RATIONALE AND OBJECTIVES: Optimal dose schedules and total dose of ionizing radiation for human central nervous system malignancy are not known. An animal model has been developed for the investigation of rat central nervous system response to proton irradiation using magnetic resonance imaging (MRI). A clinical MRI device was used to monitor the response of the rat brain after irradiation as a possible indicator for histologic injury as a function of time and dose. METHODS: Single-dose fractions of protons were delivered to the left brain of 25 adult Sprague-Dawley rats. T1- and T2-weighted images were obtained using a 1.5-T MRI device via a 12-cm diameter coil at 4- to 6-week intervals after irradiation. Coronal images were evaluated by visual inspection and relaxation maps comparing the control and irradiated hemispheres. Histologic review was conducted on all rats' brains after death. RESULTS: Proton irradiation was delivered successfully to only the left brain of the animals. Histologic review confirms the location and extent of tissue damage demonstrated on MRIs obtained in vivo. Statistically significant differences were seen in the T2-weighted relaxation times in the irradiated cerebral hemisphere compared with the unirradiated hemisphere. CONCLUSION: The proton hemibrain rat model can be used to test treatment schedules of irradiation for central nervous system response using MRI to noninvasively document early and late effects within the same animal.
RATIONALE AND OBJECTIVES: Optimal dose schedules and total dose of ionizing radiation for human central nervous system malignancy are not known. An animal model has been developed for the investigation of rat central nervous system response to proton irradiation using magnetic resonance imaging (MRI). A clinical MRI device was used to monitor the response of the rat brain after irradiation as a possible indicator for histologic injury as a function of time and dose. METHODS: Single-dose fractions of protons were delivered to the left brain of 25 adult Sprague-Dawley rats. T1- and T2-weighted images were obtained using a 1.5-T MRI device via a 12-cm diameter coil at 4- to 6-week intervals after irradiation. Coronal images were evaluated by visual inspection and relaxation maps comparing the control and irradiated hemispheres. Histologic review was conducted on all rats' brains after death. RESULTS: Proton irradiation was delivered successfully to only the left brain of the animals. Histologic review confirms the location and extent of tissue damage demonstrated on MRIs obtained in vivo. Statistically significant differences were seen in the T2-weighted relaxation times in the irradiated cerebral hemisphere compared with the unirradiated hemisphere. CONCLUSION: The proton hemibrain rat model can be used to test treatment schedules of irradiation for central nervous system response using MRI to noninvasively document early and late effects within the same animal.
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