Development of diffraction enhanced computed tomography for imaging joints

This research was inspired by a need to discover more refined technologies for imaging growing joints to facilitate research in childhood arthritis, which is among the most common chronic conditions of childhood. The objective of this project was to develop and test a new technology for imaging growing joints using diffraction enhanced imaging (DEI) combined with computed tomography (CT) using a synchrotron radiation source. DEI is a modality that derives contrast from x-ray refraction, extinction (an extreme form of scatter rejection), and absorption (as in conventional radiography). The ability to add to an image’s contrast from the refraction of x-rays, rather than that solely from absorption, generates more detailed visualization of soft tissue and of interfaces between tissues. Additionally, refraction-based imaging allows reduction of absorbed radiation dose by the sample tissue. For this research, stifle joints from four-week piglet joints were imaged by DEI-CT using the BioMedical Imaging and Therapy (BMIT) beamline at the Canadian Light Source (CLS) synchrotron facility. This new modality for imaging growing joints incorporated a novel feedback control to maintain precise alignment of the analyzer crystal, which is used to re- diffract the beam that passes through the object, throughout the scanning procedure. Results showed that high-resolution DEI-CT provided three-dimensional images of the bone and soft tissue of growing joints at a resolution on the order of microns. Fine detail within and between all joint structures and tissues, including striking detail of cartilage vasculature, a iii characteristic of growing but not mature joints, was demonstrated. This report documents for the first time that DEI combined with CT and using a synchrotron radiation source can generate more detailed images of intact, growing joints than is currently available from conventional imaging modalities. The development of this high resolution imaging system, which provides excellent contrast for both hard and soft tissues, fills an important gap in the suite of imaging modalities available for joint research, particularly during growth

Development of in vivo Raman spectroscopy for the diagnosis of breast cancer and intra-operative margin assessment

Thesis (Ph. D.)--Harvard University--MIT Division of Health Sciences and Technology, 2005.Includes bibliographical references.Breast cancer is the most commonly diagnosed cancer among women in the United States. It is the most common cause of death in women ages 45-55. Optical techniques can potentially play a diagnostic role in several aspects of breast cancer evaluation and treatment. This thesis outlines progress on the use of Raman spectroscopy to diagnose breast cancer. Laboratory studies on fresh-frozen tissues are used to demonstrate that the detailed information provided by Raman spectroscopy yields accurate breast disease diagnosis. A Raman spectroscopic-based diagnostic algorithm was developed which classifies samples into four categories according to specific pathological diagnoses: normal, fibrocystic change, fibroadenoma, and infiltrating carcinoma. Cancerous lesions were separated from non- cancerous tissues with a sensitivity of 94% and a specificity of 95%. Further, use of a spectral model based on the morphological structures that comprise breast tissue allows increased understanding of the relationship between a Raman spectrum and tissue disease state. Based on the excellent results of our laboratory work, two clinical studies were undertaken. These studies translate Raman spectroscopy from a laboratory technique into a clinically useful tool. The first study tests the diagnostic algorithm in a prospective manner on freshly excised tissue. Preliminary results are promising. The second study is the first demonstration of in vivo data acquisition of Raman spectra of breast tissue. The culmination of this research is the demonstration of accurate intra-operative margin status assessment during partial mastectomy surgeries.(cont.) Application of our previously developed diagnostic algorithm resulted in perfect sensitivity and specificity in this small in vivo data set. These preliminary findings indicate that Raman spectroscopy has the potential to lessen the need for re-excision surgeries resulting from positive margins and thereby reduce the recurrence rate of breast cancer following partial mastectomy surgeries. The experiments and theory presented throughout this thesis demonstrate that Raman spectroscopy is a viable clinical tool that can be used to accurately diagnosis breast cancer and breast disease.by Abigail Susan Haka.Ph.D

Tracking the Temporal-Evolution of Supernova Bubbles in Numerical Simulations

The study of low-dimensional, noisy manifolds embedded in a higher dimensional space has been extremely useful in many applications, from the chemical analysis of multi-phase flows to simulations of galactic mergers. Building a probabilistic model of the manifolds has helped in describing their essential properties and how they vary in space. However, when the manifold is evolving through time, a joint spatio-temporal modelling is needed, in order to fully comprehend its nature. We propose a first-order Markovian process that propagates the spatial probabilistic model of a manifold at fixed time, to its adjacent temporal stages. The proposed methodology is demonstrated using a particle simulation of an interacting dwarf galaxy to describe the evolution of a cavity generated by a Supernov

The detection of intracranial aneurysms by non-invasive imaging methods and the epidemiology of aneurysmal subarachnoid haemorrhage within the Scottish population

The aims of the research project, which led to the writing of this thesis were to: Examine whether non -invasive imaging methods could replace intra- arterial angiography (IADSA) in the detection of intracranial aneurysms by: a) systematically reviewing the literature; b) prospectively determining the accuracy of the non -invasive imaging methods currently available in Scotland, including the effect of observer experience on diagnostic performance and the patient acceptability of the alternative imaging modalities. To establish the incidence of aneurysmal subarachnoid haemorrhage (SAH) in families by a national retrospective study of occurrences of SAH in a one year period in Scotland, in parallel with a follow -up study of the families of patients who were admitted to the Institute of Neurosciences with aneurysmal SAH a decade earlier. The thesis is divided into three parts:PART ONE: a) summarises the current understanding of the epidemiology and pathophysiology of intracranial aneurysms; b) an overview of cerebrovascular anatomy with reference to aneurysm formation; c) the modalities available for imaging intracranial aneurysms and the current knowledge about their diagnostic performance are considered; d) an overview of the methods available for the treatment of intracranial aneurysms; e) the concept of screening for unruptured intracranial aneurysms is discussed and placed in context by comparison to other screening programmes.PART TWO: a) describes a systematic review of the non -invasive imaging of intracranial aneurysms. CT and MR angiography had similar accuracy compared to IADSA of ~90 %. Data on Transcranial Doppler Sonography (TCDS) were scanty but indicated poorer performance. Detection of very small aneurysms (<3mm diameter) was significantly poorer for the non -invasive tests; b) describes a prospective study of 200 patients examining CTA, MRA and TCDS vs IADSA in the detection of intracranial aneurysms. CTA and MRA had an accuracy (per subject) of 0.85. TCDS had similar accuracy per subject but poorer accuracy per aneurysm than CTA or MRA. Detection of aneurysms ≤5mm was significantly poorer than for those >5mm. Interobserver agreement was good for all modalities; c) combining TCDS with CTA or MRA improved the detection of aneurysms on a per subject basis. Non-invasive imaging tests, especially when used in combination, are reliable at detecting aneurysms >5mm; d) examines the effect of observer experience. Neuroradiologists were more consistent and had better agreement with IADSA than non - neuroradiologists. Small aneurysms and cavernous /terminal internal carotid aneurysms were poorly detected by all observers; e) assessment of patient preferences indicated that TCDS was preferred to the other non -invasive tests and CTA to MRA, with the differences being statistically significant.PART THREE describes: a) the rationale behind the epidemiological studies; b) the methodology used; c) describes the results: Comparative risk for 1st vs 2nd degree relatives suffering a SAH was 2.29 for the Scotland wide study (SWS) and 2.43 for the West of Scotland study (WOS). Absolute lifetime SAH risk was 4.7% for 1st degree and 1.9% for 2nd degree relatives in the SWS compared to 4.2% and 2.3% respectively in the WOS. Prospective 10 -year SAH risk was 1.2% for a 1st degree and 0.5% for a 2nd degree relative compared to background population risk of ~0.1%. The hierarchy of risk was greatest for a member of a family with ≥ 2 other 1st degree relatives affected by SAH, with a more than 20-fold increased risk over the background population risk; d) discusses the implications of the findings and examines the strengths and weaknesses of the study. Routine screening of families of patients who have had a SAH is not supported by these data; e) reviews the implications for i) clinical practice and ii) future research arising from the imaging and epidemiological studies