Citations

ObjectivesCrohn disease (CD) is a chronic inflammation in the digestive tract that affects millions of Americans. Bowel vascularity has important diagnostic information because inflammation is associated with blood flow changes. We recently developed an ultrasensitive ultrasound microvessel imaging (UMI) technique with high vessel sensitivity. This study aimed to evaluate the feasibility of UMI to assist CD detection and staging.MethodsUltrasound microvessel imaging was performed on 76 bowel wall segments from 48 symptomatic patients with CD. Clinically indicated computed tomographic/magnetic resonance enterography was used as the reference standard. The vessel‐length ratio (VLR, the number of vessel pixels in the bowel wall segment normalized to the segment length) was derived in both conventional color flow imaging (CFI) and UMI to quantitatively stage disease activity. Receiver operating characteristic curves were then analyzed between different disease groups.ResultsThe VLR‐CFI and VLR‐UMI detected similar correlations between vascularization and disease activity: severe inflammation had a higher VLR than normal/mildly inflamed bowels (P < .05). No significant difference was found between quiescent and mild CD due to the small sample size. The VLR‐CFI had more difficulties in distinguishing quiescent versus mild CD compared to the VLR‐UMI. After combining the VLR‐UMI with thickness, in the receiver operating characteristic curve analysis, the areas under the curves (AUCs) improved to AUC1 = 0.996 for active versus quiescent CD, AUC2 = 0.978 for quiescent versus mild CD, and AUC3 = 0.931 for mild versus severe CD, respectively, compared to those using thickness alone (AUC1 = 0.968; P = .04; AUC2 = 0.919; P = .16; AUC3 = 0.857; P = .01).ConclusionsUltrasound microvessel imaging offers a safe and cost‐effective tool for CD diagnosis and staging, which may potentially assist disease activity classification and therapy efficacy evaluation.

Skeletal development is controlled by epigenetic mechanisms that regulate chromatin compaction and suppress access to gene regulatory sequences. Post‐translational modifications in the N‐termini of histone 3 (H3), including tri‐methylated H3 lysine 9 (H3K9Me3) or lysine 27 (H3K27Me3) represent repressive chromatin marks that are recognized by a family of heterochromatin‐associated Chromobox (Cbx) proteins (i.e., Cbx1 to Cbx8). We show using RNA‐seq analysis that each of these Cbx isoforms is actively expressed in bone and osteoblasts with variable expression of distinct members (between 1 and 100 reads per million). The most prominently expressed Cbx member is Cbx3, which encodes a member of the heterochromatin protein 1 (HP1) family that interacts with H3K9me3. Cbx3 is known to be important for normal development while promoting neurogenesis, as well as renal and smooth muscle development. Therefore, we postulated that CBx3 may perform a similar role in osteoblastogenesis. We tested this hypothesis by both transient and stable knock‐down of Cbx3 by respectively siRNA or shRNA. RNA interference in MC3T3 osteoblasts effectively decreases Cbx3 mRNA levels by 2 to 5 fold, while increasing expression of bone‐related markers by RT‐qPCR (e.g., Alpl/alkaline phosphatase, Ibsp/bone sialoprotein, Bglap/osteocalcin, and Col1a1/Collagen Type I α1 chain). In addition, Cbx3 depletion increases mineral deposition as measured by Alizarin Red staining. Thus, Cbx3 normally appears to suppress osteoblastic differentiation, unlike its essential function in the neuronal differentiation. Because Cbx3 recognizes H3K9me3, we examined whether Cbx3 controls the levels of this histone mark. Loss of Cbx3 did not affect total H3K9me3 levels unless Cbx1 and Cbx5 were simultaneously depleted by siRNA. We propose that Cbx3 may suppress osteoblastogenesis by controlling select loci with H3K9me3 marks.

Strain-promoted alkyne–azide cycloaddition (SPAAC) click chemistry was applied for the rapid conjugation of nanoparticles, proteins, and siRNA-micelles to ultrasound microbubbles.

Ultrafast plane wave imaging enables acquisition and accumulation of a large number of Doppler ensembles in a short period of time, which substantially boosts ultrasound Doppler sensitivity by at least an order of magnitude. As a key component, spatiotemporal clutter filtering based on singular value decomposition (SVD) has recently demonstrated superior performance in tissue clutter suppression and microvessel signal extraction over conventional high-pass-filter-based clutter filtering techniques. This presentation introduces several novel SVD clutter filter techniques from our recent work, focusing on addressing the technical challenges (complex tissue motion, high computational cost, and noise) of SVD clutter filter during clinical translations of the ultrafast microvessel imaging technology for human imaging. We present a block-wise adaptive SVD filter method that can robustly threshold singular values on a local level, a real-time feasible SVD clutter filtering method based on partial SVD and randomized spatial downsampling, and a noise equalization and suppression method that can significantly improve microvessel imaging quality at a low cost. In vivo performance of these methods will be demonstrated in different organs.

AbstractBecause of the rapidly growing use of ultrasound shear wave elastography (SWE) in clinical practices, there is a significant need for development of clinical physics performance assessment methods for this technology. This study aims to report two clinical medical physicists’ tasks: (a) acceptance testing (AT) of SWE function on ten commercial ultrasound systems for clinical liver application and (b) comparison of SWE measurements of targets across vendors for clinical musculoskeletal application. For AT, ten GE LOGIQ E9 XDclear 2.0 scanners with ten C1‐6‐D and ten 9L‐D transducers were studied using two commercial homogenous phantoms. Five measurements were acquired at two depths for each scanner/transducer pair by two operators. Additional tests were performed to access effects of different coupling media, phantom locations and operators. System deviations were less than 5% of group mean or three times standard deviation; therefore, all systems passed AT. A test protocol was provided based on results that no statistically significant difference was observed between using ultrasound gel and salt water for coupling, among different phantom locations, and that interoperator and intraoperator coefficient of variation was less than 3%. For SWE target measurements, two systems were compared — a Supersonic Aixplorer scanner with a SL10‐2 and a SL15‐4 transducer, and an abovementioned GE scanner with 9L‐D transducer. Two stepped cylinders with diameters of 4.05–10.40 mm were measured both longitudinally and transaxially. Target shear wave speed quantification was performed using an in‐house MATLAB program. Using the target shear wave speed deduced from phantom specs as a reference, SL15‐4 performed the best at the measured depth. However, it was challenging to reliably measure a 4.05 mm target for either system. The reported test methods and results could provide important information when dealing with SWE‐related tasks in the clinical environment.

AbstractBackgroundIn treatment planning for intensity‐modulated proton therapy (IMPT), we aim to deliver the prescribed dose to the target yet minimize the dose to adjacent healthy tissue. Mixed‐integer programming (MIP) has been applied in radiation therapy to generate treatment plans. However, MIP has not been used effectively for IMPT treatment planning with dose‐volume constraints. In this study, we incorporated dose‐volume constraints in an MIP model to generate treatment plans for IMPT.MethodsWe created a new MIP model for IMPT with dose volume constraints. Two groups of IMPT treatment plans were generated for each of three patients by using MIP models for a total of six plans: one plan was derived with the Limited‐memory Broyden–Fletcher–Goldfarb–Shanno (L‐BFGS) method while the other plan was derived with our MIP model with dose‐volume constraints. We then compared these two plans by dose‐volume histogram (DVH) indices to evaluate the performance of the new MIP model with dose‐volume constraints. In addition, we developed a model to more efficiently find the best balance between tumor coverage and normal tissue protection.ResultsThe MIP model with dose‐volume constraints generates IMPT treatment plans with comparable target dose coverage, target dose homogeneity, and the maximum dose to organs at risk (OARs) compared to treatment plans from the conventional quadratic programming method without any tedious trial‐and‐error process. Some notable reduction in the mean doses of OARs is observed.ConclusionsThe treatment plans from our MIP model with dose‐volume constraints can meet all dose‐volume constraints for OARs and targets without any tedious trial‐and‐error process. This model has the potential to automatically generate IMPT plans with consistent plan quality among different treatment planners and across institutions and better protection for important parallel OARs in an effective way.

Shear wave elasticity imaging determines the mechanical parameters of soft tissue by analyzing measured shear waves induced by an acoustic radiation force. Currently, the widely used time-of-flight method calculates the correlation between shear waveforms at adjacent lateral observation points to estimate the shear elasticity value. Although this method provides accurate estimates of the shear elasticity in purely elastic media, our experience suggests that this approach overestimates the shear elasticity values in viscoelastic media because the effects of diffraction, attenuation, and dispersion are not taken into account. To address this problem, we have developed an approach that directly accounts for all of these effects when estimating the shear elasticity. This new approach simulates shear waveforms using a Green’s function-based approach with a Voigt model, while the shear elasticity and viscosity values are estimated using an optimization-based approach by comparing measured shear waveforms with simulated shear waveforms in the time-domain. This operation is then performed on a point-by-point basis to generate images. The results indicate that there is good agreement between the simulated and measured shear velocity waveforms, and that this approach yields improved images of the shear elasticity and shear viscosity. [Work supported, in part, by NIH Grant R01DK092255.]

Shear wave elastography (SWE) is clinically used for the measurement of soft tissue mechanical properties. Most SWE methods assume that the tissue is elastic, but soft tissues are inherently viscoelastic. The viscoelasticity can be characterized by examining phase velocity dispersion. Methods to extract the phase velocities from the spatiotemporal data, v(x,t), involve using a two-dimensional Fourier transform. The Fourier representation, V(k,f), is searched for peaks that correspond to the phase velocities. We present a method that uses the Multiple Signal Classification (MUSIC) method to provide robust estimation of the phase velocity dispersion curves. We compared results from the MUSIC method with the current approach of searching for peaks in the V(k,f) representation. We tested this method on digital phantom data created using finite element models (FEMs) in viscoelastic media excited by a simulated acoustic radiation force push from a curved linear array. We evaluated the algorithm with different levels of added noise. Additionally, we tested the methods on data acquired in viscoelastic phantoms with a Verasonics system. The MUSIC algorithm provided dispersion estimation with lower errors than the conventional peak search strategy. This method can be used for evaluation of wave velocity dispersion in viscoelastic tissues and guided wave propagation. [This work was supported in part by grant R01DK092255.]

AimThe aim of this study was to compare passive muscle stiffness in children with cerebral palsy (CP) and children with typical development using a novel ultrasound technique: ultrasound shear wave elastography (SWE).MethodWe conducted a prospective study of 13 children with CP (six females and seven males, median age 5y 1mo [interquartile range 4y 4mo–7y 8mo]) and 13 children with typical development (six females and seven males, median age 5y 3mo [interquartile range 4y 4mo–9y 4mo]). Demographic information and physical exam measurements were obtained in addition to shear modulus measurements (passive muscle stiffness) of the lateral gastrocnemius muscle at 20° plantar flexion, 10° plantar flexion, and 0° plantar flexion using SWE.ResultsChildren with CP had significantly greater shear modulus measurements at all three foot positions (p<0.050). When the shear modulus values were normalized to the baseline value for each child, there was no significant difference between the two groups.InterpretationPassive muscle stiffness, measured without the influence of spasticity, is greater in children with CP than in children with typical development when a muscle is at slack and at stretch. When shear modulus was normalized, the results indicate that muscle in children in both groups responds similarly to passive stretch. Further work includes evaluating effect of botulinum toxin on passive muscle properties.