Characterizing sclerotic skin stiffness with Acoustic Radiation Force Impulse (ARFI) and Shear Wave Elasticity Imaging (SWEI)

ARFI and shear wave imaging of the prostate to delineate clinically-significant cancers

Shear Wave Elasticity Imaging (SWEI) is commonly used to characterize tissue elasticity, but conventional, multiple-track-location SWEI (MTL-SWEI) techniques are resolution-limited by speckle. MTL-SWEI techniques use plane wave ultrasound to monitor an induced shear wave as it propagates across a set of tracking beams within a region of interest. The scattering process creates a random, yet stationary, spatial sensitivity pattern for each beamformed location, called speckle bias, which causes errors in MTL-SWEI shear wave speed estimates that cannot be improved through averaging. Single Track Location SWEI (STL-SWEI) overcomes speckle bias by using a single track beam, subsequently exciting and tracking different push locations, and comparing the timing of the recorded shear wave signals from different push locations to estimate shear wave speed. Two and three-dimensional STL-SWEI imaging techniques are presented and compared to MTL-SWEI and Acoustic Radiation Force Impulse (ARFI) imaging in phantoms and in vivo experiments. Tradeoffs and techniques for sequencing, beamforming, shear wave speed estimation, and image formation are discussed. For applications where tissue heating and motion are not limiting factors, STL-SWEI provides superior imaging in terms of lateral resolution and contrast-to-noise ratio compared to MTL-SWEI and ARFI. [This work was supported by NIHR37HL096023 and NIHR01EB01248.]

It has been observed that many pathological process increase the elastic modulus of soft tissue compared to normal. In order to image tissue stiffness using ultrasound, a mechanical compression is applied to tissues of interest and local tissue deformation is measured. Based on the mechanical excitation, ultrasound stiffness imaging methods are classified as compression or strain imaging which is based on external compression and Acoustic Radiation Force Impulse (ARFI) imaging which is based on force generated by focused ultrasound. When ultrasound is focused on tissue, shear wave is generated in lateral direction and shear wave velocity is proportional to stiffness of tissues. The work presented in this paper investigates strain elastography and ARFI imaging in clinical cancer diagnostics using real time patient data. Ultrasound B-mode imaging, strain imaging, ARFI displacement and ARFI shear wave velocity imaging were conducted on 50 patients (31 Benign and 23 malignant categories) using Siemens S2000 machine. True modulus contrast values were calculated from the measured shear wave velocities. For ultrasound B-mode, ARFI displacement imaging and strain imaging, observed image contrast and Contrast to Noise Ratio were calculated for benign and malignant cancers. Observed contrast values were compared based on the true modulus contrast values calculated from shear wave velocity imaging. In addition to that, student unpaired t-test was conducted for all the four techniques and box plots are presented. Results show that, strain imaging is better for malignant cancers whereas ARFI imaging is superior than strain imaging and B-mode for benign lesions representations.

Currently, the evaluation of lesions in the gastrointestinal (GI) tract using ultrasound suffers from poor contrast between healthy and diseased tissue. Acoustic radiation force impulse (ARFI) imaging provides information about the mechanical properties of tissue using brief, high-intensity, focused ultrasound to generate radiation force, and conventional, ultrasonic correlation-based methods to track tissue displacement. Using conventional linear arrays, ARFI imaging has shown improved contrast over B-mode images when applied to solid masses in the breast and liver. The purpose of this work is to (1) demonstrate that ARFI imaging can be performed with an endocavity probe, and (2) demonstrate that ARFI imaging can provide improvements over conventional B-mode imaging of GI lesions. An EC94, 6.2 MHz, endocavity probe was modified to perform ARFI imaging in tissue-mimicking phantoms using a Siemens SONOLINE Antares/spl trade/ scanner. ARFI imaging was performed on fresh, surgically excised, GI lesions using a 75L40, 7.2 MHz. linear array on a modified Siemens SONOLINE Elegra/spl trade/ scanner. The endocavity probe created ARFI images to a depth of over 2 cm in tissue-mimicking phantoms, with maximum displacements of 5 /spl mu/m. The endocavity probe did not heat appreciably during ARFI imaging, demonstrating that the probe's small size will not limit in vivo ARFI imaging. ARFI images of an adenocarcinoma of the gastroesophageal (GE) junction status post chemotherapy and radiation treatment, demonstrate better contrast between healthy and fibrotic/malignant tissue than standard B-mode images. ARFI images of healthy gastric, esophageal, and colonic tissue specimens differentiate normal anatomic tissue planes (i.e., mucosal, muscularis, and adventitial layers), as confirmed by histologic evaluation. ARFI imaging of an ex vivo colon cancer portrays interesting contrast and structure not present in B-mode images. These findings support the clinical feasibility of endoscopic ARFI imaging to guide diagnosis and staging of disease processes in the GI tract.

Preliminary Results on the Feasibility of Using ARFI/SWEI to Assess Cutaneous Sclerotic Diseases

Constructive shear wave interference imaging to characterize skin sclerosis

Quantifying Skin Stiffness in Graft-Versus-Host Disease, Morphea, and Systemic Sclerosis Using Acoustic Radiation Force Impulse Imaging and Shear Wave Elastography

Children receiving multiple blood cell transfusions are prone to iron overload and successive tissue damage in liver parenchyma, making noninvasive screening options desirable. Ultrasound (US) elastography using acoustic radiation force impulse (ARFI) imaging enables evaluation of liver parenchyma stiffness, and MRI allows for quantification of liver iron concentration. The objective was to correlate US elastography with MRI in children who had undergone bone marrow transplantation and to evaluate the modification of liver tissue with US in combination with clinical parameters at follow-up. ARFI, T2*-weighted MRI and a clinical score (HepScore, based on parameters of liver function) were performed in 45 patients (24 male; mean age 9.7years) before and 100days and 365days after transplantation. All received multiple blood transfusions (mean number 22.2 up until 1year after transplantation). We correlated US findings and HepScore with MRI findings. We observed signs of iron accumulation in 29/45 (64.4%) patients on MRI (T2*<10ms) and 15/45 (33.3%) showed increased tissue stiffness (ARFI>5.5kPa). Correlation of elastography and MRI was not significant (P=0.57; n=51 matched measurements). Comparing US elastography with HepScore in receiver operating characteristic (ROC) curve analysis indicated a cut-off for affected parenchyma if HepScore was >5 points (sensitivity 67%, specificity 68%). Simultaneous increases of both indicated tissue alteration. Combining US and HepScore enabled detection of liver tissue alteration through iron overload, but we found no direct significant effect of estimated iron from MRI on ARFI imaging.

Prostate cancer (PCa) is conventionally diagnosed using transrectal ultrasound (TRUS) guided biopsy. B-mode ultrasound is used to direct the biopsy needle to regions of the prostate gland, but is not used to target cancer-suspicious regions due to its low specificity for PCa. We are developing multiparametric quantitative ultrasound imaging approaches to facilitate targeting ultrasound-guided biopsies toward regions suspicious for PCa. To identify PCa during TRUS imaging, we combine information from four ultrasonic techniques: acoustic radiation force impulse (ARFI) imaging, shear wave elasticity imaging (SWEI), quantitative ultrasound (QUS) and B-mode ultrasound. 3-D co-registered in vivo ultrasound data, and MRI T2-weighted and ADC data volumes have been acquired from 30 patients prior to radical prostatectomy, obtaining estimates of ARFI displacement, shear wave speed, QUS midband fit, B-mode brightness, T2 intensity, and ADC values. In each data volume, healthy and cancerous regions were manually segmented with guidance from whole mount histology; the intersection of the cancerous segmentations from all modalities was labeled as the ground truth. We will present a range of classification approaches, including LDA and SVM, to combine information from each modality in order to develop automated tools for targeted biopsy.Prostate cancer (PCa) is conventionally diagnosed using transrectal ultrasound (TRUS) guided biopsy. B-mode ultrasound is used to direct the biopsy needle to regions of the prostate gland, but is not used to target cancer-suspicious regions due to its low specificity for PCa. We are developing multiparametric quantitative ultrasound imaging approaches to facilitate targeting ultrasound-guided biopsies toward regions suspicious for PCa. To identify PCa during TRUS imaging, we combine information from four ultrasonic techniques: acoustic radiation force impulse (ARFI) imaging, shear wave elasticity imaging (SWEI), quantitative ultrasound (QUS) and B-mode ultrasound. 3-D co-registered in vivo ultrasound data, and MRI T2-weighted and ADC data volumes have been acquired from 30 patients prior to radical prostatectomy, obtaining estimates of ARFI displacement, shear wave speed, QUS midband fit, B-mode brightness, T2 intensity, and ADC values. In each data volume, healthy and cancerous regions were manually segm...

To assess the performance of conventional high frequency ultrasound (US) and US elastography in diagnosis of complex cystic and solid breast lesions. Ninety three lesions in 93 patients underwent conventional US and US elastography, including strain elastography, acoustic radiation force impulse (ARFI) imaging, and point shear wave speed (SWS) measurement. Pathological examination revealed 31 (33.3%) of the 93 lesions were malignant and the remaining 62 (66.7%) were benign. Multivariate analysis showed that elder patient (OR: 25.301), internal vascularity (OR: 4.518), and not circumscribed margin (OR: 3.813) were independent predictors for malignancy, while predominately cystic lesions (OR: 0.178) was a predictor for benign lesions (all p < 0.05). Invalid SWS measurement was occurred in 19 of 31 (61.3%) malignant lesions and 16 of 62 (25.8%) benign lesions, respectively (p < 0.05). The mean SWS value for malignant lesions was significantly lower than that for benign ones, being 1.60±0.63 m/s (range, 0.68-2.70 m/s) versus 2.33±0.77 m/s (range, 0.67-3.97 m/s) (p < 0.05). Areas under the ROC curve (Azs) for Breast Imaging Reporting and Data System (BI-RADS) assessment, strain elasticity score, ARFI imaging and valid point SWS measurement were 0.844, 0.734, 0.763 and 0.778,respectively. US BI-RADS category, strain elastography score, ARFI imaging patterns and point SWS measurement are useful for malignancy prediction of complex cystic and solid breast lesions. The result that SWS for malignant lesions is lower than benign one should be carefully interpreted since invalid SWS measurement is excluded for analysis. The true stiffness of malignant cystic and solid lesions should be further evaluated with a new generation of two-dimensional SWS imaging.

When the Spleen Gets Tough, the Varices Get Going

Characterizing Stiffness of Human Prostates Using Acoustic Radiation Force

Four pigs, three with focal infarctions in the apical intraventricular septum (IVS) and/or left ventricular free wall (LVFW), were imaged with an intracardiac echocardiography (ICE) transducer. Custom beam sequences were used to excite the myocardium with focused acoustic radiation force (ARF) impulses and image the subsequent tissue response. Tissue displacement in response to the ARF excitation was calculated with a phase-based estimator, and transverse wave magnitude and velocity were each estimated at every depth. The excitation sequence was repeated rapidly, either in the same location to generate 40 Hz M-modes at a single steering angle, or with a modulated steering angle to synthesize 2-D displacement magnitude and shear wave velocity images at 17 points in the cardiac cycle. Both types of images were acquired from various views in the right and left ventricles, in and out of infarcted regions. In all animals, acoustic radiation force impulse (ARFI) and shear wave elasticity imaging (SWEI) estimates indicated diastolic relaxation and systolic contraction in noninfarcted tissues. The M-mode sequences showed high beat-to-beat spatio-temporal repeatability of the measurements for each imaging plane. In views of noninfarcted tissue in the diseased animals, no significant elastic remodeling was indicated when compared with the control. Where available, views of infarcted tissue were compared with similar views from the control animal. In views of the LVFW, the infarcted tissue presented as stiff and non-contractile compared with the control. In a view of the IVS, no significant difference was seen between infarcted and healthy tissue, whereas in another view, a heterogeneous infarction was seen to be presenting itself as non-contractile in systole.

Prostate lesions and healthy regions from 12 radical prostatectomy patients were identified in acoustic radiation force impulse (ARFI) imaging, shear wave elasticity imaging (SWEI), and multi-parametric magnetic resonance imaging (mpMRI) apparent diffusion coefficient (ADC) data and confirmed by histopathology. Custom sequencing and processing techniques led to ARFI and SWEI images which demonstrate strong structural concordance. The combination of quantitative metrics from multiple imaging modalities using a principal component binary discriminator improved the diagnostic capability over individual modalities with areas under the receiver operating characteristic curve reaching 0.94. The correlations among the separate modality parameters were moderate with R-squared values between 0.47 (ADC and ARFI) and 0.71 (ARFI and SWEI).

Recurrence of atrial fibrillation after transcatheter ablation (TCA) is common because there is no imaging modality that can visually confirm the presence of radiofrequency ablation (RFA) lesions. We have previously shown that acoustic radiation force impulse (ARFI) imaging can visualize the relative tissue stiffness changes caused by RFA. The objective of this study was to determine if intra-procedurally acquired ARFI images could identify RFA lesions. In 8 canines, an integrated ARFI imaging-electroanatomical mapping (EAM) system was used to map the geometry of the right atrium and acquire ARFI images along an inter-caval line before and after RFA. RF-energy delivery sites were marked in the EAM geometry to guide the ARFI imaging plane to RFA lesion locations. The ARFI images were randomized and three separate reviewers read the images for the presence of RFA lesion. The majority assessment for each ARFI image was counted in a 2 × 2 contingency table according to the presence/absence of a RFA treatment marker in the EAM geometry at the ARFI imaging plane. EAM guided intra-procedure ARFI imaging of RFA treatment sites. Reviewers of the ARFI images identified RFA lesion with a high sensitivity (96.3%) and specificity (93.2%). Incorporating an integrated ARFI imaging-EAM system into TCA for the visualization of RFA lesions could potentially improve the procedure efficacy.