Imaging Lung Function in Mice Using SPECT/CT and Per-Voxel Analysis

Abstract

Chronic lung disease is a major worldwide health concern but better tools are required to understand the underlying pathologies. Ventilation/perfusion (V/Q) single photon emission computed tomography (SPECT) with per-voxel analysis allows for non-invasive measurement of regional lung function. A clinically adapted V/Q methodology was used in healthy mice to investigate V/Q relationships. Twelve week-old mice were imaged to describe normal lung function while 36 week-old mice were imaged to determine how age affects V/Q. Mice were ventilated with Technegas™ and injected with 99mTc-macroaggregated albumin to trace ventilation and perfusion, respectively. For both processes, SPECT and CT images were acquired, co-registered, and quantitatively analyzed. On a per-voxel basis, ventilation and perfusion were moderately correlated (R = 0.58±0.03) in 12 week old animals and a mean log(V/Q) ratio of −0.07±0.01 and standard deviation of 0.36±0.02 were found, defining the extent of V/Q matching. In contrast, 36 week old animals had significantly increased levels of V/Q mismatching throughout the periphery of the lung. Measures of V/Q were consistent across healthy animals and differences were observed with age demonstrating the capability of this technique in quantifying lung function. Per-voxel analysis and the ability to non-invasively assess lung function will aid in the investigation of chronic lung disease models and drug efficacy studies.

Detection of Lung Dysfunction Using Ventilation and Perfusion SPECT in a Mouse Model of Chronic Cigarette Smoke Exposure

“…The studies described here were approved by the Animal Research Ethics Board of McMaster University (Hamilton, Ontario, Canada) in accordance with the guidelines of the Canadian Council on Animal Care. Baseline and 24-wk control V/Q and CT data were published previously in a related article (16).…”

“…Imaging was performed as previously described (16). In brief, the mice were tracheally intubated through the oral cavity after anesthetization with ketamine and xylazine (90 and 6 mg/kg, respectively).…”

“…SPECT and CT images were reconstructed, fused, and coregistered as previously described (16). Calibration of each CT image for Hounsfield unit (HU) scaling was performed using a waterfilled tube included in each scan and air within the field of view but external to the animal.…”

“…An example of an axial slice of the lung ROI is shown in Figure 1A. In-house-developed software was used to fuse the perfusion CT and SPECT images by a process that maximized mutual information through rigid-body transformation within the lung region as defined by the lung ROI, as previously described (16). Mutual information-derived parameters obtained from fusion of the perfusion SPECT and CT images were then applied to the ventilation SPECT and CT images.…”

“…Respiration-gated images were then reconstructed and calibrated as described for the ungated image used in the V/Q analysis. Lung-associated air volume from respiration-gated CT images was extracted by a method previously described based on a segmentation of the entire thoracic cavity (16,19). Functional residual capacity and tidal volume were calculated from these data.…”