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.

The splenial angle: a novel radiological index for idiopathic normal pressure hydrocephalus

“…With increasing clinical applications of DTI, it may be apt to integrate simple DTI sequences into the routine neuroradiological assessment of NPH. The SA is unique in its sensitivity to ventricular morphological changes and capacity to bypass traditional concerns of imaging markers in NPH, including variability of the CA, complex image post-processing requisites for 3D volumetry or validity of DTI parametric comparisons across sites and scanner makes [2,4,7,9,13,15,[19][20][21][22]. Our excellent ICC scores for the SA measurement after effortless training attest to its reproducibility.…”

“…Twenty patients were prospectively recruited from the NPH program at a tertiary referral center. All patients were diagnosed based on key clinical and neuroimaging features according to established criteria in published international NPH guidelines [3,12], including supplementary neuropsychological testing and confirmation with cerebrospinal fluid (CSF) drainage using an in-house protocol adapted from the guidelines [3,4,13]. Patients deemed unlikely to have NPH or fit the diagnostic criteria for AD, PD, and/or had response to levodopa were excluded.…”

The role of diffusion tensor imaging in idiopathic normal pressure hydrocephalus: A literature review

“…Many measures were used as assessments of cognitive function (Mini Mental State Examination (MMSE), 21–29,31,32,35–37,43–45,48,49 trail making test A (TMT-A), 23,32,33,35,36,43,49 DemTect test, 25 , 32 Montreal Cognitive Assessment (MOCA) 54 ; learning and memory (Hopkins Verbal Learning Task-Revised (HVLT-R) 39 ); verbal fluency and executive function (COWAT), 20 , 39 Wechsler Memory Scale III (WMS-WL), 20 Rey complex figure test (RCFT), 20 according to Deckersbach et al. 71 ); conceptualization, mental flexibility, motor programming, sensitivity to interference, inhibitory control and environmental autonomy due to frontal lobe dysfunction (frontal assessment battery (FAB) 22,24,33,36,37,41,45,49 ); grade of dementia (Clinical Dementia Rating Scale (CDR), 29,35,36 , Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB) 29 ); motor impairment and gait (gait velocity, 43 Timed Up and Go (TUG) test, 22,23,30,35–38,41,…”

“…16–17 in 1994, and recently, many papers investigated its role in analyzing white matter (WM) alterations in patients with iNPH. 12 , 18–54 DTI is a non-invasive MR technique that provides information about the orientation and anisotropy of the WM tracts, and may delineate microstructural changes in cerebral WM; high-resolution, multitensor imaging (more than six diffusion directions) is currently combined with various other advanced MR techniques to study connectivity within the brain. In fact, illnesses that disrupt the normal organization or integrity of cerebral WM have a qualitative and quantitative impact on DTI measures.…”

Mining multi-site clinical data to develop machine learning MRI biomarkers: application to neonatal hypoxic ischemic encephalopathy

“…However, existing clinical diffusion MRI protocols in our hospitals used 24–32 diffusion directions. Similar settings are adopted in other hospitals or clinical database for HIE populations [115–117]. One reason is that the purpose is not to construct high angular resolution fibers, but to only create ADC and FA maps for clinical neuroradiology interpretation [24, 60].…”