Diffusion Tensor Imaging

The perivascular space (PVS) is integral to glymphatic function, facilitating fluid exchange and waste clearance in the brain. Diffusion tensor imaging along the perivascular space (DTI-ALPS) has been proposed as a noninvasive marker of perivascular diffusion, yet its specificity remains unclear. ALPS measures assume radial symmetry in white matter (characterized by equal transverse diffusion eigenvalues, λ2 = λ3) and interpret deviations (i.e., radial asymmetry, where λ2 > λ3) as reflecting PVS contributions. However, anatomical and microstructural confounds may influence these metrics. We systematically evaluated potential biases in ALPS-derived measures using high-resolution, multishell diffusion MRI from the Human Connectome Project (HCP) and high-field imaging. Specifically, we examined (1) the prevalence of radial asymmetry across white matter, (2) the influence of crossing fibers on ALPS indices, (3) the impact of axonal undulations and dispersion, and (4) the spatial alignment of vasculature with white matter in ALPS-associated regions. Radial asymmetry is widespread across white matter and persists even at high b-values, suggesting a dominant contribution from axonal geometry rather than faster PVS-specific diffusion. Crossing fibers significantly inflate ALPS indices, with greater radial asymmetry observed in regions with a greater prevalence of crossing fibers. Furthermore, anisotropic axonal dispersion and undulations introduce systematic asymmetry independent of perivascular diffusion. Finally, high-resolution vascular imaging reveals substantial heterogeneity in medullary vein orientation, challenging the assumption that PVS consistently aligns with the left-right axis in ALPS regions. ALPS indices are significantly influenced by white matter microstructure, including fiber crossings, undulations, and dispersion. These findings suggest that ALPS-derived metrics may not provide a direct measure of glymphatic function but rather reflect underlying axonal geometry. Interpretations of ALPS-derived metrics as biomarkers of glymphatic function must consider these anatomical complexities, and future studies should integrate advanced modeling approaches to disentangle perivascular contributions from white matter structure.

Thanks to recent developments in cardiovascular magnetic resonance (CMR), cardiac diffusion-weighted magnetic resonance is fast emerging in a range of clinical applications. Cardiac diffusion-weighted imaging (cDWI) and diffusion tensor imaging (cDTI) now enable investigators and clinicians to assess and quantify the tridimensional microstructure of the heart. Free-contrast DWI is uniquely sensitized to the presence and displacement of water molecules within the myocardial tissue, including the intracellular, extracellular, and intravascular spaces. CMR can determine changes in microstructure by quantifying: a) mean diffusivity (MD)-measuring the magnitude of diffusion; b) fractional anisotropy (FA)-specifying the directionality of diffusion; c) helix angle (HA) and transverse angle (TA)-indicating the orientation of the cardiomyocytes; d) absolute sheetlet angle (E2A) and E2A mobility-measuring the alignment and systolic-diastolic mobility of the sheetlets, respectively. This document provides recommendations for both clinical and research cDWI and cDTI, based on published evidence when available and expert consensus when not. It introduces the cardiac microstructure focusing on the cardiomyocytes and their role in cardiac physiology and pathophysiology. It highlights methods, observations, and recommendations in terminology, acquisition schemes, postprocessing pipelines, data analysis, and interpretation of the different biomarkers. Despite the ongoing challenges discussed in the document and the need for ongoing technical improvements, it is clear that cDTI is indeed feasible, can be accurately and reproducibly performed and, most importantly, can provide unique insights into myocardial pathophysiology.

BackgroundImpaired glymphatic clearance may contribute to pathological accumulations in Parkinson's (PD), but how it interacts with other processes causing dementia remains unclear. Diffusion tensor image analysis along the perivascular space (DTI-ALPS) has been proposed as an indirect proxy for glymphatic clearance.ObjectivesTo clarify DTI-ALPS' relationship with cognition in PD, and its relationship with established imaging markers.MethodsWe assessed DTI-ALPS in 98 PD patients (31 PD poor outcomes: dementia, mild cognitive impairment, frailty, or death within a 3-year follow-up; 67 PD good outcomes) and 28 controls. We assessed DTI-ALPS' relationship to cognition, white matter (fiber cross-section), cortical thickness, iron accumulation (quantitative susceptibility mapping [QSM]), and plasma markers [phosphorylated tau-181 (p-tau181 and neurofilament light (NfL)] cross-sectionally and longitudinally).ResultsDTI-ALPS was lower in PD-poor outcomes compared with PD good outcomes and controls (P = 0.005) with further longitudinal reductions only in PD poor outcomes (group × time interaction: β = -0.013, P = 0.021). Lower DTI-ALPS was associated with lower fiber cross-section in PD, at baseline and longitudinally but with different spatial distribution from white matter changes relating to PD cognition. There was no correlation between baseline DTI-ALPS and plasma p-tau181 (P = 0.642), NFL (P = 0.448), or baseline cortical thickness. Lower DTI-ALPS was associated with accelerated cortical thinning within left precentral gyrus and changes in brain iron distribution.ConclusionsPD patients who develop poor outcomes show lower DTI-ALPS, potentially reflecting impaired glymphatic clearance. DTI-ALPS correlated with white matter integrity and brain iron accumulation. However, both showed different spatial distribution than that seen in PD dementia, suggesting DTI-ALPS captures a distinct contribution to cognitive decline. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

BackgroundGlioblastoma (GBM) may disrupt glymphatic function and neurofluid dynamics locally and in distant brain regions. However, the prognostic relevance of such alterations remains unclear. We investigated whether diffusion tensor image analysis along the perivascular space (DTI-ALPS) and free water (FW) imaging serve as biomarkers of glymphatic dysfunction and survival in patients with IDH wild-type GBM.MethodsWe retrospectively analyzed preoperative MRI data from 277 patients in the UPENN-GBM and 269 patients in the UCSF-PDGM cohorts. The ALPS index was quantified in tumor regions and normal-appearing white matter (NAWM) in both hemispheres, and the FW volume fraction in the contralateral NAWM. Data harmonization was performed using ComBat to adjust for intersite variability. Survival analyses were conducted using log-rank tests and Cox regression models. Optimal ALPS index and FW thresholds were derived from the UPENN-GBM dataset and validated in the UCSF-PDGM.ResultsThe ALPS index was significantly lower in tumor regions than NAWM (P ConclusionsNeurofluid dynamic alterations in the contralateral hemisphere, assessed using DTI-ALPS and FW imaging, were independently associated with survival in patients with IDH wild-type GBM. These findings support the use of glymphatic imaging markers for prognostic stratification and therapeutic targeting.