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Use of diffusion spectrum imaging in preliminary longitudinal evaluation of amyotrophic lateral sclerosis: Development of an imaging biomarker

Abhinav, K and Yeh, FC and El-Dokla, A and Ferrando, LM and Chang, YF and Lacomis, D and Friedlander, RM and Fernandez-Miranda, JC (2014) Use of diffusion spectrum imaging in preliminary longitudinal evaluation of amyotrophic lateral sclerosis: Development of an imaging biomarker. Frontiers in Human Neuroscience, 8 (1 APR).

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Previous diffusion tensor imaging (DTI) studies have shown white matter pathology in amyotrophic lateral sclerosis (ALS), predominantly in the motor pathways. Further these studies have shown that DTI can be used longitudinally to track pathology over time, making white matter pathology a candidate as an outcome measure in future trials. DTI has demonstrated application in group studies, however its derived indices, for example fractional anisotropy, are susceptible to partial volume effects, making its role questionable in examining individual progression. We hypothesize that changes in the white matter are present in ALS beyond the motor tracts, and that the affected pathways and associated pattern of disease progression can be tracked longitudinally using automated diffusion connectometry analysis. Connectometry analysis is based on diffusion spectrum imaging and overcomes the limitations of a conventional tractography approach and DTI. The identified affected white matter tracts can then be assessed in a targeted fashion using High definition fiber tractography (a novel white matter MR imaging technique). Changes in quantitative and qualitative markers over time could then be correlated with clinical progression. We illustrate these principles toward developing an imaging biomarker for demonstrating individual progression, by presenting results for five ALS patients, including with longitudinal data in two. Preliminary analysis demonstrated a number of changes bilaterally and asymmetrically in motoric and extramotoric white matter pathways. Further the limbic system was also affected possibly explaining the cognitive symptoms in ALS. In the two longitudinal subjects, the white matter changes were less extensive at baseline, although there was evidence of disease progression in a frontal pattern with a relatively spared postcentral gyrus, consistent with the known pathology in ALS. © 2014 Abhinav, Yeh, El-Dokla, Ferrando, Chang, Lacomis, Friedlander and Fernandez-Miranda.


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Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Abhinav, K
Yeh, FCfrank.yeh@pitt.eduYEHFC
El-Dokla, A
Ferrando, LMlmf78@pitt.eduLMF78
Chang, YFyuc2@pitt.eduYUC2
Lacomis, Dlacomisd@pitt.eduLACOMISD
Friedlander, RMrmf66@pitt.eduRMF66
Fernandez-Miranda, JCjcf51@pitt.eduJCF51
Date: 29 April 2014
Date Type: Publication
Journal or Publication Title: Frontiers in Human Neuroscience
Volume: 8
Number: 1 APR
DOI or Unique Handle: 10.3389/fnhum.2014.00270
Schools and Programs: School of Medicine > Neurobiology
School of Medicine > Neurological Surgery
School of Medicine > Neurology
Refereed: Yes
Date Deposited: 05 May 2015 16:05
Last Modified: 02 Feb 2019 13:58


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