Structural Stability of Carotid Plaque and Symptomatology
Structural Stability of Carotid Plaque and Symptomatology
The purpose of the research is to understand structural plaque abnormalities that make a
 carotid plaque unstable and brake off (embolize) which would help to predict and treat
 individuals who are likely to suffer not only classic episodic major strokes but also
 cognitive impairment.
This study examines the relationship between the structural stability of carotid
 atherosclerotic plaque forming at the bifurcation of the common internal/external carotids
 and the ability of such lesions to cause disease. The theory behind this work is the
 hypothesis that carotid atherosclerotic stroke presents not only as a classical episodic
 clinical condition, but may also involve elements of a continuous process involving large and
 small vessel circulations, microcirculatory changes, cellular metabolic resistance to
 ischemia and micro embolic events. Recent studies suggest for every recognized clinical
 stroke, 5 silent strokes take place.

 The patient implications are enormous as imaging suggests 11 million "silent strokes" occur
 yearly in the US with poor understanding of the pathophysiology or cognitive consequences for
 our patients. Within this framework, the investigators choose to study the hypothesis that
 carotid artery atherosclerosis is likely to cause microemboli, as well as classic
 macroemboli, which may result in more subtle disturbances than those ordinarily detected by
 more obvious clinical events such as stroke and transient ischemia attacks.

 Understanding the structural plaque abnormalities that render a carotid plaque unstable and
 at risk of embolization would help to predict and treat individuals who are likely to suffer
 not only classic episodic major strokes, but also cognitive impairment from the contribution
 of microemboli to this overall disease process. The investigators have previously described a
 non-invasive ultrasound based measure of plaque structural stability which will be further
 studied in this proposal. This study will expand on previous work performed at the University
 of Wisconsin-Madison, and will include patients with carotid artery stenosis, both with and
 without classic stroke symptoms, as well as a control group of patients without known
 atherosclerotic disease.

 Patients will be recruited from the population of patients scheduled to undergo carotid
 endarterectomy for established clinical indications. These indications include patients
 scheduled to have a carotid endarterectomy due to the presence of a high-grade
 atherosclerotic cervical internal carotid artery stenosis with or without clinical symptoms,
 following the ACAS (Asymptomatic Carotid Atherosclerosis Study) or NASCET criteria (The North
 American Symptomatic Carotid Endarterectomy Trial) (carotid artery stenosis of 60% or greater
 without clinical symptoms; stenosis 70% or greater with clinical symptoms). Patients will be
 recruited from University of Wisconsin Hospital and Clinics Neurosurgery Clinic and inpatient
 units. With this renewal the investigators would like to complete previously approved sample
 size of 194 patient-subjects. In the previous protocol 75 patients-subjects were enrolled,
 remaining 69 patient-subjects to be enrolled in this study.

 The investigators also have previously approved enrollment for 50 control-subjects. Having
 enrolled 20 in the previous protocol the investigators will complete enrollment with
 enrolling additional 30 control-subjects These controls will be recruited by the
 patient-subjects. The investigators will ask the patient-subjects to speak to a spouse or
 family member to see if they are interested in participating. If they do have an interest
 they will contact the research team/study coordinator(s). In case, a spouse or a family
 member is accompanying the patient-subject, they will be recruited at the same time as the
 patient-subject. The Investigators have demonstrated by their experience of carotid
 endarterectomy in asymptomatic and symptomatic disease (>25 per year) and their very high
 recruitment rates in their pilot study (>95%) that sufficient experience exists for
 successful recruitment of this population over the time of the study.

 All patients will undergo confirmation of the degree of stenosis by standard clinical
 methodology including angiography, magnetic resonance imaging, computerized tomographic
 angiography, and/or ultrasonic determination. Patients enrolled in the study will obtain a
 health questionnaire highlighting atherosclerotic risk factors, history of other
 atherosclerotic events involving other organs, known history of hyperlipidemia, smoking,
 hypertension, diabetes, cardiac disorders, or family history of above. Results will be
 stratified according to these risk factors.

 All these patients will undergo preoperative neuropsychological cognitive testing. These
 patients will undergo ultrasound testing of the atherosclerotic plaque for determination of
 elasticity and strain as outlined, as well as TCD measurement of emboli. At the time of
 surgery, the atherosclerotic plaque through the carotid bifurcation will be removed in total
 and will be examined histopathologically at a point by point comparison with the ultrasonic
 strain and quantitative ultrasound mapping of the attenuation coefficient, scatterer size and
 integrated backscatter measurements. These will be studied for gross ulceration, micro
 ulceration, formation of thrombus and platelet deposition, inflammatory cells and
 neovascularity as measured with immunostaining for the CD 34 marker for microvascular
 endothelial presence. All studies but the histopathologic evaluation will be obtained in the
 immediate preoperative period and will be repeated at one year post surgery to determine if
 CEA durably stabilizes vessel wall elasticity and halts microemboli and cognitive decline.

 The study will run for 5 years from IRB (Institutional Review Board) approval. Recruitment of
 subjects will take place over the first three and half years. All patient-subjects will have
 1-year follow-up, MRI, ultrasound, TCD, blood collection and cognitive study to see if
 endarterectomy affected pre-op change. Change in cognition will be compared to report studies
 in the normal control group. In past, the investigators have recruited carotid patients at a
 greater pace. Given the complexity of these studies the investigators anticipate recruitment
 and complete analysis of 20 patients/year. During this time initial psychological testing
 will be done pre-operatively. During the final year of the study, the data analysis of the
 plaque ultrasounds, MRI and histopathology and 1-year follow-up the patient received in the
 last year of recruitment will take place. Investigators can recruit additional patients to
 fill any missing data points if these results identify a subset of classically asymptomatic
 patients with significant carotid plaques and microemboli causing vascular cognitive decline.
Inclusion Criteria (Patients):

 -  Patients undergoing carotid endarterectomy for established clinical criteria

 -  Age > 18 years

 -  Male or Female

 -  English speaking

 -  Patients must sign written informed consent form

 Inclusion Criteria (Controls):

 -  A spouse or sibling of a Patient Subject

 -  Age > 18 years

 -  Male or Female

 -  English speaking

 -  Control-Subject must sign a written informed consent form

 Exclusion Criteria (Patients):

 -  Previous history of carotid artery surgery (endovascular or open)

 -  Previous cervical radiation

 -  Patients not felt be suitable for carotid endarterectomy

 -  Patients with impaired consent capacity

 -  Contraindication to MRI scans (impaired renal function, need for sedative medication
 during scans, inability to lie in scanner for 60 minutes)

 -  Prisoner status

 Exclusion Criteria (Controls):

 -  Control-Subjects with impaired consent capacity

 -  Prisoner status

 -  Previous history of Stroke or TIAs

 -  Previous history of carotid artery surgery (endovascular or open)