Pressure-enhanced sensing of tissue oxygenation via endogenous porphyrin: Implications for dynamic visualization of cancer in surgery.

Fluorescence guidance is routinely used in surgery to enhance perfusion contrast in multiple types of diseases. Pressure-enhanced sensing of tissue oxygenation (PRESTO) via fluorescence is a technique extensively analyzed here, that uses an FDA-approved human precursor molecule, 5-aminolevulinic acid (ALA), to stimulate a unique delayed fluorescence signal that is representative of tissue hypoxia. The ALA precontrast agent is metabolized in most tissues into a red fluorescent molecule, protoporphyrin IX (PpIX), which has both prompt fluorescence, indicative of the concentration, and a delayed fluorescence, that is amplified in low tissue oxygen situations. Applied pressure from palpation induces transient capillary stasis and a resulting transient PRESTO contrast, dominant when there is near hypoxia. This study examined the kinetics and behavior of this effect in both normal and tumor tissues, with a prolonged high PRESTO contrast (contrast to background of 7.3) across 5 tumor models, due to sluggish capillaries and inhibited vasodynamics. This tissue function imaging approach is a fundamentally unique tool for real-time palpation-induced tissue response in vivo, relevant for chronic hypoxia, such as vascular diseases or oncologic surgery.

Integrating Learning-based Priors with Physics-based Models in Ultrasound Elasticity Reconstruction.

Ultrasound elastography images which enable quantitative visualization of tissue stiffness can be reconstructed by solving an inverse problem. Classical model-based methods are usually formulated in terms of constrained optimization problems. To stabilize the elasticity reconstructions, regularization techniques such as Tikhonov method are used with the cost of promoting smoothness and blurriness in the reconstructed images. Thus, incorporating a suitable regularizer is essential for reducing the elasticity reconstruction artifacts while finding the most suitable one is challenging. In this work, we present a new statistical representation of the physical imaging model which incorporates effective signal-dependent colored noise modeling. Moreover, we develop a learning-based integrated statistical framework which combines a physical model with learning-based priors. We use a dataset of simulated phantoms with various elasticity distributions and geometric patterns to train a denoising regularizer as the learning-based prior. We use fixed-point approaches and variants of gradient descent for solving the integrated optimization task following learning-based plug-and-play (PnP) prior and regularization by denoising (RED) paradigms. Finally, we evaluate the performance of the proposed approaches in terms of relative mean square error (RMSE) with nearly 20% improvement for both piece-wise smooth simulated phantoms and experimental phantoms compared to the classical model-based methods and 12% improvement for both spatially-varying breast-mimicking simulated phantoms and an experimental breast phantom, demonstrating the potential clinical relevance of our work. Moreover, the qualitative comparisons of reconstructed images demonstrate the robust performance of the proposed methods even for complex elasticity structures that might be encountered in clinical settings.

Brain elastography in aging relates to fluid/solid trendlines.

The relatively new tools of brain elastography have established a general trendline for healthy, aging adult humans, whereby the brain's viscoelastic properties 'soften' over many decades. Earlier studies of the aging brain have demonstrated a wide spectrum of changes in morphology and composition towards the later decades of lifespan. This leads to a major question of causal mechanisms: of the many changes documented in structure and composition of the aging brain, which ones drive the long term trendline for viscoelastic properties of grey matter and white matter? The issue is important for illuminating which factors brain elastography is sensitive to, defining its unique role for study of the brain and clinical diagnoses of neurological disease and injury. We address these issues by examining trendlines in aging from our elastography data, also utilizing data from an earlier landmark study of brain composition, and from a biophysics model that captures the multiscale biphasic (fluid/solid) structure of the brain. Taken together, these imply that long term changes in extracellular water in the glymphatic system of the brain along with a decline in the extracellular matrix have a profound effect on the measured viscoelastic properties. Specifically, the trendlines indicate that water tends to replace solid fraction as a function of age, then grey matter stiffness decreases inversely as water fraction squared, whereas white matter stiffness declines inversely as water fraction to the 2/3 power, a behavior consistent with the cylindrical shape of the axons. These unique behaviors point to elastography of the brain as an important macroscopic measure of underlying microscopic structural change, with direct implications for clinical studies of aging, disease, and injury.

2-D Slicewise Waveform Inversion of Sound Speed and Acoustic Attenuation for Ring Array Ultrasound Tomography Based on a Block LU Solver.

Ultrasound tomography is an emerging imaging modality that uses the transmission of ultrasound through tissue to reconstruct images of its mechanical properties. Initially, ray-based methods were used to reconstruct these images, but their inability to account for diffraction often resulted in poor resolution. Waveform inversion overcame this limitation, providing high-resolution images of the tissue. Most clinical implementations, often directed at breast cancer imaging, currently rely on a frequency-domain waveform inversion to reduce computation time. For ring arrays, ray tomography was long considered a necessary step prior to waveform inversion in order to avoid cycle skipping. However, in this paper, we demonstrate that frequency-domain waveform inversion can reliably reconstruct high-resolution images of sound speed and attenuation without relying on ray tomography to provide an initial model. We provide a detailed description of our frequency-domain waveform inversion algorithm with open-source code and data that we make publicly available.