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Regional susceptibility to dose-dependent white matter damage after brain radiotherapy.

ABSTRACT: BACKGROUND AND PURPOSE:Regional differences in sensitivity to white matter damage after brain radiotherapy (RT) are not well-described. We characterized the spatial heterogeneity of dose-response across white matter tracts using diffusion tensor imaging (DTI). MATERIALS AND METHODS:Forty-nine patients with primary brain tumors underwent MRI with DTI before and 9-12months after partial-brain RT. Maps of fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were generated. Atlas-based white matter tracts were identified. A secondary analysis using skeletonized tracts was also performed. Linear mixed-model analysis of the relationship between mean and max dose and percent change in DTI metrics was performed. RESULTS:Tracts with the strongest correlation of FA change with mean dose were the fornix (-0.46 percent/Gy), cingulum bundle (-0.44 percent/Gy), and body of corpus callosum (-0.23 percent/Gy), p<.001. These tracts also showed dose-sensitive changes in MD and RD. In the skeletonized analysis, the fornix and cingulum bundle remained highly dose-sensitive. Maximum and mean dose were similarly predictive of DTI change. CONCLUSIONS:The corpus callosum, cingulum bundle, and fornix show the most prominent dose-dependent changes following RT. Future studies examining correlation with cognitive functioning and potential avoidance of critical white matter regions are warranted.

SUBMITTER: Connor M

PROVIDER: S-EPMC5518466 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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Regional susceptibility to dose-dependent white matter damage after brain radiotherapy.

Connor Michael M Karunamuni Roshan R McDonald Carrie C Seibert Tyler T White Nathan N Moiseenko Vitali V Bartsch Hauke H Farid Nikdokht N Kuperman Joshua J Krishnan Anitha A Dale Anders A Hattangadi-Gluth Jona A JA

Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology 20170502 2

<h4>Background and purpose</h4>Regional differences in sensitivity to white matter damage after brain radiotherapy (RT) are not well-described. We characterized the spatial heterogeneity of dose-response across white matter tracts using diffusion tensor imaging (DTI).<h4>Materials and methods</h4>Forty-nine patients with primary brain tumors underwent MRI with DTI before and 9-12months after partial-brain RT. Maps of fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and ...[more]

PMID: 28460824

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Project description:White matter disruption is an important determinant of cognitive impairment after brain injury, but conventional neuroimaging underestimates its extent. In contrast, diffusion tensor imaging provides a validated and sensitive way of identifying the impact of axonal injury. The relationship between cognitive impairment after traumatic brain injury and white matter damage is likely to be complex. We applied a flexible technique-tract-based spatial statistics-to explore whether damage to specific white matter tracts is associated with particular patterns of cognitive impairment. The commonly affected domains of memory, executive function and information processing speed were investigated in 28 patients in the post-acute/chronic phase following traumatic brain injury and in 26 age-matched controls. Analysis of fractional anisotropy and diffusivity maps revealed widespread differences in white matter integrity between the groups. Patients showed large areas of reduced fractional anisotropy, as well as increased mean and axial diffusivities, compared with controls, despite the small amounts of cortical and white matter damage visible on standard imaging. A stratified analysis based on the presence or absence of microbleeds (a marker of diffuse axonal injury) revealed diffusion tensor imaging to be more sensitive than gradient-echo imaging to white matter damage. The location of white matter abnormality predicted cognitive function to some extent. The structure of the fornices was correlated with associative learning and memory across both patient and control groups, whilst the structure of frontal lobe connections showed relationships with executive function that differed in the two groups. These results highlight the complexity of the relationships between white matter structure and cognition. Although widespread and, sometimes, chronic abnormalities of white matter are identifiable following traumatic brain injury, the impact of these changes on cognitive function is likely to depend on damage to key pathways that link nodes in the distributed brain networks supporting high-level cognitive functions.

Project description:PurposeQuantitative assessment of white matter hyperintensities (WMH) on structural Magnetic Resonance Imaging (MRI) is challenging. It is important to harmonise results from different software tools considering not only the volume but also the signal intensity. Here we propose and evaluate a metric of white matter (WM) damage that addresses this need.MethodsWe obtained WMH and normal-appearing white matter (NAWM) volumes from brain structural MRI from community dwelling older individuals and stroke patients enrolled in three different studies, using two automatic methods followed by manual editing by two to four observers blind to each other. We calculated the average intensity values on brain structural fluid-attenuation inversion recovery (FLAIR) MRI for the NAWM and WMH. The white matter damage metric is calculated as the proportion of WMH in brain tissue weighted by the relative image contrast of the WMH-to-NAWM. The new metric was evaluated using tissue microstructure parameters and visual ratings of small vessel disease burden and WMH: Fazekas score for WMH burden and Prins scale for WMH change.ResultsThe correlation between the WM damage metric and the visual rating scores (Spearman ρ > =0.74, p < 0.0001) was slightly stronger than between the latter and WMH volumes (Spearman ρ > =0.72, p < 0.0001). The repeatability of the WM damage metric was better than WM volume (average median difference between measurements 3.26% (IQR 2.76%) and 5.88% (IQR 5.32%) respectively). The follow-up WM damage was highly related to total Prins score even when adjusted for baseline WM damage (ANCOVA, p < 0.0001), which was not always the case for WMH volume, as total Prins was highly associated with the change in the intense WMH volume (p = 0.0079, increase of 4.42 ml per unit change in total Prins, 95%CI [1.17 7.67]), but not with the change in less-intense, subtle WMH, which determined the volumetric change.ConclusionThe new metric is practical and simple to calculate. It is robust to variations in image processing methods and scanning protocols, and sensitive to subtle and severe white matter damage.

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Regional susceptibility to dose-dependent white matter damage after brain radiotherapy.

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Regional susceptibility to dose-dependent white matter damage after brain radiotherapy.

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