Accurate assessment of microvasculature and oxygen saturation is vital for diagnosing and monitoring diseases, including cancer. However, the current clinical need for point-of-care (POC), non-invasive, and cost-effective imaging approaches remains unmet. Photoacoustic imaging, offering natural blood contrast, holds potential for high-resolution vascular imaging. Yet, the requirement for bulky and expensive lasers impedes its clinical translation, particularly in resource-limited settings. Recent advances in using high-power LED arrays for photoacoustic imaging are promising due to their portability, affordability, and ease-of-use in clinical settings. In this work, we demonstrate the potential of LED-based photoacoustic imaging for microvascular health assessment through in vivo human volunteer imaging. Real-time 2D and 3D experiments evaluated LED-based photoacoustic imaging in assessing vascular density, arterial distensibility, and blood oxygen saturation with high resolution. Our results confirm that LED-based photoacoustic imaging may serve as an invaluable POC tool for microvascular health assessment in resource-limited settings. The affordability and simplicity of LED arrays present a compelling alternative to laser-based approaches, expanding accessibility in clinical practice. This advancement has the potential to enhance early disease detection and treatment monitoring, particularly in areas with limited access to sophisticated imaging technologies.
Visualizing blood vessel networks in 3D is helpful in many superficial vascular imaging applications. We previously reported the feasibility of LED-based photoacoustic imaging in visualizing human vasculature in 3D by linear translation of combined photoacoustic/ultrasound imaging probe. In this work, we improved this 3D imaging functionality by 1) automatic removal of skin PA signal in different 2D slices by ultrasound-based lineation , 2) encoding depth information with different colors and 3)improving the grayscale and hot color maps. All these new features were implemented in the system software and we validated these using phantom and human in vivo imaging experiments. Results demonstrate that the newly implemented features significantly improved the 3D imaging capability in our LED-based photoacoustic and ultrasound imaging system. We believe that the improved 3D imaging functionality in the system will be potentially useful for multiple preclinical and clinical applications in which the visualization of vasculature in 3D is a prerequisite.
Since hypoxia is an early marker for cancer and several microvascular disorders, imaging oxygen saturation with high resolution has profound importance in multiple preclinical and clinical imaging studies. In this work, we demonstrate the potential of dual-wavelength (690/850 nm) LED-based photoacoustic imaging in high resolution real-time oxygen saturation imaging in vivo. We performed two live rat imaging experiments in which the oxygen saturation of the blood vessels in the left hindlimb was imaged for 20 seconds while the animal was breathing pure nitrogen gas to induce hypoxia. For a comparison, we continuously monitored the oxygen level using a pulse oximeter connected to the forelimb. In another experiment, we performed imaging of oxygen saturation changes in the tail vein of the rat while hypoxia was induced over the period of 40 seconds. In this case also, pulse oximeter readings were recorded for a comparison. In all the experiments, photoacoustic-based oxygen saturation values measured over time followed the same trend as the reference values provided by the pulse oximeter. Also, our two wavelength LED-based photoacoustic imaging approach was found to be sensitive even for 3% change in oxygen saturation. Results give a direct confirmation about the potential of LED-based photoacoustic imaging in detection of oxygen saturation with high spatio-temporal resolution, making it an ideal tool for hypoxia detection in longitudinal preclinical and clinical imaging studies.
Lymphaticovenous anastomosis (LVA) is a surgical method of redirecting excess lymphatic fluid into the venous system to improve the lymphatic flow and prevent the recurrence of edema. In this work, using phantom and human volunteer experiments, we explore the potential of a portable LED-based dual-wavelength photoacoustic imaging system in 3D visualization of human lymphatic vessels and veins when using ICG as a contrast agent. Our results demonstrate that LED-based photoacoustic imaging system used in this study can visualize and separate lymphatic vessels and veins with high spatial resolution, and thus holds potential in guiding LVA procedure.
Peripheral arterial disease (PAD) is a condition affecting a large population globally. It is important to identify and treat PAD at an early stage. In this work, we demonstrate the potential of an LED-based photoacoustic and ultrasound imaging system (AcousticX) in PAD diagnosis and treatment monitoring. We used AcousticX to image micro-vasculature networks in palm and foot of a human volunteer. Also, we performed human volunteer imaging experiments to evaluate the efficacy of 3D LED-based photoacoustic and ultrasound imaging in assessing the constriction of microvasculature in response to cold exposure and to study the impact of occlusion in peripheral microvasculature.
Photoacoustic imaging is a hybrid technique which offers high contrast and specificity of optical imaging techniques and excellent spatial resolution of ultrasound imaging. In recent years, there has been tremendous developments in this field and photoacoustic imaging is now facing an exciting challenge of clinical translation. We developed a multispectral LED-based photoacoustic and ultrasound imaging system (AcousticX), which has been already proven to be useful in multiple preclinical and clinical superficial imaging applications. In the first version of AcousticX, acoustic detection was performed using linear array ultrasound probes with center frequencies of 5, 7 and 10 MHz. With these probes, we were able to achieve an imaging depth of 1 cm in tissue in vivo with spatial resolution of around 150-250 μm. However, it is important to improve the imaging depth for exploring wide range of deep-tissue applications. In this work, we developed a new broadband 2.5 MHz ultrasound probe to improve the imaging depth. Using this ultrasound probe and 850 nm LED arrays, we performed phantom, ex vivo and in vivo human volunteer studies and achieved an imaging depth of 2.5-3 cm. We compared the imaging performance of the newly developed probe with the already available US probes and conformed that the 2.5 MHz probe is 3-4 times more sensitive with spatial resolution suitable for deep-tissue applications. When imaging the brachial artery of a human volunteer, we achieved an imaging depth of 2.6 cm at a frame rate of 6 Hz, which is the highest reported in vivo imaging depth in LED-based photoacoustic imaging. We believe that this is the first step towards real-time deep tissue LED-based photoacoustic imaging with potential in multiple clinical applications.
Photoacoustic imaging holds promise in wide range of clinical and preclinical applications. Since photoacoustic imaging can be implemented in a conventional ultrasound scanner by adding light illumination, it is straight forward to realize dual-mode imaging offering complementary contrast. We recently developed an LED-based photoacoustic and ultrasound imaging system (AcousticX) with unprecedented 2D and 3D functional and structural imaging capabilities. Pulse energy offered by our LED arrays is orders of magnitude lower than conventional lasers and we perform frame averaging to keep up with the SNR, reducing the display frame rate. Even though the pulse repetition frequency of our LED arrays is 4 KHz, image frame rate we can achieve is limited by the large number of frame averages used to improve SNR. In this work, we present a deep learning-based approach to reduce the frame averaging in LED-based photoacoustic imaging without compromising the SNR. We have used convolutional neural network (U-Net) model in deep learning for improving the images with less averaging. When compared with traditional denoising methods, deep learning enables us to optimize parameters through network training. We used images from various other photoacoustic imaging systems with higher laser energy and broadband ultrasound transducers, which can generate PA images with high resolution and SNR with minimal or no averaging as training data. We validate our algorithm using LED-based photoacoustic images of phantoms utilizing Indocyanine green and methylene blue as contrast agents. In all cases, we achieved improvement in the SNR by denoising the images with lesser averaging, thereby increasing the framerate. Results demonstrate the potential of deep learning algorithms in improving temporal resolution and SNR in LED-based photoacoustic imaging.
Photoacoustic imaging is a hybrid modality with advantages of both the ultrasound and optical imaging. This technique with optical spectroscopic contrast and acoustic resolution holds promise in wide range of clinical and preclinical applications. Since photoacoustic imaging also involves ultrasound detection, it is straight forward to implement pointof- care dual mode systems with capability of structural and functional imaging. High signal generated from skin-melanin layer is an important problem in any handheld reflection-mode photoacoustic probes. This problem caused by high light fluence just beneath the ultrasound probe results in reduction of vascular contrast and also causes difficulty in image interpretation. In this work, using our LED-based photoacoustic and ultrasound imaging system (AcousticX), we demonstrate the potential of using ultrasound acquisitions dynamically to suppress high photoacoustic signal from skin surface and qualitatively improve the image contrast and quality. In AcousticX, photoacoustic and conventional pulseecho acquisitions are performed in an intermittent manner resulting in a dual-mode display frame rate of 30 Hz. We make use of the line-by-line/planewave ultrasound acquisitions to automatically delineate the skin surface in quasi realtime and suppress photoacoustic signal from the identified area, resulting in improved image interpretation and contrast without losing temporal resolution. Real-time 2D and 3D (linear scan) imaging experiments were performed on finger and foot dorsum of healthy human volunteers to validate the new skin-signal suppression technique. Results give a direct confirmation that our ultrasound-assisted skin-signal reduction feature holds strong potential in enhancing vascular contrast and visual quality in real-time 2D and 3D LED-based photoacoustic imaging.
KEYWORDS: Imaging systems, Oxygen, Light emitting diodes, Blood, In vivo imaging, Tissue optics, Real time imaging, Ultrasonography, Photoacoustic spectroscopy, Signal detection
Photoacoustic imaging is a hybrid medical imaging technique that combines the contrast and spectral sensitivity of optical imaging with resolution and tissue penetration of ultrasound. Due to the difference between the optical absorption spectra of deoxygenated and oxygenated hemoglobin, multispectral photoacoustic imaging holds strong potential in noninvasive local blood oxygen saturation imaging. Oxygen saturation imaging is one of the most promising applications of photoacoustic imaging and has been widely explored in studies related to tumor hypoxia, cancer therapy etc. However, clinical translation of this technology has often been limited by bulky and expensive excitation sources. Recently, we introduced a multi-wavelength real-time LED-based photoacoustic/ultrasound imaging system. In this work, potential of this LED-based system in real-time oxygen saturation imaging is demonstrated using an in vivo measurement on a human volunteer. We used ultra-fast switching two-wavelength LED arrays (750nm/850nm) along with a linear-array 7 MHz US probe for the experiments. 2D PA, US, and oxygen saturation imaging were performed on the index finger of a human volunteer. Results demonstrate that LED-based PA imaging system used in this study is promising for generating 2D/3D oxygen saturation maps along with PA and US images in real-time. We believe that these results will have profound impact in non-invasive blood oxygen saturation imaging and subsequent clinical translation of PA-based oximetry.
Precise and efficient guidance is of paramount importance for minimally invasive vascular access procedures. Ultrasound (US) imaging is commonly used in clinics for this purpose, but the visualization of medical needles and tissue targets are often challenging. Photoacoustic (PA) imaging holds potential in guiding vascular access procedures, but clinical translation of this technology has often been hindered by bulky and expensive excitation sources. In this work, potential of a portable LED-based PA and US imaging system in guiding minimally invasive vascular access procedures is demonstrated using phantom studies and in vivo measurements on human volunteers. In the first experiment, a 14-gauge medical needle was inserted into chicken breast tissue at multiple angles and US/PA images were acquired at a frame rate of 30 Hz, to study the effect of needle insertion angles on US/PA contrast. To obtain a preliminary indication about the potential of PA/US system in imaging superficial vasculature in vivo, brachial artery of a healthy volunteer was imaged in free-hand probe guidance. With the capability of providing real-time visualization of clinical metal needles and tissue targets at clinically relevant imaging depth and spatial resolution, the LED-based PA/US system used in this study holds strong potential in guiding minimally invasive peripheral vascular access procedures.
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