Abstract-Recent evidence indicates that the type of atherosclerotic plaque, rather than the degree of obstruction to flow, is an important determinant of the risk of cardiovascular complications. In previous work, the feasibility of using MRI for the characterization of plaque components was shown. This study extends the previous work to all the plaque components and shows the accuracy of this method. Twenty-two human carotid endarterectomy specimens underwent ex vivo MRI and histopathological examination. Sixty-six cross sections were matched between MRI and histopathology. In each cross section, the presence or absence of plaque components were prospectively identified on the MRI images. The overall sensitivity and specificity for each tissue component were very high. Calcification and fibrocellular tissue were readily identified. Lipid core was also identifiable. However, thrombus was the plaque component for which MRI had the lowest sensitivity. A semiautomated algorithm was created to identify all major atherosclerotic plaque components. MRI can characterize carotid artery plaques with a high level of sensitivity and specificity. isruption of atherosclerotic plaques is the most frequent underlying cause of the unpredictable onset of acute thromboembolic vascular events including sudden death, myocardial infarction, unstable angina, stroke, transient cerebral ischemia, and peripheral thromboemboli. 1,2 Although clinical risk factors for atherosclerosis help predict risk of these events, identification of patients with plaques vulnerable to disruption is not possible by angiography that only visualizes the lumen. There is therefore a need for an in vivo noninvasive method for characterizing atherosclerotic plaques and identifying the "vulnerable" plaque.Previous work has shown that MRI can characterize both ex vivo 3-7 and in vivo 8 -11 the composition of human atherosclerotic plaques. However, the sensitivity and specificity of MRI have not been determined.This study reports the development of high-resolution MRI criteria for the ex vivo tissue characterization of human carotid atherosclerotic plaques and their sensitivity and specificity in comparison with histopathology. Using these criteria, a semiautomatic segmentation algorithm is developed for characterizing the constituents of an atherosclerotic plaque. Methods SpecimensHuman carotid endarterectomy specimens were studied. Specimens were obtained fresh and intact from the operating room, washed in phosphate buffered saline, grossly described, and samples taken for routine surgical pathology. The remaining 1-to 2-cm-long segments were flash frozen at Ϫ80°C until imaged. On the day of imaging, the specimens were placed in saline and slowly warmed to 37°C in a water bath. The artery was placed in either a 10-or 12-mm MR tube (Wilmad Glass) using the smallest possible tube for a given specimen. Care was taken to remove any air bubbles. Previous studies have shown no change in the T1 and T2 of atheromatous plaques under these conditions of freezing and rewa...

One hypothesis that couples infection with autoimmune disease is molecular mimicry. Molecular mimicry is characterized by an immune response to an environmental agent that cross-reacts with a host antigen, resulting in disease 1,2 . This hypothesis has been implicated in the pathogenesis of diabetes, lupus and multiple sclerosis (MS) 1-4 . There is limited direct evidence linking causative agents with pathogenic immune reactions in these diseases. Our study establishes a clear link between viral infection, autoimmunity and neurological disease in humans. As a model for molecular mimicry, we studied patients with human T-lymphotropic virus type 1 (HTLV-1)-associated myelopathy/ tropical spastic paraparesis (HAM/TSP), a disease that can be indistinguishable from MS (refs. 5 -7 ). HAM/TSP patients develop antibodies to neurons 8 . We hypothesized these antibodies would identify a central nervous system (CNS) autoantigen. Immunoglobulin G isolated from HAM/TSP patients identified heterogeneous nuclear ribonuclear protein-A1 (hnRNP-A1) as the autoantigen. Antibodies to hnRNP-A1 cross-reacted with HTLV-1-tax, the immune response to which is associated with HAM/TSP (refs. 5 ,9 ). Immunoglobulin G specifically stained human Betz cells, whose axons are preferentially damaged 7 . Infusion of autoantibodies in brain sections inhibited neuronal firing, indicative of their pathogenic nature. These data demonstrate the importance of molecular mimicry between an infecting agent and hnRNP-A1 in autoimmune disease of the CNS. To test for molecular mimicry between an environmental agent and the central nervous system (CNS), we isolated immunoglobulin G (IgG) from the serum of patients with human Tlymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and tested it for reactivity with human tissues (Fig. 1a). There was intense staining of neurons in brain and no staining of glia, dorsal root ganglion (peripheral nervous system) or systemic organs. A monoclonal antibody to HTLV-1-tax (tax mAb) mimicked IgG staining of neurons. To identify the protein, cortical neurons were isolated, proteins extracted and subjected to SDS-PAGE and western-blot analysis. The IgG recognized a band of approximately 33 kD (Fig. 1b), whereas IgG isolated from controls did not. Importantly, the tax mAb that stained CNS neurons reacted with the antigen. All patients with HAM/TSP (13/13) developed antibodies recognizing the neuronal antigen 8 . Nine of ten HTLV-1-seropositive patients without neurological symptoms and 12 HTLV-1-seronegative controls showed no reactivity (P < 0.0001 versus HAM/TSP) 8 . Clinically, the HAM/TSP patients presented with progressive neurological disease in which corticospinal tract damage (weakness, spasticity and pathological reflexes) predominated 6 . Many of our patients were originally diagnosed with MS. In fact, one of our patients was diagnosed with MS for 20 years before HTLV-1 testing 10 .To establish a direct link between the immune response to HTLV-1 and the neurological...