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.
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.
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.
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.
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.
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.
High power light emitting diodes (LEDs) can serve as fast, robust and affordable excitation sources for photoacoustic imaging. We test the in vivo imaging capabilities of a multi-modal imaging platform that comprises of LED-based photoacoustic (PA) and conventional ultrasound imaging. We characterized the dynamics of a fluorescent contrast agent and modulation of tissue oxygenation in vivo. Fast dynamic PA imaging shows an increase in PA signal with increasing fluorescent agent concentration (Tmax ~ 8 min). Oxygen challenge studies revealed changes in blood oxygenation saturation (SO2) levels in relation to the modulation of breathing air and oxygen.
Photoacoustic imaging is expected to be a next-generation diagnostic modality. However, systems using a solid state laser (SSL) are expensive, large in size and poor in operability of probes. In addition, protective goggles are required because of laser light. Therefore, we have adopted the LED technology and improved the signal-to-noise-ratio (SNR) of the LED-based system, which had been 1 / 2.3 million of the SSL, to the same level with four innovative technologies. These innovative technologies include a) High power and high density LED array technology: Use of high power LED chips with luminous efficiency comparable to laser diode, high density mounting of LED chips on Aluminum base and compact design, b) Giant and ultra-short-pulse drive circuit technology: High speed on-and-off by low-resistance Metal Oxide Semiconductor Field Effect Transistor (MOSFET), and position separation of high-voltage drive circuit from ultrasonic probe (USP) by series connection of LEDs, c) Optical pulse generation technology optimum for frequency response characteristic of USP, d) Noise reduction technology for faint signals using ultra-amplification: Minimization of quantization noise of Analog-digital-converter (ADC) by wide band ultra-amplification of 86 dB, and noise reduction by averaging of <100 times. Using these technologies, we have developed an LED-based photoacoustic imaging system. To use the system, we have discovered the mechanism of the absorption of pulsed light converted into photoacoustic signal detection is a "linear system" by frequency response characteristic analysis using an ideal point source phantom, and clarified the ultra-amplification over 80 dB and the SNR over 4 are required for real-time imaging using a biological phantom. Furthermore human in-vivo real-time functional imaging using dual-wavelength of both 820nm and 940nm has showed that the LED-based system can be used clinically.
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.
It is of vital importance to understanding the relation between image quality and excitation light pulse characteristics in LED-based photoacoustic imaging system. We have tried to change pulse waveform of LED light source to detect several kinds of photoacoustic signals related to the image quality. As a result, in order to understand the photoacoustic signal, it is necessary to consider the characteristics of the optical pulse waveform and the ultrasonic probe well.
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.
Photoacoustic imaging (PAI) has traditionally relied on slow, fragile and expensive lasers as excitation sources. Advances in solid-state device technology have recently resulted in the development of a new class of high power light emitting diodes (LEDs) that can be used as fast, robust and cheap excitation sources for PAI.
Here, we report the characterization and technical validation of a dual-mode multi-wavelength LED-based PAI/ultrasound imaging system (AcousticX) that has the potential to perform real-time in vivo imaging. LEDs operating with a pulse length of 70 ns and a repetition rate of up to 4 KHz at wavelengths of 690, 750, 810, 850 and 980 nm were tested. Ultrasound detection was made using a linear-array transducer with a center frequency of 10.05 MHz and a fractional bandwidth of 77%. We performed several systematic studies to evaluate the precision, penetration depth, spatial resolution, and sensitivity of the system. Measurements were made in tissue-mimicking phantoms to independently assess the impact of system variables on precision, including sample positioning and frame averaging. Temporal variation was assessed by repeated measurements over minutes, hours and days in the phantoms. Sensitivity to spectral differences was established by imaging the phantoms using all available multi-wavelength LEDs. The LED-based PAI system was able to detect small molecule dyes at 500 nM concentration at depth and to differentiate oxy- and deoxy-hemoglobin in mouse blood. Our studies indicate that LED-based PAI would be capable of providing real-time structural, functional and molecular imaging information up to depths of 2.5 cm in tissue.
Minimally invasive fetal interventions, such as those used for therapy of twin-to-twin transfusion syndrome (TTTS), require accurate image guidance to optimise patient outcomes. Currently, TTTS can be treated fetoscopically by identifying anastomosing vessels on the chorionic (fetal) placental surface, and then performing photocoagulation. Incomplete photocoagulation increases the risk of procedure failure. Photoacoustic imaging can provide contrast for both haemoglobin concentration and oxygenation, and in this study, it was hypothesised that it can resolve chorionic placental vessels. We imaged a term human placenta that was collected after caesarean section delivery using a photoacoustic/ultrasound system (AcousticX) that included light emitting diode (LED) arrays for excitation light and a linear-array ultrasound imaging probe. Two-dimensional (2D) co-registered photoacoustic and B-mode pulse-echo ultrasound images were acquired and displayed in real-time. Translation of the imaging probe enabled 3D imaging. This feasibility study demonstrated that photoacoustic imaging can be used to visualise chorionic placental vasculature, and that it has strong potential to guide minimally invasive fetal interventions.
Recently we developed a multispectral LED-based photoacoustic/ultrasound imaging system (AcousticX) and have been continuously working on its technical/functional improvements. AcousticX is a linear array ultrasound transducer (128 elements, 10 MHz)-based system in which LED arrays (selectable wavelengths, pulse repetition frequency: 4 kHz, pulse width: tunable from 40 – 100 ns) are fixed on both sides of the transducer to illuminate the tissue for photoacoustic imaging. The ultrasound/photoacoustic data from all 128 elements can be simultaneously acquired, processed and displayed. We already demonstrated our system’s capability to perform photoacoustic/ultrasound imaging for dynamic imaging of the tissue at a frame rate of 10 Hz (for example to visualize the pulsation of arteries in vivo in human subjects). In this work, we present the development of a new high-speed imaging mode in AcousticX. In this mode, instead of toggling between ultrasound and photoacoustic measurements, it is possible to continuously acquire only photoacoustic data for 1.5 seconds with a time interval of 1 ms. With this improvement, we can record photoacoustic signals from the whole aperture (38 mm) at fast rate and can be reviewed later at different speeds for analyzing dynamic changes in the photoacoustic signals. We believe that AcousticX with this new high-speed mode opens up a feasible technical path for multiple dynamic studies, for example one which focus on imaging the response of voltage sensitive dyes. We envisage to improve the acquisition speed further in future for exploring ultra-high-speed applications.
KEYWORDS: Lymphatic system, Veins, Imaging systems, Light emitting diodes, Visualization, Blood, In vivo imaging, Real time imaging, Absorption, Blood vessels, Photoacoustic imaging, Ultrasound real time imaging
Non-invasive in vivo imaging of lymphatic system is of paramount importance for analyzing the functions of lymphatic vessels, and for investigating their contribution to metastasis. Recently, we introduced a multi-wavelength real-time LED-based photoacoustic/ultrasound system (AcousticX). In this work, for the first time, we demonstrate that AcousticX is capable of real-time imaging of human lymphatic system. Results demonstrate the capability of this system to image vascular and lymphatic vessels simultaneously. This could potentially provide detailed information regarding the interconnected roles of lymphatic and vascular systems in various diseases, therefore fostering the growth of therapeutic interventions.
Photoacoustic imaging is a hybrid biomedical imaging modality that has emerged over the last decade. In photoacoustic imaging, pulsed-light absorbed by the target emits ultrasound that can be detected using a conventional ultrasound array. This ultrasound data can be used to reconstruct the location and spatial details of the intrinsic/extrinsic light absorbers in the tissue. Recently we reported on the development of a multi-wavelength high frame-rate LED-based photoacoustic/ultrasound imaging system (AcousticX). In this work, we photoacoustically characterize the absorption spectrum of ICG and porcine blood using LED arrays with multiple wavelengths (405, 420, 470, 520, 620, 660, 690, 750, 810, 850, 925, 980 nm). Measurements were performed in a simple reflection mode configuration in which LED arrays where fixed on both sides of the linear array ultrasound probe. Phantom used consisted of micro-test tubes filled with ICG and porcine blood, which were placed in a tank filled with water. The photoacoustic spectrum obtained from our measurements matches well with the reference absorption spectrum. These results demonstrate the potential capability of our system in performing clinical/pre-clinical multispectral photoacoustic imaging.
Recently, various type of photoacoustic imaging (PAI) that can visualize properties and distribution of light absorber have been researched. We developed PAI system using LED light source and evaluated characteristics of photoacoustic signal intensity versus Indocyanine Green (ICG) concentration. In this experiment, a linear type PZT array transducer (128-elements, 10.0MHz center frequency) was used to be able to transmit and receive ultrasound and also detect photoacoustic signal from the target object. The transducer was connected to the PAI system, and two sets of LED light source that had 850nm wavelength chip array were set to the both side of the transducer. The transducer head was placed at a distance of 20 mm from the target in the water bath. The target object was a tube filled with ICG in it. The tubes containing ICG at concentrations from 300nanomolar to 3millimolar were made by diluting original ICG solution. We measured the photoacoustic signal strength from RF signal generated from the ICG in the tube, and the results showed that the intensity of the signal was almost linear response to the concentration in log-log scale.
We have achieved penetration depth of 30mm by photoacoustic imaging system using LED light source integrated transducer to image a clinical metal needle inserted into a tissue mimicking phantom. We developed the transducer that integrated near-infrared LED array light source, which was connected to a photoacoustic imaging system which drove LED array light source and controlled photoacoustic data acquisition process. Conventionally solid-state laser has been used as the light source for photoacoustic imaging system. Because LED is diffused light source, laser safety glasses is not necessary, also inflexible fibers are not used to guide light close to a transducer, and we integrated LED light source inside the transducer, which became compact and practical size for conventional ultrasound equipment users. We made LED light source unit as detachable to the transducer easily, so wave-length of light can be selectable by changing the LED light source unit.
We have successfully imaged photoacoustic differences of light absorbance between two images acquired by different wave-length LED array light source. Compared to photoacoustic imaging system using conventional solid-state laser light source, LED light source can be driven at higher frequency pulses, so we were able to get the subtraction image at higher frame rate that calculated from two images which were captured at each wave-length LED light pulse timing. We developed LED array light source which is composed to have two different wave-length chips, so each wave-length light pulse can be controlled and emitted freely. Thus LED array light source can be composed as multiple selectable wavelength more than two, and a various combination of subtraction image may become available at high frame rate.
When we consider the needle visualization in the field of point of care by utilizing the photoacoustic imaging system, and using the conventional solid state laser light source, the issue arises such as device size and not a green system due to the high power consumption. Therefore, we aimed at an environmentally friendly and compact system with low power consumption by using a NIR-LED array light source. The intensity of NIR-LED light is weak, but, by averaging photoacoustic signals with multiple pulse, we have improved S/N of the photoacoustic signal. As a result, we’ve achieved penetration depth of 30mm.
We’ve successfully measured photoacoustic signal by NIR-LED array that has very small power, approx. 1/1500 of light amount compared with Nd:YAG OPO light. In order to achieve high output power, we drove NIR-LED array with unusual amount of electric current. The experiment results showed that the photoacoustic signal strength was about 1/40 of the laser, which suggests NIR-LED array has good photoacoustic reception efficiency versus the ultrasound transducer bandwidth. NIR-LED array photoacoustic system may be able to achieve high-speed imaging which cannot be obtained by the solid-state laser. NIR-LED system can be a game changer for photoacoustic imaging.
We’ve developed NIR-LED array light source module for photoacoustic imaging system, which is ultra-small and consumes extremely low power. Conventional photoacoustic imaging system uses solid state laser light source, which consumes large amount of electricity. Instead, we’ve developed high intensity NIR-LED chips on a 1cm x 6cm board, which produces approx. 1.0kW output power and obtained photoacoustic signal by driving NIR-LED light source module with about 100 ns pulse. Comparing to the laser light source, our module is much smaller than 1/15000 the volume and less than 1/1000 the power consumption approximately. We’ve achieved penetration depth of 30mm.
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