Vanderbilt University Medical Center
Department of Neuro-Immunology

Author Of 4 Presentations

Imaging Poster Presentation

P0532 - 2D conventional and synthetic brain MRI in the assessment of multiple sclerosis (ID 407)

Speakers
Presentation Number
P0532
Presentation Topic
Imaging

Abstract

Background

Synthetic MRI reduces acquisition time and could be an alternative to conventional sequences for the assessment of multiple sclerosis (MS).

Objectives

To perform a qualitative and quantitative comparison of conventional and synthetic MRI sequences to evaluate their value in the assessment of brain demyelinating lesions.

Methods

Twenty-seven RRMS patients (18 women), mean age of 44.0 years, median EDSS of 3.5 were examined in a 1.5T MRI scanner. A 2D QRAPMASTER sequence was added to the brain MRI protocol (proton density [PD] and T2w fast spin-echo, fast T2w FLAIR, and T1w spin-echo sequences). SyMRI software version 8.0.4 used QRAPMASTER images to generate synthetic images with the same TR, TE and TI used for conventional MRI.

Four raters performed a blinded qualitative analysis of the images in a random order to evaluate global image quality (GIQ), global image contrast, presence of flow artifacts in posterior fossa, contrast of lesions to white matter, and level of confidence for supratentorial and infratentorial lesion assessment. Moreover, the number of periventricular, juxtacortical, brainstem, and cerebellum lesions, and the contrast-to-noise ratio (CNR) between regions were evaluated.

Statistical analysis was performed in SPSS v. 25. Crosstabs were used to evaluate the degree of agreement between sequences for qualitative data. Wilcoxon signed rank test was used to evaluate differences for quantitative data.

Results

GIQ showed a predominance of better scores for conventional MRI. All other image quality parameters showed a degree of agreement similar or greater to the predominance of better scores for conventional MRI. There were no significant differences in the degree of agreement between pairs of raters in the assessment of conventional and synthetic MRI except between raters 1 and 2. However, we found a clear predominance of disagreement for all pairs of raters. Synthetic PD, T2w and T2w-FLAIR showed higher CNR than conventional sequences for most of the regions. Two raters found a greater number of brainstem lesions in conventional PD and one in synthetic T2w-FLAIR images. Three raters found a greater number of cerebellum lesions in conventional PD, and two of them in conventional T2w-FLAIR images.

Conclusions

Synthetic MRI obtained lower scores for some qualitative rater-related parameters while quantitative CNR data showed higher values. Synthetic MRI shows potential to be used as an alternative to conventional brain MRI sequences in the assessment of MS.

Collapse
Imaging Poster Presentation

P0547 - Axonal injury in multiple sclerosis: a multi-compartment diffusion MRI study using high-resolution probabilistic tractography (ID 1749)

Speakers
Presentation Number
P0547
Presentation Topic
Imaging

Abstract

Background

Axonal injury is a key contributor to physical disability in persons with multiple sclerosis (pwMS). Yet, assessing axonal damage in vivo is challenged by the lack of pathologically and topographically specific imaging methods.

Objectives

We use the spherical mean technique (SMT) and neurite orientation density and dispersion index (NODDI) combined with high-resolution probabilistic tractography and propose an improved assessment of the degree of regional axonal injury and its association with measures of disability in pwMS.

Methods

Eighteen pwMS and nine age-sex matched heathy controls underwent a brain MRI inclusive of clinical scans, SMT and NODDI. Parametric maps of the apparent axonal volume fraction (Vax), intrinsic diffusivity (Dax), neurite density index (ndi), orientation dispersion index (odi), and isotropic volume fraction (isovf) were estimated. Tract-specific values were measured in transcallosal (TC) and corticospinal (CS) white matter tracts implicated with motor functions. This included the TC bundles from the paracentral lobules, and both the TC and the CS fibers from the ventral premotor areas, dorsal premotor areas, presupplementary motor areas, supplementary motor areas, and primary motor cortex, all of which were reconstructed by probabilistic tractography. Unpaired t-tests assessed group-differences in tract-specific SMT and NODDI-derived metrics between healthy controls and pwMS, and Spearman rank correlations analyses assessed associations between SMT and NODDI metrics and physical disability metrics.

Results

Differences (p<=0.018) were seen only for the isovf of the TC bundles from the paracentral lobules, the presupplementary motor areas and supplementary motor areas, and both the TC and the CS fibers from the ventral premotor areas. However, associations were seen between several NODDI derived metrics and clinical scores of motor impairment (p<=0.054).

Conclusions

Our preliminary findings show that NODDI-derived isovf has a higher radiological discriminatory capacity compared to SMT and NODDI-derived measures, but several NODDI and SMT indices measured in topographically specific regions explain motor disability variations in pwMS.

Collapse
Imaging Poster Presentation

P0614 - Perilesional neurodegenerative injury in MS: relations with focal lesions and disability (ID 1849)

Speakers
Presentation Number
P0614
Presentation Topic
Imaging

Abstract

Background

Chronic black holes (cBHs), characterized by severe myelin and axonal loss, are associated with higher disability levels in patients with multiple sclerosis (MS). However, whether cBHs impact perilesional tissue via retrograde and/or antegrade degeneration and how this remote pathology affects patient disability has not been investigated in vivo. Novel MRI techniques, such as selective inversion recovery quantitative magnetization transfer imaging (SIR-qMT) and multi-compartment microscopic diffusion MRI spherical mean technique (SMT) have the potential to more accurately assess myelin and axonal injury in vivo, thus allowing us to measure remote tissue injury and its impact on patient clinical disability.

Objectives

To compare the macromolecular-to-free pool size ratio (PSR), derived from SIR-qMT, and apparent axonal volume fraction (Vax), from SMT, values among cBHs, perilesional normal-appearing white matter (NAWM) and contra-lateral (distant) NAWM and test associations of these measures with disability in vivo.

Methods

Eighteen MS patients underwent 3T MRI consisting of clinical protocols, SIR-qMT and SMT. Regions of interest (ROIs) were manually placed on CBHs, perilesional NAWM and distant NAWM areas; PSR/Vaxwere calculated and compared using a mixed effects model. Pearson correlation analyses tested the associations between PSR/Vax values and patient clinical and MRI metrics.

Results

Compared to perilesional NAWM, both PSR (-43.3%, p<0.001) and Vax (-29.7%, p<0.001) values were reduced in cBHs and increased in distant NAWM (10.2%, p<0.001 for PSR and 20%, p<0.001 for Vax). A strong correlation was seen for cBH and perilesional NAWM Vaxvalues (rho=0.63 p<0.001). No significant associations were seen between PSR/Vaxvalues and other clinical or MRI metrics of disease apart from cBHs PSR, which correlated with the EDSS score (rho=-0.63, p=0.03). There was a trend for decreasing PSR and Vaxvalues in all regions with worsening disease phenotype.

Conclusions

Our results show that myelin and axonal integrity, detected by PSR and Vax, are reduced in perilesional NAWM, as a function of the degree of focal cBH axonal injury. This is indicative of an ongoing anterograde and retrograde degeneration and suggests that preventing cBH development is a key factor for preserving NAWM integrity in surrounding tissue. PSR and Vaxlargely failed to capture associations with clinical and MRI characteristics. However, the trends observed with disease phenotypes suggest that longitudinal assessment of a larger cohort may indeed unravel the impact of this pathology on disease progression.

Collapse
Imaging Poster Presentation

P0659 - White matter tracts that overlap with hubs are preferentially protected against multiple sclerosis pathology (ID 926)

Speakers
Presentation Number
P0659
Presentation Topic
Imaging

Abstract

Background

The thalamus and the putamen, highly-connected brain areas (hubs), are vulnerable to MS-induced atrophy. Here we investigate if white matter (WM) tracts that pass through hubs have different susceptibility to MS pathology, due to anterograde and retrograde neurodegeneration, compared to tracts do not pass through these hubs. We use the apparent intra-axonal volume fraction (Vax) derived from the multi-compartment diffusion MRI spherical mean technique (SMT) as well as the neurite density index (NDI) and isotropic volume fraction (IVF) derived from the neurite orientation dispersion and density imaging (NODDI) coupled with high-resolution tractography to assess the degree of tract-specific axonal integrity.

Objectives

(1) To compare tract-specific lesion burden, Vax, NDI and IVF between WM tracts that overlap with either the thalamus or the putamen (hub+ tracts) and those that do not (hub- tracts); and (2) to assess the relationship between these MRI metrics and those of physical impairment, as measured by the Expanded Disability Status Scale (EDSS) and the Timed 25-Foot Walk test (T25FW).

Methods

EIghteen patients underwent 3T MRI inclusive of T1- and T2-weighted sequences, SMT and NODDI. Using probabilistic tractography, we reconstructed 49 WM tracts, 12 hub+ tracts and 37 hub- tracts. Using T-tests, we compared the following MRI metrics between hub+ and hub- tracts: T1 and T2 lesion burden (calculated as percentage of tracts occupied by T1 and T2 lesions) as well as whole tract and normal-appearing WM (NAWM) average NDI, IVF and Vax values. Spearman correlation assessed the relationship between these MRI metrics and those of clinical impairment.

Results

Hub+ tracts had a lower mean %T1 lesions (0.86 vs. 1.99) and %T2 lesions (2.90 vs. 5.42), as well as higher whole tract NDI (0.61 vs. 0.57), NAWM NDI (0.61 vs. 0.58), whole tract Vax (0.49 vs 0.44) and NAWM Vax (0.50 vs. 0.44), all significant at the p<0.001 level. Stronger correlations were seen between clinical measures and hub+ tracts compared to hub- tracts, with the strongest correlation for %T1 lesions and the T25FW (r= -0.59, p<0.0001).

Conclusions

WM tracts that overlap with the thalamus and the putamen have a higher degree of axonal integrity and lower lesional burden, suggesting a protective role of hubs. However, given the ramifications of disease present at the level of hub+ tracts, disease here retains a major impact on disability. If confirmed, our data suggest the role of disease location in relation to hubs as guidance for treatment personalization, considering more aggressive approaches for patients presenting with MRI changes in hub+ fiber tracks.

Collapse

Presenter Of 2 Presentations

Imaging Poster Presentation

P0614 - Perilesional neurodegenerative injury in MS: relations with focal lesions and disability (ID 1849)

Speakers
Presentation Number
P0614
Presentation Topic
Imaging

Abstract

Background

Chronic black holes (cBHs), characterized by severe myelin and axonal loss, are associated with higher disability levels in patients with multiple sclerosis (MS). However, whether cBHs impact perilesional tissue via retrograde and/or antegrade degeneration and how this remote pathology affects patient disability has not been investigated in vivo. Novel MRI techniques, such as selective inversion recovery quantitative magnetization transfer imaging (SIR-qMT) and multi-compartment microscopic diffusion MRI spherical mean technique (SMT) have the potential to more accurately assess myelin and axonal injury in vivo, thus allowing us to measure remote tissue injury and its impact on patient clinical disability.

Objectives

To compare the macromolecular-to-free pool size ratio (PSR), derived from SIR-qMT, and apparent axonal volume fraction (Vax), from SMT, values among cBHs, perilesional normal-appearing white matter (NAWM) and contra-lateral (distant) NAWM and test associations of these measures with disability in vivo.

Methods

Eighteen MS patients underwent 3T MRI consisting of clinical protocols, SIR-qMT and SMT. Regions of interest (ROIs) were manually placed on CBHs, perilesional NAWM and distant NAWM areas; PSR/Vaxwere calculated and compared using a mixed effects model. Pearson correlation analyses tested the associations between PSR/Vax values and patient clinical and MRI metrics.

Results

Compared to perilesional NAWM, both PSR (-43.3%, p<0.001) and Vax (-29.7%, p<0.001) values were reduced in cBHs and increased in distant NAWM (10.2%, p<0.001 for PSR and 20%, p<0.001 for Vax). A strong correlation was seen for cBH and perilesional NAWM Vaxvalues (rho=0.63 p<0.001). No significant associations were seen between PSR/Vaxvalues and other clinical or MRI metrics of disease apart from cBHs PSR, which correlated with the EDSS score (rho=-0.63, p=0.03). There was a trend for decreasing PSR and Vaxvalues in all regions with worsening disease phenotype.

Conclusions

Our results show that myelin and axonal integrity, detected by PSR and Vax, are reduced in perilesional NAWM, as a function of the degree of focal cBH axonal injury. This is indicative of an ongoing anterograde and retrograde degeneration and suggests that preventing cBH development is a key factor for preserving NAWM integrity in surrounding tissue. PSR and Vaxlargely failed to capture associations with clinical and MRI characteristics. However, the trends observed with disease phenotypes suggest that longitudinal assessment of a larger cohort may indeed unravel the impact of this pathology on disease progression.

Collapse
Imaging Poster Presentation

P0659 - White matter tracts that overlap with hubs are preferentially protected against multiple sclerosis pathology (ID 926)

Speakers
Presentation Number
P0659
Presentation Topic
Imaging

Abstract

Background

The thalamus and the putamen, highly-connected brain areas (hubs), are vulnerable to MS-induced atrophy. Here we investigate if white matter (WM) tracts that pass through hubs have different susceptibility to MS pathology, due to anterograde and retrograde neurodegeneration, compared to tracts do not pass through these hubs. We use the apparent intra-axonal volume fraction (Vax) derived from the multi-compartment diffusion MRI spherical mean technique (SMT) as well as the neurite density index (NDI) and isotropic volume fraction (IVF) derived from the neurite orientation dispersion and density imaging (NODDI) coupled with high-resolution tractography to assess the degree of tract-specific axonal integrity.

Objectives

(1) To compare tract-specific lesion burden, Vax, NDI and IVF between WM tracts that overlap with either the thalamus or the putamen (hub+ tracts) and those that do not (hub- tracts); and (2) to assess the relationship between these MRI metrics and those of physical impairment, as measured by the Expanded Disability Status Scale (EDSS) and the Timed 25-Foot Walk test (T25FW).

Methods

EIghteen patients underwent 3T MRI inclusive of T1- and T2-weighted sequences, SMT and NODDI. Using probabilistic tractography, we reconstructed 49 WM tracts, 12 hub+ tracts and 37 hub- tracts. Using T-tests, we compared the following MRI metrics between hub+ and hub- tracts: T1 and T2 lesion burden (calculated as percentage of tracts occupied by T1 and T2 lesions) as well as whole tract and normal-appearing WM (NAWM) average NDI, IVF and Vax values. Spearman correlation assessed the relationship between these MRI metrics and those of clinical impairment.

Results

Hub+ tracts had a lower mean %T1 lesions (0.86 vs. 1.99) and %T2 lesions (2.90 vs. 5.42), as well as higher whole tract NDI (0.61 vs. 0.57), NAWM NDI (0.61 vs. 0.58), whole tract Vax (0.49 vs 0.44) and NAWM Vax (0.50 vs. 0.44), all significant at the p<0.001 level. Stronger correlations were seen between clinical measures and hub+ tracts compared to hub- tracts, with the strongest correlation for %T1 lesions and the T25FW (r= -0.59, p<0.0001).

Conclusions

WM tracts that overlap with the thalamus and the putamen have a higher degree of axonal integrity and lower lesional burden, suggesting a protective role of hubs. However, given the ramifications of disease present at the level of hub+ tracts, disease here retains a major impact on disability. If confirmed, our data suggest the role of disease location in relation to hubs as guidance for treatment personalization, considering more aggressive approaches for patients presenting with MRI changes in hub+ fiber tracks.

Collapse