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Purpose To implement and optimize a single-shot spiral encoding strategy for rapid 2D IDEAL projection imaging of hyperpolarized (Hp) 129Xe in the gas phase, and in the pulmonary tissue (PT) and red blood cells (RBCs) compartments of the rat lung, respectively. Theory and Methods A theoretical and experimental point spread function analysis was used to optimize the spiral k-space read-out time in a phantom. Hp 129Xe IDEAL images from five healthy rats were used to: (i) optimize flip angles by a Bloch equation analysis using measured kinetics of gas exchange and (ii) investigate the feasibility of the approach to characterize the exchange of Hp 129Xe. Results A read-out time equal to approximately 1.8 × was found to provide the best trade-off between spatial resolution and signal-to-noise ratio (SNR). Spiral IDEAL approaches that use the entire dissolved phase magnetization should give an SNR improvement of a factor of approximately three compared with Cartesian approaches with similar spatial resolution. The IDEAL strategy allowed imaging of gas, PT, and RBC compartments with sufficient SNR and temporal resolution to permit regional gas exchange measurements in healthy rats. Conclusion Single-shot spiral IDEAL imaging of gas, PT and RBC compartments and gas exchange is feasible in rat lung using Hp 129Xe. Magn Reson Med, 2015. © 2015 Wiley Periodicals, Inc.

Purpose Radiation-induced lung injury (RILI) is still the major dose-limiting toxicity related to lung cancer radiation therapy, and it is difficult to predict and detect patients who are at early risk of severe pneumonitis and fibrosis. The goal of this proof-of-concept preclinical demonstration was to investigate the potential of hyperpolarized 129Xe diffusion-weighted MRI to detect the lung morphological changes associated with early stage RILI. Methods Hyperpolarized 129Xe MRI was performed using eight different diffusion sensitizations (0.0–115 s/cm2) in a small group of control rats (n = 4) and rats 2 wk after radiation exposure (n = 5). The diffusion-weighted images were used to obtain morphological estimates of the pulmonary parenchyma including external radius (R), internal radius (r), alveolar sleeve depth (h), and mean airspace chord length (Lm). The histological mean linear intercept (MLI) were obtained for five control and five irradiated animals. Results Mean R, r, and Lm were both significantly different (P

MRI of hyperpolarized 129Xe gas and 13C-enriched substrates (e.g. pyruvate) presents an unprecedented opportunity to map anatomical, functional and metabolic changes associated with lung injury. In particular, inhaled hyperpolarized 129Xe gas is exquisitely sensitive to changes in alveolar microanatomy and function accompanying lung inflammation through decreases in the apparent diffusion coefficient (ADC) of alveolar gas and increases in the transfer time (Ttr) of xenon exchange from the gas and into the dissolved phase in the lung. Furthermore, metabolic changes associated with hypoxia arising from lung injury may be reflected by increases in lactate-to-pyruvate signal ratio obtained by magnetic resonance spectroscopic imaging following injection of hyperpolarized [1-13C]pyruvate. In this work, the application of hyperpolarized 129Xe and 13C MRI to radiation-induced lung injury (RILI) is reviewed and results of ADC, Ttr and lactate-to-pyruvate signal ratio changes in a rat model of RILI are summarized. These results are consistent with conventional functional (i.e. blood gases) and histological (i.e. tissue density) changes, and correlate significantly with inflammatory cell counts (i.e. macrophages). Hyperpolarized MRI may provide an earlier indication of lung injury associated with radiotherapy of thoracic tumors, potentially allowing adjustment of treatment before the onset of severe complications and irreversible fibrosis. Copyright © 2014 John Wiley & Sons, Ltd.

Purpose 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 18.5Gy 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 (p a O 2 ). 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 p a O 2 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.

To implement and optimize a single-shot spiral encoding strategy for rapid 2D IDEAL projection imaging of hyperpolarized (Hp) (129) Xe in the gas phase, and in the pulmonary tissue (PT) and red blood cells (RBCs) compartments of the rat lung, respectively.A theoretical and experimental point spread function analysis was used to optimize the spiral k-space read-out time in a phantom. Hp (129) Xe IDEAL images from five healthy rats were used to: (i) optimize flip angles by a Bloch equation analysis using measured kinetics of gas exchange and (ii) investigate the feasibility of the approach to characterize the exchange of Hp (129) Xe.A read-out time equal to approximately 1.8 × T2* was found to provide the best trade-off between spatial resolution and signal-to-noise ratio (SNR). Spiral IDEAL approaches that use the entire dissolved phase magnetization should give an SNR improvement of a factor of approximately three compared with Cartesian approaches with similar spatial resolution. The IDEAL strategy allowed imaging of gas, PT, and RBC compartments with sufficient SNR and temporal resolution to permit regional gas exchange measurements in healthy rats.Single-shot spiral IDEAL imaging of gas, PT and RBC compartments and gas exchange is feasible in rat lung using Hp (129) Xe. Magn Reson Med 76:566-576, 2016. © 2015 Wiley Periodicals, Inc.

Radiation-induced lung injury (RILI) is still the major dose-limiting toxicity related to lung cancer radiation therapy, and it is difficult to predict and detect patients who are at early risk of severe pneumonitis and fibrosis. The goal of this proof-of-concept preclinical demonstration was to investigate the potential of hyperpolarized (129) Xe diffusion-weighted MRI to detect the lung morphological changes associated with early stage RILI.Hyperpolarized (129) Xe MRI was performed using eight different diffusion sensitizations (0.0-115 s/cm(2) ) in a small group of control rats (n = 4) and rats 2 wk after radiation exposure (n = 5). The diffusion-weighted images were used to obtain morphological estimates of the pulmonary parenchyma including external radius (R), internal radius (r), alveolar sleeve depth (h), and mean airspace chord length (Lm ). The histological mean linear intercept (MLI) were obtained for five control and five irradiated animals.Mean R, r, and Lm were both significantly different (P 0.02) in the irradiated rats (74 ± 17 µm, 43 ± 12 µm, and 54 ± 17 µm, respectively) compared with the control rats (100 ± 12 µm, 67 ± 10 µm, and 79 ± 12 µm, respectively). Changes in measured Lm values were consistent with changes in MLI values observed by histology.Hyperpolarized (129) Xe MRI provides a way to detect and measure regional microanatomical changes in lung parenchyma in a preclinical model of RILI. Magn Reson Med 75:2421-2431, 2016. © 2015 Wiley Periodicals, Inc.

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).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.TTr_tissue values at two weeks post-irradiation (51.6 ± 6.8 ms) were found to be significantly elevated (p0.05) 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 p0.05) and uncorrelated in the irradiated groups. Measurements of arterial partial pressure of oxygen obtained by arterial blood sampling were found to be significantly decreased (p0.05) 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 (p0.05). At six weeks post-irradiation, TTr_tissue returned to values (35.6 ± 9.6 ms) that were not significantly different from baseline.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.

MRI of hyperpolarized (129)Xe gas and (13)C-enriched substrates (e.g. pyruvate) presents an unprecedented opportunity to map anatomical, functional and metabolic changes associated with lung injury. In particular, inhaled hyperpolarized (129)Xe gas is exquisitely sensitive to changes in alveolar microanatomy and function accompanying lung inflammation through decreases in the apparent diffusion coefficient (ADC) of alveolar gas and increases in the transfer time (T(tr)) of xenon exchange from the gas and into the dissolved phase in the lung. Furthermore, metabolic changes associated with hypoxia arising from lung injury may be reflected by increases in lactate-to-pyruvate signal ratio obtained by magnetic resonance spectroscopic imaging following injection of hyperpolarized [1-(13)C]pyruvate. In this work, the application of hyperpolarized (129)Xe and (13)C MRI to radiation-induced lung injury (RILI) is reviewed and results of ADC, T(tr) and lactate-to-pyruvate signal ratio changes in a rat model of RILI are summarized. These results are consistent with conventional functional (i.e. blood gases) and histological (i.e. tissue density) changes, and correlate significantly with inflammatory cell counts (i.e. macrophages). Hyperpolarized MRI may provide an earlier indication of lung injury associated with radiotherapy of thoracic tumors, potentially allowing adjustment of treatment before the onset of severe complications and irreversible fibrosis.

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.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.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.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.

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