Technical and Translational Development of Cardiovascular Magnetic Resonance (CMR) Imaging

The purpose of this protocol is to develop and test new MRI techniques applicable to patients
undergoing cardiovascular evaluation with the ultimate goal of translating the technical
advances into improving clinical diagnosis and management of patients undergoing
cardiovascular evaluation. Patients undergoing cardiovascular evaluation and healthy
volunteers will be scanned under the protocol. We will evaluate new developments in
non-contrast and contrast MRI of the heart and blood vessels and novel postprocessing
methods.

The use of the newer sequences will be used to improve clinical imaging workflow and disease
diagnosis. We hope to use this protocol to clearly describe cardiovascular disease and
associated problems using novel MRI methods and follow certain subsets of patients with
disease as part of a natural history process. Inter-related physiologic systems may be
phenotyped by MRI with characterization of disease associations between different organ
systems.

Additionally, information regarding gadolinium deposition of the brain will be gathered. The
literature regarding deposition of gadolinium in the brain has a large void regarding
information of prevalence of the phenomenon in healthy subjects. The National Institutes of
Health has a large healthy subject pool who have participated in gadolinium contrast MRI
studies. This pool of healthy subjects is not easily available at most clinical MRI centers,
and thus, we are uniquely well-situated to be able to answer this outstanding question.

For all objectives, MRI studies will be conducted in the NIH MRI systems located at the NIH
Clinical Center in Bethesda, Maryland. These procedures may involve the intravenous
administration of commercially available MR contrast media and exercise or pharmacologic
stress testing. Results will be used to evaluate the performance of various research pulse
sequences, gradient coils, and radiofrequency receiver coils on human subjects and will
provide essential ground work for specific patient protocols, both diagnostic and
therapeutic.

- INCLUSION CRITERIA FOR HEALTHY VOLUNTEERS:

- Age greater than or equal to 7 years

- Able to follow instructions and lie still in the MRI scanner

- Currently without known cardiovascular disease

- Able to provide informed consent in writing or provide guardian consent

- Willingness to cooperate with all study procedures and available for scheduled study
events

EXCLUSION CRITERIA FOR HEALTHY VOLUNTEERS:

- Important past medical illness

- Conditions that are thought to make MRI unsafe (that will be determined by filling out
a separate form) including:

- Cardiac pacemaker or implantable defibrillator unless it is labeled safe or
conditional for MRI

- Cerebral aneurysm clip unless it is labeled safe for MRI

- Neural stimulator (e.g. TENS-Unit) unless it is labeled safe for MRI

- Any type of ear or cochlear implant unless it is labeled safe for MRI

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

- Metal shrapnel or bullet unless cleared by plain x-ray as safe for MRI

- Any implanted device (e.g. insulin pump, drug infusion device), unless it is
labeled safe or conditional for MRI

- eGFR < 60 mL/min/1.73m^2 using the CKD-EPI equation or equivalent and a serum
creatinine measured within 2 weeks without intercurrent change in medical condition or
medications. Subjects meeting this exclusion criterion may still be included in the
study but may not be exposed to gadolinium-based contrast agents

- Pregnancy. When uncertain of pregnancy status, subjects will undergo serum or urine
pregnancy testing on the day of examination. Among those subjects who will receive MRI
contrast , subjects of child-bearing potential will under serum or urine pregnancy
testing on the day of the examination. Post-menopausal and surgically sterilized
subjects are automatically exempt from this testing.

- If receiving contrast, children and breast feeding women (unless subject is willing to
discard breast milk for 24 hours) are excluded

- In a year s time, healthy volunteers are not restricted as to the number of
non-contrast MRI examinations they undergo, but they may not undergo more than two
examinations involving gadolinium-based contrast agents (GBCA) and those exposures
will be at least 18 hours (12 half-ives) apart.

INCLUSION CRITERIA FOR SUBJECTS WITH KNOWN OR SUSPECTED WITH HEART DISEASE:

- Age greater than or equal to 7 years

- Subjects with known or suspected cardiovascular disease

- Able to provide informed consent in writing or provide guardian consent

- Willingness to cooperate with all study procedures (including food restriction) and
available for scheduled study events

EXCLUSION CRITERIA FOR SUBJECTS WITH KNOWN OR SUSPECTED HEART DISEASE:

- Conditions that are thought to make MRI unsafe (that will be determined by filling out
a separate form) including:

- Cardiac pacemaker or implantable defibrillator unless it is labeled safe or
conditional for MRI

- Cerebral aneurysm clip unless it is labeled safe for MRI

- Neural stimulator (e.g. TENS-Unit) unless it is labeled safe for MRI

- Any type of ear or cochlear implant unless it is labeled safe for MRI

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

- Metal shrapnel or bullet unless cleared by plain x-ray as safe for MRI

- Any implanted device (e.g. insulin pump, drug infusion device), unless it is
labeled safe or conditional for MRI

- Pregnancy. When uncertain of pregnancy status, subjects will undergo serum or urine
pregnancy testing on the day of examination. Among those subjects who will receive MRI
contrast , subjects of child-bearing potential will undergo serum or urine pregnancy
testing on the day of the examination. Post-menopausal and surgically sterilized
subjects are automatically exempt from this testing.

- Breast feeding (unless subject is willing to discard breast milk for 24 hours if
receiving contrast)

- eGFR < 30 mL/min/1.73m^2 using the CKD-EPI equation or equivalent and a serum
creatinine measured within 2 weeks without intercurrent change in medical condition or
medications. Subjects meeting this exclusion criterion may still be included in the
study but may not be exposed to gadolinium-based contrast agents

- Cardiorespiratory instability as determined by the enrolling clinician

INCLUSION CRITERIA FOR SUBJECTS WITH NON-CARDIAC DISEASE:

- Age greater than or equal to 7 years

- Able to provide informed consent in writing or provide guardian consent

- Willingness to cooperate with all study procedures (including food restriction) and
available for scheduled study events

- Known or suspected brain, hematology, oncology, endocrine, pulmonary, or other
non-cardiac disease.

EXCLUSION CRITERIA FOR SUBJECTS WITH NON- CARDIAC DISEASE:

- Conditions that are thought to make MRI unsafe (that will be determined by filling out
a separate screening form) including:

- Cardiac pacemaker or implantable defibrillator unless it is labeled safe or
conditional for MRI

- Cerebral aneurysm clip unless it is labeled safe for MRI

- Neural stimulator (e.g. TENS-Unit) unless it is labeled safe for MRI

- Any type of ear or cochlear implant unless it is labeled safe for MRI

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

- Metal shrapnel or bullet unless cleared by plain x-ray as safe for MRI

- Any implanted device (e.g. insulin pump, drug infusion device), unless it is
labeled safe or conditional for MRI

- Pregnancy. When uncertain of pregnancy status, subjects will undergo serum or urine
pregnancy testing on the day of examination. Among those subjects who will receive MRI
contrast , subjects of child-bearing potential will undergo serum or urine pregnancy
testing on the day of the examination. Post-menopausal and surgically sterilized
subjects are automatically exempt from this testing.

- Breast feeding in those subjects receiving contrast (unless subject is willing to
discard breast milk for 24 hours

- eGFR < 30 mL/min/1.73m^2 using the CKD-EPI equation14 or equivalent and a serum
creatinine measured within 2 weeks without intercurrent change in medical condition or
medications. Subjects meeting this exclusion criterion may still be included in the
study but may not be exposed to gadolinium-based contrast agents

- Cardiorespiratory instability or as determined by the enrolling clinician