Elasticity mapping for breast cancer diagnosis using tactile imaging and auxiliary sensor fusion

Tactile Imaging (TI) is a technology utilising capacitive pressure sensors to image elasticity distributions within soft tissues such as the breast for cancer screening. TI aims to solve critical problems in the cancer screening pathway, particularly: low sensitivity of manual palpation, patient discomfort during X-ray mammography, and the poor quality of breast cancer referral forms between primary and secondary care facilities. TI is effective in identifying ‘non-palpable’, early-stage tumours, with basic differential ability that reduced unnecessary biopsies by 21% in repeated clinical studies. TI has its limitations, particularly: the measured hardness of a lesion is relative to the background hardness, and lesion location estimates are subjective and prone to operator error. TI can achieve more than simple visualisation of lesions and can act as an accurate differentiator and material analysis tool with further metric development and acknowledgement of error sensitivities when transferring from phantom to clinical trials. This thesis explores and develops two methods, specifically inertial measurement and IR vein imaging, for determining the breast background elasticity, and registering tactile maps for lesion localisation, based on fusion of tactile and auxiliary sensors. These sensors enhance the capabilities of TI, with background tissue elasticity determined with MAE < 4% over tissues in the range 9 kPa – 90 kPa and probe trajectory across the breast measured with an error ratio < 0.3%, independent of applied load, validated on silicone phantoms. A basic TI error model is also proposed, maintaining tactile sensor stability and accuracy with 1% settling times < 1.5s over a range of realistic operating conditions. These developments are designed to be easily implemented into commercial systems, through appropriate design, to maximise impact, providing a stable platform for accurate tissue measurements. This will allow clinical TI to further reduce benign referral rates in a cost-effective manner, by elasticity differentiation and lesion classification in future works.Tactile Imaging (TI) is a technology utilising capacitive pressure sensors to image elasticity distributions within soft tissues such as the breast for cancer screening. TI aims to solve critical problems in the cancer screening pathway, particularly: low sensitivity of manual palpation, patient discomfort during X-ray mammography, and the poor quality of breast cancer referral forms between primary and secondary care facilities. TI is effective in identifying ‘non-palpable’, early-stage tumours, with basic differential ability that reduced unnecessary biopsies by 21% in repeated clinical studies. TI has its limitations, particularly: the measured hardness of a lesion is relative to the background hardness, and lesion location estimates are subjective and prone to operator error. TI can achieve more than simple visualisation of lesions and can act as an accurate differentiator and material analysis tool with further metric development and acknowledgement of error sensitivities when transferring from phantom to clinical trials. This thesis explores and develops two methods, specifically inertial measurement and IR vein imaging, for determining the breast background elasticity, and registering tactile maps for lesion localisation, based on fusion of tactile and auxiliary sensors. These sensors enhance the capabilities of TI, with background tissue elasticity determined with MAE < 4% over tissues in the range 9 kPa – 90 kPa and probe trajectory across the breast measured with an error ratio < 0.3%, independent of applied load, validated on silicone phantoms. A basic TI error model is also proposed, maintaining tactile sensor stability and accuracy with 1% settling times < 1.5s over a range of realistic operating conditions. These developments are designed to be easily implemented into commercial systems, through appropriate design, to maximise impact, providing a stable platform for accurate tissue measurements. This will allow clinical TI to further reduce benign referral rates in a cost-effective manner, by elasticity differentiation and lesion classification in future works

Coded aperture breast tumour imaging using a full-size clinical gamma camera

EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Imaging of the Breast

Early detection of breast cancer combined with targeted therapy offers the best outcome for breast cancer patients. This volume deal with a wide range of new technical innovations for improving breast cancer detection, diagnosis and therapy. There is a special focus on improvements in mammographic image quality, image analysis, magnetic resonance imaging of the breast and molecular imaging. A chapter on targeted therapy explores the option of less radical postoperative therapy for women with early, screen-detected breast cancers

DEVELOPMENT OF A MULTIPLE ENERGY SYNCHROTRON BIOMEDICAL IMAGING SYSTEM

A multiple energy imaging (MEI) system that can extract multiple endogenous or induced contrast materials as well as water and bone images would be ideal for imaging of biological subjects. The continuous spectrum available from synchrotron light facilities provides a nearly perfect source for MEI. This dissertation is on a novel MEI imaging system developed for biomedical imaging applications at the BioMedical Imaging and Therapy bend magnet beamline, Canadian Light Source. The developed MEI system prepares a horizontally focused polychromatic x-ray imaging beam. Its components are: a cylindrically bent Laue single silicon (5, 1, 1) crystal monochromator, scanning and positioning stages for the subjects, flat panel (area) detector, and a data acquisition and control system. The Si crystal is bent by means of a frame bender and has a bent radius of 0.5 m. Depending on the horizontal beam width of filtered synchrotron radiation (20 to 50 keV) incident on the monochromator; the size and spectral energy range of the focused beam prepared vary, and can be up to 15 keV. The spectral energy range covers the K-edges of iodine (33.17 keV), xenon (34.56 keV), cesium (35.99 keV), and barium (37.44 keV). Iodine, xenon and barium are commonly used biomedical and clinical contrast agents. A phantom composed of six materials: iodine, xenon, cesium, barium, water, and bone was imaged using the MEI system and their projected concentrations successfully extracted. For quantification of iodine, cesium and barium, the minimum detection limit of the MEI system is about 1.0 mg/ml for iodine and barium, and 0.5 mg/ml for cesium. The estimated dose rate to the phantom imaged at a ring current of 200 mA is 8.7 mGy/s, corresponding to a cumulative dose of 1.3 Gy. A crossover correction algorithm has also been developed to suppress crossover artifacts associated with the MEI system, dual-beam KES and spectral KES systems. Potential biomedical applications of the imaging system will include projection imaging that requires any of the extracted K-edges as a contrast agent and multi-contrast K-edge imaging

High-resolution fluorescence endomicroscopy for rapid evaluation of breast cancer margins

Breast cancer is a major public health problem world-wide and the second leading cause of cancer-related female deaths. Breast conserving surgery (BCS), in the form of wide local excision (WLE), allows complete tumour resection while maintaining acceptable cosmesis. It is the recommended treatment for a large number of patients with early stage disease or, in more advanced cases, following neoadjuvant chemotherapy. About 30% of patients undergoing BCS require one or more re-operative interventions, mainly due to the presence of positive margins. The standard of care for surgical margin assessment is post-operative examination of histopathological tissue sections. However, this process is invasive, introduces sampling errors and does not provide real-time assessment of the tumour status of radial margins. The objective of this thesis is to improve intra-operative assessment of margin status by performing optical biopsy in breast tissue. This thesis presents several technical and clinical developments related to confocal fluorescence endomicroscopy systems for real-time characterisation of different breast morphologies. The imaging systems discussed employ flexible fibre-bundle based imaging probes coupled to high-speed line-scan confocal microscope set-up. A preliminary study on 43 unfixed breast specimens describes the development and testing of line-scan confocal laser endomicroscope (LS-CLE) to image and classify different breast pathologies. LS-CLE is also demonstrated to assess the intra-operative tumour status of whole WLE specimens and surgical excisions with high diagnostic accuracy. A third study demonstrates the development and testing of a bespoke LS-CLE system with methylene blue (MB), an US Food and Drug Administration (FDA) approved fluorescent agent, and integration with robotic scanner to enable large-area in vivo imaging of breast cancer. The work also addresses three technical issues which limit existing fibre-bundle based fluorescence endomicroscopy systems: i) Restriction to use single fluorescence agent due to low-speed, single excitation and single fluorescence spectral band imaging systems; ii) Limited Field of view (FOV) of fibre-bundle endomicroscopes due to small size of the fibre tip and iii) Limited spatial resolution of fibre-bundle endomicroscopes due to the spacing between the individual fibres leading to fibre-pixelation effects. Details of design and development of a high-speed dual-wavelength LS-CLE system suitable for high-resolution multiplexed imaging are presented. Dual-wavelength imaging is achieved by sequentially switching between 488 nm and 660 nm laser sources for alternate frames, avoiding spectral bleed-through, and providing an effective frame rate of 60 Hz. A combination of hand-held or robotic scanning with real-time video mosaicking, is demonstrated to enable large-area imaging while still maintaining microscopic resolution. Finally, a miniaturised piezoelectric transducer-based fibre-shifting endomicroscope is developed to enhance the resolution over conventional fibre-bundle based imaging systems. The fibre-shifting endomicroscope provides a two-fold improvement in resolution and coupled to a high-speed LS-CLE scanning system, provides real-time imaging of biological samples at 30 fps. These investigations furthered the utility and applications of the fibre-bundle based fluorescence systems for rapid imaging and diagnosis of cancer margins.Open Acces

Proceedings of the International Workshop on Medical Ultrasound Tomography: 1.- 3. Nov. 2017, Speyer, Germany

Ultrasound Tomography is an emerging technology for medical imaging that is quickly approaching its clinical utility. Research groups around the globe are engaged in research spanning from theory to practical applications. The International Workshop on Medical Ultrasound Tomography (1.-3. November 2017, Speyer, Germany) brought together scientists to exchange their knowledge and discuss new ideas and results in order to boost the research in Ultrasound Tomography

A versatile imaging system for in vivo small animal research

In vivo small animal imaging has become an essential technique for molecular biology studies. However, requirements of spatial resolution, sensitivity and image quality are quite challenging for the development of small-animal imaging systems. The capabilities of the system are also significant for carrying out small animal imaging in a wide range of biological studies. The goal of this dissertation is to develop a high-performance imaging system that can readily meet a wide range of requirements for a variety of small animal imaging applications. Several achievements have been made in order to fulfill this goal.;To supplement our system for parallel-hole single photon emission computed tomography (SPECT) based upon a 110 mm diameter circular detector, we have developed novel compact gamma cameras suitable for imaging an entire mouse. These gamma cameras facilitate multi-head (\u3e2) parallel-hole SPECT with the mouse in close proximity to the detector face in order to preserve spatial resolution. Each compact gamma cameras incorporates pixellated Nal(Tl) scintillators and a pair of Hamamatsu H8500 position sensitive photomultiplier tubes (PSPMTs). Two types of copper-beryllium parallel-hole collimators have been designed. These provide high-sensitivity imaging of I-125 or excellent spatial resolution over a range of object-detector distances. Both phantom and animal studies have demonstrated that these gamma cameras perform well for planar scintigraphy and parallel-hole SPECT of mice.;To further address the resolution limitations in parallel-hole SPECT and the sensitivity and limited field of view of single-pinhole SPECT, we have developed novel multipinhole helical SPECT based upon a 110 mm diameter circular detector equipped with a pixellated Nal(Tl) scintillator array. A brass collimator has been designed and produced containing five 1 mm diameter pinholes. Results obtained in SPECT studies of various phantoms show an enlarged field of view, very good resolution and improved sensitivity using this new imaging technique.;These studies in small-animal imaging have been applied to in vivo biological studies related to human health issues including studies of the thyroid and breast cancer. A re-evaluation study of potassium iodide blocking efficiency in radioiodine uptake in mice suggests that the FDA-recommended human dose of stable potassium iodide may not be sufficient to effectively protect the thyroid from radioiodine contamination. Another recent study has demonstrated that multipinhole helical SPECT can resolve the fine structure of the mouse thyroid using a relatively low dose (200 muCi). Another preclinical study has focused on breast tumor imaging using a compact gamma camera and an endogenous reporter gene. In that ongoing study, mammary tumors are imaged at different stages. Preliminary results indicate different functional patterns in the uptake of radiotracers and their potential relationship with other tumor parameters such as tumor size.;In summary, we have developed a versatile imaging system suitable for in vivo small animal research as evidenced by a variety of applications. The modular construction of this system will allow expansion and further development as new needs and new opportunities arise

Digital Image Processing

This book presents several recent advances that are related or fall under the umbrella of 'digital image processing', with the purpose of providing an insight into the possibilities offered by digital image processing algorithms in various fields. The presented mathematical algorithms are accompanied by graphical representations and illustrative examples for an enhanced readability. The chapters are written in a manner that allows even a reader with basic experience and knowledge in the digital image processing field to properly understand the presented algorithms. Concurrently, the structure of the information in this book is such that fellow scientists will be able to use it to push the development of the presented subjects even further

Advancing fluorescent contrast agent recovery methods for surgical guidance applications

Fluorescence-guided surgery (FGS) utilizes fluorescent contrast agents and specialized optical instruments to assist surgeons in intraoperatively identifying tissue-specific characteristics, such as perfusion, malignancy, and molecular function. In doing so, FGS represents a powerful surgical navigation tool for solving clinical challenges not easily addressed by other conventional imaging methods. With growing translational efforts, major hurdles within the FGS field include: insufficient tools for understanding contrast agent uptake behaviors, the inability to image tissue beyond a couple millimeters, and lastly, performance limitations of currently-approved contrast agents in accurately and rapidly labeling disease. The developments presented within this thesis aim to address such shortcomings. Current preclinical fluorescence imaging tools often sacrifice either 3D scale or spatial resolution. To address this gap in high-resolution, whole-body preclinical imaging tools available, the crux of this work lays on the development of a hyperspectral cryo-imaging system and image-processing techniques to accurately recapitulate high-resolution, 3D biodistributions in whole-animal experiments. Specifically, the goal is to correct each cryo-imaging dataset such that it becomes a useful reporter for whole-body biodistributions in relevant disease models. To investigate potential benefits of seeing deeper during FGS, we investigated short-wave infrared imaging (SWIR) for recovering fluorescence beyond the conventional top few millimeters. Through phantom, preclinical, and clinical SWIR imaging, we were able to 1) validate the capability of SWIR imaging with conventional NIR-I fluorophores, 2) demonstrate the translational benefits of SWIR-ICG angiography in a large animal model, and 3) detect micro-dose levels of an EGFR-targeted NIR-I probe during a Phase 0 clinical trial. Lastly, we evaluated contrast agent performances for FGS glioma resection and breast cancer margin assessment. To evaluate glioma-labeling performance of untargeted contrast agents, 3D agent biodistributions were compared voxel-by-voxel to gold-standard Gd-MRI and pathology slides. Finally, building on expertise in dual-probe ratiometric imaging at Dartmouth, a 10-pt clinical pilot study was carried out to assess the technique’s efficacy for rapid margin assessment. In summary, this thesis serves to advance FGS by introducing novel fluorescence imaging devices, techniques, and agents which overcome challenges in understanding whole-body agent biodistributions, recovering agent distributions at greater depths, and verifying agents’ performance for specific FGS applications