ECTRIMS eLearning

Long range effects of focal lesions on normal appearing brain tissue vary depending on the disease phenotype in multiple sclerosis
Author(s): ,
A Pitiot
Affiliations:
School of Psychology
,
R Abdel-Fahim
Affiliations:
School of Medicine
,
O Mougin
Affiliations:
SPMIC, University of Nottingham, Nottingham, United Kingdom
,
P.S Morgan
Affiliations:
School of Medicine
,
P.A Gowland
Affiliations:
SPMIC, University of Nottingham, Nottingham, United Kingdom
N Evangelou
Affiliations:
School of Medicine
ECTRIMS Learn. Pitiot A. 09/16/16; 145718; P1034
Alain Pitiot
Alain Pitiot
Contributions
Abstract

Abstract: P1034

Type: Poster

Abstract Category: Pathology and pathogenesis of MS - Imaging

Introduction: The evolution of clinical disability in Multiple Sclerosis (MS) is a complex process with significant contributions from both focal lesions and diffused abnormalities in Normal Appearing Tissues (NAT), which have been shown to be more affected in progressive MS. Yet, the role played by focal demyelination in determining NAT pathology has not been systematically explored due to the difficulties in detecting Grey Matter (GM) demyelination and very small White Matter (WM) lesions using conventional Magnetic Resonance (MR) imaging. A clearer picture of what cause diffuse damage in NAT could produce better treatment strategies.

The enhanced signal to noise ratio and sensitivity to Magnetisation Transfer (MT) respectively afforded by Phase Sensitive Inversion Recovery (PSIR) and Magnetisation Transfer Ratio (MTR) at ultra-high field make it possible to study small variations across both WM and GM.

Objective: To explore the influence of disease phenotype on the effect of focal lesions on NAT in patients with MS, using ultra-high field MR imaging.

Method: 40 MS patients (16 males/24 females; 10 participants for each major subtype; age= 46±10 years; EDSS= 3.5±2.4; disease duration= 6.3±5.7 years) were recruited from the MS outpatient clinics at Nottingham University Hospitals. Each patient was scanned at 7T to acquire high-resolution, 0.63 mm3, MTR and PSIR images. We estimated tissue maps from the PSIR images using SPM8. Finally we calculated the mean MTR ratios in NAT as a function of the topological distance to the nearest GM or WM lesion, where ratios were obtained by dividing the mean value at each distance by the overall mean across all distances.

Results: As previously reported, the NAT MTR ratios decreased with the distance to the nearest lesion with a long-range influence of WM lesions on NAWM, and a shorter-range influence of GM lesions on both NAGM and NAWM. Importantly, the decrease was modulated by the disease subtype and was twice as strong in primary and secondary progressive MS patients than in relapsing remitting and clinically isolated syndrome patients.

Discussion: Our findings suggests that MS lesions continue to have a destructive effect on NAT over many years and are possibly associated with continuing inflammation at the borders of the lesions. Prevention of lesion development and better control of residual inflammation are possible strategies to reduce long lasting progressive NAT damage.

Disclosure: Alain Pitiot: nothing to disclose

Rasha Abdel Fahim: nothing to disclose

Olivier Mougin: nothing to disclose

Paul Morgan: nothing to disclose

Penny Gowland: nothing to disclose

Nikos Evangelou: nothing to disclose

Abstract: P1034

Type: Poster

Abstract Category: Pathology and pathogenesis of MS - Imaging

Introduction: The evolution of clinical disability in Multiple Sclerosis (MS) is a complex process with significant contributions from both focal lesions and diffused abnormalities in Normal Appearing Tissues (NAT), which have been shown to be more affected in progressive MS. Yet, the role played by focal demyelination in determining NAT pathology has not been systematically explored due to the difficulties in detecting Grey Matter (GM) demyelination and very small White Matter (WM) lesions using conventional Magnetic Resonance (MR) imaging. A clearer picture of what cause diffuse damage in NAT could produce better treatment strategies.

The enhanced signal to noise ratio and sensitivity to Magnetisation Transfer (MT) respectively afforded by Phase Sensitive Inversion Recovery (PSIR) and Magnetisation Transfer Ratio (MTR) at ultra-high field make it possible to study small variations across both WM and GM.

Objective: To explore the influence of disease phenotype on the effect of focal lesions on NAT in patients with MS, using ultra-high field MR imaging.

Method: 40 MS patients (16 males/24 females; 10 participants for each major subtype; age= 46±10 years; EDSS= 3.5±2.4; disease duration= 6.3±5.7 years) were recruited from the MS outpatient clinics at Nottingham University Hospitals. Each patient was scanned at 7T to acquire high-resolution, 0.63 mm3, MTR and PSIR images. We estimated tissue maps from the PSIR images using SPM8. Finally we calculated the mean MTR ratios in NAT as a function of the topological distance to the nearest GM or WM lesion, where ratios were obtained by dividing the mean value at each distance by the overall mean across all distances.

Results: As previously reported, the NAT MTR ratios decreased with the distance to the nearest lesion with a long-range influence of WM lesions on NAWM, and a shorter-range influence of GM lesions on both NAGM and NAWM. Importantly, the decrease was modulated by the disease subtype and was twice as strong in primary and secondary progressive MS patients than in relapsing remitting and clinically isolated syndrome patients.

Discussion: Our findings suggests that MS lesions continue to have a destructive effect on NAT over many years and are possibly associated with continuing inflammation at the borders of the lesions. Prevention of lesion development and better control of residual inflammation are possible strategies to reduce long lasting progressive NAT damage.

Disclosure: Alain Pitiot: nothing to disclose

Rasha Abdel Fahim: nothing to disclose

Olivier Mougin: nothing to disclose

Paul Morgan: nothing to disclose

Penny Gowland: nothing to disclose

Nikos Evangelou: nothing to disclose

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