Biodosimetric quantification of short-term synchrotron microbeam versus broad-beam radiation damage to mouse skin using a dermatopathological scoring system

Abstract

Objectives: Microbeam radiotherapy (MRT) with wafers of microscopically narrow, synchrotron generated X-rays is being used for pre-clinical cancer trials in animal models. It has been shown that high dose MRT can be effective at destroying tumours in animal models, while causing unexpectedly little damage to normal tissue. The aim of this study was to use a dermatopathological scoring system to quantify and compare the acute biological response of normal mouse skin with microplanar and broad-beam (BB) radiation as a basis for biological dosimetry. Method: The skin flaps of three groups of mice were irradiated with high entrance doses (200 Gy, 400 Gy and 800 Gy) of MRT and BB and low dose BB (11 Gy, 22 Gy and 44 Gy). The mice were culled at different time-points post-irradiation. Skin sections were evaluated histologically using the following parameters: epidermal cell death, nuclear enlargement, spongiosis, hair follicle damage and dermal inflammation. The fields of irradiation were identified by cH2AX-positive immunostaining. Results: The acute radiation damage in skin from high dose MRT was significantly lower than from high dose BB and, importantly, similar to low dose BB. Conclusion: The integrated MRT dose was more relevant than the peak or valley dose when comparing with BB fields. In MRT-treated skin, the apoptotic cells of epidermis and hair follicles were not confined to the microbeam paths.

Treating Brain Tumor with Microbeam Radiation Generated by a Compact Carbon-Nanotube-Based Irradiator: Initial Radiation Efficacy Study

“…Priyadarshika et al . reported significantly less skin damage, including leukocyte infiltration, from high-dose MRT (800 Gy) than from high-dose (44 Gy) BRT (33). Dilmanian et al .…”

“…Priyadarshika et al . suggested that the integrated dose of MRT, which is the microbeam dose averaged over the entire radiation volume, might be more relevant than the peak or valley dose when compared to broad-beam radiation (33). Recently, Ibahim et al .…”

An Evaluation of Dose Equivalence between Synchrotron Microbeam Radiation Therapy and Conventional Broadbeam Radiation Using Clonogenic and Cell Impedance Assays

“…The study by Priyadarshika et al [27] concluded that the acute response of normal mouse skin to MRT may be dictated by the integrated MRT dose rather than the peak or valley dose. The integrated doses for the 175/25 and 150/50 µm collimator geometries are approximately a factor of 1/8 and 1/4 the peak dose respectively [28].…”

Microbeam-irradiated tumour tissue possesses a different infrared absorbance profile compared to broad beam and sham-irradiated tissue

“…We recognise the observed diff erences in infrared absorbance profi les between MRT and BB modalities may be due to the total dose diff erences between the two modalities in addition to the geometrical diff erences between BB and MRT distributions. We made some related comments on the diffi culties of comparing MRT and BB dosimetry in our 2011 paper (Priyadarshika et al 2011). A detailed dose response study would prove useful in trying to better understand the role of absorbed dose in infrared spectroscopy of irradiated tissue.…”