Focus on Interventional Photoacoustic Imaging

Percutaneous radiofrequency ablation (RFA) is gaining importance as a locoregional treatment for tumors in several organs including the liver, lung, kidney and bone. In RFA, the tumor is eradicated with the direct application of heat using alternating current through a needle electrode positioned under imaging guidance. Various imaging methods are used in the RFA ablation procedure but these have drawbacks. In this work, we introduce photoacoustic (PA) imaging as a new method with potential to visualize the targeting of RFA needle into a region of interest and to report on the extent of ablation achieved. We demonstrate the proof-of-concept in using PA imaging together with ultrasound imaging on ex vivo biological samples in the laboratory simulating relevant clinical scenarios in RFA. These include guidance of the RFA needle to target tissue, mapping of simulated blood vessels during needle insertion and differentiation between ablated and surrounding tissue. The results of this first investigation into the use of PA imaging to assist RFA procedures are encouraging. We discuss the challenges encountered, the scope for future work and envisaged clinical application.

Clinical translation of optoacoustic imaging is fostered by the rapid technical advances in imaging performance as well as the growing number of clinicians recognizing the immense diagnostic potential of this technology. Clinical optoacoustic systems are available in multiple configurations, including hand-held and endoscopic probes as well as raster-scan approaches. The hardware design must be adapted to the accessible portion of the imaged region and other application-specific requirements pertaining the achievable depth, field of view or spatio-temporal resolution. Equally important is the adequate choice of the signal and image processing approach, which is largely responsible for the resulting imaging performance. Thus, new image reconstruction algorithms are constantly evolving in parallel to the newly-developed set-ups. This review focuses on recent progress on optoacoustic image formation algorithms and processing methods in the clinical setting. Major reconstruction challenges include real-time image rendering in two and three dimensions, efficient hybridization with other imaging modalitites as well as accurate interpretation and quantification of bio-markers, herein discussed in the context of ongoing progress in clinical translation.

Imaging guidance is paramount to procedural success in minimally invasive interventions. Catheter-based therapies are the standard of care in the treatment of many cardiac disorders, including coronary artery disease, structural heart disease and electrophysiological conditions. Many of these diseases are caused by, or effect, a change in vasculature or cardiac tissue composition, which can potentially be detected by photoacoustic imaging. This review summarizes the state of the art in photoacoustic imaging approaches that have been proposed for intervention guidance in cardiovascular care. All of these techniques are currently in the preclinical phase. We will conclude with an outlook towards clinical applications.

The increasing personalization of medical treatment demands refined imaging and increased monitoring capabilities, as well as an improved efficacy through targeted drug delivery. Such a transition in health care can be facilitated by the use of multimodal contrast agents. In this paper, we present a novel type of multimodal contrast agents, that enhances contrast both in ultrasound and in photoacoustic imaging, while at the same time being capable of triggered drug delivery. Upon pulsed laser irradiation, polymeric microparticles—containing a dye and an oil core—can create a cavitation bubble that subsequently emits a strong acoustic wave. We investigated different formulations of these particles, by changing the oil content, dye concentration and probing conditions using a combination of pulsed laser excitation and an ultrasound chirp. We demonstrated that capsules with a core containing a low boiling point oil give the highest photoacoustic and acoustic response. The laser activation threshold for this system is high in the visible range, but within the near infrared medical limits. The same system also produces a stable bubble. US scattering by these stable bubbles results in medically relevant frequencies, making the particles of interest for biomedical and pre-clinical imaging. Finally, the system has potential to carry a functional drug-load, and a route to these applications is discussed.

Intravascular photoacoustic (IVPA) imaging has been developed in recent years as a viable imaging modality for the assessment of atherosclerotic plaques. Exogenous imaging contrast and therapeutic agents further enhance this imaging modality and provide significant benefits. Imaging contrast agents can significantly increase photoacoustic signal, resulting in enhanced plaque detection and characterization. The ability to use these particles to molecularly target markers of disease progression makes it possible to determine patient-specific levels of risk and plan treatments accordingly. With improved diagnosis, clinicians will be able to use therapeutic agents that are synergistic with IVPA imaging to treat atherosclerotic patients. Pre-clinical and clinical studies with relevance to IVPA imaging have shown promise in the area of diagnosis and therapeutics. In this review, we present a variety of imaging contrast agents that are either designed for or are compatible with IVPA imaging, cover uses of therapeutic agents that compliment this imaging modality, and discuss future directions of research in the field.

The objective of this study is to demonstrate in vivo the feasibility of optoacoustic temperature imaging during cryotherapy of prostate cancer. We developed a preclinical prototype optoacoustic temperature imager that included pulsed optical excitation at a wavelength of 805 nm, a modified clinical transrectal ultrasound probe, a parallel data acquisition system, image processing and visualization software. Cryotherapy of a canine prostate was performed in vivo using a commercial clinical system, Cryocare^® CS, with an integrated ultrasound imaging. The universal temperature-dependent optoacoustic response of blood was employed to convert reconstructed optoacoustic images to temperature maps. Optoacoustic imaging of temperature during prostate cryotherapy was performed in the longitudinal view over a region of 30 mm (long)  ×  10 mm (deep) that covered the rectum, the Denonvilliers fascia, and the posterior portion of the treated gland. The transrectal optoacoustic images showed high-contrast vascularized regions, which were used for quantitative estimation of local temperature profiles. The constructed temperature maps and their temporal dynamics were consistent with the arrangement of the cryoprobe and readouts of the thermal needle sensors. The temporal profiles of the readouts from the thermal needle sensors and the temporal profile estimated from the normalized optoacoustic intensity of the selected vascularized region showed significant resemblance, except for the initial overshoot, that may be explained as a result of the physiological thermoregulatory compensation. The temperature was mapped with errors not exceeding  ±2 °C (standard deviation) consistent with the clinical requirements for monitoring cryotherapy of the prostate. In vivo results showed that the optoacoustic temperature imaging is a promising non-invasive technique for real-time imaging of tissue temperature during cryotherapy of prostate cancer, which can be combined with transrectal ultrasound—the current standard for guiding clinical cryotherapy procedure.

It is well known that there are structural differences between cortical and cancellous bone. However, spinal surgeons currently have no reliable method to non-invasively determine these differences in real-time when choosing the optimal starting point and trajectory to insert pedicle screws and avoid surgical complications associated with breached or weakened bone. This paper explores 3D photoacoustic imaging of a human vertebra to noninvasively differentiate cortical from cancellous bone for this surgical task. We observed that signals from the cortical bone tend to appear as compact, high-amplitude signals, while signals from the cancellous bone have lower amplitudes and are more diffuse. In addition, we discovered that the location of the light source for photoacoustic imaging is a critical parameter that can be adjusted to non-invasively determine the optimal entry point into the pedicle. Once inside the pedicle, statistically significant differences in the contrast and SNR of signals originating from the cancellous core of the pedicle (when compared to signals originating from the surrounding cortical bone) were obtained with laser energies of 0.23–2.08 mJ (p  <  0.05). Similar quantitative differences were observed with an energy of 1.57 mJ at distances  ⩾6 mm from the cortical bone of the pedicle. These quantifiable differences between cortical and cancellous bone (when imaging with an ultrasound probe in direct contact with each bone type) can potentially be used to ensure an optimal trajectory during surgery. Our results are promising for the introduction and development of photoacoustic imaging systems to overcome a wide range of longstanding challenges with spinal surgeries, including challenges with the occurrence of bone breaches due to misplaced pedicle screws.