Novel treatment system using endoscopic ultrasound-guided high-intensity focused ultrasound: A proof-of-concept study.

AIM: High-intensity focused ultrasound (HIFU) is a novel minimally invasive local treatment of solid tumors. Endoscopic ultrasound-guided HIFU (EUS-HIFU) using mechanical effects would have potential benefits, including precise detection of target lesions and enhance drug delivery. The aim of this study is to develop EUS-HIFU device and to prove our concept in porcine model using a locally injected phase change nano droplet (PCND) as the sensitizer. METHOD: A phospholipid PCND contained volatile perfluoro-carbon liquids. The prototype HIFU apparatus comprised a small (20 × 20 mm) transducer with center frequency of 2.1 MHz, attachable to a linear EUS transducer. Under general anesthetic, a single porcine received EUS-guided injection of PCND. The HIFU transducer was placed laparotomically in the stomach, and the liver was ablated through the gastric wall. RESULTS: PCND was injected successfully and a distinct lesion was generated at the HIFU transducer focus only in injected areas that received HIFU exposure at 4.7 kW/cm2 at a duty cycle of 5 % (mean temporal intensity, 0.245 kW/cm2) for 30 s. The generated lesions were mechanically fractionated in macroscopic view. CONCLUSION: The concept of transluminal HIFU ablation using novel EUS-HIFU system was proved in a porcine animal model. This novel treatment system has great potential for future cancer treatment although further investigation in more animals and different organs are warranted.

Experimental study on temperature rise of acoustic radiation force elastography.

INTRODUCTION: Acoustic radiation force (ARF) elastography is potentially useful for imaging the elasticity of human tissue. Because a "push wave" that is used to generate ARF is a long burst wave comparable to that used in regular clinical imaging, detailed investigation of its safety is required. MATERIALS AND METHODS: We focus on the transient temperature rise in the far field, where the beam paths are overlapped. Soft tissue mimicking a phantom and bone samples were exposed to a 2-MHz plane wave for 20 s. The temperature rises in the far field were measured using a thermocouple. The temperature rises at 1 ms, the time required for the displacement measurement, were estimated by fitting the experimental results. The results showed that the thermosensitivity of the bone was 36 times higher than that of the phantom, and the use of a repeated push wave may have exceeded the allowable maximum temperature rise, 1°C, on the bone surface. CONCLUSION: In conclusion, the imaging area, including the path of the push wave, should be carefully checked and the time interval for consecutive use should be adjusted to prevent thermal risk on the surface of the bone.

Ultrasonic Vascular Vector Flow Mapping for 2-D Flow Estimation.

A vascular vector flow mapping (VFM) method visualizes 2-D cardiac flow dynamics by estimating the radial component of flow from the Doppler velocities and wall motion velocities using the mass conservation equation. Although VFM provides 2-D flow, the algorithm is applicable only to bounded regions. Here, a modified VFM algorithm, vascular VFM, is proposed so that the velocities are estimated regardless of the flow geometry. To validate the algorithm, a phantom mimicking a carotid artery was fabricated and VFM velocities were compared with optical particle image velocimetry (PIV) data acquired in the same imaged plane. The validation results indicate that given optimal beam angle condition, VFM velocitiy is fairly accurate, where the correlation coefficient R between VFM and PIV velocities is 0.95. The standard deviation of the total VFM error, normalized by the maximum velocity, ranged from 8.1% to 16.3%, whereas the standard deviation of the measured input errors ranged from 8.9% to 12.7% for color flow mapping and from 4.5% to 5.9% for subbeam calculation. These results indicate that vascular VFM is reliable as its accuracy is comparable to that of conventional Doppler-flow images.

Correction to: Accuracy and limitations of vector flow mapping: left ventricular phantom validation using stereo particle image velocimetory.

The original version of this article unfortunately contained a mistake. The conflict of interest statement was missing in the article. The CoI statement is given below.

Accuracy and limitations of vector flow mapping: left ventricular phantom validation using stereo particle image velocimetory.

BACKGROUND: The accuracy of vector flow mapping (VFM) was investigated in comparison to stereo particle image velocimetry (stereo-PIV) measurements using a left ventricular phantom. VFM is an echocardiographic approach to visualizing two-dimensional flow dynamics by estimating the azimuthal component of flow from the mass-conservation equation. VFM provides means of visualizing cardiac flow, but there has not been a study that compared the flow estimated by VFM to the flow data acquired by other methods. METHODS: A reproducible three-dimensional cardiac blood flow was created in an optically and acoustically transparent left-ventricle phantom, that allowed color-flow mapping (CFM) data and stereo-PIV to be simultaneously acquired on the same plane. A VFM algorithm was applied to the CFM data, and the resulting VFM estimation and stereo-PIV data were compared to evaluate the accuracy of VFM. RESULTS: The velocity fields acquired by VFM and stereo-PIV were in excellent agreement in terms of the principle flow features and time-course transitions of the main vortex characteristics, i.e., the overall correlation of VFM and PIV vectors was R = 0.87 (p < 0.0001). The accuracy of VFM was suggested to be influenced by both CFM signal resolution and the three-dimensional flow, which violated the algorithm's assumption of planar flow. Statistical analysis of the vectors revealed a standard deviation of discrepancy averaging at 4.5% over the CFM velocity range for one cardiac cycle, and that value fluctuated up to 10% depending on the phase of the cardiac cycle. CONCLUSIONS: VFM provided fairly accurate two-dimensional-flow information on cardio-hemodynamics. These findings on VFM accuracy provide the basis for VFM-based diagnosis.

A posteriori accuracy estimation of ultrasonic vector-flow mapping (VFM).

ABSTRACT: A novel method, called a posteriori "VFM accuracy estimation" (VAE), for resolving an intrinsic VFM problem is proposed. The problem is that VFM uncertainty can easily vary according to blood flows through an echocardiographic imaged plane (i.e., "through-plane" flows), and it is unknown. Knowing the VFM uncertainty for each patient will make it possible to refine the quality of VFM-based diagnosis. In the present study, VAE was derived on the basis of an error-propagation analysis and a statistical analysis. The accuracy of VAE with a pulsatile left-ventricle phantom was experimentally investigated for realistic cases with through-plane flows. VAE was validated by comparing VFM uncertainty (S.D.) estimated by VAE with VFM uncertainty measured by particle-image velocimetry (PIV) for different imaged planes. VAE accurately estimated the S.D. of VFM uncertainty measured by PIV for all cases with different image planes (R > 0.6 and p < 0.001). These findings on VFM accuracy will provide the basis for widespread clinical application of VFM-based diagnosis.

New approach for local cancer treatment using pulsed high-intensity focused ultrasound and phase-change nanodroplets.

PURPOSE: The aim of this study was to investigate the combination effects of pulsed HIFU (pHIFU) and phase-change nanodroplets (PCND) as a sensitizer on efficient induction of mechanical effects of pHIFU and chemically enhanced tumor growth inhibition for local anti-tumor therapy. METHOD: Changes in growth of colon 26 tumor tissue inoculated onto CDF1 mice were evaluated by the following treatments. (1) pHIFU exposure (1.1 MHz, 3.2 kW/cm(2), 300 cycles, and 50 ms interval) for 60 s, (2) PCND (1 %) injection, (3) adriamycin (4 mg/kg) injection, (4) pHIFU exposure after PCND injection, and (5) pHIFU exposure after PCND + adriamycin injection simultaneously. RESULTS: Significant changes in tumor growth were observed in the group with combination of pHIFU and PCND, although single therapy did not show any significant difference. PCND enhanced mechanical tissue fractionation by pHIFU, which was detectable by Real-time tissue elastography. Moreover, the combination of pHIFU and PCND + Adriamycin suppressed the tumor growth for 2 weeks, and 3 of 4 mice did not show any sign of regrowth during the 30-day observation. CONCLUSION: The combination of pHIFU and PCND exerted a significant anti-tumor effect and may be a new candidate for treatment of locally advanced cancer.