Development of a medical imaging-based technology for cancer treatment

The Electrical Impedance Mammography (EIM) device is an imaging system developed at the University of Sussex for the detection of breast lesions in vivo using quadrature detection of impedance. The work describes a novel technique to integrate Ultrasound-guided Focused Ultrasound Surgery (USgFUS) with the existing EIM system. The benefits that such a system could provide include the possibility of non-invasive detection, diagnosis and treatment of breast cancer all within a single device and involving no radiation. Furthermore the timescales involved would allow the process to be considered an outpatient procedure such that a patient can be diagnosed and treated on the same day using the same device. Various geometries of transducer were investigated for physical compatibility as well as the ability to target the entire specified volume, based on the dimensions of the existing system. Simulations were performed using a custom written code based on Huygen’s principle, allowing minimum surface area and power requirements to be determined and feasibility of designs to be evaluated. The use of phase differences in the excitation signals applied to individual elements was also investigated, thus the effect of steering the simulated focus could be observed, an important factor to consider when attempting to incorporate a transducer into a device with restricted dimensions. Resulting simulated pressure fields were used to obtain acoustic intensity fields, which could then be used as inputs in the Pennes Bio-Heat Transfer Equation (BHTE) allowing temperature distributions to be observed. Preliminary studies proved the feasibility of using the suggested transducer design in conjunction with the existing EIM system. Pressure fields and heating patterns were all within acceptable limits, confirming the ability of the device to effectively ablate cancerous tissue. Additionally the capability to steer the resultant focal point was validated, and a thermal dose model was implemented allowing different heating patterns to be quantitatively compared

Clinical applications of high-intensity focused ultrasound

published_or_final_versio

Acoustic Droplet Vaporization: Strategies for Control of Bubble Generation and its Application in Minimally Invasive Surgery.

As a minimally invasive alternative to current cancer treatment, the use of encapsulated, superheated liquid perfluorocarbon droplets has been proposed to treat cancer by occlusion therapy. In response to an acoustic field, these droplets, which are small enough to pass through capillaries, vaporize into large gas bubbles that subsequently lodge in the vasculature. This research investigates strategies to reduce the pressures necessary to achieve acoustic droplet vaporization (ADV), what implications they may have on efficiency, and how the resulting location of bubbles may alter the acoustic field. Two methods to lower the ADV threshold were explored. The first investigated the role of pulse duration on ADV. The second investigated the role of inertial cavitation (IC) external to a droplet by adding ultrasound contrast agent (CA), which has a low IC threshold. At 1.44 MHz, the threshold was found to be 5.5-5.9 MPa peak rarefactional pressure (Pr) for short microsecond pulses and decreased for millisecond pulses to 3.8-4.6 MPa Pr. When CAs were added and long millisecond pulses were used, the ADV threshold decreased to values as low as 0.41 MPa Pr. With the help of CA, the same amount of power was necessary to achieve ADV through an attenuating tissue mimicking (TM) phantom as it was without attenuation and with only droplets. When comparing ADV pressure thresholds, where in situ pressures were used when a TM phantom was present, rarefactional pressure appeared to be the salient determinant. However, careful consideration must be taken when choosing pulse repetition frequencies and amplitude as inertial collapse of both ADV and IC bubbles appears to affect efficient droplet conversion. During in vivo application, treatment planning may be important as backscattering properties of microbubbles created by ADV can augment or obstruct the sound field in the affected area. With strategic targeting and subsequent conversion of droplets into microbubbles, constructive interference due to these effects reduces the transmitted pressures required for proximal ADV, and the attenuation from these bubbles can create a protective boundary for distal areas. The potential result can be a confined area for further ADV where lower pressures are required to cause vaporization.Ph.D.Biomedical EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/57723/2/ahlo_1.pd

Focused ultrasound transducer spatial peak intensity estimation: a comparison of methods

Characterisation of the spatial peak intensity at the focus of high intensity focused ultrasound transducers is difficult because of the risk of damage to hydrophone sensors at the high focal pressures generated. Hill et al (1994 Ultrasound Med. Biol. 20 259-69) provided a simple equation for estimating spatial-peak intensity for solid spherical bowl transducers using measured acoustic power and focal beamwidth. This paper demonstrates theoretically and experimentally that this expression is only strictly valid for spherical bowl transducers without a central (imaging) aperture. A hole in the centre of the transducer results in over-estimation of the peak intensity. Improved strategies for determining focal peak intensity from a measurement of total acoustic power are proposed. Four methods are compared: (i) a solid spherical bowl approximation (after Hill et al 1994 Ultrasound Med. Biol. 20 259-69), (ii) a numerical method derived from theory, (iii) a method using measured sidelobe to focal peak pressure ratio, and (iv) a method for measuring the focal power fraction (FPF) experimentally. Spatial-peak intensities were estimated for 8 transducers at three drive powers levels: low (approximately 1 W), moderate (~10 W) and high (20-70 W). The calculated intensities were compared with those derived from focal peak pressure measurements made using a calibrated hydrophone. The FPF measurement method was found to provide focal peak intensity estimates that agreed most closely (within 15%) with the hydrophone measurements, followed by the pressure ratio method (within 20%). The numerical method was found to consistently over-estimate focal peak intensity (+40% on average), however, for transducers with a central hole it was more accurate than using the solid bowl assumption (+70% over-estimation). In conclusion, the ability to make use of an automated beam plotting system, and a hydrophone with good spatial resolution, greatly facilitates characterisation of the FPF, and consequently gives improved confidence in estimating spatial peak intensity from measurement of acoustic power

Ultrasound Based Method and Apparatus for Stone Detection and to Facilitate Clearance Thereof

Described herein are methods and apparatus for detecting stones by ultrasound, in which the ultrasound reflections from a stone are preferentially selected and accentuated relative to the ultrasound reflections from blood or tissue. Also described herein are methods and apparatus for applying pushing ultrasound to in vivo stones or other objects, to facilitate the removal of such in vivo objects

Imaging Feedback for Pulsed Cavitational Ultrasound Therapy: Histotripsy.

Histotripsy is a cavitational ultrasound therapy which mechanically fractionates soft tissue into subcellular debris using high intensity short ultrasound pulses. Histotripsy can be an effective tool for many clinical applications where non-invasive tissue removal is desired, including tumor therapy. For non-invasive tissue ablation therapy like histotripsy, image based feedback information allowing for accurate targeting, optimization of the on-going process, and prediction of the treatment efficacy in real time is the key to successful treatments. The overall goal of this research is to develop image based feedback methods that can accurately predict the clinical outcomes during and after histotripsy treatments. To achieve this goal, the research was conducted in two stages. In the first stage, new treatment strategies were investigated to produce homogeneous tissue fractionation. This ensures that feedback metrics obtained with any tissue characterization method are representative of the whole lesion instead of a misleading average of fully homogenized and non-homogenized zones. Specifically, two treatment strategies were developed. A focal zone sharpening technique, which limited the spatial extent of cavitation by preconditioning the cavitation nuclei in the surrounding area, was developed to create highly confined lesions with minimum scattered damage in the lesion boundaries. A cavitation memory removal strategy, which allowed for random distribution of cavitation in response to each therapy pulse, was developed to produce homogeneously fractionated lesions with a dramatically reduced therapy dose. In the second stage, three ultrasound image based methods were investigated to provide quantitative feedback information regarding the degree of tissue damage. These methods included ultrasound backscatter intensity analysis, ultrasound shear wave elasticity imaging, and characterization of shear wave propagation patterns. Strong correlations existed between the quantitative metrics derived from these methods and the degree of tissue fractionation as examined with histology, demonstrating the feasibility of using these metrics as quantitative feedback for histotripsy treatments. In conclusion, this research demonstrates that histotripsy can be a highly controllable tissue ablation therapy via precise control of cavitation. Significant potential exists for histotripsy to be developed into an image-guided modality for noninvasive ultrasound tissue ablation therapy.Ph.D.Biomedical EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/89658/1/tzuyin_1.pd

A study of stone fragmentation in shock wave lithotripsy by customizing the acoustic field and waveform shape

Shock wave lithotripsy is the preferred treatment modality for kidney stones in the United States. Despite clinical use for over twenty-five years, the mechanisms of stone fragmentation are still under debate. A piezoelectric array was employed to examine the effect of waveform shape and pressure distribution on stone fragmentation in lithotripsy. The array consisted of 170 elements placed on the inner surface of a 15 cm-radius spherical cap. Each element was driven independently using a 170 individual pulsers, each capable of generating 1.2 kV. The acoustic field was characterized using a fiber optic probe hydrophone with a bandwidth of 30 MHz and a spatial resolution of 100 μm. When all elements were driven simultaneously, the focal waveform was a shock wave with peak pressures p+ =65±3MPa and p−=−16±2MPa and the −6 dB focal region was 13 mm long and 2 mm wide. The delay for each element was the only control parameter for customizing the acoustic field and waveform shape, which was done with the aim of investigating the hypothesized mechanisms of stone fragmentation such as spallation, shear, squeezing, and cavitation. The acoustic field customization was achieved by employing the angular spectrum approach for modeling the forward wave propagation and regression of least square errors to determine the optimal set of delays. Results from the acoustic field customization routine and its implications on stone fragmentation will be discussed.National Institutes of Health DK04388