Structural Stability of Carotid Plaque and Symptomatology

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 144 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, ultrasound
testing of the atherosclerotic plaque for determination of elasticity and strain, as well as
TCD (transcranial doppler) measurement of emboli, MRI testing for analysis of MRI predictors
of cognition and ischemic vascular disease as per our preliminary studies, as well as blood
collection. 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 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 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 (Carotid Endarterectomy) durably stabilizes vessel wall elasticity and halts microemboli
on MRI 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 undergoing carotid endarterectomy for established clinical criteria

- Age > 18 years

- Male or Female

- English speaking

- Patients must sign written informed consent form

Exclusion Criteria:

- 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

- Prisoner status