Non-invasive ultrasound monitoring of regional carotid wall structure and deformation in atherosclerosis

Thesis (Ph. D.)--Harvard--Massachusetts Institute of Technology Division of Health Sciences and Technology, 2001.Includes bibliographical references (p. 223-242).Atherosclerosis is characterized by local remodeling of arterial structure and distensibility. Developing lesions either progress gradually to compromise tissue perfusion or rupture suddenly to cause catastrophic myocardial infarction or stroke. Reliable measurement of changes in arterial structure and composition is required for assessment of disease progression. Non-invasive carotid ultrasound can image the heterogeneity of wall structure and distensibility caused by atherosclerosis. However, this capability has not been utilized for clinical monitoring because of speckle noise and other artifacts. Clinical measures focus instead on average wall thickness and diameter distension in the distal common carotid to reduce sensitivity to noise. The goal of our research was to develop an effective system for reliable regional structure and deformation measurements since these are more sensitive indicators of disease progression. We constructed a system for freehand ultrasound scanning based on custom software which simultaneously acquires real-time image sequences and 3D frame localization data from an electromagnetic spatial localizer. With finite element modeling, we evaluated candidate measures of regional wall deformation.(cont.) Finally, we developed a multi-step scheme for robust estimation of local wall structure and deformation. This new strategy is based on a directionally-sensitive segmentation functional and a motion-region-of-interest constrained optical flow algorithm. We validated this estimator with simulated images and clinical ultrasound data. The results show structure estimates that are accurate and precise, with inter- and intra-observer reproducibility surpassing existing methods. Estimates of wall velocity and deformation likewise show good overall accuracy and precision. We present results from a proof-of-principle evaluation conducted in a pilot study of normal subjects and clinical patients. For one example, we demonstrate the combination of 2D image processing with 3D frame localization for visualization of the carotid volume. With slice localization, estimates of carotid wall structure and deformation can be derived for all axial positions along the carotid artery. The elements developed here provide the tools necessary for reliable quantification of regional wall structure and composition changes which result from atherosclerosis.by Raymond C. Chan.Ph.D

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

Quantitative Mapping of Strains and Young Modulus Based on Phase-Sensitive OCT

In this chapter we consider mapping of local strains and tissue elasticity in optical coherence tomography (OCT) based on analysis of phase-sensitive OCT scans. Conventional structural OCT scans correspond to spatially resolved mapping of the backscattering intensity of the probing optical beam. Deeper analysis of such sequentially acquired multiple OCT scans can be used to extract additional information about motion of scatterers in the examined region. Such detailed analysis of OCT scans has already resulted in creation of OCT-based visualization of blood microcirculation, which has been implemented in several commercially available devices, especially for ophthalmic applications. Another functional extension of OCT emerging in recent years is the OCT-based elastography, i.e., mapping of local strains and elastic properties in the imaged region. Here, we describe the main principles of local strain mapping in phase-sensitive OCT with a special focus on the recently proposed efficient vector method of estimation of interframe phase-variation gradients. The initially performed mapping of local strains is then used for realization of quantitative compressional elastography, i.e., mapping of the Young modulus and obtaining stress-strain dependences for the studied samples. The discussed principles are illustrated by simulated and experimental examples of elastographic OCT-based visualization. The presented elastographic principles are rather general and can be used in a wide area of biomedical and technical applications

Optical Coherence Tomography and Its Non-medical Applications

Optical coherence tomography (OCT) is a promising non-invasive non-contact 3D imaging technique that can be used to evaluate and inspect material surfaces, multilayer polymer films, fiber coils, and coatings. OCT can be used for the examination of cultural heritage objects and 3D imaging of microstructures. With subsurface 3D fingerprint imaging capability, OCT could be a valuable tool for enhancing security in biometric applications. OCT can also be used for the evaluation of fastener flushness for improving aerodynamic performance of high-speed aircraft. More and more OCT non-medical applications are emerging. In this book, we present some recent advancements in OCT technology and non-medical applications

Spatio-Temporal Nonrigid Registration for Ultrasound Cardiac Motion Estimation

We propose a new spatio-temporal elastic registration algorithm for motion reconstruction from a series of images. The specific application is to estimate displacement fields from two-dimensional ultrasound sequences of the heart. The basic idea is to find a spatio-temporal deformation field that effectively compensates for the motion by minimizing a difference with respect to a reference frame. The key feature of our method is the use of a semi-local spatio-temporal parametric model for the deformation using splines, and the reformulation of the registration task as a global optimization problem. The scale of the spline model controls the smoothness of the displacement field. Our algorithm uses a multiresolution optimization strategy to obtain a higher speed and robustness. We evaluated the accuracy of our algorithm using a synthetic sequence generated with an ultrasound simulation package, together with a realistic cardiac motion model. We compared our new global multiframe approach with a previous method based on pairwise registration of consecutive frames to demonstrate the benefits of introducing temporal consistency. Finally, we applied the algorithm to the regional analysis of the left ventricle. Displacement and strain parameters were evaluated showing significant differences between the normal and pathological segments, thereby illustrating the clinical applicability of our method

Tomographic measurement of all orthogonal components of three-dimensional displacement fields within scattering materials using wavelength scanning interferometry

Experimental mechanics is currently contemplating tremendous opportunities of further advancements thanks to a combination of powerful computational techniques and also fullfield non-contact methods to measure displacement and strain fields in a wide variety of materials. Identification techniques, aimed to evaluate material mechanical properties given known loads and measured displacement or strain fields, are bound to benefit from increased data availability (both in density and dimensionality) and efficient inversion methods such as finite element updating (FEU) and the virtual fields method (VFM). They work at their best when provided with dense and multicomponent experimental displacement (or strain) data, i.e. when all orthogonal components of displacements (or all components of the strain tensor) are known at points closely spaced within the volume of the material under study. Although a very challenging requirement, an increasing number of techniques are emerging to provide such data. In this Thesis, a novel wavelength scanning interferometry (WSI) system that provides three dimensional (3-D) displacement fields inside the volume of semi-transparent scattering materials is proposed. Sequences of two-dimensional interferograms are recorded whilst tuning the frequency of a laser at a constant rate. A new approach based on frequency multiplexing is used to encode the interference signal corresponding to multiple illumination directions at different spectral bands. Different optical paths along each illumination direction ensure that the signals corresponding to each sensitivity vector do not overlap in the frequency domain. All the information required to reconstruct the location and the 3-D displacement vector of scattering points within the material is thus recorded simultaneously in a single wavelength scan. By comparing phase data volumes obtained for two successive scans, all orthogonal components of the three dimensional displacement field introduced between scans (e.g. by means of loading or moving the sample under study) are readily obtained with high displacement sensitivity. The fundamental principle that describes the technique is presented in detail, including the correspondence between interference signal frequency and its associated depth within the sample, depth range, depth resolution, transverse resolution and displacement sensitivity. Data processing of the interference signal includes Fourier transformation, noise reduction, re-registration of data volumes, measurement of the illumination and sensitivity vectors from experimental data using a datum surface, phase difference evaluation, 3-D phase unwrapping and 3-D displacement field evaluation. Experiments consisting of controlled rigid body rotations and translations of a phantom were performed to validate the results. Both in-plane and the out-of-plane displacement components were measured for each voxel in the resulting data volume, showing an excellent agreement with the expected 3-D displacement

Use of advanced echocardiography imaging techniques in the critically ill

Background: Critical care echocardiography has become standard of care in the ICU. New technologies have been developed and have shown potential clinical utility to elucidate myocardial dysfunction not seen with conventional imaging. We sought to determine the feasibility and potential clinical benefit of these techniques in common situations seen in the ICU. Hypothesis: Advanced echo techniques would be feasible in the majority of critically ill patients and have prognostic significance, clinical utility and diagnose cardiac abnormalities, potentially in a more sensitive manner than conventional techniques. Results: (a) Speckle tracking echocardiography (STE) Left ventricle and RV analysis with STE was feasibly in ~80% of patients. More dysfunction was found using STE vs conventional analysis. RV dysfunction assessed by STE held significant prognostic relevance in those with septic shock and highlighted subtle dysfunction induced by mechanical ventilation, both in animal and human studies. (b) 3D transthoracic echocardiography (3D TTE) Despite finding 3D TTE feasible in mechanically ventilated ICU patients (LV 72% and RV 55%), it lacked necessary low variability and high precision vs standard measures. (c) Myocardial contrast perfusion echocardiography (MCPE) Assessing acute coronary artery occlusion in the ICU patient is challenging. Troponin elevation, acute ECG changes, regional wall motion analysis on echo and overall clinical acumen often lack diagnostic capabilities. MCPE was found to be feasible in the critically ill and had better association predicting acute coronary artery occlusion vs clinical acumen alone. Conclusions: STE, 3D TTE and MCPE are feasible in the majority of ICU patients. STE may show dysfunction not recognised by conventional imaging. 3D TTE for volumetric analysis is likely not suitable for clinical use at this stage. MCPE may help guide interventions in acute coronary artery occlusion

Ultrasound Speckle Image Velocimetry: Studies on System Performance and Application to Cardiovascular Fluid Dynamics

Knowledge of detailed blood flow characteristics can be extremely valuable in a variety of settings. Examples range from studying disease processes such as atherosclerosis to aiding in the design of medical devices such as prosthetic cardiac valves. For in vivo and optically inaccessible in vitro flows, accurate measurements of velocity fields and shear stresses can be difficult to obtain. Doppler ultrasound and magnetic resonance imaging are the most commonly used techniques, but have important limitations. Recently, there has been increased interest in the application of particle image velocimetry principles towards tracking of ultrasound speckle patterns to determine multidimensional flow velocities with increased temporal resolution. We refer to our implementation as ultrasound speckle image velocimetry (USIV). In this research project, our first objective was to obtain a detailed characterization of the factors unique to ultrasound imaging that can influence the accuracy of velocity measurements. By conducting in vitro experiments with uniform speckle phantom translation as well as steady tube flow, we have shown that characteristics such as transducer focal depth and beam sweep speed as well as particle motion direction and velocity can all influence USIV results. Our second objective was to demonstrate the utility of USIV for analyzing in vivo blood flows. After administering ultrasound contrast agent to anesthetized pigs, we were able to obtain detailed images of both left ventricular flow and abdominal aortic flow. Velocity profiles were measured during both left ventricular filling and ejection. Our most interesting finding was the presence in certain cases of highly asymmetric retrograde flow in the infrarenal aorta. The factors that lead to such flows may have relevance to the development of atherosclerosis and abdominal aneurysms. USIV is likely to be very useful for further studies both in vivo and with in vitro elastic aorta models

Towards targeted colorectal cancer biopsy based on tissue morphology assessment by compression optical coherence elastography

Identifying the precise topography of cancer for targeted biopsy in colonoscopic examination is a challenge in current diagnostic practice. For the first time we demonstrate the use of compression optical coherence elastography (C-OCE) technology as a new functional OCT modality for differentiating between cancerous and non-cancerous tissues in colon and detecting their morphological features on the basis of measurement of tissue elastic properties. The method uses pre-determined stiffness values (Young’s modulus) to distinguish between different morphological structures of normal (mucosa and submucosa), benign tumor (adenoma) and malignant tumor tissue (including cancer cells, gland-like structures, cribriform gland-like structures, stromal fibers, extracellular mucin). After analyzing in excess of fifty tissue samples, a threshold stiffness value of 520 kPa was suggested above which areas of colorectal cancer were detected invariably. A high Pearson correlation (r =0.98; p <0.05), and a negligible bias (0.22) by good agreement of the segmentation results of C-OCE and histological (reference standard) images was demonstrated, indicating the efficiency of C-OCE to identify the precise localization of colorectal cancer and the possibility to perform targeted biopsy. Furthermore, we demonstrated the ability of C-OCE to differentiate morphological subtypes of colorectal cancer – low-grade and high-grade colorectal adenocarcinomas, mucinous adenocarcinoma, and cribriform patterns. The obtained ex vivo results highlight prospects of C-OCE for high-level colon malignancy detection. The future endoscopic use of C-OCE will allow targeted biopsy sampling and simultaneous rapid analysis of the heterogeneous morphology of colon tumors