A review of a strategic roadmapping exercise to advance clinical translation of photoacoustic imaging: From current barriers to future adoption.

Photoacoustic imaging (PAI), also referred to as optoacoustic imaging, has shown promise in early-stage clinical trials in a range of applications from inflammatory diseases to cancer. While the first PAI systems have recently received regulatory approvals, successful adoption of PAI technology into healthcare systems for clinical decision making must still overcome a range of barriers, from education and training to data acquisition and interpretation. The International Photoacoustic Standardisation Consortium (IPASC) undertook an community exercise in 2022 to identify and understand these barriers, then develop a roadmap of strategic plans to address them. Here, we outline the nature and scope of the barriers that were identified, along with short-, medium- and long-term community efforts required to overcome them, both within and beyond the IPASC group.

Noninvasive calibrated tissue temperature estimation using backscattered energy of acoustic harmonics.

PURPOSE: A real-time and non-invasive thermometry technique is essential in thermal therapies to monitor and control the treatment. Ultrasound is an attractive thermometry modality due to its relatively high sensitivity to change in temperature and fast data acquisition and processing capabilities. A temperature-sensitive acoustic parameter is required for ultrasound thermometry in order to track the changes in that parameter during the treatment. Currently, the main ultrasound thermometry methods are based on variation in the attenuation coefficient, the change in backscattered energy of the signal (CBE), the backscattered radio-frequency (RF) echo-shift due to change in the speed of sound and thermal expansion of the medium, and change in the amplitudes of the acoustic harmonics. In this work, an ultrasound thermometry method based on second harmonic CBE (CBEh2) and combined fundamental and second harmonic CBE (CBEcomb) is used to produce 2D temperature maps, detect localized heated region generated by low intensity focused ultrasound (LIFU), and control temperature in the heated region. MATERIALS AND METHODS: Ex vivo pork muscle tissue samples were exposed to localized LIFU heating source and 2D temperature maps were produced from the RF data acquired by a 4.2 MHz linear array probe using a Verasonics Vantage™ ultrasound scanner (Verasonics Inc., Redmond, WA) after the exposure. Calibrated needle thermocouples were also placed in the ex vivo tissue sample close to the LIFU focal zone for temperature calibration purposes. The estimated temperature maps were the established echo-shift technique. A tissue motion compensation algorithm was also used to reduce the susceptibility to motion artifacts. RESULTS: 2D temperature maps were generated using CBE of acoustic harmonic and echo-shift techniques. The results show a direct correlation between the CBE of acoustic harmonics and focal tissue temperature for a range of temperatures from 37 °C (baseline) to 47 °C. CONCLUSIONS: The findings of this study show that the CBE of acoustic harmonics technique can be used to noninvasively estimate temperature change in tissue in the hyperthermia temperature range.

Real-Time Control of Nanoparticle-Mediated Thermal Therapy Using Photoacoustic Imaging.

OBJECTIVE: This work aims to determine whether photoacoustic (PA) thermometry from a commercially available PA imaging system can be used to control the temperature in nanoparticle-mediated thermal therapies. METHODS: The PA imaging system was interfaced to obtain PA images while scanning ex-vivo tissue. These images were then used to obtain temperature maps in real-time during heating. Validation and calibration of the PA thermometry were done using a fluoroptic thermometer. This thermometer was also used to develop and tune a software-based proportional integral derivative (PID) controller. Finally, a PA-based PID closed-loop controller was used to control gold nanorod (GNR) mediated laser therapy. RESULTS: The use of GNRs substantially enhanced laser heating; the temperature rise increased 7-fold by injecting a GNR solution with a concentration of 0.029 mg/mL. The control experiments showed that the desired temperature could be achieved and maintained at a targeted location in the ex-vivo tissue. The steady-state mean absolute deviations (MAD) from the targeted temperature during control were between 0.16 [Formula: see text] and 0.5 [Formula: see text], depending on the experiment. CONCLUSION: It was possible to control hyperthermia treatments using a software-based PID controller and a commercial PA imaging system. SIGNIFICANCE: The monitoring and control of the temperature in thermal-based therapies are important for assuring a prescribed temperature to the target tissue while minimizing the temperature of the surrounding healthy tissue. This easily implemented non-invasive control system will facilitate the realization of a broad range of hyperthermia treatments.

Fluence-matching technique using photoacoustic radiofrequency spectra for improving estimates of oxygen saturation.

Photoacoustic (PA) signals encode information about the optical absorption and spatial distribution of absorbing chromophores as well as the light distribution in the medium. The wavelength dependence of the latter affects the accuracy in chromophore quantification, including estimations of oxygen saturation (sO2) with depth. We propose the use of the ratio of the PA radiofrequency (RF) spectral slopes (SS) at different optical wavelengths to generate frequency filters which can be used to match the fluence profiles across separate images generated with different optical wavelengths. Proof-of-principle experiments were carried on a plastic tube with blood of a known oxygenation inserted into a porcine tissue. The algorithm was tested in-vivo in the hind leg of six CD1 mice, each under three different breathing conditions (100 % O2, room air and 100 % CO2). Imaging was done using the VevoLAZR system at the wavelengths 720 and 870 nm. The SS was calculated from the linear fit of the ratio of the photoacoustic RF power spectra at the two wavelengths. An ultrasound frequency filter was designed and applied to each segmented PA signal in the frequency domain and inversely transformed into the time domain to correct for the differences in the fluence profiles at both wavelengths. Linear spectral unmixing was used to estimate sO2 before and after applying the ultrasound frequency filter. The estimated blood sO2 in the plastic tube for the porcine tissue experiment improved by 10.3% after applying the frequency filter when compared to the sO2 measured by a blood gas analyzer. For the in-vivo mouse experiments, the applied sO2 correction was 2.67, 1.33 and -3.33% for every mm of muscle tissue for mice breathing 100% O2, room air and 100% CO2, respectively. The approach presented here provides a new approach for fluence matching that can potentially improve the accuracy of sO2 estimates by removing the fluence depth dependence at different optical wavelengths.

A perfectly matched layer formulation for modeling transient wave propagation in an unbounded fluid-solid medium.

Wave propagation in an infinite medium can be numerically simulated by surrounding a finite region by a perfectly matched layer (PML). When the medium is heterogeneous consisting of both solids and liquids, careful consideration is needed in specifying the properties of the PML especially because parts of it lie at the solid-fluid interface. While such a situation could arise in many important fields including marine seismology, where water is in contact with earth, and in biomedical ultrasound, where soft tissue is in contact with bone, no PML formulation exists to appropriately model such coupled problems. Here, a second-order time-domain PML formulation for fluid-solid heterogeneous media in two dimensions that satisfies the interface coupling boundary condition throughout the computational domain is presented. Numerical results are given to establish the applicability and accuracy of such a PML formulation in discrete settings without causing stability issues, spurious reflections, or any other problems. In particular, the effectiveness of the PML in absorbing all kinds of bulk waves, as well as surface and evanescent waves, is studied.