Computational ultrasound tissue characterisation for brain tumour resection

In brain tumour resection, it is vital to know where critical neurovascular structuresand tumours are located to minimise surgical injuries and cancer recurrence. Theaim of this thesis was to improve intraoperative guidance during brain tumourresection by integrating both ultrasound standard imaging and elastography in thesurgical workflow. Brain tumour resection requires surgeons to identify the tumourboundaries to preserve healthy brain tissue and prevent cancer recurrence. Thisthesis proposes to use ultrasound elastography in combination with conventionalultrasound B-mode imaging to better characterise tumour tissue during surgery.Ultrasound elastography comprises a set of techniques that measure tissue stiffness,which is a known biomarker of brain tumours. The objectives of the researchreported in this thesis are to implement novel learning-based methods for ultrasoundelastography and to integrate them in an image-guided intervention framework.Accurate and real-time intraoperative estimation of tissue elasticity can guide towardsbetter delineation of brain tumours and improve the outcome of neurosurgery. We firstinvestigated current challenges in quasi-static elastography, which evaluates tissuedeformation (strain) by estimating the displacement between successive ultrasoundframes, acquired before and after applying manual compression. Recent approachesin ultrasound elastography have demonstrated that convolutional neural networkscan capture ultrasound high-frequency content and produce accurate strain estimates.We proposed a new unsupervised deep learning method for strain prediction, wherethe training of the network is driven by a regularised cost function, composed of asimilarity metric and a regularisation term that preserves displacement continuityby directly optimising the strain smoothness. We further improved the accuracy of our method by proposing a recurrent network architecture with convolutional long-short-term memory decoder blocks to improve displacement estimation and spatio-temporal continuity between time series ultrasound frames. We then demonstrateinitial results towards extending our ultrasound displacement estimation method toshear wave elastography, which provides a quantitative estimation of tissue stiffness.Furthermore, this thesis describes the development of an open-source image-guidedintervention platform, specifically designed to combine intra-operative ultrasoundimaging with a neuronavigation system and perform real-time ultrasound tissuecharacterisation. The integration was conducted using commercial hardware andvalidated on an anatomical phantom. Finally, preliminary results on the feasibilityand safety of the use of a novel intraoperative ultrasound probe designed for pituitarysurgery are presented. Prior to the clinical assessment of our image-guided platform,the ability of the ultrasound probe to be used alongside standard surgical equipmentwas demonstrated in 5 pituitary cases

Novel Ultrasound Elastography Imaging System for Breast Cancer Assessment

Abstract Most conventional methods of breast cancer screening such as X-ray, Ultrasound (US) and MRI have some issues ranging from weaknesses associated with tumour detection or classification to high cost or excessive time of image acquisition and reconstruction. Elastography is a non- invasive technique to visualize suspicious areas in soft tissues such as the breast, prostate and myocardium using tissue stiffness as image contrast mechanism. In this study, a breast Elastography system based on US imaging is proposed. This technique is fast, expected to be cost effective and more sensitive and specific compared to conventional US imaging. Unlike current Elastography techniques that image relative elastic modulus, this technique is capable of imaging absolute Young\u27s modulus (YM). In this technique, tissue displacements and surface forces used to mechanically stimulate the tissue are acquired and used as input to reconstruct the tissue YM distribution. For displacements acquisition, two techniques were used in this research: 1) a modified optical flow technique, which estimates the displacement of each node from US pre- and post-compression images and 2) Radio Frequency (RF) signal cross-correlation technique. In the former, displacements are calculated in 2 dimensions whereas in the latter, displacements are calculated in the US axial direction only. For improving the quality of elastography images, surface force data was used to calculate the stress distribution throughout the organ of interest by using an analytical model and a statistical numerical model. For force data acquisition, a system was developed in which load cells are used to measure forces on the surface of the breast. These forces are input into the stress distribution models to estimate the tissue stress distribution. By combining the stress field with the strain field calculated from the acquired displacements using Hooke\u27s law, the YM can be reconstructed efficiently. To validate the proposed technique, numerical and tissue mimicking phantom studies were conducted. For the numerical phantom study, a 3D breast-shape phantom was created with synthetic US pre- and post-compression images where the results showed the feasibility of reconstructing the absolute value of YM of tumour and background. In the tissue mimicking study, a block shape gelatine- agar phantom was constructed with a cylindrical inclusion. Results obtained from this study also indicated reasonably accurate reconstruction of the YM. The quality of the obtained elasticity images shows that image quality is improved by incorporating the adapted stress calculation techniques. Furthermore, the proposed elastography system is reasonably fast and can be potentially used in real-time clinical applications

Development of a Harmonic Motion Imaging guided Focused Ultrasound system for breast tumor characterization and treatment monitoring

Breast cancer is the most common cancer and the second leading cause of cancer death among women. About 1 in 8 U.S. women (about 12%) will develop invasive breast cancer over the course of their lifetime. Existing methods of early detection of breast cancer include mammography and palpation, either by patient self-examination or clinical breast exam. Palpation is the manual detection of differences in tissue stiffness between breast tumors and normal breast tissue. The success of palpation relies on the fact that the stiffness of breast tumors is often an order of magnitude greater than that of normal breast tissue, i.e., breast lesions feel ''hard'' or ''lumpy'' as compared to normal breast tissue. A mammogram is an x-ray that allows a qualified specialist to examine the breast tissue for any suspicious areas. Mammography is less likely to reveal breast tumors in women younger than 50 years with denser breast than in older women. When a suspicious site is detected in the breast through a breast self-exam or on a screening mammogram, the doctor may request an ultrasound of the breast tissue. A breast ultrasound can provide evidence about whether the lump is a solid mass, a cyst filled with fluid, or a combination of the two. An invasive needle biopsy is the only diagnostic procedure that can definitely determine if the suspicious area is cancerous. In the clinic, 80% of women who have a breast biopsy do not have breast cancer. Most women with breast cancer diagnosed will have some type of surgery to remove the tumor. Depending on the type of breast cancer and how advanced it is, the patient might need other types of treatment as well, such as chemotherapy and radiation therapy. Image-guided minimally-invasive treatment of localized breast tumor as an alternative to traditional breast surgery, such as high intensity focused ultrasound (HIFU) treatment, has become a subject of intensive research. HIFU applies extreme high temperatures to induce irreversible cell injury, tumor apoptosis and coagulative necrosis. Compared with conventional surgical procedures the main advantages of HIFU ablation lie in the fact that it is non-invasive, less scarring and less painful, allowing for shorter recovery time. HIFU can be guided by MRI (MRgFUS) or by conventional diagnostic ultrasound (USgFUS). Worldwide, thousands of patients with uterine fibroids, liver cancer, breast cancer, pancreatic cancer, bone tumors, and renal cancer have been treated by USgFUS. In this dissertation, the objective is to develop an integrated Harmonic Motion Imaging guided Focused Ultrasound (HMIgFUS) system as a clinical monitoring technique for breast HIFU with the added capability of detecting tumors for treatment planning, evaluation of tissue stiffness changes during HIFU ablation for treatment monitoring in real time, and assessment of thermal lesion sizes after treatment evaluation. A new HIFU treatment planning method was described that used oscillatory radiation force induced displacement amplitude variations to detect the HIFU focal spot before lesioning. Using this method, we were able to visualize the HMIgFUS focal region at variable depths. By comparing the estimated displacement profiles with lesion locations in pathology, we demonstrated the feasibility of using this HMI-based technique to localize the HIFU focal spot and predict lesion location during the planning phase. For HIFU monitoring, a HIFU lesion detection and ablation monitoring method was first developed using oscillatory radiation force induced displacement amplitude variations in real time. Using this method, the HMIgFUS focal region and lesion formation were visualized in real time at a feedback rate of 2.4 Hz. By comparing the estimated lesion size against gross pathology, the feasibility of using HMIgFUS to monitor treatment and lesion formation without interruption is demonstrated. In order to reduce the imaging time, it is shown in this dissertation that using the steered FUS beam, HMI can be used to image a 2.3 times larger ROI without requiring physical movement of the transducer. Using steering for HMI can be used to shorten the total imaging duration without requiring physical movement of the transducer. For the application of breast tumor, HMI and HMIgFUS were optimized and applied to ex vivo breast tissue. The results showed that HMI is experimentally capable of mapping and differentiating stiffness in normal and abnormal breast tissues. HMIgFUS can also successfully generate thermal lesions on normal and pathological breast tissues. HMI has also been applied to post-surgical breast mastectomy specimens to mimic the in vivo environment. In the end, the first HMI clinical system has been built with added capability of GUP-based parallel beamforming. A clinical trial has been approved at Columbia University to image breast tumor on patient. The HMI clinical system has shown to be able to map fibroadenoma mass on two patients with valid HMI displacement. The study in this dissertation may yield an early-detection technique for breast cancer without any age discrimination and thus, increase the survival rate

Keselesaan ke tempat kerja mempengaruhi kualiti hidup masyarakat bandar di Mukim Kajang, Selangor

Keselesaan penduduk ke tempat bekerja boleh mempengaruhi kualiti hidup masyarakat. Kajian ini telah mengenalpasti bahawa keselesaan ke tempat bekerja merupakan aspek yang boleh menyumbang kepada kualiti hidup yang baik. Oleh itu, aspek keselesaan ke tempat kerja harus diambilkira dalam menilai kualiti hidup masyarakat di bandar. Permasalah kajian ini ialah isu ketidakselesaan penduduk ke tempat bekerja telah menyebabkan gangguan pada kualiti hidup. Objektif kajian ialah mengkaji persepsi penduduk di bandar terhadap keselesaan ke tempat kerja. Kajian dijalankan di Bandar Kajang dan Bandar Baru Bangi. Kaedah soal selidik telah digunakan di lapangan. Sejumlah 700 responden telah dipilih secara rawak bebas di kawasan kajian. Data-data yang dikumpul telah dianalisis menggunakan program SPSS. Hasil kajian mendapati paling ramai responden iaitu 135 orang bekerja di tempat lain-lain, 112 bekerja di Kajang,105 bekerja di Bandar Baru Bangi, 36 bekerja di Universiti Kebangsaan Malaysia dan 26 bekerja di Serdang. Analisis perkaitan antara jarak rumah ke tempat bekerja menunjukkan nilai khi kuasa dua sebanyak 89.329 dan signifikan pada aras 0.05 (p=0.000), perkaitan antara jarak rumah ke tempat kerja dengan tempoh terlibat kesesakan lalu lintas menunjukkan nilai khi kuasa dua sebanyak 227.568 dan signifikan pada aras 0.05 (p=0.000). Sejumlah 208 responden terganggu emosi semasa berhadapan dengan kesesakkan lalu lintas, manakala 150 menyatakan masih boleh bersabar. Seramai 359 responden menyatakan tidak selesa ke tempat kerja sekiranya berlaku kesesakan lalu lintas.Kajian merumuskan bahawa kajian keselesaan ke tempat kerja wajar digunakan sebagai penunjuk kualiti hidup masyarakat di bandar, berdasarkan konflik-konflik yang dialami penduduk di bandar semasa berinteraksi ke tempat bekerja

Novel Techniques for Tissue Imaging and Characterization Using Biomedical Ultrasound

The use of ultrasound technology in the biomedical field has been widely increased in recent decades. Ultrasound modalities are considered more safe and cost effective than others that use ionizing radiation. Moreover, the use of high-frequency ultrasound provides means of high-resolution and precise tissue assessment. Consequently, ultrasound elastic waves have been widely used to develop non-invasive techniques for tissue assessment. In this work, ultrasound waves have been used to develop non-invasive techniques for tissue imaging and characterization in three different applications.;Currently, there is a lack of imaging modalities to accurately predict minute structures and defects in the jawbone. In particular, the inability of 2D radiographic images to detect bony periodontal defects resulted from infection of the periodontium. They also may carry known risks of cancer generation or may be limited in accurate diagnosis scope. Ultrasonic guided waves are sensitive to changes in microstructural properties, while high-frequency ultrasound has been used to reconstruct high-resolution images for tissue. The use of these ultrasound techniques may provide means for early diagnosis of marrow ischemic disorders via detecting focal osteoporotic marrow defect, chronic nonsuppurative osteomyelitis, and cavitations in the mandible (jawbone). The first part of this work investigates the feasibility of using guided waves and high frequency ultrasound for non-invasive human jawbone assessment. The experimental design and the signal/image processing procedures for each technique are developed, and multiple in vitro studies are carried out using dentate and non-dentate mandibles. Results from both the ultrasonic guided waves analysis and the high frequency 3D echodentographic imaging suggest that these techniques show great potential in providing non-invasive methods to characterize the jawbone and detect periodontal diseases at earlier stages.;The second part of this work describes indirect technique for characterization via reconstructing high-resolution microscopic images. The availability of well-defined genetic strains and the ability to create transgenic and knockout mice makes mouse models extremely significant tools in different kinds of research. For example, noninvasive measurement of cardiovascular function in mouse hearts has become a valuable need when studying the development or treatment of various diseases. This work describes the development and testing of a single-element ultrasound imaging system that can reconstruct high-resolution brightness mode (B-mode) images for mouse hearts and blood vessels that can be used for quantitative measurements in vitro. Signal processing algorithms are applied on the received ultrasound signals including filtering, focusing, and envelope detection prior to image reconstruction. Additionally, image enhancement techniques and speckle reduction are adopted to improve the image resolution and quality. The system performance is evaluated using both phantom and in vitro studies using isolated mouse hearts and blood vessels from APOE-KO and its wild type control. This imaging system shall provide a basis for early and accurate detection of different kinds of diseases such as atherosclerosis in mouse model.;The last part of this work is initialized by the increasing need for a non-invasive method to assess vascular wall mechanics. Endothelial dysfunction is considered a key factor in the development of atherosclerosis. Flow-mediated vasodilatation (FMD) measurement in brachial and other conduit arteries has become a common method to assess the endothelial function in vivo. In spite of the direct relationship that could be between the arterial wall multi-component strains and the FMD response, direct measurement of wall strain tensor due to FMD has not yet been reported in the literature. In this work, a noninvasive direct ultrasound-based strain tensor measuring (STM) technique is presented to assess changes in the mechanical parameters of the vascular wall during post-occlusion reactive hyperemia and/or FMD, including local velocities and displacements, diameter change, local strain tensor and strain rates. The STM technique utilizes sequences of B-mode ultrasound images as its input with no extra hardware requirement. The accuracy of the STM algorithm is assessed using phantom, and in vivo studies using human subjects during pre- and post-occlusion. Good correlations are found between the post-occlusion responses of diameter change and local wall strains. Results indicate the validity and versatility of the STM algorithm, and describe how parameters other than the diameter change are sensitive to reactive hyperemia following occlusion. This work suggests that parameters such as local strains and strain rates within the arterial wall are promising metrics for the assessment of endothelial function, which can then be used for accurate assessment of atherosclerosis