Detectability of radiation-induced changes in magnetic resonance biomarkers following stereotactic radiosurgery: A pilot study

Abstract

Our objective was to investigate direct voxel-wise relationship between dose and early MR biomarker changes both within and in the high-dose region surrounding brain metastases following stereotactic radiosurgery (SRS). Specifically, we examined the apparent diffusion coefficient (ADC) from diffusion-weighted imaging and the contrast transfer coefficient (Ktrans) and volume of extracellular extravascular space (ve) derived from dynamic contrast-enhanced (DCE) MRI data. We investigated 29 brain metastases in 18 patients using 3 T MRI to collect imaging data at day 0, day 3 and day 20 following SRS. The ADC maps were generated by the scanner and Ktrans and ve maps were generated using in-house software for dynamic tracer-kinetic analysis. To enable spatially-correlated voxel-wise analysis, we developed a registration pipeline to register all ADC, Ktrans and ve maps to the planning MRI scan. To interrogate longitudinal changes, we computed absolute ΔADC, ΔKtrans and Δve for day 3 and 20 post-SRS relative to day 0. We performed a Kruskall-Wallice test on each biomarker between time points and investigated dose correlations within the gross tumour volume (GTV) and surrounding high dose region > 12 Gy via Spearman’s rho. Only ve exhibited significant differences between day 0 and 20 (p < 0.005) and day 3 and 20 (p < 0.05) within the GTV following SRS. Strongest dose correlations were observed for ADC within the GTV (rho = 0.17 to 0.20) and weak correlations were observed for ADC and Ktrans in the surrounding > 12 Gy region. Both ΔKtrans and Δve showed a trend with dose at day 20 within the GTV and > 12 Gy region (rho = -0.04 to -0.16). Weak dose-related decreases in Ktrans and ve within the GTV and high dose region at day 20 most likely reflect underlying vascular responses to radiation. Our study also provides a voxel-wise analysis schema for future MR biomarker studies with the goal of elucidating surrogates for radionecrosis.

DCE-MRI assessment of response to neoadjuvant SABR in early stage breast cancer: Comparisons of single versus three fraction schemes and two different imaging time delays post-SABR

“…However, Wang et al [13] showed a significant increase in v e at 1 week post-SABR for the PTV and CTV, but did not report v e for the GTV which most closely corresponds to the volumes used in our study. On the contrary, Winter et al [36] found significant decreases in v e at 20 days post stereotactic radiosurgery for brain metastases. Furthermore, most studies do not find a significant change in v e following therapy [34][35][36]39,41].…”

“…On the contrary, Winter et al [36] found significant decreases in v e at 20 days post stereotactic radiosurgery for brain metastases. Furthermore, most studies do not find a significant change in v e following therapy [34][35][36]39,41]. These variable results may be due to the long scan times required for precise measurement of v e [5,46].…”

“…In the context of previous studies, our results suggest that 2.5 weeks post-SABR is sufficient in order to minimize acute transient inflammatory effects. In other sites, it has been shown that at short times post-stereotactic radiotherapy (~1-2 weeks posttherapy), there are transient increases in K trans following therapy, primarily attributed to endothelial cell death and permeability increases accompanying acute inflammatory effects [5,13,[34][35][36][37][38]. A recent early stage breast cancer study [13] found significant increases in the initial area under an enhancement curve for the entire GTV at one-week post-single dose SABR.…”

Diffusion and Perfusion MRI Predicts Response Preceding and Shortly After Radiosurgery to Brain Metastases: A Pilot Study

“…v e and K trans are derived from DCE-MRI, which has been extensively utilized to evaluate brain tumors. 9,19,20,[30][31][32] For example, Taunk et al found that post-SRS K trans standard deviation within 12 weeks of treatment was a significant predictive biomarker for lung cancer brain metastases. Almeida-Freitas et al found that an increase of 15% in K trans 4-8 weeks after SRS was predictive of tumor progression.…”

“…The near‐immediate effects of SRS in human brain metastases have not yet been clearly defined by histopathologic or imaging analysis. A recent prospective imaging study assessed changes in DWI and DCE‐MRI parameters at day 0 and day 3 post‐SRS for brain metastases, finding no significant difference in imaging parameters between these two early timepoints 19 . Another prospective imaging study assessed changes in blood volume in brain metastases 1 week and 1 month post‐SRS using DCE‐MRI and IVIM, 20 demonstrating significant changes in blood volume only at 1 month.…”