Journal
RADIOLOGY
Volume 287, Issue 3, Pages 955-964Publisher
RADIOLOGICAL SOC NORTH AMERICA
DOI: 10.1148/radiol.2018162967
Keywords
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Funding
- NIH/NCRR [CTSA KL2TR000440]
- National Institute of Neurologic Disorders and Stroke Clinical Research in ALS and Related Disorders for Therapeutic Development Clinical Research Scholarship [U5NS092091]
- Cleveland Clinic Education Department Body Donation Program
- Brightside of the Road Foundation
- Cleveland Clinic, Radiology Department Pilot Funding
- Amyotrophic Lateral Sclerosis Association [2152, 16-IIP-318]
- National Institute of Neurologic Disorders and Stroke (Clinical Research in ALS and Related Disorders) [R35NS09730]
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Purpose: To determine if magnetic resonance (MR) imaging metrics can estimate primary motor cortex (PMC) motor neuron (MN) density in patients with amyotrophic lateral sclerosis (ALS). Materials and Methods: Between 2012 and 2014, in situ brain MR imaging was performed in 11 patients with ALS (age range, 35-81 years; seven women and four men) soon after death (mean, 5.5 hours after death; range, 3.2-9.6 hours). The brain was removed, right PMC (RPMC) was excised, and MN density was quantified. RPMC metrics (thickness, volume, and magnetization transfer ratio) were calculated from MR images. Regression modeling was used to estimate MN density by using RPMC and global MR imaging metrics (brain and tissue volumes); clinical variables were subsequently evaluated as additional estimators. Models were tested at in vivo MR imaging by using the same imaging protocol (six patients with ALS; age range, 54-66 years; three women and three men). Results: RPMC mean MN density varied over a greater than threefold range across patients and was estimated by a linear function of normalized gray matter volume (adjusted R-2 = 0.51; P = .008; < 10% error in most patients). When considering only sporadic ALS, a linear function of normalized RPMC and white matter volumes estimated MN density (adjusted R-2 = 0.98; P = .01; < 10% error in all patients). In vivo data analyses detected decreases in MN density over time. Conclusion: PMC mean MN density varies widely in end-stage ALS possibly because of disease heterogeneity. MN density
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