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 imaging (PAI) is being actively investigated as a non-invasive and non-radioactive imaging technique for sentinel lymph node (SLN) biopsy. By taking advantage of optical and ultrasound imaging, PAI probes SLNs non-invasively with methylene blue (MB) in both live animals and breast cancer patients. However, these PAI systems have limitations for widespread use in clinics and commercial marketplaces because the lasers used by the PAI systems, e.g., tunable liquid dye laser systems and optical parametric oscillator (OPO) lasers, are bulky in size, not economical, and use risky flammable and toxic liquid dyes. To overcome these limitations, we are proposing a novel dual-modal photoacoustic and ultrasound imaging system based on a solid-state dye laser (SD-PAUSI), which is compact, convenient, and carries far less risk of flammability and toxicity. Using a solid-state dye handpiece that generates 650-nm wavelength, we successfully imaged the MB tube positioned deeply (~3.9 cm) in chicken breast tissue. The SLNs were also photoacoustically detected in the in vivo rats beneath a 2.2-cm-thick layer of chicken breast, which is deeper than the typical depth of SLNs in humans (1.2 ± 0.5 cm). Furthermore, we showed the multispectral capability of the PAI by switching the dye handpiece, in which the MB-dyed SLN was selectively highlighted from the surrounding vasculature. These results demonstrated the great potential of the SD-PAUSI as an easy but effective modality for SLN detection.

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.

Assessing the risk of carotid plaque rupture remains limited because current imaging methods cannot provide both plaque composition and structural information in real time. Here, we present human carotid plaque risk imaging (hCAPRI), a multiparametric photoacoustic and ultrasound (PA/US) fusion method for real-time carotid plaque assessment. hCAPRI combines PA imaging for detecting intraplaque hemorrhage (IPH) with US imaging for evaluating the plaque structure. PA imaging measured IPH size and methemoglobin content, while US imaging assessed stenosis severity, calcification, and plaque thickness. Combining these PA/US parameters, we compute an hCAPRI score. In 171 carotid arteries (CAs) from 120 patients, hCAPRI revealed the relationships among the PA/US parameters. In 36 CAs validated with magnetic resonance imaging (MRI), hCAPRI showed high agreement with MRI. The hCAPRI score achieved 89% sensitivity and 84% specificity for high-risk plaque classification. hCAPRI offers a low-cost, real-time, and contrast-free approach for carotid plaque risk imaging.