Comparative evaluation of brain
neurometabolites and DTI indices following
whole body and cranial irradiation: a magnetic
resonance imaging and spectroscopy study
Mamta Gupta
a
, Poonam Rana
a
, Richa Trivedi
a
, B. S. Hemanth Kumar
a
,
Ahmad Raza Khan
a
, Ravi Soni
b
, R. K. S. Rathore
c
and Subash Khushu
a
*
Understanding early differential response of brain during whole body radiation or cranial radiation exposure is of
significant importance for better injury management during accidental or intentional exposure to ionizing radiation.
We investigated the early microstructural and metabolic profiles using in vivo diffusion tensor imaging (DTI) and
proton magnetic resonance spectroscopy (
1
H MRS) following whole body and cranial radiation exposure of 8 Gy
in mice using a 7.0 T animal MRI system and compared profiles with sham controls at days 1, 3, 5 and 10 post
irradiation. A significant decrease in fractional anisotropy (FA) values was found in hippocampus, thalamic and
hypothalamic regions (p < 0.05) in both whole body and cranial irradiated groups compared with controls, suggesting
radiation induced reactive astrogliosis or neuroinflammatory response. In animals exposed to whole body radiation, FA
was significantly decreased in some additional brain regions such as sensory motor cortex and corpus callosum in
comparison with cranial irradiation groups and controls. Changes in FA were observed till day 10 post irradiation
in both the groups. However, MRS study from hippocampus revealed changes only in the whole body radiation dose
group. Significant reduction in the ratios of the metabolites myoinositol (mI, p = 0.02) and taurine (tau, p = 0.03) to
total creatine were observed, and these metabolic alterations persisted till day 10 post irradiation. To the best of
our knowledge this study has for the first time documented a comparative account of microstructural and metabolic
aspects of whole body and cranial radiation induced early brain injury using in vivo MRI. Overall our findings suggest
differential response at microstructure and metabolite levels following cranial or whole body radiation exposure.
Copyright © 2013 John Wiley & Sons, Ltd.
Keywords: radiation exposure; acute injury; cranial irradiation; whole body irradiation; astrogliosis;
1
H MRS; DTI
INTRODUCTION
The central nervous system (CNS) is exposed to ionizing radiation in
a number of situations, predominantly involving cancer treatment
or during radiation accidents at nuclear reactors and radiological
terrorist attacks. The pathophysiology of radiation injury to the
CNS is not fully understood. It may vary with the type of exposure
(partial or whole body), radiation dose, size of radiation field etc.
While local irradiation of a specific tissue produces a localised lesion
characterized by that tissue, total body irradiation produces a more
generalised syndrome. Radiotherapy remains a major treatment
modality for primary and metastatic neoplasms located in the
CNS. Based on time of expression, cranial radiation induced CNS
injury has been divided into three reactions: acute (days to weeks
post irradiation), early delayed (1 to 6 months post irradiation)
and late delayed (more than 6 months post irradiation). Acute and
early delayed post-irradiation changes are associated with transient
cerebral parenchyma oedematous and transient demyelination
changes (1,2). The late delayed changes are irreversible and
associated with neurological complications, white matter changes
and neurocognitive deficits in long-term survivors (3). During whole
body radiation induced acute radiation sickness (ARS), the role of the
CNS has been underestimated, but now there is increasing scienti fic
information showing whole body radiation induced neuroimmune
and inflammatory response. These neuroinflammatory responses
following whole body radiation exposure could contribute to the
* Correspondence to: S. Khushu, NMR Research Centre, Institute of Nuclear
Medicine and Allied Sciences, Delhi, India.
E-mail: skhushu@yahoo.com
a M. Gupta, P. Rana, R. Trivedi, B. S. H. Kumar, A. R. Khan, S. Khushu
NMR Research Centre, Institute of Nuclear Medicine and Allied Sciences, Delhi,
India
b R. Soni
Division of Radiation Biosciences, Institute of Nuclear Medicine and Allied
Sciences, Delhi, India
c R. K. S. Rathore
Department of Mathematics and Statistics, Indian Institute of Technology,
Kanpur, India
Abbreviations used:
1
H MRS, proton magnetic resonance spectroscopy; DTI,
diffusion tensor imaging; FA, fractional anisotropy; MD, mean diffusivity; λ
a
,
axial diffusivity; λ
r
, radial diffusivity; mI, myoinositol; tau, taurine; CNS, central
nervous system; SSD, surface to source distance; BW, body weight; FOV, field of
view; SMC, sensory–motor cortex; CC, corpus callosum; Hip, hippocampus; TH,
thalamus; HTH, hypothalamus; tCr, creatine plus phosphocreatine; tCh,
glycerophosphocholine plus phosphocholine; NAA, N-acetyl aspartate; Glx, total
glutamine plus glutamate.
Research article
Received: 09 April 2013, Revised: 27 June 2013, Accepted: 15 July 2013, Published online in Wiley Online Library
(wileyonlinelibrary.com) DOI: 10.1002/nbm.3010
NMR Biomed. 2013 Copyright © 2013 John Wiley & Sons, Ltd.
1
Journal Code Article ID Dispatch: 15.08.13 CE:
N B M 3 0 1 0 No. of Pages: 9 ME:
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