DTI Profiles for Rapid Description of Cohorts at the Clinical-Research Interface.

Abstract

Normal pressure hydrocephalus (NPH) is a syndrome comprising gait disturbance, cognitive decline and urinary incontinence that is an unique model of reversible brain injury, but it presents as a challenging spectrum of disease cohorts. Diffusion Tensor Imaging (DTI), with its ability to interrogate structural white matter patterns at a microarchitectural level, is a potentially useful tool for the confirmation and characterization of disease cohorts at the clinical-research interface. However, obstacles to its widespread use involve the need for consistent DTI analysis and interpretation tools across collaborator sites. We present the use of DTI profiles, a simplistic methodology to interpret white matter injury patterns based on the morphology of diffusivity parameters. We examined 13 patients with complex NPH, i.e., patients with NPH and overlay from multiple comorbidities, including vascular risk burden and neurodegenerative disease, undergoing extended CSF drainage, clinical assessments, and multi-modal MR imaging. Following appropriate exclusions, we compared the morphology of DTI profiles in such complex NPH patients (n = 12, comprising 4 responders and 8 non-responders) to exemplar DTI profiles from a cohort of classic NPH patients (n = 16) demonstrating responsiveness of white matter injury to ventriculo-peritoneal shunting. In the cohort of complex NPH patients, mean age was 71.3 ± 7.6 years (10 males, 2 females) with a mean MMSE score of 21.1. There were 5 age-matched healthy controls, mean age was 73.4 ± 7.2 years (1 male, 4 females) and mean MMSE score was 26.8. In the exemplar cohort of classic NPH patients, mean age was 74.7 ± 5.9 years (10 males, 6 females) and mean MMSE score was 24.1. There were 9 age-matched healthy controls, mean age was 69.4 ± 9.7 years (4 males, 5 females) and mean MMSE score was 28.6. We found that, despite the challenges of acquiring DTI metrics from differing scanners across collaborator sites and NPH patients presenting as differing cohorts along the spectrum of disease, DTI profiles for responsiveness to interventions were comparable. Distinct DTI characteristics were demonstrated for complex NPH responders vs. non-responders. The morphology of DTI profiles for complex NPH responders mimicked DTI patterns found in predominantly shunt-responsive patients undergoing intervention for classic NPH. However, DTI profiles for complex NPH non-responders was suggestive of atrophy. Our findings suggest that it is possible to use DTI profiles to provide a methodology for rapid description of differing cohorts of disease at the clinical-research interface. By describing DTI measures morphologically, it was possible to consistently compare white matter injury patterns across international collaborator datasets.