title: Detection of radiation induced lung injury in rats using dynamic hyperpolarized (129)Xe magnetic resonance spectroscopy.
abstract: OBJECTIVE
  Radiation induced lung injury (RILI) is a common side effect for patients undergoing thoracic radiation therapy (RT). RILI can lead to temporary or permanent loss of lung function and in extreme cases, death. Combining functional lung imaging information with conventional radiation treatment plans may lead to more desirable treatment plans that reduce lung toxicity and improve the quality of life for lung cancer survivors. Magnetic Resonance Imaging of the lung following inhalation of hyperpolarized(129)Xe may provide a useful nonionizing approach for probing changes in lung function and structure associated with RILI before, during, or after RT (early and late time-points).
  
  
  METHODS
  In this study, dynamic(129)Xe MR spectroscopy was used to measure whole-lung gas transfer time constants for lung tissue and red blood cells (RBC), respectively (TTr_tissue and TTr_RBC) in groups of rats at two weeks and six weeks following 14 Gy whole-lung exposure to radiation from a (60)Co source. A separate group of six healthy age-matched rats served as a control group.
  
  
  RESULTS
  TTr_tissue values at two weeks post-irradiation (51.6 ± 6.8 ms) were found to be significantly elevated (p < 0.05) with respect to the healthy control group (37.2 ± 4.8 ms). TTr_RBC did not show any significant changes between groups. TTr_tissue was strongly correlated with TTr_RBC in the control group (r = 0.9601 p < 0.05) and uncorrelated in the irradiated groups. Measurements of arterial partial pressure of oxygen obtained by arterial blood sampling were found to be significantly decreased (p < 0.05) in the two-week group (54.2 ± 12.3 mm Hg) compared to those from a representative control group (85.0 ± 10.0 mm Hg). Histology of a separate group of similarly irradiated animals confirmed the presence of inflammation due to radiation exposure with alveolar wall thicknesses that were significantly different (p < 0.05). At six weeks post-irradiation, TTr_tissue returned to values (35.6 ± 9.6 ms) that were not significantly different from baseline.
  
  
  CONCLUSIONS
  Whole-lung tissue transfer time constants for(129)Xe (TTr_tissue) can be used to detect the early phase of RILI in a rat model involving 14 Gy thoracic (60)Co exposure as early as two weeks post-irradiation. This knowledge combined with more sophisticated models of gas exchange and imaging techniques, may allow functional lung avoidance radiation therapy planning to be achievable, providing more beneficial treatment plans and improved quality of life for recovering lung cancer patients.
authors.affiliation: Department of Physics and Astronomy, Western University, London, Ontario, N6A 3K7, Canada and Imaging Research Laboratories, Robarts Research Institute, Western University, London, Ontario, N6A 5B7, Canada.
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Fox
authors.affiliation: Imaging Research Laboratories, Robarts Research Institute, Western University, London, Ontario, N6A 5B7, Canada.
authors.forename: Alexei
authors.initials: A
authors.lastname: Ouriadov
authors.affiliation: Department of Medical Biophysics, Western University, London, Ontario, N6A 5C1, Canada and Imaging Research Laboratories, Robarts Research Institute, Western University, London, Ontario, N6A 5B7, Canada.
authors.forename: Kundan
authors.initials: K
authors.lastname: Thind
authors.affiliation: Imaging Research Laboratories, Robarts Research Institute, Western University, London, Ontario, N6A 5B7, Canada.
authors.forename: Elaine
authors.initials: E
authors.lastname: Hegarty
authors.affiliation: Department of Physics and Astronomy, Western University, London, Ontario, N6A 3K7, Canada and London Regional Cancer Program, London, Ontario, N6C 2R6, Canada.
authors.forename: Eugene
authors.initials: E
authors.lastname: Wong
authors.affiliation: Department of Radiation Oncology, University of Toronto, Toronto, Ontario, M5S 3E2, Canada and Radiation Medicine Program, Princess Margaret Hospital, Toronto, Ontario, M5T 2M9, Canada.
authors.forename: Andrew
authors.initials: A
authors.lastname: Hope
authors.affiliation: Department of Medical Biophysics, Western University, London, Ontario, N6A 5C1, Canada; Imaging Research Laboratories, Robarts Research Institute, Western University, London, Ontario, N6A 5B7, Canada; and Department of Medical Imaging, Western University, London, Ontario, N6A 5B7, Canada.
authors.forename: Giles E
authors.initials: GE
authors.lastname: Santyr
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D001784:Blood Gas Analysis; D003037:Cobalt Radioisotopes / Q000009:adverse effects; D004912:Erythrocytes / Q000378:metabolism; D008168:Lung / Q000378:metabolism* / Q000473:pathology / Q000528:radiation effects; D055370:Lung Injury / Q000378:metabolism* / Q000473:pathology; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D010100:Oxygen / Q000378:metabolism; D010313:Partial Pressure; D011650:Pulmonary Alveoli / Q000378:metabolism / Q000473:pathology; D011832:Radiation Injuries / Q000378:metabolism* / Q000473:pathology; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014979:Xenon Isotopes
chemical_list: D003037:Cobalt Radioisotopes; D014979:Xenon Isotopes; D010100:Oxygen