Eigenspace-based minimum variance beamformer combined with sign coherence factor: Application to linear-array photoacoustic imaging.

Photoacoustic (PA) imaging combining the advantages of high resolution of ultrasound imaging and high contrast of optical imaging provides images with good quality. PA imaging often suffers from disadvantages such as clutter noises and decreased signal-to-noise-ratio at higher depths. One studied method to reduce clutter noises is to use weighting factors such as coherence factor (CF) and its modified versions that improve resolution and contrast of images. In this study, we combined the Eigen-space based minimum variance (EIBMV) beamformer with the sign coherence factor (SCF) and show the ability of these methods for noise reduction when they are used in combination with each other. In addition, we compared the proposed method with delay-and-sum (DAS) and minimum variance (MV) beamformers in simulated and experimental studies. The simulation results show that the proposed EIBMV-SCF method improves the SNR about 94 dB, 87.65 dB, and 62.29 dB compared to the DAS, MV, and EIBMV, respectively, and the corresponding improvements were 79.37/34.43 dB, 77.25/26.96 dB, and 33.19/25.56 dB in the ex vivo/in vivo experiments.

In vivo optoacoustic monitoring of percutaneous laser ablation of tumors in a murine breast cancer model.

Laser ablation (LA) is a promising approach for minimally invasive cancer treatments. Its in vivo applicability is often impeded by the lack of efficient monitoring tools that can help to minimize collateral tissue damage and aid in determining the optimal treatment end-points. We have devised a new, to the best of our knowledge, hybrid LA approach combining simultaneous volumetric optoacoustic (OA) imaging to monitor the lesion progression accurately in real time and 3D. Time-lapse imaging of laser ablation of solid tumors was performed in a murine breast cancer model in vivo by irradiation of subcutaneous tumors with a 100 mJ short-pulsed (${\sim}{5}\;{\rm ns}$∼5ns) laser operating at 1064 nm and 100 Hz pulse repetition frequency. Local changes in the OA signal intensity ascribed to structural alterations in the tumor vasculature were clearly observed, while the OA volumetric projections recorded in vivo appeared to correlate with cross sections of the excised tumors.

Sparsity-based beamforming to enhance two-dimensional linear-array photoacoustic tomography.

In linear-array photoacoustic imaging (PAI), beamforming methods can be used to reconstruct the images. Delay-and-sum (DAS) beamformer is extensively used due to its simple implementation. However, this algorithm results in high level of sidelobes and low resolution. In this paper, it is proposed to form the photoacoustic (PA) images through a regularized inverse problem to address these limitations and improve the image quality. We define a forward/backward problem of the beamforming and solve the inverse problem using a sparse constraint added to the model which forces the sparsity of the output beamformed data. It is shown that the proposed Sparse beamforming (SB) method is robust against noise due to the sparsity nature of the problem. Numerical results show that the SB method improves the signal-to-noise ratio (SNR) for about 98.69 dB, 82.26 dB and 74.73 dB, in average, compared to DAS, delay-multiply-and-sum (DMAS) and double stage-DMAS (DS-DMAS), respectively. Also, quantitative evaluation of the experimental results shows a significant noise reduction using SB algorithm. In particular, the contrast ratio of the wire phantom at the depth of 30 mm is improved about 103.97 dB, 82.16 dB and 65.77 dB compared to DAS, DMAS and DS-DMAS algorithms, respectively, indicating a better performance of the proposed SB in terms of noise reduction.

1064 nm acoustic resolution photoacoustic microscopy.

Photoacoustic imaging is a noninvasive imaging technique having the advantages of high-optical contrast and good acoustic resolution at improved imaging depths. Light transport in biological tissues is mainly characterized by strong optical scattering and absorption. Photoacoustic microscopy is capable of achieving high-resolution images at greater depth compared to conventional optical microscopy methods. In this work, we have developed a high-resolution, acoustic resolution photoacoustic microscopy (AR-PAM) system in the near infra-red (NIR) window II (NIR-II, eg, 1064 nm) for deep tissue imaging. Higher imaging depth is achieved as the tissue scattering at 1064 nm is lesser compared to visible or near infrared window-I (NIR-I). Our developed system can provide a lateral resolution of 130 µm, axial resolution of 57 µm, and image up to 11 mm deep in biological tissues. This 1064-AR-PAM system was used for imaging sentinel lymph node and the lymph vessel in rat. Urinary bladder of rat filled with black ink was also imaged to validate the feasibility of the developed system to study deeply seated organs.

Validation of delay-multiply-and-standard-deviation weighting factor for improved photoacoustic imaging of sentinel lymph node.

Delay-and-sum (DAS) is one of the most common algorithms used to construct the photoacoustic images due to its low complexity. However, it results in images with high sidelobes and low resolution. Delay-and-standard-deviation (DASD) weighting factor can improve the contrast of the images compared to DAS. However, it still suffers from high sidelobes. In this work, a new weighting factor, named delay-multiply-and-standard-deviation (DMASD) is introduced to enhance the contrast of the reconstructed images compared to other mentioned methods. In the proposed method, the SD of the mutual multiplied delayed signals are calculated, normalized and multiplied to DAS beamformed data. The results show that DMASD improves the signal-to-noise-ratio about 19.29 and 7.3 dB compared to DAS and DASD, respectively, for in vivo imaging of the sentinel lymph node. Moreover, the contrast ratio is improved by the DMASD about 23.61 and 10.81 dB compared to DAS and DASD, respectively.

Efficient nonlinear beamformer based on P'th root of detected signals for linear-array photoacoustic tomography: application to sentinel lymph node imaging.

In linear-array transducer-based photoacoustic (PA) imaging, B-scan PA images are formed using the raw channel PA signals. Delay-and-sum (DAS) is the most prevalent algorithm due to its simple implementation, but it leads to low-quality images. Delay-multiply-and-sum (DMAS) provides a higher image quality in comparison with DAS while it imposes a computational burden of O ( M2 ) . We introduce a nonlinear (NL) beamformer for linear-array PA imaging, which uses the p'th root of the detected signals and imposes the complexity of DAS [O ( M ) ]. The proposed algorithm is evaluated numerically and experimentally [wire-target and in-vivo sentinel lymph node (SLN) imaging], and the effects of the parameter p are investigated. The results show that the NL algorithm, using a root of p (NL_p), leads to lower sidelobes and higher signal-to-noise ratio compared with DAS and DMAS, for (p > 2). The sidelobes level (for the wire-target phantom), at the depth of 11.4 mm, are about -31, -52, -52, -67, -88, and -109 dB, for DAS, DMAS, NL_2, NL_3, NL_4, and NL_5, respectively, indicating the superiority of the NL_p algorithm. In addition, the best value of p for SLN imaging is reported to be 12.

Hand-held, clinical dual mode ultrasound - photoacoustic imaging of rat urinary bladder and its applications.

Urinary bladder imaging is critical to diagnose urinary tract disorders, and bladder cancer. There is a great need for safe, non-invasive, and sensitive imaging technique which enables bladder imaging. Photoacoustic imaging is a rapidly growing imaging technique for various biological applications. It can be combined with clinical ultrasound imaging system for hand-held, dual modal ultrasound-photoacoustic real-time imaging. Structural (bladder wall) and functional (accretion of nanoparticles) bladder imaging is shown here with combined ultrasound and photoacoustic imaging in rats. Photoacoustic images of bladder wall is shown using black ink as the contrast agent. Chicken tissues were stacked on the abdomen of the animal to demonstrate the feasibility of photoacoustic imaging till a depth of 2 cm. Also, the feasibility of photoacoustic imaging for a common bladder disorder, vesicoureteral reflux is studied using urinary tract mimicking phantom. It is also shown that a clinical ultrasound system can be used for photoacoustic imaging of non-invasive clearance study of gold nanorods from circulation by monitoring the gradual accumulation of the gold nanorods in the bladder. The time taken for accumulation of nanorods in the bladder can be used as an indicator of the clearance rate of the nanoparticle circulation from the body.

Non-invasive sentinel lymph node mapping and needle guidance using clinical handheld photoacoustic imaging system in small animal.

Translating photoacoustic imaging (PAI) into clinical setup is a challenge. Handheld clinical real-time PAI systems are not common. In this work, we report an integrated photoacoustic (PA) and clinical ultrasound imaging system by combining light delivery with the ultrasound probe for sentinel lymph node imaging and needle guidance in small animal. The open access clinical ultrasound platform allows seamless integration of PAI resulting in the development of handheld real-time PAI probe. Both methylene blue and indocyanine green were used for mapping the sentinel lymph node using 675 and 690 nm wavelength illuminations, respectively. Additionally, needle guidance with combined ultrasound and PAI was demonstrated using this imaging system. Up to 1.5 cm imaging depth was observed with a 10 Hz laser at an imaging frame rate of 5 frames per second, which is sufficient for future translation into human sentinel lymph node imaging and needle guidance for fine needle aspiration biopsy.

Hand-held Clinical Photoacoustic Imaging System for Real-time Non-invasive Small Animal Imaging.

Translation of photoacoustic imaging into the clinic is a major challenge. Handheld real-time clinical photoacoustic imaging systems are very rare. Here, we report a combined photoacoustic and clinical ultrasound imaging system by integrating an ultrasound probe with light delivery for small animal imaging. We demonstrate this by showing sentinel lymph node imaging in small animals along with minimally invasive real-time needle guidance. A clinical ultrasound platform with access to raw channel data allows the integration of photoacoustic imaging leading to a handheld real-time clinical photoacoustic imaging system. Methylene blue was used for sentinel lymph node imaging at 675 nm wavelength. Additionally, needle guidance with dual modal ultrasound and photoacoustic imaging was shown using the imaging system. Depth imaging of up to 1.5 cm was demonstrated with a 10 Hz laser at a photoacoustic imaging frame rate of 5 frames per second.

Advances in Monte Carlo Simulation for Light Propagation in Tissue.

Monte Carlo (MC) simulation for light propagation in tissue is the gold standard for studying the light propagation in biological tissue and has been used for years. Interaction of photons with a medium is simulated based on its optical properties. New simulation geometries, tissue-light interaction methods, and recording techniques recently have been designed. Applications, such as whole mouse body simulations for fluorescence imaging, eye modeling for blood vessel imaging, skin modeling for terahertz imaging, and human head modeling for sinus imaging, have emerged. Here, we review the technical advances and recent applications of MC simulation.

A High-performance Compact Photoacoustic Tomography System for In Vivo Small-animal Brain Imaging.

In vivo small-animal imaging has an important role to play in preclinical studies. Photoacoustic tomography (PAT) is an emerging hybrid imaging modality that shows great potential for both preclinical and clinical applications. Conventional optical parametric oscillator-based PAT (OPO-PAT) systems are bulky and expensive and cannot provide high-speed imaging. Recently, pulsed-laser diodes (PLDs) have been successfully demonstrated as an alternative excitation source for PAT. Pulsed-laser diode PAT (PLD-PAT) has been successfully demonstrated for high-speed imaging on photoacoustic phantoms and biological tissues. This work provides a visualized experimental protocol for in vivo brain imaging using PLD-PAT. The protocol includes the compact PLD-PAT system configuration and its description, animal preparation for brain imaging, and a typical experimental procedure for 2D cross-sectional rat brain imaging. The PLD-PAT system is compact and cost-effective and can provide high-speed, high-quality imaging. Brain images collected in vivo at various scan speeds are presented.

Optimizing light delivery through fiber bundle in photoacoustic imaging with clinical ultrasound system: Monte Carlo simulation and experimental validation.

Translating photoacoustic (PA) imaging into clinical setup is a challenge. We report an integrated PA and ultrasound imaging system by combining the light delivery to the tissue with the ultrasound probe. First, Monte Carlo simulations were run to study the variation in absorbance within tissue for different angles of illumination, fiber-to-probe distance (FPD), and fiber-to-tissue distance (FTD). This is followed by simulation for different depths of the embedded sphere (object of interest). Several probe holders were designed for different light launching angles. Phantoms were developed to mimic a sentinel lymph node imaging scenario. It was observed that, for shallower imaging depths, the variation in signal-to-noise ratio (SNR) values could be as high as 100% depending on the angle of illumination at a fixed FPD and FTD. Results confirm that different light illumination angles are required for different imaging depths to get the highest SNR PA images. The results also validate that one can use Monte Carlo simulation as a tool to optimize the probe holder design depending on the imaging needs. This eliminates a trial-and-error approach generally used for designing a probe holder.

Importance sampling-based Monte Carlo simulation of time-domain optical coherence tomography with embedded objects.

Monte Carlo simulation for light propagation in biological tissue is widely used to study light-tissue interaction. Simulation for optical coherence tomography (OCT) studies requires handling of embedded objects of various shapes. In this work, time-domain OCT simulations for multilayered tissue with embedded objects (such as sphere, cylinder, ellipsoid, and cuboid) was done. Improved importance sampling (IS) was implemented for the proposed OCT simulation for faster speed. At first, IS was validated against standard and angular biased Monte Carlo methods for OCT. Both class I and class II photons were in agreement in all the three methods. However, the IS method had more than tenfold improvement in terms of simulation time. Next, B-scan images were obtained for four types of embedded objects. All the four shapes are clearly visible from the B-scan OCT images. With the improved IS B-scan OCT images of embedded objects can be obtained with reasonable simulation time using a standard desktop computer. User-friendly, C-based, Monte Carlo simulation for tissue layers with embedded objects for OCT (MCEO-OCT) will be very useful for time-domain OCT simulations in many biological applications.

Monte Carlo simulation of light transport in turbid medium with embedded object--spherical, cylindrical, ellipsoidal, or cuboidal objects embedded within multilayered tissues.

Monte Carlo modeling of light transport in multilayered tissue (MCML) is modified to incorporate objects of various shapes (sphere, ellipsoid, cylinder, or cuboid) with a refractive-index mismatched boundary. These geometries would be useful for modeling lymph nodes, tumors, blood vessels, capillaries, bones, the head, and other body parts. Mesh-based Monte Carlo (MMC) has also been used to compare the results from the MCML with embedded objects (MCML-EO). Our simulation assumes a realistic tissue model and can also handle the transmission/reflection at the object-tissue boundary due to the mismatch of the refractive index. Simulation of MCML-EO takes a few seconds, whereas MMC takes nearly an hour for the same geometry and optical properties. Contour plots of fluence distribution from MCML-EO and MMC correlate well. This study assists one to decide on the tool to use for modeling light propagation in biological tissue with objects of regular shapes embedded in it. For irregular inhomogeneity in the model (tissue), MMC has to be used. If the embedded objects (inhomogeneity) are of regular geometry (shapes), then MCML-EO is a better option, as simulations like Raman scattering, fluorescent imaging, and optical coherence tomography are currently possible only with MCML.

Monte Carlo simulation of light transport in tissue for optimizing light delivery in photoacoustic imaging of the sentinel lymph node.

Noninvasive or minimally invasive identification of sentinel lymph node (SLN) is essential to reduce the surgical effects of SLN biopsy. Photoacoustic (PA) imaging of SLN in animal models has shown its promise for clinical use in the future. Here, we present a Monte Carlo simulation for light transport in the SLN for various light delivery configurations with a clinical ultrasound probe. Our simulation assumes a realistic tissue layer model and also can handle the transmission/reflectance at SLN-tissue boundary due to the mismatch of refractive index. Various light incidence angles show that for deeply situated SLNs the maximum absorption of light in the SLN is for normal incidence. We also show that if a part of the diffused reflected photons is reflected back into the skin using a reflector, the absorption of light in the SLN can be increased significantly to enhance the PA signal.