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

Biomechanical Modeling and Inverse Problem Based Elasticity Imaging for Prostate Cancer Diagnosis

Early detection of prostate cancer plays an important role in successful prostate cancer treatment. This requires screening the prostate periodically after the age of 50. If screening tests lead to prostate cancer suspicion, prostate needle biopsy is administered which is still considered as the clinical gold standard for prostate cancer diagnosis. Given that needle biopsy is invasive and is associated with issues including discomfort and infection, it is desirable to develop a prostate cancer diagnosis system that has high sensitivity and specificity for early detection with a potential to improve needle biopsy outcome. Given the complexity and variability of prostate cancer pathologies, many research groups have been pursuing multi-parametric imaging approach as no single modality imaging technique has proven to be adequate. While imaging additional tissue properties increases the chance of reliable prostate cancer detection and diagnosis, selecting an additional property needs to be done carefully by considering clinical acceptability and cost. Clinical acceptability entails ease with respect to both operating by the radiologist and patient comfort. In this work, effective tissue biomechanics based diagnostic techniques are proposed for prostate cancer assessment with the aim of early detection and minimizing the numbers of prostate biopsies. The techniques take advantage of the low cost, widely available and well established TRUS imaging method. The proposed techniques include novel elastography methods which were formulated based on an inverse finite element frame work. Conventional finite element analysis is known to have high computational complexity, hence computation time demanding. This renders the proposed elastography methods not suitable for real-time applications. To address this issue, an accelerated finite element method was proposed which proved to be suitable for prostate elasticity reconstruction. In this method, accurate finite element analysis of a large number of prostates undergoing TRUS probe loadings was performed. Geometry input and displacement and stress fields output obtained from the analysis were used to train a neural network mapping function to be used for elastopgraphy imaging of prostate cancer patients. The last part of the research presented in this thesis tackles an issue with the current 3D TRUS prostate needle biopsy. Current 3D TRUS prostate needle biopsy systems require registering preoperative 3D TRUS to intra-operative 2D TRUS images. Such image registration is time-consuming while its real-time implementation is yet to be developed. To bypass this registration step, concept of a robotic system was proposed which can reliably determine the preoperative TRUS probe position relative to the prostate to place at the same position relative to the prostate intra-operatively. For this purpose, a contact pressure feedback system is proposed to ensure similar prostate deformation during 3D and 2D image acquisition in order to bypass the registration step

DESIGN AND DEVELOPMENT OF OPTICAL ELASTOGRAPHY SETUP

The mechanical properties of the skin are an indication of its physiological condition. The properties can serve as potential information for dermatologists for diagnosis and qualitative assessment. Elastography is a medical imaging modality developed to extract the elastic properties of a tissue by application of an external force. Optical elastography is a technique of elastography which uses laser speckle tracking to study the elastic properties of several soft tissue including skin. This work is aimed at developing an optical elastography setup that can study the elastic properties of skin. The setup includes an imaging system and a force-application system controlled by a user-friendly Graphical User Interface(GUI). This thesis describes, in detail, the hardware and software components involved in the setup and also, the results obtained with the use of this setup

Entwicklung und Anwendung der in vivo abdominellen Magnetresonanzelastographie

Magnetic Resonance Elastography (MRE) is a well-established non-invasive imaging technique used to quantify the mechanical properties of tissues in vivo for the diagnosis of liver fibrosis. However, MRE is limited by its spatial resolution, sensitivity to motion artifacts, and insensitivity to metabolic function. Therefore, three studies of abdominal MRE were conducted to improve the quality of mechanical maps for characterizing liver tumors, to correct for motion artifacts induced by breathing, and to implement MRE on a PET/MRI scanner to correlate mechanical liver properties with metabolic functions in small animals through technical improvements in image acquisition and post-processing. High-resolution stiffness (shear wave speed in m/s), wave penetration (penetration rate in m/s), and fluidity (phase of the complex shear modulus in rad) maps were generated using multifrequency MRE, novel actuators, and tomoelastography post-processing. The first study characterized the stiffness and fluidity of a total of 141 liver tumors in 70 patients. The second study analyzed the motion of abdominal organs and its effect on their stiffness using different acquisition paradigms and image registration in 12 subjects. The third study examined the relationship of liver stiffness and wave penetration to central metabolic liver functions in 19 rabbits. Malignant liver tumors were distinguished from the surrounding liver (stiffness area under the curve [AUC]: 0.88 and fluidity AUC: 0.95) and benign tumors (stiffness AUC: 0.85 and fluidity AUC: 0.86) due to their increased stiffness and fluidity. In the second study, no significant differences in stiffness were observed despite significant differences in examination time, organ motion, and image quality with different image acquisition paradigms. Motion correction by image registration increased image sharpness, so that no significant difference was measurable between MRE in free breathing and breath-hold. Healthy rabbit livers showed heterogeneous liver stiffness, such that division into low and high stiffness (>1.6 m/s) groups resulted in significant differences in central metabolic functions. Stiffness and fluidity measured by multifrequency MRE hold promise as quantitative biomarkers for the diagnosis of malignant liver tumors. Abdominal MRE with free breathing, followed by image registration, is recommended as the best balance between fast examination time and good image quality. Additionally, the applicability of abdominal MRE in small animals in a clinical MRI was demonstrated, and correlations between mechanical liver properties and metabolic functions were found. This study demonstrates improvements in the quality of maps of biophysical parameters for both clinical and preclinical studies, making an important contribution to the clinical translation of multifrequency MRE as a non-invasive imaging modality for abdominal organs and pathologies.Die Magnetresonanzelastographie (MRE) ist eine nichtinvasive Bildgebungsmethode zur Quantifizierung mechanischer Gewebeeigenschaften in vivo bei der Diagnose von Leberfibrose. Limitationen bestehen aufgrund örtlicher Bildauflösung, Bewegungsempfindlichkeit und Insensitivität zu metabolischen Funktionen. Aufgrund technischer Verbesserung in der Bildaufnahme und der Bildauswertung wurde daher anhand von drei Studien zur abdominellen MRE die Bildqualität mechanischer Karten zur Charakterisierung von Lebertumoren verbessert, atmungsinduzierte Organbewegungen korrigiert und die MRE an klinischen PET/MRT implementiert, um an Kleintieren die mechanischen Lebereigenschaften mit metabolischen Funktionen zu korrelieren. Mittels multifrequenter MRE, neuartiger Aktoren und tomoelastographischer Auswertung wurden hochaufgelöste Karten der Steifigkeit (Scherwellengeschwindigkeit in m/s), Wellenpenetration (Wellenpenetrationsrate in m/s) und Fluidität (Phase des komplexen Schermoduls in rad) generiert. Die erste Studie charakterisierte die Steifigkeit und Fluidität von insgesamt 141 Lebertumoren an 70 Patienten. Eine zweite Studie analysierte die Bewegung und den Einfluss auf die Steifigkeit abdomineller Organe mittels unterschiedlicher Aufnahmeparadigmen und Bildregistrierung in 12 Probanden. In einer dritten Studie wurde der Zusammenhang von Lebersteifigkeit und Wellenpenetration zu zentralen metabolischen Leberfunktionen an 19 Kaninchen untersucht. Maligne Lebertumoren können durch erhöhte Steifigkeit und Fluidität (Steifigkeit AUC: 0.88 und Fluidität AUC: 0.95) gut von gutartigen Tumoren (Steifigkeit AUC: 0.85 und Fluidität AUC: 0.86) unterschieden werden. In der zweiten Studie wurden trotz verschiedener Aufnahmeparadigmen und Unterschiede in Untersuchungsdauer, Organbewegung und Bildqualität keine signifikanten Unterschiede in der Organsteifigkeit festgestellt. Die Bildregistrierung verbesserte die Bildschärfe, sodass kein signifikanter Unterschied zwischen freier Atmung und Atempause messbar war. Kaninchenlebern zeigten heterogene Steifigkeiten, sodass eine Zweiteilung in niedrige und hohe Steifigkeit (>1.6 m/s) signifikante Unterschiede in zentralen metabolischen Funktionen zeigte. Steifigkeit und Fluidität, die mittels der Mehrfrequenz-MRE gemessen werden, stellen vielversprechende quantitative Biomarker für die Diagnose maligner Lebertumoren dar. Abdominelle MRE in freier Atmung mit Bildregistrierung ist der beste Kompromiss aus schneller Untersuchungsdauer und guter Bildqualität. Die Anwendbarkeit an Kleintieren in einem klinischen MRT wurde gezeigt, inklusive Korrelationen zwischen mechanischen Lebereigenschaften und metabolischen Funktionen. Diese Arbeit konnte somit die Bildqualität mechanischer Karten sowohl für klinische als auch präklinische Untersuchungen verbessern und damit einen wichtigen Beitrag zur Translation der Multifrequenz-MRE als klinisch angewandte nichtinvasive Bildgebungsmethode abdomineller Organe und Pathologien leisten

Robotic Ultrasound Imaging: State-of-the-Art and Future Perspectives

Ultrasound (US) is one of the most widely used modalities for clinical intervention and diagnosis due to the merits of providing non-invasive, radiation-free, and real-time images. However, free-hand US examinations are highly operator-dependent. Robotic US System (RUSS) aims at overcoming this shortcoming by offering reproducibility, while also aiming at improving dexterity, and intelligent anatomy and disease-aware imaging. In addition to enhancing diagnostic outcomes, RUSS also holds the potential to provide medical interventions for populations suffering from the shortage of experienced sonographers. In this paper, we categorize RUSS as teleoperated or autonomous. Regarding teleoperated RUSS, we summarize their technical developments, and clinical evaluations, respectively. This survey then focuses on the review of recent work on autonomous robotic US imaging. We demonstrate that machine learning and artificial intelligence present the key techniques, which enable intelligent patient and process-specific, motion and deformation-aware robotic image acquisition. We also show that the research on artificial intelligence for autonomous RUSS has directed the research community toward understanding and modeling expert sonographers' semantic reasoning and action. Here, we call this process, the recovery of the "language of sonography". This side result of research on autonomous robotic US acquisitions could be considered as valuable and essential as the progress made in the robotic US examination itself. This article will provide both engineers and clinicians with a comprehensive understanding of RUSS by surveying underlying techniques.Comment: Accepted by Medical Image Analysi

Intraoperative ultrasound in brain tumor surgery: A review and implementation guide.

Accurate and reliable intraoperative neuronavigation is crucial for achieving maximal safe resection of brain tumors. Intraoperative MRI (iMRI) has received significant attention as the next step in improving navigation. However, the immense cost and logistical challenge of iMRI precludes implementation in most centers worldwide. In comparison, intraoperative ultrasound (ioUS) is an affordable tool, easily incorporated into existing theatre infrastructure, and operative workflow. Historically, ultrasound has been perceived as difficult to learn and standardize, with poor, artifact-prone image quality. However, ioUS has dramatically evolved over the last decade, with vast improvements in image quality and well-integrated navigation tools. Advanced techniques, such as contrast-enhanced ultrasound (CEUS), have also matured and moved from the research field into actual clinical use. In this review, we provide a comprehensive and pragmatic guide to ioUS. A suggested protocol to facilitate learning ioUS and improve standardization is provided, and an outline of common artifacts and methods to minimize them given. The review also includes an update of advanced techniques and how they can be incorporated into clinical practice

What scans we will read: imaging instrumentation trends in clinical oncology

Oncological diseases account for a significant portion of the burden on public healthcare systems with associated costs driven primarily by complex and long-lasting therapies. Through the visualization of patient-specific morphology and functional-molecular pathways, cancerous tissue can be detected and characterized non- invasively, so as to provide referring oncologists with essential information to support therapy management decisions. Following the onset of stand-alone anatomical and functional imaging, we witness a push towards integrating molecular image information through various methods, including anato-metabolic imaging (e.g., PET/ CT), advanced MRI, optical or ultrasound imaging. This perspective paper highlights a number of key technological and methodological advances in imaging instrumentation related to anatomical, functional, molecular medicine and hybrid imaging, that is understood as the hardware-based combination of complementary anatomical and molecular imaging. These include novel detector technologies for ionizing radiation used in CT and nuclear medicine imaging, and novel system developments in MRI and optical as well as opto-acoustic imaging. We will also highlight new data processing methods for improved non-invasive tissue characterization. Following a general introduction to the role of imaging in oncology patient management we introduce imaging methods with well-defined clinical applications and potential for clinical translation. For each modality, we report first on the status quo and point to perceived technological and methodological advances in a subsequent status go section. Considering the breadth and dynamics of these developments, this perspective ends with a critical reflection on where the authors, with the majority of them being imaging experts with a background in physics and engineering, believe imaging methods will be in a few years from now. Overall, methodological and technological medical imaging advances are geared towards increased image contrast, the derivation of reproducible quantitative parameters, an increase in volume sensitivity and a reduction in overall examination time. To ensure full translation to the clinic, this progress in technologies and instrumentation is complemented by progress in relevant acquisition and image-processing protocols and improved data analysis. To this end, we should accept diagnostic images as “data”, and – through the wider adoption of advanced analysis, including machine learning approaches and a “big data” concept – move to the next stage of non-invasive tumor phenotyping. The scans we will be reading in 10 years from now will likely be composed of highly diverse multi- dimensional data from multiple sources, which mandate the use of advanced and interactive visualization and analysis platforms powered by Artificial Intelligence (AI) for real-time data handling by cross-specialty clinical experts with a domain knowledge that will need to go beyond that of plain imaging

High frame rate multi-perspective cardiac ultrasound imaging using phased array probes

Ultrasound (US) imaging is used to assess cardiac disease by assessing the geometry and function of the heart utilizing its high spatial and temporal resolution. However, because of physical constraints, drawbacks of US include limited field-of-view, refraction, resolution and contrast anisotropy. These issues cannot be resolved when using a single probe. Here, an interleaved multi-perspective 2-D US imaging system was introduced, aiming at improved imaging of the left ventricle (LV) of the heart by acquiring US data from two separate phased array probes simultaneously at a high frame rate. In an ex-vivo experiment of a beating porcine heart, parasternal long-axis and apical views of the left ventricle were acquired using two phased array probes. Interleaved multi-probe US data were acquired at a frame rate of 170 frames per second (FPS) using diverging wave imaging under 11 angles. Image registration and fusion algorithms were developed to align and fuse the US images from two different probes. First- and second-order speckle statistics were computed to characterize the resulting probability distribution function and point spread function of the multi-probe image data. First-order speckle analysis showed less overlap of the histograms (reduction of 34.4%) and higher contrast-to-noise ratio (CNR, increase of 27.3%) between endocardium and myocardium in the fused images. Autocorrelation results showed an improved and more isotropic resolution for the multi-perspective images (single-perspective: 0.59 mm × 0.21 mm, multi-perspective: 0.35 mm × 0.18 mm). Moreover, mean gradient (MG) (increase of 74.4%) and entropy (increase of 23.1%) results indicated that image details of the myocardial tissue can be better observed after fusion. To conclude, interleaved multi-perspective high frame rate US imaging was developed and demonstrated in an ex-vivo experimental setup, revealing enlarged field-of-view, and improved image contrast and resolution of cardiac images.</p