Quantitative Magnetic Resonance Spectroscopy Reveals a Potential Relationship between Radiation-Induced Changes in Rat Brain Metabolites and Cognitive Impairment

Abstract

To test the efficacy of magnetic resonance spectroscopy (MRS) in identifying radiation-induced brain injury, adult male Fischer 344 rats received fractionated whole-brain irradiation (40 or 45 Gy given in 5-Gy fractions twice a week for 4 or 4.5 weeks, respectively); control rats received sham irradiation. Twelve and 52 weeks after whole-brain irradiation, rats were subjected to high-resolution MRI and proton MRS. No apparent lesions or changes in T(1)- or T(2)-weighted images were noted at either time. This is in agreement with no gross changes being found in histological sections from rats 50 weeks postirradiation. Analysis of the MR spectra obtained 12 weeks after fractionated whole-brain irradiation also failed to show any significant differences (P > 0.1) in the concentration of brain metabolites between the whole-brain-irradiated and sham-irradiated rats. In contrast, analysis of the MR spectra obtained 52 weeks postirradiation revealed significant differences between the irradiated and sham-irradiated rats in the concentrations of several brain metabolites, including increases in the NAA/tCr (P < 0.005) and Glx/tCr (P < 0.001) ratios and a decrease in the mI/tCr ratio (P < 0.01). Although the cognitive function of these rats measured by the object recognition test was not significantly different (P > 0.1) between the irradiated and sham-irradiated rats at 14 weeks postirradiation, it was significantly different (P < 0.02) at 54 weeks postirradiation. These findings suggest that MRS may be a sensitive, noninvasive tool to detect changes in radiation-induced brain metabolites that may be associated with the radiation-induced cognitive impairments observed after prolonged fractionated whole-brain irradiation.

Measurement of Lactate Content and Amide Proton Transfer Values in the Basal Ganglia of a Neonatal Piglet Hypoxic-Ischemic Brain Injury Model Using MRI

“…The Cramer-Rao Lower Bound estimating produced by the LCModel avoids extensive examination of each spectroscopic image and helps reject low-quality spectra (Fig 4). 46 Studies 47,48 have suggested that the coefficient of variation of absolute substance content calculated by the LCModel is lower than that for the ratio of metabolites.…”

Quantitative/Objective Analyses of RT-Induced Late Normal Tissue Injury Using Functional Imaging

“…They suggested a potential relationship between RT-induced brain injury and neurocognitive dysfunction (Fig. 17) (Atwood et al 2007). …”

“…Significant metabolites changes (c) and reduced cognitive function (d) after 52 and 54 weeks of whole brain irradiation, respectively (*, **, and, *** represent statistically significant results; p-values are less than 0.01). Reproduced with permission from Atwood et al (2007) 5.3 PET A study from M.D. Anderson reported hepatic radiation injury using FDG-PET in patients with distal esophageal cancer treated with chemoradiation.…”

Pharmacological strategies to spare normal tissues from radiation damage: useless or overlooked therapeutics?

“…As mentioned by Jeraj and colleagues, there is a need to develop non-invasive functional and molecular imaging that is able to identify early imaging manifestations of IR-related effects (i.e., before clinical manifestations) in order to propose candidate mitigators [115]. Magnetic resonance spectroscopy (MRS) recently showed promising imaging results after fractionated brain irradiation in rats [116]. The particularity of this functional imaging is its capacity to identify metabolic distribution in the brain.…”