Multimodal imaging systems are in high demand for preclinical research, experimental medicine, and clinical practice. Combinations of photoacoustic technology with other modalities including fluorescence, ultrasound, MRI, OCT have been already applied in feasibility studies. Nevertheless, only the combination of photoacoustics with ultrasound in a single setup is commercially available now. A combination of photoacoustics and fluorescence is another compelling approach because those two modalities naturally complement each other. Here, we presented a bimodal contrast agent based on the indocyanine green dye (ICG) as a single signalling compound embedded in the biocompatible and biodegradable polymer shell. We demonstrate its remarkable characteristics by imaging using a commercial photoacoustic/fluorescence tomography system (TriTom, PhotoSound Technologies). It was shown that photoacoustic signal of the particles depends on the amount of dye loaded into the shell, while fluorescence signal depends on the total amount of dye per particle. For the first time to our knowledge, a commercial bimodal photoacoustic/fluorescence setup was used for characterization of ICG doped polymer particles. Additionally, we conducted cell toxicity studies for these particles as well as studied biodistribution over time in vivo and ex vivo using fluorescent imaging. The obtained results suggest a potential for the application of biocompatible and biodegradable bimodal contrast agents as well as the integrated photoacoustic/fluorescence imaging system for preclinical and clinical studies.

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. Significance To effectively study preclinical animal models, medical imaging technology must be developed with a high enough resolution and sensitivity to perform anatomical, functional, and molecular assessments. Photoacoustic (PA) tomography provides high resolution and specificity, and fluorescence (FL) molecular tomography provides high sensitivity; the combination of these imaging modes will enable a wide range of research applications to be studied in small animals. Aim We introduce and characterize a dual-modality PA and FL imaging platform using in vivo and phantom experiments. Approach The imaging platform’s detection limits were characterized through phantom studies that determined the PA spatial resolution, PA sensitivity, optical spatial resolution, and FL sensitivity. Results The system characterization yielded a PA spatial resolution of in the transverse plane and in the longitudinal axis, a PA sensitivity detection limit not less than that of a sample with absorption coefficient , an optical spatial resolution of in the vertical axis and in the horizontal axis, and a FL sensitivity detection limit not concentration of IR-800. The scanned animals displayed in three-dimensional renders showed high-resolution anatomical detail of organs. Conclusions The combined PA and FL imaging system has been characterized and has demonstrated its ability to image mice in vivo , proving its suitability for biomedical imaging research applications.

The ability to perform dynamic imaging of time-varying physiological processes in small animal models is critically needed to understand the progression of human diseases and develop new therapies. Photoacoustic computed tomography (PACT) has been recognized as a promising tool for small animal imaging because of its relatively low expense, high resolution, and good signal-to-noise ratio. By exploiting the optical absorption of hemoglobin or exogenous contrast agents, dynamic PACT holds excellent potential for measuring important time-varying biomarkers like tumor vascular perfusion. Nonetheless, current dynamic PACT technologies possess several limitations. Most three-dimensional (3D) PACT imagers employ a tomographic measurement process in which a gantry containing acoustic transducers is rotated about the animal. Such a rotating gantry is advantageous for limiting the cost of the system due to the decreased number of acoustic transducers and associated electronics and for enabling convenient delivery of the light to the object. However, this presents significant challenges for dynamic image reconstruction because only a few tomographic views are available to reconstruct each temporal frame. This work presents an efficient and accurate dynamic image reconstruction method that can be deployed with widely available 3D imagers using rotating gantries. In particular, a low-rank matrix estimationbased spatiotemporal image reconstruction (LRME-STIR) algorithm is proposed. In a stylized virtual dynamic contrast-enhanced imaging study, the proposed LRME-STIR algorithm is shown to accurately recover a wellcharacterized dynamic numerical murine phantom in which tumor vascular perfusion and breathing motion are modeled.

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