Abstract
Radiation therapy is widely used for the treatment of brain tumors and may result in cellular, vascular and axonal injury and further behavioral deficits. The non-invasive longitudinal imaging assessment of brain injury caused by radiation therapy is important for determining patient prognoses. Several rodent studies have been performed using magnetic resonance imaging (MRI), but further studies in rabbits and large mammals with advanced magnetic resonance (MR) techniques are needed. Previously, we used diffusion tensor imaging (DTI) to evaluate radiation-induced rabbit brain injury. However, DTI is unable to resolve the complicated neural structure changes that are frequently observed during brain injury after radiation exposure. Generalized q-sampling imaging (GQI) is a more accurate and sophisticated diffusion MR approach that can extract additional information about the altered diffusion environments. Therefore, herein, a longitudinal study was performed that used GQI indices, including generalized fractional anisotropy (GFA), quantitative anisotropy (QA), and the isotropic value (ISO) of the orientation distribution function and DTI indices, including fractional anisotropy (FA) and mean diffusivity (MD) over a period of approximately half a year to observe long-term, radiation-induced changes in the different brain compartments of a rabbit model after a hemi-brain single dose (30 Gy) radiation exposure. We revealed that in the external capsule, the GFA right to left (R/L) ratio showed similar trends as the FA R/L ratio, but no clear trends in the remaining three brain compartments. Both the QA and ISO R/L ratios showed similar trends in the all four different compartments during the acute to early delayed post-irradiation phase, which could be explained and reflected the histopathological changes of the complicated dynamic interactions among astrogliosis, demyelination and vasogenic edema. We suggest that GQI is a promising non-invasive technique and as compared with DTI, it has better potential ability in detecting and monitoring the pathophysiological cascades in acute to early delayed radiation-induced brain injury by using clinical MR scanners.
Highlights
Radiation therapy plays an important role in the treatment of both primary and metastatic brain tumors and can improve tumor control and overall survival in patients with inoperable or unresectable brain tumors
To improve the evaluation of the neurotoxic adverse effects of irradiation treatment in both gray and white matter structures, we longitudinally evaluated the changes in various brain compartments with a clinical magnetic resonance (MR) scanner using Generalized q-sampling imaging (GQI) indices mappings, including generalized fractional anisotropy (GFA), quantitative anisotropy (QA), and the isotropic value (ISO) of the orientation distribution function (ODF) on our previously established adult rabbit model
Not all five rabbits completed the magnetic resonance imaging (MRI) studies at all following time points and only the MRI data from the baseline to the 24th week were included for forward statistical analysis
Summary
Radiation therapy plays an important role in the treatment of both primary and metastatic brain tumors and can improve tumor control and overall survival in patients with inoperable or unresectable brain tumors. It can be used as adjuvant therapy after resection of high grade brain tumors. The exposure of normal brain tissues to radiation can lead to various side effects, such as cellular, axonal and vascular injury, and result in further neurological and behavioral deficits [1,2,3]. Neither the glial nor the vascular hypotheses can fully explain radiation-induced brain injury. The pathophysiology of radiation-induced brain injury is not completely understood, and it remains a challenge for both basic scientists and clinical investigators
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