This paper introduces two real-time elastography techniques based on analytic minimization (AM) of regularized cost functions. The first method (1D AM) produces axial strain and integer lateral displacement, while the second method (2D AM) produces both axial and lateral strains. The cost functions incorporate similarity of radio-frequency (RF) data intensity and displacement continuity, making both AM methods robust to small decorrelations present throughout the image. We also exploit techniques from robust statistics to make the methods resistant to large local decorrelations. We further introduce Kalman filtering for calculating the strain field from the displacement field given by the AM methods. Simulation and phantom experiments show that both methods generate strain images with high SNR, CNR and resolution. Both methods work for strains as high as 10% and run in real-time. We also present in vivo patient trials of ablation monitoring. An implementation of the 2D AM method as well as phantom and clinical RF-data can be downloaded.

This paper introduces a 2-D strain imaging technique based on minimizing a cost function using dynamic programming (DP). The cost function incorporates similarity of echo amplitudes and displacement continuity. Since tissue deformations are smooth, the incorporation of the smoothness into the cost function results in reduced decorrelation noise. As a result, the method generates high-quality strain images of freehand palpation elastography with up to 10% compression, showing that the method is more robust to signal decorrelation (caused by scatterer motion in high axial compression and nonaxial motions of the probe) in comparison to the standard correlation techniques. The method operates in less than 1 s and is thus also potentially suitable for real time elastography.

Background Clinical use of image-guided needle placement robots has lagged behind laboratory-demonstrated robotic capability. Bridging this gap requires reliable and easy-to-use robotic systems.

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Voltage-sensitive dyes (VSDs) are designed to monitor membrane potential by detecting fluorescence changes in response to neuronal or muscle electrical activity. However, fluorescence imaging is limited by depth of penetration and high scattering losses, which leads to low sensitivity in vivo systems for external detection. By contrast, photoacoustic (PA) imaging, an emerging modality, is capable of deep tissue, noninvasive imaging by combining near-infrared light excitation and ultrasound detection. Here, we show that voltage-dependent quenching of dye fluorescence leads to a reciprocal enhancement of PA intensity. We synthesized a near-infrared photoacoustic VSD (PA-VSD), whose PA intensity change is sensitive to membrane potential. In the polarized state, this cyanine-based probe enhances PA intensity while decreasing fluorescence output in a lipid vesicle membrane model. A theoretical model accounts for how the experimental PA intensity change depends on fluorescence and absorbance properties of the dye. These results not only demonstrate PA voltage sensing but also emphasize the interplay of both fluorescence and absorbance properties in the design of optimized PA probes. Together, our results demonstrate PA sensing as a potential new modality for recording and external imaging of electrophysiological and neurochemical events in the brain.

Neurosurgeries to remove pituitary tumors using the endonasal, transsphenoidal approach often incur the risk of patient death caused by injury to the carotid arteries hidden by surrounding sphenoid bone. To avoid this risk, we propose intraoperative photoacoustic vessel visualization with an optical fiber attached to the surgical tool and an external ultrasound transducer placed on the temple. Vessel detection accuracy is limited by acoustic propagation properties, which were investigated with k-Wave simulations. In a two-layer model of temporal bone (3200 m/s sound speed, 1-4 mm thickness) and surrounding tissues, the localization error was ≤2 mm in the tranducer's axial dimension, while temporal bone curvature further degraded target localization. Phantom experiments revealed that multiple image targets (e.g. sphenoid bone and vessels) can be visualized, particularly with coherence-based beamforming, to determine tool-to-vessel proximity despite expected localization errors. In addition, the potential flexibility of the fiber position relative to the transducer and vessel was elucidated.

We conducted a canine study to investigate the in vivo feasibility of photoacoustic imaging for intraoperative updates to brachytherapy treatment plans. A fiber coupled to a 1064-nm Nd:YAG laser was inserted into high-dose-rate brachytherapy needles, which diffused light spherically. These needles were inserted through the perineum into the prostate for interstitial light delivery and the resulting acoustic waves were detected with a transrectal ultrasound probe. Postoperative computed tomography images and ex vivo photoacoustic images confirmed seed locations. Limitations with insufficient light delivery were mitigated with short-lag spatial coherence (SLSC) beamforming, providing a 10-20 dB contrast improvement over delay-and-sum (DAS) beamforming for pulse energies ranging from 6.8 to 10.5 mJ with a fiber-seed distance as large as 9.5 mm. For the same distance and the same range of energy densities, signal-to-noise ratios (SNRs) were similar while the contrast-to-noise ratio (CNR) was higher in SLSC compared to DAS images. Challenges included visualization of signals associated with the interstitial fiber tip and acoustic reverberations between seeds separated by ≤ 2 mm. Results provide insights into the potential for clinical translation to humans.

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.