Photoacoustic is an emerging biomedical imaging modality, which allows imaging optical absorbers in the tissue by acoustic detectors (light in - sound out). Such a technique has an immense potential for clinical translation since it allows high resolution, sufficient imaging depth, with diverse endogenous and exogenous contrast, and is free from ionizing radiation. In recent years, tremendous developments in both the instrumentation and imaging agents have been achieved. These opened avenues for clinical imaging of various sites allowed applications such as brain functional imaging, breast cancer screening, diagnosis of psoriasis and skin lesions, biopsy and surgery guidance, the guidance of tumor therapies at the reproductive and urological systems, as well as imaging tumor metastases at the sentinel lymph nodes. Here we survey the various clinical and pre-clinical literature and discuss the potential applications and hurdles that still need to be overcome.

Thyroid cancer is one of the most common cancers, with a global increase in incidence rate for both genders. Ultrasound-guided fine-needle aspiration is the current gold standard to diagnose thyroid cancers, but the results are inaccurate, leading to repeated biopsies and unnecessary surgeries. To reduce the number of unnecessary biopsies, we explored the use of multiparametric photoacoustic (PA) analysis in combination with the American Thyroid Association (ATA) Guideline (ATAP). In this study, we performed in vivo multispectral PA imaging on thyroid nodules from 52 patients, comprising 23 papillary thyroid cancer (PTC) and 29 benign cases. From the multispectral PA data, we calculated hemoglobin oxygen saturation level in the nodule area, then classified the PTC and benign nodules with multiparametric analysis. Statistical analyses showed that this multiparametric analysis of multispectral PA responses could classify PTC nodules. Combining the photoacoustically indicated probability of PTC and the ATAP led to a new scoring method that achieved a sensitivity of 83% and a specificity of 93%. This study is the first multiparametric analysis of multispectral PA data of thyroid nodules with statistical significance. As a proof of concept, the results show that the proposed new ATAP scoring can help physicians examine thyroid nodules for fine-needle aspiration biopsy, thus reducing unnecessary biopsies. Significance: This report highlights a novel photoacoustic scoring method for risk stratification of thyroid nodules, where malignancy of the nodules can be diagnosed with 83% sensitivity and 93% specificity.

Currently, there are no non-invasive tools to accurately diagnose wound and surgical site infections before they become systemic or cause significant anatomical damage. Fluorescence and photoacoustic imaging are cost-effective imaging modalities that can be used to noninvasively diagnose bacterial infections when paired with a molecularly targeted infection imaging agent. Here, we develop a fluorescent derivative of maltotriose (Cy7-1-maltotriose), which is shown to be taken up in a variety of gram-positive and gram-negative bacterial strains in vitro. In vivo fluorescence and photoacoustic imaging studies highlight the ability of this probe to detect infection, assess infection burden, and visualize the effectiveness of antibiotic treatment in E. coli-induced myositis and a clinically relevant S. aureus wound infection murine model. In addition, we show that maltotriose is an ideal scaffold for infection imaging agents encompassing better pharmacokinetic properties and in vivo stability than other maltodextrins (e.g. maltohexose).

Transrectal ultrasound and photoacoustic imaging simultaneously provide structural and molecular contrasts of normal and cancerous human prostates.

Photoacoustic (PA) imaging can revolutionize medical ultrasound by augmenting it with molecular information. However, clinical translation of PA imaging remains a challenge due to the limited viewing angles and imaging depth. Described here is a new robust algorithm called Superiorized Photo-Acoustic Non-NEgative Reconstruction (SPANNER), designed to reconstruct PA images in real-time and to address the artifacts associated with limited viewing angles and imaging depth. The method utilizes precise forward modeling of the PA propagation and reception of signals while accounting for the effects of acoustic absorption, element size, shape, and sensitivity, as well as the transducer’s impulse response and directivity pattern. A fast superiorized conjugate gradient algorithm is used for inversion. SPANNER is compared to three reconstruction algorithms: delay-and-sum (DAS), universal back-projection (UBP), and model-based reconstruction (MBR). All four algorithms are applied to both simulations and experimental data acquired from tissue-mimicking phantoms, ex vivo tissue samples, and in vivo imaging of the prostates in patients. Simulations and phantom experiments highlight the ability of SPANNER to improve contrast to background ratio by up to 20 dB compared to all other algorithms, as well as a 3-fold increase in axial resolution compared to DAS and UBP. Applying SPANNER on contrast-enhanced PA images acquired from prostate cancer patients yielded a statistically significant difference before and after contrast agent administration, while the other three image reconstruction methods did not, thus highlighting SPANNER’s performance in differentiating intrinsic from extrinsic PA signals and its ability to quantify PA signals from the contrast agent more accurately.

Osteoporosis affects one-third of the elderly population worldwide with associated health care costs amounting to tens of billions of dollars annually. Identifying and treating the population at risk of fracture, but had not yet suffered from a fracture, can substantially reduce fracture incidence. Unfortunately, molecular changes in the bone, which are of great importance for early diagnosis, are not detected by current low-cost diagnostic methods. To address this issue, presented here is a clinically translatable, dual-modality multispectral photoacoustic system. Ex vivo experiments demonstrated sensitivity to the molecular changes. Specifically, the system enabled a quantitative measurement of the marrow's blood/fat ratio. First-in-human demonstration on healthy human volunteers showed the repeatability and accuracy of the photoacoustic method and its potential for early diagnosis of bone pathologies.