Equilibrium Mechanical Properties of the Nonhuman Primate Cervix.

Cervical remodeling is critical for a healthy pregnancy. Premature tissue changes can lead to preterm birth (PTB), and the absence of remodeling can lead to post-term birth, causing significant morbidity. Comprehensive characterization of cervical material properties is necessary to uncover the mechanisms behind abnormal cervical softening. Quantifying cervical material properties during gestation is challenging in humans. Thus, a nonhuman primate (NHP) model is employed for this study. In this study, cervical tissue samples were collected from Rhesus macaques before pregnancy and at three gestational time points. Indentation and tension mechanical tests were conducted, coupled with digital image correlation (DIC), constitutive material modeling, and inverse finite element analysis (IFEA) to characterize the equilibrium material response of the macaque cervix during pregnancy. Results show, as gestation progresses: (1) the cervical fiber network becomes more extensible (nonpregnant versus pregnant locking stretch: 2.03 ± 1.09 versus 2.99 ± 1.39) and less stiff (nonpregnant versus pregnant initial stiffness: 272 ± 252 kPa versus 43 ± 43 kPa); (2) the ground substance compressibility does not change much (nonpregnant versus pregnant bulk modulus: 1.37 ± 0.82 kPa versus 2.81 ± 2.81 kPa); (3) fiber network dispersion increases, moving from aligned to randomly oriented (nonpregnant versus pregnant concentration coefficient: 1.03 ± 0.46 versus 0.50 ± 0.20); and (4) the largest change in fiber stiffness and dispersion happen during the second trimester. These results, for the first time, reveal the remodeling process of a nonhuman primate cervix and its distinct regimes throughout the entire pregnancy.

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.

US Quantification of Liver Fat: Past, Present, and Future.

Fatty liver disease has a high and increasing prevalence worldwide, is associated with adverse cardiovascular events and higher long-term medical costs, and may lead to liver-related morbidity and mortality. There is an urgent need for accurate, reproducible, accessible, and noninvasive techniques appropriate for detecting and quantifying liver fat in the general population and for monitoring treatment response in at-risk patients. CT may play a potential role in opportunistic screening, and MRI proton-density fat fraction provides high accuracy for liver fat quantification; however, these imaging modalities may not be suited for widespread screening and surveillance, given the high global prevalence. US, a safe and widely available modality, is well positioned as a screening and surveillance tool. Although well-established qualitative signs of liver fat perform well in moderate and severe steatosis, these signs are less reliable for grading mild steatosis and are likely unreliable for detecting subtle changes over time. New and emerging quantitative biomarkers of liver fat, such as those based on standardized measurements of attenuation, backscatter, and speed of sound, hold promise. Evolving techniques such as multiparametric modeling, radiofrequency envelope analysis, and artificial intelligence-based tools are also on the horizon. The authors discuss the societal impact of fatty liver disease, summarize the current state of liver fat quantification with CT and MRI, and describe past, currently available, and potential future US-based techniques for evaluating liver fat. For each US-based technique, they describe the concept, measurement method, advantages, and limitations. © RSNA, 2023 Online supplemental material is available for this article. Quiz questions for this article are available through the Online Learning Center.

Comparison of four commercial immunomagnetic separation kits for the detection of Cryptosporidium.

Cryptosporidium spp. are protozoan parasites of significant health importance found in environmental waters globally. Four commercially available Cryptosporidium-specific immunomagnetic separation (IMS) kits used in various water sample matrices were analysed and compared. Beads were characterised by flow cytometry and tested for the recovery efficiencies for oocysts spiked into different matrices: river water sediment, clay sample, and filter backwash sample. Results showed that Dynabeads™ Cryptosporidium and Waterborne Crypto-Grab™ kits contained immunoglobulin IgM antibody-coated beads. In contrast, the BioPoint CryptoBead and the TCS Isolate kits contained immunoglobulin IgG antibody-coated beads. BioPoint CryptoBead was significantly coated with more antibodies and were able to capture oocysts more rapidly compared to the other beads. Recovery efficiencies of Dynabeads™, TCS Isolate® beads, and BioPoint CryptoBead ranged from 55 to 93% when tested against different sample matrices, with BioPoint CryptoBead resulting in the highest at 93% in reagent-grade water and Dynabeads™ at 55%, the lowest against clay samples. The Waterborne beads did not perform well on any samples, with recovery efficiencies ranging from 0 to 8%. Fluorescence microscopy analyses showed that both the IMS method and the sample matrix processed affect the quality of the membranes, with the cleanest samples for microscopy examination observed from BioPoint CryptoBead.

A Geometric Model of Ultrasound Backscatter to Describe Microstructural Anisotropy of Tissue.

Methods to assess ultrasound backscatter anisotropy from clinical array transducers have recently been developed. However, they do not provide information about the anisotropy of microstructural features of the specimens. This work develops a simple geometric model, referred to as the secant model, of backscatter coefficient anisotropy. Specifically, we evaluate anisotropy of the frequency dependence of the backscatter coefficient parameterized in terms of effective scatterer size. We assess the model in phantoms with known scattering sources and in a skeletal muscle, a well-known anisotropic tissue. We demonstrate that the secant model can determine the orientation of the anisotropic scatterers, as well as accurately determining effective scatterer sizes, and it may classify isotropic versus anisotropic scatterers. The secant model may find utility in monitoring disease progression as well as characterizing normal tissue architectures.

Pulse-Echo Quantitative US Biomarkers for Liver Steatosis: Toward Technical Standardization.

Excessive liver fat (steatosis) is now the most common cause of chronic liver disease worldwide and is an independent risk factor for cirrhosis and associated complications. Accurate and clinically useful diagnosis, risk stratification, prognostication, and therapy monitoring require accurate and reliable biomarker measurement at acceptable cost. This article describes a joint effort by the American Institute of Ultrasound in Medicine (AIUM) and the RSNA Quantitative Imaging Biomarkers Alliance (QIBA) to develop standards for clinical and technical validation of quantitative biomarkers for liver steatosis. The AIUM Liver Fat Quantification Task Force provides clinical guidance, while the RSNA QIBA Pulse-Echo Quantitative Ultrasound Biomarker Committee develops methods to measure biomarkers and reduce biomarker variability. In this article, the authors present the clinical need for quantitative imaging biomarkers of liver steatosis, review the current state of various imaging modalities, and describe the technical state of the art for three key liver steatosis pulse-echo quantitative US biomarkers: attenuation coefficient, backscatter coefficient, and speed of sound. Lastly, a perspective on current challenges and recommendations for clinical translation for each biomarker is offered.

Radiological Society of North America/Quantitative Imaging Biomarker Alliance Shear Wave Speed Bias Quantification in Elastic and Viscoelastic Phantoms.

OBJECTIVES: To quantify the bias of shear wave speed (SWS) measurements between different commercial ultrasonic shear elasticity systems and a magnetic resonance elastography (MRE) system in elastic and viscoelastic phantoms. METHODS: Two elastic phantoms, representing healthy through fibrotic liver, were measured with 5 different ultrasound platforms, and 3 viscoelastic phantoms, representing healthy through fibrotic liver tissue, were measured with 12 different ultrasound platforms. Measurements were performed with different systems at different sites, at 3 focal depths, and with different appraisers. The SWS bias across the systems was quantified as a function of the system, site, focal depth, and appraiser. A single MRE research system was also used to characterize these phantoms using discrete frequencies from 60 to 500 Hz. RESULTS: The SWS from different systems had mean difference 95% confidence intervals of ±0.145 m/s (±9.6%) across both elastic phantoms and ± 0.340 m/s (±15.3%) across the viscoelastic phantoms. The focal depth and appraiser were less significant sources of SWS variability than the system and site. Magnetic resonance elastography best matched the ultrasonic SWS in the viscoelastic phantoms using a 140 Hz source but had a - 0.27 ± 0.027-m/s (-12.2% ± 1.2%) bias when using the clinically implemented 60-Hz vibration source. CONCLUSIONS: Shear wave speed reconstruction across different manufacturer systems is more consistent in elastic than viscoelastic phantoms, with a mean difference bias of < ±10% in all cases. Magnetic resonance elastographic measurements in the elastic and viscoelastic phantoms best match the ultrasound systems with a 140-Hz excitation but have a significant negative bias operating at 60 Hz. This study establishes a foundation for meaningful comparison of SWS measurements made with different platforms.

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.

Three-dimensional Ultrasound Elasticity Imaging on an Automated Breast Volume Scanning System.

Ultrasound elasticity imaging has demonstrated utility in breast imaging, but it is typically performed with handheld transducers and two-dimensional imaging. Two-dimensional (2D) elastography images tissue stiffness of only a plane and hence suffers from errors due to out-of-plane motion, whereas three-dimensional (3D) data acquisition and motion tracking can be used to track out-of-plane motion that is lost in 2D elastography systems. A commercially available automated breast volume scanning system that acquires 3D ultrasound data with precisely controlled elevational movement of the 1D array ultrasound transducer was employed in this study. A hybrid guided 3D motion-tracking algorithm was developed that first estimated the displacements in one plane using a modified quality-guided search method, and then performed an elevational guided-search for displacement estimation in adjacent planes. To assess the performance of the method, 3D radiofrequency echo data were acquired with this system from a phantom and from an in vivo human breast. For both experiments, the axial displacement fields were smooth and high cross-correlation coefficients were obtained in most of the tracking region. The motion-tracking performance of the new method was compared with a correlation-based exhaustive-search method. For all motion-tracking volume pairs, the average motion-compensated cross-correlation values obtained by the guided-search motion-tracking method were equivalent to those by the exhaustive-search method, and the computation time was about a factor of 10 lesser. Therefore, the proposed 3D ultrasound elasticity imaging method was a more efficient approach to produce a high quality of 3D ultrasound strain image.

A new paradigm for the role of smooth muscle cells in the human cervix.

BACKGROUND: Premature cervical remodeling resulting in spontaneous preterm birth may begin with premature failure or relaxation at the internal os (termed "funneling"). To date, we do not understand why the internal os fails or why funneling occurs in some cases of premature cervical remodeling. Although the human cervix is thought to be mostly collagen with minimal cellular content, cervical smooth muscle cells are present in the cervix and can cause cervical tissue contractility. OBJECTIVE: To understand why the internal os relaxes or why funneling occurs in some cases of premature cervical remodeling, we sought to evaluate cervical smooth muscle cell content and distribution throughout human cervix and correlate if cervical smooth muscle organization influences regional cervical tissue contractility. STUDY DESIGN: Using institutional review board-approved protocols, nonpregnant women <50 years old undergoing hysterectomy for benign indications were consented. Cervical tissue from the internal and external os were immunostained for smooth muscle cell markers (α-smooth muscle actin, smooth muscle protein 22 calponin) and contraction-associated proteins (connexin 43, cyclooxygenase-2, oxytocin receptor). To evaluate cervical smooth muscle cell morphology throughout the entire cervix, whole cervical slices were obtained from the internal os, midcervix, and external os and immunostained with smooth muscle actin. To correlate tissue structure with function, whole slices from the internal and external os were stimulated to contract with 1 µmol/L of oxytocin in organ baths. In separate samples, we tested if the cervix responds to a common tocolytic, nifedipine. Cervical slices from the internal os were treated with oxytocin alone or oxytocin + increasing doses of nifedipine to generate a dose response and half maximal inhibitory concentration. Student t test was used where appropriate. RESULTS: Cervical tissue was collected from 41 women. Immunohistochemistry showed cervical smooth muscle cells at the internal and external os expressed mature smooth muscle cell markers and contraction-associated proteins. The cervix exhibited a gradient of cervical smooth muscle cells. The area of the internal os contained 50-60% cervical smooth muscle cells that were circumferentially organized in the periphery of the stroma, which may resemble a sphincter-like pattern. The external os contained approximately 10% cervical smooth muscle cells that were randomly scattered in the tissue. In organ bath studies, oxytocin stimulated the internal os to contract with more than double the force of the external os (1341 ± 693 vs 523 ± 536 integrated grams × seconds, respectively, P = .009). Nifedipine significantly decreased cervical tissue muscle force compared to timed vehicle control (oxytocin alone) at doses of 10(-5) mol/L (vehicle 47% ± 15% vs oxytocin + nifedipine 24% ± 16%, P = .007), 10(-4) mol/L (vehicle 46% ± 16% vs oxytocin + nifedipine -4% ± 20%, P = .003), and 10(-3) mol/L (vehicle 42% ± 14% vs oxytocin + nifedipine -15% ± 18%, P = .0006). The half maximal inhibitory concentration for nifedipine was 1.35 × 10(-5) mol/L. CONCLUSION: Our findings suggest a new paradigm for cervical tissue morphology-one that includes the possibility of a specialized sphincter at the internal os. This new paradigm introduces novel avenues to further investigate potential mechanisms of normal and premature cervical remodeling.

A Tactile Sensor for Ultrasound Imaging Systems.

Medical ultrasound systems are capable of monitoring a variety of health conditions while avoiding invasive procedures. However this function is complicated by ultrasound contrast of the tissue varying with contact pressure exerted by the probe. The knowledge of the contact pressure is beneficial for a variety of screening and diagnostic procedures involving ultrasound. This paper introduces a solid-state sensor array which measures the contact pressure distribution between the probe and the tissue marginally affecting the ultrasound imaging capabilities. The probe design utilizes the dielectrostriction mechanism which relates the change in dielectric properties of the sensing layer to deformation. The concept, structure, fabrication, and performance of this sensor array are discussed. The prototype device is highly tolerant to overloads (>1 MPa tested) and provides stress measurements in the range of 0.14 to 10 kPa. Its loss of ultrasound transmissivity is less 3dB at 9 MHz ultrasound frequency. This performance is satisfactory for clinical and biomedical research in ultrasound image formation and interpretation, however for commercial product, a higher ultrasound transmissivity is desired. Directions for improving the sensor ultrasound transparency and electrical performance are discussed. The sensor array described in this paper has been developed specifically for ultrasound diagnosis during breast cancer screening. However, the same sensing mechanism, similar configuration and sensor array structure can be applied to other applications involving ultrasound tools for medical diagnostics.

Acoustic Properties of Breast Fat.

OBJECTIVES: The American College of Radiology Breast Imaging Reporting and Data System (BI-RADS) atlas for ultrasound (US) qualitatively describes the echogenicity and attenuation of a mass, where fat lobules serve as a standard for comparison. This study aimed to estimate acoustic properties of breast fat under clinical imaging conditions to determine the degree to which properties vary among patients. METHODS: Twenty-four women with solid breast masses scheduled for biopsy were scanned with a Siemens S2000 scanner and 18L6 linear array transducer (Siemens Medical Solutions, Malvern, PA). Offline analysis estimated the attenuation coefficient and backscatter coefficients (BSCs) from breast fat using the reference phantom method. The average BSC was calculated over 6 to 12 MHz to objectively quantify the BI-RADS US echo pattern descriptor, and effective scatterer diameters were also estimated. RESULTS: A power law fit to the attenuation coefficient versus frequency yielded an attenuation coefficient of 1.28 dB·cm(-1) MHz(-0.73). The mean attenuation coefficient versus frequency slope ± SD at 7 MHz was 0.73 ± 0.23 dB·cm(-1) MHz(-1), in agreement with previously reported values. The BSC versus frequency showed close agreement among all patients, both in magnitude and frequency dependence, with a power law fit of (0.6 ± 0.25) ×10(-4) sr(-1) cm(-1) MHz(-2.49). The average backscatter in the 6-12-MHz range was 0.004 ± 0.002 sr(-1) cm(-1). The mean effective scatterer diameter for fat was 60.2 ± 9.5 µm. CONCLUSIONS: The agreement in parameter estimates for breast fat among these patients supports the use of fat as a standard for comparison with tumors. Results also suggest that objective quantification of these BI-RADS US descriptors may reduce subjectivity when interpreting B-mode image data.

Quantitative Ultrasound Comparison of MAT and 4T1 Mammary Tumors in Mice and Rats Across Multiple Imaging Systems.

OBJECTIVES: Quantitative ultrasound estimates such as the frequency-dependent backscatter coefficient (BSC) have the potential to enhance noninvasive tissue characterization and to identify tumors better than traditional B-mode imaging. Thus, investigating system independence of BSC estimates from multiple imaging platforms is important for assessing their capabilities to detect tissue differences. METHODS: Mouse and rat mammary tumor models, 4T1 and MAT, respectively, were used in a comparative experiment using 3 imaging systems (Siemens, Ultrasonix, and VisualSonics) with 5 different transducers covering a range of ultrasonic frequencies. RESULTS: Functional analysis of variance of the MAT and 4T1 BSC-versus-frequency curves revealed statistically significant differences between the two tumor types. Variations also were found among results from different transducers, attributable to frequency range effects. At 3 to 8 MHz, tumor BSC functions using different systems showed no differences between tumor type, but at 10 to 20 MHz, there were differences between 4T1 and MAT tumors. Fitting an average spline model to the combined BSC estimates (3-22 MHz) demonstrated that the BSC differences between tumors increased with increasing frequency, with the greatest separation above 15 MHz. Confining the analysis to larger tumors resulted in better discrimination over a wider bandwidth. CONCLUSIONS: Confining the comparison to higher ultrasonic frequencies or larger tumor sizes allowed for separation of BSC-versus-frequency curves from 4T1 and MAT tumors. These constraints ensure that a greater fraction of the backscattered signals originated from within the tumor, thus demonstrating that statistically significant tumor differences were detected.

Effective scatterer diameter estimates for broad scatterer size distributions.

Acoustic form factors have been used to model the frequency dependence of acoustic scattering in phantoms and tissues. This work demonstrates that a broad range of scatterer sizes, individually well represented by Faran theory or a Gaussian form factor, is not accurately described by a single effective scatterer from either of these models. Contributions from a distribution of discrete scatterer sizes for two different form factor functions (Gaussian form factors and scattering functions from Faran's theory) were calculated and linearly combined. Composite form factors created from Gaussian distributions of scatterer sizes centered at 50 µm with standard deviations of up to σ = 40 µm were fit to each scattering model between 2 and 12 MHz. Scatterer distributions were generated using one of two assumptions: the number density of the scatterer diameter distribution was Gaussian distributed, or the volume fraction of each scatterer diameter in the distribution was Gaussian distributed. Each simulated form factor was fit to a single-diameter form factor model for Gaussian and exponential form factors. The mean-squared error (MSE) between the composite simulated data and the best-fit single-diameter model was smaller with an exponential form factor model, compared with a Gaussian model, for distributions with standard deviations larger than 30% of the centroid value. In addition, exponential models were shown to have better ability to distinguish between Faran scattering model-based distributions with varying center diameters than the Gaussian form factor model. The evidence suggests that when little is known about the scattering medium, an exponential scattering model provides a better first approximation to the scattering correlation function for a broad distribution of spherically symmetric scatterers than when a Gaussian form factor model is assumed.

Two-dimensional simulations of displacement accumulation incorporating shear strain.

Using ultrasound images to track large tissue deformations usually requires breaking up the deformation into steps and then summing the resulting displacement estimates. The accumulated displacement estimation error therefore depends not only on the error in each step but also on the statistical relationships between estimation steps. These relationships have not been thoroughly studied. Building on previous work with one-dimensional (1-D) simulations, the work reported here measured error variance for single-step and accumulated displacement estimates using two-dimensional (2-D) numerical simulations of ultrasound echo signals, subjected to both normal and axial shear strain as well as electronic noise. Previous results from 1-D simulations were confirmed, showing that errors due to electronic noise are negatively correlated between steps and accumulate slowly, while errors due to strain are positively correlated and accumulate quickly. These properties hold for both normal and axial shear strain. An analysis of 2-D kernel size for tissue under normal and axial shear strain was also performed. Under axial shear strain, error variance tends to increase with larger lateral kernel sizes but decrease for larger axial kernel sizes; the opposite relationship holds under normal strain. A combination of these two types of strain limits the practical kernel size in both dimensions.

A Systematized Review of Quantitative Ultrasound Based on First-Order Speckle Statistics.

Since the late 1970s, the speckle interference patterns ubiquitous in pulse-echo ultrasound images have been used to characterize sub-resolution tissue structure. During this time, new models, estimation methods, and processing techniques have proliferated, offering a wealth of recommendations for the task of tissue characterization. A literature review was performed to draw attention to these various methods and to critically track assumptions and gaps in knowledge. A total of 388 articles were collected from a systematic search for first-order speckle statistics in diagnostic ultrasound in the NIH PubMed database and Elsevier's Scopus database. Articles were grouped by basic characteristics and evaluated for addressing fundamental assumptions. A sampling of models and methods is presented in order to reveal the state of the art in speckle statistics as well as sources of measurement error and other important considerations. While this body of literature emphasizes the value of speckle analysis in diagnostic ultrasound, it is shown that relatively little attention is devoted to basic assumptions such as the linearity of system response and scatterer geometry. Additionally, several areas of investigation are available to improve upon speckle statistics analysis, potentially leading to the advancement of this unique tool.

A Force-Matched Approach to Large-Strain Nonlinearity in Elasticity Imaging for Breast Lesion Characterization.

OBJECTIVE: Ultrasound elasticity imaging is a class of ultrasound techniques with applications that include the detection of malignancy in breast lesions. Although elasticity imaging traditionally assumes linear elasticity, the large strain elastic response of soft tissue is known to be nonlinear. This study evaluates the nonlinear response of breast lesions for the characterization of malignancy using force measurement and force-controlled compression during ultrasound imaging. METHODS: 54 patients were recruited for this study. A custom force-instrumented compression device was used to apply a controlled force during ultrasound imaging. Motion tracking derived strain was averaged over lesion or background ROIs and matched with compression force. The resulting force-matched strain was used for subsequent analysis and curve fitting. RESULTS: Greater median differences between malignant and benign lesions were observed at higher compressional forces (p-value < 0.05 for compressional forces of 2-6N). Of three candidate functions, a power law function produced the best fit to the force-matched strain. A statistically significant difference in the scaling parameter of the power function between malignant and benign lesions was observed (p-value = 0.025). CONCLUSIONS: We observed a greater separation in average lesion strain between malignant and benign lesions at large compression forces and demonstrated the characterization of this nonlinear effect using a power law model. Using this model, we were able to differentiate between malignant and benign breast lesions. SIGNIFICANCE: With further development, the proposed method to utilize the nonlinear elastic response of breast tissue has the potential for improving non-invasive lesion characterization for potential malignancy.

Delivering a Quantitative Imaging Agenda.

In a digital image, each voxel contains quantitative information dependent on the technique used to generate the image [...].

A Multimodal Phantom for Visualization and Assessment of Histotripsy Treatments on Ultrasound and X-Ray Imaging.

OBJECTIVE: Histotripsy is an emerging non-invasive, non-ionizing and non-thermal focal tumor therapy. Although histotripsy targeting is currently based on ultrasound (US), other imaging modalities such as cone-beam computed tomography (CBCT) have recently been proposed to enable the treatment of tumors not visible on ultrasound. The objective of this study was to develop and evaluate a multi-modality phantom to facilitate the assessment of histotripsy treatment zones on both US and CBCT imaging. METHODS: Fifteen red blood cell phantoms composed of alternating layers with and without barium were manufactured. Spherical 25-mm histotripsy treatments were performed, and treatment zone size and location were measured on CBCT and ultrasound. Sound speed, impedance and attenuation were measured for each layer type. RESULTS: The average ± standard deviation signed difference between measured treatment diameters was 0.29 ± 1.25 mm. The Euclidean distance between measured treatment centers was 1.68 ± 0.63 mm. The sound speed in the different layers ranged from 1491 to 1514 m/s and was within typically reported soft tissue ranges (1480-1560 m/s). In all phantoms, histotripsy resulted in sharply delineated treatment zones, allowing segmentation in both modalities. CONCLUSION: These phantoms will aid in the development and validation of X-ray-based histotripsy targeting techniques, which promise to expand the scope of treatable lesions beyond only those visible on ultrasound.

Optical coherence tomography of human fetal membrane sub-layers during loading.

Fetal membranes have important mechanical and antimicrobial roles in maintaining pregnancy. However, the small thickness (<800 µm) of fetal membranes places them outside the resolution limits of most ultrasound and magnetic resonance systems. Optical imaging methods like optical coherence tomography (OCT) have the potential to fill this resolution gap. Here, OCT and machine learning methods were developed to characterize the ex vivo properties of human fetal membranes under dynamic loading. A saline inflation test was incorporated into an OCT system, and tests were performed on n = 33 and n = 32 human samples obtained from labored and C-section donors, respectively. Fetal membranes were collected in near-cervical and near-placental locations. Histology, endogenous two photon fluorescence microscopy, and second harmonic generation microscopy were used to identify sources of contrast in OCT images of fetal membranes. A convolutional neural network was trained to automatically segment fetal membrane sub-layers with high accuracy (Dice coefficients >0.8). Intact amniochorion bilayer and separated amnion and chorion were individually loaded, and the amnion layer was identified as the load-bearing layer within intact fetal membranes for both labored and C-section samples, consistent with prior work. Additionally, the rupture pressure and thickness of the amniochorion bilayer from the near-placental region were greater than those of the near-cervical region for labored samples. This location-dependent change in fetal membrane thickness was not attributable to the load-bearing amnion layer. Finally, the initial phase of the loading curve indicates that amniochorion bilayer from the near-cervical region is strain-hardened compared to the near-placental region in labored samples. Overall, these studies fill a gap in our understanding of the structural and mechanical properties of human fetal membranes at high resolution under dynamic loading events.