Effect of the Maximum Dose on White Matter Fiber Bundles Using Longitudinal Diffusion Tensor Imaging

Abstract

Purpose Previous efforts to decrease neurocognitive effects of radiation focused on sparing isolated cortical structures. We hypothesize that understanding temporal, spatial and dosimetric patterns of radiation damage of whole brain white matter (WBWM) after partial brain irradiation might also be important. Therefore, we carried out a study to develop the methodology to assess radiotherapy-induced damage to WBWM bundles. Methods An atlas-based, automated WM tractography analysis was implemented to quantify longitudinal changes in indices of diffusion tensor imaging (DTI) of 22 major WM fibers in 33 patients with predominantly low-grade/benign brain tumors treated by radiotherapy. Six DTI scans per patient were performed from pre-RT to 18 months post-RT. The DTI indices and planned doses (maximum and mean doses) were mapped onto profiles of each of 22 WM bundles. A multivariate linear regression was performed to determine the main dose effect as well as the influence of other clinical factors on longitudinal percentage changes in axial and radial diffusivity (AD and RD) from pre-RT. Results Of 22 fiber bundles, AD/RD changes in 12 bundles were affected significantly by doses (P<0.05), as the effect was progressive over time. In nine elongated tracts, decreased AD/RD was significantly related to maximum doses received, consistent with a serial-structure. In individual bundles, AD changes were up to 11.5% at the maximum dose locations 18 months post-RT. The dose effect on WM was greater in older females than younger males. Conclusion Our study demonstrates for the first time that the maximum dose to the elongated WM bundles causes post-radiotherapy damage in WM. Validation and correlative studies are necessary to determine the ability and impact of sparing these bundles on preserving neurocognitive function post-radiotherapy.

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

“…In patients with MCI, changes within the ventral cingulum are predictive of (and detectable prior to) hippocampal volume loss and memory performance [35]. While a previous study of radiation effects on white matter found dose sensitivity to DTI changes in the parahippocampal cingulum [36], we did not detect robust dose-sensitivity in this structure. Indeed the distinction between the dorsal and ventral aspects of the cingulum are rather arbitrary, and may vary by DTI atlas [25,32].…”

“…With respect to dose, a recent DTI study found that elongated white matter tracts after partial brain RT responded more to maximum dose rather than mean dose [36]. The possibility of serial structure response carries important implications for RT planning, as this suggests that limiting hot spots within a tract is more important than limiting the mean dose delivered to the entire structure.…”

Dose-dependent degeneration of non-cancerous brain tissue in post-radiotherapy patients: A diffusion tensor imaging study

“…Studies on tissue-dose interaction, as the current one, aid in understanding radiation-induced cognitive decline, which may be the consequence of, but not restricted to, demyelination and loss of axonal integrity with increasing radiation doses. Research in neuroscience, especially on aging [47,48] and cognitive impairment [49,50] ROIs receiving certain dose levels or aim to avoid PVE by restricting the masking to connected voxels that only include WM structure by excluding voxels with FA lower than 0.2 [17,29,55].…”

“…We further assumed that tissue change relates linearly to the applied dose. While this framework is widely applied by the RT-community [17,29,55,75], these assumptions may only approximate the true underlying relations. Further biophysical modeling is .…”

Mechanisms of radiotherapy-associated cognitive disability in patients with brain tumours

“…Another recent study found that diffusion changes in individual white matter bundles were associated with maximum dose to those tracts, implying serial radiation injury. 149 There also appears to be regional susceptibility of white matter damage. A study of medulloblastoma survivors found greater diffusion changes in the frontal versus parietal lobes.…”