Acoustic Radiation Force Impulse (ARFI) Ultrasound for Noninvasive, Diagnostic Atherosclerosis Imaging

The purpose of this study is to evaluate Acoustic Radiation Force Impulse (ARFI) ultrasound
imaging for describing the composition and structure of atherosclerotic plaques. The surgical
atherosclerotic plaques of 16 patient volunteers undergoing clinically indicated carotid
endarterectomy (surgical removal of plaque from the carotid artery) will be imaged
preoperatively by ARFI. ARFI imaging will occur during the volunteers' preoperative workup
visits (inpatient or outpatient), in the surgical holding area (inpatient or outpatient), or
at the patient bedside (inpatient). Then, the routinely excised plaque specimens will be sent
for histopathological processing to determine plaque composition and structure. The
histopathological data will be used to validate ARFI imaging performance for plaque material
and structural characterization. This will end the participant's involvement in the study.

There are two experimental components to this study beyond what is standard practice for
carotid endarterectomy patients: 1) preoperative ARFI ultrasound imaging of ipsilateral
(surgical) carotid arteries, and 2) submission of sections of the carotid plaque excised
intraoperatively to the UNC Hospitals clinical laboratories for immunohistochemical analysis.

This study will commence with ARFI ultrasound imaging at the time of the patient volunteer's
preoperative workup for carotid endarterectomy surgery (outpatients and inpatients), while
the patient is in the holding area for surgery (outpatients and inpatients), or at the
patient bedside (inpatients). If the patient volunteer is an outpatient, ARFI ultrasound
imaging will be performed up to two weeks prior to surgery. Preoperative ARFI ultrasound
imaging will be performed in addition to the patient volunteer's routine preoperative duplex
ultrasound and any other exams used to determine if carotid endarterectomy is clinically
indicated.

ARFI ultrasound is a noninvasive diagnostic imaging technology performed using commercially
available clinical ultrasound imaging equipment - the Siemens SONOLINE or Acuson Antares
imaging systems equipped for research purposes and VF10-5 or VF7-3 linear array transducers
(Siemens Medical Solutions, USA Inc. Ultrasound Division). ARFI imaging will be carried out
by a professional sonographer trained in peripheral vascular ultrasound and faculty (Caterina
Gallippi, Ph.D., Associate Professor, study PI) and/or graduate student research assistants
in the UNC-CH Joint Department of Biomedical Engineering. The sonographer will acquire ARFI
ultrasound data with matched B-Mode (for anatomical reference) in ipsilateral (surgical)
carotid arteries of patient volunteers. Patient volunteers will be asked to lie on an
examination table (outpatients) or to remain in their hospital beds (inpatients). The head of
the exam table/bed may be raised to an approximate 45 degree angle to best visualize the
carotid arteries with ultrasound imaging.

Once the patient volunteer is positioned, ultrasound gel will be applied to the patient
volunteer's neck. The ultrasound imaging transducer will then be placed on top of the gel.
Once the carotid artery is located, ARFI ultrasound imaging will begin. In the ipsilateral
(surgical) carotid artery, the imaging field of view will be centered on the carotid plaque,
with axial focal depth directed to the position of the near or far wall containing the
thickest portion of the plaque. Data acquisitions will be gated to diastole. Two repeated
acquisitions will be acquired for each of four ARFI imaging sequences. The position of
landmarks such as arterial branch points and morphological features such as arterial wall
thickness will be recorded for spatial registration to duplex ultrasound and histology.

The length of time for ARFI data collection in the carotid artery is estimated to be less
than 30 minutes. Once the ipsilateral (surgical) carotid artery is imaged, the study
procedure will be completed for the first portion of the study.

For the second part of the study, sections of the carotid plaque specimen routinely extracted
during carotid endarterectomy surgery will be photographed and then fixed and paraffin
embedded in the UNC Tissue Procurement core facility. The specimens will then undergo
sectioning and staining in the UNC Histopathology core facility. These experimental sections
will be in addition to the sections routinely sent for immunohistochemical processing after
carotid endarterectomy. Sectioning will be directed by the surgeon per standard
histopathology protocol and per laboratory sampling protocol. The sections will be stained
with hematoxylin and eosin (H&E) for baseline, Verhoeff van Giesen (VVG) for elastin, Sirius
Red (SR) with polarized light microscopy for collagen sub-types I and III, von Kossa (VK) for
calcium, and/or Lillie modification of Masson's trichrome (MT) for fibrin, or other
comparable stains. This will conclude part two of the study. However, excised plaque
specimens will be stored in Dr. Gallippi's (PI) laboratory for a period of up to five years
following study completion. Their storage will enable re-sectioning as need to achieve proper
spatial alignment with ARFI imaging. The stored specimens will not be used for future
research; they are for verification purposes only. The specimens will be submerged in
formalin and stored in sealed plastic containers. No identifiable information will be
recorded with the samples, and all HIPAA guidelines and procedures will be observed.

Patient volunteers' participation will end once both study parts one (ARFI ultrasound
imaging) and two (immunohistochemical processing of excised plaque specimens) are completed.
Therefore, there will be no follow-up visits required or additional demands placed on the
patient volunteers. A Patient volunteer is asked to consent to (1) ARFI ultrasound imaging of
his/her ipsilateral (surgical) carotid arteries before his/her clinically indicated
endarterectomy surgery, and (2) sections of his/her routinely excised plaques specimens
undergoing immunohistochemical processing (in addition to any sections routinely sent for
immunohistochemical processing after carotid endarterectomy). No additional procedures or
requirements are proposed. Every other aspect of the volunteers' preoperative workup for
surgery and the endarterectomy surgery itself will be carried out in the normal standard of
care as clinically indicated.

There is no control group in this study. This is a pilot study to determine if ARFI
ultrasound imaging in this patient population may be relevant to delineating the composition
and structure of carotid plaques with immunohistochemical validation.

Inclusion Criteria:

- Patients scheduled to undergo clinically indicated carotid endarterectomy

- Determination of clinical need for carotid endarterectomy will be made by the vascular
surgeons on this protocol, but the general criteria include symptomatic carotid
disease with a stenosis or lesion in the carotid artery thought to be the source of
emboli or asymptomatic carotid artery disease with a > 60% internal carotid artery
stenosis in the ipsilateral (surgical) artery.

- Male or Female

- >18 years of age with no upper limit

- Ability to provide informed consent

- Surgeon's approval

- Any ethnicity or race (meeting all other criteria)

Exclusion Criteria:

- Inability to communicate in English

- Inability to provide valid consent

- Inability to remain motionless for at least 15 minutes

- Carotid arteries deeper than 35 mm

- Pregnancy*

- Pregnant women will be excluded from this study because carotid dissection is
more likely than carotid plaque in women of child-bearing age.