding past and current substance use was collected from all participants. Participants also completed structural and DTI scans. Consistent with previous DTI studies, significant differences were found between CocUD and controls. These differences were in fractional anisotropy and axial diffusivity but not other diffusivity metrics. Lifetime alcohol consumption was greater in the CocUD group, but lifetime alcohol consumption did not show significant linear relationship with any of the DTI metrics in within-group regression analyses. These data align with previously reported declines in white matter integrity in chronic cocaine users. However, it is less clear whether comorbid alcohol consumption results in an additive deleterious effect on white matter microstructure.

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Increased radial diffusivity in spinal cord lesions in neuromyelitis optica compared with multiple sclerosis

Multiple Sclerosis Journal ◽

10.1177/1352458512436593 ◽

2012 ◽

Vol 18 (9) ◽

pp. 1259-1268 ◽

Cited By ~ 36

Author(s):

Eric C Klawiter ◽

Junqian Xu ◽

Robert T Naismith ◽

Tammie LS Benzinger ◽

Joshua S Shimony ◽

...

Keyword(s):

Multiple Sclerosis ◽

Spinal Cord ◽

Diffusion Tensor Imaging ◽

White Matter ◽

Neuromyelitis Optica ◽

Diffusion Tensor ◽

Healthy Controls ◽

Radial Diffusivity ◽

Spinal Cord Lesions ◽

T2 Lesions

Background: Multiple sclerosis (MS) and neuromyelitis optica (NMO) both affect spinal cord with notable differences in pathology. Objective: Determine the utility of diffusion tensor imaging (DTI) to differentiate the spinal cord lesions of NMO from MS within and outside T2 lesions. Methods: Subjects greater than or equal to 12 months from a clinical episode of transverse myelitis underwent a novel transaxial cervical spinal cord DTI sequence. Ten subjects with NMO, 10 with MS and 10 healthy controls were included. Results: Within T2 affected white matter regions, radial diffusivity was increased in both NMO and MS compared with healthy controls ( p<0.001, respectively), and to a greater extent in NMO than MS ( p<0.001). Axial diffusivity was decreased in T2 lesions in both NMO and MS compared with controls ( p<0.001, p=0.001), but did not differ between the two diseases. Radial diffusivity and fractional anisotropy within white matter regions upstream and downstream of T2 lesions were different from controls in each disease. Conclusions: Higher radial diffusivity within spinal cord white matter tracts derived from diffusion tensor imaging were appreciated in NMO compared with MS, consistent with the known greater tissue destruction seen in NMO. DTI also detected tissue alterations outside T2 lesions and may be a surrogate of anterograde and retrograde degeneration.

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