Brian Fowlkes

Disintegration of tissue using high intensity focused ultrasound: Two approaches that utilize shock waves

Introduction Surgery is moving more and more toward minimally-invasive procedures – using laparoscopic approaches with instruments inserted through tiny incisions or catheters placed in blood vessels through puncture sites. These techniques minimize the risks to the patient such as bleeding complications or infection during surgery. Taken a step further, high-intensity focused ultrasound (HIFU) can provide a tool to accomplish many of the same procedures without any incision at all. With HIFU, an ultrasound transducer can be positioned outside the body and focused through the skin and overlying tissue to deliver high-amplitude ultrasound to a target structure such as a tumor (Fig. 1). Absorption of acoustic energy within the focal volume is high enough to rapidly heat the tissue, effectively ‘cooking’ it within seconds or even a fraction of a second. This procedure also removes the need for a sterile operating room: without the risk of infection, HIFU noninvasive therapy could be done in the doctor’s office or outpatient clinic. For many years, HIFU surgery was centered on utilizing a thermal effect— tissue heating and denaturation caused by absorption of ultrasound. As the heating rate is dependent on local acoustic intensity, the temperature rises significantly enough to ablate tissue only in the focal region. While thermal ablation is the dominant interaction at lower HIFU focal intensities, higher intensities can introduce other bioeffects (Fig. 2). If the temperature rises to 100C during sonication, boiling bubbles appear in the tissue, inducing additional mechanical as well as thermal damage. At higher focal intensities, mechanical effects of the ultrasound wave itself become significant. The large tension phase of the wave can cause sporadic inertial cavitation or even a cloud of cavitation bubbles in the focal region in tissue—a process where the small gas bubbles grow and violently collapse, creating destructive effects on the tissue. Nonlinear propagation effects result in formation of high-amplitude shock waves around the focus which themselves create mechanical stress in the tissue. In addition, significantly enhanced heat deposiDISINTEGRATION OF TISSUE USING HIGH INTENSITY FOCUSED ULTRASOUND: TWO APPROACHES THAT UTILIZE SHOCK WAVES

Effects of ultrasound frequency and tissue stiffness on the histotripsy intrinsic threshold for cavitation.

Histotripsy is an ultrasound ablation method that depends on the initiation of a cavitation bubble cloud to fractionate soft tissue. Previous work has indicated that a cavitation cloud can be formed by a single pulse with one high-amplitude negative cycle, when the negative pressure amplitude directly exceeds a pressure threshold intrinsic to the medium. We hypothesize that the intrinsic threshold in water-based tissues is determined by the properties of the water inside the tissue, and changes in tissue stiffness or ultrasound frequency will have a minimal impact on the histotripsy intrinsic threshold. To test this hypothesis, the histotripsy intrinsic threshold was investigated both experimentally and theoretically. The probability of cavitation was measured by subjecting tissue phantoms with adjustable mechanical properties and ex vivo tissues to a histotripsy pulse of 1-2 cycles produced by 345-kHz, 500-kHz, 1.5-MHz and 3-MHz histotripsy transducers. Cavitation was detected and characterized by passive cavitation detection and high-speed photography, from which the probability of cavitation was measured versus pressure amplitude. The results revealed that the intrinsic threshold (the negative pressure at which probability = 0.5) is independent of stiffness for Youngs moduli (E) <1 MPa, with only a small increase (∼2-3 MPa) in the intrinsic threshold for tendon (E = 380 MPa). Additionally, results for all samples revealed only a small increase of ∼2-3 MPa when the frequency was increased from 345 kHz to 3 MHz. The intrinsic threshold was measured to be between 24.7 and 30.6 MPa for all samples and frequencies tested in this study. Overall, the results of this study indicate that the intrinsic threshold to initiate a histotripsy bubble cloud is not significantly affected by tissue stiffness or ultrasound frequency in the hundreds of kilohertz to megahertz range.

Effects of Ultrasound Frequency on Nanodroplet-Mediated Histotripsy.

Nanodroplet-mediated histotripsy (NMH) is a targeted ultrasound ablation technique combining histotripsy with nanodroplets that can be selectively delivered to tumor cells for targeted tumor ablation. In a previous study, it was reported that by use of extremely short, high-pressure pulses, histotripsy cavitation bubbles were generated in regions containing nanodroplets at significantly lower pressure (∼10.8 MPa) than without nanodroplets (∼28 MPa) at 500 kHz. Furthermore, it was hypothesized that lower frequency would improve the effectiveness of NMH by increasing the size of the focal region, increasing bubble expansion, and decreasing the cavitation threshold. In this study, we investigated the effects of ultrasound frequency (345 kHz, 500 kHz, 1.5 MHz, and 3 MHz) on NMH. First, the NMH cavitation threshold was measured in tissue phantoms with and without nanodroplets, with results indicating that the NMH threshold was significantly below the histotripsy intrinsic threshold at all frequencies. Results also indicated that the NMH threshold decreased at lower frequency, ranging from 7.4 MPa at 345 kHz to 13.2 MPa at 3 MHz. In the second part of this study, the effects of frequency on NMH bubble expansion were investigated, with results indicating larger expansion at lower frequency, even at a lower pressure. In the final part of this study, the ability of perfluoropentane-encapsulated nanodroplets to act as sustainable cavitation nuclei over multiple pulses was investigated, with results indicating that the nanodroplets are destroyed by the cavitation process and only function as cavitation nuclei for the first few pulses, with this effect being most pronounced at higher frequencies. Overall, the results of this study support our hypothesis that using a lower frequency will improve the effectiveness of NMH by increasing the size of the focal region, increasing bubble expansion and decreasing the cavitation threshold.

FPGA implementation of low-power 3D ultrasound beamformer

3D ultrasound is common for non-invasive medical imaging in cardiology and OB-GYN because of its accuracy, safety, and real-time ease of use. However, high bandwidth requirements and extreme computational complexity have precluded hand-held and low-power 3D systems, limiting 3D applications. In previous work, we presented Sonic Millip3De, a hardware design that can efficiently handle the high computational demand of real-time 3D synthetic aperture beamforming, even in handheld and mobile applications. The design combines a custom, highly parallel hardware system with a novel delay approximation method to quickly produce high quality 3D image data within an estimated 15 W full-system power budget. Prior evaluations of the design relied on software prototypes; this work extends previous evaluations with an FPGA implementation of the beamforming accelerator, validating the results of earlier prototypes. In particular, we carry out image quality analyses of our beamforming architecture using simulated 3D echo data (from Field II) and 2D artificial tissue phantom data acquired using a Verasonics V-1 system and Philips P4-1 probe. We compare results from the FPGA implementation to an ideal software beamformer and prior software prototypes of the Sonic Millip3De design.

Acoustic droplet vaporization for the enhancement of ultrasound thermal therapy

Acoustic droplet vaporization (ADV) is an ultrasound method for converting biocompatible microdroplets into microbubbles. The objective is to demonstrate that ADV bubbles can enhance high intensity focused ultrasound (HIFU) therapy by controlling and increasing energy absorption at the focus. Thermal phantoms were made with or without droplets. Compound lesions were formed in the phantoms by 5-second exposures with 5-second delays. Center to center spacing of individual lesions was 5.5 mm in either a linear pattern or a spiral pattern. Prior to the HIFU, 10 cycle tone bursts with 0.25% duty cycle were used to vaporize the droplets, forming an “acoustic trench” within 30 seconds. The transducer was then focused in the middle of the back bubble wall to form thermal lesions in the trench. All lesions were imaged optically and with 2T MRI. With the use of ADV and the acoustic trench, a uniform thermal ablation volume of 15 cm3 was achieved in 4 minutes; without ADV only less than 15% of this volume was filled. The commonly seen tadpole shape characteristic of bubble-enhanced HIFU lesions was not evident with the acoustic trench. In conclusion, ADV shows promise for the spatial control and dramatic acceleration of thermal lesion production by HIFU.

Functional imaging with intraoperative ultrasound: Detection of somatosensory cortex in dogs with color-duplex sonography

OBJECTIVE:To evaluate the capability of intraoperative color-duplex sonography to detect eloquent flow-activated areas and their anatomic relationship in dogs. METHODS:After craniotomy, the sensory cortex of eight dogs was identified by recording the highest amplitude detected with a grid electrode evoked with somatosensory evoked potential stimulation of the nervus ischiadicus. A 7.5-MHz linear array transducer was placed on the dura, and eight images were taken in color-coded capture mode during baseline and somatosensory evoked potential stimulation of the ipsilateral (nonevoked) and contralateral (evoked) sensory cortex. The differences in flow velocity intensities were statistically compared (Wilcoxon test) in three arbitrary velocity ranges and across all colored pixels in a region of interest between baseline and stimulation in both hemispheres. RESULTS:Comparing both hemispheres during stimulation, the evoked sensory cortex demonstrated an increase of 10% in the number of counted colored pixels during stimulation, whereas the number of counted colored pixels in the ipsilateral sensory cortex decreased by 2% (P < 0.05), indicating an overall increase in measured flow during stimulation. Comparing differences during nonstimulation and stimulation in single hemispheres, the lowest of the three velocity ranges (∼10–20 mm/s) demonstrated a statistically significant (P = 0.01) increase during stimulation, whereas no change was observed during stimulation in the ipsilateral hemisphere. This increase has been confirmed by regional cerebral blood flow measurement with colored microspheres. CONCLUSION:This study indicates, for the first time, the capability of intraoperative ultrasound to detect functionally important areas during evoked stimulation.

Histotripsy beyond the “intrinsic” cavitation threshold using very short ultrasound pulses: “Microtripsy”

Conventional histotripsy uses pulses with ≥3 cycles wherein the bubble cloud formation relies on the pressure-release scattering of the positive shock fronts from sparsely distributed cavitation bubbles. In a recent work, the peak negative pressure (P(-)) threshold for the generation of dense bubble clouds directly by a negative half cycle were measured, and this threshold has been called the “intrinsic threshold.” In this work, characteristics of lesions generated with this intrinsic threshold mechanism were investigated using RBC phantoms and excised canine tissues. A 32-element, PZT-8, 500 kHz therapy transducer was used to generate short (<2 cycles) histotripsy pulses at PRF = 1Hz and P(-) = 24.5–80.7 MPa. The results showed that the spatial extent of the histotripsy-induced lesions increased as the applied P(-) increased, and the lesion sizes corresponded well to the estimates of the focal regions above the intrinsic threshold. The sizes for the smallest reproducible lesions averaged 0.9 × 1.7mm (lateral × axial), significantly smaller than −6 dB beamwidth of the transducer (1.8 × 4.0 mm). These results suggest that predictable, well-confined and microscopic lesions can be precisely generated using the intrinsic threshold mechanism. Since the supra-threshold portion of the negative half cycle can be precisely controlled, lesions considerably less than a wavelength are easily produced (“microtripsy”).

High volume rate, high resolution 3D plane wave imaging

3D plane-wave imaging systems can support the high volume acquisition rates that are essential for 3D vector flow imaging and sonoelastography but suffer from low resolution and low SNR. Coherent compounding is a technique to improve the image quality of plane-wave systems at the expense of significant increase in beamforming computational complexity. In this paper, we propose a new separable beamforming method for 3D plane-wave imaging with coherent compounding that has computational complexity comparable to that of a non-separable non-compounding baseline system. The new method with 9-fire-angle compounding helps improve average CNR from 1.6 to 2.2 and achieve a SNR increase of 9.0 dB compared to the baseline system. We also propose several enhancements to our beamforming accelerator, Sonic Millip3De, including additional SRAM arrays, configurable interconnect, and embedded DRAM. Overall, our system is capable of generating high resolution images at 1000 volumes per second.

Quantitative Ultrasound Imaging to Assess the Biceps Brachii Muscle in Chronic Post-Stroke Spasticity: Preliminary Observation

We prospectively investigated the feasibility of using quantitative ultrasound imaging (QUI) to assess the biceps brachii muscle (BBM) in individuals with chronic post-stroke spasticity. To quantify muscle echogenicity and stiffness, we measured QUI parameters (gray-scale pixel value and shear wave velocity [SWV, m/s]) of the BBM in three groups: 16 healthy BBMs; 12 post-stroke, non-spastic BBMs; and 12 post-stroke, spastic BBMs. The QUI results were compared with the Modified Ashworth Scale and Tardieu Scale. A total of 20 SWVs were measured in each BBM, once at elbow in 90° flexion and again at maximally achievable extension using acoustic radiation force impulse imaging. BBM pixel value was measured in gray-scale images captured at 90° elbow flexion using ImageJ software. Statistical analyses included analysis of variance for examining the difference in SWV and pixel values among the three groups; Bonferroni correction for testing the difference in SWV and pixel values in a paired group; t-test for examining the difference in SWV values measured at two elbow angles; and Pearson correlation coefficient for analyzing the correlation of QUI to Modified Ashworth Scale and Tardieu Scale. SWV significantly differed between spastic BBMs and non-spastic or healthy BBMs. For pixel values, each of the three groups significantly differed from the others at elbow 90° flexion. The difference in SWV measured between the two elbow angles was also significant (p <0.01). A strong negative correlation was found between SWV and passive range of motion (R2 = -0.88, p <0.0001) in spastic upper limbs. These results suggest that the use of QUI is feasible in quantitative assessment of spastic BBM.

Numerical Study of Temperature Profile During ADV Enhanced HIFU Thermal Ablation of Tumor

By focusing the highly intensified ultrasound beams to a tiny region, the temperature at the focus could be enhanced to be more than 60°C and ablate the undesired tissues. Due to its non-invasiveness, the treatment (HIFU) is getting more popular.Copyright