Citations

The mechanical response of tissues to external forces has gained considerable interest in medical diagnosis. Typically, a force is needed to produce displacement in the tissue for estimation of the tissue’s elasticity. One approach is to apply an external force on the body’s surface. Another emerging technique is to generate a localized force inside the tissue with ultrasound. Shear waves can be used in bulky tissues for estimating the tissue’s elasticity. The bending wave can be generated and measured in vessels for noninvasive estimation of a vessel’s elasticity. We have found that the Rayleigh surface wave can be generated on the tissue’s surface, [X. Zhang et al., Proc. International Congress on Ultrasonics, Vienna, April 9–13, 2007], [X. Zhang et al., IEEE Trans. Medical Imaging, 26, 843–852 (2007)]. In our method, a localized radiation force of ultrasound is remotely and noninvasively applied inside the tissue. This force can generate the shear wave as well as compression wave inside the tissue. However, only the surface wave can exist on the body’ surface. The surface wave can be used to estimate and image the stiffness of tissue. Some results of using the surface wave are presented.

Abnormal secretion of PTH by the parathyroid glands contributes to a variety of common skeletal disorders. Prior studies implicate platelet-derived growth factor-A (PDGF-A) as an important mediator of selective PTH actions on bone. The present studies used targeted gene profiling and small-molecule antagonists directed against candidate gene products to elucidate the roles of specific PTH-regulated genes and signaling pathways. A group of 29 genes in rats continuously infused with PTH and cotreated with the PDGF receptor antagonist trapidil were differentially expressed compared with PTH treatment alone. Several of the identified genes were functionally clustered as regulators of fibroblast differentiation and extracellular matrix modeling, including the matrix cross-linking enzyme lysyl oxidase (LOX). Treatment with β-aminopropionitrile, an irreversible inhibitor of LOX activity, dramatically reduced diffuse mineralization but had no effect on PTH-induced fibrosis. In contrast, the receptor tyrosine kinase inhibitor Gleevec and the phosphoinositide 3-kinase inhibitor wortmannin each reduced bone marrow fibrosis. In summary, the present studies support the hypotheses that PTH-induced bone marrow fibrosis is mediated by PDGF-A via a phosphoinositide 3-kinase-dependent signaling pathway and that increased LOX gene expression plays a key role in abnormal mineralization, a hallmark of chronic hyperparathyroidism.

Abstract Catechol O-methyltransferase (COMT)-catalyzed methylation of catecholestrogens has been proposed to play a protective role in estrogen-induced genotoxic carcinogenesis. We have taken a comprehensive approach to test the hypothesis that genetic variation in COMT might influence breast cancer risk. Fifteen COMT single nucleotide polymorphisms (SNPs) selected on the basis of in-depth resequencing of the COMT gene were genotyped in 1,482 DNA samples from a Mayo Clinic breast cancer case control study. Two common SNPs in the distal promoter for membrane-bound (MB) COMT, rs2020917 and rs737865, were associated with breast cancer risk reduction in premenopausal women in the Mayo Clinic study, with allele-specific odds ratios (OR) of 0.70 [95% confidence interval (CI), 0.52–0.95] and 0.68 (95% CI, 0.51–0.92), respectively. These two SNPs were then subjected to functional genomic analysis and were genotyped in an additional 3,683 DNA samples from two independent case control studies (GENICA and GESBC). Functional genomic experiments showed that these SNPs could up-regulate transcription and that they altered DNA-protein binding patterns. Furthermore, substrate kinetic and exon array analyses suggested a role for MB-COMT in catecholestrogen inactivation. The GENICA results were similar to the Mayo case control observations, with ORs of 0.85 (95% CI, 0.72–1.00) and 0.85 (95% CI, 0.72–1.01) for the two SNPs. No significant effect was observed in the GESBC study. These studies showed that two SNPs in the COMT distal promoter were associated with breast cancer risk reduction in two of three case control studies, compatible with the results of functional genomic experiments, suggesting a role for MB-COMT in breast cancer risk. [Cancer Res 2008;68(14):5997–6005]

A new method for imaging and detecting modal shapes of vessels is introduced. Theory is developed that predicts the measured velocity is proportional to the value of the mode shape at the focal point of the ultrasound beam. Experimental a cylindrical gel phantom of large radius. This model simulates approximately a large artery and the surrounding body. The fundamental frequency was measured 83 Hz for the tube-phantom system. At this frequency the ultrasound transducer was scanned across the vessel plane with velocity measurement at one single point on the vessel and on the phantom by laser. The images obtained show clearly the interior tube and the modal shape of the tube.

Vibro-acoustography is a new noncontact imaging method based on the radiation force of ultrasound. We extend this new technique for tissue characterization of arterial vessels by vibration techniques. In this paper a theoretical model for vibration analysis of arterial vessel with tissue is developed. Experimental studies were carried out on a silicone rubber tube embedded in a cylindrical gelatin phantom of larger radius, which simulates a large artery and the tissue body. The fundamental mode is well excited by the radiation force of ultrasound. The fundamental frequency was measured 81.8 Hz for a tube-phantom structure that is quite close to our theoretical prediction of 83.3 Hz.

Considerable interest in the elastic properties of soft tissue has increased in medicine due to their clinical relevance for monitoring various diseases as well as a biomarker for cancer. A recent emerging field is the use of acoustic radiation force for imaging and estimating the elastic properties of tissue. Newly developed imaging modalities include shear wave elasticity imaging, supersonic shear wave imaging, acoustic radiation force impulse imaging, and vibro-acoustography. In these new methods, the shear wave is used to estimate the elasticity of tissue. We have developed a novel surface wave method for noninvasively estimating the elasticity of tissue [X. Zhang et al., J. Acoust. Soc. Am., 122, 2522-2525 (2007)]. In this method, a localized ultrasound radiation force is remotely and noninvasively applied inside the tissue. The surface wave speed is used to estimate the elasticity of tissue. This method has been further developed and applied to estimate the viscoelasticity of animal myocardium tissue. In this abstract, we report our recent results of in vitro studies on animal myocardium tissue. Both the surface wave and shear wave are measured and analyzed. Noninvasive characterization of viscoelastic properties of myocardium tissue may be a very important tool for assessing heart function.

Harmonic or pulsed radiation pressure and subsequent measurement of the tissue response can be used to accurately quantitatively measure fundamental material properties of tissue. The measurement of shear wave dispersion can be used to estimate elastic shear moduli of tissue using an appropriate model. Fundamental model free properties such as complex modulus can also be measured. Ultrasound radiation pressure is used to induce free propagating shear waves. The measurable properties of the shear waves such as speed are sensitive to only the local material properties of the tissue under certain circumstances. A model relating the shear wave speed as a function of frequency is related to the elastic and viscous moduli within small regions of tissue according to, for instance, the Voigt model. Shear and elastic moduli in tissue are measured with high accuracy and precision given appropriate models of wave propagation within the geometry of the tissue. Complex modulus in liver of live pig and other tissues have been made. Careful use of shear wave propagation and subsequent measurements can provide fundamental quantitative measurements of tissue mechanical properties if models are accurate. An application of this method is the noninvasive measurement of liver stiffness as a surrogate for fibrosis.

Background— Previous studies that assessed the risk of life-threatening cardiac events in patients with congenital long-QT syndrome (LQTS) have focused mainly on the first 4 decades of life, whereas the clinical course of this inherited cardiac disorder in the older population has not been studied. Methods and Results— The risk of aborted cardiac arrest or death from age 41 though 75 years was assessed in 2759 subjects from the International LQTS Registry, categorized into electrocardiographically affected (corrected QT interval [QTc] ≥470 ms), borderline (QTc 440 to 469 ms), and unaffected (QTc <440 ms) subgroups. The affected versus unaffected adjusted hazard ratio for aborted cardiac arrest or death was 2.65 ( P <0.001) in the age range of 41 to 60 years and 1.23 ( P =0.31) in the age range of 61 to 75 years. The clinical course of study subjects displayed gender differences: Affected LQTS women experienced a significantly higher cumulative event rate (26%) than borderline (16%) and unaffected (12%) women ( P =0.001), whereas event rates were similar among the 3 respective subgroups of men (29%, 26%, and 27%; P =0.16). Recent syncope (<2 years in the past) was the predominant risk factor in affected subjects (hazard ratio 9.92, P <0.001), and the LQT3 genotype was identified as the most powerful predictor of outcome in a subset of 871 study subjects who were genetically tested for a known LQTS mutation (hazard ratio 4.76, P =0.02). Conclusions— LQTS subjects maintain a high risk for life-threatening cardiac events after age 40 years. The phenotypic expression of affected subjects is influenced by age-specific factors related to gender, clinical history, and the LQTS genotype.