Photoacoustic clinical applications: Musculoskeletal and abdominal imaging.

Photoacoustic (PA) imaging has been extensively investigated in application in biomedicine over the last decade. This article reviews the motivation, significance, and system configuration of a few ongoing studies of implementing photoacoustic technology in musculoskeletal imaging, abdominal imaging, and interstitial sensing. The review then summarizes the methodologies and latest progress of relevant projects. Finally, we discuss our expectations for the future of translation research in PA imaging.

Fabrication of a translational photoacoustic needle sensing probe for interstitial photoacoustic spectral analysis.

In our previous study, we demonstrated the feasibility of using an all-optical interstitial photoacoustic (PA) needle sensing probe for quantitative study of tissue architectures with PA spectral analysis (PASA). In this work, we integrated the optical components into an 18 G steel needle sheath for clinical translation. The dimensions of the needle probe are identical to those of a core biopsy probe and are fully compatible with standard procedures such as prostate biopsy. To our knowledge, this is the first interstitial PA probe that can acquire signals with sufficient temporal length for statistics-based PASA. We treated the inner surface of the steel needle sheath and successfully suppressed the vibrational PA signals generated at the surface. Purposed at boosting the measurement sensitivity and extending sensing volume, we upgraded the Fabry-Pérot hydrophone with a plano-concave structure. The performance of the translational needle PA sensing probe was examined with phantoms containing microspheres. The trend of the linear spectral slopes shows negatively correlated to the microsphere dimensions while the midband-fits are positively correlated to microsphere diameters and concentrations. The PASA quantifications show the ability to differentiate microspheres with varied dimensions.

3D imaging of aqueous veins and surrounding sclera using a dual-wavelength photoacoustic microscopy.

Understanding aqueous outflow resistance at the level of aqueous veins has been a challenge to the management of glaucoma. This study investigated resolving the anatomies of aqueous veins and the textures of surrounding sclera using photoacoustic microscopy (PAM). A dual wavelength PAM system was established and validated using imaging phantoms, porcine and human globes perfused with an optical contrast agent ex vivo. The system shows lateral resolution of 8.23 µm and 4.70 µm at 1200 nm and 532 nm, respectively, and an axial resolution of 27.6 µm. The system is able to separately distinguish the aqueous veins and the sclera with high contrast in full circumference of the porcine and human globes.

Assessment of prostate cancer progression using a translational needle photoacoustic sensing probe: Preliminary study with intact human prostates ex-vivo.

In our previous studies, we demonstrated the ability of an interstitial all-optical needle photoacoustic (PA) sensing probe and PA spectral analysis (PASA) to assess the aggressiveness of prostate cancer. In this clinical translation investigation, we integrated the optical components of the needle PA sensing probe into a 18G steel needle. The translational needle PA sensing probe was evaluated using intact human prostates in a simulated ultrasound-guided transperineal prostate biopsy. PA signals were acquired at 1220 nm, 1370 nm, 800 nm and 266 nm at each interstitial measurement location and quantified by PASA within the frequency range of 8-28 MHz. The measurement locations were stained for establishing spatial correlations between the quantitative measurements and the histological diagnosing. Most of the quantitative PA assessments reveal statistically significant differences between the benign and cancerous regions. Multivariate analysis combining the PASA quantifications shows an accuracy close to 90% in differentiating the benign and cancerous regions in the prostates.

Prototype endoscopic photoacoustic-ultrasound balloon catheter for characterizing intestinal obstruction.

In our previous studies, we have demonstrated the feasibility of characterizing intestinal inflammation and fibrosis using endoscopic photoacoustic imaging. Purposed at te clinical translation of the imaging technology, we developed a photoacoustic/ultrasound imaging probe by integrating a miniaturized ultrasound array and an angle-tipped optical fiber in a hydrostatic balloon catheter. When collapsed, the catheter probe may potentially be compatible with a clinical ileo-colonoscope. In addition, the flexible surface of the hydrostatic balloon allows for acoustic coupling at the uneven surfaces of the gas-filled intestine. Tissue phantom studies show that the catheter probe possesses an imaging penetration of at least 12 mm. Experiments with a rabbit model in vivo validated the probe in differentiating normal, acute and chronic conditions in intestinal obstruction.

Method for the biomechanical analysis of aqueous veins and perilimbal sclera by three-dimensional photoacoustic imaging and strain field calculation.

A method motivated by the eye's aqueous veins is described for the imaging and strain calculation within soft biological tissues. A challenge to the investigation of the biomechanics of the aqueous vein-perilimbal sclera tissue complex is resolution of tissue deformations as a function of intraocular pressure and the subsequent calculation of strain (a normalized measure of deformation). The method involves perfusion of the eye with a contrast agent during conduction of non-invasive, optical resolution photoacoustic microscopy. This imaging technique permits three-dimensional displacement measurements of tracked points on the inner walls of the veins which are used in a finite element model to determine the corresponding strains. The methods are validated against two standard strain measurement methods. Representative porcine globe perfusion experiments are presented that demonstrate the power of the method to determine complex strain fields in the veins dependent on intraocular pressure as well as vein anatomy. In these cases, veins are observed to move radially outward during increases in intraocular pressure and to possess significant spatial strain variation, possibly influenced by their branching patterns. To the authors' knowledge, these are the only such quantitative, data driven, calculations of the aqueous vein strains available in the open literature.

Characterizing the aggressiveness of prostate cancer using an all-optical needle photoacoustic sensing probe: feasibility study.

In our previous studies, we have developed a prototype interstitial needle sensing probe that can acquire broadband A-line photoacoustic (PA) signals encoding both tissue microarchitecture and histochemical information comparable to that accessible by histology. Paving the road toward clinical translation of this technology, we replaced the piezoelectric hydrophone in the needle PA probe with a fiber optic hydrophone that enabled both broader bandwidth and sufficient signal-to-noise ratio (SNR) for PA signal detection. Such an all-optical design also facilitated disposability and significantly reduced the footprint of the needle PA sensing probe. Experiments were performed on well-controlled phantoms and human prostate tissues. The microarchitectures in each sample were quantitatively evaluated by both the nonlinear spectral slope of the PA signal power spectrum and the generalized gamma (GG) parameter a by implementing envelope statistics to the PA signal. In the studies on phantoms containing optically absorbing microspheres with various sizes and concentrations, the nonlinear spectral slope showed a strong correlation of r=-0.80 with the microsphere dimensions, and a relatively weak correlation of r=-0.54 with the microsphere concentrations, while the GG parameter a showed a strong correlation with the microsphere dimensions (r=0.72) and a moderate correlation with the microsphere concentrations (r=0.63). In the studies on human prostate tissues containing progressive cancer stages, both the nonlinear spectral slope and the GG parameter a demonstrated a statistically significant difference between benign and nonaggressive cancer tissues (p<0.01), and between nonaggressive and aggressive cancer tissues (p<0.01). In addition, a multivariate analysis combining the two quantitative measurements demonstrated the boundaries among the different progressive stages of prostate cancer.

Photoacoustic spectral analysis at ultraviolet wavelengths for characterizing the Gleason grades of prostate cancer.

The diagnosis of aggressive prostate cancer (PCa) has relied on microscopic architectures, namely Gleason patterns, of tissues extracted through core biopsies. Technology capable of assessing the tissue architecture without tissue extraction will reduce the invasiveness of PCa diagnosis and improve diagnostic accuracy by allowing for more sampling locations. Our recently developed photoacoustic spectral analysis (PASA) has achieved quantification of tissue architectural heterogeneity interstitially. Taking advantage of the unique optical absorption of cell nuclei at ultraviolet (UV) wavelengths, this study investigated PASA at 266 nm for quantifying the tissue architecture heterogeneity in prostates. The results have shown significant differences among the normal, early cancer, and late cancer stages in mouse prostates ex vivo and in vivo (n=20, p<0.05). The study with human samples ex vivo has shown a correlation of 0.80 (n=11, p<0.05) between PASA quantification and pathologic diagnosis.