Technical Development of Cardiovascular Magnetic Resonance Imaging (CMR) Using a Low Specific Absorption Rate (SAR) Scanner System

Magnetic resonance imaging (MRI) generates medical images of organs inside the body and can
provide accurate and reproducible measures of cardiac chamber volumes, cardiac function,
blood flow, myocardial scar, extracellular volume as a measure of collagen content, iron
content, and others, all without exposure to ionizing radiation. The prevailing wisdom is
that MRI using high specific absorption rate (SAR) scanning modes produces highest image
quality. We propose a method of MRI that can be performed with low SAR but that nevertheless
preserves image quality because of efficient use of MRI signal. MRI using low SAR is
attractive because it may reduce heating of metallic structures. This may allow safe MRI in
patients with metallic implants, and it may allow MRI catheterization using metallic
guidewires and catheter devices.

The goal of this non-significant risk (NSR) medical device study is to test initial technical
feasibility of low SAR MRI in healthy volunteers by technical optimization of scanner
protocols, to test comparative accuracy of standard CMR measurements in healthy volunteers
using low SAR MRI versus conventional MRI.

A secondary goal is to assess the potential of this new low-SAR MRI system to perform
cardiovascular diagnostic imaging and non-cardiovascular radiological diagnostic imaging by
testing comparative diagnostic accuracy of standard MR measurements in adult patients with
known disease using the low SAR MRI system vs conventional MR exam.

- INCLUSION CRITERIA FOR HEALTHY VOLUNTEERS:

- Men and women age greater than or equal to 8 years

- Currently healthy

- Able to provide informed consent in writing

- Willingness to cooperate with all study procedures (including food restriction) 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 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 implant unless it is labeled safe for MRI

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

- Metal shrapnel or bullet

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

- When gadolinium based contrast agent (GBCA) exposure is planned

- No gadolinium based contrast agent exposure is permitted if 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, or without eGFR determination, may
still be included in the study but may not be exposed to gadolinium-based
contrast agents

- Pregnancy. When uncertain, subjects will undergo serum pregnancy testing. Results from
up to 7 days prior to the examiation will be used. Post-menopausal and surgically
sterilized subjects are exempt from this testing.

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

- Healthy volunteers may undergo up to three paired CMR examinations, but they may not
receive more than one pair of examinations involving gadolinium-based contrast agents
(GBCA)

INCLUSION CRITERIA FOR ADULTS WITH HEART DISEASE:

- Men and women age greater than or equal to 18 years

- Able to provide informed consent in writing

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

- Having known heart disease including but not limited to

- Stable angina pectoris due to epicardial coronary artery obstruction

- Past myocardial infarction

- Heart failure with reduced ejection fraction

- Valvular heart disease

- Pulmonary artery hypertension

- Congenital heart disease with or without prior repair

- Myocarditis

- Infiltrative cardiomyopathy

- Hypertrophic cardiomyopathy

EXCLUSION CRITERIA FOR ADULTS WITH HEART DISEASE:

- Unstable angina, acute coronary syndrome, or myocardial infarction not attributable to
PCI, within 2 weeks unless after coronary revascularization of the culprit lesion.

- Any hemodynamic instability or decompensated heart failure as determined by the
enrolling physician.

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

- Certain cardiac implanted electronic devices (CIED) such as cardiac pacemaker or
implantable defibrillator

- 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 implant unless it is labeled safe for MRI

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

- Metal shrapnel or bullet

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

- Pregnancy. When uncertain, subjects will undergo serum pregnancy testing. Results from
up to 7 days prior to the examination will be used. Post-menopausal and surgically
sterilized subjects are exempt from this testing.

- Breast feeding (unless subject is willing to discard breast milk for 24 hours

- When gadolinium based contrast agent (GBCA) exposure is planned:

--No gadolinium based contrast agent exposure is permitted if 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, or without eGFR determination, may still be
included in the study but may not be exposed to gadolinium-based contrast agents

- Patients with asthma or chronic obstructive pulmonary disease are (ineligible for
vasodilator stress CMR)

- Patients with advanced heart block on baseline ECG are (ineligible for vasodilator
stress CMR)

EXCLUSION CRITERIA FOR ADULTS WITH CARDIAC IMPLANTED ELECTRONIC DEVICES (CIED, PACEMAKERS
OR DEFIBRILLATORS):

- Low-SAR MRI: Subjects with CIED are not excluded, based on the intrinsic safety of
low-SAR MRI.

- Conventional MRI

- In order to undergo conventional MRI, subjects with CIEDs must have CIEDs that
are labeled as MRI conditional or MRI safe and that are not implanted < 4 weeks
prior to MRI exam.

- Subjects with CIED are excluded from conventional MRI unless they have CIEDs that
are labeled as MRI conditional or MRI safe, and that are implanted >= 4 weeks
prior to MRI

INCLUSION CRITERIA FOR ADULTS WITH NON-CARDIAC DISEASE:

- Men and women age >= 18 years

- Able to provide informed consent in writing

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

- Having known brain disease including but not limited to

- Transient ischemic attack or stroke after 24 hours of onset

- Infection, inflammation meningitis

- Cognitive decline, neurodegenerative disorders

- Demyelinating disease, multiple sclerosis

- Loss of consciousness, seizures, epilepsy

- Brain tumor, metastases, abscess, lesion

- Vascular pathology

- Headache

- Hemorrhage

- Trauma

- Have known musculoskeletal disease including but not limited to:

- Persistent neck pain or radiculopathy

- Cancer or tumors of the spine

- Congenital abnormalities of the spinal cord or knee

- Multiple sclerosis

- Injury or trauma

- Fracture evaluation

- Infectious or inflammatory processes

- Soft tissue damage

- Muscle or tendon disorders

- Knee meniscal disorders

- Marrow abnormalities

- Mechanical knee symptoms

- Vascular conditions

- Have known abdominal diseases including but not limited to:

- Bowel obstruction

- Masses and tumors

- Crohns disease

- Diffuse liver disease such as hemochromatosis, hemosiderosis, fatty infiltration

- Focal hepatic lesions

- Cirrhotic liver

- Iron content determination

- Cystic kidney disease

- Vascular abnormalities

- Have known lung disease including but not limited to:

- Cancer, tumors and masses

- Vascular and lymphatic abnormalities

- Pulmonary thromboembolic disease

- Trauma

- Suspected bronchiolitis

- Bronchiectasis or pneumonitis

- Asthma and other obstructive lung diseases

Pulmonary lymphangioleiomyomatosis

--Cystic and interstitial lung diseases such as pulmonary lymphangioleiomyomatosis and
cystic fibrosis

- Have other known non-cardiovascular disease

EXCLUSION CRITERIA FOR ADULTS WITH DISEASE:

- Acute illness for which investigational imaging might delay care (such as acute stroke
before treatment), as determined by the enrolling physician

- Any hemodynamic instability as determined by the enrolling physician.

- 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 MRI
conditional or MRI safe

- 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 implant unless it is labeled safe for MRI

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

- Metal shrapnel or bullet

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

- Pregnancy. When uncertain, subjects will undergo serum pregnancy testing. Results from
up to 7 days prior to the examination will be used. Post-menopausal and surgically
sterilized subjects are exempt from this testing.

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

- - When gadolinium based contrast agent (GBCA) exposure is planned

- No gadolinium based contrast agent exposure is permitted if eGFR < 30
mL/min/1.73m 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, or without eGFR determination, may
still be included in the study but may not be exposed to gadolinium-based
contrast agents

EXCLUSION CRITERIA FOR OXYGEN INHALTION:

- Severe chronic obstructive pulmonary disease defined as requiring more than one
bronchodilator medication every day or oxygen requiring

- Prior treatment with bleomycin