Citations

Abstract The myocardium is known to be an anisotropic medium where the muscle fiber orientation changes through the thickness of the wall. Shear wave elastography methods use propagating waves which are measured by ultrasound or magnetic resonance imaging (MRI) techniques to characterize the mechanical properties of various tissues. Ultrasound- or MR-based methods have been used and the excitation frequency ranges for these various methods cover a large range from 24–500 Hz. Some of the ultrasound-based methods have been shown to be able to estimate the fiber direction. We constructed a model with layers of elastic, transversely isotropic materials that were oriented at different angles to simulate the heart wall in systole and diastole. We investigated the effect of frequency on the wave propagation and the estimation of fiber direction and wave speeds in the different layers of the assembled models. We found that waves propagating at low frequencies such as 30 or 50 Hz showed low sensitivity to the fiber direction but also had substantial bias in estimating the wave speeds in the layers. Using waves with higher frequency content (>200 Hz) allowed for more accurate fiber direction and wave speed estimation. These results have particular relevance for MR- and ultrasound-based elastography applications in the heart.

Many methods for characterization of the mechanical properties of soft tissues using propagating shear waves have been developed over the past two decades. Most of these methods assume that the shear wave is traveling in an elastic, isotropic tissue. However, many soft tissues are viscoelastic and have material properties that are directionally dependent or anisotropic. We have been developing methods to measure waves propagating in soft tissues to estimate the anisotropic viscoelastic material properties. To refine our measurement methods, we have also developed techniques and models for simulating the wave propagation in these types of materials. We have developed specialized finite element and pseudo-spectral models that can simulate viscoelastic transversely isotropic materials and compared our results with measurements in ex vivo porcine muscle. Additionally, we have developed a finite element model that simulates wave propagation in the myocardium by creating a model of layered transverse isotropic media oriented at different angles. We examined the effect of frequency of the waves for estimating of the angle of propagation. We compared these simulation results with experimental results from an ex vivo porcine left ventricular wall. These simulation methods provide insight for optimizing our measurement methods for in vivo characterization of material properties.

The mechanism of heme oxygenase-1 gene ( ho-1) activation by heme in immortalized rat proximal tubular epithelial cells was examined. Analysis of the ho-1promoter identified the heme-responsive sequences as the stress-response element (StRE), multiple copies of which are present in two enhancer regions, E1 and E2. Electrophoretic mobility shift assays identified Nrf2, MafG, ATF3, and Jun and Fos family members as StRE-binding proteins; binding of Nrf2, MafG, and ATF3 was increased in response to heme. Dominant-negative mutants of Nrf2 and Maf, but not of c-Fos and c-Jun, inhibited basal and heme-induced expression of an E1-controlled luciferase gene. Heme did not affect the transcription activity of Nrf2, dimerization between Nrf2 and MafG, or the level of MafG, but did stimulate expression of Nrf2. Heme did not influence the level of Nrf2 mRNA but increased the half-life of Nrf2 protein from ∼10 min to nearly 110 min. These results indicate that heme promotes stabilization of Nrf2, leading to accumulation of Nrf2 · MafG dimers that bind to StREs to activate the ho-1 gene.

Pre‐surgical measurement of supraspinatus muscle extensibility is important for rotator cuff repair. The purpose of the present study was to explore the potential feasibility of a shear wave ultrasound elastography (SWE)‐based method, combined with B‐mode ultrasound, to measure the in vivo stiffness of the supraspinatus muscle non‐invasively and thus obtain key information about supraspinatus muscle extensibility. Our investigation comprised two steps. First, we determined the orientation of the supraspinatus muscle fibers in cadaveric shoulders without rotator cuff tear in order to optimize the ultrasound probe positions for SWE imaging. Second, we investigated the feasibility of quantifying the stiffness of the normal supraspinatus muscle by SWE in vivo. The supraspinatus muscle was divided into four anatomical regions: anterior superficial (AS), posterior superficial (PS), anterior deep (AD), and posterior deep (PD). Each region was examined by SWE. The SWE stiffnesses of AD, AS, PD, and PS were 40.0 ± 12.4, 34.0 ± 9.9, 32.7 ± 12.7, 39.1 ± 15.7 kPa, respectively. SWE combined with B‐Mode ultrasound imaging could be a feasible method for quantifying the local stiffness of the rotator cuff muscles. Clin. Anat. 28:213–218, 2015. © 2014 Wiley Periodicals, Inc.

Objective The objective of this article is to evaluate electrically evoked thresholds for cortical spreading depression (CSD) and stress-induced activation of trigeminal afferents in a rat model of medication-overuse headache (MOH). Methods Sumatriptan or saline was delivered subcutaneously by osmotic minipump for six days to Sprague-Dawley rats. Two weeks after pump removal, animals were anesthetized and recording/stimulating electrodes implanted. The animals were pretreated with vehicle or topiramate followed by graded electrical stimulation within the visual cortex. CSD events were identified by decreased EEG amplitude and DC potential shift. Additional unanesthetized sumatriptan or saline-pretreated rats were exposed to bright light environmental stress and periorbital and hindpaw withdrawal thresholds were measured. Following CSD stimulation or environmental stress, immunohistochemical staining for Fos in the trigeminal nucleus caudalis (TNC) was performed. Results Sumatriptan pre-exposure significantly decreased electrical stimulation threshold to generate a CSD event. Topiramate normalized the decreased CSD threshold as well as stress-induced behavioral withdrawal thresholds in sumatriptan-treated rats compared to saline-treated animals. Moreover, CSD and environmental stress increased Fos expression in the TNC of sumatriptan-treated rats, and these effects were blocked by topiramate. Environmental stress did not elicit cutaneous allodynia or elevate TNC Fos expression in saline-treated rats. Conclusions A previous period of sumatriptan exposure produced long-lasting increased susceptibility to evoked CSD and environmental stress-induced activation of the TNC that was prevented by topiramate. Lowered CSD threshold, and enhanced consequences of CSD events (increased activation of TNC), may represent an underlying biological mechanism of MOH related to triptans.

Robust shear-wave motion detection is essential for producing reliable shear elasticity measurements for ultrasound shear-wave elastography (SWE). However, because shear-wave motion is extracted from radiofrequency signals which can be heavily contaminated by noise, shear-wave motion detection can be very challenging, especially for in vivo applications. This study investigated the implementation of harmonic imaging (HI) to facilitate more robust shear-wave tracking based on HI’s effectiveness in suppressing imaging noise associated with ultrasound reverberation, phase aberration, and clutter noise. A HI shear-wave tracking sequence was developed combining the pulse-inversion HI method with the plane wave imaging technique to transmit phase-inverted pulses at a high frame rate of several kilohertz. The backscattered ultrasound signals from phase-inverted pulses were added to suppress the fundamental and enhance the second harmonic component, from which the shear-wave motion was extracted. A pork belly phantom experiment showed that HI could significantly improve shear-wave motion detection by producing almost three-fold less underestimation of shear-wave motion and over ten-fold more precision for shear-wave speed measurements than fundamental imaging. An in vivo transthoracic case study of a human heart showed that HI substantially improved the success rate of shear-wave motion detection and could provide consistent estimates of the left ventricle myocardium stiffness.

Thyroid cancer is the fastest growing age and gender adjusted cancer in 2011 according the American Cancer Society. The majority of the clinically diagnosed thyroid nodules are benign while less than 5% represent intrathyroidal cancers. Currently, the clinical gold-standard procedure for assessing the thyroid nodules is needle biopsy, a procedure that is associated with significant financial burden as well as pain and risk for patients. Therefore, a noninvasive, affordable, and potentially widely available method to differentiate between benign and malignant thyroid nodules can play an important role in reducing the number of unnecessary biopsies. In this study, we investigate the feasibility of two acoustic radiation force elastography techniques, shear wave dispersion ultrasound vibrometry (SDUV) and comb-push ultrasound shear wave elastography (CUSE imaging), in identifying thyroid nodules (imaging) and differentiating between benign and malignant pathologies based on their elasticity and viscosity (SDUV measurements). Our preliminary results show that the measured shear elasticity and shear viscosity parameters depend on tissue type; hence, these measurements may be utilized to differentiate between healthy normal thyroid tissue, benign nodules, and malignant nodules. Further studies on a large population of patients is required to better evaluate the role of the combination of elasticity and viscosity properties of tissue in differentiating various thyroid nodules.

Tissue mechanical properties can be obtained by algebraic direct inversion (ADI) of the shear-wave motion differential equation, which is insensitive to reflection and geometry of the pushing beam. Shear waves normally generated by a focused ultrasound pushing beam have limited spatial extent in depth and are transient in time, leading to noisy and unstable ADI results. A comb-shape acoustic radiation force distribution can generate shear waves with longer spatial extent and time duration, facilitating more robust ADI. For 400 μs, a linear array transducer simultaneously transmitted four unfocused pushing beams (12 on elements for each pushing beam, 8 off elements between beams) into a tissue-mimicking phantom (∼1.5 kPa) with a cylindrical inclusion (∼4 kPa). The ultrasound system (Verasonics Inc.) then immediately switched to flash imaging mode (frame rate = 2 kHz, spatial resolution = 0.31 mm) to measure shear-wave displacements in a 38 mm by 30 mm domain that was used for ADI. The reconstructed 2D shear elasticity map provides accurate shear elasticity estimates (background = 1.5 kPa with 7% variance; inclusion = 3.9 kPa with 15% variance) and excellent contrast between the background and inclusion.