Clustering patients with vascular cognitive impairment using quantitative magnetic resonance imaging data and a finite mixture model

Abstract

AbstractBackgroundBlood‐brain barrier (BBB) leakage is a marker of vascular cognitive impairment and dementia (VCID). The advance of in vivo imaging enabled us to quantify the degree of BBB transfer rates in VCID patients. However, a consensus has not been reached on the role of BBB in the differential diagnosis of VCI subtypes. The objective of this work was to use neuroinflammatory and in vivo imaging data on BBB health to identify clusters of VCID patients with distinct underlying pathologies.MethodPatients included were on average 61 (SD = 15.94, M/F = 27/34) years old. The MRI data were collected by using a 1.5 Tesla Siemens Sonata scanner. Pixel‐by‐pixel BBB transfer rate (Ki) was calculated using Patlak compartmental analysis on dynamic contrast‐enhanced T1 maps. The mean BBB transfer rate was calculated for the brain section above the ventricular zone (sampled by six consecutive slices). MR Spectroscopy was used to investigate N‐Acetylaspartate (NAA), Creatine (Cr), and Choline (Cho) levels. Moreover, Active MMP3 data were used in patients clustering. Thirty‐eight patients enrolled in the study have all data for three entities; NAA, mean Ki, and active MMP3 used for clustering. A multi‐parametric model‐based classification method was used to blindly classify VCID data based on Ki, NAA, and active MMPs.ResultBBB leakage increased by age, which is more pronounced in patients diagnosed with cognitive impairment when compared with 17 controls, r2 = 0.060, P = 0.021. Statistical classifiers identified three clusters in VCID patients. Identified VCID clusters are similar to the distinction that was made on this VCID cohort based on the clinical scores and psychological entities that we have published earlier.ConclusionThe results suggest that a statistical combination of imaging and inflammatory attributes renders a tool to blindly separate VCID patients into distinct groups that may have different underlying pathology.