title: Early radiotherapy dose response and lack of hypersensitivity effect in normal brain tissue: a sequential dynamic susceptibility imaging study of cerebral perfusion.
abstract: OBJECTIVE
  To determine if magnetic resonance perfusion markers can be used as an analytical marker of subclinical normal brain injury after radiotherapy, by looking for a dose-effect relationship.
  
  
  METHODS
  Four patients undergoing conformal radiotherapy to 54Gy in 30 fractions for low-grade gliomas were imaged with conventional T(2)-weighted and fluid attenuated inversion recovery imaging as well as dynamic contrast susceptibility perfusion imaging. Forty regions of interest were determined from the periventricular white matter. All conventional sequences were examined for evidence of radiation-induced changes. Patients were imaged before radiotherapy, after one fraction, at the end of treatment and then at 1 and 3 months from the end of radiotherapy. For each region the relative cerebral blood volume (rCBV), relative cerebral blood flow (rCBF) and mean transit time (MTT) expressed as a ratio of the baseline value, and radiotherapy dose were determined.
  
  
  RESULTS
  Of the 40 regions, seven occurred within the gross tumour volume and a further four occurred in regions later infiltrated by tumour, and were thus excluded. Regions within the 80% isodose showed a reduction in rCBV and rCBF over the 3 month period. There was no significant alteration in rCBV or rCBF in regions outside the 60% isodose (i.e. <32Gy). MTT did not alter in any region. There seemed to be a threshold effect at 132 days from the end of radiotherapy of 47% (standard error of the mean 11.5, about 25.4Gy) for rCBV and 59% (standard error of the mean 14.2, about 31.9Gy) for rCBF.
  
  
  CONCLUSIONS
  There was a dose-related reduction in rCBV and rCBF in normal brain after radiotherapy at higher dose levels. Although this study used a limited number of patients, it suggests that magnetic resonance perfusion imaging seems to act as a marker of subclinical response of normal brain and that there is an absence of an early hypersensitivity effect with small doses per fraction. Further studies are required with larger groups of patients to show that these results are statistically robust.
authors.affiliation: Academic Neurosurgical Unit, Cambridge University and Addenbrooke's Hospital, Cambridge, UK. sjp58@cam.ac.uk
authors.forename: S J
authors.initials: SJ
authors.lastname: Price
authors.forename: R
authors.initials: R
authors.lastname: Jena
authors.forename: H A L
authors.initials: HA
authors.lastname: Green
authors.forename: N F
authors.initials: NF
authors.lastname: Kirkby
authors.forename: A G
authors.initials: AG
authors.lastname: Lynch
authors.forename: C E
authors.initials: CE
authors.lastname: Coles
authors.forename: J D
authors.initials: JD
authors.lastname: Pickard
authors.forename: J H
authors.initials: JH
authors.lastname: Gillard
authors.forename: N G
authors.initials: NG
authors.lastname: Burnet
mesh_terms: D000328:Adult; D001921:Brain / Q000098:blood supply / Q000528:radiation effects*; D004307:Dose-Response Relationship, Radiation; D004342:Drug Hypersensitivity; D005260:Female; D005910:Glioma / Q000532:radiotherapy*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D010477:Perfusion; D011446:Prospective Studies; D011878:Radiotherapy / Q000009:adverse effects*; D013997:Time Factors