In vivo Mapping of Cellular Resolution Neuropathology in Brain Ischemia by Diffusion MRI.
Dan WuVictoria TurnbillHong-Hsi LeeXiaoli WangRuicheng BaPiotr WalczakLee J MartinEls FieremansDmitry S NovikovFrances J NorthingtonJiangyang ZhangPublished in: bioRxiv : the preprint server for biology (2023)
Non-invasive mapping of cellular pathology can provide critical diagnostic and prognostic information. Recent developments in diffusion MRI have produced new tools for examining tissue microstructure at a level well below the imaging resolution. Here, we report the use of diffusion time ( t )-dependent diffusion kurtosis imaging ( t DKI) to simultaneously assess the morphology and transmembrane permeability of cells and their processes in the context of pathological changes in hypoxic-ischemic brain (HI) injury. Through Monte Carlo simulations and cell culture organoid imaging, we demonstrate feasibility in measuring effective size and permeability changes based on the peak and tail of t DKI curves. In a mouse model of HI, in vivo imaging at 11.7T detects a marked shift of the t DKI peak to longer t in brain edema, suggesting swelling and beading associated with the astrocytic processes and neuronal neurites. Furthermore, we observed a faster decrease of the t DKI tail in injured brain regions, reflecting increased membrane permeability that was associated with upregulated water exchange upon astrocyte activation at acute stage as well as necrosis with disrupted membrane integrity at subacute stage. Such information, unavailable with conventional diffusion MRI at a single t, can predict salvageable tissues. For a proof-of-concept, t DKI at 3T on an ischemic stroke patient suggested increased membrane permeability in the stroke region. This work therefore demonstrates the potential of t DKI for in vivo detection of the pathological changes in microstructural morphology and transmembrane permeability after ischemic injury using a clinically translatable protocol.
Keyphrases
- high resolution
- white matter
- resting state
- cerebral ischemia
- endothelial cells
- magnetic resonance imaging
- mouse model
- contrast enhanced
- monte carlo
- diffusion weighted imaging
- atrial fibrillation
- gene expression
- computed tomography
- intensive care unit
- healthcare
- mass spectrometry
- social media
- blood brain barrier
- case report
- brain injury
- respiratory failure
- cell cycle arrest
- loop mediated isothermal amplification
- fluorescence imaging
- quantum dots