A Coded Excitation Framework for High SNR Transcranial Ultrasound Imaging.

Robust transcranial ultrasound imaging is difficult due to poor image quality. In particular, low signal-to-noise ratio (SNR) limits sensitivity to blood flow and has hindered clinical translation of transcranial functional ultrasound neuroimaging thus far. In this work, we present a coded excitation framework to increase SNR in transcranial ultrasound without negatively impacting frame rate or image quality. We applied this coded excitation framework in phantom imaging and showed SNR gains as large as 24.78 dB and signal-to-clutter ratio gains as high as 10.66 dB with a 65 bit code. We also analyzed how imaging sequence parameters can impact image quality and showed how coded excitation sequences can be designed to maximize image quality for a given application. In particular, we show that considering the number of active transmit elements and the transmit voltage is critical for coded excitation with long codes. Finally, we applied our coded excitation technique in transcranial imaging of ten adult subjects and showed an average SNR gain of 17.91 ± 0.96 dB without a significant increase in clutter using a 65 bit code. We also performed transcranial power Doppler imaging in three adult subjects and showed contrast and contrast-to-noise ratio improvements of 27.32 ± 8.08 dB and 7.25 ± 1.61 dB, respectively with a 65 bit code. These results show that transcranial functional ultrasound neuroimaging may be possible using coded excitation.

Spatiotemporal Coherence to Quantify Sources of Image Degradation in Ultrasonic Imaging.

Thermal noise and acoustic clutter signals degrade ultrasonic image quality and contribute to unreliable clinical assessment. When both noise and clutter are prevalent, it is difficult to determine which one is a more significant contributor to image degradation because there is no way to separately measure their contributions in vivo. Efforts to improve image quality often rely on an understanding of the type of image degradation at play. To address this, we derived and validated a method to quantify the individual contributions of thermal noise and acoustic clutter to image degradation by leveraging spatial and temporal coherence characteristics. Using Field II simulations, we validated the assumptions of our method, explored strategies for robust implementation, and investigated its accuracy and dynamic range. We further proposed a novel robust approach for estimating spatial lag-one coherence. Using this robust approach, we determined that our method can estimate the signal-to-thermal noise ratio (SNR) and signal-to-clutter ratio (SCR) with high accuracy between SNR levels of -30 to 40 dB and SCR levels of -20 to 15 dB. We further explored imaging parameter requirements with our Field II simulations and determined that SNR and SCR can be estimated accurately with as few as two frames and sixteen channels. Finally, we demonstrate in vivo feasibility in brain imaging and liver imaging, showing that it is possible to overcome the constraints of in vivo motion using high-frame rate M-Mode imaging.

Seeing through the Skin: Photoacoustic Tomography of Skin Vasculature and Beyond.

Skin diseases are the most common human diseases and manifest in distinct structural and functional changes to skin tissue components such as basal cells, vasculature, and pigmentation. Although biopsy is the standard practice for skin disease diagnosis, it is not sufficient to provide in vivo status of the skin and highly depends on the timing of diagnosis. Noninvasive imaging technologies that can provide structural and functional tissue information in real time would be invaluable for skin disease diagnosis and treatment evaluation. Among the modern medical imaging technologies, photoacoustic (PA) tomography (PAT) shows great promise as an emerging optical imaging modality with high spatial resolution, high imaging speed, deep penetration depth, rich contrast, and inherent sensitivity to functional and molecular information. Over the last decade, PAT has undergone an explosion in technical development and biomedical applications. Particularly, PAT has attracted increasing attention in skin disease diagnosis, providing structural, functional, metabolic, molecular, and histological information. In this concise review, we introduce the principles and imaging capability of various PA skin imaging technologies. We highlight the representative applications in the past decade with a focus on imaging skin vasculature and melanoma. We also envision the critical technical developments necessary to further accelerate the translation of PAT technologies to fundamental skin research and clinical impacts.

Effect of Experimental Manipulation of the Orbitofrontal Cortex on Short-Term Markers of Compulsive Behavior: A Theta Burst Stimulation Study.

OBJECTIVE: Compulsive behaviors are a core feature of obsessive-compulsive spectrum disorders but appear across a broad spectrum of psychological conditions. It is thought that compulsions reflect a failure to override habitual behaviors "stamped in" through repeated practice and short-term distress reduction. Animal models suggest a possible causal role of the orbitofrontal cortex (OFC) in compulsive behaviors, but human studies have largely been limited by correlational designs. The goal of this study was to establish the first experimental evidence in humans for a mechanistic model in order to inform further experimental work and the eventual development of novel mechanistic treatments involving synergistic biological-behavioral pairings. METHODS: After a baseline assessment, 69 individuals with compulsive behavior disorders were randomly assigned, in a double-blind, between-subjects design, to receive a single session of one of two active stimulation conditions targeting the left OFC: intermittent theta burst stimulation (iTBS), expected to increase OFC activity, or continuous TBS (cTBS), expected to decrease activity (both conditions, 600 pulses at 110% of target resting motor threshold). In both conditions, brain modulation was paired with a subsequent computer task providing practice in overriding a clinically relevant habit (an overlearned shock avoidance behavior), delivered during the expected window of OFC increase or decrease. Pre- and post-TBS functional MRI assessments were conducted of target engagement and compulsive behaviors performed in response to an idiographically designed stressful laboratory probe. RESULTS: cTBS and iTBS modulated OFC activation in the expected directions. cTBS, relative to iTBS, exhibited a beneficial impact on acute laboratory assessments of compulsive behaviors 90 minutes after TBS. These acute behavioral effects persisted 1 week after cTBS. CONCLUSIONS: Experimental modulation of the OFC, within the behavioral context of habit override training, affected short-term markers of compulsive behavior vulnerability. The findings help delineate a causal translational model, serving as an initial precursor to mechanistic intervention development.

Dual-view acoustic-resolution photoacoustic microscopy with enhanced resolution isotropy.

Acoustic-resolution photoacoustic microscopy (AR-PAM) can provide penetration depths beyond the optical diffusion limit, but its lateral resolution is typically much worse than its axial resolution, resulting in a low-resolution isotropy. We herein present a dual-view AR-PAM (DV-AR-PAM) system that exploits two orthogonally arranged focused ultrasonic transducers. Taking advantage of their complementary acoustic detecting profiles, DV-AR-PAM allows the fusion of the dual-view signals, resulting in an enhancement in the resolution isotropy from 29% to 95% within one imaging plane, as demonstrated by simulation results on densely packed particles and experimental results on a single carbon fiber. The application of this method in vivo revealed distinct microvasculature structures in mouse skin that were previously indistinguishable with single-view detection, demonstrating the potential of DV-AR-PAM for vascular and neurological studies.

Correcting the limited view in optical-resolution photoacoustic microscopy.

Optical-resolution photoacoustic microscopy (OR-PAM) has proven useful for anatomical and functional imaging with high spatial resolutions. However, the coherent signal generation and the desired reflection-mode detection in OR-PAM can result in a limited detectability of features aligned with the acoustic axis (ie, vertical structures). Here, we investigated the limited-view phenomenon in OR-PAM by simulating the generation and propagation of the acoustic pressure waves and determined the key optical parameters affecting the visibility of vertical structures. Proof-of-concept numerical experiments were performed with different illumination angles, optical foci and numerical apertures (NA) of the objective lens. The results collectively show that an NA of 0.3 can readily improve the visibility of vertical structures in a typical reflection-mode OR-PAM system. This conclusion was confirmed by numerical simulations on the cortical blood vessels in a mouse brain and by experiments in a suture-cross phantom and in a mouse brain in vivo.