title: MRI changes in the rat hippocampus following proton radiosurgery.
abstract: OBJECTIVE
  To define radiographic dose-response relationships for proton radiosurgery using a rat brain model.
  
  
  METHODS
  A group of 23 rats was treated with Bragg peak proton beam irradiation involving the right hippocampus. Single doses of 5, 12, 20, 30, 60, 90 and 130 cobalt gray equivalents (CGE) were delivered to groups of 3 animals using single fraction technique. One extra animal was included at the 130- and 30-CGE doses. Animals were imaged using a standard 1.5-tesla GE Signa MRI. A 3-inch surface coil was employed to obtain T1-weighted sagittal images (TR 600 and TE 30) and dual echo T2-weighted coronal images (TR 3,000 and TE 30/90). Animals were imaged at 1.5, 3, 4.5, 6 and 9 months. Volumetric analysis with custom software was done to evaluate areas of increased signal on T2-weighted images, and signal change versus time curves were generated. Gadolinium-enhanced T1-weighted imaging was also done at the 9-month time point to further evaluate tissue injury. The development of hydrocephalus was also examined.
  
  
  RESULTS
  Peak tissue injury was greater and occurred earlier with higher versus lower doses of radiation. Statistically significant differences were seen between the 130- and 90-CGE animals and between the 90- and 60-CGE animals (p < 0.0016) using ANOVA. Signal changes can be seen in at least 1 of the animals at 20 CGE. The largest volume of tissue enhancement at 9 months was seen in animals at 60 CGE, which may represent an intermediate zone of tissue injury and gliosis compared with greater tissue loss at higher doses and less injury at lower doses. Hydrocephalus developed first in the untreated hemisphere in 130- and 90-CGE animals as a result of mass effect while it occurred at a later time in the treated hemisphere in lower-dose animals.
  
  
  CONCLUSIONS
  Following single-dose proton radiosurgery of rat hippocampus, serial MRIs show T2 signal changes in animals ranging from 130 down to 20 CGE as well as the development of hydrocephalus. Dose-effect relationships using proton radiosurgery in rats will be a helpful step in guiding further studies on radiation injury to brain tissue.
authors.affiliation: Division of Neuroradiology, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA. jrabinov@partners.org
authors.forename: James D
authors.initials: JD
authors.lastname: Rabinov
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Brisman
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Cole
authors.forename: Patricia Lani
authors.initials: PL
authors.lastname: Lee
authors.forename: Marc R
authors.initials: MR
authors.lastname: Bussiere
authors.forename: Paul H
authors.initials: PH
authors.lastname: Chapman
authors.forename: Jay S
authors.initials: JS
authors.lastname: Loeffler
authors.forename: G Rees
authors.initials: GR
authors.lastname: Cosgrove
authors.forename: Tina
authors.initials: T
authors.lastname: Chaves
authors.forename: R Gilberto
authors.initials: RG
authors.lastname: Gonzalez
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005682:Gadolinium; D006624:Hippocampus / Q000473:pathology* / Q000601:surgery*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D011183:Postoperative Complications / Q000473:pathology; D011522:Protons; D011832:Radiation Injuries / Q000473:pathology*; D016634:Radiosurgery / Q000009:adverse effects*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D011522:Protons; D005682:Gadolinium