Preoperative Systems for Computer Aided Diagnosis based on Image Registration: Applications to Breast Cancer and Atherosclerosis

Computer Aided Diagnosis (CAD) systems assist clinicians including radiologists and cardiologists to detect abnormalities and highlight conspicuous possible disease. Implementing a pre-operative CAD system contains a framework that accepts related technical as well as clinical parameters as input by analyzing the predefined method and demonstrates the prospective output. In this work we developed the Computer Aided Diagnostic System for biomedical imaging analysis of two applications on Breast Cancer and Atherosclerosis. The aim of the first CAD application is to optimize the registration strategy specifically for Breast Dynamic Infrared Imaging and to make it user-independent. Base on the fact that automated motion reduction in dynamic infrared imaging is on demand in clinical applications, since movement disarranges time-temperature series of each pixel, thus originating thermal artifacts that might bias the clinical decision. All previously proposed registration methods are feature based algorithms requiring manual intervention. We implemented and evaluated 3 different 3D time-series registration methods: 1. Linear affine, 2. Non-linear Bspline, 3. Demons applied to 12 datasets of healthy breast thermal images. The results are evaluated through normalized mutual information with average values of 0.70±0.03, 0.74±0.03 and 0.81±0.09 (out of 1) for Affine, BSpline and Demons registration, respectively, as well as breast boundary overlap and Jacobian determinant of the deformation field. The statistical analysis of the results showed that symmetric diffeomorphic Demons registration method outperforms also with the best breast alignment and non-negative Jacobian values which guarantee image similarity and anatomical consistency of the transformation, due to homologous forces enforcing the pixel geometric disparities to be shortened on all the frames. We propose Demons registration as an effective technique for time-series dynamic infrared registration, to stabilize the local temperature oscillation. The aim of the second implemented CAD application is to assess contribution of calcification in plaque vulnerability and wall rupture and to find its maximum resistance before break in image-based models of carotid artery stenting. The role of calcification inside fibroatheroma during carotid artery stenting operation is controversial in which cardiologists face two major problems during the placement: (i) “plaque protrusion” (i.e. elastic fibrous caps containing early calcifications that penetrate inside the stent); (ii) “plaque vulnerability” (i.e. stiff plaques with advanced calcifications that break the arterial wall or stent). Finite Element Analysis was used to simulate the balloon and stent expansion as a preoperative patient-specific virtual framework. A nonlinear static structural analysis was performed on 20 patients acquired using in vivo MDCT angiography. The Agatston Calcium score was obtained for each patient and subject-specific local Elastic Modulus (EM) was calculated. The in silico results showed that by imposing average ultimate external load of 1.1MPa and 2.3MPa on balloon and stent respectively, average ultimate stress of 55.7±41.2kPa and 171±41.2kPa are obtained on calcifications. The study reveals that a significant positive correlation (R=0.85, p<0.0001) exists on stent expansion between EM of calcification and ultimate stress as well as Plaque Wall Stress (PWS) (R=0.92, p<0.0001), comparing to Ca score that showed insignificant associations with ultimate stress (R=0.44, p=0.057) and PWS (R=0.38, p=0.103), suggesting minor impact of Ca score in plaque rupture. These average data are in good agreement with results obtained by other research groups and we believe this approach enriches the arsenal of tools available for pre-operative prediction of carotid artery stenting procedure in the presence of calcified plaques

The use of infrared thermal imaging as a marker of tissue perfusion and predictor of arteriovenous fistula outcomes

The gold standard of vascular access is the arteriovenous fistula (AVF). Unfortunately it is associated with high rates of failing to mature. Therefore the ability to predict AVF outcomes would change clinical practice. Predictive markers of AVF outcomes were assessed in chapter 2. The literature and our study showed numerous contradictions. In chapter 3 we assessed a multifactorial approach with a systematic review on predictive models of maturation. The review found few models and the disparity between each one limits the development of a unified model. Recent development in infrared thermal imaging (IRTI) technology has made it portable and easy to use. In Chapter 4, we proved that IRTI is a valid and user-friendly method of measuring skin temperature and is comparable to traditional methods of thermometry. IRTI can be used to quantity reactive hyperaemia following a vascular occlusion test (chapter 5). In Chapter 6 we showed that IRTI is an accurate tool in predicting AVF outcome. It was shown to have superiority to intra-operative thrill and other independent patient factors. In conclusion IRTI has a definite role in patients with vascular access. There is also potential for its use in patients with other conditions such as peripheral vascular disease

Biomedical Image Processing and Classification

Biomedical image processing is an interdisciplinary field involving a variety of disciplines, e.g., electronics, computer science, physics, mathematics, physiology, and medicine. Several imaging techniques have been developed, providing many approaches to the study of the human body. Biomedical image processing is finding an increasing number of important applications in, for example, the study of the internal structure or function of an organ and the diagnosis or treatment of a disease. If associated with classification methods, it can support the development of computer-aided diagnosis (CAD) systems, which could help medical doctors in refining their clinical picture

Liquid crystal thermography in neuropathic assessment of the diabetic foot.

Primary aetiologic factors of diabetic foot disease include peripheral neuropathy and peripheral vascular disease. Assessment of circulation, neuropathy, and foot pressure is employed routinely to determine the risk of foot ulceration in the patient with diabetes mellitus. Routine neuropathic evaluation includes assessment of sensory loss in the plantar skin of the foot using both the Semmes Weinstein monofilament and the biothesiometer. Progressive degeneration of sensory nerve pathways is thought to affect thermoreceptors and mechanoreceptors. However, thermological measurements of the foot to assess responses to thermal stimuli and cutaneous thermal discrimination threshold are relatively uncommon. Recent improvements in liquid crystal technology (LCT) including insensitivity to pressure, faster response times, lower cost and fast image acquisition offer potential for routine thermographic assessment of the diabetic foot. The present study was designed to evaluate if an association exists between abnormal plantar thermal images and sensory loss under conditions of normal loading. The system comprises a robust measurement platform, thermochromic liquid crystal polyester sheet (TLC), instrumentation and analysis software. In vitro calibration was performed to characterise three physical forms of TLC on the basis of linearity, hysteresis, pressure sensitivity and response time. An in vivo pilot evaluation study of the system was performed using three sub-groups (i) neuropathic diabetic (n=30), (ii) non neuropathic diabetic (n=30) and (iii) a healthy control group (n=30). The principal results of this study indicate raised plantar temperatures for the diabetic groups at baseline and post stress relative to the control group. Furthermore, poor recovery response to thermal stimulus in the neuropathic diabetic group suggests degeneration of thermoreceptors. Thus by assessing the thermal parameters at the same sites as that of sensory testing, the new LCT based approach appears capable of providing an alternative confirmation of clinical neuropathy and offers potential as an improved method compared to existing techniques