Early Radiotherapy Dose Response and Lack of Hypersensitivity Effect in Normal Brain Tissue: a Sequential Dynamic Susceptibility Imaging Study of Cerebral Perfusion

Price, S.J.; Jena, R.; Green, H.A.L.; Kirkby, N.F.; Lynch, A.G.; Coles, C.E.; Pickard, J.D.; Gillard, J.H.; Burnet, N.G.

doi:10.1016/j.clon.2007.04.010

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Volume 19, Issue 8 , Pages 577-587, October 2007

Early Radiotherapy Dose Response and Lack of Hypersensitivity Effect in Normal Brain Tissue: a Sequential Dynamic Susceptibility Imaging Study of Cerebral Perfusion

S.J. Price
- Academic Neurosurgical Unit, Cambridge University and Addenbrooke's Hospital, Cambridge CB2 2QQ, UK
- University Department of Radiology, Cambridge University and Addenbrooke's Hospital, Cambridge CB2 2QQ, UK
- Wolfson Brain Imaging Centre, Cambridge University and Addenbrooke's Hospital, Cambridge CB2 2QQ, UK
- Author for correspondence: S. J. Price, University of Cambridge, Academic Neurosurgery Unit, Box 167, Addenbrooke's Hospital, Hills Road, Cambridge CB2 2QQ, UK. Tel: +44 1223 336935.
R. Jena
- University Department of Oncology, Cambridge University and Addenbrooke's Hospital, Cambridge CB2 2QQ, UK
H.A.L. Green
- Wolfson Brain Imaging Centre, Cambridge University and Addenbrooke's Hospital, Cambridge CB2 2QQ, UK
N.F. Kirkby
- University Department of Oncology, Cambridge University and Addenbrooke's Hospital, Cambridge CB2 2QQ, UK
- Fluids and Systems Research Centre, School of Engineering, University of Surrey, Guildford, Surrey GU2 7XH, UK
A.G. Lynch
- University Department of Oncology, Cambridge University and Addenbrooke's Hospital, Cambridge CB2 2QQ, UK
C.E. Coles
- University Department of Oncology, Cambridge University and Addenbrooke's Hospital, Cambridge CB2 2QQ, UK
J.D. Pickard
- Academic Neurosurgical Unit, Cambridge University and Addenbrooke's Hospital, Cambridge CB2 2QQ, UK
- Wolfson Brain Imaging Centre, Cambridge University and Addenbrooke's Hospital, Cambridge CB2 2QQ, UK
J.H. Gillard
- University Department of Radiology, Cambridge University and Addenbrooke's Hospital, Cambridge CB2 2QQ, UK
N.G. Burnet
- University Department of Oncology, Cambridge University and Addenbrooke's Hospital, Cambridge CB2 2QQ, UK

Received 7 November 2005; received in revised form 15 February 2007; accepted 27 April 2007.

Abstract

Aims

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.

Materials and methods

Four patients undergoing conformal radiotherapy to 54Gy in 30 fractions for low-grade gliomas were imaged with conventional T₂-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.

Key words: Brain, low-dose hypersensitivity, low-grade gliomas, normal tissue dose response, perfusion MRI, radiotherapy