Academic literature on the topic 'Ultrasound tissue characterisation'

Atherosclerosis is the leading cause of cardiovascular mortality and morbidity in the developed world. Intravascular ultrasound (IVUS) is a widely used imaging modality providing complementary diagnostic information to angiography regarding the vessel wall of the coronary arteries. IVUS has been used for assessment of ambiguous angiographic lesions, evaluation of new interventional devices and in atherosclerosis progression-regression trials. However, the standard gray-scale IVUS has limited value for the accurate identification of specific plaque components. This limitation has been partially over- come by introduction of new IVUS-based imaging methods such as: virtual histology IVUS, iMAP-IVUS and Integrated Backscatter IVUS. These methods utilise the ultrasound backscatter signal to enable a more detailed characterization of plaque morphology or tissue characterization and to provide insight on the features of vulnerable plaque.

Ultrasound has a high specificity for the diagnosis of a benign lesion in cases of classic appearing simple cyst, hemorrhagic cyst, endometrioma and dermoid. However, ultrasound can sometimes be limited for definitive characterisation and risk stratification of other types of lesions, including those with echogenic content that may appear solid, with or without blood flow. Frequently, MRI can be used to further characterise these types of lesions, due to its ability to distinguish solid tissue from non-tissue solid components such as fat, blood, or debris. Incorporating the MR imaging into the evaluation of adnexal lesions can improve diagnostic certainty and guide clinical management potentially avoiding inappropriate surgery for benign lesions and expediting appropriate treatment for malignant lesions, particularly in the females with sonographically indeterminate adnexal lesions.

Ultrasound can be used to assess injury and structural changes to the soft-tissue structure of the foot. It may be useful to assess the feet of people with diabetes who are at increased risk of plantar soft-tissue pathological changes. The aim of this study was to determine if ultrasound measurements of plantar soft-tissue thickness and assessments of tissue acoustic characteristics are reliable in people with and without diabetes mellitus. A repeated measures design was used to determine intra-observer reliability for ultrasound measurements of plantar skin and fat pad thickness and intra- and inter-observer reliability of plantar skin and fat pad tissue characterisation assessments made at foot sites which are at risk of tissue injury in people with diabetes. Thickness measurements and tissue characterisation assessments were obtained at the heel and forefoot in both the unloaded and compressed states and included discrete layers of the plantar tissues: skin, microchamber, horizontal fibrous band, macrochamber and total soft-tissue depth. At each site, relative intra-observer reliability was achieved for the measurement of at least one plantar tissue layer. The total soft-tissue thickness measured in the unloaded state (ICC 0.925–0.976) demonstrated intra-observer reliability and is the most sensitive for detecting small change on repeated measures. Intra-observer agreement was demonstrated for tissue characteristic assessments of the skin at the heel (k = 0.70), fat pad at the lateral sesamoid region (k = 0.70) and both skin and fat pad at the second (k = 0.80, k = 0.70 respectively) and third metatarsal heads (k = 0.90, k = 0.79 respectively). However, acceptable inter-observer agreement was not demonstrated for any tissue characteristic assessment, therefore the use of multiple observers should be avoided when making these assessments.

Intravascular ultrasound has, over the past decade, significantly changed the clinical diagnosis and therapeutic strategy of coronary and vascular disease assessment, as it not only allows visualisation of the vessel lumen, but gives a unique view of the pathophysiologic structure of the artery wall. This information is currently unavailable from the universally accepted instrument for artery assessment, angiography, which has on several occasions had its diagnostic accuracy questioned. With intravascular ultrasound, there is the potential to categorise diseased arterial tissue belonging to distinct pathological groups which can ultimately aid in the understanding of individual lesions as well as making a significant contribution to treatment choice and management of cardiac patients. The high resolution image information offered by intravascular ultrasound provides excellent cross-sectional views of coronary artery disease at the level of the disease process itself. This information can be used by the clinician to characterise atherosclerotic plaque composition and vessel wall morphology, both of which are important, in determining the clinical response to the disease condition. However, this visual diagnosis is in general highly subjective due to inter- and intra-observer error. To overcome the short comings inherent in the visual assessment of intravascular ultrasound images, texture analysis was used to assess plaque in regions of interest identified by a clinician. In the two dimensional images produced by intravascular ultrasound, texture is perceived as homogeneous visual patterns representing the surface composition being imaged. Since every tissue sub-group has its own texture, verified from histological analysis, it can be used as a means of characterising it. In this thesis, the findings of applying texture analysis techniques to 30 MHz intravascular ultrasound data, gathered in vitro, to assess its potential in quantitative coronary plaque characterisation are presented. Histo-pathological analysis was used to form a gold standard based upon clot composition, from which the results were verified. The ultimate aim of the work was to determine a reliable protocol based upon textural analysis for assessing plaque composition in vivo. Textural properties, in the form of features, were calculated for regions of interest using first-, second- and higher-order statistics. These were found to be computationally expensive and in certain instances produced duplicate, and hence redundant, information. Feature selection was used to increase the computational efficiency of the algorithm by optimising the feature set. In a further attempt to overcome the weaknesses of the aforementioned techniques, fractal texture analysis was used to obtain textural information on regions of interest. Fractals proved useful in describing the texture of these areas by a single measure. This measure, the fractal dimension, described the degree of irregularity in the surface texture. A new method is proposed for classifying arterial plaque which relies on a combination of the two powerful techniques previously mentioned, statistical and fractal texture analysis. The results presented show the ability of the texture analysis techniques used to discriminate certain tissue sub-groups. Limited success was achieved for the analysis on the atherosclerotic plaque groups studied, however, the approach adopted significantly discriminated the three types of clot composition studied: plasma; white thrombus; and red thrombus.

This thesis aims to investigate the acoustic properties of ultrasound contrast agents (UCAs) at high ultrasound frequencies. In recent years, there has been increasing development in the use of high frequency ultrasound in the fields of preclinical, intravascular, ophthalmology and superficial tissue imaging. Although research studying the acoustic response of UCAs at low diagnostic ultrasonic frequencies has been well documented, quantitative information on the acoustical properties of UCAs at high ultrasonic frequencies is limited. In this thesis, acoustical characterisation of three UCAs was performed using a preclinical ultrasound scanner (Vevo 770, VisualSonics Inc., Canada). Initially the acoustical characterisation of five high frequency transducers was measured using a membrane hydrophone with an active element of 0.2 mm in diameter to quantify the transmitting frequencies, pressures and spatial beam profiles of each of the transducers. Using these transducers and development of appropriate software, high frequency acoustical characterisation (speed and attenuation) of an agar-based tissue mimicking material (TMM) was performed using a broadband substitution technique. The results from this study showed that the acoustical attenuation of TMM varied nonlinearly with frequency and the speed of sound was approximately constant 1548m·s-1 in the frequency range 12-47MHz. The acoustical properties of three commercially available lipid encapsulated UCAs including two clinical UCAs Definity (Lantheus Medical Imaging, USA) and SonoVue (Bracco, Italy) and one preclinical UCAs MicroMarker (untargeted) (VisualSonics, Canada) were studied using the software and techniques developed for TMM characterisation. Attenuation, contrast-to-tissue ratio (CTR) and subharmonic to fundamental ratio were measured at low acoustic pressures. The results showed that large off-resonance and resonant MBs predominantly contributed to the fundamental response and MBs which resonated at half of the driven frequency predominantly contributed to subharmonic response. The effect of needle gauge, temperature and injection rate on the size distribution and acoustic properties of Definity and SonoVue was measured and was found to have significant impacts. Acoustic characterisations of both TMM and UCAs in this thesis extend our understanding from low frequency to high frequency ultrasound and will enable the further development of ultrasound imaging techniques and UCAs design specifically for high frequency ultrasound applications.

The second most common cause of cancer deaths in the developed world is bowel cancer. Improving the ability to detect and classify lesions as early as possible, allows treatment earlier. The work presented in this thesis is structured around the following detailed aims:Development of high frequency, broadband µUS (micro-ultrasound) imaging transducers through optimization of ultra-thinning processes for lithium niobate (LNO) and fabrication of novel ‘mass-spring’ matching layers using carefully controlled vacuum deposition is demonstrated. The effectiveness of this technique was quantified by applying multiple matching layers to 3 mm diameter 45 MHz LNO µUS transducers using carefully controlled vacuum deposition. The bandwidth of single mass-spring layer µUS transducer was measured to be 46% with an insertion loss of 21 dB. The bandwidth and insertion loss of a multiple matching layer µUS transducer was measured to be 59% and 18 dB respectively. The values were compared with an unmatched transducer which had a bandwidth and insertion loss of 28% and 34 dB respectively. All the experimentally measured values were in agreement with unidimensional acoustic model predictions. µUS tools that can detect and measure microscopic changes in precancerous tissue using a mouse small bowel model with an oncogenic mutation was developed. µUS transducer was used to test the hypothesis that the intestinal tissue morphology of WT (wild type) and ApcMin/+ (adenomatous polyposis coli) diverges with progressing age intervals (60, 90 and 120 days) of mice. A high frequency ultrasound scanning system was designed and the experiments were performed ex vivo using a focused 45 MHz, f-# = 2.85, µUS transducer. The data collected by scanning was used to compute the backscatter coefficients (BSC) and acoustic impedance (Z) of WT and ApcMin/+ mice. The 2D and 3D ultrasound images showed that µUS detects polyps < 500 µm in the scan plane. The measured values of BSC and Z showed differences between normal and precancerous tissue. The differences detected in precancerous murine intestine and human tissue using µUS were correlated with high resolution 3D optical imaging. This novel approach may provide a powerful adjunct to screening endoscopy for improved identification and monitoring, allowing earlier treatment of otherwise undetectable lesions.

This thesis addresses the challenges of measuring the acoustic (sound speed, attenuation, absorption and nonlinearity coefficients), thermal (thermal conductivity) and histological properties of soft tissues that lie within the HIFU beam during treatment. Differences in these tissue properties may affect the delivery of thermal therapies, but may also provide a basis for their monitoring with ultrasound. Novel measurement techniques have been developed and validated for each parameter. Measurements have been made in rat, bovine and human tissues. The finite amplitude insertion substitution (FAIS) method was used to obtain the attenuation coefficient and speed of sound. The absorption coefficients were determined using a thermometric method involving a Fabry-Perot fibre optic sensor. Nonlinearity coefficients were measured using the FAIS method with a large area hydrophone detector. Using these methodologies, a system that allows the measurement of all these parameters in the same region of a sample has been designed and built. Tissue thermal conductivity was determined using two methods: the first used a system designed to provide unidirectional heat flow between a source and heat sink. 35 MHz ultrasound (US) images were used to determine the volume of air trapped in the tissue sample, thus allowing corrections to the thermal conductivity to be made using the standard bio-heat equation model. The second method was a non-invasive method in which HIFU heating was combined with ultrasound thermometry. Finally, a Matlab code which allows quantification of important aspects of Haematoxylin and Eosin (H&E) stained histological images has been developed. This has been used to correlate the histological appearance of samples with their thermal and acoustic properties.

Tese de mestrado integrado em Engenharia Biomédica e Biofísica (Sinais e Imagens Médicas), apresentada à Universidade de Lisboa, através da Faculdade de Ciências, 2013
O fígado é um local frequente de ocorrência de tumores primários e secundários (do intestino, colo-rectal e cancro do estômago). A incidência de cancro do fígado a nível mundial é mais do que um milhão de casos por ano. O cancro no fígado mais comum encontrado na prática clínica são as metástases hepáticas que, juntamente com o carcinoma colo-rectal são os tipos histológicos mais predominantes. O cancro do fígado primário contribuiu com mais de 21 mil novos casos e causou 18.000 mortes nos Estados Unidos em 2008. O carcinoma hepatocelular (HCC) é o cancro primário de fígado mais comum, com uma incidência global estimada de mais de meio milhão de novos casos por ano e é a terceira maior causa de mortes por cancro em todo o mundo. Sem tratamento específico, o prognóstico é muito pobre, e as taxas de sobrevivência médias para pacientes com tumores iniciais e avançados são 6-9 meses e 1-2 meses, respectivamente. O HCC recorrente ocorre em 50% a 80% dos pacientes em 5 anos após a cirurgia de ressecção, a maioria ocorrendo no prazo de 2 anos. Após o tratamento para o HCC, 50% a 90% das mortes no pós-operatório é devido a doença recorrente. A hepatotomia (ressecção hepática) é viável apenas em 10-20% dos casos, e está associada a uma mortalidade operatória de até 5%, no entanto pode atingir taxas de sobrevivência de 5 anos em cerca de 40%. A alternativa actual à cirurgia é a combinação com quimioterapia, mas esta está associada uma taxa de resposta de 20-50%, e taxa de sobrevivência global relativamente curta (12-18 meses). Como resultado, têm sido feitos esforços consideráveis no sentido de proporcionar uma alternativa minimamente invasiva à cirurgia para estes doentes. Essas alternativas actualmente incluem a ablação por radiofrequência, crioterapia e terapia com laser. A única terapia local proposta não-invasiva até à data é High Intensity Focused Ultrasound (HIFU). HIFU é um procedimento não-invasivo que por meio de uma fonte extracorporal de ultra-sons de alta intensidade concentrada induz a necrose por coagulação total de um tecido alvo específico, sem necessidade de exposição cirúrgica ou a inserção de instrumentos no interior da lesão. A intenção do tratamento por HIFU é elevar a temperatura de uma região de tecido delimitada e isolada acima dos 55_C e manter essa temperatura durante 1 segundo ou mais. Isto, por sua vez induz a necrose por coagulação e morte celular. Os pequenos comprimentos de onda (mm) do ultra-som em frequências da ordem dos megahertz (MHz) em tecidos moles permitem que ele seja focado em pequenos volumes clinicamente relevantes. O perigo da maioria dos tratamentos ablativos, onde as células cancerígenas são destruídas pelo aumento da sua temperatura, é que o tecido saudável pode ser danificado. Com HIFU, a energia pode ser focada num volume muito pequeno e bem definido, fazendo com que a passagem do ultra-som através dos tecidos intervenientes, não cause nenhum efeito cumulativo aparente para esses tecidos. HIFU foi aprovado para terapias clínicas de tumores sólidos ou para outras doenças do fígado, rim, pâncreas, recto, próstata, mama, osso, pele e do útero. Em vários centros no mundo, o HIFU está a ser utilizado clinicamente para o tratamento de tumores sólidos (tanto malignos e benignos), incluindo os da próstata, do fígado, da mama, do rim, do osso e do pâncreas, e sarcoma de tecido mole. Tanto o cancro de fígado primário (carcinoma hepatocelular) e metástases hepáticas de cancros do cólon e estômago já foram tratados com HIFU. Apesar dos sucessos clínicos iniciais com tratamentos extracorpóreos de tumores abdominais, ainda existem alguns limites a ultrapassar – especialmente no que diz respeito ao tratamento do fígado, pâncreas e rins – antes de esta técnica poder ser utilizada de forma segura e rotineiramente no interior do corpo. Outra dificuldade importante a ter em conta é o facto de o comprimento do percurso nos tecidos que sobrepõem estes orgãos ser longo e, em geral, a sua composição ser pouco homogénea. Por exemplo, o tratamento terá que transmitir energia através da caixa torácica, o que pode aumentar o risco de queimaduras na pele e danos à superfície das costelas. Do mesmo modo, uma vez que o paciente respira, os efeitos desse movimento durante o tratamento precisa de ser explorado. Podem também ocorrer efeitos de cavitação como resultado do tratamento, e estes efeitos devem ser também considerados. Finalmente, actualmente ainda não existe uma técnica de imagem em tempo real completamente eficaz para a monitorização do tratamento, sendo este um requisito necessário para que a técnica seja utilizada e aplicada com sucesso. Para resolver estas questões, foi desenvolvido um projecto financiado pelo Engineering & Physical Sciences Research Council intitulado "THIFU - Trans-Costal High Intensity Focused Ultrasound" que tem como principal objectivo o desenvolvimento de uma nova técnica para a utilização de HIFU no tratamento de cancros na zona abdominal superior. O objectivo global do programa é desenvolver soluções práticas para esses problemas. Um dos objectivos com o projecto THIFU é a optimização da ablação do tecido no volume alvo e a minimização dos efeitos em estruturas críticas que sobrepõem o local onde queremos administrar a energia ultra-sónica, tais como a pele e a caixa torácica. O planeamento exacto do tratamento e o seu monitoramento bem como a própria administração do mesmo são fundamentais para isso. A fim de melhorar o planeamento e a administração do tratamento, é necessária proceder a uma caracterização precisa das propriedades físicas do tecido. Para isso, é indispensável uma compreensão completa dos campos acústicos, das propriedades dos tecidos no caminho de propagação do ultrassom e os mecanismos pelos quais a destruição dos tecidos é induzida pelo feixe de HIFU. Desta forma, é também importante conhecer a interacção do feixe de ultra-som com os diferentes tipos de tecido, com o fim de criar com precisão um plano de tratamento para a entrega da energia ultra-sónica no foco desejado. Assim, um dos objectivos deste projecto é obter uma estimativa precisa das propriedades acústicas dos tecidos-alvo (por exemplo, a velocidade do som e o coeficiente de atenuação). Esta informação é depois utilizada para determinar a absorção de energia e de transmissão da energia ultra-sónica nos tecidos-alvo. Estes resultados serão usados como parâmetros input para o software de planeamento de tratamento desenvolvido no projecto THIFU. O objectivo do trabalho descrito nesta dissertação foi abordar os dessafios de medir as propriedades acústicas (velocidade do som, coeficiente de atenuação e o coeficiente de não-linearidade) dos tecidos moles - mais concretamente em amostras de fígado humano obtidas logo após uma hepatotomia - que são atravessados pelo feixe HIFU durante o tratamento, com um sistema \all in one" que permite avaliar estas propriedades numa única amostra e num curto espaço de tempo, evitando assim a degradação das amostras. Foi feita uma investigação inicial com o intuito de validar o sistema all in one construído para o efeito com materiais considerados de referência (as suas propriedades acústicas são bastante conhecidas), como por exemplo phantoms em gel e óleo de rícino. Foram também recolhidos dados referentes a amostras de tecidos de origem animal e mais tarde procedeu-se à quantificação das propriedades acústicas de tecido hepático humano. Os valores obtidos com um líquido de referência { óleo de rícino { medido no sistema all-in-one a 23_C estão de acordo com valores publicados por outros estudos. Foram analisadas seis amostras de fígado humano de diferentes patologias. Um total de três tipos de tecidos foi estudado: saudável/normal, cancerígeno e cirrótico. Os resultados obtidos para as amostras de tecido de fígado humano, não mostram clara diferenciação entre o tumor e tecido normal e grande variação entre as amostras. Devido ao tamanho pequeno da amostra não é possível retirar conclusões estatisticamente significativas e precisas nesta fase. No entanto, os resultados gerais mostram que o sistema all-in-one é capaz de determinar estes parâmetros em amostras de referência - como phantoms de criogel e amostras de óleo de rícino - amostras de tecido animal ex-vivo e de tecido hepático humano. Trabalho futuro irá envolver a optimização de certos factores referentes aos materiais e métodos utilizados bem como melhoramentos nos protocolos de preparação das amostras, estudos adicionais com um tamanho de amostra maiores, estudo destas propriedades nos tecidos entre um intervalo de temperaturas relevante para a técnica de HIFU, etc. A dissertação está dividida em 5 capítulos. O primeiro capítulo consiste numa introdução ao tema abordado e a descrição dos principais conceitos inerentes ao trabalho desenvolvido. O segundo capítulo descreve os materiais e metodologias utilizadas. No terceiro e quarto capítulo encontram-se descritos os principais resultados e as conclusões, respectivamente.
High-intensity focused ultrasound (HIFU) provides a potential noninvasive alternative to conventional therapies. In spite of early clinical successes with extracorporeal treatments of abdominal tumours, there are some remaining challenges, especially related to access to the liver, pancreas and kidney. This thesis addresses the challenges of measuring the acoustic (sound speed, attenuation and non-linearity coefficients) properties of soft tissues that lie within the HIFU beam during treatment. Differences in these tissue properties may affect the delivery of thermal therapies, but may also provide a basis for their monitoring with ultrasound. Novel measurement techniques have been developed and applied in the construction of an "all-in-one" tissue characterisation system that allows for the determination of all these parameters in the same region of a single sample. The finite amplitude insertion substitution (FAIS) method was used to obtain the attenuation coefficient and speed of sound. Nonlinearity coefficients were measured using an adapted version of the FAIS method. The attenuation coefficient, sound speed and the acoustic nonlinearity parameter B/A were determined for explant human liver tissue samples with different pathological characteristics. A total of three tissue types were studied: healthy/normal, tumorous and cirrhotic. The results obtained for the human liver tissue samples show no clear differentiation between tumour and normal tissue and big variation between samples. However, as a result of the small sample size and no clear pattern observed, it is not statistically possible to draw accurate and statistically significant conclusions at this stage.The overall results show that the system is able to determine these parameters in reference samples such as cryogel phantoms and castor oil samples, animal ex-vivo tissue and explant human liver tissue. Future studies with a bigger sample size will be required in order to validate the system and also explore thoroughly the relationship between the acoustic properties and temperature variations in the tissue. in reference samples such as cryogel phantoms and castor oil samples, animal ex-vivo tissue and explant human liver tissue. Future studies with a bigger sample size will be required in order to validate the system and also explore thoroughly the relationship between the acoustic properties and temperature variations in the tissue.

Breast elastography has become a key complementary technique. A modality in the framework of breast pathology, complementary of B-mode imaging and colour doppler analysis. Breast ultrasound has provided morphological grayscale images and functional flow analysis of the soft breast tissues. Elastography now brings new physio-pathological information through the assessment of tissue elasticity. There are two different modalities: Real Time Elastography (RTE) and Shear Waves (SWE) ultrafast Imaging. Both techniques require a minimum adhesion to the skill rules for acquisition and interpretation so as to limit the operator dependant dimension and diagnostic errors. Elastography thus becomes perfectly reproducible with good accuracy in the different scores of the RTE or SWE classification. The aim of elastography in cancer screening is to achieve reliable lesion characterisation and better therapy monitoring/management.

The main goal of surgical oncology is to achieve complete resection of cancerous tissue with minimal iatrogenic injury to the adjacent healthy structures. Brain tumour surgery is particularly demanding due to the eloquence of the tissue involved. There is evidence that increasing the extent of tumour resection substantially improves overall and progression-free survival. Realtime intraoperative tools which inform of residual disease are invaluable. Intraoperative Ultrasound (iUS) has been established as an efficient tool for tissue characterisation during brain tumour resection in neurosurgery [1]. The integration of iUS into the operating theatre is characterised by significant challenges related to the interpretation and quality of the US data. The capturing of high-quality US images requires substantial experi- ence and visuo-tactile skills during manual operation. Recently, robotically-controlled US scanning systems have been proposed (see e.g. [2]) but the scanning of brain tissue poses major challenges to robotic systems because of the safety-critical nature of the procedure, the very low and precise contact forces required, the narrow access space and the large variety of tissue properties (hard scull, soft brain structure). The aim of this paper is to introduce a robotic platform for autonomous iUS tissue scanning to optimise intraop- erative diagnosis and improve surgical resection during robot-assisted operations. To guide anatomy specific robotic scanning and generate a representation of the robot task space, fast and accurate techniques for the recovery of 3D morphological structures of the surgical cavity are developed. The prototypic DLR MIRO surgi- cal robotic arm [3] is used to control the applied force and the in-plane motion of the US transducer. A key application of the proposed platform is the scanning of brain tissue to guide tumour resection.