Integrated Backscatter Coefficient Research Articles

Ultrasonic Characterization of Human Scalp.

The ultrasonic properties of scalp may be relevant to a variety of applications including transcranial ultrasound. However, there is no information about the ultrasonic properties of scalp available in the literature. While ultrasonic studies of skin from other anatomic regions have been previously reported, scalp tissue is generally thicker with a higher density of hair follicles, blood vessels and sebaceous glands. Thus, it is unknown if the ultrasonic properties of scalp are similar to skin from other regions. The goal of this study was to measure the ultrasonic properties of human scalp. Pulse-echo measurements were performed with a 7.5 MHz ultrasound transducer to determine the speed of sound (SOS), frequency slope of attenuation (FSA) and integrated backscatter coefficient (IBC) of 32 specimens of formalin-fixed human scalp from four donors. The means ± standard deviations for these three ultrasonic quantities measured in the frequency range 2.83-7.74 MHz over all specimens were SOS=1525 ± 16.92 m/s, FSA=2.59 ± 0.724 dB/cm/MHz and IBC=0.122 ± 0.0746 cm-1 Sr-1. These values are comparable to reported values for human skin from other parts of the body, but some differences in SOS and IBC exist.

Amplitude modulation excitation for cancellous bone evaluation using a portable ultrasonic backscatter instrumentation

The ultrasonic backscatter (UB) has the advantage of non-invasively obtaining bone density and structure, expected to be an assessment tool for early diagnosis osteoporosis. All former UB measurements were based on exciting a short single-pulse and analyzing the ultrasonic signals backscattered in bone. This study aims to examine amplitude modulation (AM) ultrasonic excitation with UB measurements for predicting bone characteristics. The AM multiple lengths excitation and backscatter measurement (AM-UB) functions were integrated into a portable ultrasonic instrument for bone characterization. The apparent integrated backscatter coefficient in the AM excitation (AIBAM) was evaluated on the AM-UB instrumentation. The correlation coefficients of the AIBAM estimating volume fraction (BV/TV), structure model index (SMI), and bone mineral density (BMD) were then analyzed. Significant correlations (|R| = 0.82–0.93, p < 0.05) were observed between the AIBAM, BV/TV, SMI, and BMD. By growing the AM excitation length, the AIBAM values exhibit more stability both in 1.0-MHz and 3.5-MHz measurements. The recommendations in AM-UB measurement were that the avoided length (T1) should be lower than AM excitation length, and the analysis length (T2) should be enough long but not more than AM excitation length. The authors conducted an AM-UB measurement for cancellous bone characterization. Increasing the AM excitation length could substantially enhance AIBAM values stability with varying analyzed signals. The study suggests the portable AM-UB instrument with the integration of real-time analytics software that might provide a potential tool for osteoporosis early screening.

A multiparametric volumetric quantitative ultrasound imaging technique for soft tissue characterization.

Quantitative ultrasound (QUS) offers a non-invasive and objective way to quantify tissue health. We recently presented a spatially adaptive regularization method for reconstruction of a single QUS parameter, limited to a two dimensional region. That proof-of-concept study showed that regularization using homogeneity prior improves the fundamental precision-resolution trade-off in QUS estimation. Based on the weighted regularization scheme, we now present a multiparametric 3D weighted QUS (3D QUS) method, involving the reconstruction of three QUS parameters: attenuation coefficient estimate (ACE), integrated backscatter coefficient (IBC) and effective scatterer diameter (ESD). With the phantom studies, we demonstrate that our proposed method accurately reconstructs QUS parameters, resulting in high reconstruction contrast and therefore improved diagnostic utility. Additionally, the proposed method offers the ability to analyze the spatial distribution of QUS parameters in 3D, which allows for superior tissue characterization. We apply a three-dimensional total variation regularization method for the volumetric QUS reconstruction. The 3D regularization involving N planes results in a high QUS estimation precision, with an improvement of standard deviation over the theoretical 1/N rate achievable by compounding N independent realizations. In the in vivo liver study, we demonstrate the advantage of adopting a multiparametric approach over the single parametric counterpart, where a simple quadratic discriminant classifier using feature combination of three QUS parameters was able to attain a perfect classification performance to distinguish between normal and fatty liver cases.

Reference Phantom Method for Ultrasonic Imaging of Thin Dynamic Constructs

Quantitative ultrasound has a great potential for the non-destructive evaluation of tissue engineered constructs, where the local attenuation and the integrated backscatter coefficient (IBC) can be used for monitoring the development of biological processes. The local determination of both parameters can be achieved using the reference phantom method (RPM). However, its accuracy can be affected when evaluating constructs of evolving sound speed, attenuation and thickness, for example, when evaluating biodegradable hydrogels developing neocartilage. To assess the feasibility of using the RPM under such dynamic conditions while employing a 50-MHz transducer, we conducted a series of experiments on 3-mm-thick acellular hydrogels laden with microspheres. The ultrasonic evaluation procedure used was validated by detecting and compensating for large attenuation variations occurring in the construct, up to 20-fold with respect to the reference phantom, with estimations errors below 1%. We found that sound speed mismatch does not affect the local attenuation estimation, but causes a strong diffraction effect by reducing the backscatter intensity. Such intensity reduction was compensated by determining the IBC percentage change (IBCΔ) as function of sound speed mismatch with respect to the reference phantom (ΔSS), with the equation IBCΔ = (0.63 ± 0.07) ΔSS + (8.54 ± 0.76) 10–3 ΔSS2. The investigated ΔSS interval was up to 120 m/s and using two different concentrations of microspheres, with estimation errors below 7% relative to the construct's actual IBC. Finally, we found that the spectral difference method is sufficient to measure within a few millimetres in depth mismatch, and when combining with sound speed mismatch, we found negligible additional effects. These results pave the way for the use of a generic reference phantom for the evaluation of thin dynamic constructs, thus simplifying the need for using different phantoms depending on the construct's properties.

Multiparametric ultrasound examination for response assessment in breast cancer patients undergoing neoadjuvant therapy

To investigate the performance of multiparametric ultrasound for the evaluation of treatment response in breast cancer patients undergoing neoadjuvant chemotherapy (NAC). The IRB approved this prospective study. Breast cancer patients who were scheduled to undergo NAC were invited to participate in this study. Changes in tumour echogenicity, stiffness, maximum diameter, vascularity and integrated backscatter coefficient (IBC) were assessed prior to treatment and 7 days after four consecutive NAC cycles. Residual malignant cell (RMC) measurement at surgery was considered as standard of reference. RMC < 30% was considered a good response and > 70% a poor response. The correlation coefficients of these parameters were compared with RMC from post-operative histology. Linear Discriminant Analysis (LDA), cross-validation and Receiver Operating Characteristic curve (ROC) analysis were performed. Thirty patients (mean age 56.4 year) with 42 lesions were included. There was a significant correlation between RMC and echogenicity and tumour diameter after the 3rd course of NAC and average stiffness after the 2nd course. The correlation coefficient for IBC and echogenicity calculated after the first four doses of NAC were 0.27, 0.35, 0.41 and 0.30, respectively. Multivariate analysis of the echogenicity and stiffness after the third NAC revealed a sensitivity of 82%, specificity of 90%, PPV = 75%, NPV = 93%, accuracy = 88% and AUC of 0.88 for non-responding tumours (RMC > 70%). High tumour stiffness and persistent hypoechogenicity after the third NAC course allowed to accurately predict a group of non-responding tumours. A correlation between echogenicity and IBC was demonstrated as well.

High-frequency quantitative ultrasound for characterizing collagen fiber alignment in murine tendon using angular dependence of integrated backscatter

Two major complications following tendon surgery are adhesion formation and re-rupture. There is a need to develop an ultrasound imaging system for non-invasive, non-destructive, longitudinal monitoring of tendon structure throughout a rehabilitation protocol to optimize restoration of range of motion and mechanical properties. Type I collagen is the primary extracellular matrix protein in tendon, and its organization impacts tendon function. The objective of the present study is to develop a high-frequency quantitative ultrasound spectral analysis technique to characterize collagen fiber alignment in murine tendon. This work tests the hypothesis that the integrated backscatter coefficient (IBC) will exhibit anisotropy in murine tendon with aligned structure, and isotropy in murine liver with inhomogeneous structure. Backscattered echoes from murine tail tendon and liver were acquired at varying insonification angles using 38-MHz and 55-MHz single-element transducers. B-mode and IBC parametric images were computed, and the average IBC value in a region of interest was determined at each insonification angle. The IBC was angular-dependent in tendon and isotropic in liver. These data suggest that the IBC can be used to detect collagen fiber alignment in murine tendon, and contribute to establishing the foundation for a dedicated device to non-invasively monitor collagen remodeling during tendon healing.

A Combined Ultrasonic Backscatter Parameter for Bone Status Evaluation in Neonates.

Metabolic bone disease (MBD) is one of the major complications of prematurity. Ultrasonic backscatter technique has the potential to be a portable and noninvasive method for early diagnosis of MBD. This study firstly applied CAS to neonates, which was defined as a linear combination of the apparent integrated backscatter coefficient (AIB) and spectral centroid shift (SCS). The objective was to evaluate the feasibility of ultrasonic backscatter technique for assessing neonatal bone health using AIB, SCS, and CAS. Ultrasonic backscatter measurements at 3.5 MHz, 5.0 MHz, and 7.5 MHz were performed on a total of 505 newborns within 48 hours after birth. The values of backscatter parameters were calculated and compared among gestational age groups. Correlations between backscatter parameters, gestational age, anthropometric indices, and biochemical markers were analyzed. The optimal predicting models for CAS were determined. The results showed term infants had lower SCS and higher AIB and CAS than preterm infants. Gestational age and anthropometric indices were negatively correlated with SCS (|r| = 0.45 – 0.57, P < 0.001), and positively correlated with AIB (|r| = 0.36 – 0.60, P < 0.001) and CAS (|r| = 0.56 – 0.69, P < 0.001). Biochemical markers yielded weak or nonsignificant correlations with backscatter parameters. CAS had relatively stronger correlations with the neonatal variables than AIB and SCS. At 3.5 MHz and 5.0 MHz, only gestational age (P < 0.001) independently contributed to the measurements of CAS, and could explain up to 40.5% – 44.3% of CAS variation. At 7.5 MHz, the combination of gestational age (P < 0.001), head circumference (P = 0.002), and serum calcium (P = 0.037) explained up to 40.3% of CAS variation. This study suggested ultrasonic backscatter technique was feasible to evaluate neonatal bone status. CAS was a promising parameter to provide more information about bone health than AIB or SCS alone.

Validation of Ash/Dust Detections from SEVIRI Data Using ACTRIS/EARLINET Ground-Based LIDAR Measurements

Two tailored configurations of the Robust Satellite Technique (RST) multi-temporal approach, for airborne volcanic ash and desert dust detection, have been tested in the framework of the European Natural Airborne Disaster Information and Coordination System for Aviation (EUNADICS-AV) project. The two algorithms, running on Spinning Enhanced Visible Infra-Red Imager (SEVIRI) data, were previously assessed over wide areas by comparison with independent satellite-based aerosol products. In this study, we present results of a first validation analysis of the above mentioned satellite-based ash/dust products using independent, ground-based observations coming from the European Aerosol Research Lidar Network (EARLINET). The aim is to assess the capabilities of RST-based ash/dust products in providing useful information even at local scale and to verify their applicability as a “trigger” to timely activate EARLINET measurements during airborne hazards. The intense Saharan dust event of May 18–23 2008—which affected both the Mediterranean Basin and Continental Europe—and the strong explosive eruptions of Eyjafjallajökull (Iceland) volcano of April–May 2010, were analyzed as test cases. Our results show that both RST-based algorithms were capable of providing reliable information about the investigated phenomena at specific sites of interest, successfully detecting airborne ash/dust in different geographic regions using both nighttime and daytime SEVIRI data. However, the validation analysis also demonstrates that ash/dust layers remain undetected by satellite in the presence of overlying meteorological clouds and when they are tenuous (i.e., with an integrated backscatter coefficient less than ~0.001 sr−1 and with aerosol backscatter coefficient less than ~1 × 10−6 m−1sr−1). This preliminary analysis confirms that the continuity of satellite-based observations can be used to timely “trigger” ground-based LIDAR measurements in case of airborne hazard events. Finally, this work confirms that advanced satellite-based detection schemes may provide a relevant contribution to the monitoring of ash/dust phenomena and that the synergistic use of (satellite-based) large scale, continuous and timely records with (ground-based) accurate and quantitative measurements may represent an added value, especially in operational scenarios.

Frequency dependence of attenuation and backscatter coefficient of ex vivo human lymphedema dermis.

Radio-frequency (RF) signals from the most dominant scatterer in a dermis, i.e., collagen fibers, are collected as backscattered signals. We aim to confirm the frequency dependence of the spatial distribution of features in ultrasound images, as well as the attenuation coefficient (AC) and backscatter coefficient (BSC) of skin tissue without [LE (-)] and with lymphedema [LE (+)]. Measurement samples (n = 13) were excised from human skin tissue with LE (-) and middle severity LE (+). A laboratory-made scanner and single-element concave transducers (range 9-47MHz) were used to measure RF data. A localized AC was computed from the normalized power spectrum using the linear least squares technique. The reflector method and compensation technique of the attenuation of tissue were applied to calculate the BSC. In addition, effective scatterer diameter (ESD), effective acoustic concentration (EAC), and integrated BSC (IBS) were calculated from the BSC as the benchmark to differentiate LE (-) and LE (+) tissues. High-frequency ultrasound displayed different echogenicity and texture compared between LE (-) and LE (+) in all transducers. The AC for LE (-) (0.22dB/mm/MHz) and LE (+) (0.29dB/mm/MHz) was comparable. BSC in LE (-) and LE (+) increased linearly with each transducer. The difference of intercept of the BSC between LE (-) and LE (+) indicated that both EAC and IBS of LE (+) were higher than that of LE (-). In contrast, ESD correlated with the slope of the BSC demonstrated the same tendency for both LE (-) and LE (+). These tendencies appeared for each transducer independent of the frequency bandwidth. Frequency independence of AC and BSC in LE (-) and LE (+) was confirmed. Several 9- to 19-MHz ultrasound beams are sufficient for BSC analysis to discriminate LE (-) and LE (+) in terms of the penetration depth of the ultrasound.

Monitoring the response to neoadjuvant chemotherapy in patients with breast cancer using ultrasound scattering coefficient: A preliminary report

ObjectiveNeoadjuvant chemotherapy was initially used in locally advanced breast cancer, and currently it is recommended for patients with Stage 3 and with early-stage disease with human epidermal growth factor receptors positive or triple-negative breast cancer. Ultrasound imaging in combination with a quantitative ultrasound method is a novel diagnostic approach.Aim of studyThe aim of this study was to analyze the variability of the integrated backscatter coefficient, and to evaluate their use to predict the effectiveness of treatment and compare to ultrasound examination results.Material and methodTen patients (mean age 52.9) with 13 breast tumors (mean dimension 41 mm) were selected for neoadjuvant chemotherapy. Ultrasound was performed before the treatment and one week after each course of neoadjuvant chemotherapy. The dimensions were assessed adopting the RECIST criteria. Tissue responses were classified as pathological response into the following categories: not responded to the treatment (G1, cell reduction by ≤9%) and responded to the treatment partially: G2, G3, G4, cell reduction by 10–29% (G2), 30–90% (G3), >90% (G4), respectively, and completely.ResultsIn B-mode examination partial response was observed in 9/13 cases (completely, G1, G3, G4), and stable disease was demonstrated in 3/13 cases (completely, G1, G4). Complete response was found in 1/13 cases. As for backscatter coefficient, 10/13 tumors (completely, and G2, G3, and G4) were characterized by an increased mean value of 153%. Three tumors 3/13 (G1) displayed a decreased mean value of 31%.ConclusionThe variability of backscatter coefficient, could be associated with alterations in the structure of the tumor tissue during neoadjuvant chemotherapy. There were unequivocal differences between responded and non-responded patients. The backscatter coefficient analysis correlated better with the results of histopathological verification than with the B-mode RECIST criteria.

Aerosol characteristics in the upper troposphere and lower stratosphere region during successive and contrasting Indian summer monsoon season

Cloud Aerosol Lidar and Infrared Pathfinder Satellite Observation (CALIPSO)-derived aerosol vertical profiles were studied in the upper troposphere and lower stratosphere (UTLS) over the Indian summer monsoon (ISM) region during two successive and contrasting monsoon years (2008–2009). An enhanced aerosol layer was observed in the UTLS between 15 and 19 km altitude, in the vicinity of tropopause during both years. However, the optical characteristics of aerosol layers were found to be dissimilar during the two contrasting consecutive summer monsoon seasons. While the depolarization ratio of enhanced aerosol layer (exceeding 0.2) during both years suggested anisotropic nature of particles, the aerosol backscatter coefficient was observed to be more intensified with a sharp peak during the active monsoon year (2008) whereas it was relatively broader with lower magnitude during a drought year (2009). The enhanced backscatter coefficient in the UTLS was found to be closely associated with the variability in tropopause height and convection during both years, which is more pronounced during the active monsoon year as compared to a drought year. Deep convection over the ISM region may inject boundary layer aerosols into the upper troposphere as evidenced from the analysis of the outgoing long-wave radiation (OLR). Our results also showed an enhanced integrated backscatter coefficient (IBC) of about 30%, which is associated with a decrease in OLR of about 7% during the active monsoon year as compared to drought year. These findings were further corroborated using NCEP-NCAR vertical velocity and HYSPLIT air-mass backward trajectory analyses.

Evolution of stratospheric sulfate aerosol from the 1991 Pinatubo eruption: Roles of aerosol microphysical processes

AbstractThis study investigates the role of aerosol microphysics in stratospheric sulfate aerosol changes after the 1991 Mount Pinatubo eruption using an atmospheric general circulation model that is coupled interactively with a chemistry module and a modal aerosol microphysical module with three modes. Our model can reproduce the global mean stratospheric aerosol optical depth (SAOD) observed by the Stratospheric Aerosol and Gas Experiment (SAGE) II during June 1991 to January 1993. The model underestimates the observed SAOD before the eruption and after January 1993. The model also underestimates the integrated backscatter coefficient observed by ground‐based lidar at Tsukuba, Naha, and Lauder. The modeled effective radius becomes larger (about 0.5 μm) and agrees with the balloon‐borne measurements at Laramie, Wyoming (41°N, 105°W). We further investigate effects of the inclusion of evaporation along with the condensation processes and the inclusion of van der Waals and viscous forces in the coagulation processes. The inclusion of evaporation along with the condensation processes reduces the global mean effective radius by up to 0.04 μm and increases the global burden of stratospheric sulfate aerosols (about 15% in late 1993). The inclusion of van der Waals and viscous forces in the coagulation processes increases the global mean effective radius by up to 0.06–0.07 μm and decreases the global burden (15–30% in late 1993). The effects of van der Waals and viscous forces differ between two schemes. However, we do not conclude which simulation is superior because all simulations fall within error bars.

Ultrasound Imaging Techniques for Spatiotemporal Characterization of Composition, Microstructure, and Mechanical Properties in Tissue Engineering.

Ultrasound techniques are increasingly being used to quantitatively characterize both native and engineered tissues. This review provides an overview and selected examples of the main techniques used in these applications. Grayscale imaging has been used to characterize extracellular matrix deposition, and quantitative ultrasound imaging based on the integrated backscatter coefficient has been applied to estimating cell concentrations and matrix morphology in tissue engineering. Spectral analysis has been employed to characterize the concentration and spatial distribution of mineral particles in a construct, as well as to monitor mineral deposition by cells over time. Ultrasound techniques have also been used to measure the mechanical properties of native and engineered tissues. Conventional ultrasound elasticity imaging and acoustic radiation force imaging have been applied to detect regions of altered stiffness within tissues. Sonorheometry and monitoring of steady-state excitation and recovery have been used to characterize viscoelastic properties of tissue using a single transducer to both deform and image the sample. Dual-mode ultrasound elastography uses separate ultrasound transducers to produce a more potent deformation force to microscale characterization of viscoelasticity of hydrogel constructs. These ultrasound-based techniques have high potential to impact the field of tissue engineering as they are further developed and their range of applications expands.

Aerosol characteristics in the UTLS region: A satellite-based study over north India

Abstract Vertical profiles of aerosol backscatter coefficient and depolarization ratio, obtained from the Cloud–Aerosol Lidar and Infrared Pathfinder Satellite Observation (CALIPSO) satellite, were studied in the upper troposphere and lower stratosphere (UTLS) region over North India (21–30° N and 72–90° E), covering the highly polluted Indo-Gangetic Plain (IGP) for one-year period from December 2011 to November 2012. An enhanced aerosol layer was observed between 15 and 18 km altitude, in the vicinity of tropopause, with a broad layer depth of about 2 km. The aerosol layer showed strong seasonal, monthly as well as day and night time variability, with a peak value of backscatter coefficient during monsoon season (∼5.54 × 10−3 sr−1 in September). The corresponding depolarization ratio indicates anisotropic (non-spherical) nature of particles. The aerosol layer was found to be highly linked with the variability in tropopause height, showing a positive correlation between tropopause height and the height of maximum backscatter coefficient (correlation coefficient of 0.8). However, it was found to be negatively correlated with the integrated backscatter coefficient (IBC), with a correlation coefficient of 0.3. We further analyzed outgoing long-wave radiation (OLR) data during the study period to investigate the link between the observed enhanced aerosol layer in the UTLS region and prevailing deep convective activities over the study region. Low values of OLR during monsoon (about 214 W m−2) indicate the occurrence of deep convection over this region, which may cause a large-scale circulation-driven vertical transport of boundary-layer pollution into the atmosphere of UTLS region. Results may have potential implications for better understanding and assessing the chemical and radiative impacts of these aerosols in the tropical UTLS region.

Ultrasonic scattering measurements of a live single cell at 86 MHz.

Cell separation and sorting techniques have been employed biomedical applications such as cancer diagnosis and cell gene expression analysis. The capability to accurately measure ultrasonic scattering properties from cells is crucial in making an ultrasonic cell sorter a reality if ultrasound scattering is to be used as the sensing mechanism as well. To assess the performance of sensing and identifying live single cells with high-frequency ultrasound, an 86-MHz lithium niobate press-focused single-element acoustic transducer was used in a high-frequency ultrasound scattering measurement system that was custom designed and developed for minimizing noise and allowing better mobility. Peak-to-peak echo amplitude, integrated backscatter (IB) coefficient, spectral parameters including spectral slope and intercept, and midband fit from spectral analysis of the backscattered echoes were measured and calculated from a live single cell of two different types on an agar surface: leukemia cells (K562 cells) and red blood cells (RBCs). The amplitudes of echo signals from K562 cells and RBCs were 48.25 ± 11.98 mV(pp) and 56.97 ± 7.53 mV(pp), respectively. The IB coefficient was -89.39 ± 2.44 dB for K562 cells and -89.00 ± 1.19 dB for RBCs. The spectral slope and intercept were 0.30 ± 0.19 dB/MHz and -56.07 ± 17.17 dB, respectively, for K562 cells and 0.78 ± 0.092 dB/MHz and -98.18 ± 8.80 dB, respectively, for RBCs. Midband fits of K562 cells and RBCs were -31.02 ± 3.04 dB and -33.51 ± 1.55 dB, respectively. Acoustic cellular discrimination via these parameters was tested by Student's t-test. Their values, except for the IB value, showed statistically significant difference (p < 0.001). This paper reports for the first time that ultrasonic scattering measurements can be made on a live single cell with a highly focused high-frequency ultrasound microbeam at 86 MHz. These results also suggest the feasibility of ultrasonic scattering as a sensing mechanism in the development of ultrasonic cell sorters.

Noninvasive Quantitative Imaging of Collagen Microstructure in Three-Dimensional Hydrogels Using High-Frequency Ultrasound.

Collagen I is widely used as a natural component of biomaterials for both tissue engineering and regenerative medicine applications. The physical and biological properties of fibrillar collagens are strongly tied to variations in collagen fiber microstructure. The goal of this study was to develop the use of high-frequency quantitative ultrasound to assess collagen microstructure within three-dimensional (3D) hydrogels noninvasively and nondestructively. The integrated backscatter coefficient (IBC) was employed as a quantitative ultrasound parameter to detect, image, and quantify spatial variations in collagen fiber density and diameter. Collagen fiber microstructure was varied by fabricating hydrogels with different collagen concentrations or polymerization temperatures. IBC values were computed from measurements of the backscattered radio-frequency ultrasound signals collected using a single-element transducer (38-MHz center frequency, 13-47 MHz bandwidth). The IBC increased linearly with increasing collagen concentration and decreasing polymerization temperature. Parametric 3D images of the IBC were generated to visualize and quantify regional variations in collagen microstructure throughout the volume of hydrogels fabricated in standard tissue culture plates. IBC parametric images of corresponding cell-embedded collagen gels showed cell accumulation within regions having elevated collagen IBC values. The capability of this ultrasound technique to noninvasively detect and quantify spatial differences in collagen microstructure offers a valuable tool to monitor the structural properties of collagen scaffolds during fabrication, to detect functional differences in collagen microstructure, and to guide fundamental research on the interactions of cells and collagen matrices.

Non-invasive evaluation of breast cancer response to chemotherapy using quantitative ultrasonic backscatter parameters.

Tumor response to neoadjuvant chemotherapy in patients (n=30) with locally advanced breast cancer (LABC) was examined using quantitative ultrasound. Three ultrasound backscatter parameters, the integrated backscatter coefficient (IBC), average scatterer diameter (ASD), and average acoustic concentration (AAC), were estimated from tumors prior to treatment and at four times during neoadjuvant chemotherapy treatment (weeks 0, 1, 4, 8, and prior to surgery) and compared to ultimate clinical and pathological tumor responses. Results demonstrated that among all parameters, AAC was the best indicator of tumor response early after starting treatment. The AAC parameter increased substantially in treatment-responding patients as early as one week after treatment initiation, further increased at week 4, and attained a maximum at week 8. In contrast, the backscatter parameters from non-responders did not show any changes after treatment initiation. The two patient populations exhibited a statistically significant difference in changes of AAC (p<0.001) and ASD (p=0.023) over all treatment times examined. The best prediction of treatment response was achieved with the combination of AAC and ASD at week 4 (82% sensitivity, 100% specificity, and 86% accuracy) of 12-18 weeks of treatment. The survival of patients with responsive ultrasound parameters was higher than patients with non-responsive ultrasound parameters (35 ± 11 versus 27 ± 11 months, respectively, p=0.043). This study demonstrates that ultrasound parameters derived from the ultrasound backscattered power spectrum can potentially serve as non-invasive early measures of clinical tumor response to chemotherapy treatments.

Characterizing collagen microstructure using high frequency ultrasound

Collagen is the most abundant extracellular matrix protein in mammals and is widely investigated as a scaffold material for tissue engineering. Collagen provides structural properties for scaffolds and, importantly, the microstructure of collagen can affect key cell behaviors such as cell migration and proliferation. This study investigated the feasibility of using high-frequency quantitative ultrasound to characterize collagen microstructure, namely, collagen fiber density and size, nondestructively. The integrated backscatter coefficient (IBC) was employed as a quantitative ultrasound parameter to characterize collagen microstructure in 3-D engineered hydrogels. To determine the relationship between the IBC and collagen fiber density, hydrogels were fabricated with different collagen concentrations (1–4 mg/mL). Further, collagen hydrogels polymerized at different temperatures (22–37°C) were investigated to determine the relationship between the IBC and collagen microfiber size. The IBC was computed from measurements of the backscattered radio-frequency data collected using a single-element transducer (38-MHz center frequency, 13–47 MHz bandwidth). Parallel studies using second harmonic generation microscopy verified changes in collagen microstructure. Results showed that the IBC increased with increasing collagen concentration and decreasing polymerization temperature. Further, we demonstrated that parametric images of the IBC were useful for assessing spatial variations in collagen microstructure within hydrogels.

Analysis of Apparent Integrated Backscatter Coefficient and Backscattered Spectral Centroid Shift in Calcaneus in vivo for the Ultrasonic Evaluation of Osteoporosis

The purposes of our study were to evaluate the correlation among apparent integrated backscatter coefficient (AIB), spectral centroid shift (SCS) of ultrasonic backscatter signals and bone mineral density (BMD) and to examine the effectiveness of ultrasound variables as predictors of osteoporosis. A total of 1011 persons aged 21–80 y old were included. All study participants underwent BMD measurements of the lumbar spine (LSBMD) and the femoral neck (FNBMD). The participants also underwent calcaneal measurements to determine AIB and SCS with central frequencies of 3.5 (one transducer) and 5.0 MHz (the other transducer). AIB decreased with age and was positively correlated with BMD, while SCS increased with age and was negatively correlated with BMD. The correlation coefficient of SCS with LSBMD and FNBMD at 3.5 MHz was −0.72 and −0.70, respectively. The correlation coefficient at 5.0 MHz was −0.75 and −0.74, respectively. The correlation coefficient of AIB with LSBMD and FNBMD at 3.5 MHz was 0.65 and 0.63. The correlation coefficient at 5.0 MHz was 0.59 and 0.55, respectively. The correlation between SCS and BMD was significantly better than the correlation between AIB and BMD. Using receiver operating characteristic analysis, a significant difference was found between the areas under the curve for SCS and AIB at 3.5 MHz (0.781 vs. 0.715, respectively, p < 0.05), as well as at 5.0 MHz (0.782 vs. 0.709, respectively, p < 0.05). The optimum T-score threshold for SCS was -1.3 for both transducers. The sensitivity and specificity of SCS at 3.5 MHz and 5.0 MHz for the optimum threshold were 64%, 85%, 63% and 86%, respectively. In conclusion, the correlations among the ultrasound parameters and BMDs are strong. SCS performs better than AIB in differentiating patients with osteoporosis. Ultrasound variables may be taken into consideration as predictors of osteoporosis in the future considering its portability.

Estimating Cell Concentration in Three-Dimensional Engineered Tissues Using High Frequency Quantitative Ultrasound

Histology and biochemical assays are standard techniques for estimating cell concentration in engineered tissues. However, these techniques are destructive and cannot be used for longitudinal monitoring of engineered tissues during fabrication processes. The goal of this study was to develop high-frequency quantitative ultrasound techniques to nondestructively estimate cell concentration in three-dimensional (3-D) engineered tissue constructs. High-frequency ultrasound backscatter measurements were obtained from cell-embedded, 3-D agarose hydrogels. Two broadband single-element transducers (center frequencies of 30 and 38MHz) were employed over the frequency range of 13-47MHz. Agarose gels with cell concentrations ranging from 1×10(4) to 1×10(6)cellsmL(-1) were investigated. The integrated backscatter coefficient (IBC), a quantitative ultrasound spectral parameter, was calculated and used to estimate cell concentration. Accuracy and precision of this technique were analyzed by calculating the percent error and coefficient of variation of cell concentration estimates. The IBC increased linearly with increasing cell concentration. Axial and lateral dimensions of regions of interest that resulted in errors of less than 20% were determined. Images of cell concentration estimates were employed to visualize quantitatively regional differences in cell concentrations. This ultrasound technique provides the capability to rapidly quantify cell concentration within 3-D tissue constructs noninvasively and nondestructively.