Metabolic Imaging of the Heart Using Hyperpolarized (13C) Pyruvate Injection
Metabolic Imaging of the Heart Using Hyperpolarized (13C) Pyruvate Injection
The prevalence of congestive heart failure (CHF) in Canada is high, representing one of the
 health care system's most expensive diagnoses. Despite major advances in medicine, the
 mortality and morbidity from CHF remains great. Currently, magnetic resonance imaging (MRI)
 is used for non-invasive imaging of the cardiovascular system to enable the structure and
 anatomy of the organ to be visualized. However, current MRI methods have limitations when
 assessing and aiding in the management of CHF. A new imaging method has recently been
 developed that is showing great promise as a tool in the management of patients with CHF.
 Rapid imaging of biochemical reactions within myocytes using MRI has recently become possible
 through the use of the Dynamic Nuclear Polarization (DNP) and dissolution method.
 DNP-dissolution results in an intravenous contrast agent that is "hyperpolarized", producing
 a magnetic signal that is enhanced by up to 100,000 fold. The particular agent is carbon-13
 labelled pyruvate. In this study, we demonstrate the first 13C-metabolic images of the human
 heart, along with the required hardware and data acquisition methods.
For this study, the heart of control subjects and those with hypertension or hypertrophy will
 be imaged using Hyperpolarized Pyruvate 13C Injection. Different forms of Hyperpolarized
 Pyruvate 13C Injection are available, with the 13C labelling at different positions within
 the molecule. These are equivalent from a safety perspective and covered by the same
 Investigators Brochure, but offer different metabolic information. Two different labelling
 patterns are investigated in this study. If images are successfully obtained, then insights
 into heart failure treatments that normalize the detrimental metabolic changes may enable
 earlier treatment and slow disease progression to CHF, ultimately reducing the high rates of
 morbidity and mortality associated with this disease.

 Prior to enrollment, all participants will be screened in order to ensure they meet the
 study's inclusion and exclusion criteria and MRI eligibility. On the day of their scan, each
 participant will have an intravenous line inserted and receive a glucose drink, prior to
 scanning. The reason for this glucose drink is that a fed versus fasted state has been found
 to give markedly different measurements in animal models and a choice of meal would be a
 source of variability. The metabolic imaging will occur shortly after this drink.

 For each scan, a 1.47 g sample of [1-13C]-pyruvic acid will be hyperpolarized using a SpinLab
 polarizer (General Electric Co.). The solid-state sample will be dissolved to a concentration
 of 250 mM pyruvate at biological pH. A 0.1 mmol/kg dose (approximately 20 mL) of this
 solution will be injected through an intravenous line, followed by a 25 mL saline flush. The
 13C image acquisition will begin at the end of the injection and will record data during
 every heartbeat within the single breath-hold.

 Heart rate and blood pressure will be monitored non-invasively, prior to the participant
 being positioned within the MR scanner. Heart rate will continue to be monitored during and
 after the scan and the participant will be monitored by the Study's Qualified Investigator or
 medical designate for up to 1 hour post injection.

 The 13C imaging will be preceded by the standard cardiovascular MRI workup including
 breath-hold cine imaging to measure ejection fraction and LV mass (~30 minutes of scan time).

 Each participant in group 2 will also receive an injection of gadolinium as part of their MRI
 to determine evidence of late gadolinium enhancement. The recommended adult dose of 0.1ml/kg
 will be given. Multi-slice T1 weighted gradient echo images will be acquired. Gadolinium will
 be used to examine the metabolic profile in regions of scar and normal myocardium profile.
 LGE imaging will be performed to identify regions of scar tissue or fibrosis.

 All clinical procedures will be completed under the supervision of the Qualified
 Investigator, or medical designate.

 Each participant will receive a follow up telephone call on the 7th day following the
 procedure to ascertain if any study related adverse events have occurred. The length of this
 study for participants is a single visit that will require approximately 3 hours of their
 time, except for participants in Groups 1C and 1F for whom the length for the study is two
 visits separated by at least 2 weeks, each requiring 3 hours. The entire study is expected to
 take about 3 years and the results should be known approximately six months after study
 completion.
Inclusion Criteria

 -  Written consent

 -  Age: 19 to 50 in Arm 1, 30 to 75 in Arm 2

 -  Group 2A and 2E participants have left-ventricular hypertrophy

 -  Group 2B and 2F participants have diagnosed hypertrophic cardiomyopathy

 -  Group 2C and 2G participants are stable outpatients with NYHA class 1-3 heart failure
 with evidence of elevated LV mass (LVH), irrespective of LVEF.

 -  Group 2D and 2H participants are stable patients with type 2 DM who have a HcA1c
 between 6.5-9% on oral hypoglycemic agents

 Exclusion Criteria

 -  Contraindications to MRI or MRI contrast agents

 -  Hemoglobin ≤ 9.0 gm/dL (only Group 2 participants)

 -  Glomerular filtration rate (based on MDRD Equation) < 30 ml/min/1.73m2 (only Group 2
 participants)

 -  Any condition leading to a life expectancy <1 year

 -  Medically diagnosed claustrophobia

 -  Have received, or are scheduled to receive, another investigational medicinal product
 from 1 month prior to 1 month after inclusion in this study

 -  BMI of less than 18.5 or greater than 32

 -  Group 1: medically diagnosed heart disease