Microstructural and Microvascular Alterations in Psychotic Spectrum Disorders: A Three-Compartment Intravoxel Incoherent Imaging and Free Water Model

Schizophr Bull. 2023 Nov 29;49(6):1542-1553. doi: 10.1093/schbul/sbad019.

Abstract

Background and hypothesis: Microvascular and inflammatory mechanisms have been hypothesized to be involved in the pathophysiology of psychotic spectrum disorders (PSDs). However, data evaluating these hypotheses remain limited.

Study design: We applied a three-compartment intravoxel incoherent motion free water imaging (IVIM-FWI) technique that estimates the perfusion fraction (PF), free water fraction (FW), and anisotropic diffusion of tissue (FAt) to examine microvascular and microstructural changes in gray and white matter in 55 young adults with a PSD compared to 37 healthy controls (HCs).

Study results: We found significantly increased PF, FW, and FAt in gray matter regions, and significantly increased PF, FW, and decreased FAt in white matter regions in the PSD group versus HC. Furthermore, in patients, but not in the HC group, increased PF, FW, and FAt in gray matter and increased PF in white matter were significantly associated with poor performance on several cognitive tests assessing memory and processing speed. We additionally report significant associations between IVIM-FWI metrics and myo-inositol, choline, and N-acetylaspartic acid magnetic resonance spectroscopy imaging metabolites in the posterior cingulate cortex, which further supports the validity of PF, FW, and FAt as microvascular and microstructural biomarkers of PSD. Finally, we found significant relationships between IVIM-FWI metrics and the duration of psychosis in gray and white matter regions.

Conclusions: The three-compartment IVIM-FWI model provides metrics that are associated with cognitive deficits and may reflect disease progression.

Keywords: diffusion MRI; free water; gray matter; inflammation; magnetic resonance spectroscopy imaging; memory; perfusion; white matter.

MeSH terms

  • Cerebral Cortex
  • Diffusion Magnetic Resonance Imaging* / methods
  • Gray Matter / diagnostic imaging
  • Humans
  • Magnetic Resonance Imaging
  • White Matter* / diagnostic imaging
  • Young Adult