Gary Y. Hou

Multi-parametric monitoring and assessment of high-intensity focused ultrasound (HIFU) boiling by harmonic motion imaging for focused ultrasound (HMIFU): an ex vivo feasibility study.

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 11 W, 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 the expectedly chaotic 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 changes 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.

Sparse matrix beamforming and image reconstruction for 2-D HIFU monitoring using harmonic motion imaging for focused ultrasound (HMIFU) with in vitro validation.

Harmonic motion imaging for focused ultrasound (HMIFU) utilizes an amplitude-modulated HIFU beam to induce a localized focal oscillatory motion simultaneously estimated. 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. A single divergent transmit beam 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 with frame rates up to 15 Hz, a 100-fold increase compared to conventional CPU-based processing. The real-time feedback rate does not require interrupting the HIFU treatment. Results in phantom experiments showed reproducible HMI images and monitoring of 22 in vitro HIFU treatments using the new 2-D system demonstrated reproducible displacement imaging, and monitoring of 22 in vitro HIFU treatments using the new 2-D 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.

High-intensity focused ultrasound monitoring using harmonic motion imaging for focused ultrasound (HMIFU) under boiling or slow denaturation conditions

Harmonic motion imaging for focused ultrasound (HMIFU) is a recently developed high-intensity focused ultrasound (HIFU) treatment monitoring method that utilizes an amplitude-modulated therapeutic ultrasound beam to induce an oscillatory radiation force at the HIFU focus and estimates the focal tissue displacement to monitor the HIFU thermal treatment. In this study, the performance of HMIFU under acoustic, thermal, and mechanical effects was investigated. The performance of HMIFU was assessed in ex vivo canine liver specimens (n = 13) under slow denaturation or boiling regimes. A passive cavitation detector (PCD) was used to assess the acoustic cavitation activity, and a bare-wire thermocouple was used to monitor the focal temperature change. During lesioning with slow denaturation, high quality displacements (correlation coefficient above 0.97) were observed under minimum cavitation noise, indicating the tissue initial-softeningthen- stiffening property change. During HIFU with boiling, HMIFU monitored a consistent change in lesion-to-background displacement contrast (0.46 ± 0.37) despite the presence of strong cavitation noise due to boiling during lesion formation. Therefore, HMIFU effectively monitored softening-then-stiffening during lesioning under slow denaturation, and detected lesioning under boiling with a distinct change in displacement contrast under boiling in the presence of cavitation. In conclusion, HMIFU was shown under both boiling and slow denaturation regimes to be effective in HIFU monitoring and lesioning identification without being significantly affected by cavitation noise.

Simulation of HMIFU (Harmonic Motion Imaging for Focused Ultrasound) with in-vitro validation

Harmonic Motion Imaging (HMI) is a technique capable of imaging tissue mechanical properties during acoustic radiation force application. Recently, HMIFU has been shown capable for high-intensity focused ultrasound (HIFU) therapy and monitoring. Here, a theoretical analysis of the Harmonic Motion Imaging for Focused Ultrasound (HMIFU) system is performed using a 2D nonlinear wave propagation model combined with a finite-element (FE) framework and its reliability in lesion localization and size quantification is tested in both simulations and in-vitro experiments. Good agreement in both lesion size (2.86, 5.93 and 17.5 mm2, for 5-, 10-, and 20-s ablation cases, respectively) and location (4.8 cm to 5.2 cm, 4.6 cm to 5 cm, and 4.4 cm to 5.1 cm, in the 5-, 10- and 20-s ablation cases, respectively) were found between the predicted lesion maps and the HMIFU images in both simulations and in vitro. Along with preliminary Finite-element (FE) results, the presented work confirms the reliability of the HMIFU system for lesion detection, localization and quantification.

Harmonic motion imaging for abdominal tumor detection and high-intensity focused ultrasound ablation monitoring: an in vivo feasibility study in a transgenic mouse model of pancreatic cancer

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 the resulting oscillatory displacement denoting the underlying 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 radio-frequency signals using a 1-D 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 at 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.

Optimization of real-time acoustical and mechanical monitoring of high intensity focused ultrasound (HIFU) treatment using harmonic motion imaging for high focused ultrasound (HMIFU)

Harmonic Motion Imaging (HMI) for Focused Ultrasound (HMIFU) is a recently developed high-intensity focused ultrasound (HIFU) treatment monitoring method with feasibilities demonstrated in silica, in vitro and in vivo. Its principle is based on emission of an Amplitude-modulated therapeutic ultrasound beam utilizing a therapeutic transducer to induce an oscillatory radiation force while tracking the focal tissue mechanical response during the HIFU treatment using a confocally-aligned diagnostic transducer. In order to translate towards the clinical implementation of HMIFU, a complete assessment study is required in order to investigate the optimal radiation force threshold for reliable monitoring the local tissue mechanical property changes, i.e., the estimation HMIFU displacement under thermal, acoustical, and mechanical effects within focal medium (i.e., boiling, cavitation, and nonlinearity) using biological specimen. In this study, HMIFU technique is applied on HIFU treatment monitoring on freshly excised ex vivo canine liver specimens. In order to perform the multi-characteristic assessment, the diagnostic transducer was operated as either a pulse-echo imager or Passive Cavitation Detector (PCD) to assess the acoustic and mechanical response, while a bare-wire thermocouple was used to monitor the focal temperature change. As the acoustic power of HIFU treatment was ranged from 2.3 to 11.4 W, robust HMI displacement was observed across the entire range. Moreover, an optimized range for high quality displacement monitoring was found to be between 3.6 to 5.2W, where displacement showed an increase followed by significant decrease, indicating a stiffening of focal medium due to thermal lesion formation, while the correlation coefficient was maintained above 0.95.

Radiation-force-based estimation of acoustic attenuation using harmonic motion imaging (HMI) in phantoms and in vitro livers before and after HIFU ablation.

Acoustic attenuation represents the energy loss of the propagating wave through biological tissues and plays a significant role in both therapeutic and diagnostic ultrasound applications. Estimation of acoustic attenuation remains challenging but critical for tissue characterization. In this study, an attenuation estimation approach was developed using the radiation-force-based method of harmonic motion imaging (HMI). 2D tissue displacement maps were acquired by moving the transducer in a raster-scan format. A linear regression model was applied on the logarithm of the HMI displacements at different depths in order to estimate the acoustic attenuation. Commercially available phantoms with known attenuations (n = 5) and in vitro canine livers (n = 3) were tested, as well as HIFU lesions in in vitro canine livers (n = 5). Results demonstrated that attenuations obtained from the phantoms showed a good correlation (R² = 0.976) with the independently obtained values reported by the manufacturer with an estimation error (compared to the values independently measured) varying within the range of 15-35%. The estimated attenuation in the in vitro canine livers was equal to 0.32   ±   0.03 dB cm(-1) MHz(-1), which is in good agreement with the existing literature. The attenuation in HIFU lesions was found to be higher (0.58   ±   0.06 dB cm(-1) MHz(-1)) than that in normal tissues, also in agreement with the results from previous publications. Future potential applications of the proposed method include estimation of attenuation in pathological tissues before and after thermal ablation.

High intensity focused ultrasound as a tool for tissue engineering: Application to cartilage

This article promotes the use of High Intensity Focused Ultrasound (HIFU) as a tool for affecting the local properties of tissue engineered constructs in vitro. HIFU is a low cost, non-invasive technique used for eliciting focal thermal elevations at variable depths within tissues. HIFU can be used to denature proteins within constructs, leading to decreased permeability and potentially increased local stiffness. Adverse cell viability effects remain restricted to the affected area. The methods described in this article are explored through the scope of articular cartilage tissue engineering and the fabrication of osteochondral constructs, but may be applied to the engineering of a variety of different tissues.

A viscoelastic property study in canine liver before and after HIFU ablation in vitro

Elasticity imaging techniques have shown great potential in detecting High Intensity Focused Ultrasound (HIFU) lesions based on their distinct biomechanical properties. However, quantitative tissue viscoelastic properties and the optimal power to obtain the best contrast parameters remain scarce. In the present study, fresh canine livers were ablated ex vivo using six different acoustic powers and time durations, covering an energy range of 80-330 J. Biopsy samples were then extracted and examined, using rheometry, to obtain the viscoelastic properties post-ablation in vitro. All mechanical parameters were found to be frequency dependent. Both the shear complex modulus and viscosity exhibited monotonic increase for the first 4 groups (80-240 J), relatively lower HIFU powers. Similar parameters from groups 5-6 (300-330 J) showed relative decrease, still higher than unablated group 0. The tangent of the stress-strain phase shift was found to vary from unablated group 0 to ablated groups 1-6. However, no measurable difference amongst the ablated groups was found. Decreased stiffening at high powers compared to the baseline could likely be due to compromised structural integrity in the pulverized tissue well beyond the boiling point. The findings here can be used to optimize the efficient monitoring and treatment of tumors using any thermally-based methods where strong tissue damage is expected and/or warranted, respectively.

Radiation-force-based estimation of acoustic attenuation using harmonic motion imaging

Tissue characterization such as attenuation estimation remains challenging but important. Attenuation represents the energy loss during wave propagation through biological tissues, thus affects both therapeutic and diagnostic ultrasound applications. In this study, a novel attenuation estimation approach was developed using radiation-force-based method of Harmonic Motion Imaging (HMI). The HMI set-up comprised of a forcing transducer (fcenter = 4.7 MHz, AM frequency = 25 Hz) in conjunction with a confocal pulse-echo transducer (fcenter = 7.5 MHz), with the former inducing tissue displacement and the latter simultaneously acquiring RF signals. Tissue displacements were estimated from the RF signals using a 1-D cross-correlation method (window size: 1 mm; overlap: 90%). 2D displacement images were obtained through raster-scan (10 × 10 mm2). A linear regression model was applied to the displacements at different depths for calculating attenuation. Gel phantoms with known attenuation (n = 5) (CIRS Inc.) and i...