Understanding the continuum of radionecrosis and vascular disorders in the brain following gamma knife irradiation: An MRI study

Abstract

Purpose: The radiation dose delivered to brain tumors is limited by the possibility to induce vascular damage and necrosis in surrounding healthy tissue. In the present study, we assessed the ability of MRI to monitor the cascade of events occurring in the healthy rat brain after stereotactic radiosurgery, which could be used to optimize the radiation treatment planning. Methods: The primary somatosensory forelimb area (S1FL) and the primary motor cortex in the right hemisphere of Fischer rats (n ¼ 6) were irradiated with a single dose of Gamma Knife radiation (Leksell Perfexion, Elekta AG, Stockholm, Sweden). Rats were scanned with a small-animal 7 Tesla MRI scanner before treatment and 16, 21, 54, 82, and 110 days following irradiation. At every imaging session, T 2 -weighted (T 2 w), Gd-DTPA dynamic contrast-enhanced MRI (DCE-MRI), and T Ã 2 -weighted (T Ã 2 w) images were acquired to measure changes in fluid content, blood vessel permeability, and structure, respectively. At days 10, 110, and 140, histopathology was performed on brain sections. Locomotion and spatial memory ability were assessed longitudinally by behavioral tests. Results: No vascular changes were initially observed. After 54 days, a small necrotic volume in the white matter below the S1FL, surrounded by an area presenting significant vascular permeability, was revealed. Between 54 and 110 days, the necrotic volume increased and was accompanied by the formation of a ring-like region, where a mixture of necrosis and permeable blood vessels were observed, as confirmed by histology. Behavioral changes were only observed after day 82.Conclusion: Together, DCE-MRI and T Ã 2 w images supported by histology provided a coherent picture of the phenomena involved in the formation of new, leaky blood vessels, which was followed by the detection of radionecrosis in a preclinical model of brain irradiation.

Diffusion MRI monitoring of specific structures in the irradiated rat brain

“…However, despite a constant FA over the experimental time course, and even though it had received the lowest dose, the hippocampus was the most affected structure with MD increased by 29%, AD increased by 28%, and RD increased by 30% compared to the contralateral hippocampus on day 110. This is consistent with a previous report using the same animal model in the same conditions where rats demonstrated a spatial memory decline . The tissue surrounding the necrotic area was characterized by the presence of inflammation, which was paralleled by a decreased anisotropy and/or increased MD.…”

“…After 12 weeks post‐irradiation, they observed edema on T 2 ‐w images as well as hyperintense signal on MD maps into the neocortex and the hippocampus. Our study confirms the results of Harsan et al and of Perez‐Torres et al We have previously observed hypointense signals attributed to iron deposits on w images . Although it can be easily rationalized that edema can cause an increase of MD without necessarily affecting mesoscopic changes, the effect on DTI measures of strong dephasing caused by iron deposits remain unclear.…”

“…In this study, elevated MD was observed in the irradiated hippocampus (24 Gy) region on days 90 and 110, and a decreased learning spatial memory (longer escape latency in the Morris water maze task) was observed on day 134 on the same animal model as previously published . This could suggest that an elevated MD corresponds to changes in the brain functional response to radiation.…”

“…In severe diffuse reactive astrogliosis, there is pronounced up‐regulation of GFAP expression, with pronounced hypertrophy of cell body and processes, as well as astrocyte proliferation, resulting in agglutinating and overlapping of neighboring astrocyte processes (Figure ) . In our study, reactive astrogliosis can be because of necrosis but also because of the permeable neovascularization that we observed in the same animal model using w coupled to DCE‐MRI . Astrogliosis was also assessed by Wang et al It did not progress significantly with time after irradiation (for both 25 and 30 Gy) as judged from their GFAP staining results.…”

“…We previously validated the usefulness of ‐weighted images for the detection of radiation necrosis and measured blood vessel permeability using dynamic contrast‐enhanced MRI in the same animal model . The onset of radiation necrosis being dose‐dependent, as demonstrated by Jiang et al, our animal model received a high dose of radiation that enabled us to observe damage after a short delay.…”