Mapping metabolic changes associated with early Radiation Induced Lung Injury post conformal radiotherapy using hyperpolarized ¹³C-pyruvate Magnetic Resonance Spectroscopic Imaging.
OBJECTIVE
Radiation Pneumonitis (RP) limits radiotherapy. Detection of early metabolic changes in the lungs associated with RP may provide an opportunity to adjust treatment before substantial toxicities occur. In this work, regional lactate-to-pyruvate signal ratio (lac/pyr) was quantified in rat lungs and heart following administration of hyperpolarized (13)C-pyruvate magnetic resonance imaging (MRI) at day 5, 10, 15 and 25-post conformal radiotherapy. These results were also compared to histology and blood analyses.


METHODS
The lower right lungs of 12 Sprague Dawley rats were irradiated in 2 fractions with a total dose of 18.5 Gy using a modified micro-CT system. Regional lactate and pyruvate data were acquired from three irradiated and three age-matched healthy rats at each time point on days 5, 10, 15 and 25-post radiotherapy. Arterial blood was collected from each animal prior to the (13)C-pyruvate injection and was analyzed for blood lactate concentration and arterial oxygen concentration (paO₂). Macrophage count was computed from the histology of all rat lungs.


RESULTS
A significant increase in lac/pyr was observed in both right and left lungs of the irradiated cohort compared to the healthy cohort for all time points. No increase in lac/pyr was observed in the hearts of the irradiated cohort compared to the hearts of the healthy cohorts. Blood lactate concentration and paO2 did not show a significant change between the irradiated and the healthy cohorts. Macrophage count in both right and left lungs was elevated for the irradiated cohort compared to the healthy cohort.


CONCLUSIONS
Metabolic changes associated with RP may be mapped as early as five days post conformal radiotherapy. Over the small sample size in each cohort, elevated macrophage count, consistent with early phase of inflammation was highly correlated to increases in lac/pyr in both the irradiated and unirradiated lungs. Further experiments with larger sample size may improve the confidence of this finding.
Dept. of Medical Biophysics, Western University, London, Canada; Imaging Research Laboratories, Robarts Research Institute, Western University, London, Canada. Electronic address: kundanthind@gmail.com.
Kundan
K
Thind
Dept. of Medical Biophysics, Western University, London, Canada.
Michael D
MD
Jensen
Imaging Research Laboratories, Robarts Research Institute, Western University, London, Canada.
Elaine
E
Hegarty
GE Healthcare, Toronto, Canada.
Albert P
AP
Chen
Dept. of Medical Biophysics, Western University, London, Canada; Imaging Research Laboratories, Robarts Research Institute, Western University, London, Canada.
Heeseung
H
Lim
Imaging Research Laboratories, Robarts Research Institute, Western University, London, Canada.
Francisco
F
Martinez-Santiesteban
Dept. of Medical Biophysics, Western University, London, Canada; Dept. of Oncology, Western University, London, Canada.
Jake
J
Van Dyk
Dept. of Medical Biophysics, Western University, London, Canada; Imaging Research Laboratories, Robarts Research Institute, Western University, London, Canada; Dept. of Physics and Astronomy, Western University, London, Canada.
Eugene
E
Wong
Imaging Research Laboratories, Robarts Research Institute, Western University, London, Canada.
Timothy J
TJ
Scholl
Dept. of Medical Biophysics, Western University, London, Canada; Imaging Research Laboratories, Robarts Research Institute, Western University, London, Canada; Dept. of Medical Imaging, Western University, London, Canada.
Giles E
GE
Santyr
D000818:Animals; D002247:Carbon Isotopes; D066241:Carbon-13 Magnetic Resonance Spectroscopy / Q000379:methods; D006321:Heart / Q000528:radiation effects; D019344:Lactic Acid / Q000097:blood; D008168:Lung / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects*; D055370:Lung Injury / Q000097:blood / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D010100:Oxygen / Q000097:blood; D019289:Pyruvic Acid / Q000378:metabolism*; D011833:Radiation Injuries, Experimental / Q000097:blood / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D017564:Radiation Pneumonitis / Q000097:blood / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D020266:Radiotherapy, Conformal; D051381:Rats; D017207:Rats, Sprague-Dawley
D002247:Carbon Isotopes; D019344:Lactic Acid; D019289:Pyruvic Acid; D010100:Oxygen
(13)C-lactate; Conformal radiotherapy; Hyperpolarized (13)C-pyruvate; MRI; Macrophage; Radiation Induced Lungs Injury; Radiation Pneumonitis