Relationship between transmission/reception conditions of high-frequency plane wave compounding and evaluation accuracy of extended amplitude envelope statistics.

The double-Nakagami (DN) model provides a method for analyzing the amplitude envelope statistics of quantitative ultrasound (QUS). In this study, the relationship between the sound field characteristics and the robustness of QUS evaluation was evaluated using five HF linear array probes and tissue-mimicking phantoms. Compound plane-wave imaging (CPWI) was used to acquire echo data. Five phantoms containing two types of scatterers were used to mimic fatty liver tissue. After clarifying the relationship between the sound field characteristics of the probes and QUS parameters, DN QUS parameters in 10 rat livers with different lipidification were evaluated using one HF linear array probe. For both phantom and in situ liver analyses, correlations between fat content and multiple QUS parameters were confirmed, suggesting that the combination of CPWI using a HF linear array probe with the DN model is a robust method for quantifying fatty liver and has potential clinical diagnostic applications.

In-vivo high-frequency quantitative ultrasound-derived parameters of the anterior sclera correlated with level of myopia and presence of staphyloma.

BACKGROUND: A high-frequency point-of-care (POC) ultrasound instrument was used to evaluate the microstructural and biomechanical properties of the anterior sclera in vivo using parameters computed from quantitative ultrasound (QUS) methods. METHODS: In this cross-sectional study, both eyes of 85 enrolled patients were scanned with the POC instrument and ultrasound data were processed to obtain QUS parameters. Pearson correlation and multi-linear regression were used to identify relationships between QUS parameters and refractive error (RE) or axial length. After categorising eyes based on RE, binary support vector machine (SVM) classifiers were trained using the QUS or ophthalmic parameters (anterior chamber depth, central corneal thickness, corneal power, and intraocular pressure) to classify each eye. Classifier performance was evaluated by computing the area under the receiver-operating characteristic curve (AUC). RESULTS: Individual QUS parameters correlated with RE and axial length (p < 0.05). Multi-linear regression revealed significant correlation between the set of QUS parameters and both RE (R = 0.49, p < 0.001) and axial length (R = 0.46, p = 0.001). Classifiers trained with QUS parameters achieved higher AUC (𝑝 = 0.06) for identifying myopic eyes (AUC = 0.71) compared to classifiers trained with ophthalmic parameters (AUC = 0.63). QUS-based classifiers attained the highest AUC when identifying highly myopic eyes (AUC = 0.77). CONCLUSIONS: QUS parameters correlate with progressing myopia and may be indicative of myopia-induced microstructural and biomechanical changes in the anterior sclera. These methods may provide critical clinical information complementary to standard ophthalmic measurements for predicting myopia progression and risk assessment for posterior staphyloma formation.

A magnetic phantom technique for investigating structural effects on quantitative ultrasound parameters.

Media that contain ultrasound scatterers arranged in a regular spatial distribution can be considered as structured. Structural effects affect quantitative ultrasound parameters that reflect the microstructure properties. Prior studies examined structural effects using simulations or phantoms with fixed microarchitecture, focusing on a limited set of ultrasound parameters, with limited attention given to their underlying physical significance. This study aims to investigate the concordance of the physical interpretations of multiple quantitative ultrasound parameters experimentally by introducing a phantom type with an adjustable microarchitecture. The phantom consists of an aqueous solution containing superparamagnetic microspheres, acting as scatterers. The spatial arrangement of the magnetic particles is modified by applying an external magnetic field, therefore changing the degree of structure of the phantom. Quantitative ultrasound parameters are estimated in three different configurations: the magnetic field intensity is varied over time, strength, and orientation. In each experiment, the backscatter coefficient and the envelope quantitative ultrasound parameters are successfully extracted (R2 ≈ 0.94). Their physical interpretations are supported by microphotographs and geometrical considerations through concordant hypotheses. This study paves the way for the use of magnetic phantoms. This methodology could be followed to validate theoretical scattering models and the physical meanings of quantitative ultrasound parameters.

RECURRENT FLOATERS AFTER LIMITED VITRECTOMY FOR VISION DEGRADING MYODESOPSIA.

PURPOSE: Limited vitrectomy improves vision degrading myodesopsia, but the incidence of recurrent floaters postoperatively is not known. We studied patients with recurrent central floaters using ultrasonography and contrast sensitivity (CS) testing to characterize this subgroup and identify the clinical profile of patients at risk of recurrent floaters. METHODS: A total of 286 eyes (203 patients, 60.6 ± 12.9 years) undergoing limited vitrectomy for vision degrading myodesopsia were studied retrospectively. Sutureless 25G vitrectomy was performed without intentional surgical posterior vitreous detachment (PVD) induction. CS (Freiburg Acuity Contrast test: Weber index, %W) and vitreous echodensity (quantitative ultrasonography) were assessed prospectively. RESULTS: No eyes (0/179) with preoperative PVD experienced new floaters. Recurrent central floaters occurred in 14/99 eyes (14.1%) without complete preoperative PVD (mean follow-up = 39 months vs. 31 months in 85 eyes without recurrent floaters). Ultrasonography identified new-onset PVD in all 14 (100%) recurrent cases. Young (younger than 52 years; 71.4%), myopic (≥-3D; 85.7%), phakic (100%) men (92.9%) predominated. Reoperation was elected by 11 patients, who had partial PVD preoperatively in 5/11 (45.5%). At study entry, CS was degraded (3.55 ± 1.79 %W) but improved postoperatively by 45.6% (1.93 ± 0.86 %W, P = 0.033), while vitreous echodensity reduced by 86.6% ( P = 0.016). New-onset PVD postoperatively degraded CS anew, by 49.4% (3.28 ± 0.96 %W; P = 0.009) in patients electing reoperation. Repeat vitrectomy normalized CS to 2.00 ± 0.74%W ( P = 0.018). CONCLUSION: Recurrent floaters after limited vitrectomy for vision degrading myodesopsia are caused by new-onset PVD, with younger age, male sex, myopia, and phakic status as risk factors. Inducing surgical PVD at the primary operation should be considered in these select patients to mitigate recurrent floaters.

High-frequency ultrasound point-of-care device to quantify myopia-induced microstructural changes in the anterior sclera.

PURPOSE: To develop a point-of-care (POC) device using high-frequency ultrasound (US) for evaluating microstructural changes in the anterior sclera associated with myopia. METHODS: The proposed POC device must satisfy four primary requirements for effective clinical use: the measurement component is handheld; the software must be simple and provide real-time feedback; patient safety and health data security requirements set forth by relevant governing bodies must be satisfied and the measurement data must have sufficient signal-to-noise ratio (SNR) and repeatability. Radiofrequency (RF) echo data acquired by the POC device will be processed using our quantitative US methods to characterise tissue microstructure and biomechanical properties. RESULTS: All stated requirements have been met in the developed POC device. The high-frequency transducer is housed in a custom, 3D-printed, pen-like holder that allows for easy measurements of the anterior sclera. Custom software provides a simple interface for data acquisition, real-time data display and secure data storage. Exposimetry measurements of the US pressure field indicate device compliance with United States Food and Drug Administration limits for ophthalmic US. In vivo measurements on a volunteer suggest the RF data SNR and acquisition consistency are suitable for quantitative analysis. CONCLUSIONS: A fully functioning POC device using high-frequency US has been created for evaluating the microstructure of the anterior sclera. Planned studies using the POC device to scan the eyes of myopia patients will help clarify how the anterior sclera microstructure may be affected by myopia. If effective, this portable, inexpensive and user-friendly system could be an important part of routine eye examinations.

Advanced Topics in Quantitative Acoustic Microscopy.

Quantitative acoustic microscopy (QAM) reconstructs two-dimensional (2D) maps of the acoustic properties of thin tissue sections. Using ultrahigh frequency transducers (≥ 100 MHz), unstained, micron-thick tissue sections affixed to glass are raster scanned to collect radiofrequency (RF) echo data and generate parametric maps with resolution approximately equal to the ultrasound wavelength. 2D maps of speed of sound, mass density, acoustic impedance, bulk modulus, and acoustic attenuation provide unique and quantitative information that is complementary to typical optical microscopy modalities. Consequently, many biomedical researchers have great interest in utilizing QAM instruments to investigate the acoustic and biomechanical properties of tissues at the micron scale. Unfortunately, current state-of-the-art QAM technology is costly, requires operation by a trained user, and is accompanied by substantial experimental challenges, many of which become more onerous as the transducer frequency is increased. In this chapter, typical QAM technology and standard image formation methods are reviewed. Then, novel experimental and signal processing approaches are presented with the specific goal of reducing QAM instrument costs and improving ease of use. These methods rely on modern techniques based on compressed sensing and sparsity-based deconvolution methods. Together, these approaches could serve as the basis of the next generation of QAM instruments that are affordable and provide high-resolution QAM images with turnkey solutions requiring nearly no training to operate.

Biomechanical changes in myopic sclera correlate with underlying changes in microstructure.

Myopia alters the microstructural and biomechanical properties of the posterior sclera, which is characterized as a layered structure with potentially different inter-layer collagen fibril characteristics. Scanning acoustic microscopy (SAM) has been used to investigate how the micron-scale bulk mechanical properties of the posterior sclera are affected by myopia. Other investigators have employed second harmonic generation (SHG) imaging to characterize the collagen microstructure of tissues. In the present study, SAM and SHG imaging were used to investigate the existence of biomechanically-distinct scleral layers and identify relationships between mechanical properties and tissue microstructure in myopic guinea pig (GP) eyes. Diffusers were worn over the right eyes of six, 1-week-old GPs for one week to induce unilateral form-deprivation myopia. GPs were euthanized, enucleated, and eyes were cryosectioned. Twelve-micron-thick adjacent vertical cryosections were scanned with SAM or SHG. SAM maps of bulk modulus, mass density, and acoustic attenuation were estimated. A fiber-extraction algorithm applied to SHG images estimated collagen fiber length, width, straightness, alignment, and number density. Results revealed that the posterior sclera may exhibit biomechanically distinct layers that are affected differently in myopia. Specifically, a layered structure was observed in the mechanical-parameter maps of control eyes that was less apparent in myopic eyes. Collagen fibers in myopic eyes had smaller diameters and were more aligned. Myopia-associated biomechanical changes were most significant in the outermost and innermost scleral layers. SAM-measured mechanical parameters were correlated with collagen fiber microstructure, particularly fiber length, alignment, and number density, which may imply the biomechanical parameters estimated from SAM measurements are related to tissue microstructure. Interestingly, some changes were greatest in more-peripheral regions, suggesting interventions to strengthen the sclera may be effective away from the optic nerve and efficacy may be achieved best when intervention is applied to the outermost layer.

In vivo assessment of pulmonary fibrosis and edema in rodents using the backscatter coefficient and envelope statistics.

Quantitative ultrasound methods based on the backscatter coefficient (BSC) and envelope statistics have been used to quantify disease in a wide variety of tissues, such as prostate, lymph nodes, breast, and thyroid. However, to date, these methods have not been investigated in the lung. In this study, lung properties were quantified by BSC and envelope statistical parameters in normal, fibrotic, and edematous rat lungs in vivo. The average and standard deviation of each parameter were calculated for each lung as well as the evolution of each parameter with acoustic propagation time within the lung. The transport mean free path and backscattered frequency shift, two parameters that have been successfully used to assess pulmonary fibrosis and edema in prior work, were evaluated in combination with the BSC and envelope statistical parameters. Multiple BSC and envelope statistical parameters were found to provide contrast between control and diseased lungs. BSC and envelope statistical parameters were also significantly correlated with fibrosis severity using the modified Ashcroft fibrosis score as the histological gold standard. These results demonstrate the potential for BSC and envelope statistical parameters to improve the diagnosis of pulmonary fibrosis and edema as well as monitor pulmonary fibrosis.

Improved evaluation of backscatter characteristics of soft tissue using high-frequency annular array.

Clinical ultrasound is widely used for quantitative diagnosis. To clarify the relationship between anatomical and acoustic properties, high resolution imaging using high-frequency ultrasound (HFU) is required. However, when tissue properties are evaluated using HFU, the depth of field (DOF) is limited. To overcome this problem, an annular array transducer, which has a simple structure and produces high-quality images, is applied to HFU measurement. In previous phantom experiments, we demonstrated that the HFU annular array extends the DOF compared to that of a single-element transducer for quantitative ultrasound (QUS) analysis. Here, we extend that work by applying QUS methods to an ex vivo rat liver. The present study demonstrates that an annular array extends the region and improves the resolution for tissue characterization for an excised healthy rat liver. Amplitude envelope statistics and spectral-based analysis are used as QUS methods.

Quantifying scattering from dense media using two-dimensional impedance maps.

A better understanding of ultrasound scattering in a three-dimensional (3D) medium can provide more accurate methods for ultrasound tissue characterization. The possibility of using two-dimensional impedance maps (2DZMs) based on correlation coefficients has shown promise in the case of isotropic and sparse medium [Luchies and Oelze, J. Acoust. Soc. Am. 139, 1557-1564 (2016)]. The present study investigates the use of 2DZMs in order to quantify 3D scatterer properties of dense media from two-dimensional (2D) histological slices. Two 2DZM approaches were studied: one based on the correlation coefficient and the other based on the 2D Fourier transform of 2DZMs. Both 2DZM approaches consist in estimating the backscatter coefficient (BSC) from several 2DZMs, and then the resulting BSC was fit to the theoretical polydisperse structure factor model to yield 3D scatterer properties. Simulation studies were performed to evaluate the ability of both 2DZM approaches to quantify scattering of a 3D medium containing randomly distributed polydisperse spheres or monodisperse ellipsoids. Experimental studies were also performed using the histology photomicrographs obtained from HT29 cell pellet phantoms. Results demonstrate that the 2DZM Fourier transform-based approach was more suitable than the correlation coefficient-based approach for estimating scatterer properties when using a small number of 2DZMs.

Assessment of Vitreous Structure and Visual Function after Neodymium:Yttrium-Aluminum-Garnet Laser Vitreolysis.

PURPOSE: Neodymium:yttrium-aluminum-garnet (Nd:YAG) laser treatment is performed on vitreous floaters, but studies of structural and functional effects with objective outcome measures are lacking. This study evaluated Nd:YAG laser effects by comparing participants with vitreous floaters who previously underwent laser treatment with untreated control participants and healthy persons without vitreous floaters using quantitative ultrasonography to evaluate vitreous structure and by measuring visual acuity and contrast sensitivity function to assess vision. DESIGN: Retrospective, comparative study. PARTICIPANTS: One eye was enrolled for each of 132 participants: 35 control participants without vitreous floaters, 59 participants with untreated vitreous floaters, and 38 participants with vitreous floaters previously Nd:YAG-treated. Of these, 25 were dissatisfied and sought vitrectomy; 13 were satisfied with observation. METHODS: The 39-item National Eye Institute Visual Function Questionnaire (NEI-VFQ-39) to assess participant visual well-being, quantitative ultrasonography (QUS) to measure vitreous echodensity, and best-corrected visual acuity (BCVA) and contrast sensitivity function (CSF) to evaluate vision. MAIN OUTCOME MEASURES: Results of NEI-VFQ-39, QUS, BCVA, and CSF. RESULTS: Compared with control participants without vitreous floaters, participants with untreated vitreous floaters showed worse NEI-VFQ-39 results, 57% greater vitreous echodensity, and significant (130%) CSF degradation (P < 0.001 for each). Compared with untreated eyes with vitreous floaters, Nd:YAG-treated eyes had 23% less vitreous echodensity (P < 0.001), but no differences in NEI-VFQ-39 (P = 0.51), BCVA (P = 0.42), and CSF (P = 0.17) results. Of 38 participants with vitreous floaters who previously were treated with Nd:YAG, 25 were dissatisfied and seeking vitrectomy, whereas 13 were satisfied with observation. Participants seeking vitrectomy showed 24% greater vitreous echodensity (P = 0.018) and 52% worse CSF (P = 0.006). Multivariate linear regression models confirmed these findings. CONCLUSIONS: As a group, participants previously treated with Nd:YAG laser for bothersome vitreous floaters showed less dense vitreous, but similar visual function as untreated control participants with vitreous floaters. Because some treated eyes showed less dense vitreous and better visual function than those of untreated control participants, a prospective randomized study of Nd:YAG laser treatment of vitreous is warranted, using uniform laser treatment parameters and objective quantitative outcome measures.

Regional changes in the elastic properties of myopic Guinea pig sclera.

Biomechanical changes in the sclera likely underlie the excessive eye elongation of axial myopia. We studied the biomechanical characteristics of myopic sclera at the microscopic level using scanning acoustic microscopy (SAM) with 7-µm in-plane resolution. Guinea pigs underwent form-deprivation (FD) in one eye from 4 to 12 days of age to induce myopia, and 12-µm-thick scleral cryosections were scanned using a custom-made SAM. Two-dimensional maps of the bulk modulus (K) and mass density (ρ) were derived from the SAM data using a frequency-domain approach. We assessed the effect on K and ρ exerted by: 1) level of induced myopia, 2) region (superior, inferior, nasal or temporal) and 3) eccentricity from the nerve using univariate and multivariate regression analyses. Induced myopia ranged between -3D and -9.3D (Mean intraocular difference of -6.2 ±â€¯1.7D, N = 11). K decreased by 0.036 GPa for every 1.0 D increase in induced myopia across vertical sections (p < 0.001). Among induced myopia right eyes, K values in the inherently more myopic superior region were 0.088 GPa less than the inferior region (p = 0.002) and K in the proximal nasal region containing the central axis were 0.10 GPa less than temporal K (p = 0.036). K also increased 0.12 GPa for every 1 mm increase in superior vertical distance (p < 0.001), an effect that was blunted after 1 week of FD. Overall, trends for ρ were less apparent than for K. ρ values increased by 20.7 mg/cm3 for every 1.00 D increase in induced myopia across horizontal sections (p < 0.001), and were greatest in the region containing the central posterior pole. ρ values in the inherently more myopic superior region were 13.1 mg/cm3 greater than that found in inferior regions among control eyes (p = 0.002), and increased by 11.2 mg/cm3 for every 1 mm increase in vertical distance (p = 0.001). This peripheral increase in ρ was blunted after 1 week of FD. Scleral material properties vary depending on the location in the sclera and the level of induced myopia. Bulk modulus was most reduced in the most myopic regions (both induced myopia and inherent regional myopia), and suggests that FD causes microscopic local decreases in sclera stiffness, while scleral mass density was most increased in the most myopic regions.

Comprehensive backscattering characteristics analysis for quantitative ultrasound with an annular array: a basic study on homogeneous scattering phantom.

High-frequency ultrasound (HFU, >20 MHz) and quantitative ultrasound (QUS) methods permit a means to understand the relationship between anatomical and acoustic characteristics. In our previous research, we showed that analyzing the acoustic scattering with HFU was an effective method for noninvasive diagnosis. However, the depth of field (DOF) of HFU transducers was limited, which constrains the range of QUS analysis. In this study, we seek to improve the accuracy of HFU, QUS-based parameters on the envelope statistics and frequency-based analysis by using an annular array that allows for an extended DOF. A 20-MHz annular-array transducer with five elements was employed to obtain signals which were beamformed in post-processing. Two kinds of low concentration scattering phantoms were scanned with 30-µm step size. Two QUS analysis techniques were employed: the Nakagami distribution and the reflector method. The results demonstrated that the annular array provides a stable analysis over an extended axial range.

Regular chondrocyte spacing is a potential cause for coherent ultrasound backscatter in human articular cartilage.

The potential of quantitative ultrasound (QUS) to assess the regular cellular spacing in the superficial cartilage zones was investigated experimentally and numerically. Nine osteochondral samples, extracted from two human cadaver knee joints, were measured using a 50-MHz ultrasound scanning device and evaluated using Mankin score. Simulated backscattered power spectra from models with an idealized cell alignment exhibited a pronounced frequency peak. From the peak, cell spacing in the range between 15 and 40 µm between cell layers was detected with an average error of 0.2 µm. The mean QUS-based cell spacing was 28.3 ± 5.3 µm. Strong correlation (R2 = 0.59, p ≤ 0.001) between spacing estimates from light microscopy (LM) and QUS was found for samples with Mankin score ≤3. For higher scores, QUS-based spacing was significantly higher (p ≤ 0.05) compared to LM-based spacing. QUS-based spacing estimates together with other QUS parameters may serve as future biomarkers for detecting early signs of osteoarthrosis.

Material Properties of Human Ocular Tissue at 7-µm Resolution.

Quantitative assessment of the material properties of ocular tissues can provide valuable information for investigating several ophthalmic diseases. Quantitative acoustic microscopy (QAM) offers a means of obtaining such information, but few QAM investigations have been conducted on human ocular tissue. We imaged the optic nerve (ON) and iridocorneal angle in 12-µm deparaffinized sections of the human eye using a custom-built acoustic microscope with a 250-MHz transducer (7-µm lateral resolution). The two-dimensional QAM maps of ultrasound attenuation (α), speed of sound ( c), acoustic impedance ( Z), bulk modulus ( K), and mass density (ρ) were generated. Scanned samples were then stained and imaged by light microscopy for comparison with QAM maps. The spatial resolution and contrast of scanning acoustic microscopy (SAM) maps were sufficient to resolve anatomic layers of the retina (Re); anatomic features in SAM maps corresponded to those seen by light microscopy. Significant variations of the acoustic parameters were found. For example, the sclera was 220 MPa stiffer than Re, choroid, and ON tissue. To the authors' knowledge, this is the first systematic study to assess c, Z, K, ρ, and α of human ocular tissue at the high ultrasound frequencies used in this study.

Speed of sound in diseased liver observed by scanning acoustic microscopy with 80 MHz and 250 MHz.

In this study, the speed of sound (SOS) of two types of rat livers (eight normal livers, four cirrhotic livers) was measured with a scanning acoustic microscope using two transducers, one of which had an 80-MHz and the other a 250-MHz center frequency. The 250-MHz transducer had a better spatial resolution adapted to studying fiber or hepatic parenchymal cells. In normal livers, averages of the SOS values were from 1598 to 1677 m/s at 80-MHz and from 1568 to 1668 m/s at 250-MHz. In the fiber tissue of cirrhotic livers, averages of the SOS values were from 1645 to 1658 m/s at 80-MHz and from 1610 to 1695 m/s at 250-MHz, while the SOS values in the other tissue of cirrhotic livers ranged from 1644 to 1709 m/s at 80-MHz and from 1641 to 1715 m/s at 250-MHz. In one liver, SOS in fiber tissue was larger than that of tissues without fiber while in others it was lower. The resulting two-dimensional SOS maps provide a unique quantitative insight of liver acoustic microstructures in a healthy liver and in a cirrhotic ones. This study would be helpful to understand the complex relationship between acoustic properties and liver disease including fiber tissue.

Coherence-Weighted Synthetic Focusing Applied to Photoacoustic Imaging Using a High-Frequency Annular-Array Transducer.

This paper presents an adaptive synthetic-focusing scheme that, when applied to photoacoustic (PA) data acquired using an annular array, improves focusing across a greater imaging depth and enhances spatial resolution. The imaging system was based on a 40-MHz, 5-element, annular-array transducer with a focal length of 12 mm and an 800-µm diameter hole through its central element to facilitate coaxial delivery of 532-nm laser. The transducer was raster-scanned to facilitate 3D acquisition of co-registered ultrasound and PA image data. Three synthetic-focusing schemes were compared for obtaining PA A-lines for each scan location: delay-and-sum (DAS), DAS weighted with a coherence factor (DAS + CF), and DAS weighted with a sign-coherence factor (DAS + SCF). Bench-top experiments that used an 80-µm hair were performed to assess the enhancement provided by the two coherence-based schemes. Both coherence-based schemes increased the signal-to-noise ratio by approximately 10 dB. When processed using the DAS-only scheme, the lateral dimension of the hair in a PA image with 20 dB dynamic range was between 300 µm and 1 mm for imaging depth ranging from 8 to 20 mm. In comparison, the DAS + CF scheme resulted in a lateral dimension of 200 to 450 µm over the same range. The DAS + SCF synthetic focusing further improved the smallest-resolvable dimension, which was between 150 and 400 µm over the same range of imaging depth. When used on PA data obtained from a 12-day-old mouse embryo, the DAS + SCF processing improved visualization of neurovasculature.

Fine-resolution maps of acoustic properties at 250 MHz of unstained fixed murine retinal layers.

Ex vivo assessment of microscale tissue biomechanical properties of the mammalian retina could offer insights into diseases such as keratoconus, and macular degeneration. A 250-MHz scanning acoustic microscope (7-µm resolution) has been constructed to derive two-dimensional quantitative maps of attenuation (α), speed of sound (c), acoustic impedance (Z), bulk modulus (B), and mass density ( ρ). The two-dimensional maps were compared to coregistered hematoxylin-and-eosin stained sections. This study is the first to quantitatively assess α, c, Z, B, and ρ of individual retinal layers of mammalian animals at high ultrasound frequencies. Significant differences in these parameters between the layers were demonstrated.

Modeling the envelope statistics of three-dimensional high-frequency ultrasound echo signals from dissected human lymph nodes.

This work investigates the statistics of the envelope of three-dimensional (3D) high-frequency ultrasound (HFU) data acquired from dissected human lymph nodes (LNs). Nine distributions were employed, and their parameters were estimated using the method of moments. The Kolmogorov Smirnov (KS) metric was used to quantitatively compare the fit of each candidate distribution to the experimental envelope distribution. The study indicates that the generalized gamma distribution best models the statistics of the envelope data of the three media encountered: LN parenchyma, fat and phosphate-buffered saline (PBS). Furthermore, the envelope statistics of the LN parenchyma satisfy the pre-Rayleigh condition. In terms of high fitting accuracy and computationally efficient parameter estimation, the gamma distribution is the best choice to model the envelope statistics of LN parenchyma, while, the Weibull distribution is the best choice to model the envelope statistics of fat and PBS. These results will contribute to the development of more-accurate and automatic 3D segmentation of LNs for ultrasonic detection of clinically significant LN metastases.

Improved cancer risk stratification of isoechoic thyroid nodules to reduce unnecessary biopsies using quantitative ultrasound.

Objective: Gray-scale ultrasound (US) is the standard-of-care for evaluating thyroid nodules (TNs). However, the performance is better for the identification of hypoechoic malignant TNs (such as classic papillary thyroid cancer) than isoechoic malignant TNs. Quantitative ultrasound (QUS) utilizes information from raw ultrasonic radiofrequency (RF) echo signal to assess properties of tissue microarchitecture. The purpose of this study is to determine if QUS can improve the cancer risk stratification of isoechoic TNs. Methods: Patients scheduled for TN fine needle biopsy (FNB) were recruited from the Thyroid Health Clinic at Boston Medical Center. B-mode US and RF data (to generate QUS parameters) were collected in 274 TNs (163 isoechoic, 111 hypoechoic). A linear combination of QUS parameters (CQP) was trained and tested for isoechoic [CQP(i)] and hypoechoic [CQP(h)] TNs separately and compared with the performance of conventional B-mode US risk stratification systems. Results: CQP(i) produced an ROC AUC value of 0.937+/- 0.043 compared to a value of 0.717 +/- 0.145 (p >0.05) for the American College of Radiology Thyroid Imaging, Reporting and Data System (ACR TI-RADS) and 0.589 +/- 0.173 (p >0.05) for the American Thyroid Association (ATA) risk stratification system. In this study, CQP(i) avoids unnecessary FNBs in 73% of TNs compared to 55.8% and 11.8% when using ACR TI-RADS and ATA classification system. Conclusion: This data supports that a unique QUS-based classifier may be superior to conventional US stratification systems to evaluate isoechoic TNs for cancer and should be explored further in larger studies.