Flexible array transducer for photoacoustic-guided interventions: phantom and ex vivo demonstrations.

Photoacoustic imaging has demonstrated recent promise for surgical guidance, enabling visualization of tool tips during surgical and non-surgical interventions. To receive photoacoustic signals, most conventional transducers are rigid, while a flexible array is able to deform and provide complete contact on surfaces with different geometries. In this work, we present photoacoustic images acquired with a flexible array transducer in multiple concave shapes in phantom and ex vivo bovine liver experiments targeted toward interventional photoacoustic applications. We validate our image reconstruction equations for known sensor geometries with simulated data, and we provide empirical elevation field-of-view, target position, and image quality measurements. The elevation field-of-view was 6.08 mm at a depth of 4 cm and greater than 13 mm at a depth of 5 cm. The target depth agreement with ground truth ranged 98.35-99.69%. The mean lateral and axial target sizes when imaging 600 µm-core-diameter optical fibers inserted within the phantoms ranged 0.98-2.14 mm and 1.61-2.24 mm, respectively. The mean ± one standard deviation of lateral and axial target sizes when surrounded by liver tissue were 1.80±0.48 mm and 2.17±0.24 mm, respectively. Contrast, signal-to-noise, and generalized contrast-to-noise ratios ranged 6.92-24.42 dB, 46.50-67.51 dB, and 0.76-1, respectively, within the elevational field-of-view. Results establish the feasibility of implementing photoacoustic-guided surgery with a flexible array transducer.

Coherence Metrics for Reader-Independent Differentiation of Cystic From Solid Breast Masses in Ultrasound Images.

Traditional breast ultrasound imaging is a low-cost, real-time and portable method to assist with breast cancer screening and diagnosis, with particular benefits for patients with dense breast tissue. We previously demonstrated that incorporating coherence-based beamforming additionally improves the distinction of fluid-filled from solid breast masses, based on qualitative image interpretation by board-certified radiologists. However, variable sensitivity (range: 0.71-1.00 when detecting fluid-filled masses) was achieved by the individual radiologist readers. Therefore, we propose two objective coherence metrics, lag-one coherence (LOC) and coherence length (CL), to quantitatively determine the content of breast masses without requiring reader assessment. Data acquired from 31 breast masses were analyzed. Ideal separation (i.e., 1.00 sensitivity and specificity) was achieved between fluid-filled and solid breast masses based on the mean or median LOC value within each mass. When separated based on mean and median CL values, the sensitivity/specificity decreased to 1.00/0.95 and 0.92/0.89, respectively. The greatest sensitivity and specificity were achieved in dense, rather than non-dense, breast tissue. These results support the introduction of an objective, reader-independent method for automated diagnoses of cystic breast masses.

Erratum: Empirical assessment of laser safety for photoacoustic-guided liver surgeries: erratum.

[This corrects the article on p. 1205 in vol. 12, PMID: 33796347.].

Deep Learning for Ultrasound Image Formation: CUBDL Evaluation Framework and Open Datasets.

Deep learning for ultrasound image formation is rapidly garnering research support and attention, quickly rising as the latest frontier in ultrasound image formation, with much promise to balance both image quality and display speed. Despite this promise, one challenge with identifying optimal solutions is the absence of unified evaluation methods and datasets that are not specific to a single research group. This article introduces the largest known international database of ultrasound channel data and describes the associated evaluation methods that were initially developed for the challenge on ultrasound beamforming with deep learning (CUBDL), which was offered as a component of the 2020 IEEE International Ultrasonics Symposium. We summarize the challenge results and present qualitative and quantitative assessments using both the initially closed CUBDL evaluation test dataset (which was crowd-sourced from multiple groups around the world) and additional in vivo breast ultrasound data contributed after the challenge was completed. As an example quantitative assessment, single plane wave images from the CUBDL Task 1 dataset produced a mean generalized contrast-to-noise ratio (gCNR) of 0.67 and a mean lateral resolution of 0.42 mm when formed with delay-and-sum beamforming, compared with a mean gCNR as high as 0.81 and a mean lateral resolution as low as 0.32 mm when formed with networks submitted by the challenge winners. We also describe contributed CUBDL data that may be used for training of future networks. The compiled database includes a total of 576 image acquisition sequences. We additionally introduce a neural-network-based global sound speed estimator implementation that was necessary to fairly evaluate the results obtained with this international database. The integration of CUBDL evaluation methods, evaluation code, network weights from the challenge winners, and all datasets described herein are publicly available (visit https://cubdl.jhu.edu for details).

Photoacoustic-guided surgery from head to toe [Invited].

Photoacoustic imaging-the combination of optics and acoustics to visualize differences in optical absorption - has recently demonstrated strong viability as a promising method to provide critical guidance of multiple surgeries and procedures. Benefits include its potential to assist with tumor resection, identify hemorrhaged and ablated tissue, visualize metal implants (e.g., needle tips, tool tips, brachytherapy seeds), track catheter tips, and avoid accidental injury to critical subsurface anatomy (e.g., major vessels and nerves hidden by tissue during surgery). These benefits are significant because they reduce surgical error, associated surgery-related complications (e.g., cancer recurrence, paralysis, excessive bleeding), and accidental patient death in the operating room. This invited review covers multiple aspects of the use of photoacoustic imaging to guide both surgical and related non-surgical interventions. Applicable organ systems span structures within the head to contents of the toes, with an eye toward surgical and interventional translation for the benefit of patients and for use in operating rooms and interventional suites worldwide. We additionally include a critical discussion of complete systems and tools needed to maximize the success of surgical and interventional applications of photoacoustic-based technology, spanning light delivery, acoustic detection, and robotic methods. Multiple enabling hardware and software integration components are also discussed, concluding with a summary and future outlook based on the current state of technological developments, recent achievements, and possible new directions.

Photoacoustic-Guided Laparoscopic and Open Hysterectomy Procedures Demonstrated With Human Cadavers.

Hysterectomy (i.e., surgical removal of the uterus) requires severing the main blood supply to the uterus (i.e., the uterine arteries) while preserving the nearby, often overlapping, ureters. In this paper, we investigate dual-wavelength and audiovisual photoacoustic imaging-based approaches to visualize and differentiate the ureter from the uterine artery and to provide the real-time information needed to avoid accidental ureteral injuries during hysterectomies. Dual-wavelength 690/750 nm photoacoustic imaging was implemented during laparoscopic and open hysterectomies performed on human cadavers, with a custom display approach designed to visualize the ureter and uterine artery. The proximity of the surgical tool to the ureter was calculated and conveyed by tracking the surgical tool in photoacoustic images and mapping distance to auditory signals. The dual-wavelength display showed up to 10 dB contrast differences between the ureter and uterine artery at three separation distances (i.e., 4 mm, 5 mm, and 6 mm) during the open hysterectomy. During the laparoscopic hysterectomy, the ureter and uterine artery were visualized in the dual-wavelength image with up to 24 dB contrast differences. Distances between the ureter and the surgical tool ranged from 2.47 to 7.31 mm. These results are promising for the introduction of dual-wavelength photoacoustic imaging to differentiate the ureter from the uterine artery, estimate the position of the ureter relative to a surgical tool tip, map photoacoustic-based distance measurements to auditory signals, and ultimately guide hysterectomy procedures to reduce the risk of accidental ureteral injuries.

Empirical assessment of laser safety for photoacoustic-guided liver surgeries.

Photoacoustic imaging is a promising technique to provide guidance during multiple surgeries and procedures. One challenge with this technique is that major blood vessels in the liver are difficult to differentiate from surrounding tissue within current safety limits, which only exist for human skin and eyes. In this paper, we investigate the safety of raising this limit for liver tissue excited with a 750 nm laser wavelength and approximately 30 mJ laser energy (corresponding to approximately 150 mJ/cm2 fluence). Laparotomies were performed on six swine to empirically investigate potential laser-related liver damage. Laser energy was applied for temporal durations of 1 minute, 10 minutes, and 20 minutes. Lasered liver lobes were excised either immediately after laser application (3 swine) or six weeks after surgery (3 swine). Cell damage was assessed using liver damage blood biomarkers and histopathology analyses of 41 tissue samples total. The biomarkers were generally normal over a 6 week post-surgical in vivo study period. Histopathology revealed no cell death, although additional pathology was present (i.e., hemorrhage, inflammation, fibrosis) due to handling, sample resection, and fibrous adhesions as a result of the laparotomy. These results support a new protocol for studying laser-related liver damage, indicating the potential to raise the safety limit for liver photoacoustic imaging to approximately 150 mJ/cm2 with a laser wavelength of 750 nm and for imaging durations up to 10 minutes without causing cell death. This investigation and protocol may be applied to other tissues and extended to additional wavelengths and energies, which is overall promising for introducing new tissue-specific laser safety limits for photoacoustic-guided surgery.

CohereNet: A Deep Learning Architecture for Ultrasound Spatial Correlation Estimation and Coherence-Based Beamforming.

Deep fully connected networks are often considered "universal approximators" that are capable of learning any function. In this article, we utilize this particular property of deep neural networks (DNNs) to estimate normalized cross correlation as a function of spatial lag (i.e., spatial coherence functions) for applications in coherence-based beamforming, specifically short-lag spatial coherence (SLSC) beamforming. We detail the composition, assess the performance, and evaluate the computational efficiency of CohereNet, our custom fully connected DNN, which was trained to estimate the spatial coherence functions of in vivo breast data from 18 unique patients. CohereNet performance was evaluated on in vivo breast data from three additional patients who were not included during training, as well as data from in vivo liver and tissue mimicking phantoms scanned with a variety of ultrasound transducer array geometries and two different ultrasound systems. The mean correlation between the SLSC images computed on a central processing unit (CPU) and the corresponding DNN SLSC images created with CohereNet was 0.93 across the entire test set. The DNN SLSC approach was up to 3.4 times faster than the CPU SLSC approach, with similar computational speed, less variability in computational times, and improved image quality compared with a graphical processing unit (GPU)-based SLSC approach. These results are promising for the application of deep learning to estimate correlation functions derived from ultrasound data in multiple areas of ultrasound imaging and beamforming (e.g., speckle tracking, elastography, and blood flow estimation), possibly replacing GPU-based approaches in low-power, remote, and synchronization-dependent applications.

Coherence-Based Beamforming Increases the Diagnostic Certainty of Distinguishing Fluid from Solid Masses in Breast Ultrasound Exams.

Ultrasound is often used as a supplement for mammography to detect breast cancer. However, one known limitation is the high false-positive rates associated with breast ultrasound. We investigated the use of coherence-based beamforming (which directly displays spatial coherence) as a supplement to standard ultrasound B-mode images in 25 patients recommended for biopsy (26 masses in total), with the eventual goal of decreasing false-positive rates. Because of the coherent signal present within solid masses, coherence-based beamforming methods allow solid and fluid-filled masses to appear significantly different (p < 0.001). When presented to five board-certified radiologists, the inclusion of robust short-lag spatial coherence (R-SLSC) images in the diagnostic pipeline reduced the uncertainty of fluid-filled mass contents from 47.5% to 15.8% and reduced the percentage of fluid-filled masses unnecessarily recommended for biopsy from 43.3% to 13.3%. These results are promising for the potential introduction of R-SLSC (and related coherence-based beamforming methods) into the breast clinic to improve diagnostic certainty and reduce the number of unnecessary biopsies.

In Vivo Demonstration of Photoacoustic Image Guidance and Robotic Visual Servoing for Cardiac Catheter-Based Interventions.

Cardiac interventional procedures are often performed under fluoroscopic guidance, exposing both the patient and operators to ionizing radiation. To reduce this risk of radiation exposure, we are exploring the use of photoacoustic imaging paired with robotic visual servoing for cardiac catheter visualization and surgical guidance. A cardiac catheterization procedure was performed on two in vivo swine after inserting an optical fiber into the cardiac catheter to produce photoacoustic signals from the tip of the fiber-catheter pair. A combination of photoacoustic imaging and robotic visual servoing was employed to visualize and maintain constant sight of the catheter tip in order to guide the catheter through the femoral or jugular vein, toward the heart. Fluoroscopy provided initial ground truth estimates for 1D validation of the catheter tip positions, and these estimates were refined using a 3D electromagnetic-based cardiac mapping system as the ground truth. The 1D and 3D root mean square errors ranged 0.25-2.28 mm and 1.24-1.54 mm, respectively. The catheter tip was additionally visualized at three locations within the heart: (1) inside the right atrium, (2) in contact with the right ventricular outflow tract, and (3) inside the right ventricle. Lasered regions of cardiac tissue were resected for histopathological analysis, which revealed no laser-related tissue damage, despite the use of 2.98 mJ per pulse at the fiber tip (379.2 mJ/cm2 fluence). In addition, there was a 19 dB difference in photoacoustic signal contrast when visualizing the catheter tip pre- and post-endocardial tissue contact, which is promising for contact confirmation during cardiac interventional procedures (e.g., cardiac radiofrequency ablation). These results are additionally promising for the use of photoacoustic imaging to guide cardiac interventions by providing depth information and enhanced visualization of catheter tip locations within blood vessels and within the beating heart.

In vivo photoacoustic imaging of major blood vessels in the pancreas and liver during surgery.

Abdominal surgeries carry considerable risk of gastrointestinal and intra-abdominal hemorrhage, which could possibly cause patient death. Photoacoustic imaging is one solution to overcome this challenge by providing visualization of major blood vessels during surgery. We investigate the feasibility of in vivo blood vessel visualization for photoacoustic-guided liver and pancreas surgeries. In vivo photoacoustic imaging of major blood vessels in these two abdominal organs was successfully achieved after a laparotomy was performed on two swine. Three-dimensional photoacoustic imaging with a robot-controlled ultrasound (US) probe and color Doppler imaging were used to confirm vessel locations. Blood vessels in the in vivo liver were visualized with energies of 20 to 40 mJ, resulting in 10 to 15 dB vessel contrast. Similarly, an energy of 36 mJ was sufficient to visualize vessels in the pancreas with up to 17.3 dB contrast. We observed that photoacoustic signals were more focused when the light source encountered a major vessel in the liver. This observation can be used to distinguish major blood vessels in the image plane from the more diffuse signals associated with smaller blood vessels in the surrounding tissue. A postsurgery histopathological analysis was performed on resected pancreatic and liver tissues to explore possible laser-related damage. Results are generally promising for photoacoustic-guided abdominal surgery when the US probe is fixed and the light source is used to interrogate the surgical workspace. These findings are additionally applicable to other procedures that may benefit from photoacoustic-guided interventional imaging of the liver and pancreas (e.g., biopsy and guidance of radiofrequency ablation lesions in the liver).

Robust Short-Lag Spatial Coherence Imaging of Breast Ultrasound Data: Initial Clinical Results.

Ultrasound is frequently used in conjunction with mammography in order to detect breast cancer as early as possible. However, due largely to the heterogeneity of breast tissue, ultrasound images are plagued with clutter that obstructs important diagnostic features. Short-lag spatial coherence (SLSC) imaging has proven to be effective at clutter reduction in noisy ultrasound images. M -Weighted SLSC and Robust-SLSC (R-SLSC) imaging were recently introduced to further improve image quality at higher lag values, while R-SLSC imaging has the added benefit of enabling the adjustment of tissue texture to produce a tissue signal-to-noise ratio (SNR) that is quantitatively similar to B-mode speckle SNR. This paper investigates the initial application of SLSC, M -Weighted SLSC, and R-SLSC imaging to nine targets in the female breast [two simple cysts, one complicated cyst, two fibroadenomas, one hematoma, one complex cystic and solid mass, one invasive ductal carcinoma (IDC), and one ductal carcinoma in situ (DCIS)]. As expected, R-SLSC beamforming improves cyst and hematoma contrast by up to 6.35 and 1.55 dB, respectively, when compared to the original B-mode image, and similar improvements are achieved with SLSC and M -Weighted SLSC imaging. However, an interesting finding from this initial investigation is that the solid masses (i.e., fibroadenoma, complex cystic and solid mass, IDC, and DCIS), which appear as hypoechoic in the B-mode image, have similarly high coherence to that of surrounding tissue in coherence-based images. This work holds promise for using SLSC, M -Weighted SLSC, and/or R-SLSC imaging to distinguish between fluid-filled and solid hypoechoic breast masses.