LED-based Photoacoustic Imaging Research Articles

U-Net enhanced real-time LED-based photoacoustic imaging.

Photoacoustic (PA) imaging is hybrid imaging modality with good optical contrast and spatial resolution. Portable, cost-effective, smaller footprint light emitting diodes (LEDs) are rapidly becoming important PA optical sources. However, the key challenge faced by the LED-based systems is the low light fluence that is generally compensated by high frame averaging, consequently reducing acquisition frame-rate. In this study, we present a simple deep learning U-Net framework that enhances the signal-to-noise ratio (SNR) and contrast of PA image obtained by averaging low number of frames. The SNR increased by approximately four-fold for both in-class in vitro phantoms (4.39 ± 2.55) and out-of-class in vivo models (4.27 ± 0.87). We also demonstrate the noise invariancy of the network and discuss the downsides (blurry outcome and failure to reduce the salt & pepper noise). Overall, the developed U-Net framework can provide a real-time image enhancement platform for clinically translatable low-cost and low-energy light source-based PA imaging systems.

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

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. 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 traditionalmethods. 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 imagingsystem. 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 DASalgorithm. 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 clinicaltranslation.

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.

Improving needle visibility in LED-based photoacoustic imaging using deep learning with semi-synthetic datasets

Photoacoustic imaging has shown great potential for guiding minimally invasive procedures by accurate identification of critical tissue targets and invasive medical devices (such as metallic needles). The use of light emitting diodes (LEDs) as the excitation light sources accelerates its clinical translation owing to its high affordability and portability. However, needle visibility in LED-based photoacoustic imaging is compromised primarily due to its low optical fluence. In this work, we propose a deep learning framework based on U-Net to improve the visibility of clinical metallic needles with a LED-based photoacoustic and ultrasound imaging system. To address the complexity of capturing ground truth for real data and the poor realism of purely simulated data, this framework included the generation of semi-synthetic training datasets combining both simulated data to represent features from the needles and in vivo measurements for tissue background. Evaluation of the trained neural network was performed with needle insertions into blood-vessel-mimicking phantoms, pork joint tissue ex vivo and measurements on human volunteers. This deep learning-based framework substantially improved the needle visibility in photoacoustic imaging in vivo compared to conventional reconstruction by suppressing background noise and image artefacts, achieving 5.8 and 4.5 times improvements in terms of signal-to-noise ratio and the modified Hausdorff distance, respectively. Thus, the proposed framework could be helpful for reducing complications during percutaneous needle insertions by accurate identification of clinical needles in photoacoustic imaging.

Detecting joint inflammation by an LED-based photoacoustic imaging system: a feasibility study (Erratum).

.An error in the first author’s name is corrected.

Technical validation studies of a dual-wavelength LED-based photoacoustic and ultrasound imaging system

Recent advances in high power, pulsed, light emitting diodes (LEDs) have shown potential as fast, robust and relatively inexpensive excitation sources for photoacoustic imaging (PAI), yet systematic characterization of performance for biomedical imaging is still lacking. We report here technical and biological validation studies of a commercial dual-wavelength LED-based PAI and ultrasound system. Phantoms and small animals were used to assess temporal precision. In phantom studies, we found high temporal stability of the LED-based PAI system, with no significant drift in performance observed during 6 h of operation or over 30 days of repeated measurements. In vivo dual-wavelength imaging was able to map the dynamics of changes in blood oxygenation during oxygen-enhanced imaging and reveal the kinetics of indocyanine green contrast agent inflow after intravenous administration (Tmax∼6 min). Taken together, these studies indicate that LED-based excitation could be promising for future application in functional and molecular PAI.

Enhancement of Photoacoustic Signal Strength with Continuous Wave Optical Pre-Illumination: A Non-Invasive Technique.

Use of portable and affordable pulse light sources (light emitting diodes (LED) and laser diodes) for tissue illumination offers an opportunity to accelerate the clinical translation of photoacoustic imaging (PAI) technology. However, imaging depth in this case is limited because of low output (optical) power of these light sources. In this work, we developed a noninvasive technique for enhancing strength (amplitude) of photoacoustic (PA) signal. This is a photothermal-based technique in which a continuous wave (CW) optical beam, in addition to short-pulse laser beam, is employed to irradiate and, thus, raise the temperature of sample material selectively over a pre-specified region of interest (we call the process as pre-illumination). The increase in temperature, in turn enhances the PA-signal strength. Experiments were conducted in methylene blue, which is one of the commonly used contrast agents in laboratory research studies, to validate change in temperature and subsequent enhancement of PA-signal strength for the following cases: (1) concentration or optical absorption coefficient of sample, (2) optical power of CW-optical beam, and (3) time duration of pre-illumination. A theoretical hypothesis, being validated by numerical simulation, is presented. To validate the proposed technique for clinical and/or pre-clinical applications (diagnosis and treatments of cancer, pressure ulcers, and minimally invasive procedures including vascular access and fetal surgery), experiments were conducted in tissue-mimicking Agar phantom and ex-vivo animal tissue (chicken breast). Results demonstrate that pre-illumination significantly enhances PA-signal strength (up to (methylene blue), (Agar phantom), and (chicken tissue)). The proposed technique addresses one of the primary challenges in the clinical translation of LED-based PAI systems (more specifically, to obtain a detectable PA-signal from deep-seated tissue targets).

Imaging of enthesitis by an LED-based photoacoustic system

.Significance: One key pathological characteristic of seronegative spondyloarthropathy (SpA) is inflammation at the insertion of tendons and ligaments into the bone (enthesitis).Aim: We explore the potential of the emerging photoacoustic (PA) imaging in diagnosis of SpA and review its feasibility in detecting SpA-associated Achilles tendon enthesitis.Approach: A light-emitting diode (LED)-based PA and ultrasound combined system was employed. The PA images, both along the long and the short axes of each Achilles tendon insertion region, were acquired at 850-nm wavelength, which is sensitive in depicting increased blood volume (i.e., hyperemia). To assess the hyperemia indicating enthesis inflammation, two parameters were quantified in the imaged tendons, including the average intensity and the density of the color pixels in the pseudo-color PA images. Ten SpA patients, all of which met Assessment of SpA International Society (ASAS) criteria for SpA and were found to have Achilles enthesitis by clinical exam according to a board-certified rheumatologist, were included in the study.Results: The PA and Doppler ultrasound imaging of Achilles enthesitis resulting from these 10 SpA patients were compared to those from 10 healthy volunteers, leading to statistically significant differences () in the applied -tests.Conclusions: This preliminary clinical study suggests that the LED-based PA imaging holds a promise for sensitive and objective assessment of SpA enthesitis in an outpatient setting of the rheumatology clinic.

Light-Emitting Diode Based Photoacoustic Imaging System

Purpose: A Photoacoustic Imaging (PAI) as a non-invasive hybrid imaging modality has the potential to be used in a wide range of pre-clinical and clinical applications. There are different optical excitation sources that affect the performance of PAI systems. Our goal is proving the capability of the Light-Emitting Diode (LED) based PAI system for imaging of objects in different depths. Materials and Methods: In this study the Full Width of Half Maximum (FWHM) and Contrast to Noise Ratio (CNR) of LED-based PAI system is evaluated using agar, and Poly-Vinyl Alcohol Cryogel (PVA-C) phantoms. Results: The results show that axial and lateral FWHM of the photoacoustic image in agar phantom 1%, are 0.59 and 1.16 mm, respectively. It is capable of distinguishing objects about 250 µm. Furthermore, one of the main improvements of photoacoustic images is achieved by proposed LED-based system that is a 26% higher CNR versus the ultrasound images. Conclusion: Therefore, the provided technical characteristics in this study have made designed LED-based PAI system as a suitable tool for preclinical and clinical imaging.

Optimizing Irradiation Geometry in LED-Based Photoacoustic Imaging with 3D Printed Flexible and Modular Light Delivery System.

Photoacoustic (PA) imaging–a technique combining the ability of optical imaging to probe functional properties of the tissue and deep structural imaging ability of ultrasound–has gained significant popularity in the past two decades for its utility in several biomedical applications. More recently, light-emitting diodes (LED) are being explored as an alternative to bulky and expensive laser systems used in PA imaging for their portability and low-cost. Due to the large beam divergence of LEDs compared to traditional laser beams, it is imperative to quantify the angular dependence of LED-based illumination and optimize its performance for imaging superficial or deep-seated lesions. A custom-built modular 3-D printed hinge system and tissue-mimicking phantoms with various absorption and scattering properties were used in this study to quantify the angular dependence of LED-based illumination. We also experimentally calculated the source divergence of the pulsed-LED arrays to be 58° ± 8°. Our results from point sources (pencil lead phantom) in non-scattering medium obey the cotangential relationship between the angle of irradiation and maximum PA intensity obtained at various imaging depths, as expected. Strong dependence on the angle of illumination at superficial depths (−5°/mm at 10 mm) was observed that becomes weaker at intermediate depths (−2.5°/mm at 20 mm) and negligible at deeper locations (−1.1°/mm at 30 mm). The results from the tissue-mimicking phantom in scattering media indicate that angles between 30–75° could be used for imaging lesions at various depths (12 mm–28 mm) where lower LED illumination angles (closer to being parallel to the imaging plane) are preferable for deep tissue imaging and superficial lesion imaging is possible with higher LED illumination angles (closer to being perpendicular to the imaging plane). Our results can serve as a priori knowledge for the future LED-based PA system designs employed for both preclinical and clinical applications.

Evaluation of multi-wavelengths LED-based photoacoustic imaging for maximum safe resection of glioma: a proof of concept study

A real-time intra-operative imaging modality is required to update the navigation systems during neurosurgery, since precise localization and safe maximal resection of gliomas are of utmost clinical importance. Different intra-operative imaging modalities have been proposed to delineate the resection borders, each with advantages and disadvantages. This preliminary study was designed to simulate the photoacoustic imaging (PAI) to illustrate the brain tumor margin vessels for safe maximal resection of glioma. In this study, light emitting diode (LED)-based PAI was selected because of its lower cost, compact size and ease of use. We developed a simulation framework based on multi-wavelength LED-based PAI to further facilitate PAI during neurosurgery. This framework considers a multilayer model of the tumoral and normal brain tissue. The simulation of the optical fluence and absorption map in tissue at different depths was computed by Monte Carlo. Then, the propagation of initial photoacoustic pressure was simulated by using k-wave toolbox. To evaluate the LED-based PAI, we used three evaluation criteria: signal-to-noise ratio (SNR), contrast ratio (CR) and full width of half maximum (FWHM). Results showed that by using proper wavelengths, the vessels were recovered with the same axial and lateral FWHM. Furthermore, by increasing the wavelength from 532 to 1064nm, SNR and CR were increased in the deep region. The results showed that vessels with larger diameters at same wavelength have a higher CR with average improvement 28%. Multi-wavelength LED-based PAI provides detailed images of the blood vessels which are crucial for detection of the residual glioma: The longer wavelengths like 1064nm can be used for the deeper tumor margins, and the shorter wavelengths like 532nm for tumor margins closer to the surface. LED-based PAI may be considered as a promising intra-operative imaging modality to delineate tumor margins.

Towards Clinical Translation of LED-Based Photoacoustic Imaging: A Review.

Photoacoustic imaging, with the capability to provide simultaneous structural, functional, and molecular information, is one of the fastest growing biomedical imaging modalities of recent times. As a hybrid modality, it not only provides greater penetration depth than the purely optical imaging techniques, but also provides optical contrast of molecular components in the living tissue. Conventionally, photoacoustic imaging systems utilize bulky and expensive class IV lasers, which is one of the key factors hindering the clinical translation of this promising modality. Use of LEDs which are portable and affordable offers a unique opportunity to accelerate the clinical translation of photoacoustics. In this paper, we first review the development history of LED as an illumination source in biomedical photoacoustic imaging. Key developments in this area, from point-source measurements to development of high-power LED arrays, are briefly discussed. Finally, we thoroughly review multiple phantom, ex-vivo, animal in-vivo, human in-vivo, and clinical pilot studies and demonstrate the unprecedented preclinical and clinical potential of LED-based photoacoustic imaging.

Dictionary learning technique enhances signal in LED-based photoacoustic imaging.

There has been growing interest in low-cost light sources such as light-emitting diodes (LEDs) as an excitation source in photoacoustic imaging. However, LED-based photoacoustic imaging is limited by low signal due to low energy per pulse-the signal is easily buried in noise leading to low quality images. Here, we describe a signal de-noising approach for LED-based photoacoustic signals based on dictionary learning with an alternating direction method of multipliers. This signal enhancement method is then followed by a simple reconstruction approach delay and sum. This approach leads to sparse representation of the main components of the signal. The main improvements of this approach are a 38% higher contrast ratio and a 43% higher axial resolution versus the averaging method but with only 4% of the frames and consequently 49.5% less computational time. This makes it an appropriate option for real-time LED-based photoacoustic imaging.

Effect of Amplifier Gain on Photoacoustic SNR (Signal to Noise Ratio) in an LED-based Photoacoustic Imaging System.

The possibility of using photoacoustic imaging for functional diagnosis has attracted much attention especially in the clinical field. Among such imaging systems, a system, which offers real-time imaging using compact and low-priced LEDs as a light source, has appeared. Compared to solid state lasers, the LED pulse energy was extremely small, so it had been thought that imaging would be extremely difficult, but by adding a pre-amplifier, real time photoacoustic imaging became possible. However the signal-to-noise ratio (SNR) and the amplifier gain needed for making real time imaging possible have remained unclear. The present study was designed to clarify these data. The results showed that, using a tissue phantom and human fingers, an SNR > 4 and amplifier gain > 80dB were required, and demonstrated why making an image without a pre-amplifier had proved difficult.

LED-Based Photoacoustic Imaging for Monitoring Angiogenesis in Fibrin Scaffolds

Noninvasive imaging techniques provide insight into physiology that is complementary to tissue morphology obtained by invasive histology. Optical imaging techniques, such as laser speckle contrast analysis, are used in vivo to longitudinally evaluate vascularization. Despite their high spatial resolution, these techniques have a limited imaging depth. In this study, we demonstrate how a dual LED-based photoacoustic (PA) and ultrasound system can delineate changes in perfusion at depth within scaffolds containing basic fibroblast growth factor. Perfusion changes detected by PA corroborated with vessel density. PA imaging could be a noninvasive and sensitive method for evaluating vascularization at depth in larger constructs.

Molecular imaging of oxidative stress using an LED-based photoacoustic imaging system

LED-based photoacoustic imaging has practical value in that it is affordable and rugged; however, this technology has largely been confined to anatomic imaging with limited applications into functional or molecular imaging. Here, we report molecular imaging reactive oxygen and nitrogen species (RONS) with a near-infrared (NIR) absorbing small molecule (CyBA) and LED-based photoacoustic imaging equipment. CyBA produces increasing photoacoustic signal in response to peroxynitrite (ONOO−) and hydrogen peroxide (H2O2) with photoacoustic signal increases of 3.54 and 4.23-fold at 50 µM of RONS at 700 nm, respectively. CyBA is insensitive to OCl−, ˙NO, NO2−, NO3−, tBuOOH, O2−, C4H9O˙, HNO, and ˙OH, but can detect ONOO− in whole blood and plasma. CyBA was then used to detect endogenous RONS in macrophage RAW 246.7 cells as well as a rodent model; these results were confirmed with fluorescence microscopy. Importantly, CyB suffers photobleaching under a Nd:YAG laser but the signal decrease is <2% with the low-power LED-based photoacoustic system and the same radiant exposure time. To the best of our knowledge, this is the first report to describe molecular imaging with an LED-based photoacoustic scanner. This study not only reveals the sensitive photoacoustic detection of RONS but also highlights the utility of LED-based photoacoustic imaging.

Noninvasive staging of pressure ulcers using photoacoustic imaging

Ulcers including pressure ulcers and diabetic foot ulcers damage the skin and underlying tissue in people with compromised blood circulation. They are classified into four stages of severity and span from mild reddening of the skin to tissue damage and muscle/bone infections. Here, we used photoacoustic imaging as a noninvasive method for detecting early tissue damage that cannot be visually observed while also staging the disease using quantitative image analysis. We used a mouse model of pressure ulcers by implanting subdermal magnets in the dorsal flank and periodically applying an external magnet to the healed implant site. The magnet-induced pressure was applied in cycles, and the extent of ulceration was dictated by the number of cycles. We used both laser- and light-emitting diode (LED)-based photoacoustic imaging tools with 690 nm excitation to evaluate the change in photoacoustic signal and depth of injury. Using laser-based photoacoustic imaging system, we found a 4.4-fold increase in the photoacoustic intensity in stage I vs. baseline (no pressure). We also evaluated the depth of injury using photoacoustics. We measured a photoacoustic ulcer depth of 0.38 ± 0.09 mm, 0.74 ± 0.11 mm, 1.63 ± 0.4 mm, and 2.7 ± 0.31 mm (n = 4) for stages I-IV, respectively. The photoacoustic depth differences between each stage were significant (p < 0.05). We also used an LED-based photoacoustic imaging system to detect early stage (stage I) pressure ulcers and observed a 2.5-fold increase in photoacoustic signal. Importantly, we confirmed the capacity of this technique to detect dysregulated skin even before stage I ulcers have erupted. We also observed significant changes in photoacoustic intensity during healing suggesting that this approach can monitor therapy. These findings were confirmed with histology. These results suggest that this photoacoustic-based approach might have clinical value for monitoring skin diseases including pressure ulcers.

Light Emitting Diodes based Photoacoustic Imaging and Potential Clinical Applications

Using low cost and small size light emitting diodes (LED) as the alternative illumination source for photoacoustic (PA) imaging has many advantages, and can largely benefit the clinical translation of the emerging PA imaging technology. Here, we present our development of LED-based PA imaging integrated with B-mode ultrasound. To overcome the challenge of achieving sufficient signal-to-noise ratio by the LED light that is orders of magnitude weaker than lasers, extensive signal averaging over hundreds of pulses is performed. Facilitated by the fast response of the LED and the high-speed driving as well as the high pulse repetition rate up to 16 kHz, B-mode PA images superimposed on gray-scale ultrasound of a biological sample can be achieved in real-time with frame rate up to 500 Hz. The LED-based PA imaging could be a promising tool for several clinical applications, such as assessment of peripheral microvascular function and dynamic changes, diagnosis of inflammatory arthritis, and detection of head and neck cancer.

Handheld Real-Time LED-Based Photoacoustic and Ultrasound Imaging System for Accurate Visualization of Clinical Metal Needles and Superficial Vasculature to Guide Minimally Invasive Procedures.

Ultrasound imaging is widely used to guide minimally invasive procedures, but the visualization of the invasive medical device and the procedure’s target is often challenging. Photoacoustic imaging has shown great promise for guiding minimally invasive procedures, but clinical translation of this technology has often been limited by bulky and expensive excitation sources. In this work, we demonstrate the feasibility of guiding minimally invasive procedures using a dual-mode photoacoustic and ultrasound imaging system with excitation from compact arrays of light-emitting diodes (LEDs) at 850 nm. Three validation experiments were performed. First, clinical metal needles inserted into biological tissue were imaged. Second, the imaging depth of the system was characterized using a blood-vessel-mimicking phantom. Third, the superficial vasculature in human volunteers was imaged. It was found that photoacoustic imaging enabled needle visualization with signal-to-noise ratios that were 1.2 to 2.2 times higher than those obtained with ultrasound imaging, over insertion angles of 26 to 51 degrees. With the blood vessel mimicking phantom, the maximum imaging depth was 38 mm. The superficial vasculature of a human middle finger and a human wrist were clearly visualized in real-time. We conclude that the LED-based system is promising for guiding minimally invasive procedures with peripheral tissue targets.

The characterization of an economic and portable LED-based photoacoustic imaging system to facilitate molecular imaging

Photoacoustic imaging (PAI) is a non-invasive, high-resolution hybrid imaging modality that combines optical excitation and ultrasound detection. PAI can image endogenous chromophores (melanin, hemoglobin, etc.) and exogenous contrast agents in different medical applications. However, most current equipment uses sophisticated and complicated OPO lasers with tuning and stability features inconsistent with broad clinical deployment. As the number of applications of PAI in medicine increases, there is an urgent need to make the imaging equipment more compact, portable, and affordable. Here, portable light emitting diode – based photoacoustic imaging (PLED-PAI) was introduced and characterized in terms of system specifications, light source characterizations, photoacoustic spatial/temporal resolution, and penetration. The system uses two LED arrays attached to the sides of a conventional ultrasound transducer. The LED pulse repetition rate is tunable between 1 K Hz, 2 K Hz, 3 K Hz, and 4 K Hz. The axial resolution was 0.268 mm, and the lateral resolution was between 0.55 and 0.59 mm. The system could detect optical absorber (pencil lead) at a depth of 3.2 cm and the detection limits of indocyanine green (ICG) and methylene blue (MB) were 9 μM and 0.78 mM. In vivo imaging of labeled human mesenchymal stem cells was achieved to confirm compatibility with small animal imaging. The characterization we report here may have value to other groups evaluating commercially available photoacoustic imaging equipment.