Simultaneous functional photoacoustic and ultrasonic endoscopy of internal organs in vivo.
ABSTRACT: At present, clinicians routinely apply ultrasound endoscopy in a variety of interventional procedures that provide treatment solutions for diseased organs. Ultrasound endoscopy not only produces high-resolution images, but also is safe for clinical use and broadly applicable. However, for soft tissue imaging, its mechanical wave-based image contrast fundamentally limits its ability to provide physiologically specific functional information. By contrast, photoacoustic endoscopy possesses a unique combination of functional optical contrast and high spatial resolution at clinically relevant depths, ideal for imaging soft tissues. With these attributes, photoacoustic endoscopy can overcome the current limitations of ultrasound endoscopy. Moreover, the benefits of photoacoustic imaging do not come at the expense of existing ultrasound functions; photoacoustic endoscopy systems are inherently compatible with ultrasound imaging, thereby enabling multimodality imaging with complementary contrast. Here we present simultaneous photoacoustic and ultrasonic dual-mode endoscopy and show its ability to image internal organs in vivo, thus illustrating its potential clinical application.
Project description:Recently, perfluorocarbon (PFC) nanodroplets were introduced as contrast agents for imaging and image-guided therapy. For example, in sonography, high-intensity ultrasound pulses were used to phase-transition liquid perfluorocarbon to produce gas microbubbles. More recently, perfluorocarbon nanodroplets with encapsulated gold nanorods were used as dual ultrasound/photoacoustic contrast agents. To expedite clinical translation, we synthesized and characterized ICG-loaded perfluorocarbon nanodroplets, i.e., constructs comprising biocompatible, nontoxic and biologically safe materials. We then demonstrated enhanced photoacoustic contrast through optically triggered phase transition of PFC nanodroplets and ultrasound contrast from the resulting PFC bubbles. We assessed the quality enhancement of photoacoustic and ultrasound images through analysis of contrast and contrast-to-noise ratio. We further investigated the changes in image contrast due to increased ambient temperature. Our studies suggest that ICG-loaded perfluorocarbon nanodroplets may become a valuable tool for various imaging modalities, and have promising therapeutic applications.
Project description:Optical-resolution photoacoustic microscopy (OR-PAM) has become a major experimental tool of photoacoustic tomography, with unique imaging capabilities for various biological applications. However, conventional imaging systems are all table-top embodiments, which preclude their use in internal organs. In this study, by applying the OR-PAM concept to our recently developed endoscopic technique, called photoacoustic endoscopy (PAE), we created an optical-resolution photoacoustic endomicroscopy (OR-PAEM) system, which enables internal organ imaging with a much finer resolution than conventional acoustic-resolution PAE systems. OR-PAEM has potential preclinical and clinical applications using either endogenous or exogenous contrast agents.
Project description:Video capsule endoscopy (VCE) is now a clinically accepted diagnostic modality in which miniaturized technology, an on-board power supply and wireless telemetry stand as technological foundations for other capsule endoscopy (CE) devices. However, VCE does not provide therapeutic functionality, and research towards therapeutic CE (TCE) has been limited. In this paper, a route towards viable TCE is proposed, based on multiple CE devices including important acoustic sensing and drug delivery components. In this approach, an initial multimodal diagnostic device with high-frequency quantitative microultrasound that complements video imaging allows surface and subsurface visualization and computer-assisted diagnosis. Using focused ultrasound (US) to mark sites of pathology with exogenous fluorescent agents permits follow-up with another device to provide therapy. This is based on an US-mediated targeted drug delivery system with fluorescence imaging guidance. An additional device may then be utilized for treatment verification and monitoring, exploiting the minimally invasive nature of CE. While such a theranostic patient pathway for gastrointestinal treatment is presently incomplete, the description in this paper of previous research and work under way to realize further components for the proposed pathway suggests it is feasible and provides a framework around which to structure further work.
Project description:Small size polymer microring resonators have been exploited for photoacoustic (PA) imaging. To demonstrate the advantages of the wide acceptance angle of ultrasound detection of small size microrings, photoacoustic tomography (PAT), and delay-and-sum beamforming PA imaging was conducted. In PAT, we compared the imaging quality using different sizes of detectors with similar noise-equivalent pressures and the same wideband response: 500 μm hydrophone and 100, 60, and 40 μm microrings. The results show significantly improved imaging contrast and high resolution over the whole imaging region using smaller size detectors. The uniform high resolution in PAT imaging using 40 μm microrings indicates the potential to resolve microvasculature over a large imaging region. The improved lateral resolution of two-dimensional and three-dimensional delay-and-sum beamforming PA imaging using a synthetic array demonstrate another advantageous application of small microrings. The small microrings can also be applied to other ultrasound-related imaging applications.
Project description:A miniature forward-viewing endoscopic probe that provides high-resolution 3D photoacoustic images is demonstrated. The probe is of outer diameter 3.2?mm and comprised of a transparent Fabry-Pérot (FP) polymer-film ultrasound sensor that is located at the distal end of a rigid optical fiber bundle. Excitation laser pulses are coupled simultaneously into all cores of the bundle and are transmitted through the FP sensor to provide wide-field tissue illumination at the distal end. The resulting photoacoustic waves are mapped in 2D by sequentially scanning the input end of the bundle with an interrogation laser beam in order to individually address different points on the FP sensor. In this way, the sensor acts as a high-density ultrasound array that is comprised of 50,000 individual elements, each of which is 12?µm in diameter, within the 3.2?mm diameter footprint of the probe. The fine spatial sampling that this affords, along with the wide bandwidth (f -3dB?=?34?MHz) of the sensor, enables a high-resolution photoacoustic image to be reconstructed. The measured on-axis lateral resolution of the probe was depth-dependent and ranged from 45-170?µm for depths between 1 and 7?mm, and the vertical resolution was 31?µm over the same depth range. The system was evaluated by acquiring 3D images of absorbing phantoms and the microvascular anatomies of a duck embryo and mouse skin. Excellent image fidelity was demonstrated. It is anticipated that this type of probe could find application as a tool for guiding laparoscopic procedures, fetal surgery and other minimally invasive interventions that require a millimeter-scale forward-viewing 3D photoacoustic imaging probe.
Project description:Photoacoustic microscopy (PAM) does not rely on contrast agent to image the optical absorption contrast in biological tissue. It is uniquely suited for measuring several tissue physiological parameters, such as hemoglobin oxygen saturation, that would otherwise remain challenging. Researchers are designing new clinical diagnostic tools and multimodal microscopic systems around PAM to fully unleash its potential. However, the sizeable and opaque piezoelectric ultrasonic detectors commonly used in PAM impose a serious constraint. Our solution is a coverslip-style optically transparent ultrasound detector based on a polymeric optical micro-ring resonator (MRR) with a total thickness of 250??m. It enables highly-sensitive ultrasound detection over a wide receiving angle with a bandwidth of 140?MHz, which corresponds to a photoacoustic saturation limit of 287?cm(-1), at an estimated noise-equivalent pressure (NEP) of 6.8?Pa. We also established a theoretical framework for designing and optimizing the MRR for PAM.
Project description:Abdominal surgeries carry considerable risk of gastrointestinal and intra-abdominal hemorrhage, which could possibly cause patient death. Photoacoustic imaging is one solution to overcome this challenge by providing visualization of major blood vessels during surgery. We investigate the feasibility of in vivo blood vessel visualization for photoacoustic-guided liver and pancreas surgeries. In vivo photoacoustic imaging of major blood vessels in these two abdominal organs was successfully achieved after a laparotomy was performed on two swine. Three-dimensional photoacoustic imaging with a robot-controlled ultrasound (US) probe and color Doppler imaging were used to confirm vessel locations. Blood vessels in the in vivo liver were visualized with energies of 20 to 40 mJ, resulting in 10 to 15 dB vessel contrast. Similarly, an energy of 36 mJ was sufficient to visualize vessels in the pancreas with up to 17.3 dB contrast. We observed that photoacoustic signals were more focused when the light source encountered a major vessel in the liver. This observation can be used to distinguish major blood vessels in the image plane from the more diffuse signals associated with smaller blood vessels in the surrounding tissue. A postsurgery histopathological analysis was performed on resected pancreatic and liver tissues to explore possible laser-related damage. Results are generally promising for photoacoustic-guided abdominal surgery when the US probe is fixed and the light source is used to interrogate the surgical workspace. These findings are additionally applicable to other procedures that may benefit from photoacoustic-guided interventional imaging of the liver and pancreas (e.g., biopsy and guidance of radiofrequency ablation lesions in the liver).
Project description:The gold-standard periodontal probe is an aging tool that can detect periodontitis and monitor gingival health but is highly error-prone, does not fully characterize the periodontal pocket, and causes pain. Photoacoustic imaging is a noninvasive technique that can address these limitations. Here, a range of ultrasound frequencies between 16-40?MHz were used to image the periodontium and a contrast medium based on cuttlefish ink was used to label the pockets. A 40?MHz ultrasound frequency could spatially resolve the periodontal anatomy, including tooth, gum, gingival margin, and gingival thickness of tooth numbers 7-10 and 22-27. The photoacoustic-ultrasound measurements were more precise (0.01?mm) than those taken with physical probes by a dental hygienist. Furthermore, the full geometry of the pockets could be visualized with relative standard deviations of 10% (n?=?5). This study shows the potential for non-invasive monitoring of periodontal health with photoacoustic-ultrasound imaging in the dental clinic.
Project description:A biopsy of the first lymph node to which a tumor drains-the sentinel lymph node (SLN)-is commonly performed to identify micrometastases. Image guidance of the SLN biopsy procedure has the potential to improve its accuracy and decrease its morbidity. We have developed a new stable contrast agent for photoacoustic image-guided SLN biopsy: silica-coated gold nanoplates (Si-AuNPs). The Si-AuNPs exhibit high photothermal stability when exposed to pulsed and continuous wave laser irradiation. This makes them well suited for in vivo photoacoustic imaging. Furthermore, Si-AuNPs are shown to have low cytotoxicity. We tested the Si-AuNPs for SLN mapping in a mouse model where they exhibited a strong, sustained photoacoustic signal. Real-time ultrasound and photoacoustic imaging revealed that the Si-AuNPs quickly drain to the SLN, gradually spreading throughout a large portion of the node.
Project description: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.