Simon Fung-Kee-Fung

Theoretical Quality Assessment of Myocardial Elastography with In Vivo Validation

Myocardial elastography (ME), a radio frequency (RF)-based speckle tracking technique with one-dimensional (1-D) cross correlation and novel recorrelation methods in a 2-D search was proposed to estimate and fully image 2-1) transmural deformation field and to detect abnormal cardiac function. A theoretical framework was first developed in order to evaluate the performance of 2-D myocardial elastography based on a previously developed 3-D finite-element model of the canine left ventricle. A normal (control) and an ischemic (left-circumflex, LCx) model, which more completely represented myocardial deformation than a kinematic model, were considered. A 2-D convolu-tional image formation model was first used to generate RF signals for quality assessment of ME in the normal and ischemic cases. A 3-D image formation model was further developed to investigate the effect of the out-of-plane motion on the 2-D, in-plane motion estimation. Both orthogonal, in-plane displacement components (i.e., lateral and axial) between consecutive RF frames were iteratively estimated. All the estimated incremental 2-D displacements from end-diastole (ED) to end-systole (ES) were then accumulated to acquire the cumulative 2-D displacements, which were further used to calculate the cumulative 2-D systolic finite strains. Furthermore, the cumulative systolic radial and circumferential strains, which were angle-and frame-rate independent, were obtained from the 2-D finite-strain components and imaged in full view to detect the ischemic region. We also explored the theoretical understanding of the limitations of our technique for the accurate depiction of disease and validated it in vivo against tagged magnetic resonance imaging (tMRI) in the case of a normal human myocardium in a 2-D short-axis (SA) echocardiographic view. The theoretical framework succeeded in demonstrating that the 2-D myocardial elastography technique was a reliable tool for the complete estimation and depiction of the in-plane myocardial deformation field as well as for accurate identification of pathological mechanical function using established finite-element, left-ventricular canine models. In a preliminary study, the 2-D myocardial elastography was shown capable of imaging myocardial deformation comparable to equivalent tMRI estimates in a clinical setting.

A novel, view-independent method for strain mapping in myocardial elastography: eliminating angle and centroid dependence

Robust indices of regional and global cardiac function are a key factor in detection and treatment of heart disease as well as understanding of the fundamental mechanisms of a healthy heart. Myocardial elastography provides a noninvasive method for imaging and measuring displacement and strain of the myocardium for the early detection of cardiovascular disease. However, two-dimensional in-plane axial and lateral strains measured depend on the sonographic view used. This becomes especially critical in a clinical setting and may induce large variations in the measured strains, potentially leading to false diagnoses. A novel method in myocardial elastography is proposed for eliminating this view dependence by deriving the polar, principal and classified principal strains. The performance of the proposed methodology is assessed by employing 3D finite-element left-ventricular models of a control and an ischemic canine heart. Although polar strains are angle-independent, they are sensitive to the selected reference coordinate system, which requires the definition of a centroid of the left ventricle (LV). In contrast, principal strains derived through eigenvalue decomposition exhibit the inherent characteristic of coordinate system independence, offering view (i.e., angle and centroid)-independent strain measurements. Classified principal strains are obtained by assigning the principal components in the physical ventricular coordinate system. An extensive strain analysis illustrates the improvement in interpretation and visualization of the full-field myocardial deformation by using the classified principal strains, clearly depicting the ischemic and non-ischemic regions. Strain maps, independent of sonographic views and imaging planes, that can be used to accurately detect regional contractile dysfunction are demonstrated.

Imaging the mechanics and electromechanics of the heart

The heart is a mechanical pump that is electrically driven. We have previously shown that the contractility of the cardiac muscle can reliably be used in order to assess the extent of ischemia using myocardial elastography. Myocardial elastography estimates displacement and strain during the natural contraction of the myocardium using signal processing techniques on echocardiograms in order to assess the change in mechanical properties as a result of disease. In this paper, we showed that elastographic techniques can be used to estimate and image both the mechanics and electromechanics of normal and pathological hearts in vivo. In order to image the mechanics throughout the entire cardiac cycle, the minimum frame rate was determined to be on the order of 150 fps in a long-axis view and 300 fps in a short-axis view. The incremental and cumulative displacement and strains were measured and imaged for the characterization of normal function and differentiation from infracted myocardium. In order to image the electromechanical function, the incremental displacement was imaged inconsecutive cardiac cycles during end-systole in both dogs and humans. The contraction wave velocity in normal dogs was found to be twice higher than in normal humans and twice lower than in ischemic dogs. In conclusion, we have demonstrated that elastographic techniques can be used to detect and quantify the mechanics and electromechanics of the myocardium in vivo. Ongoing investigations entail assessment of myocardial elastography in characterizing and quantifying ischemia and infarction in vivo.

Therapeutic approaches in the management of locally advanced rectal cancer

Combined-modality therapy, using radiotherapy and chemotherapy with surgery, has been the traditional therapeutic algorithm for locally advanced rectal cancer. Standard of care in the United States has evolved to include neoadjuvant concurrent chemotherapy and radiotherapy followed by surgical excision and adjuvant chemotherapy. This approach has led to a significant improvement in local recurrences (LR), to the point where distant sites are the more common site of failure. Further improvements in local control have failed to improve overall survival. This article reviews historical trials that shifted the treatment paradigm to the current standard of care, as well as recent research trials, which have sought to incorporate new treatment methodologies, and treatment agents to improve outcomes. Finally this article describes ongoing studies and their potential impact on the future of therapeutic management of locally-advanced rectal cancer.

Angle-independent strain mapping in myocardial elastography 2D strain tensor characterization and principal component imaging

A current limitation of the implementation of myocardial elastography in a clinical setting is the difficulty of interpreting the one-dimensional strain maps due to varying strain values in the wall of the left ventricle (LV). In this paper, we demonstrate a robust angle-independent method for 2D myocardial elastography on simulated 2D ultrasonic images of a 3D finite-element analysis (FEA) model of the LV. Two FEA, a control and a regionally ischemic, canine left-ventricular models, were used and model states were obtained in increments and accumulated from end-diastole (ED) to end-systole (ES). Two- dimensional (2D) displacement in the myocardium was estimated between ED to ES. These estimates were good approximations of the FEA solution (rms errors of 0.18 mm for lateral displacement and 0.12 mm for axial displacement). The 2D symmetric strain tensor was calculated from the displacements and angle- independent principal strains were obtained using eigenvalue decomposition of the strain tensor. Principal strains in the myocardium have been shown to approximate normal strains with respect to an anatomical coordinate system (5). To test this angle-independence, displacements were obtained from two different orthogonally placed transducer locations. Principal strains were estimated from both locations and showed good correlation to the FEA solution. Rms errors between the FEA model and 2D elastography (2DE) estimation of principal strains from both transducer locations were 1.7% and 2.4% strain, respectively. Visualizing the transmural strain using principal strains greatly simplified their interpretation. Moreover, abnormal deformation of the ischemic region, which was difficult to observe with axial and lateral strains, was clearly visible in the principal strain images. In summary, the feasibility of 2D elastography estimation of myocardial displacement and strain was shown. In this paper, we propose the use of principal strains as a more useful tool in the visualization of abnormal wall motion and the detection of ischemia and other related heart diseases.

A prospective trial of volumetric intensity-modulated arc therapy vs conventional intensity modulated radiation therapy in advanced head and neck cancer

AIM To prospectively compare volumetric intensity-modulated arc therapy (VMAT) and conventional intensity-modulated radiation therapy (IMRT) in coverage of planning target volumes and avoidance of multiple organs at risk (OARs) in patients undergoing definitive chemoradiotherapy for advanced (stage III or IV) squamous cell cancer of the head and neck. METHODS Computed tomography scans of 20 patients with advanced tumors of the larynx, naso-, oro- and hypopharynx were prospectively planned using IMRT (7 field) and VMAT using two arcs. Calculated doses to planning target volume (PTV) and OAR were compared between IMRT and VMAT plans. Dose-volume histograms (DVH) were utilized to obtain calculated doses to PTV and OAR, including parotids, cochlea, spinal cord, brainstem, anterior tongue, pituitary and brachial plexus. DVHs for all structures were compared between IMRT and VMAT plans. In addition the plans were compared for dose conformity and homogeneity. The final treatment plan was chosen by the treating radiation oncologist. RESULTS VMAT was chosen as the ultimate plan in 18 of 20 patients (90%) because the plans were thought to be otherwise clinically equivalent. The IMRT plan was chosen in 2 of 20 patients because the VMAT plan produced concentric irradiation of the cord which was not overcome even with an avoidance structure. For all patients, VMAT plans had a lower number of average monitor units on average (MU = 542.85) than IMRT plans (MU = 1612.58) (P < 0.001). Using the conformity index (CI), defined as the 95% isodose volume divided by the PTV, the IMRT plan was more conformal with a lower conformity index (CI = 1.61) than the VMAT plan (CI = 2.00) (P = 0.003). Dose homogeneity, as measured by average standard deviation of dose distribution over the PTV, was not different with VMAT (1.45 Gy) or IMRT (1.73 Gy) (P = 0.069). There were no differences in sparing organs at risk. CONCLUSION In this prospective study, VMAT plans were chosen over IMRT 90% of the time. Compared to IMRT, VMAT plans used only one third of the MUs, had shorter treatment times, and similar sparing of OAR. Overall, VMAT provided similar dose homogeneity but less conformity in PTV irradiation compared to IMRT. This difference in conformity was not clinically significant.

Angle-Independent Myocardial Elastography - Theoretical Analysis and Clinical Validation

Several methods have been introduced in the past few years to quantify left-ventricular strain in order to detect myocardial ischemia and infarction. Myocardial Elastography is one of these methods, which is based on ultrasound Radio-Frequency (RF) signal processing at high frame rates for the highest precision and resolution of strain estimation. Myocardial elastography estimates displacement and strain during the natural contraction of the myocardium using cross-correlation techniques. We have previously shown that imaging of the myocardial strain at high precision allows the correct assessment of the contractility of the cardiac muscle and thus measurement of the extent of ischemia or infarct. In this paper, for the first time in echocardiography, we show how angle-independent techniques can be used to estimate and image the mechanics of normal and pathological myocardia, both in simulations and in vivo. First, the fundamental limits of 2D normal and principal strain component estimation are determined using an ultrasound image formation model and a 2D short-axis view of a 3D left-ventricular, finite-element model, in normal and ischemic configurations. Two-dimensional (i.e., lateral and axial) cumulative displacement and strain components were iteratively estimated and imaged using 1D cross-correlation and recorrelation techniques in a 2D search. Validation of these elastographic findings in one normal human subject was performed. Principal strains were also imaged for the characterization of normal myocardium. In conclusion, the feasibility of angle-independent, 2D myocardial elastography technique was shown through the calculation of the in-plane principal strains, which was proven essential in the reliable depiction of strains independent of the beam-tissue angle or the type of sonographic view used.

Stereotactic Body Radiotherapy for the Treatment of Renal Tumors.

The purpose of this study was to evaluate the response of actively growing renal masses to stereotactic body radiation therapy (SBRT). We retrospectively reviewed our institutional review board–approved kidney database and identified 4 patients who underwent SBRT, 15 Gy dose, for their rapidly growing renal masses. Three patients had a decreased tumor size after radiation treatment by 20.8%, 38.1%, and 20%. The other patient had a size gain of 5.6%. This patient maintained a similar tumor growth rate before and after SBRT. Mean follow-up time was 13.8 months. SBRT represents an effective management option in select patients with larger rapidly growing kidney masses.

Elastographic imaging of strain distribution within the anterior cruciate ligament and at the acl-bone insertions

The anterior cruciate ligament (ACL) functions as a mechanical stabilizer in the tibiofemoral joint. Over 250,000 Americans each year suffer from ACL ruptures and tears, making the ACL the most commonly injured knee ligament. A long term goal of our research program is to promote graft-bone integration via the regeneration of the native ligament-bone interface. To this end, we have focused on the design of biomimetic scaffolds combined with tissue engineering to induce organized interface regeneration. An understanding of mechanical properties of the ligament-bone interface is critical for biomimetic scaffold design and clinical evaluation. To date, experimental determination has been difficult due to the small length scale (< 1 mm) involved at the ACL insertions. This study utilizes ultrasound elastography to characterize the functional properties of the ACL and the ACL-bone interface under applied loading. Specifically, the tibiofemoral joints were mounted on a biomechanics material testing system and loaded in tension while RF data was collected. Axial elastograms between successive RF frames were generated using cross-correlation and recorrelation techniques. Elastography analyses revealed that when the joint is in tension, complex strains with both compressive and tensile components were found at the tibial insertion. These results are in agreement with those of prior finite element analysis (FEA) model predictions. In addition, the magnitude of displacement was found to be the highest at the ACL proper and decreased in value from ligament to bone. Our results indicate that elastography is a novel and useful method in understanding the mechanical properties of the ligament itself and the ligament-bone interface.