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Title: Detection of radiation induced lung injury in rats using dynamic hyperpolarized {sup 129}Xe magnetic resonance spectroscopy

Abstract

Purpose: 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{sup 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{sup 129}Xe MR spectroscopy was used to measure whole-lung gas transfer time constants for lung tissue and red blood cells (RBC), respectively (T{sub Tr-tissue} and T{sub Tr-RBC}) in groups of rats at two weeks and six weeks following 14 Gy whole-lung exposure to radiation from a {sup 60}Co source. A separate group of six healthy age-matched rats served as a control group. Results: T{sub Tr-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).more » T{sub Tr-RBC} did not show any significant changes between groups. T{sub Tr-tissue} was strongly correlated with T{sub Tr-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, T{sub Tr-tissue} returned to values (35.6 ± 9.6 ms) that were not significantly different from baseline. Conclusions: Whole-lung tissue transfer time constants for{sup 129}Xe (T{sub Tr-tissue}) can be used to detect the early phase of RILI in a rat model involving 14 Gy thoracic {sup 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.« less

Authors:
 [1]; ;  [2];  [3];  [4];  [5];  [6];  [7];  [7]
  1. 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)
  2. Imaging Research Laboratories, Robarts Research Institute, Western University, London, Ontario, N6A 5B7 (Canada)
  3. 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)
  4. Department of Physics and Astronomy, Western University, London, Ontario, N6A 3K7, Canada and London Regional Cancer Program, London, Ontario, N6C 2R6 (Canada)
  5. Department of Radiation Oncology, University of Toronto, Toronto, Ontario, M5S 3E2, Canada and Radiation Medicine Program, Princess Margaret Hospital, Toronto, Ontario, M5T 2M9 (Canada)
  6. Department of Medical Biophysics, Western University, London, Ontario, N6A 5C1 (Canada)
  7. (Canada)
Publication Date:
OSTI Identifier:
22412469
Resource Type:
Journal Article
Resource Relation:
Journal Name: Medical Physics; Journal Volume: 41; Journal Issue: 7; Other Information: (c) 2014 American Association of Physicists in Medicine; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ANIMAL TISSUES; BLOOD CELLS; COBALT 60; LUNGS; NEOPLASMS; NMR IMAGING; RADIOTHERAPY; RATS; XENON 129

Citation Formats

Fox, Matthew S., Ouriadov, Alexei, Hegarty, Elaine, Thind, Kundan, Wong, Eugene, Hope, Andrew, Santyr, Giles E., E-mail: gsantyr@robarts.ca, Imaging Research Laboratories, Robarts Research Institute, Western University, London, Ontario, N6A 5B7, and Department of Medical Imaging, Western University, London, Ontario, N6A 5B7. Detection of radiation induced lung injury in rats using dynamic hyperpolarized {sup 129}Xe magnetic resonance spectroscopy. United States: N. p., 2014. Web. doi:10.1118/1.4881523.
Fox, Matthew S., Ouriadov, Alexei, Hegarty, Elaine, Thind, Kundan, Wong, Eugene, Hope, Andrew, Santyr, Giles E., E-mail: gsantyr@robarts.ca, Imaging Research Laboratories, Robarts Research Institute, Western University, London, Ontario, N6A 5B7, & Department of Medical Imaging, Western University, London, Ontario, N6A 5B7. Detection of radiation induced lung injury in rats using dynamic hyperpolarized {sup 129}Xe magnetic resonance spectroscopy. United States. doi:10.1118/1.4881523.
Fox, Matthew S., Ouriadov, Alexei, Hegarty, Elaine, Thind, Kundan, Wong, Eugene, Hope, Andrew, Santyr, Giles E., E-mail: gsantyr@robarts.ca, Imaging Research Laboratories, Robarts Research Institute, Western University, London, Ontario, N6A 5B7, and Department of Medical Imaging, Western University, London, Ontario, N6A 5B7. Tue . "Detection of radiation induced lung injury in rats using dynamic hyperpolarized {sup 129}Xe magnetic resonance spectroscopy". United States. doi:10.1118/1.4881523.
@article{osti_22412469,
title = {Detection of radiation induced lung injury in rats using dynamic hyperpolarized {sup 129}Xe magnetic resonance spectroscopy},
author = {Fox, Matthew S. and Ouriadov, Alexei and Hegarty, Elaine and Thind, Kundan and Wong, Eugene and Hope, Andrew and Santyr, Giles E., E-mail: gsantyr@robarts.ca and Imaging Research Laboratories, Robarts Research Institute, Western University, London, Ontario, N6A 5B7 and Department of Medical Imaging, Western University, London, Ontario, N6A 5B7},
abstractNote = {Purpose: 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{sup 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{sup 129}Xe MR spectroscopy was used to measure whole-lung gas transfer time constants for lung tissue and red blood cells (RBC), respectively (T{sub Tr-tissue} and T{sub Tr-RBC}) in groups of rats at two weeks and six weeks following 14 Gy whole-lung exposure to radiation from a {sup 60}Co source. A separate group of six healthy age-matched rats served as a control group. Results: T{sub Tr-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). T{sub Tr-RBC} did not show any significant changes between groups. T{sub Tr-tissue} was strongly correlated with T{sub Tr-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, T{sub Tr-tissue} returned to values (35.6 ± 9.6 ms) that were not significantly different from baseline. Conclusions: Whole-lung tissue transfer time constants for{sup 129}Xe (T{sub Tr-tissue}) can be used to detect the early phase of RILI in a rat model involving 14 Gy thoracic {sup 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.},
doi = {10.1118/1.4881523},
journal = {Medical Physics},
number = 7,
volume = 41,
place = {United States},
year = {Tue Jul 15 00:00:00 EDT 2014},
month = {Tue Jul 15 00:00:00 EDT 2014}
}
  • Purpose: To assess the feasibility of hyperpolarized (HP) {sup 129}Xe MRI for detection of early stage radiation-induced lung injury (RILI) in a rat model involving unilateral irradiation by assessing differences in gas exchange dynamics between irradiated and unirradiated lungs. Methods: The dynamics of gas exchange between alveolar air space and pulmonary tissue (PT), PT and red blood cells (RBCs) was measured using single-shot spiral iterative decomposition of water and fat with echo asymmetry and least-squares estimation images of the right and left lungs of two age-matched cohorts of Sprague Dawley rats. The first cohort (n = 5) received 18 Gymore » irradiation to the right lung using a {sup 60}Co source and the second cohort (n = 5) was not irradiated and served as the healthy control. Both groups were imaged two weeks following irradiation when radiation pneumonitis (RP) was expected to be present. The gas exchange data were fit to a theoretical gas exchange model to extract measurements of pulmonary tissue thickness (L{sub PT}) and relative blood volume (V{sub RBC}) from each of the right and left lungs of both cohorts. Following imaging, lung specimens were retrieved and percent tissue area (PTA) was assessed histologically to confirm RP and correlate with MRI measurements. Results: Statistically significant differences in L{sub PT} and V{sub RBC} were observed between the irradiated and non-irradiated cohorts. In particular, L{sub PT} of the right and left lungs was increased approximately 8.2% and 5.0% respectively in the irradiated cohort. Additionally, V{sub RBC} of the right and left lungs was decreased approximately 36.1% and 11.7% respectively for the irradiated cohort compared to the non-irradiated cohort. PTA measurements in both right and left lungs were increased in the irradiated group compared to the non-irradiated cohort for both the left (P < 0.05) and right lungs (P < 0.01) confirming the presence of RP. PTA measurements also correlated with the MRI measurements for both the non-irradiated (r = 0.79, P < 0.01) and irradiated groups (r = 0.91, P < 0.01). Conclusions: Regional RILI can be detected two weeks post-irradiation using HP {sup 129}Xe MRI and analysis of gas exchange curves. This approach correlates well with histology and can potentially be used clinically to assess radiation pneumonitis associated with early RILI to improve radiation therapy outcomes.« less
  • Low thermal-equilibrium nuclear spin polarizations and the need for sophisticated instrumentation render conventional nuclear magnetic resonance (NMR) spectroscopy and imaging (MRI) incompatible with small-scale microfluidic devices. Hyperpolarized 129Xe gas has found use in the study of many materials but has required very large and expensive instrumentation. Recently a microfabricated device with modest instrumentation demonstrated all-optical hyperpolarization and detection of 129Xe gas. This device was limited by 129Xe polarizations less than 1%, 129Xe NMR signals smaller than 20 nT, and transport of hyperpolarized 129Xe over millimeter lengths. Higher polarizations, versatile detection schemes, and flow of 129Xe over larger distances are desirablemore » for wider applications. Here we demonstrate an ultra-sensitive microfabricated platform that achieves 129Xe polarizations reaching 7%, NMR signals exceeding 1 μT, lifetimes up to 6 s, and simultaneous two-mode detection, consisting of a high-sensitivity in situ channel with signal-to-noise of 10 5 and a lower-sensitivity ex situ detection channel which may be useful in a wider variety of conditions. 129Xe is hyperpolarized and detected in locations more than 1 cm apart. Our versatile device is an optimal platform for microfluidic magnetic resonance in particular, but equally attractive for wider nuclear spin applications benefitting from ultra-sensitive detection, long coherences, and simple instrumentation.« less
  • The major obstacle to the use of 129-xenon (I = {1/2}) as a new source of contrast in magnetic resonance is its low sensitivity. The hyperpolarized {sup 129}Xe-MRI technique using laser optical pumping of rubidium promises to resolve this problem. The potential of xenon-based MRI for the body tissues other than the lung air spaces depends on the {sup 129}Xe polarization lifetime (T1) in the blood at a magnetic field of commonly available clinical MRI systems. Xenon with natural abundance of {sup 129}Xe (26%) was dissolved in human blood and studied at 36{degrees}C in a 2.35 T 40 cm boremore » MRI spectrometer (27.6 MHz). Zeeman relaxation (T1) of six blood samples was measured by the progressive saturation method for periods of 4-8 h each. NMR spectra revealed two peaks at 216.0 ppm (A) and 194.0 ppm (B) relative to the xenon gas above the blood volume. Assignment and {sup 129}Xe T1 values were 4.5 {+-} 1 s for red blood cells (A), 0.6 {+-} 2 s for plasma (B) and 11.9 {+-} 1.6 s for xenon gas at atmospheric oxygen pressure. Xenon dissolved in distilled water appears at 189.8 ppm and has T1 = 26.3 {+-} 1.4 s. These relaxation times, though shorter than expected, are comparable to the transport time of blood, and are long enough to encourage use of hyperpolarized xenon for MRI studies in tissues, in addition to lung. 18 refs., 2 figs.« less
  • While the recent demonstrations of in vivo magnetic resonance imaging using laser-polarized {sup 3}He are impressive, there is great interest in utilizing the technique for {sup 129}Xe. The high solubility of {sup 129}Xe in tissue (10-20mM) and the large chemical shift separation between gas and solution environments (200 ppm) make spectroscopic differentiation of gas phase and tissue compartments facile. To understand the physicological and magnetic behavior of {sup 129}Xe, for imaging, the authors have obtained MR spectra from the mouse thorax in vivo using laser-polarized {sup 129}Xe. These show many peaks and much detail: (1) Alveolar gas phase {sup 129}Xemore » shows intensity and frequency fluctuations correlated with breathing-induced variations in bulk magnetic susceptibility (BMS) of the lung. (2) {sup 129}Xe dissolved in the lung parenchyma also shows BMS correlated variation as well as very rapid T{sub 2} relaxation (< 20ms), attributable to BMS broadening and respiratory motion. (3) Blood and thoracic muscle components are easily distinguished by their different frequencies and intensity buildup rates. These show T{sub 2} times of 60 and 80 ms, respectively. (4) Effective T{sub 1} relaxation times, (including {sup 129}Xe washout) are long in all tissue environments, about 25-30 s. The authors will discuss these results as well as advances toward systems capable of producing large quantities of laser-polarized {sup 129}Xe.« less
  • Purpose: Hyperpolarized xenon-129 dissolved-phase MRI is the first imaging technique that allows 3-dimensional regional mapping of ventilation and gas uptake by tissue and blood the in human lung. Multiple outcome measures can be produced from this method. Existing studies in subjects with major lung diseases compared to healthy controls demonstrated high sensitivities of this method to pulmonary physiological factors including ventilation, alveolar tissue density, surface-to-volume ratio, pulmonary perfusion and gas-blood barrier thickness. The purpose of this study is to evaluate the utility of this new imaging tool to assess the lung function in patients with non-small cell lung cancer (NSCLC).more » Methods: Ten healthy controls (age: 63±10) and five patients (age: 62±13) with NSCLC underwent the xenon-129 dissolved-phase MRI, pulmonary function test (PFT) and CT for clinical purpose. Three outcome measures were produced from xenon-129 dissolved-phase MRI, including ventilation defect fraction (Vdef%) reflecting the airflow obstruction, tissue-to-gas ratio reflecting lung tissue density, and RBC-to-tissue ratio reflecting pulmonary perfusion and gas exchange. Results: Compared to healthy controls, patients with NSCLC showed more ventilation defects (NSCLC: 22±6%; control: 40±18%; P=0.01), lower tissue-to-gas (NSCLC: 0.82±0.31%; control: 1.07±0.13%; P=0.05) and RBC-to-tissue ratios (NSCLC: 0.82±0.31%; control: 1.07±0.13%; P=0.01). Maps for ventilation and gas uptake by tissue and blood were highly heterogeneous in the lungs of patients. Vdef% and RBC-to-tissue ratios in all 15 subjects correlated with corresponding global lung functional measures from PFT: FEV1/FVC (R=−0.91, P<0.001) and DLCO % predicted (R=0.54, P=0.03), respectively. The tissue-to-gas ratios correlated with tissue density (HU) measured by CT (R=0.88, P<0.001). Conclusion: With the unique ability to provide detailed information about lung function including ventilation, tissue density, perfusion and gas exchange with 3D resolution, hyperpolarized xenon-129 dissolved-phase MRI has high potential to be used as an important reference for radiotherapy treatment planning and for evaluating the side effects of the treatment. Receive research support and funding from Siemens.« less