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%.

Inter- and Intra-Operator Variability of Regularized Backscatter Quantitative Ultrasound for the Characterization of Breast Masses.

OBJECTIVES: Here we report on the intra- and inter-operator variability of the backscatter coefficient (BSC) estimated with a new low-variance quantitative ultrasound (QUS) approach applied to breast lesions in vivo. METHODS: Radiofrequency (RF) echo signals were acquired from 29 BIRADS 4 and 5 breast lesions in 2 sequential cohorts following 2 imaging protocols: cohort 1) radial and antiradial views, and cohort 2) short- and long-axis views. Protocol 2 was implemented after retraining and discussion on how to improve reproducibility. Each patient was scanned by at least 2 of 3 radiologists; each performed 3 acquisitions with transducer and patient repositioning in between acquisitions. BSC was estimated using a low-variance QUS approach based on regularization. Intra- and inter-operator variability of the intra-lesion median BSC was evaluated with a multifactorial ANOVA test (P-values) and the intraclass correlation coefficient (ICC). RESULTS: Inter-operator variability was only significant in the first protocol (P < .007); ICCinter = .77 (95% CI .71-.82), indicating good inter-operator agreement. In the second protocol, the inter-operator variability was not significant (P > .05) and agreement was excellent (ICCinter = .92 [.89-.94]). In both protocols, the intra-operator variability was not significant. CONCLUSIONS: Our findings demonstrate the need for standardizing image acquisition protocols for backscatter-based QUS to reduce inter-operator variability and ensure its successful translation to the characterization of suspicious breast masses.

Optimization of Ultrasound Backscatter Spectroscopy to Assess Neurotoxic Effects of Anesthesia in the Newborn Non-human Primate Brain.

Studies in animal models have revealed that long exposures to anesthetics can induce apoptosis in the newborn and young developing brain. These effects have not been confirmed in humans because of the lack of a non-invasive, practical in vivo imaging tool with the ability to detect these changes. Following the successful use of ultrasound backscatter spectroscopy (UBS) to monitor in vivo cell death in breast tumors, we aimed to use UBS to assess the neurotoxicity of the anesthetic sevoflurane (SEVO) in a non-human primate (NHP) model. Sixteen 2- to 7-day-old rhesus macaques were exposed for 5 h to SEVO. Ultrasound scanning was done with a phased array transducer on a clinical ultrasound scanner operated at 10 MHz. Data consisting of 10-15 frames of radiofrequency (RF) echo signals from coronal views of the thalamus were obtained 0.5 and 6.0 h after initiating exposure. The UBS parameter "effective scatterer size" (ESS) was estimated by fitting a scattering form factor (FF) model to the FF measured from RF echo signals. The approach involved analyzing the frequency dependence of the measured FF to characterize scattering sources and selecting the FF model based on a χ2 goodness-of-fit criterion. To assess data quality, a rigorous acceptance criterion based on the analysis of prevalence of diffuse scattering (an assumption in the estimation of ESS) was established. ESS changes after exposure to SEVO were compared with changes in a control group of five primates for which ultrasound data were acquired at 0 and 10 min (no apoptosis expected). Over the entire data set, the average measured FF at 0.5 and 6.0 h monotonically decreased with frequency, justifying fitting a single FF over the analysis bandwidth. χ2 values of a (inhomogeneous continuum) Gaussian FF model were one-fifth those of the discrete fluid sphere model, suggesting that a continuum scatterer model better represents ultrasound scattering in the young rhesus brain. After application of the data quality criterion, only 5 of 16 subjects from the apoptotic group and 5 of 5 subjects from the control group fulfilled the acceptance criteria. All subjects in the apoptotic group that passed the acceptance criterion exhibited a significant ESS reduction at 6.0 h. These changes (-6.4%, 95% Interquartile Range: -14.3% to -3.3%) were larger than those in the control group (-0.8%, 95% Interquartile Range: -2.0% to 1.5%]). Data with a low prevalence of diffuse scattering corresponded to possibly biased results. Thus, ESS has the potential to detect changes in brain microstructure related to anesthesia-induced apoptosis.

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.