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.

Harmonic Motion Imaging for Focused Ultrasound (HMIFU) is a novel high-intensity focused ultrasound (HIFU) therapy monitoring method with feasibilities demonstrated in vitro, ex vivo and in vivo. Its principle is based on Amplitude-modulated (AM) - Harmonic Motion Imaging (HMI), an oscillatory radiation force used for imaging the tissue mechanical response during thermal ablation. In this study, a theoretical framework of HMIFU is presented, comprising a customized nonlinear wave propagation model, a finite-element (FE) analysis module, and an image-formation model. The objective of this study is to develop such a framework in order to 1) assess the fundamental performance of HMIFU in detecting HIFU lesions based on the change in tissue apparent elasticity, i.e., the increasing Young's modulus, and the HIFU lesion size with respect to the HIFU exposure time and 2) validate the simulation findings ex vivo. The same HMI and HMIFU parameters as in the experimental studies were used, i.e., 4.5-MHz HIFU frequency and 25 Hz AM frequency. For a lesion-to-background Young's modulus ratio of 3, 6, and 9, the FE and estimated HMI displacement ratios were equal to 1.83, 3.69, 5.39 and 1.65, 3.19, 4.59, respectively. In experiments, the HMI displacement followed a similar increasing trend of 1.19, 1.28, and 1.78 at 10-s, 20-s, and 30-s HIFU exposure, respectively. In addition, moderate agreement in lesion size growth was also found in both simulations (16.2, 73.1 and 334.7 mm2) and experiments (26.2, 94.2 and 206.2 mm2). Therefore, the feasibility of HMIFU for HIFU lesion detection based on the underlying tissue elasticity changes was verified through the developed theoretical framework, i.e., validation of the fundamental performance of the HMIFU system for lesion detection, localization and quantification, was demonstrated both theoretically and ex vivo.

Elasticity imaging has shown great promise in detecting High Intensity Focused Ultrasound (HIFU) lesions based on their distinct biomechanical properties. However, quantitative mechanical properties of the tissue and the optimal intensity for obtaining the best contrast parameters remain scarce. In this study, fresh canine livers were ablated using combinations of ISPTA intensities of 5.55, 7.16 and 9.07 kW/cm2 and time durations of 10 and 30 s ex vivo; leading to six groups of ablated tissues. Biopsy samples were then interrogated using dynamic shear mechanical testing within the range of 0.1-10 Hz to characterize the post-ablation tissue viscoelastic properties. All mechanical parameters were found to be frequency dependent. Compared to the unablated cases, all six groups of ablated tissues showed statistically-significant higher complex shear modulus and shear viscosity. However, among the ablated groups, both complex shear modulus and shear viscosity were found to monotonically increase in groups 1-4 (5.55 kW/cm2 for 10 s, 7.16 kW/cm2 for 10 s, 9.07 kW/cm2 & 10 s, and 5.55 kW/cm2 & 30 s, respectively), but decrease in groups 5 and 6 (7.16 kW/cm2 for 30 s, and 9.07 kW/cm2 for 30 s, respectively). For groups 5 and 6, the temperature was expected to exceed the boiling point, and therefore, the decreased stiffening could be due to the compromised integrity of the tissue microstructure. Future studies are needed to estimate the tissue mechanical properties in vivo and perform real-time monitoring of tissue alterations during ablation.

Harmonic Motion Imaging for Focused Ultrasound (HMIFU) is a recently developed high-intensity focused ultrasound (HIFU) treatment monitoring method with feasibilities demonstrated in vitro and in vivo. Here, a multi-parametric study is performed to investigate both elastic and acoustics-independent viscoelastic tissue changes using the Harmonic Motion Imaging (HMI) displacement, axial compressive strain and change in relative phase-shift during high energy HIFU treatment with tissue boiling. Forty three (n=43) thermal lesions were formed in ex vivo canine liver specimens (n=28). Two dimensional (2D) transverse HMI displacement maps were also obtained before and after lesion formation. The same method was repeated in 10-s, 20-s and 30-s HIFU durations at three different acoustic powers of 8, 10, and 11W, which were selected and verified as treatment parameters capable of inducing boiling using both thermocouple and Passive Cavitation Detection (PCD) measurements. Although a steady decrease in the displacement, compressive strain, and relative change in the focal phase shift (Δφ) were obtained in numerous cases, indicating an overall increase in relative stiffness, the study outcomes also showed that during boiling, a reverse lesion-to-background displacement contrast was detected, indicating potential change in tissue absorption, geometrical change and/or, mechanical gelatification or pulverization. Following treatment, corresponding 2D HMI displacement images of the thermal lesions also mapped consistent discrepancy in the lesion-to-background displacement contrast. Despite unpredictable changes in acoustic properties with boiling, the relative change in phase shift showed a consistent decrease, indicating its robustness to monitor biomechanical properties independent of the acoustic property change throughout the HIFU treatment. In addition, the 2D HMI displacement images confirmed and indicated the increase in the thermal lesion size with treatment duration, which was validated against pathology. In conclusion, multi-parametric HMIFU was shown capable of monitoring and mapping tissue viscoelastic response changes during and after HIFU boiling, some of which were independent of the acoustic parameter changes.

Harmonic motion imaging (HMI) is a radiation force-based elasticity imaging technique that tracks oscillatory tissue displacements induced by sinusoidal ultrasonic radiation force to assess relative tissue stiffness. The objective of this study was to evaluate the feasibility of HMI in pancreatic tumor detection and high-intensity focused ultrasound (HIFU) treatment monitoring. The HMI system consisted of a focused ultrasound transducer, which generated sinusoidal radiation force to induce oscillatory tissue motion at 50 Hz, and a diagnostic ultrasound transducer, which detected the axial tissue displacements based on acquired radiofrequency signals using a 1D cross-correlation algorithm. For pancreatic tumor detection, HMI images were generated for pancreatic tumors in transgenic mice and normal pancreases in wild-type mice. The obtained HMI images showed a high contrast between normal and malignant pancreases with an average peak-to-peak HMI displacement ratio of 3.2. Histological analysis showed that no tissue damage was associated with HMI when it was used for the sole purpose of elasticity imaging. For pancreatic tumor ablation monitoring, the focused ultrasound transducer was operated with a higher acoustic power and longer pulse length than that used in tumor detection to simultaneously induce HIFU thermal ablation and oscillatory tissue displacements, allowing HMI monitoring without interrupting tumor ablation. HMI monitoring of HIFU ablation found significant decreases in the peak-to-peak HMI displacements before and after HIFU ablation with a reduction rate ranging from 15.8% to 57.0%. The formation of thermal lesions after HIFU exposure was confirmed by histological analysis. This study demonstrated the feasibility of HMI in abdominal tumor detection and HIFU ablation monitoring.