Lindsey C. Drehfal

Analysis of Coherent and Diffuse Scattering Using a Reference Phantom

The estimation of many spectral-based quantitative ultrasound parameters assumes that backscattered echo signals are from a stationary, incoherent scattering process. The accuracy of these assumptions in real tissue can limit the diagnostic value of these parameters and the physical insight about tissue microstructure they can convey. This work presents an empirical decision test to determine the presence of significant coherent contributions to echo signals and whether they are caused by low scatterer number densities or the presence of specular reflectors or scatterers with periodic spacing. This is achieved by computing parameters from echo signals that quantify stationary or nonstationary features related to coherent scattering, and then comparing their values to thresholds determined from a reference material providing diffuse scattering. The paper first presents a number of parameters with demonstrated sensitivity to coherent scattering and describes criteria to select those with the highest sensitivity using simulated and phantom-based echo data. Results showed that the echo amplitude signal-to-noise ratio and the multitaper-generalized spectrum were the parameters with the highest sensitivity to coherent scattering with stationary and nonstationary features, respectively. These parameters were incorporated into the reference-based decision test, which successfully identified regions in simulated and tissue-mimicking phantoms with different incoherent and coherent scattering conditions. When scatterers with periodic organization were detected, the combination of stationary and nonstationary analysis permitted the estimation of the mean spacing below and above the resolution limit imposed by the pulse size. Preliminary applications of this algorithm to human cervical tissue ex vivo showed correspondence between regions of B-mode images showing bright reflectors, tissue interfaces, and hypoechoic regions with regions classified as specular reflectors and low scatterer number density. These results encourage further application of the algorithm to more structurally complex phantoms and tissue.

Quantifying Backscatter Anisotropy Using the Reference Phantom Method

Acoustic properties can be exploited to infer and evaluate tissue microstructure. However, common assumptions are that the medium of interest is homogeneous and isotropic, and that its underlying physical properties cause diffuse scattering. In this paper, we describe how we developed and tested novel parameters designed to address isotropy/anisotropy in backscattered echo signal power in complex biological tissues. Specifically, we explored isotropy/anisotropy in backscattered power in isotropic phantoms (spherical glass beads), an anisotropic phantom (dialysis phantom with rodlike fibers), and an in vivo human tissue with well-described anisotropy (bicep muscle). Our approach uses the reference phantom method to compensate for system transfer and diffraction losses when electronically beamsteering a linear array transducer. We define three parameters to quantify the presence and orientation of anisotropic scatterers, as well as address magnitude of anisotropy. We found that these parameters can detect and sense the degree of anisotropy in backscatter in both phantoms and bicep muscle. Bias of the summary anisotropy parameters, induced through a speed of sound mismatch of sample media and reference phantom, was less than 0.2 dB if the speed of sound was within ±20 m/s of the sample media. In summary, these new parameters may be useful for testing the assumption of isotropy as well as providing more detailed information about the underlying microstructural sources of backscatter in complex biological tissues.

Estimation of Shear Wave Speed in the Rhesus Macaques’ Uterine Cervix

Cervical softness is a critical parameter in pregnancy. Clinically, preterm birth is associated with premature cervical softening and postdates birth is associated with delayed cervical softening. In practice, the assessment of softness is subjective, based on digital examination. Fortunately, objective, quantitative techniques to assess softness, and other parameters associated with microstructural cervical change are emerging. One of these is shear wave speed (SWS) estimation. In principle, this allows objective characterization of stiffness because waves travel more slowly in softer tissue. We are studying SWS in humans and rhesus macaques, the latter in order to accelerate translation from bench to bedside. For the current study, we estimated SWS in ex vivo cervices of rhesus macaques, n=24 nulliparous (never given birth) and n=9 multiparous (delivered at least one baby). Misoprostol (a prostaglandin used to soften human cervices prior to gynecological procedures) was administered to 13 macaques prior to necropsy (nulliparous: 7; multiparous: 6). SWS measurements were made at predetermined locations from the distal to proximal end of the cervix on both the anterior and posterior cervix, with five repeat measures at each location. The intent was to explore macaque cervical microstructure, including biological and spatial variability, to elucidate the similarities and differences between the macaque and the human cervix in order to facilitate future in vivo studies. We found that SWS is dependent on location in the normal nonpregnant macaque cervix, as in the human cervix. Unlike the human cervix, we detected no difference between ripened and unripened rhesus macaque cervix samples, nor nulliparous versus multiparous samples, although we observed a trend toward stiffer tissue in nulliparous samples. We found rhesus macaque cervix to be much stiffer than human, which is important for technique refinement. These findings are useful for guiding study of cervical microstructure in both humans and macaques.

Biological factors affecting shear wave speed measurements in the Rhesus macaque non-pregnant cervix

We are studying shear wave speed (SWS) as a biomarker to detect abnormal cervical softening that could lead to spontaneous preterm birth. Elucidating factors affecting the stiffness of the in vivo non-pregnant (NP) cervix is the first step to understand the pregnant cervix. Animal models with anatomy and physiology akin to humans, such as the Rhesus macaque, can help achieve this task. Here we investigate biological and experimental factors affecting SWS estimates in the in vivo Rhesus macaque NP cervix.

Biological and experimental factors affecting the assessment of cervical softening during pregnancy with shear wave elasticity imaging

Spontaneous preterm birth, the foremost source of neonatal mortality, could potentially be prevented by objectively detecting abnormal changes in the uterine cervix. Shear Wave Elasticity Imaging (SWEI) biomarkers can quantify cervical softening that precedes vaginal delivery. This task can be complicated by biological (i.e., heterogeneity of cervical stiffness and pregnancy history) and experimental confounders (i.e., posture during scanning). Here we investigate how these confounders influence shear wave speed (SWS) as an objective biomarker of cervical softening during pregnancy. We apply SWEI longitudinally in pregnant Rhesus macaques and compare SWS estimates from supine transabdominal (TA) and prone inter-cavitary (IC) approaches.

EP22.12: A multi-biomarker approach to evaluation of the human pregnant cervix using quantitative ultrasound (QUS) imaging biomarkers

Methods: 16 normotensive pregnant women between 24 and 40 weeks gestation with low-risk pregnancy were recruited for this study. The Samsung HS 70A ultrasound system and linear probe (L3-12A) were used by a single operator to identify a longitudinal section of the right carotid artery. A cine loop was recorded while participants were in the semi-recumbent position. CIMT was calculated using an in-built computer semi-automated programme. Measurements were repeated in each participant and the average difference was calculated. Identifying the carotid artery, obtaining a cine loop and automatically calculating IMT typically took less than a minute. No discomfort was reported by the participants. Results: Maternal CIMT values were obtained in all participants. CIMT values ranged from 0.26mm to 0.96mm. The mean difference between repeated CIMT values was 0.007mm. In our cohort CIMT did not change with increasing gestation. Conclusions: This novel semi-automated technique was able to obtain CIMT values in pregnant women rapidly. This technique can be used by a novice operator with limited technical skills and has good reproducibility. This technique may be applicable as a non-invasive bedside test for CIMT in pregnant women between 24-40 weeks gestation.

Changes in cervical stiffness during pregnancy: Preliminary assessment with shear wave elasticity imaging in the rhesus macaque

The stiffness of the uterine cervix changes during pregnancy, significantly softening at term. A pathologically rapid softening can result in preterm birth. Shear Wave Elasticity Imaging (SWEI) methods can be used to track these changes. Difficulties of in vivo human research during pregnancy motivate the study of animal models with anatomy and physiology similar to humans. This work presents preliminary results of the use of SWEI methods to assess cervical stiffness changes during pregnancy in a rhesus macaque non-human primate (NHP) model. Pregnant NHP subjects are being scanned during two consecutive menstrual cycles before pregnancy and five times between weeks 4 to 23 after conception and once two weeks after delivery. Shear waves are remotely induced with an Acoustic Radiation Force Impulse excitation within regions of interest (ROIs) centered in the uterine end of cervix. Shear wave speed (SWS) was quantified with different estimators and at various ROI locations to choose the more consistent and p...

Quantitative ultrasound of the uterine cervix

We are developing methods to objectively describe the acoustic and viscoelastic properties of the in vivo cervix to monitor the structural changes that occur during pregnancy. Clinicians commonly use digital palpation to subjectively judge cervical softness knowing the cervix softens prior to parturition. Premature softening of the cervix is a risk factor for preterm birth which has enormous morbidity and financial consequences. However, this is a challenging tissue for quantitative ultrasound (QUS) investigations because its microstructure is layered and pseudo-aligned within each layer. Also, data are typically acquired with a transducer that is in contact with the outer layer of the cervix, so QUS analysis is necessarily done very close to the transducer surface. To avoid violating assumptions used in QUS algorithm development, we use a prototype transducer that allows us to perform QUS parameter estimation as close as 3mm from the transducer surface. Further, we systematically test for various forms o...