Brain diseases including neurological disorders and tumors remain under treated due to the challenge to access the brain, and blood-brain barrier (BBB) restricting drug delivery which, also profoundly limits the development of pharmacological treatment. Focused ultrasound (FUS) with microbubbles is the sole method to open the BBB noninvasively, locally, and transiently and facilitate drug delivery, while translation to the clinic is challenging due to long procedure, targeting limitations, or invasiveness of current systems. In order to provide rapid, flexible yet precise applications, we have designed a noninvasive FUS and monitoring system with the protocol tested in monkeys (from in silico preplanning and simulation, real-time targeting and acoustic mapping, to post-treatment assessment). With a short procedure (30 min) similar to current clinical imaging duration or radiation therapy, the achieved targeting (both cerebral cortex and subcortical structures) and monitoring accuracy was close to the predicted 2-mm lower limit. This system would enable rapid clinical transcranial FUS applications outside of the MRI system without a stereotactic frame, thereby benefiting patients especially in the elderly population.

Harmonic Motion Imaging for Focused Ultrasound (HMIFU) is a recently developed High-Intensity Focused Ultrasound (HIFU) treatment monitoring method. HMIFU utilizes an Amplitude-Modulated (fAM = 25 Hz) HIFU beam to induce a localized focal oscillatory motion, which is simultaneously estimated and imaged by confocally-aligned imaging transducer. HMIFU feasibilities have been previously shown in silico, in vitro, and in vivo in 1-D or 2-D monitoring of HIFU treatment. The objective of this study is to develop and show the feasibility of a novel fast beamforming algorithm for image reconstruction using GPU-based sparse-matrix operation with real-time feedback. In this study, the algorithm was implemented onto a fully integrated, clinically relevant HMIFU system composed of a 93-element HIFU transducer (fcenter = 4.5MHz) and coaxially-aligned 64-element phased array (fcenter = 2.5MHz) for displacement excitation and motion estimation, respectively. A single transmit beam with divergent beam transmit was used while fast beamforming was implemented using a GPU-based delay-and-sum method and a sparse-matrix operation. Axial HMI displacements were then estimated from the RF signals using a 1-D normalized cross-correlation method and streamed to a graphic user interface. The present work developed and implemented a sparse matrix beamforming onto a fully-integrated, clinically relevant system, which can stream displacement images up to 15 Hz using a GPU-based processing, an increase of 100 fold in rate of streaming displacement images compared to conventional CPU-based conventional beamforming and reconstruction processing. The achieved feedback rate is also currently the fastest and only approach that does not require interrupting the HIFU treatment amongst the acoustic radiation force based HIFU imaging techniques. Results in phantom experiments showed reproducible displacement imaging, and monitoring of twenty two in vitro HIFU treatments using the new 2D system showed a consistent average focal displacement decrease of 46.7±14.6% during lesion formation. Complementary focal temperature monitoring also indicated an average rate of displacement increase and decrease with focal temperature at 0.84±1.15 %/ °C, and 2.03± 0.93%/ °C, respectively. These results reinforce the HMIFU capability of estimating and monitoring stiffness related changes in real time. Current ongoing studies include clinical translation of the presented system for monitoring of HIFU treatment for breast and pancreatic tumor applications.

Current methods of cardiac strain imaging at high frame rate suffer from motion matching artifacts or poor lateral resolution. Coherent compounding has been shown to improve echocardiographic image quality while maintaining high frame rate but has never been used to image cardiac strain. However, myocardial velocity can have an impact on coherent compounding due to displacements between frames. The objective of this study was to investigate the feasibility and performance of coherent compounding for cardiac strain imaging at a low and a high myocardial velocity. Left ventricular contraction in short-axis view was modeled as an annulus with radial thickening and circumferential rotation. Simulated radiofrequency channel data with a cardiac phased array were obtained using three different beamforming methods: single diverging wave, coherent compounding of diverging waves and conventional focusing. Axial and lateral displacements and strains as well as radial strains were estimated and compared to their true value. In vivo feasibility of cardiac strain imaging with coherent compounding was performed and compared to single diverging wave imaging. At low myocardial velocities, the axial, lateral and radial strain relative error for 9 compounded waves (16.3%, 40.4%, 18.9%) were significantly lower than those obtained with single diverging wave imaging (19.9%, 80.3%, 30.6%) and closer to that obtained with conventional focusing (16.7%, 43.7%, 16.0%). In vivo left-ventricular radial strains exhibited higher quality with 9 compounded waves than with single diverging wave imaging. These results indicate that cardiac strain can be imaged using coherent compounding of diverging waves with a better performance than with single diverging wave imaging while maintaining a high frame rate and therefore has the potential to improve diagnosis of myocardial strain-based cardiac diseases.

Background Accurate determination of regional areas of arrhythmic triggers is of key interest to diagnose arrhythmias and optimize their treatment. Electromechanical wave imaging (EWI) is an ultrasound technique that can image the transient deformation in the myocardium following electrical activation and therefore has the potential to detect and characterize location of triggers of arrhythmias. Objectives The objectives of this study are to investigate the relationship between electromechanical and electrical activation of the left-ventricular (LV) endocardial surface during epicardial and endocardial pacing as well as during sinus rhythm and also to investigate the distribution of electromechanical delays. Methods In this study, six canines were investigated. Two external electrodes were sutured onto the epicardial surface of the left ventricle (LV). A 64-electrode basket catheter was inserted through the apex of the LV. Ultrasound channel data were acquired at 2000 frames/s during epicardial and endocardial pacing as well as during sinus rhythm. Electromechanical and electrical activation maps were synchronously obtained from the ultrasound data and the basket catheter respectively. Results The mean correlation coefficient between electromechanical and electrical activation was R=0.81 for epicardial anterior pacing, R=0.79 for epicardial lateral pacing, R=0.69 for endocardial pacing and R=0.56 for sinus rhythm. Conclusions The electromechanical activation sequence determined by EWI follows the electrical activation sequence and more specifically in the case of pacing. This finding is of key interest in the role that EWI can play in the detection of the anatomical source of arrhythmias and the planning of pacing therapies such as cardiovascular resynchronization therapy.

A significant risk of femoral neck (FN) fracture exists for men and women with an areal bone mineral density (aBMD) higher than the osteoporotic range, as measured with dual-energy X-ray absorptiometry (DXA). Separately measuring the cortical and trabecular FN compartments and combining the results would likely be a critical aspect of enhancing the diagnostic capabilities of a new technique. Because the cortical shell determines a large part of FN strength a novel quantitative ultrasound (QUS) technique that probes the FN cortical compartment was implemented. The sensitivity of the method to variations of FN cortical properties and FN strength was tested. Nine femurs (women, mean age 83 years) were subjected to QUS to measure the through transmission time-of-flight (TOF) at the FN and mechanical tests to assess strength. Quantitative computed tomography (QCT) scans were performed to enable analysis of the dependence of TOF on bone parameters. DXA was also performed for reference. An ultrasound wave propagating circumferentially in the cortical shell was measured in all specimens. Its TOF was not influenced by the properties of the trabecular compartment. Because the method involves mechanical guided waves, the QUS variable is related to the geometric and material properties of the cortical shell (cortical thickness, tissue elasticity, and porosity). This work opens the way to a multimodal QUS assessment of the proximal femur, combining our approach targeting the cortical shell with the existing modality sensitive to the trabecular compartment. In vivo feasibility of our approach has to be confirmed with experimental data in patients. ß