Significance: Detection and characterization of circulating tumor cells (CTCs), a key determinant of metastasis, are critical for determining risk of disease progression, understanding metastatic pathways, and facilitating early clinical intervention.
Aim: We aim to demonstrate label-free imaging of suspected melanoma CTCs.
Approach: We use a linear-array-based photoacoustic tomography system (LA-PAT) to detect melanoma CTCs, quantify their contrast-to-noise ratios (CNRs), and measure their flow velocities in most of the superficial veins in humans.
Results: With LA-PAT, we successfully imaged suspected melanoma CTCs in patients in vivo, with a CNR >9. CTCs were detected in 3 of 16 patients with stage III or IV melanoma. Among the three CTC-positive patients, two had disease progression; among the 13 CTC-negative patients, 4 showed disease progression.
Conclusions: We suggest that LA-PAT can detect suspected melanoma CTCs in patients in vivo and has potential clinical applications for disease monitoring in melanoma.
Vasculatures enable nutrient transportation, waste disposal, and immune surveillance. Due to these diverse functions, abnormal changes in vascular morphology are commonly associated with the development of various diseases, including tumor growth and metastasis, inflammatory disorders, and pulmonary hypertension. Many models linking vascular morphogenesis to the development of a particular disease have been developed for prognosis, diagnosis, or disease management. To apply these models in clinical assessment, however, a tissue biopsy of the lesion is needed. This procedure is invasive and occasionally clinically infeasible. Photoacoustic endoscopy offers in vivo label-free examination of visceral vascular morphology, but its volumetric imaging process is vulnerable to breathing movement and peristalsis, because its typical B-scan rate is ~ 10 Hz, restricted by the speed of the scanning unit and the laser pulse repetition rate. Here, we present a transvaginal fast-scanning optical-resolution photoacoustic endoscope with a 250 Hz B-scan rate over a 3 mm scanning range. After demonstrating its imaging capability and safety, we not only illustrate the morphological differences in the vasculatures of the human ectocervix, uterine body, and sublingual mucosa, but also show the longitudinal and cross-sectional differences in the cervical vasculatures of pregnant women. This technology is promising for screening the visceral pathological changes associated with angiogenesis.
Premature cervical remodeling is an indicator of impending spontaneous preterm birth, however, current clinical measurements of cervical remodeling are mainly obtained by digital examinations, which are subjective and detect only late events, such as cervical effacement and dilation. The incompletely understood mechanisms of cervical remodeling lead to degradation of extracellular matrix proteins and inflammation, and these physiological changes are associated with increased tissue hydration. Near-infrared spectroscopy is routinely used in industrial applications to quantify the water content in various products, because this method does not require sample preparation and is nondestructive. Spectroscopic photoacoustic tomography is an embodiment of near-infrared spectroscopy and has been demonstrated in the quantification of various biochemical constituents. However, the dimensions of those tabletop systems in the previous demonstrations preclude in vivo use in the gastrointestinal tract and urogenital tract. Photoacoustic endoscopy (PAE) incorporates an acoustic detector, optical components, and electronic components in a millimeter-diameter-scale probe to image tissue that is inaccessible by the tabletop systems. Here, we present a near-infrared spectroscopic PAE system. We analyze the measured photoacoustic near-infrared (PANIR) spectra by linear regression. We demonstrate that this method successfully quantifies the water contents of tissue-mimicking phantoms made of gelatin hydrogel. Applying this method to the cervices of pregnant women, we observe their physiological water contents and a progressive increase throughout gestation. The application of this technique in maternal health care may advance our understanding of cervical remodeling and provide a sensitive method for predicting preterm birth.
Photoacoustic endoscopy offers in vivo examination of the visceral tissue using endogenous contrast, but its typical B-scan rate is ∼10 Hz, restricted by the speed of the scanning unit and the laser pulse repetition rate. Here, we present a transvaginal fast-scanning optical-resolution photoacoustic endoscope with a 250-Hz B-scan rate over a 3-mm scanning range. Using this modality, we not only illustrated the morphological differences of vasculatures among the human ectocervix, uterine body, and sublingual mucosa but also showed the longitudinal and cross-sectional differences of cervical vasculatures in pregnant women. This technology is promising for screening the visceral pathological changes associated with angiogenesis.
KEYWORDS: Scattering, Photoacoustic spectroscopy, Tissue optics, Tissues, Connective tissue, In vivo imaging, Cervix, Infrared photography, Infrared radiation, Monte Carlo methods
Premature cervical remodeling is a critical precursor of spontaneous preterm birth, and the remodeling process is characterized by an increase in tissue hydration. Nevertheless, current clinical measurements of cervical remodeling are subjective and detect only late events, such as cervical effacement and dilation. Here, we present a photoacoustic endoscope that can quantify tissue hydration by measuring near-infrared cervical spectra. We quantify the water contents of tissue-mimicking hydrogel phantoms as an analog of cervical connective tissue. Applying this method to pregnant women in vivo, we observed an increase in the water content of the cervix throughout pregnancy. The application of this technique in maternal healthcare may advance our understanding of cervical remodeling and provide a sensitive method for predicting preterm birth.
Conventional photoacoustic computed tomography (PACT) images the spatial distribution of optical absorption, which is approximated as an isotropic optical property. The optical absorption of many biological tissues, however, is anisotropic. This anisotropy, known as dichroism or diattenuation, encodes rich information about molecular conformation and structural alignment. Here we report a novel imaging method called dichroism-sensitive PACT (DS-PACT). Using a lock-detection strategy, our method can measure the amplitude of tissue’s dichroism and the orientation of the optic axis of uniaxial dichroic tissue, even at a depth of 3.25 transport mean free paths. We experimentally demonstrated DS-PACT by imaging plastic polarizers and ex vivo bovine tendons deep inside scattering media. Our method extends the functionality of PACT to include a new capability, imaging tissue absorption anisotropy.
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