Yao, Junjie

Abstract Photoacoustic tomography (PAT), a hybrid imaging modality that acoustically detects the optical absorption contrast, is a promising technology for imaging hemodynamic functions in deep tissues. Particularly, PAT is capable of measuring the blood oxygenation level using hemoglobin as the endogenous contrast. However, the most clinically compatible PAT configuration usually employs a linear ultrasound transducer array and often suffers from the poor image fidelity, mostly due to the limited detection view of the transducer array. PAT can be improved by employing highly-absorbing contrast agents such as droplets and nanoparticles, which, however, have low clinical translation potential due to safety concerns and regulatory hurdles. Moreover, unlike hemoglobin, these exogenous contrast agents cannot report the functional hemodynamic information. In this work, we have developed a new methodology that can improve PAT’s image fidelity without hampering its functional capability or clinical translation potential. By using clinically-approved microbubbles as virtual point sources that strongly scatter the local pressure waves generated by surrounding hemoglobin, we can overcome the limited-detection-view problem and achieve high-fidelity functional PAT in deep tissues, a technology referred to as virtual-point-source PAT (VPS-PAT). We have thoroughly investigated the working principle of VPS-PAT by numerical simulations and phantom validations, showing the acoustic origin of signal enhancement and the superiority over traditional PAT. We have also demonstrated proof-of-concept applications of functional VPT-PAT for in vivo small-animal studies with physiological challenges. We expect that VPS-PAT can find broad applications in biomedical research and accelerated translation to clinical impact.

Mechanical high-intensity focused ultrasound (HIFU) has been used for cancer treatment and drug delivery. Existing monitoring methods for mechanical HIFU therapies such as MRI and ultrasound imaging often suffer from high cost, poor spatial-temporal resolution, and/or low sensitivity to tissue’s hemodynamic changes. Evaluating vascular injury during mechanical HIFU treatment, therefore, remains challenging. Photoacoustic computed tomography (PACT) is a promising tool to meet this need. Intrinsically sensitive to optical absorption, PACT provides high-resolution imaging of blood vessels using hemoglobin as the endogenous contrast. In this study, we have developed an integrated HIFU-PACT system for detecting vascular rupture in mechanical HIFU treatment. We have demonstrated singular value decomposition for enhancing hemorrhage detection. We have validated the HIFU-PACT performance on phantoms and in vivo animal tumor models. We expect that PACT-HIFU will find practical applications in oncology research using small animal models.