Dual-mode photoacoustic/ultrasound endoscopy (ePAUS) is a promising tool for preclinical and clinical interventions. To be clinically useful, ePAUS must deliver high-performance ultrasound imaging comparable to commercial systems and maintain high photoacoustic imaging performance at long working distances. This requires a transducer with an intact physical aperture and coaxial alignment of acoustic and optical beams within the probe, a challenging integration task. We present a high-performance ePAUS probe with a miniaturized, optically transparent ultrasonic transducer (TUT) called ePAUS-TUT. The 1.8-mm-diameter probe, fitting into standard endoscopic channels, aligns acoustic and optical beams efficiently, achieving commercial-level ultrasound and high-resolution photoacoustic imaging over long distances. These imaging capabilities were validated through in vivo imaging of a rat’s rectum and a pig’s esophagus. The ePAUS-TUT system substantially enhances feasibility and potential for clinical applications.

The standard-of-care for evaluating lymph node status in breast cancers and melanoma metastasis is sentinel lymph node (SLN) assessment performed with a handheld gamma probe and radioisotopes. However, this method inevitably exposes patients and physicians to radiation, and the special facilities required limit its accessibility. Here, we demonstrate a non-ionizing, cost-effective, handheld photoacoustic finder (PAF) fully integrated with a solid-state dye laser and transparent ultrasound transducer (TUT). The solid-state dye laser handpiece is coaxially aligned with the spherically focused TUT. The integrated finder readily detected photoacoustic signals from a tube filled with methylene blue (MB) beneath a 22 mm thick layer of chicken tissue. In live animals, we also photoacoustically detected both SLNs injected with MB and subcutaneously injected melanomas. We believe that our radiation-free and inexpensive PAF can play a vital role in SLN assessment.

Photoacoustic microscopy (PAM) is used to visualize blood vessels and to monitor their time-dependent changes. Photoplethysmography (PPG) measures hemodynamic time-series changes such as heart rate. However, PPG’s limited visual access to the dynamic changes of blood vessels has prohibited further understanding of hemodynamics. Here, we propose a novel, fully integrated PAM and photoplethysmography (PAM-PPG) system to understand hemodynamic features in detail. Using the PAM-PPG system, we simultaneously acquire vascular images (by PAM) and changes in the blood volume (by PPG) from human fingers. Next, we determine the heart rate from changes in the PA signals, which match well with the PPG signals. These changes can be measured if the blood flow is not blocked. From the results, we believe that PAM-PPG could be a useful clinical tool in various clinical fields such as cardiology and endocrinology.

Multimodal optical and ultrasound imaging (USI) provides complementary diagnostic insights. However, because conventional USI uses opaque ultrasound (US) transducers, integrating these two modalities results in a bulky and complicated handheld probe in which neither modality performs efficiently. Although transparent ultrasound transducers (TUTs) solve these issues by acting as optical windows, enabling the seamless combination of light and US beams, single-element TUTs are not common in clinical environments. Here, we demonstrate a clinical triple-modal US, photoacoustic, and fluorescence imaging system, seamlessly integrated via a linear TUT-array. This system, with 64 channels and a 7-MHz center frequency achieves 72.7% optical transparency in the near infrared region. The system’s handheld opto-US probe coaxially integrates the TUT-array with a miniaturized camera and an optical fiber in a small form factor. The triple-modal imaging system effectively visualizes tissue structures, vasculatures, and lymphatics in real time in live animals, healthy volunteers, and lymphedema patients. By accurately mapping superficial tissues, blood vessels, and lymphatic vessels, we use the prototype system to successfully guide lymphovenous anastomosis microsurgery. These preclinical demonstrations illustrate the potential use of our system in various clinical procedures requiring microsurgical guidance, paving the way for future advances in multimodal imaging.

The sentinel lymph node (SLNb) is generally performed using radioisotopes, blue dyes, or both to improve false negative rate. However, ionizing radiation is involved in a gamma probe with radioisotopes and the blue dye detection relies on native visual inspection by an operator. To overcome these limitations, we developed the photoacoustic finder (PAF), a highly sensitive, non-radioactive detector that uses only blue dye and a photoacoustic signal to detect SLNs. A total of 121 patients with breast cancer were enrolled, and 375 lymph nodes were excised using conventional SLNb. The PAF was used to measure the signal from the excised lymph nodes. We compared the SLN detection rates of each method (gamma probe, visual inspection, and PAF) and conducted a non-inferiority test. The PAF detected 87 % of SLNs, comparable to the gamma probe (85 %) and superior to visual inspection (73 %). Non-inferiority tests confirmed PAF's performance was not inferior to visual inspection (p < 0.001) or the gamma probe (p < 0.015). Using the dual-modal method (gamma probe + visual inspection) as the gold standard, PAF showed a sensitivity of 0.81 and specificity of 0.63. This study demonstrates that PAF, using only blue dye, offers a non-inferior alternative to the standard dual-modal SLN detection method with radioactive materials, opening new avenues for radiation-free SLNb in the future.