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Guidelines for the conduct of clinical trials in spinal cord injury: Neuroimaging biomarkers.


Seif, Maryam; Gandini Wheeler-Kingshott, Claudia Am; Cohen-Adad, Julien; Flanders, Adam E; Freund, Patrick (2019). Guidelines for the conduct of clinical trials in spinal cord injury: Neuroimaging biomarkers. Spinal Cord, 57(9):717-728.

Abstract

Traumatic spinal cord injury (SCI) leads to immediate neuronal and axonal damage at the focal injury site and triggers secondary pathologic series of events resulting in sensorimotor and autonomic dysfunction below the level of injury. Although there is no cure for SCI, neuroprotective and regenerative therapies show promising results at the preclinical stage. There is a pressing need to develop non-invasive outcome measures that can indicate whether a candidate therapeutic agent or a cocktail of therapeutic agents are positively altering the underlying disease processes. Recent conventional MRI studies have quantified spinal cord lesion characteristics and elucidated their relationship between severity of injury to clinical impairment and recovery. Next to the quantification of the primary cord damage, quantitative MRI measures of spinal cord (rostrocaudally to the lesion site) and brain integrity have demonstrated progressive and specific neurodegeneration of afferent and efferent neuronal pathways. MRI could therefore play a key role to ultimately uncover the relationship between clinical impairment/recovery and injury-induced neurodegenerative changes in the spinal cord and brain. Moreover, neuroimaging biomarkers hold promises to improve clinical trial design and efficiency through better patient stratification. The purpose of this narrative review is therefore to propose a guideline of clinically available MRI sequences and their derived neuroimaging biomarkers that have the potential to assess tissue damage at the macro- and microstructural level after SCI. In this piece, we make a recommendation for the use of key MRI sequences-both conventional and advanced-for clinical work-up and clinical trials.

Abstract

Traumatic spinal cord injury (SCI) leads to immediate neuronal and axonal damage at the focal injury site and triggers secondary pathologic series of events resulting in sensorimotor and autonomic dysfunction below the level of injury. Although there is no cure for SCI, neuroprotective and regenerative therapies show promising results at the preclinical stage. There is a pressing need to develop non-invasive outcome measures that can indicate whether a candidate therapeutic agent or a cocktail of therapeutic agents are positively altering the underlying disease processes. Recent conventional MRI studies have quantified spinal cord lesion characteristics and elucidated their relationship between severity of injury to clinical impairment and recovery. Next to the quantification of the primary cord damage, quantitative MRI measures of spinal cord (rostrocaudally to the lesion site) and brain integrity have demonstrated progressive and specific neurodegeneration of afferent and efferent neuronal pathways. MRI could therefore play a key role to ultimately uncover the relationship between clinical impairment/recovery and injury-induced neurodegenerative changes in the spinal cord and brain. Moreover, neuroimaging biomarkers hold promises to improve clinical trial design and efficiency through better patient stratification. The purpose of this narrative review is therefore to propose a guideline of clinically available MRI sequences and their derived neuroimaging biomarkers that have the potential to assess tissue damage at the macro- and microstructural level after SCI. In this piece, we make a recommendation for the use of key MRI sequences-both conventional and advanced-for clinical work-up and clinical trials.

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Additional indexing

Item Type:Journal Article, refereed, further contribution
Communities & Collections:04 Faculty of Medicine > Balgrist University Hospital, Swiss Spinal Cord Injury Center
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:September 2019
Deposited On:10 Sep 2019 12:02
Last Modified:01 Oct 2019 12:31
Publisher:Nature Publishing Group
ISSN:1362-4393
OA Status:Green
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.1038/s41393-019-0309-x
PubMed ID:31267015

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