OBJECTIVE:Periodontal diseases affect 46% of adults aged ≥30 years in the United States, yet current clinical diagnostic approaches are subjective, semi-quantitative and late-stage indicators. This gap highlights a critical unmet need for alternative biomarkers. Ultrasonography is emerging to fill this gap as a surrogate for non-invasive and quantitative assessments of oral diseases. This study presents the first quantification of the ultrasound attenuation coefficient slope (ACS) as a key acoustic property and potential biomarker of oral tissues, using standard techniques. METHODS:In a swine cohort (N = 10), we characterized the high-frequency (24 MHz) ACSs of healthy periodontal tissues (gingiva) in vivo using the spectral difference method. First, we validated the technique using custom tissue-mimicking phantoms with known ACSs. Five interproximal oral sites from each of the oral quadrants were enrolled and imaged: Premolar 3 - Mesial, Premolar 3 - Distal, Premolar 4 - Distal, Molar 1 - Distal and Molar 2 - Distal. A total of 162 oral sites were analyzed after applying exclusion criteria. RESULTS:The respective median (first quartile|third quartile) ACSs for the five oral sites were 1.66 (1.25|1.99), 1.37 (1.06|1.64), 0.99 (0.8|1.25), 1.08 (0.89|1.47) and 1.28 (0.94|1.24) dB/MHz.cm. The gingival ACS mean at Premolar 3 - Mesial was significantly higher than any other oral site (p ≤ 0.05), while the rest of the sites showed a non-significant difference in their means. The average ACS was 1.17 (±0.48) dB/MHz.cm across non-significant oral sites. CONCLUSION:The high-frequency ultrasound ACSs of periodontal soft tissues were quantified in vivo using standardized techniques. This work not only characterizes an important acoustic property of oral tissues for the first time, but also contributes to the future development of quantitative ultrasound biomarkers for dental healthcare that rely on attenuation knowledge.

In the USA, periodontal diseases, a spectrum of inflammatory conditions, affect 4 out of 10 adults (>=30 years). Current standards of care in clinical assessment of these diseases are invasive, subjective, only semi-quantitative, and primarily detecting later stages. Applications of ultrasonography in periodontology has been emerging in recent years. Despite such growing interest, Quantitative ultrasound (QUS) approaches remain largely unexplored and their utility for longitudinal characterization of oral inflammation has yet to be established. Here, we present one of the early investigations into the potential of QUS techniques for inflammation monitoring. In a staggered study involving a pig cohort (N=8), interdental gingival tissues at three interproximal oral sites from four quadrants were enrolled. The study involved baseline and five inflammation timepoints. Inflammation was induced using two complementary approaches at each site. Two QUS parameters of attenuation coefficient slope (ACS) and backscatter intensity (BSI) were investigated. Sex and oral sites were also used to stratify the longitudinal QUS estimates with inflammation. Results showed that both ACS and BSI were statistically significant from the healthy baseline across all oral sites at week 2 and|or 4 (combined sexes). Overall, inflammation inoculation was associated with a decrease in ACS and an increase in BSI. For BSI, week4 and/or week 2 remained statistically significant across males and females at all oral sites. ACS variations were spread across oral sites and sexes, with PM4-Dis as overall non-significant. The 2D classification (baseline from week 2) accuracy, were 92

Rationale and Objectives This study aims to (1) describe a periodontal and implant ultrasound imaging phantom designed for training of common periodontal and peri-implant soft- and hard-tissue deficiencies, and (2) detail the specific anatomical phantom features and showcase imaging data obtained from intraoral scans, cone beam computed tomography (CBCT) as well as ultrasound. Materials and Methods A prototype, full-sized, three-dimensional (3D), periodontal ultrasound phantom was created. To mimic periodontal and peri-implant soft-tissue, a phantom material similar to soft-tissue was attached. Several features were added to imitate clinical scenarios and enable use as a teaching tool. To understand hard-tissue anatomy, the phantom was imaged using a commercially available CBCT scanner. In addition, an optical scan was taken to generate a 3D surface model. Images obtained were analyzed using a public domain software (3D Slicer). Ultrasound brightness mode images (B-mode) were taken of the regions of interest. Results CBCT and intraoral reference scans are overlaid with the ultrasound images obtained. Four different views are provided: facial, occlusal, lingual, and transverse. Our group was able to scan and delineate in ultrasound images vertical and horizontal bone loss, peri-implant bone loss, buccal dehiscence, apical fenestrations, and edentulous crest soft- and hard-tissue. Conclusion To our knowledge, this is the first study to present a prototype (full-sized, 3D, for periodontal ultrasound) phantom for intraoral periodontal and peri-implant ultrasound scanning training. Creating training scenarios that mimic clinical reality might allow trainees to obtain skills and build toward acceptable and individualized technical performance.

BACKGROUND:Protocol standardization and optimization for clinical translation of emerging quantitative multiparametric (mp)MRI biomarkers of high-risk prostate cancer requires imaging references that mimic realistic tissue value combinations for bias assessment in derived relaxation and diffusion parameters. PURPOSE:This work aimed to develop a novel class of hydrogel-based synthetic materials with simultaneously controlled quantitative relaxation, diffusion, and kurtosis parameters that mimic in vivo prostate value combinations in the same spatial compartment and allow stable assemblies of adjacent structures. METHODS:A set of materials with tunable T2, diffusion, and kurtosis were assembled to create quantitative biomimetic (mp)MRI references. T2 was controlled with variable agarose concentration, monoexponential diffusion by polyvinylpyrrolidone (PVP), and kurtosis by addition of lamellar vesicles. The materials were mechanically stabilized by UV cross-linked polyacrylamide gels (PAG) to allow biomimetic morphologies. The reference T2 were measured on a 3T scanner using multi-echo CPMG, and diffusion kurtosis-with multi-b DWI. RESULTS:Agarose concentration controls T2 values which are nominally independent of PVP or vesicle concentration. For agarose PVP hydrogels, monoexponential diffusion values are a function of PVP concentration and independent of agarose concentration. Compared to free vesicles, for agarose-PAG combined with vesicles, diffusion was predominantly controlled by vesicles and PAG, while kurtosis was affected by agarose and vesicle concentration. Both hydrogel classes achieved image voxel parameter values (T2, Da, Ka) for relaxation (T2: 65-255 ms), apparent diffusion (Da: 0.8-1.7 μm2/ms), and kurtosis (Ka: 0.5-1.25) within the target literature ranges for normal prostate zones and cancer lesions. Relaxation and diffusion parameters remained stable for over 6 months for layered material assemblies. CONCLUSION:A stable biomimetic mpMR reference based on hydrogels has been developed with a range of multi-compartment diffusion and relaxation parameter combinations observed in cancerous and healthy prostate tissue.

ObjectivesTo 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.MethodsTwo 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.ResultsThe 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.ConclusionsShear 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.

Purpose: The purpose of this phantom study is to demonstrate that thermoacoustic range verification could be performed clinically. Thermoacoustic emissions generated in an anatomical multimodality imaging phantom during delivery of a clinical plan are compared to simulated emissions to estimate range shifts compared to the treatment plan. Methods: A single-field 12-layer proton pencil beam scanning (PBS) treatment plan created in Pinnacle prescribing 6 Gy/fraction was delivered by a superconducting synchrocyclotron to a triple modality (CT, MRI, and US) abdominal imaging phantom. Data was acquired by four acoustic receivers rigidly affixed to a linear ultrasound array. Receivers 1-2 were located distal to the treatment volume, whereas 3-4 were lateral. Receivers-room coordinates were computed relative to the ultrasound image plane after co-registration to the planning CT volume. For each prescribed beamlet, a set of thermoacoustic emissions corresponding to varied beam energies were computed. Simulated emissions were compared to measured emissions to estimate shifts of the Bragg peak. Results: Shifts were small for high-dose beamlets that stopped in soft tissue. Signals acquired by channels 1-2 yielded shifts of -0.2 +/- 0.7 mm relative to Monte Carlo simulations for high dose spots (similar to 40 cGy) in the second layer. Additionally, for beam energy >125 MeV, thermoacoustic emissions qualitatively tracked lateral motion of pristine beams in a layered gelatin phantom, and time shifts induced by changing phantom layers were self-consistent within nanoseconds. Conclusions: Acoustic receivers tuned to spectra of thermoacoustic emissions may enable range verification during proton therapy. (C) 2021 Elsevier B.V. All rights reserved.

Using ultrasonic shear wave speed (SWS) estimates has become popular to noninvasively evaluate liver fibrosis, but significant inter-system variability in liver SWS measurements can preclude meaningful comparison of measurements performed with different systems. The RSNA Quantitative Imaging Biomarker Alliance (QIBA) ultrasound SWS committee has been developing elastic and viscoelastic (VE) phantoms to evaluate system dependencies of SWS estimates. The objective of this study is to compare SWS measurements between commercially-available systems using phantoms that have viscoelastic properties similar to those observed in normal and fibrotic liver. CIRS, Inc. fabricated three phantoms using a proprietary oil-water emulsion infused in a Zerdine ® hydrogel that were matched in viscoelastic behavior to healthy and fibrotic human liver data. Phantoms were measured at academic, clinical, government and vendor sites using different systems with curvilinear arrays at multiple focal depths (3.0, 4.5 & 7.0 cm). The results of this study show that current-generation ultrasound SWS measurement systems are able to differentiate viscoelastic materials that span healthy to fibrotic liver. The deepest focal depth (7.0 cm) yielded the greatest inter-system variability for each phantom (maximum of 17.7%) as evaluated by IQR. Inter-system variability was consistent across all 3 phantoms and was not a function of stiffness. Median SWS estimates for the greatest outlier system for each phantom/focal depth combination ranged from 12.7–17.6%. Future efforts will include performing more robust statistical analyses of these data, comparing these phantom data trends with viscoelastic digital phantom data, providing vendors with study site data to refine their systems to have more consistent measurements, and integrating these data into the QIBA ultrasound shear wave speed measurement profile.

Purpose: The Doppler string phantom provides accurate velocity of the string motion; it can be used to calibrate Doppler ultrasound (US) velocity measurements and to evaluate variations due to intrinsic spectral broadening. We developed a semi‐automated method to estimate the mode velocity (Vmode) and peak velocity (Vmax) based on duplex US images from a string phantom, and use them to assess clinical Doppler US velocity measurement.Methods: Steady motion of a rubber O‐ring (20 – 110 cm/s) in a CIRS Doppler String phantom (Model 043) was studied using GE LOGIQ E9 system with a 9L probe. 5 s of Doppler spectral data was averaged to generate a mean spectral profile. It was fitted by a Gaussian function and Vmode was defined as the velocity of the Gaussian peak, while Vmax is defined as the velocity at which the spectral profile falls to within 1 SD of the background. Vmode and Vmax were evaluated against the prescribed motor velocity. Repeatability and variation to scanning parameters were analyzed and reported in % range, i.e. (max – min) / mean.Results: Vmode and Vmax had good repeatability over six days (6.0% for Vmode, 2.9% for Vmax). Gain, compression, scale, sample volume (SV) depth and length, frequency and beam steering all had minimal impact on Vmode and Vmax (variations ≤ 4.4%). Doppler angle θ had minimal effect on Vmode (2.2%) but a strong effect on Vmax (26% increase as θ increased from 10° to 60°). Vmode was linearly correlated with but overestimated the motor velocity (Pearson’s r = 1.05, R2 = 1).Conclusion: This study developed a simple yet robust Vmode and Vmax estimation method. Combined with a string phantom, these velocity estimators are shown to be a useful tool to evaluate clinical Doppler US system performance. For the tested system, only Doppler angle has an appreciable impact on Vmax estimation.--------------------------------------------Cite this article as: Zhang Y, Lynch T, Hangiandreou NJ. Doppler string phantom for assessment of clinical doppler ultrasound velocity measurement. Int J Cancer Ther Oncol 2014; 2(2):020246. DOI:10.14319/ijcto.0202.46

Elastographic techniques used in addition to imaging techniques (ultrasound, resonance magnetic or optical) provide new clinical information on the pathological state of soft tissues. However, system-dependent variation in elastographic measurements may limit the clinical utility of these measurements by introducing uncertainty into the measurement. This work is aimed at showing differences in the evaluation of the elastic properties of phantoms performed by four different techniques: quasi-static compression, dynamic mechanical analysis, vibration-controlled transient elastography and hyper-frequency viscoelastic spectroscopy. Four Zerdine® gel materials were tested and formulated to yield a Young’s modulus over the range of normal and cirrhotic liver stiffnesses. The Young’s modulus and the shear wave speed obtained with each technique were compared. Results suggest a bias in elastic property measurement which varies with systems and highlight the difficulty in finding a reference method to determine and assess the elastic properties of tissue-mimicking materials. Additional studies are needed to determine the source of this variation, and control for them so that accurate, reproducible reference standards can be made for the absolute measurement of soft tissue elasticity.

An interlaboratory study of shear wave speed (SWS) estimation was performed. Commercial shear wave elastography systems from Fibroscan, Philips, Siemens and Supersonic Imagine, as well as several custom laboratory systems, were involved. Fifteen sites were included in the study. CIRS manufactured and donated 11 pairs of custom phantoms designed for the purposes of this investigation. Dynamic mechanical tests of equivalent phantom materials were also performed. The results of this study demonstrate that there is very good agreement among SWS estimation systems, but there are several sources of bias and variance that can be addressed to improve consistency of measurement results.

Ultrasound has been widely used to nondestructively evaluate various materials, including biological tissues. Quantitative ultrasound has been used to assess bone quality and fracture risk. A pulsed phase-locked loop (PPLL) method has been proven for very sensitive tracking of ultrasound time-of-flight (TOF) changes. The objective of this work was to determine if the PPLL TOF tracking is sensitive to bone deformation changes during loading. The ability to noninvasively detect bone deformations has many implications, including assessment of bone strength and more accurate osteoporosis diagnostics and fracture risk prediction using a measure of bone mechanical quality. Fresh sheep femur cortical bone shell samples were instrumented with three 3-element rosette strain gauges and then tested under mechanical compression with eight loading levels using an MTS machine. Samples were divided into two groups based on internal marrow cavity content: with original marrow, or replaced with water. During compressive loading ultrasound waves were measured through acoustic transmission across the mid-diaphysis of bone. Finite element analysis (FEA) was used to describe ultrasound propagation path length changes under loading based on µCT-determined bone geometry. The results indicated that PPLL output correlates well to measured axial strain, with R(2) values of 0.70 ± 0.27 and 0.62 ± 0.29 for the marrow and water groups, respectively. The PPLL output correlates better with the ultrasound path length changes extracted from FEA. For the two validated FEA tests, correlation was improved to R(2) = 0.993 and R(2) = 0.879 through cortical path, from 0.815 and 0.794 via marrow path, respectively. This study shows that PPLL readings are sensitive to displacement changes during external bone loading, which may have potential to noninvasively assess bone strain and tissue mechanical properties.

OBJECTIVE:Liver fibrosis has been found to increase the mechanical stiffness of the liver. To mimic different stages of liver fibrosis, commercially available phantoms (Model 039, CIRS, Inc.) have been produced for clinical quality assurance and research purposes. The purpose of this study was to investigate the mechanical property variability of the phantoms in two lots of CIRS Model 039 phantoms.METHODS:Each lot consisted of phantoms of four stiffness types, and there were 8-10 phantoms of each type. Shear wave elastography measurements were conducted on each phantom at 10 different angles. Group velocity measurements and phase velocity curves were calculated for every SWE acquisition. Multilevel functional principal component analysis (MFPCA) was performed on phase velocity data, which decomposes each phase velocity curve into the sum of eigenfunctions of two levels. The variance of the component scores of levels 1 and 2 were used to represent inter-phantom and intra-phantom variability, respectively. The 95% confidence intervals of phase velocity in a phantom type were calculated to reflect curve variability.DISCUSSION:The standard deviations of the group velocity for phantoms of any type were less than 0.04 and 0.02 m/s for lots 1 and 2, respectively. For both lots, in every type, the phase velocity curves of most individual phantoms fall within the 95% confidence interval.CONCLUSION:MFPCA is an effective tool for analyzing the inter- and intra-phantom variability of phase velocity curves. Given the known variability of a fully tested lot, estimation of the variability of a new lot can be performed with a reduced number of phantoms tested.

A set of materials with tunable T2, diffusion, and kurtosis were assembled to create quantitative biomimetic MRI phantoms. T2 is controlled with variable agarose concentration, mono-exponential diffusion by polyvinylpyrrolidone, and kurtosis by addition of lamellar vesicles. The phantoms are mechanically stabilized by polyacrylamide gels to allow biomimetic morphologies. These nanostructured systems provide an ideal platform for moldable multiparametric MRI phantoms that are useful for pulse sequence design and protocol standardization for multi-site multi-vendor imaging trials, as well as for refinement of emerging AI analysis methods.

Recently developed quantitative phantom based on lamellar-vesicles provides the range of tissue relevant diffusion kurtosis parameters for accurate evaluation of advanced multi-b DWI protocols and parametric diffusion models. This work studies temperature dependence of phantom diffusion kurtosis parameters to supply accurate nominal parameter values for typical scan room temperature range.