The use of ultrasound to create tissue hyperthermia to support the treatment of cancer

The value of mild hyperthermia in improving the outcome of radiotherapy and chemotherapy treatments is well established. However, clinical applications are currently restricted to accessible tumours, with the application of controlled hyperthermia in solid tumours deep within the body presenting an unresolved problem. Ultrasound is an attractive heating technique because of its ability to create a focus at depth which can be steered around the tumour volume. However, despite considerable research no clinically usable transducers for deep tumour applications have resulted. In this thesis the underlying principles that govern the characteristics of phased array transducers have been examined. The concept of an idealised phased array has been introduced, and analysis of simulated fields from such arrays has enabled a new set of equations to be defined which relate the geometry of the field to the fundamental array design parameters (including the array diameter, radius of curvature and frequency of operation). Further simulations have examined the impact of secondary array design parameters (such as the individual element size, number density and layout geometry) which modify the field from that of the idealised case. Analysis of these has enabled an upper limit to be placed on the element size within any planar array in order to prevent undesirable changes in the characteristics of the focal region. A fifteen element phased array with a random element distribution has been constructed based on the design principles established in the simulation work. Measurements of the inter-element cross-coupling have been made, demonstrating that acoustic coupling dominated for inter-element pitches of less than 8 mm, while electrical coupling dominated at larger inter-element pitches. The field produced by the array in an acoustic tank has been characterised and compared against simulation predictions, showing good agreement in terms of the geometries of the focal region and the grating lobes. However, a number of differences have also been identified. In particular, the focal region was closer to the surface of the physical transducer in the measured fields compared to the simulation results, and there were numerous small high intensity regions between the surface of the transducer and the focus which were absent from the simulated fields. A sensitivity analysis, using a simulated factorial experiment, has been performed to identify the origin of these differences, with the results indicating that the presence of a secondary vibrational mode within the elements of the array was the principal causative factor. Finally, calculations have been performed which demonstrate the feasibility of manufacturing an array suitable for the application of mild hyperthermia in deep tumours based on the array design scheme presented in this thesis. Potential extensions of the array design have also been described which would improve the behaviour of the array under steering and provide further increase in the focal intensity

The use of ultrasound to create tissue hyperthermia to support the treatment of cancer

The value of mild hyperthermia in improving the outcome of radiotherapy and chemotherapy treatments is well established. However, clinical applications are currently restricted to accessible tumours, with the application of controlled hyperthermia in solid tumours deep within the body presenting an unresolved problem. Ultrasound is an attractive heating technique because of its ability to create a focus at depth which can be steered around the tumour volume. However, despite considerable research no clinically usable transducers for deep tumour applications have resulted. In this thesis the underlying principles that govern the characteristics of phased array transducers have been examined. The concept of an idealised phased array has been introduced, and analysis of simulated fields from such arrays has enabled a new set of equations to be defined which relate the geometry of the field to the fundamental array design parameters (including the array diameter, radius of curvature and frequency of operation). Further simulations have examined the impact of secondary array design parameters (such as the individual element size, number density and layout geometry) which modify the field from that of the idealised case. Analysis of these has enabled an upper limit to be placed on the element size within any planar array in order to prevent undesirable changes in the characteristics of the focal region. A fifteen element phased array with a random element distribution has been constructed based on the design principles established in the simulation work. Measurements of the inter-element cross-coupling have been made, demonstrating that acoustic coupling dominated for inter-element pitches of less than 8 mm, while electrical coupling dominated at larger inter-element pitches. The field produced by the array in an acoustic tank has been characterised and compared against simulation predictions, showing good agreement in terms of the geometries of the focal region and the grating lobes. However, a number of differences have also been identified. In particular, the focal region was closer to the surface of the physical transducer in the measured fields compared to the simulation results, and there were numerous small high intensity regions between the surface of the transducer and the focus which were absent from the simulated fields. A sensitivity analysis, using a simulated factorial experiment, has been performed to identify the origin of these differences, with the results indicating that the presence of a secondary vibrational mode within the elements of the array was the principal causative factor. Finally, calculations have been performed which demonstrate the feasibility of manufacturing an array suitable for the application of mild hyperthermia in deep tumours based on the array design scheme presented in this thesis. Potential extensions of the array design have also been described which would improve the behaviour of the array under steering and provide further increase in the focal intensity.EThOS - Electronic Theses Online ServiceEngineering and Physical Sciences Research Council (Great Britain) (EPSRC)GBUnited Kingdo

Predicting the abatement rates of soil organic carbon sequestration management in Western European vineyards using random forest regression

The implementation of soil organic carbon sequestration (SCS) practices on agricultural land has the potential to help to mitigate climate change at the global level. However, our understanding of the extent to which viticultural soils can contribute to this global effort remains limited. In this study, we used a random forest regression to predict the change in soil organic carbon stocks in vineyards of Western Europe under five SCS practices: organic amendments (OA), cover cropping (CC), organic amendments and no-tillage (OA+NT), no-tillage and cover cropping (NT+CC), and a combination of organic amendments, no-tillage and cover cropping (OA+NT+CC). The abatement rate of each SCS practice was modelled and mapped for six countries in Western Europe: Spain, France, Italy, Portugal, Germany and Austria. Overall, the highest abatement rate was reached under OA+NT+CC (8.29 ​Mg CO2-eq. ha−1 yr−1), whereas the lowest was observed under CC (7.03 Mg CO2-eq. ha−1 yr−1). Results showed major differences in abatement rates at the regional and national level. Despite these differences, the adoption of SCS practices was associated with a high abatement potential in the six countries and should be encouraged in the viticulture sector as a way to offset greenhouse gas emissions via soil carbon sequestration

The design and characterization of an ultrasound phased array suitable for deep tissue hyperthermia

In this paper we describe the design and evaluation of a planar phased-array ultrasound transducer suitable for producing localized hyperthermia in solid tumors deep within the body. Simulation using a customized version of Ultrasim has been used to determine the relationship between the size and position of the focus and parameters of the array. These parameters include the overall size of the array and the size, shape and distribution of the individual elements. A 15-element prototype array has been constructed using the results of the simulation. Beam profile measurements on this transducer made in an acoustic tank were compared with the beam profile predicted by simulation. The results showed good agreement in the shape of the focal region, but with the focus closer to the surface of the physical transducer when compared with the simulation and with small high-intensity areas between the surface of the transducer and the focus in the measured profile. A sensitivity analysis using a simulated factorial experiment indicated that the presence of a secondary vibrational mode within the elements of the array was the principal cause for both the shift in the position of the focus and for the unwanted maxima close to the surface of the array. The results also showed that the array was tolerant of a large variation in output intensity of the individual elements in the array in producing a focal region. Extrapolation of the results obtained in this study indicate that an array of 60 elements, based on the design described, driven by 550 V peak-to-peak pulses would be capable of producing a peak focal intensity of 50 Wcm(-2) at a depth of 60 mm in tissue, which would be appropriate for hyperthermia used as an adjunct to radiotherapy or chemotherapy. (E-mail: [email protected]) (C) 2008 World Federation for Ultrasound in Medicine & Biology

An analysis of the origin of differences between measured and simulates fields produced by a 15-element ultrasound phased array

Modeling provides an attractive approach for the design of phased array ultrasound transducers for hyperthermia. However, measurements on physical transducers reveal differences from the idealized field profiles predicted by simulation. In this paper we report a method of analyzing the origins of these differences. The measured performance of a 15-element sparse phased array is described and compared with simulated fields calculated using the point source method. It highlighted two notable differences: First, that the focal region was located closer to the surface of the physical transducer than in the simulated fields; and second, that numerous intensity maxima were present between the surface of the transducer and the focal zone in the experimental data, but not in the simulated fields. We identified six factors that could potentially affect the field but were not taken into account by the default simulations, and we performed a sensitivity analysis on these: (i) Variation in the amplitude of the output from each element, (ii) the presence of square-wave harmonics in the drive signals, (iii) nonpistonlike vibration of elements, (iv) quantization of the applied phases, (v) errors in the spatial positioning of each element; and (vi) interelement cross-coupling. Both the independent impact of each factor and the interactions between multiple factors were analyzed by using a full-factorial experimental design composed of 64 (2(6)) simulations. The results indicated that nonpistonlike motion of elements is likely to be the primary cause of differences between the measured and modelled fields. Determination of the precise vibrational modes of elements in an array is complex and would require full finite element analysis. However, the simple vibrational mode considered within the present work, corresponding to the addition of a surface Rayleigh wave originating at the element center and propagating radially, produced simulation results that were in good agreement with the measured data. (E-mail: [email protected]) (C) 2010 World Federation for Ultrasound in Medicine & Biology

Pitfalls in the beam modelling process of Monte Carlo calculations for proton pencil beam scanning.

OBJECTIVE Monte Carlo (MC) simulations substantially improve the accuracy of predicted doses. This study aims to determine and quantify the uncertainties of setting up such a MC system. METHODS Doses simulated with two Geant4-based MC calculation codes, but independently tuned to the same beam data, have been compared. Different methods of MC modelling of a pre-absorber have been employed, either modifying the beam source parameters (descriptive) or adding the pre-absorber as a physical component (physical). RESULTS After the independent beam modelling of both systems in water (resulting in excellent range agreement) range differences of up to 3.6/4.8 mm (1.5% of total range) in bone/brain-like tissues were found, which resulted from the use of different mean water ionisation potentials during the energy tuning process. When repeating using a common definition of water, ranges in bone/brain agreed within 0.1 mm and gamma-analysis (global 1%,1mm) showed excellent agreement (>93%) for all patient fields. However, due to a lack of modelling of proton fluence loss in the descriptive pre-absorber, differences of 7% in absolute dose between the pre-absorber definitions were found. CONCLUSION This study quantifies the influence of using different water ionisation potentials during the MC beam modelling process. Furthermore, when using a descriptive pre-absorber model, additional Faraday cup or ionisation chamber measurements with pre-absorber are necessary. ADVANCES IN KNOWLEDGE This is the first study quantifying the uncertainties caused by the MC beam modelling process for proton pencil beam scanning, and a more detailed beam modelling process for MC simulations is proposed to minimise the influence of critical parameters