TY - JOUR
T1 - Optimization of Ultrasound Backscatter Spectroscopy to Assess Neurotoxic Effects of Anesthesia in the Newborn Non-human Primate Brain
AU - Castañeda-Martinez, Laura
AU - Noguchi, Kevin K.
AU - Ikonomidou, Chrysanthy
AU - Zagzebski, James A.
AU - Hall, Timothy J.
AU - Rosado-Mendez, Ivan M.
N1 - Funding Information:
The authors thank Hayley Whitson and Dr. Mohammadreza Kari for helping in data acquisition. The authors are grateful for the technical support from Siemens Ultrasound and for the experimental support of the staff at the Wisconsin National Primate Research Center. Research reported in this publication was supported by National Institutes of Health Grants P51OD011106 to the Wisconsin National Primate Research Center, R01HD072077 and R01HD083001. This work was also supported by the Intellectual and Developmental Disabilities Research Center at Washington University in St. Louis (NIH/NICHD U54-HD087011) and UNAM-PAPIIT IN107916 and IA104518. The authors are also grateful to the Consejo Nacional de Ciencia y Tecnología of Mexico for SNI-III (M. E. Brandan) assistant support and the graduate studies and international mobility support of L. Castañeda-Martínez (CVU/ Reg. 886959).
Funding Information:
The authors thank Hayley Whitson and Dr. Mohammadreza Kari for helping in data acquisition. The authors are grateful for the technical support from Siemens Ultrasound and for the experimental support of the staff at the Wisconsin National Primate Research Center. Research reported in this publication was supported by National Institutes of Health Grants P51OD011106 to the Wisconsin National Primate Research Center, R01HD072077 and R01HD083001. This work was also supported by the Intellectual and Developmental Disabilities Research Center at Washington University in St. Louis (NIH/NICHD U54-HD087011) and UNAM-PAPIIT IN107916 and IA104518. The authors are also grateful to the Consejo Nacional de Ciencia y Tecnolog?a of Mexico for SNI-III (M. E. Brandan) assistant support and the graduate studies and international mobility support of L. Casta?eda-Mart?nez (CVU/ Reg. 886959). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Last, but not least, we thank the reviewers of this article for the valuable input. T. Hall receives support from the RSNA (through the University of Wisconsin) for his involvement in QIBA leadership. The other authors have no conflict of interest to disclose.
Publisher Copyright:
© 2020 World Federation for Ultrasound in Medicine & Biology
PY - 2020/8
Y1 - 2020/8
N2 - 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.
AB - 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.
KW - Apoptosis
KW - Effective scatterer size
KW - Newborn brain
KW - Quantitative ultrasound
KW - Sevoflurane
KW - Thalamus
UR - http://www.scopus.com/inward/record.url?scp=85085547225&partnerID=8YFLogxK
U2 - 10.1016/j.ultrasmedbio.2020.04.004
DO - 10.1016/j.ultrasmedbio.2020.04.004
M3 - Article
C2 - 32475715
AN - SCOPUS:85085547225
VL - 46
SP - 2044
EP - 2056
JO - Ultrasound in Medicine and Biology
JF - Ultrasound in Medicine and Biology
SN - 0301-5629
IS - 8
ER -