Arc-to-line frame registration method for ultrasound and photoacoustic image-guided intraoperative robot-assisted laparoscopic prostatectomy.

PURPOSE: To achieve effective robot-assisted laparoscopic prostatectomy, the integration of transrectal ultrasound (TRUS) imaging system which is the most widely used imaging modality in prostate imaging is essential. However, manual manipulation of the ultrasound transducer during the procedure will significantly interfere with the surgery. Therefore, we propose an image co-registration algorithm based on a photoacoustic marker (PM) method, where the ultrasound/photoacoustic (US/PA) images can be registered to the endoscopic camera images to ultimately enable the TRUS transducer to automatically track the surgical instrument. METHODS: An optimization-based algorithm is proposed to co-register the images from the two different imaging modalities. The principle of light propagation and an uncertainty in PM detection were assumed in this algorithm to improve the stability and accuracy of the algorithm. The algorithm is validated using the previously developed US/PA image-guided system with a da Vinci surgical robot. RESULTS: The target-registration-error (TRE) is measured to evaluate the proposed algorithm. In both simulation and experimental demonstration, the proposed algorithm achieved a sub-centimeter accuracy which is acceptable in practical clinics (i.e., 1.15 ± 0.29 mm from the experimental evaluation). The result is also comparable with our previous approach (i.e., 1.05 ± 0.37 mm), and the proposed method can be implemented with a normal white light stereo camera and does not require highly accurate localization of the PM. CONCLUSION: The proposed frame registration algorithm enabled a simple yet efficient integration of commercial US/PA imaging system into laparoscopic surgical setting by leveraging the characteristic properties of acoustic wave propagation and laser excitation, contributing to automated US/PA image-guided surgical intervention applications.

Real-time intraoperative surgical guidance system in the da Vinci surgical robot based on transrectal ultrasound/photoacoustic imaging with photoacoustic markers: an ex vivo demonstration.

This paper introduces the first integrated real-time intraoperative surgical guidance system, in which an endoscope camera of da Vinci surgical robot and a transrectal ultrasound (TRUS) transducer are co-registered using photoacoustic markers that are detected in both fluorescence (FL) and photoacoustic (PA) imaging. The co-registered system enables the TRUS transducer to track the laser spot illuminated by a pulsed-laser-diode attached to the surgical instrument, providing both FL and PA images of the surgical region-of-interest (ROI). As a result, the generated photoacoustic marker is visualized and localized in the da Vinci endoscopic FL images, and the corresponding tracking can be conducted by rotating the TRUS transducer to display the PA image of the marker. A quantitative evaluation revealed that the average registration and tracking errors were 0.84 mm and 1.16°, respectively. This study shows that the co-registered photoacoustic marker tracking can be effectively deployed intraoperatively using TRUS+PA imaging providing functional guidance of the surgical ROI.

Automatic search for photoacoustic marker using automated transrectal ultrasound.

Real-time transrectal ultrasound (TRUS) image guidance during robot-assisted laparoscopic radical prostatectomy has the potential to enhance surgery outcomes. Whether conventional or photoacoustic TRUS is used, the robotic system and the TRUS must be registered to each other. Accurate registration can be performed using photoacoustic (PA markers). However, this requires a manual search by an assistant [IEEE Robot. Autom. Lett8, 1287 (2023).10.1109/LRA.2022.3191788]. This paper introduces the first automatic search for PA markers using a transrectal ultrasound robot. This effectively reduces the challenges associated with the da Vinci-TRUS registration. This paper investigated the performance of three search algorithms in simulation and experiment: Weighted Average (WA), Golden Section Search (GSS), and Ternary Search (TS). For validation, a surgical prostate scenario was mimicked and various ex vivo tissues were tested. As a result, the WA algorithm can achieve 0.53°±0.30° average error after 9 data acquisitions, while the TS and GSS algorithm can achieve 0.29∘±0.31∘ and 0.48°±0.32° average errors after 28 data acquisitions.

Laser diode photoacoustic point source detection: machine learning-based denoising and reconstruction.

A new development in photoacoustic (PA) imaging has been the use of compact, portable and low-cost laser diodes (LDs), but LD-based PA imaging suffers from low signal intensity recorded by the conventional transducers. A common method to improve signal strength is temporal averaging, which reduces frame rate and increases laser exposure to patients. To tackle this problem, we propose a deep learning method that will denoise point source PA radio-frequency (RF) data before beamforming with a very few frames, even one. We also present a deep learning method to automatically reconstruct point sources from noisy pre-beamformed data. Finally, we employ a strategy of combined denoising and reconstruction, which can supplement the reconstruction algorithm for very low signal-to-noise ratio inputs.

Synthetic radial aperture focusing to regulate manual volumetric scanning for economic transrectal ultrasound imaging.

In this paper, we present a volumetric transrectal ultrasound (TRUS) imaging under the presence of radial scanning angle disorientation (SAD) in a resource-limited diagnostic setting. Herein, we test our hypothesis that a synthetic radial aperture focusing (TRUS-rSAF) technique, in which a radial plane in target volume is reconstructed by coherent compounding of multiple transmittance/reception events, will reject a randomized SAD in a free-hand scanning setup based on external angular tracking. Based on an analytical model of the TRUS-rSAF technique, we first tested specific scenarios using a clinically available TRUS transducer under different SADs in a range of normal distributions (σ = 0.1°, 0.2°, 0.5°, 1°, 2°, and 5°). We found a benefit of the TRUS-rSAF technique for higher robustness when the SAD is contained within the radial synthetic aperture window, i.e., ±0.71° from a target scanning angle. However, no enhancement was found in spatial resolution because of the limited transmit beam field of the clinical TRUS transducer, limiting the synthetic aperture window. We further evaluated the TRUS-rSAF technique with a modified TRUS transducer for an extended synthetic aperture window to test whether higher spatial resolution and robustness to SAD can be obtained in the same evaluation setup. Widening of the synthetic aperture window (±3.54°, ± 5.91°, ± 8.27°, ± 10.63°, ± 12.99°, ± 15.35°) resulted in proportional enhancements of spatial resolution, but it also progressively built up sidelobe artifacts due to randomized synthesis with limited phase cancellations. The results suggest the need for careful calibration of the TRUS-rSAF technique to enable TRUS imaging with free-hand radial scanning and external angle tracking in resource-limited settings.

Wearable Mechatronic Ultrasound-integrated AR Navigation System for Lumbar Puncture Guidance.

As one of the most commonly performed spinal interventions in routine clinical practice, lumbar punctures are usually done with only hand palpation and trial-and-error. Failures can prolong procedure time and introduce complications such as cerebrospinal fluid leaks and headaches. Therefore, an effective needle insertion guidance method is desired. In this work, we present a complete lumbar puncture guidance system with the integration of (1) a wearable mechatronic ultrasound imaging device, (2) volume-reconstruction and bone surface estimation algorithms and (3) two alternative augmented reality user interfaces for needle guidance, including a HoloLens-based and a tablet-based solution. We conducted a quantitative evaluation of the end-to-end navigation accuracy, which shows that our system can achieve an overall needle navigation accuracy of 2.83 mm and 2.76 mm for the Tablet-based and the HoloLens-based solutions, respectively. In addition, we conducted a preliminary user study to qualitatively evaluate the effectiveness and ergonomics of our system on lumbar phantoms. The results show that users were able to successfully reach the target in an average of 1.12 and 1.14 needle insertion attempts for Tablet-based and HoloLens-based systems, respectively, exhibiting the potential to reduce the failure rates of lumbar puncture procedures with the proposed lumbar-puncture guidance.

A novel design framework of synthetic radial aperture focusing for volumetric transrectal ultrasound imaging.

In this paper, we present a novel design framework of synthetic radial aperture focusing for three-dimensional (3D) transrectal ultrasound imaging (TRUS-rSAF), in which multiple transmittance/reception events at different scanning angles are synthesized to reconstruct a radial plane in the target volume, securing high spatial resolution and texture uniformity. A theory-based design approach has not been available to push the envelope of the 3D rSAF technique. Herein, a closed-form analytical description of the TRUS-rSAF method is presented for the first time, effectively delineating spatial resolution and grating lobe positions in the radial dimension of a TRUS transducer. We demonstrate a solid optimization workflow based on the theoretical foundation to improve its spatiotemporal resolution, grating lobe artifacts, and signal-to-noise ratio. A specific design criterion was considered to outperform a clinical 3D TRUS imaging as a reference (TRUS-REF), where each radial plane is reconstructed with a single transmittance/reception event using a motorized actuator. The optimized TRUS-rSAF method significantly enhanced spatial resolution up to 50% over the TRUS-REF method while providing clinically effective temporal resolution (2-8 volume/sec) with negligible grating lobe artifacts. The results indicate that the proposed design approach would enable a novel TRUS imaging solution in clinics.

System-level optimization in spectroscopic photoacoustic imaging of prostate cancer.

This study presents a system-level optimization of spectroscopic photoacoustic (PA) imaging for prostate cancer (PCa) detection in three folds. First, we present a spectral unmixing model to segregate spectral system error (SSE). We constructed two noise models (NMs) for the laser spectrotemporal fluctuation and the ultrasound system noise. We used these NMs in linear spectral unmixing to denoise and to achieve high temporal resolution. Second, we employed a simulation-aided wavelength optimization to select the most effective subset of wavelengths. NMs again were considered so that selected wavelengths were not only robust to the collinearity of optical absorbance, but also to noise. Third, we quantified the effect of frame averaging on improving spectral unmixing accuracy through theoretical analysis and numerical validation. To validate the whole framework, we performed comprehensive studies in simulation and an in vivo experiment which evaluated prostate-specific membrane antigen (PSMA) expression in PCa on a mice model. Both simulation analysis and in vivo studies confirmed that the proposed framework significantly enhances image signal-to-noise ratio (SNR) and spectral unmixing accuracy. It enabled more sensitive and faster PCa detection. Moreover, the proposed framework can be generalized to other spectroscopic PA imaging studies for noise reduction, wavelength optimization, and higher temporal resolution.

Photoacoustic assessment of the fetal brain and placenta as a method of non-invasive antepartum and intrapartum monitoring.

A noninvasive monitor for concurrent evaluation of placental and fetal sagittal sinus sO 2 for both antepartum surveillance at the late 2nd and 3rd trimesters and intrapartum monitoring would be a great advantage over current methods. A PA fetal brain and placental monitor has potential value to rapidly identify the fetus at risk for developing hypoxia and ischemia of a sufficient degree that brain injury or death may develop, which may be prevented by intervention with delivery and other follow-up treatments.

Transcranial photoacoustic characterization of neurovascular physiology during early-stage photothrombotic stroke in neonatal pigletsin vivo.

OBJECTIVE: Perinatal ischemic stroke is estimated to occur in 1/2300-1/5000 live births, but early differential diagnosis from global hypoxia-ischemia is often difficult. In this study, we tested the ability of a hand-held transcranial photoacoustic (PA) imaging probe to non-invasively detect a focal photothrombotic stroke (PTS) within 2 h of stroke onset in a gyrencephalic piglet brain. APPROACH: About 17 stroke lesions of approximately 1 cm2area were introduced randomly in anterior or posterior cortex via the light/dye PTS technique in anesthetized neonatal piglets (n= 11). The contralateral non-ischemic region served as control tissue for discrimination contrast for the PA hemoglobin metrics: oxygen saturation, total hemoglobin (tHb), and individual quantities of oxygenated and deoxygenated hemoglobin (HbO2and HbR). MAIN RESULTS: The PA-derived tissue oxygen saturation at 2 h yielded a significant separation between control and affected regions-of-interest (p< 0.0001), which were well matched with 24 h post-stroke cerebral infarction confirmed in the triphenyltetrazolium chloride-stained image. The quantity of HbO2also displayed a significant contrast (p= 0.021), whereas tHb and HbR did not. The analysis on receiver operating characteristic curves and multivariate data analysis also agreed with the results above. SIGNIFICANCE: This study shows that a hand-held transcranial PA neuroimaging device can detect a regional thrombotic stroke in the cerebral cortex of a neonatal piglet. In particular, we conclude that the oxygen saturation metric can be used alone to identify regional stroke lesions. The lack of change in tHb may be related to arbitrary hand-held imaging configuration and/or entrapment of red blood cells within the thrombotic stroke.

Dual contrast agents for fluorescence and photoacoustic imaging: evaluation in a murine model of prostate cancer.

Prostate-specific membrane antigen (PSMA) is a promising diagnostic and therapeutic target for prostate cancer (PC). Poly(amidoamine) [PAMAM] dendrimers serve as versatile scaffolds for imaging agents and drug delivery that can be tailored to different sizes and compositions depending upon the application. We have developed PSMA-targeted PAMAM dendrimers for real-time detection of PC using fluorescence (FL) and photoacoustic (PA) imaging. A generation-4, ethylenediamine core, amine-terminated dendrimer was consecutively conjugated with on average 10 lysine-glutamate-urea PSMA targeting moieties and a different number of sulfo-cyanine7.5 (Cy7.5) near-infrared dyes (2, 4, 6 and 8 denoted as conjugates II, III, IV and V, respectively). The remaining terminal primary amines were capped with butane-1,2-diol functionalities. We also prepared a conjugate composed of Cy7.5-lysine-suberic acid-lysine glutamate-urea (I) and control dendrimer conjugate (VI). Among all conjugates, IV showed superior in vivo target specificity in male NOD-SCID mice bearing isogenic PSMA+ PC3 PIP and PSMA- PC3 flu xenografts and suitable physicochemical properties for FL and PA imaging. Such agents may prove useful in PC cancer detection and subsequent surgical guidance during excision of PSMA-expressing lesions.

Real-time, functional intra-operative localization of rat cavernous nerve network using near-infrared cyanine voltage-sensitive dye imaging.

Despite current progress achieved in the surgical technique of radical prostatectomy, post-operative complications such as erectile dysfunction and urinary incontinence persist at high incidence rates. In this paper, we present a methodology for functional intra-operative localization of the cavernous nerve (CN) network for nerve-sparing radical prostatectomy using near-infrared cyanine voltage-sensitive dye (VSD) imaging, which visualizes membrane potential variations in the CN and its branches (CNB) in real time. As a proof-of-concept experiment, we demonstrate a functioning complex nerve network in response to electrical stimulation of the CN, which was clearly differentiated from surrounding tissues in an in vivo rat prostate model. Stimulation of an erection was confirmed by correlative intracavernosal pressure (ICP) monitoring. Within 10 minutes, we performed trans-fascial staining of the CN by direct VSD administration. Our findings suggest the applicability of VSD imaging for real-time, functional imaging guidance during nerve-sparing radical prostatectomy.

An economic photoacoustic imaging platform using automatic laser synchronization and inverse beamforming.

We present a proof-of-concept of an automatic integration of photoacoustic (PA) imaging on clinical ultrasound (US) imaging platforms. Here we tackle two critical challenges: the laser synchronization and the inaccessibility to the beamformer core embedded in commercial US imaging platform. In particular, the line trigger frequency (LTF) estimation and the asynchronous synthetic aperture inverse beamforming (ASAIB) were developed and evaluated in both k-Wave simulation and phantom experiment. The proposed method is an economical solution to enable PA imaging on a greater number of US equipment to further thrive the PA imaging research community.

Transcranial photoacoustic imaging of NMDA-evoked focal circuit dynamics in the rat hippocampus.

OBJECTIVE: We report the transcranial functional photoacoustic (fPA) neuroimaging of N-methyl-D-aspartate (NMDA) evoked neural activity in the rat hippocampus. Concurrent quantitative electroencephalography (qEEG) and microdialysis were used to record real-time circuit dynamics and excitatory neurotransmitter concentrations, respectively. APPROACH: We hypothesized that location-specific fPA voltage-sensitive dye (VSD) contrast would identify neural activity changes in the hippocampus which correlate with NMDA-evoked excitatory neurotransmission. MAIN RESULTS: Transcranial fPA VSD imaging at the contralateral side of the microdialysis probe provided NMDA-evoked VSD responses with positive correlation to extracellular glutamate concentration changes. qEEG validated a wide range of glutamatergic excitation, which culminated in focal seizure activity after a high NMDA dose. We conclude that transcranial fPA VSD imaging can distinguish focal glutamate loads in the rat hippocampus, based on the VSD redistribution mechanism which is sensitive to the electrophysiologic membrane potential. SIGNIFICANCE: Our results suggest the future utility of this emerging technology in both laboratory and clinical sciences as an innovative functional neuroimaging modality.

Transcranial Recording of Electrophysiological Neural Activity in the Rodent Brain in vivo Using Functional Photoacoustic Imaging of Near-Infrared Voltage-Sensitive Dye.

Minimally-invasive monitoring of electrophysiological neural activities in real-time-that enables quantification of neural functions without a need for invasive craniotomy and the longer time constants of fMRI and PET-presents a very challenging yet significant task for neuroimaging. In this paper, we present in vivo functional PA (fPA) imaging of chemoconvulsant rat seizure model with intact scalp using a fluorescence quenching-based cyanine voltage-sensitive dye (VSD) characterized by a lipid vesicle model mimicking different levels of membrane potential variation. The framework also involves use of a near-infrared VSD delivered through the blood-brain barrier (BBB), opened by pharmacological modulation of adenosine receptor signaling. Our normalized time-frequency analysis presented in vivo VSD response in the seizure group significantly distinguishable from those of the control groups at sub-mm spatial resolution. Electroencephalogram (EEG) recording confirmed the changes of severity and frequency of brain activities, induced by chemoconvulsant seizures of the rat brain. The findings demonstrate that the near-infrared fPA VSD imaging is a promising tool for in vivo recording of brain activities through intact scalp, which would pave a way to its future translation in real time human brain imaging.

Phantom with multiple active points for ultrasound calibration.

Accurate tracking and localization of ultrasound (US) images are used in various computer-assisted interventions. US calibration is a preoperative procedure to recover the transformation bridging the tracking sensor and the US image coordinate systems. Although many calibration phantom designs have been proposed, a limitation that hinders the resulted calibration accuracy is US elevational beam thickness. Previous studies have proposed an active-echo (AE)-based calibration concept to overcome this limitation by utilizing dynamic active US feedback from a single PZT element-based phantom, which assists in placing the phantom within the US elevational plane. However, the process of searching elevational midplane is time-consuming and requires dedicated hardware to enable "AE" functionality. Extending this active phantom, we present a US calibration concept and associated mathematical framework enabling fast and accurate US calibration using multiple "active" points. The proposed US calibration can simplify the calibration procedure by minimizing the number of times midplane search is performed and shortening calibration time. This concept is demonstrated with a configuration mechanically tracking a US probe using a robot arm. We validated the concept through simulation and experiment, and achieved submillimeter calibration accuracy. This result indicates that the multiple active-point phantom has potential to provide superior calibration performance for applications requiring high tracking accuracy.

Voltage-sensitive dye delivery through the blood brain barrier using adenosine receptor agonist regadenoson.

Optical imaging of brain activity has mostly employed genetically manipulated mice, which cannot be translated to clinical human usage. Observation of brain activity directly is challenging due to the difficulty in delivering dyes and other agents through the blood brain barrier (BBB). Using fluorescence imaging, we have demonstrated the feasibility of delivering the near-infrared voltage-sensitive dye (VSD) IR-780 perchlorate to the brain tissue through pharmacological techniques, via an adenosine agonist (regadenoson). Comparison of VSD fluorescence of mouse brains without and with regadenoson showed significantly increased residence time of the fluorescence signal in the latter case, indicative of VSD diffusion into the brain tissue. Dose and timing of regadenoson were varied to optimize BBB permeability for VSD delivery.

Correction to: RF-ablation pattern shaping employing switching channels of dual bipolar needle electrodes: ex vivo results.

The original version of this article was published without funding note. The funding note is given below.

Validation of noninvasive photoacoustic measurements of sagittal sinus oxyhemoglobin saturation in hypoxic neonatal piglets.

We hypothesize that noninvasive photoacoustic imaging can accurately measure cerebral venous oxyhemoglobin saturation (So2) in a neonatal model of hypoxia-ischemia. In neonatal piglets, which have a skull thickness comparable to that of human neonates, we compared the photoacoustic measurement of sagittal sinus So2 against that measured directly by blood sampling over a wide range of conditions. Systemic hypoxia was produced by decreasing inspired oxygen stepwise (i.e., 100, 21, 19, 17, 15, 14, 13, 12, 11, and 10%) with and without unilateral or bilateral ligation of the common carotid arteries to enhance hypoxia-ischemia. Transcranial photoacoustic sensing enabled us to detect changes in sagittal sinus O2 saturation throughout the tested range of 5-80% without physiologically relevant bias. Despite lower cortical perfusion and higher oxygen extraction in groups with carotid occlusion at equivalent inspired oxygen, photoacoustic measurements successfully provided a robust linear correlation that approached the line of identity with direct blood sample measurements. Receiver-operating characteristic analysis for discriminating So2 <30% showed an area under the curve of 0.84 for the pooled group data, and 0.87, 0.91, and 0.92 for hypoxia alone, hypoxia plus unilateral occlusion, and hypoxia plus bilateral occlusion subgroups, respectively. The detection precision in this critical range was confirmed with sensitivity (87.0%), specificity (86.5%), accuracy (86.8%), positive predictive value (90.5%), and negative predictive value (81.8%) in the combined dataset. These results validate the capability of photoacoustic sensing technology to accurately monitor sagittal sinus So2 noninvasively over a wide range and support its use for early detection of neonatal hypoxia-ischemia. NEW & NOTEWORTHY We present data to validate the noninvasive photoacoustic measurement of sagittal sinus oxyhemoglobin saturation. In particular, this paper demonstrates the robustness of this methodology during a wide range of hemodynamic and physiological changes induced by the stepwise decrease of fractional inspired oxygen to produce hypoxia and by unilateral and bilateral ligation of the common carotid arteries preceding hypoxia to produce hypoxia-ischemia. This technique may be useful for diagnosing risk of neonatal hypoxic-ischemic encephalopathy.

Correction to: Ultrasound thermal monitoring with an external ultrasound source for customized bipolar RF ablation shapes.

The original article has been published without article note.