Simulation of ultrasonic scattering from scatterer size distributions using Field II.

Quantitative analysis of radio frequency (RF) signals obtained from ultrasound scanners can yield objective parameters that are gaining clinical relevance as imaging biomarkers. These include the backscatter coefficient (BSC) and the effective scatterer diameter (ESD). Biomarker validation is typically performed in phantoms which do not provide the flexibility of systematic variation of scattering properties. Computer simulations, such as those from the ultrasound simulator Field II, can allow more flexibility. However, Field II does not allow simulation of RF data from a distribution of scatterers with finite size. In this work, a simulation method is presented which builds upon previous work by including Faran theory models representative of distributions of scatterer size. These are systematically applied to RF data simulated in Field II. The method is validated by measuring the root mean square error of the estimated BSC and percent bias of the ESD and comparing to experimental results. The results indicate the method accurately simulates distributions of scatterer sizes and provides scattering similar to that seen in data from clinical scanners. Because Field II is widely used by the ultrasound community, this method can be adopted to aid in validation of quantitative ultrasound imaging biomarkers.

Quantitative ultrasound and apoptotic death in the neonatal primate brain.

Apoptosis is triggered in the developing mammalian brain by sedative, anesthetic or antiepileptic drugs during late gestation and early life. Whether human children are vulnerable to this toxicity mechanism remains unknown, as there are no imaging techniques to capture it. Apoptosis is characterized by distinct structural features, which affect the way damaged tissue scatters ultrasound compared to healthy tissue. We evaluated whether apoptosis, triggered by the anesthetic sevoflurane in the brains of neonatal rhesus macaques, can be detected using quantitative ultrasound (QUS). Neonatal (n = 15) rhesus macaques underwent 5 h of sevoflurane anesthesia. QUS images were obtained through the sagittal suture at 0.5 and 6 h. Brains were collected at 8 h and examined immunohistochemically to analyze apoptotic neuronal and oligodendroglial death. Significant apoptosis was detected in white and gray matter throughout the brain, including the thalamus. We measured a change in the effective scatterer size (ESS), a QUS biomarker derived from ultrasound echo signals obtained with clinical scanners, after sevoflurane-anesthesia in the thalamus. Although initial inclusion of all measurements did not reveal a significant correlation, when outliers were excluded, the change in the ESS between the pre- and post-anesthesia measurements correlated strongly and proportionally with the severity of apoptotic death. We report for the first time in vivo changes in QUS parameters, which may reflect severity of apoptosis in the brains of infant nonhuman primates. These findings suggest that QUS may enable in vivo studies of apoptosis in the brains of human infants following exposure to anesthetics, antiepileptics and other brain injury mechanisms.

Physics-Inspired Regularized Pulse-Echo Quantitative Ultrasound: Efficient Optimization With ADMM.

Pulse-echo quantitative ultrasound (PEQUS), which estimates the quantitative properties of tissue microstructure, entails estimating the average attenuation and the backscatter coefficient (BSC). Growing recent research has focused on the regularized estimation of these parameters. Herein, we make two contributions to this field: first, we consider the physics of the average attenuation and backscattering to devise regularization terms accordingly. More specifically, since the average attenuation gradually alters in different parts of the tissue, while BSC can vary markedly from tissue to tissue, we apply L2 and L1 norms for the average attenuation and the BSC, respectively. Second, we multiply different frequencies and depths of the power spectra with different weights according to their noise levels. Our rationale is that the high-frequency contents of the power spectra at deep regions have a low signal-to-noise ratio (SNR). We exploit the alternating direction method of multipliers (ADMM) for optimizing the cost function. The qualitative and quantitative evaluations of bias and variance exhibit that our proposed algorithm improves the estimations of the average attenuation and the BSC up to about 100%.