Detection of invasive pulmonary aspergillosis in mice using lung perfusion single-photon emission computed tomography with [99mTc]MAA

Abstract

There is an urgent need for development of better diagnostic strategies to improve outcomes in patients with invasive pulmonary aspergillosis (IPA). We hypothesized that lung perfusion single-photon emission computed tomography (SPECT) may be more sensitive and specific than computed tomography (CT) of the chest for detection of IPA because it is an angioinvasive pulmonary infection with characteristics that are different from those of bacterial pneumonia. We used SPECT with injection of technetium-99m-labeled macroaggregated albumin ([99mTc]MAA) to measure pulmonary perfusion in noninfected mice, mice with IPA, and mice with bacterial pneumonia. Histopathologic analysis was performed to evaluate the correlation between the perfusion defect and mould invasion. We also attempted to quantitatively evaluate the SPECT images to identify differences in decreased perfusion levels in affected areas in the mouse lung. Histopathologic analysis in the IPA mouse model showed a clear match between areas with a perfusion defect and the presence of mold, indicating that the location of the perfusion defect on a SPECT image reflects angioinvasion of the mould in the lungs. Some of these perfusion defects could be seen before appearance of the infiltrate of CT images. Quantitative analysis confirmed that perfusion in the affected areas was significantly decreased in the IPA model but not in the bacterial pneumonia model (P < .0001). This imaging method may be preferable to the alternative methods presently used to identify the presence of mold in a patient's lungs.

Keywords: diagnosis; invasive pulmonary aspergillosis; perfusion single-photon emission computed tomography.