New Heart Imaging Techniques to Evaluate Possible Heart Disease

Specialized imaging techniques now available allow a unique opportunity to characterize the
micro-environment of the human body. Magnetic Resonance (MR) vascular wall imaging and
angiography (MRA) are developing techniques that permit non-invasive evaluation of arterial
and venous structures without the need for x-ray based catheter angiography. In addition,
vessel wall imaging provides unprecedented non-invasive tools to assess vascular endothelial
function. While dramatic progress has been made to cardiovascular MR imaging in the last few
years, there are still substantial limitations in the resolution, accuracy, and
reproducibility of MRA and wall imaging in the comprehensive structural and functional
evaluation of coronary artery. The first aim of this study is to develop and optimize
clinical imaging protocols and techniques for fast high-resolution coronary MRA and wall
imaging for the assessment of coronary and other main arteries structural, distensibility,
and endothelial functional parameters. Technique optimization and performance evaluation will
be accomplished in normal subjects without known or suspected coronary atherosclerosis. The
second aim of this protocol is to evaluate early MR imagery signs of arterial structural,
distensibility, and endothelial functional disorders associated with atherosclerosis in a
cohort of patients with known or suspected coronary atherosclerosis. Results from accelerated
high-resolution MRA will be correlated with corresponding Computerized Tomography Coronary
Angiogram (CTA) results. The third aim of this protocol is to develop, implement, and
optimize new non-invasive methods for characterization of the micro-environment in the
thoracic and abdominal area utilizing specialized techniques such as MR Spectroscopy, MR
Elastography, and blood oxygenation level dependent (BOLD) imaging. The long-term objective
of this study and research initiative is to optimize coronary MRA, wall, and body imaging
techniques to the point that it can reliably be used for routine prevention and assessment of
early atherosclerosis and other diseases.

- INCLUSION:

1. Subjects with or without history of cardiovascular diseases and with various
degrees of cardiovascular risk factor. Subjects with known or suspected
atherosclerotic disease based on clinical findings or documented by angiography
(conventional, CTA or MRA), or Doppler ultrasound. And, healthy volunteers and
subjects with known or suspected diseases affecting the thoracic organs,
abdominal organs, and other organs affected by metabolic diseases such as body
fat and muscles. Subjects at risk for atherosclerosis including: smoking,
obesity, hyperlipidemia, low levels of high density lipoproteins (<50 mg/dl for
women and <40 mg/dl for men), hypertension, family history (early onset
atherosclerosis <55 year old in male and < 65 year old in female who is first
degree relative), and diabetes mellitus or metabolic syndrome.

2. Subject must be willing to participate in the protocol.

3. Subject age greater than 18 years old.

4. Subject must be able to provide informed consent.

5. Subject must be clinically stable and be able to come to the Clinical Center to
participate in the study.

EXCLUSION CRITERIA:

1. Subjects with contraindication to MRI scanning. These contraindications include but
are not limited to the following devices or conditions:

1. Implanted cardiac pacemaker or defibrillator

2. Cochlear Implants

3. Ocular foreign body (e.g. metal shavings)

4. Embedded shrapnel fragments

5. Central nervous system aneurysm clips

6. Implanted neural stimulator

7. Medical infusion pumps

8. Any implanted device that is incompatible with MRI.

2. Unsatisfactory performance status as judged by the referring physician such that the
subject could not tolerate an MRI scan. Examples of medical conditions that would not
be accepted would include unstable angina and dyspnea at rest.

3. Subjects requiring sedation for MRI studies.

4. Subjects with a condition precluding entry into the scanner (e.g. morbid obesity,
claustrophobia, etc.).

5. Pregnant or lactating women.

6. Subjects with severe back-pain or motion disorders who will be unable to tolerate
supine positioning within the MRI scanner and hold still for the duration of the
examination.

7. Subjects who are unable to undergo a CTA within 2 months of the MRA part of this
study, or are unable to undergo or be scheduled for a cardiac catheterization within 2
months of the MRA.

EXCLUSION CRITERIA - FOR GADOLINIUM BASED MRI STUDIES ONLY:

1. History of allergic reaction to gadolinium contrast agents despite the use of
premeditation with an anti-histaminic and cortisone.

2. eGFR < 60 ml/min/1.73m^2

EXCLUSION CRITERIA - FOR CORONARY CTA:

1. Contraindication to the use of CTA contrast agents:

1. Creatinine value > 1.4 mg/dl

2. History of multiple myeloma

3. Use of metformin-containing products less than 24 hrs prior to contrast
administration

4. History of allergic reaction to CTA contrast agents despite the use of pre-
medication with an anti-histaminic and cortisone.

2. Subjects with contraindication precluding the use of beta blockers (Appendix C)
necessary to perform the coronary CTA. These include:

1. Asthma

2. Active bronchospasm

3. Moderate or severe COPD

4. 2nd or 3rd degree AV block

5. Decompensated cardiac failure

6. Allergy to beta blockers

7. Systolic blood pressure < 100 mm Hg

8. Pregnancy or nursing

EXCLUSION CRITERIA - FOR NITROGLYCERIN USE:

Subjects reporting a history of the following conditions will be excluded:

1. Severe aortic stenosis

2. Hypertrophic cardiomyopathy

3. Inferior myocardial infarction with right ventricular involvement

4. Cardiac tamponade

5. Constrictive pericarditis

6. Severe hypotension (systolic BP <90 mmHg)

7. Uncorrected hypovolemia

8. Raised intracranial pressure

9. Glaucoma

10. Severe anemia

11. Concomitant use of phosphodiesterase-5 inhibitors (sildenafil-Viagra,
tadalifil-Cialis, verdenafil-Levitra)

12. History of hypersensitivity to nitroglycerin