In Vivo Tumor Vascular Imaging with Light Emitting Diode-Based Photoacoustic Imaging System.

Photoacoustic (PA) imaging has shown tremendous promise for imaging tumor vasculature and its function at deeper penetration depths without the use of exogenous contrast agents. Traditional PA imaging systems employ expensive and bulky class IV lasers with low pulse repetition rate, due to which its availability for preclinical cancer research is hampered. In this study, we evaluated the capability of a Light-Emitting Diode (LED)-based PA and ultrasound (US) imaging system for monitoring heterogeneous microvasculature in tumors (up to 10 mm in depth) and quantitatively compared the PA images with gold standard histology images. We used a combination of a 7 MHz linear array US transducer and 850 nm excitation wavelength LED arrays to image blood vessels in a subcutaneous tumor model. After imaging, the tumors were sectioned and stained for endothelial cells to correlate with PA images across similar cross-sections. Analysis of 30 regions of interest in tumors from different mice showed a statistically significant R-value of 0.84 where the areas with high blood vessel density had high PA response while low blood vessel density regions had low PA response. Our results confirm that LED-based PA and US imaging can provide 2D and 3D images of tumor vasculature and the potential it has as a valuable tool for preclinical cancer research.

Improvement of LED-based photoacoustic imaging using lag-coherence factor (LCF) beamforming.

BACKGROUND: Owing to its portability, affordability, and energy-efficiency, LED-based photoacoustic (PA) imaging is increasingly becoming popular when compared to its laser-based alternative, mainly for superficial vascular imaging applications. However, this technique suffers from low SNR and thereby limited imaging depth. As a result, visual image quality of LED-based PA imaging is not optimal, especially in sub-surface vascular imaging applications. PURPOSE: Combination of linear ultrasound (US) probes and LED arrays are the most common implementation in LED-based PA imaging, which is currently being explored for different clinical imaging applications. Traditional delay-and-sum (DAS) is the most common beamforming algorithm in linear array-based PA detection. Side-lobes and reconstruction-related artifacts make the DAS performance unsatisfactory and poor for a clinical-implementation. In this work, we explored a new weighting-based image processing technique for LED-based PAs to yield improved image quality when compared to the traditional methods. METHODS: We are proposing a lag-coherence factor (LCF), which is fundamentally based on the combination of the spatial auto-correlation of the detected PA signals. In LCF, the numerator contains lag-delay-multiply-and-sum (DMAS) beamformer instead of a conventional DAS beamformer. A spatial auto-correlation operation is performed between the detected US array signals before using DMAS beamformer. We evaluated the new method on both tissue-mimicking phantom (2D) and human volunteer imaging (3D) data acquired using a commercial LED-based PA imaging system. RESULTS: Our novel correlation-based weighting technique showed LED-based PA image quality improvement when it is combined with conventional DAS beamformer. Both phantom and human volunteer imaging results gave a direct confirmation that by introducing LCF, image quality was improved and this method could reduce side-lobes and artifacts when compared to the DAS and coherence-factor (CF) approaches. Signal-to-noise ratio, generalized contrast-to-noise ratio, contrast ratio and spatial resolution were evaluated and compared with conventional beamformers to assess the reconstruction performance in a quantitative way. Results show that our approach offered image quality enhancement with an average signal-to-noise ratio and spatial resolution improvement of around 20% and 25% respectively, when compared with conventional CF based DAS algorithm. CONCLUSIONS: Our results demonstrate that the proposed LCF based algorithm performs better than the conventional DAS and CF algorithms by improving signal-to-noise ratio and spatial resolution. Therefore, our new weighting technique could be a promising tool to improve the performance of LED-based PA imaging and thus accelerate its clinical translation.

LED-based photoacoustic imaging for preoperative visualization of lymphatic vessels in patients with secondary limb lymphedema.

Lymphedema is the accumulation of protein-rich fluid in the interstitium (i.e., dermal backflow (DBF)). Preoperative imaging of the lymphatic vessels is a prerequisite for lymphovenous bypass surgical planning. We investigated the visualization of lymphatic vessels and veins using light-emitting diode (LED)-based photoacoustic imaging (PAI). Indocyanine-green mediated near-infrared fluorescence lymphography (NIRF-L) was done in fifteen patients with secondary limb lymphedema. Photoacoustic images were acquired in locations where lymphatic vessels and DBF were observed with NIRF-L. We demonstrated that LED-based PAI can visualize and differentiate lymphatic vessels and veins even in the presence of DBF. We observed lymphatic and blood vessels up to depths of 8.3 and 8.6 mm, respectively. Superficial lymphatic vessels and veins can be visualized using LED-based PAI even in the presence of DBF showing the potential for pre-operative assessment. Further development of the technique is needed to improve its usability in clinical settings.

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.

Photoacoustic reflection artifact reduction using photoacoustic-guided focused ultrasound: comparison between plane-wave and element-by-element synthetic backpropagation approach.

Reflection artifacts caused by acoustic inhomogeneities constitute a major problem in epi-mode biomedical photoacoustic imaging. Photoacoustic transients from the skin and superficial optical absorbers traverse into the tissue and reflect off echogenic structures to generate reflection artifacts. These artifacts cause difficulties in the interpretation of images and reduce contrast and imaging depth. We recently developed a method called PAFUSion (photoacoustic-guided focused ultrasound) to circumvent the problem of reflection artifacts in photoacoustic imaging. We already demonstrated that the photoacoustic signals can be backpropagated using synthetic aperture pulse-echo data for identifying and reducing reflection artifacts in vivo. In this work, we propose an alternative variant of PAFUSion in which synthetic backpropagation of photoacoustic signals is based on multi-angled plane-wave ultrasound measurements. We implemented plane-wave and synthetic aperture PAFUSion in a handheld ultrasound/photoacoustic imaging system and demonstrate reduction of reflection artifacts in phantoms and in vivo measurements on a human finger using both approaches. Our results suggest that, while both approaches are equivalent in terms of artifact reduction efficiency, plane-wave PAFUSion requires less pulse echo acquisitions when the skin absorption is the main cause of reflection artifacts.

Photoacoustic-guided focused ultrasound for accurate visualization of brachytherapy seeds with the photoacoustic needle.

An important problem in minimally invasive photoacoustic (PA) imaging of brachytherapy seeds is reflection artifacts caused by the high signal from the optical fiber/needle tip reflecting off the seed. The presence of these artifacts confounds interpretation of images. In this letter, we demonstrate a recently developed concept called photoacoustic-guided focused ultrasound (PAFUSion) for the first time in the context of interstitial illumination PA imaging to identify and remove reflection artifacts. In this method, ultrasound (US) from the transducer is focused on the region of the optical fiber/needle tip identified in a first step using PA imaging. The image developed from the US diverging from the focus zone at the tip region visualizes only the reflections from seeds and other acoustic inhomogeneities, allowing identification of the reflection artifacts of the first step. These artifacts can then be removed from the PA image. Using PAFUSion, we demonstrate reduction of reflection artifacts and thereby improved interstitial PA visualization of brachytherapy seeds in phantom and

In vivo demonstration of reflection artifact reduction in photoacoustic imaging using synthetic aperture photoacoustic-guided focused ultrasound (PAFUSion).

Reflection artifacts caused by acoustic inhomogeneities are a critical problem in epi-mode biomedical photoacoustic imaging. High light fluence beneath the probe results in photoacoustic transients, which propagate into the tissue and reflect back from echogenic structures. These reflection artifacts cause problems in image interpretation and significantly impact the contrast and imaging depth. We recently proposed a method called PAFUSion (Photoacoustic-guided focused ultrasound) to identify such reflection artifacts in photoacoustic imaging. In its initial version, PAFUSion mimics the inward-travelling wavefield from small blood vessel-like PA sources by applying ultrasound pulses focused towards these sources, and thus provides a way to identify the resulting reflection artifacts. In this work, we demonstrate reduction of reflection artifacts in phantoms and in vivo measurements on human volunteers. In view of the spatially distributed PA sources that are found in clinical applications, we implemented an improved version of PAFUSion where photoacoustic signals are backpropagated to imitate the inward travelling wavefield and thus the reflection artifacts. The backpropagation is performed in a synthetic way based on the pulse-echo acquisitions after transmission on each single element of the transducer array. The results provide a direct confirmation that reflection artifacts are prominent in clinical epi-photoacoustic imaging, and that PAFUSion can strongly reduce these artifacts to improve deep-tissue photoacoustic imaging.