This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The magnitude of radiation-induced function loss in the rat lung is known to be dependent on which region is irradiated. However, the underlying cause of these regional differences is poorly understood. One hypothesis is that the effect may result from a non-uniform distribution of function over the lung, prior to irradiation. To determine the extent to which regional variations in local function can explain regional variations in radiation-induced function loss, we want to measure the distribution of function over the lung by measuring the spatial distribution of the following parameters: 1) Ventilation: This will be measured by imaging hyperpolarized Xenon gas in gas phase. 2) Surface-to-volume ratio: The MR frequency of Xenon dissolved in tissue differs from Xenon in gas phase. By measuring the 197ppm signal of dissolved hyperpolarized Xenon for short period after applying a depolarizing rf-pulse, we want to obtain signals proportional to the available gas-exchange surface. 3) Gas uptake in red blood cells: When Xenon is taken up in red blood cells, its MR frequency undergoes a second shift to 211ppm. Thus gas uptake by red blood cells can be measured specifically by imaging on this frequency. This measurement provides a regional distribution of capillary blood volume coupled with blood-gas barrier health. 4) Whole-lung dynamic spectroscopy showing recovery of the 197 and 211 ppm resonances. 5) Proton MRI for chest volume estimation: To allow the calculation of volume averages, proton images revealing the anatomy are needed. From these images for all regions used in the irradiation experiments, pre-treatment values will be obtained and correlated the available post-treatment function loss data. 6) Optional - MR perfusion of a thick slab of lung using Gd injection We intend to scan 3-6 rats according to the outlined protocol. Exact numbers will depend on the variability in the results. Parts 1-5 of the protocol are identical to those carried out in the Driehuys PNAS submission. Item 6 would be included as an optional component to the study if there is benefit to CIVM students and faculty.
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