Page 162 - 2014 Printable Abstract Book
P. 162
establishing the existence of a dose threshold in radiation cataractogenesis, with likely increasing impact
in the radioprotection field.
(PS2-46) Utilization of radiographic and respiratory parameters for assessing the natural history of
radiation-induced lung damage in CBA/J mice. Chiwei Hung; Francis N. Murigi; Jingping Hu; Shabnam
Salimi; Radmila Pavlovic; Carolyn M.S. Buck; Wilfried Goetz; Nilesh Mistry; Isabel L. Jackson; and Zeljko
Vujaskovic, University of Maryland School of Medicine, Baltimore, MD
PURPOSE/OBJECTIVE: The objective of the study is to determine whether CT radiographic
parameters and/or changes in respiratory function can predict risk for development of radiation lung
injury in a murine model of whole thorax lung irradiation (WTLI). MATERIALS/METHODS: Eighty age and
sex matched CBA/J mice were divided into groups to receive a single fraction of 0 Gy or 14 Gy to the whole
thorax (WTLI). Mice were observed daily to monitor for morbidities during the 18 week in-life phase.
Longitudinal assessment of respiratory function (frequency, enhanced pause (Penh index), inspiration and
expiration time) was carried out by whole body plethysmography (Buxco electronics, Wilmington, NC)
every 3 weeks during the post-WTLI period. MicroCT for lung density and volume measurements were
performed at the same time points (n=10/group). Serial histopathological analysis of pulmonary
inflammation and other markers of lung damage were performed on a parallel-treated cohort of mice at
each time point (n=5/group per time point) RESULTS: Differences in CT density were observed as early as
9 week post-radiation (p<0.001) between sham-irradiated (-663±1.8HU, mean ±SEM) and irradiated mice
(-644±3.2HU), while significant differences in respiratory frequency were not observed until week 12
(p<0.001). Results also showed a linear regression between CT density and the lung density (lung weight
to lung volume ratio, P<0.001, R2=0.60). Mice with increased CT density (≥-650HU) and increased lung
density (≥0.8g/mL) showed a significant increase in pulmonary fibrosis and macrophage counts, compared
to those with lower CT density or lung density (p<0.05). CONCLUSION: CT lung density analysis, coupled
with respiratory function parameters, has the potential to serve as a non-invasive surrogate marker for
predicting early radiation pulmonary injury and mapping the natural history of WTLI. CT imaging and
functional respiratory parameters have the ability to significantly reduce the time for early proof-of-
concept medical countermeasure screens where survival is the primary endpoint driven by biomarkers of
natural history changes.
(PS2-47) Neulasta significantly improves survival and recovery of CBC in lethally irradiated Jackson
Diversity Outbred (J: DO) mice, a new murine model of the hematopoietic acute radiation syndrome (H-
1
1
1
1
ARS). P. Artur Plett, PhD ; Carol H. Sampson, M.S. ; Hui Lin Chua, PhD ; Rajendran Sellamuthu, PhD ; Alexa
2
1
2
1
1
Fett, BS ; Hailin Feng, M.S. ; Barry P. Katz, PhD ; Ann M. Farese, M.S. ; Thomas J. MacVittie, PhD ; and
1
Christie M. Orschell, PhD, Indiana University School of Medicine, Indianapolis, IN and University of
1
Maryland School of Medicine, Baltimore, MD
2
Inbred mice have been used for decades in medical research due to their homogeneity, allowing
reproducible studies and obviating the need for large “n”. However, establishing LD50 “population” values
in inbred strains can be problematic since genetically identical mice can be expected to respond to
treatment as a single entity, not a population. We have previously documented a relatively steep radiation
dose/lethality curve in our mouse model of H-ARS in inbred C57BL/6 mice (slope=2.56) compared to non-
160 | P a g e
in the radioprotection field.
(PS2-46) Utilization of radiographic and respiratory parameters for assessing the natural history of
radiation-induced lung damage in CBA/J mice. Chiwei Hung; Francis N. Murigi; Jingping Hu; Shabnam
Salimi; Radmila Pavlovic; Carolyn M.S. Buck; Wilfried Goetz; Nilesh Mistry; Isabel L. Jackson; and Zeljko
Vujaskovic, University of Maryland School of Medicine, Baltimore, MD
PURPOSE/OBJECTIVE: The objective of the study is to determine whether CT radiographic
parameters and/or changes in respiratory function can predict risk for development of radiation lung
injury in a murine model of whole thorax lung irradiation (WTLI). MATERIALS/METHODS: Eighty age and
sex matched CBA/J mice were divided into groups to receive a single fraction of 0 Gy or 14 Gy to the whole
thorax (WTLI). Mice were observed daily to monitor for morbidities during the 18 week in-life phase.
Longitudinal assessment of respiratory function (frequency, enhanced pause (Penh index), inspiration and
expiration time) was carried out by whole body plethysmography (Buxco electronics, Wilmington, NC)
every 3 weeks during the post-WTLI period. MicroCT for lung density and volume measurements were
performed at the same time points (n=10/group). Serial histopathological analysis of pulmonary
inflammation and other markers of lung damage were performed on a parallel-treated cohort of mice at
each time point (n=5/group per time point) RESULTS: Differences in CT density were observed as early as
9 week post-radiation (p<0.001) between sham-irradiated (-663±1.8HU, mean ±SEM) and irradiated mice
(-644±3.2HU), while significant differences in respiratory frequency were not observed until week 12
(p<0.001). Results also showed a linear regression between CT density and the lung density (lung weight
to lung volume ratio, P<0.001, R2=0.60). Mice with increased CT density (≥-650HU) and increased lung
density (≥0.8g/mL) showed a significant increase in pulmonary fibrosis and macrophage counts, compared
to those with lower CT density or lung density (p<0.05). CONCLUSION: CT lung density analysis, coupled
with respiratory function parameters, has the potential to serve as a non-invasive surrogate marker for
predicting early radiation pulmonary injury and mapping the natural history of WTLI. CT imaging and
functional respiratory parameters have the ability to significantly reduce the time for early proof-of-
concept medical countermeasure screens where survival is the primary endpoint driven by biomarkers of
natural history changes.
(PS2-47) Neulasta significantly improves survival and recovery of CBC in lethally irradiated Jackson
Diversity Outbred (J: DO) mice, a new murine model of the hematopoietic acute radiation syndrome (H-
1
1
1
1
ARS). P. Artur Plett, PhD ; Carol H. Sampson, M.S. ; Hui Lin Chua, PhD ; Rajendran Sellamuthu, PhD ; Alexa
2
1
2
1
1
Fett, BS ; Hailin Feng, M.S. ; Barry P. Katz, PhD ; Ann M. Farese, M.S. ; Thomas J. MacVittie, PhD ; and
1
Christie M. Orschell, PhD, Indiana University School of Medicine, Indianapolis, IN and University of
1
Maryland School of Medicine, Baltimore, MD
2
Inbred mice have been used for decades in medical research due to their homogeneity, allowing
reproducible studies and obviating the need for large “n”. However, establishing LD50 “population” values
in inbred strains can be problematic since genetically identical mice can be expected to respond to
treatment as a single entity, not a population. We have previously documented a relatively steep radiation
dose/lethality curve in our mouse model of H-ARS in inbred C57BL/6 mice (slope=2.56) compared to non-
160 | P a g e
