Fatemi, Mostafa

Healthy human bladder is a viscoelastic shell capable of expanding to allow storage of urine at low pressures. The ability to maintain low pressures as the urine volume increases is called bladder compliance. Compliance is a key in proper functioning of urinary system. Spinal cord injuries and other neurogenic diseases can cause deterioration in bladder expansion capability (e.g., through excessive growth of fibrotic tissue), which in turn can increase the rigidity of the wall and reduce bladder compliance. Urodynamic study (UDS) is the clinical standard for evaluation of the bladder compliance through observation of bladder pressure-volume behavior. However, this method is costly and invasive. Ultrasound bladder vibrometry (UBV) has been introduced as noninvasive technique for evaluation of bladder viscoelasticity through excitation of the bladder using ultrasound radiation force and tracking the resulting Lamb waves. Here, we present the results of UBV from 44 patients undergoing concurrent UDS and UBV studies. Our results show that elasticity parameters obtained from the UBV closely correlate with the UDS pressure-volume data with a median Pearson’s correlation value of more than 0.8. These results prove the potential utility of UBV as an alternative noninvasive method for bladder compliance assessment. [Work supported by NIH grant DK99231.]

There is an urgent need for a noninvasive but more accurate method to assess breast masses before referring the patient to biopsy. In this study, we use the slow viscoelastic creep response to evaluate breast masses at low (<1 Hz) frequencies. This method uses an automated ramp-and-hold compression device and a high-frame-rate ultrasound imaging to track tissue strain. The study cohort included 30 pre-biopsy patients with suspicious masses. Sequential high-frame-rate images were recorded during the ramp-and-hold process. The data were used to calculate the creep response at each point. Then, using a classic linear model, the retardation-time map was created within the field of view. The resulting retardation-time maps exhibited clear distinction of the mass margins. The results showed that benign breast lesions appear with an increase in creep retardation-time compared to surrounding breast glandular tissue, and the opposite trend was true for the malignant lesions. Statistical analysis of the viscoelasticity features revealed that a contrast feature based on the retardation-time is an accurate classifier of malignant and benign masses (P<0.0003). It is concluded that the retardation time is a promising biomarker for differentiation of breast masses. [Work supported by NIH Grant CA168575.]

Ultrasound transient elastography has emerged as a promising imaging modality for noninvasive evaluation of tissue mechanical properties. Most of the established techniques, however, rely on a pointwise measurement of the induced shear wave speed based on a localized planar wave propagation assumption. This assumption is not always true as most tissues exhibit heterogamous characteristics. Complex interaction of different geometries, boundary conditions, and tissue composition limit the ability of these techniques such that additional spatial-temporal filtering and signal truncations are required. These signal conditionings might lead to improvement in elasticity estimation for some cases (e.g. certain geometries, material properties) but the fact that they do not stem from a comprehensive framework can lead to unrealistic mechanical properties in more complex scenarios. We present a generalized framework based on inverse solution of the elasto-dynamic equations which can simultaneously solve for material properties and geometries without requiring any prior knowledge of the wave types. The method is based on a modified error in constitutive equation (MECE) without requiring additional filtering. We present the results of standard phantom studies based on acoustic radiation force excitation and fast ultrasound tracking where MECE technique successfully estimated the elastic moduli and geometry. [Work supported by NIH grant CA174723.]

In this work, an ultrasound-guided remote measurement technique is proposed for bone demineralization assessment. Utilizing an acoustic radiation force (ARF) beam as our excitation source and a receiving hydrophone, the mechanical properties of a bone can be noninvasively assessed. Focusing the ARF beam on the bone surface acts as point force generating vibrational waves. Coupling the bone surface and hydrophone, the ensuing radiating acoustic pressure from these vibrational waves are captured for analysis. Of particular interest, are the features best related to the bone’s mechanical properties. Conducting ex-vivo experiments demonstrated that the velocity feature best delineates intact and demineralized bones. The typical velocity of an intact bone (3000 m/s) is higher in comparison to a 72 h demineralized bone (1600 m/s). According to the receiver operating characteristic (ROC) curve, the optimal velocity cut-off value of 3096 m/s yields 80% sensitivity and 82.61% specificity between the intact and demineralized bones. Other features, such as the spectra of the demineralized bones’ acoustic response, exhibited higher attenuation for frequencies below 200 kHz in comparison to the intact bones. A time-frequency analysis demonstrated a frequency shift with demineralization. These results demonstrate the potential application of our proposed technique for monitoring bone demineralization.

Low frequency harmonic force excitation can be used for both imaging and tissue characterization. This type of excitation can be achieved via intersecting two beams that slightly differ in frequency. One requirement of this technique is creating focused intersecting beams using available hardware. Previous studies have suggested different configurations for creating harmonic radiation force using linear arrays. However, these methods rely on identical frequency response assumption across all elements of the aperture. In practice, this assumption can be easily violated, especially if the transmit frequencies are not around the center frequency of the probe. When using electronic steering and focusing at different locations, this can result in a non-uniform radiation force pattern due to frequency changes in the sub-aperture. When used for vibro-acoustography, this manifests as vertical streaks in the final image that can severely degrade the quality of the image. We present a novel technique that minimizes element transmit frequency switching which in turn results in a more uniform excitation intensity. The results of applying this aperture configuration for vibro-acoustography imaging of breast phantoms with hard inclusions show significant improvements over previous methods. [This work was supported by NIH Grant R01 EB17213.]

In this work, the results from our Comb Push Ultrasound Shear Elastography (CUSE) assessment of suspicious breast lesions are presented. The elasticity value of the breast lesions are correlated to histopathological findings to evaluate their diagnostic value in differentiating between malignant and benign breast lesions. A total of 44 patients diagnosed with suspicious breast lesions were evaluated using CUSE prior to biopsy. All patient study procedures were conducted according to the protocol approved by Mayo Clinic Institutional Review Board (IRB). Our cohort consisted of 27 malignant and 17 benign breast lesions. The results indicate an increase in shear wave velocity in both benign and malignant lesions compared to normal breast tissue. Furthermore, the Young’s modulus is significantly higher in malignant lesions. An optimal cut-off value of the Young’s modulus ≥ 80 kPa was observed for the receiver operating characteristic (ROC) curve. This is concordant with the published cut-off values of elasticity for suspicious breast lesions. [This work is supported in part by the grant 3R01CA148994-04S1 and 5R01CA148994-04 from NIH.]

Acoustic radiation force (ARF) provides a simple and yet non-invasive mechanism to induce a localized stress inside human body. The response to this excitation is used to estimate the mechanical properties of the targeted tissue in vivo. This talk covers an overview of three studies that use ARF for estimation of elastic properties of thyroid, breast, and the bladder in patients. The studies on thyroid and breast were aimed at differentiating between malignant and benign nodules. The study on the bladder was aimed at indirect evaluation of bladder compliance; hence, only a global measurement was needed. The study on breast showed that 16 out of 18 benign masses and 21 out of 25 malignant masses were correctly identified. The study on 9 thyroid patients with 7 benign and 2 malignant nodules showed all malignant nodules were correctly classified and only 2 of the 7 benign nodules were misclassified. The bladder compliance study revealed a high correlation between our method and independent clinical measurement of compliance (R-squared of 0.8–0.9). Further investigations on larger groups of patients are needed to fully evaluate the performances of the methods.

Vibro-acoustography has gained interest in the recent years as a new modality for medical imaging. This method is based on low-frequency vibrations induced in the object by the radiation force of ultrasound. This paper focuses on potential applications of vibro-acoustography in breast imaging, including detection of microcalcifications, detection of arterial calcifications, and soft tissue imaging. In addition, we will briefly discuss our recent results of in vivo breast vibro-acoustography. Future developments and potential impact of vibro-acoustography in breast imaging are also discussed.

Bladder compliance is defined as bladder’s ability to expand in volume without a significant change in pressure. The bladder wall is a multi-layered structure including a muscular layer and fibrous connective tissue. As the percent of connective tissue in the bladder interstitium increases compared to smooth muscle, the bladder becomes more rigid and less capable of expanding during filling. Currently, urodynamic studies (UDS) are considered as the clinical gold standard for bladder compliance assessment. This procedure is invasive and is associated with patient discomfort and is expensive. Ultrasound bladder vibrometry (UBV) is a novel acoustic-radiation-forced-based method for noninvasive assessment of bladder compliance. In UBV, an impulsive acoustic radiation force is focused on the bladder wall (under B-mode ultrasound image guidance) to induce vibrations which may be modeled by as a Lamb wave. High frame rate ultrasound is then utilized to detect the induced waves. This wave motion is then used to estimate the viscoelastic properties and the compliance of the bladder wall. Our results reveal a remarkable agreement between UBV and UDS cystometry measures, suggesting the potential of UBV as a viable clinical tool for the assessment of bladder compliance.