Photoacoustic Imaging of Muscle Tissue Oxygenation as a Noninvasive Biomarker in Mouse Models of Sickle Cell Disease.

Abstract

PURPOSE: To develop and validate photoacoustic imaging (PAI) as a method to assess hemoglobin counts and muscle tissue oxygen saturation in a mouse model of Sickle Cell Disease (SCD. PROCEDURES: In vivo PAI was performed on mice with a SCD phenotype and results were compared to those from animals carrying a homozygous knockout of Bisphosphoglycerate mutase (BPGM), meant to annul the SCD phenotype, as well as controls (129 strain), then further compared to sickling assay results of blood collected from the same mice. RESULTS: PAI of the hindlimb muscles of SCD mice demonstrated significant decrease in tissue oxygen saturation (sO2) compared to control mice (28.4% vs 35.5%). Further PAI of mice with a genetic knock out of BPGM on an SCD background revealed tissue sO2 significantly greater (32.6%) than SCD mice and close to those in controls. These results correlate well with standard measurements of RBC sickling via cell counts. Hemoglobin counts derived from PAI further confirm the reduced tissue oxygen saturation measurements in SCD mice. CONCLUSIONS: PAI synergizes the specificity of optical imaging with the depth penetration capability of ultrasound to measure tissue oxygen saturation at deeper levels of tissue. The results of this study suggest this imaging method can be used to non-invasively measure hemoglobin counts and tissue oxygen levels as in vivo biomarkers in preclinical models of SCD, and potentially in the clinic as well.