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PURPOSE: Radio(chemo)therapy (RCT) as part of the standard treatment of glioma patients, inevitably leads to radiation exposure of the tumor-surrounding normal-appearing (NA) tissues. The effect of radiotherapy on the brain microstructure can be assessed by magnetic resonance imaging (MRI) using diffusion tensor imaging (DTI). The aim of this study was to analyze regional DTI changes of white matter (WM) structures and to determine their dose- and time-dependency. METHODS: As part of a longitudinal prospective clinical study (NCT02824731), MRI data of 23 glioma patients treated with proton or photon beam therapy were acquired at three-monthly intervals until 36 months following irradiation. Mean, radial and axial diffusivity (MD, RD, AD) as well as fractional anisotropy (FA) were investigated in the NA tissue of 15 WM structures and their dependence on radiation dose, follow-up time and distance to the clinical target volume (CTV) was analyzed in a multivariate linear regression model. Due to the small and non-comparable patient numbers for proton and photon beam irradiation, a separate assessment of the findings per treatment modality was not performed. RESULTS: Four WM structures (i.e., internal capsule, corona radiata, posterior thalamic radiation, and superior longitudinal fasciculus) showed statistically significantly decreased RD and MD after RT, whereas AD decrease and FA increase occurred less frequently. The posterior thalamic radiation showed the most pronounced changes after RCT [i.e., ΔRD = -8.51 % (p = 0.012), ΔMD = -6.14 % (p = 0.012)]. The DTI changes depended significantly on mean dose and time. CONCLUSION: Significant changes in DTI for WM substructures were found even at low radiation doses. These findings may prompt new radiation dose constraints sparing the vulnerable structures from damage and subsequent side-effects.
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INTRODUCTION: Loss of blood-brain barrier (BBB) integrity is hypothesised to be one of the earliest microvascular signs of Alzheimer's disease (AD). Existing BBB integrity imaging methods involve contrast agents or ionising radiation, and pose limitations in terms of cost and logistics. Arterial spin labelling (ASL) perfusion MRI has been recently adapted to map the BBB permeability non-invasively. The DEveloping BBB-ASL as a non-Invasive Early biomarker (DEBBIE) consortium aims to develop this modified ASL-MRI technique for patient-specific and robust BBB permeability assessments. This article outlines the study design of the DEBBIE cohorts focused on investigating the potential of BBB-ASL as an early biomarker for AD (DEBBIE-AD). METHODS AND ANALYSIS: DEBBIE-AD consists of a multicohort study enrolling participants with subjective cognitive decline, mild cognitive impairment and AD, as well as age-matched healthy controls, from 13 cohorts. The precision and accuracy of BBB-ASL will be evaluated in healthy participants. The clinical value of BBB-ASL will be evaluated by comparing results with both established and novel AD biomarkers. The DEBBIE-AD study aims to provide evidence of the ability of BBB-ASL to measure BBB permeability and demonstrate its utility in AD and AD-related pathologies. ETHICS AND DISSEMINATION: Ethics approval was obtained for 10 cohorts, and is pending for 3 cohorts. The results of the main trial and each of the secondary endpoints will be submitted for publication in a peer-reviewed journal.