Radiation-induced regional cerebral blood volume (rCBV) changes in normal brain and low-grade astrocytomas: quantification and time and dose-dependent occurrence

Abstract

Purpose: New tumor-conformal radiation-treatment modalities have been established with the intention to spare normal tissue while maintaining or improving local tumor control. To document radiation-induced changes in normal brain and low-grade astrocytoma we measured regional cerebral blood volumes (rCBV) using a dynamic susceptibility-weighted contrast-enhanced MR technique (DSC-MRI). We attempted to assess pretherapeutic rCBV values and time- and dose-dependent changes following radiotherapy. Methods and Materials: For prospective and longitudinal assessment of rCBV in normal brain and low-grade astrocytoma, 25 patients with histologically proven fibrillary astrocytoma (WHO Grade II) were examined before radiotherapy and during follow-up. Based on CT- and MR-data sets in a stereotactic setup, three-dimensional (3D) treatment planning was done. Radiotherapy was delivered using fractionated stereotactic radiotherapy (FSRT) to mean and median total doses of 60.9 and 60 Gy, respectively (range, 55.8–66 Gy). During MR imaging for treatment planning and follow-up examinations, 55 T2-weighted gradient echo images were acquired before, during, and after intravenous contrast bolus injection. The acquired signal–time curves were converted into concentration–time curves. The area under the tissue concentration–time curve was calculated and normalized to an integrated arterial input function. Thus, absolute rCBV values could be calculated. Results: Pretherapeutic mean rCBV for normal gray (GM) and white brain matter (WM) were 7.2 ± 2.7 and 3.6 ± 1.5 mL/100 g tissue, respectively. Mean rCBV for astrocytoma was 6.5 ± 3.7 mL/100 g tissue. After radiotherapy, rCBV for GM and WM was significantly reduced ( p < 0.01) in high-dose areas (40–100% of total dose). A nonsignificant reduction was measured in low-dose areas (up to 40% of total dose). Reduction of rCBV in astrocytomas to a plateau level of 4.6 ± 0.4 mL/100 g tissue was measured at 6 months after radiotherapy and remained stable in locally controlled tumors. Conclusion: Monitoring of rCBV changes in normal brain and low-grade astrocytoma was feasible using a DSC-MRI technique. The method was able to document radiation effects in low-grade astrocytoma, even if the majority of tumors showed no change in diagnostic MR-imaging. Radiation induced decrease of rCBV in GM and WM was correlated to total dose delivered to a tissue area, with high doses causing a significant decrease. Minor decline of rCBV in GM and WM outside high-dose areas after stereotactic radiotherapy confirms the efficacy to spare normal brain tissue by the use of modern conformal radiotherapy techniques. Nonetheless, a critical minimal dose initiating rCBV changes is yet unknown.