Metastasis causes as many as 90% of cancer-related deaths, especially for the deadliest skin cancer, melanoma. Since hematogenous dissemination of circulating tumor cells is the major route of metastasis, detection and destruction of circulating tumor cells are vital for impeding metastasis and improving patient prognosis. Exploiting the exquisite intrinsic optical absorption contrast of circulating melanoma cells, we developed dual-wavelength photoacoustic flow cytography coupled with a nanosecond-pulsed melanoma-specific laser therapy mechanism. We have successfully achieved in vivo label-free imaging of rare single circulating melanoma cells in both arteries and veins of mice. Further, the photoacoustic signal from a circulating melanoma cell immediately hardware-triggers a lethal pinpoint laser irradiation to kill it on the spot in a thermally confined manner without causing collateral damage. A pseudo-therapy study including both in vivo and in vitro experiments demonstrated the performance and the potential clinical value of our method, which can facilitate early treatment of metastasis by clearing circulating tumor cells from vasculature.

We report the development of an optically transparent high-frequency ultrasonic transducer using lithium niobate single-crystal and indium-tin-oxide electrodes with up to 90% optical transmission in the visible-to-near-infrared spectrum. The center frequency of the transducer was at 36.9 MHz with 33.9%, at -6 dB fractional bandwidth. The photoacoustic imaging capability of the fabricated transducer was also demonstrated by successfully imaging a resolution target and mouse-ear vasculatures in vivo, which were irradiated by a 532 nm pulse laser transmitted through the transducer.

Pharmacokinetics is the study of the absorption, distribution, and excretion of materials such as drugs, radiotracers, and fluorophores in the body.¹ Compartment modeling is a classic approach for pharmacokinetic analysis, and the exchange rates of materials between different compartments are defined as pharmacokinetic rates.² Pharmacokinetic analysis is a promising method for tumor detection, drug development, and metabolic research. Therefore, it has been widely studied in the field of positron emission tomography and magnetic resonance imaging.^3,4 Fluorescence molecular tomography (FMT) is a rapidly growing imaging technique that allows noninvasive, highly sensitive, and three-dimensional (3-D) resolution of the metabolic process of fluorophores in small animals in vivo. Recently, FMT has been successfully used to obtain images of pharmacokinetic rates for tumor detection by analyzing time-sequential datasets acquired from boundaries of the imaged objects.²

Label-free noninvasive functional imaging of the brain is highly desirable.^{1 – 4} The most widely used contrast to probe neural activities is the hyperemic response resulted from neurovascular coupling.^{4 – 6} However, this process will undergo considerable spatiotemporal broadening from the neuronal activation sites,^7,8 making it difficult to interpret and less accurate. The initial dip in hemoglobin oxygenation, due to increased oxygen consumption from activated neurons,^{6,9 – 11} is considered to be a spatially and temporally more confined localizer for the neural activity than the hyperemic response^1,8,10,12,13 and has attracted profound interest^{1,6,8 – 18} since its discovery by optical spectroscopy.¹⁹ Two label-free imaging techniques, functional magnetic resonance imaging^{6,10,15 – 17} (fMRI) and wide-field (reflection-mode) optical microscopy,^{1,11 – 14} have both made valuable contributions to the understanding of the initial dip. fMRI, currently the mainstay of neuroimaging, noninvasively obtains cortical-wide mapping of brain function through the detection of paramagnetic deoxy-hemoglobin.^4,10 Even in the small-bore form for small-animal imaging, fMRI lacks the spatial resolution to discern the dynamics of cerebral microvessels with diameters $<50\mu \mathrm{m}$,²⁰ where the initial dip is thought to originate.^8,10 Wide-field optical microscopy, in theory, has sufficient spatial resolution, but it suffers from heavy round-trip optical scattering and low sensitivity to small absorption change when resolving deep vessels;²¹ it also lacks depth resolution.² As a result, the initial dip phenomenon is still not fully explored.^6,12,15 Further, we question whether a single-impulse stimulus, much shorter than the response delay, could produce an observable initial dip without repeated stimulation since this is necessary for applications such as the brain–computer interface.