Correction: Bulsink et al. Oxygen Saturation Imaging Using LED-Based Photoacoustic System. Sensors 2021, 21, 283.

The authors wish to make the following corrections to this paper [...].

Biomedical Photoacoustic Imaging and Sensing Using Affordable Resources.

The photoacoustic (PA) effect, also called the optoacoustic effect, was discovered in the 1880s by Alexander Graham Bell and has been utilized for biomedical imaging and sensing applications since the early 1990s [...].

Oxygen Saturation Imaging Using LED-Based Photoacoustic System.

Oxygen saturation imaging has potential in several preclinical and clinical applications. Dual-wavelength LED array-based photoacoustic oxygen saturation imaging can be an affordable solution in this case. For the translation of this technology, there is a need to improve its accuracy and validate it against ground truth methods. We propose a fluence compensated oxygen saturation imaging method, utilizing structural information from the ultrasound image, and prior knowledge of the optical properties of the tissue with a Monte-Carlo based light propagation model for the dual-wavelength LED array configuration. We then validate the proposed method with oximeter measurements in tissue-mimicking phantoms. Further, we demonstrate in vivo imaging on small animal and a human subject. We conclude that the proposed oxygen saturation imaging can be used to image tissue at a depth of 6-8 mm in both preclinical and clinical applications.

Photoacoustic Imaging of Human Vasculature Using LED versus Laser Illumination: A Comparison Study on Tissue Phantoms and In Vivo Humans.

Vascular diseases are becoming an epidemic with an increasing aging population and increases in obesity and type II diabetes. Point-of-care (POC) diagnosis and monitoring of vascular diseases is an unmet medical need. Photoacoustic imaging (PAI) provides label-free multiparametric information of deep vasculature based on strong absorption of light photons by hemoglobin molecules. However, conventional PAI systems use bulky nanosecond lasers which hinders POC applications. Recently, light-emitting diodes (LEDs) have emerged as cost-effective and portable optical sources for the PAI of living subjects. However, state-of-art LED arrays carry significantly lower optical energy (<0.5 mJ/pulse) and high pulse repetition frequencies (PRFs) (4 KHz) compared to the high-power laser sources (100 mJ/pulse) with low PRFs of 10 Hz. Given these tradeoffs between portability, cost, optical energy and frame rate, this work systematically studies the deep tissue PAI performance of LED and laser illuminations to help select a suitable source for a given biomedical application. To draw a fair comparison, we developed a fiberoptic array that delivers laser illumination similar to the LED array and uses the same ultrasound transducer and data acquisition platform for PAI with these two illuminations. Several controlled studies on tissue phantoms demonstrated that portable LED arrays with high frame averaging show higher signal-to-noise ratios (SNRs) of up to 30 mm depth, and the high-energy laser source was found to be more effective for imaging depths greater than 30 mm at similar frame rates. Label-free in vivo imaging of human hand vasculature studies further confirmed that the vascular contrast from LED-PAI is similar to laser-PAI for up to 2 cm depths. Therefore, LED-PAI systems have strong potential to be a mobile health care technology for diagnosing vascular diseases such as peripheral arterial disease and stroke in POC and resource poor settings.

Portable and Affordable Light Source-Based Photoacoustic Tomography.

Photoacoustic imaging is a hybrid imaging modality that offers the advantages of optical (spectroscopic contrast) and ultrasound imaging (scalable spatial resolution and imaging depth). This promising modality has shown excellent potential in a wide range of preclinical and clinical imaging and sensing applications. Even though photoacoustic imaging technology has matured in research settings, its clinical translation is not happening at the expected pace. One of the main reasons for this is the requirement of bulky and expensive pulsed lasers for excitation. To accelerate the clinical translation of photoacoustic imaging and explore its potential in resource-limited settings, it is of paramount importance to develop portable and affordable light sources that can be used as the excitation light source. In this review, we focus on the following aspects: (1) the basic theory of photoacoustic imaging; (2) inexpensive light sources and different implementations; and (3) important preclinical and clinical applications, demonstrated using affordable light source-based photoacoustics. The main focus will be on laser diodes and light-emitting diodes as they have demonstrated promise in photoacoustic tomography-the key technological developments in these areas will be thoroughly reviewed. We believe that this review will be a useful opus for both the beginners and experts in the field of biomedical photoacoustic 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.

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.

Photoacoustic imaging of the human placental vasculature.

Minimally invasive fetal interventions require accurate imaging from inside the uterine cavity. Twin-to-twin transfusion syndrome (TTTS), a condition considered in this study, occurs from abnormal vascular anastomoses in the placenta that allow blood to flow unevenly between the fetuses. Currently, TTTS is treated fetoscopically by identifying the anastomosing vessels, and then performing laser photocoagulation. However, white light fetoscopy provides limited visibility of placental vasculature, which can lead to missed anastomoses or incomplete photocoagulation. Photoacoustic (PA) imaging is an alternative imaging method that provides contrast for hemoglobin, and in this study, two PA systems were used to visualize chorionic (fetal) superficial and subsurface vasculature in human placentas. The first system comprised an optical parametric oscillator for PA excitation and a 2D Fabry-Pérot cavity ultrasound sensor; the second, light emitting diode arrays and a 1D clinical linear-array ultrasound imaging probe. Volumetric photoacoustic images were acquired from ex vivo normal term and TTTS-treated placentas. It was shown that superficial and subsurface branching blood vessels could be visualized to depths of approximately 7 mm, and that ablated tissue yielded negative image contrast. This study demonstrated the strong potential of PA imaging to guide minimally invasive fetal therapies.

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.

Photoacoustic-guided focused ultrasound (PAFUSion) for identifying reflection artifacts in photoacoustic imaging.

Influence of acoustic inhomogeneities and resulting reflection artifacts is an important problem in reflection-mode photoacoustic imaging. Absorption of light by skin and superficial optical absorbers will generate photoacoustic transients, which traverse into the tissue and get reflected from structures having different acoustic impedance. These reflected photoacoustic signals, when reconstructed, may appear in the region of interest, which causes difficulties in image interpretation. We propose a novel method to identify and potentially eliminate reflection artifacts in photoacoustic images using photoacoustic-guided focused ultrasound [PAFUSion]. Our method uses focused ultrasound pulses to mimic the wave field produced by photoacoustic sources and thus provides a way to identify reflection artifacts in clinical combined photoacoustic and pulse-echo ultrasound. Simulation and phantom results are presented to demonstrate the validity and impact of this method. Results show that PAFUSion can identify reflections in photoacoustic images and thus envisages potential for improving photoacoustic imaging of acoustically inhomogeneous tissue.