Cardiac MRI can be used to assess cardiac metabolism through various techniques. Conventional cardiac MRI can measure myocardial triglyceride content through proton magnetic resonance spectroscopy. This technique has shown increased triglycerides in the myocardium of obese individuals and those with diabetes, related to circulating fatty acids and ectopic fat accumulation. Hyperpolarized MRI is also being developed to directly image metabolic processes in the heart like pyruvate to lactate conversion. These techniques provide insights into abnormal cardiac metabolism associated with diseases.

1. Cardiac MRI
Budi Susetyo Pikir
Department of Cardiology
Faculty of Medicine
Dr Soetomo General hospital /
Airlangga University Hospital
Airlangga university
S U R A B A Y A
Role for Assessment of Cardiac Metabolism

2. Imaging in Heart Disease
1. Chest X-ray
2. Echocardiography
3. Nuclear scintigraphy
4. Catheterisation
Resolution
Information Radiation
Invasiveness
• Cardiac MRI

3. What CMR has to offer

4. The Comprehensive Cardiac MR (CMRI & CMRS)
1. Cardiac and great vessel anatomy
2. Coronary artery lumen, wall anatomy, blood flow
3. Cardiac volumes and mass
4. Global and regional contractile function
5. Regional myocardial tissue perfusion
6. Regional myocardial tissue characteristics :
a. Viability,
b. Fibrosis
c. Edema,
d. Inflammation,
e. Metabolism
7. Stem Cell Tracking
Goal: <30 min acquisition, <10 min post-processing

5. CARDIAC DISEASES & ABNORMAL METABOLISM
CARDIAC DISEASES
CARDIAC DISEASES
ABNORMAL METABOLISM
Intra-Cardiac Metab Abnorm
Extracardiac Metab Abnorm
ABNORMAL METABOLISM
Intra-Cardiac Metab Abnorm
Extracardiac Metab Abnorm

6. Some of these radiotracers have been designed
to bind to receptors and other targets that are overexpressed in
cancer
cells versus normal cells; such molecular imaging agents

7. Cardiac Metabolic Imaging
I. Conventional Cardiac Metabolic MRI
II. Hyperpolarized Cardiac Metabolic MRI

8. Cardiac Metabolic Imaging
I. Conventional Cardiac Metabolic MRI
II. Hyperpolarized Cardiac Metabolic MRI

9. Proton Cardiac Magnetic Resonance Spectroscopy

10. Foetal Metabolic Profile :
Beating Heart utilizes Carbohydrate (Glucose & Lactate) as Primary Source of
Energy
Myocardial Triglyceride
Adult Normal Metabolic Profile :
Beating Heart utilizes Fatty Acid as Primary Source of Energy
Stephen C. Kolwicz Jr and Rong Tian. Glucose metabolism and cardiac hypertrophy. Cardiovascular
Research (2011) 90, 194–201.
Adult Cardiac Hypertrophy  Foetal Metabolic Profile :
Beating Heart utilizes Carbohydrate (Glucose & Lactate) as Primary Source of
Energy
Increase Intramyocardial Triglyceride  Lipotoxicity

11. Increase Myocardial Triglyceride content result in Lipotoxicity &
may contribute to development of Myocardial Dysfunction
Myocardial Triglyceride
Stephen C. Kolwicz Jr and Rong Tian. Glucose metabolism and cardiac hypertrophy. Cardiovascular
Research (2011) 90, 194–201.
Figure 2 Altered glucose metabolism
in cardiac hypertrophy. Key changes
in the metabolic pathway have been
colour coded. Green: increased;
Red:decreased; Blue: no change;
Black: unknown. F-6-P, fructose-6-
phosphate; G-6-P, glucose-6-
phosphate; G6PD, glucose-6-
phosphate dehydrogenase;
GFAT, glutamine fructose-6-phosphate
amidotransferase; GLUT, glucose
transporter; LDH, lactate
dehydrogenase; ME, malic enzyme;
NADH, reduced nicotinamide adenine
dinucleotide; OMC, oxoglutarate-
malate carrier; TCA, tricarboxylic acid.

12. Grigorios Korosoglou, MD, Dimitrios Oikonomou, MD, Sebastian J. Buss, MD, Angelika Bierhaus, PhD, Per
M. Humpert, MD, Nael F. Osman, PhD, Henning Steen, MD, Peter P. Nawroth, MD, Johannes Ahrens, MS,
Gitsios Gitsioudis, MD, Bernhardt Schnackenburg, PhD, and Hugo A. Katus, MD. Left Ventricular Diastolic
Function in Type 2 Diabetes Mellitus Is Associated With Myocardial Triglyceride Content But Not With Impaired
Myocardial Perfusion Reserve. J MAGNETIC RESONANCE IMAGING 2012; 35:804–811.
Figure 1. Imaging protocol in patients with type 2 diabetes mellitus, which included the quantitative assessment
of 1) systolic and diastolic LV-function using SENC, 2) myocardial triglyceride content, and 3) myocardial
perfusion reserve during adenosine stimulation. [Color figure can be viewed in the online issue, which is
available at wileyonlinelibrary.com.]
Protocol Proton Cardiac Magnetic Resonance Imaging / Spectroscopy

13. FIG. 1. Two schemes for cardio/respiratory
double triggering.
Method B: Experimental scheme based on
pressure differences in inhaled and expired air.
The breathing curve (top row) is detected by
home-built electronic circuitry. When the airflow
is nearly zero (dashed box), trigger 1 is initiated
and together with the next ECG trigger leads to
the effective trigger 2. Retriggering during the
same breathold is delayed by choice of a long
TR on the scanner.
Method C: Experimental scheme based on
respiration-related amplitude variations of the
ECG signal. Because the amplitude of the ECG
signal depends on respiration and the rotation of
the heart, the position of the heart can be
monitored. Demodulation of the ECG amplitude
produces a respiration curve. The double trigger
is enabled when the QRS amplitude is in a
narrow range defining expiration in two
consecutive heartbeats. An optical feedback was
added such that the subject had control over
theexpiration excursions with respect to the
target position.
Cardiac/Respiratory Double-Triggered
1H-MR Spectroscopy of the Human Heart
Jacques Felblinger, Bruno Jung, Johannes Slotboom, Chris Boesch, and Roland Kreis/
Methods and Reproducibility of Cardiac/Respiratory Double-Triggered 1H-MR
Spectroscopy of the Human Heart/ Magnetic Resonance in Medicine 1000; 42:903±910.

14. FIG. 2. MR spectra acquired from the same volunteer using
the three described double triggering methods: method A
(a), method B (b),and method C (c). Number of averages
per spectrum, precise placement of ROI in septum, size of
ROI, and type of receive coil are not identical because of
steadyimprovements in methodology anddifferent software
and hardware versions. a: 5.1 cm3, sum of 4 x 64
acquisitions, flexible receive coil, voxel not oblique. b: 4.9
cm, oblique voxel, sum of 2 x 64 acquisitions, 13 cm
receive coil. c: 3.6 cm3, oblique voxel, sum of 3 x 64
acquisitions, 13 cm receive coil. (All spectra with 1 Hz
FIG. 3. Signal phase fluctuations recorded in 64 subsequent scans without
water suppression as a function of triggering mode and double triggering
method: method B (a) and method C (b). Fluctuations were reduced by single
triggering but were still too large for 1H-MRS. Double triggering with either
method B or C reduced the phase fluctuations and the other effects of motion
satisfactorily.
(Respiration triggering only is not possible with method C; thus, corresponding
data are missing from b.) (The single outlyer in the double triggered data in b
is of unknown origin, possibly hardware malfunction.) c: The signal shapes
achieved in the respective triggering mode (using method B for double
triggering).
Jacques Felblinger, Bruno
Jung, Johannes Slotboom,
Chris Boesch, and Roland
Kreis/ Methods and
Reproducibility of
Cardiac/Respiratory Double-
Triggered 1H-MR
Spectroscopy of the Human
Heart/ Magnetic Resonance
in Medicine 1000;
42:903±910.
Cardiac/Respiratory Double-Triggered
1H-MR Spectroscopy of the Human Heart

15. OBESITY
Obesity increase in Epicardial & Intramyocardial Fat
Mikko Kankaanpa¨a¨ , Hanna-Riikka Lehto, Jussi P. Pa¨ rkka¨ , Markku Komu, Antti Viljanen, Ele Ferrannini, Juhani Knuuti,
Pirjo Nuutila, Riitta Parkkola, and Patricia Iozzo. Myocardial Triglyceride Content and Epicardial Fat Mass in Human
Obesity: Relationship to Left Ventricular Function and Serum Free Fatty Acid Levels/ Journal of Clinical. Endocrinology &
Metabolism 91(11):4689–4695
FIG. 1. VOI location in the septal wall, as confirmed in short-axis (left)
and four-chamber orientations (right).
Myocardial Triglyceride Content and Epicardial Fat
Mass in Human Obesity: Relationship to Left Ventricular
Function and Serum Free Fatty Acid Levels

16. OBESITY
Mikko Kankaanpa¨a¨ , Hanna-Riikka Lehto, Jussi P. Pa¨ rkka¨ , Markku Komu, Antti Viljanen, Ele Ferrannini, Juhani Knuuti,
Pirjo Nuutila, Riitta Parkkola, and Patricia Iozzo. Myocardial Triglyceride Content and Epicardial Fat Mass in Human
Obesity: Relationship to Left Ventricular Function and Serum Free Fatty Acid Levels/ Journal of Clinical. Endocrinology &
Metabolism 91(11):4689–4695
FIG. 2. Examples of spectra in one lean and one obese study subject. Filtering of the signal was carried out with the
5-Hz line-broadening exponential function. The main methylene peak is visible at 1.3 ppm. Amplitude is expressed
in arbitrary units.
Myocardial Triglyceride Content and Epicardial Fat
Mass in Human Obesity: Relationship to Left Ventricular
Function and Serum Free Fatty Acid Levels

17. OBESITY
Obesity increase in Epicardial & Intramyocardial Fat
Mikko Kankaanpa¨a¨ , Hanna-Riikka Lehto, Jussi P. Pa¨ rkka¨ , Markku Komu, Antti Viljanen, Ele Ferrannini, Juhani
Knuuti, Pirjo Nuutila, Riitta Parkkola, and Patricia Iozzo. Myocardial Triglyceride Content and Epicardial Fat Mass
in Human Obesity: Relationship to Left Ventricular Function and Serum Free Fatty Acid Levels/ Journal of Clinical.
Endocrinology & Metabolism 91(11):4689–4695
FIG. 3. Consensual increase in ectopic fat and circulating FFA levels in
patients with obesity. Age-adjusted P values are 0.039 (myocardial fat
percent), 0.001 (epicardial fat), 0.002 (waist), and 0.006 (FFA).
FIG. 4. Myocardial fat in subjects with higher vs.
lower alanine transaminase (ALT).

18. OBESITY
Obesity increase in Epicardial & Intramyocardial Fat
Mikko Kankaanpa¨a¨ , Hanna-Riikka Lehto, Jussi P. Pa¨ rkka¨ , Markku Komu, Antti Viljanen,
Ele Ferrannini, Juhani Knuuti, Pirjo Nuutila, Riitta Parkkola, and Patricia Iozzo. Myocardial
Triglyceride Content and Epicardial Fat Mass in Human Obesity: Relationship to Left
Ventricular Function and Serum Free Fatty Acid Levels/ Journal of Clinical. Endocrinology &
Metabolism 91(11):4689–4695
FIG. 5. Regression
analysis showing
significant associations
of FFA with myocardial
fat and LV mass, or
between epicardial fat
and the cardiac index in
obese (Œ) and lean (f)
men.

19. OBESITY
Myocardial Triglyceride Content and Epicardial Fat
Mass in Human Obesity: Relationship to Left Ventricular
Function and Serum Free Fatty Acid Levels
the accumulation of triglyceride in and around the
myocardium of moderately obese individuals is significant,
and it is related to
• FFA exposure,
• generalized ectopic fat excess, and
• peripheral vascular resistance.
These changes precede LV overload and hypertrophy.

20. Measurement of myocardial triglyceride content by localized MRS. Left, Cine 4-chamber cardiac
image. In this image, heart muscle appears dark gray; blood in myocardial chambers and
pericardial and adipose fat appear light gray. The volume for testing myocardial triglyceride
content is placed within the intraventricular septum (yellow rectangle). Right, Spectrum from
myocardial tissue collected during simultaneous end expiration and end systole with respiratory
gating and ECGguided triggering. RA indicates right atrium; LA, left atrium; and RV, right
ventricle.
Jonathan M. McGavock, PhD; Ildiko Lingvay, MD, MPH; Ivana Zib, MD; Tommy Tillery, BSc;
Naomi Salas, BSc; Roger Unger, MD; Benjamin D. Levine, MD; Philip Raskin, MD;
Ronald G. Victor, MD; Lidia S. Szczepaniak, PhD. Cardiac Steatosis in Diabetes Mellitus. A 1H-
Magnetic Resonance Spectroscopy Study. Circulation. 2007;116:1170-1175
Myocardial Triglyceride content in Diabetes Mellitus
TYPE-2 DIABETES MELLITUS

21. Myocardial steatosis in IGT and T2D in humans. Myocardial triglyceride is higher in
individuals with IGT and T2D (DM-2) vs lean individuals (*P0.01).
Jonathan M. McGavock, PhD; Ildiko Lingvay, MD, MPH; Ivana Zib, MD; Tommy Tillery, BSc;
Naomi Salas, BSc; Roger Unger, MD; Benjamin D. Levine, MD; Philip Raskin, MD;
Ronald G. Victor, MD; Lidia S. Szczepaniak, PhD. Cardiac Steatosis in Diabetes Mellitus. A
1H-Magnetic Resonance Spectroscopy Study. Circulation. 2007;116:1170-1175
Myocardial Triglyceride content in Diabetes Mellitus
1H-Magnetic Resonance Spectroscopy Study

22. Common metabolic variables are poor predictors of myocardial triglyceride in
humans. Neither hepatic triglyceride (r0.3, P0.01; A) nor serum triglycerides (r0.55,
P0.22; B) provide adequate estimates of myocardial triglyceride in humans.
Jonathan M. McGavock, PhD; Ildiko Lingvay, MD, MPH; Ivana Zib, MD; Tommy Tillery, BSc, Naomi Salas,
BSc; Roger Unger, MD; Benjamin D. Levine, MD; Philip Raskin, MD; Ronald G. Victor, MD; Lidia S.
Szczepaniak, PhD. Cardiac Steatosis in Diabetes Mellitus. A 1H-Magnetic Resonance Spectroscopy Study.
Circulation. 2007;116:1170-1175
Myocardial Triglyceride contentin Diabetes Mellitus
1H-Magnetic Resonance Spectroscopy Study

23. Representative cardiac 13C images,
obtained from a healthy person,
displayed as colour overlays on top
of greyscale anatomical images in a
mid-left ventricle (LV) slice from two
subjects.
The [1-13C]pyruvate substrate was seen
mainly in the blood pool within the
cardiac chambers (a,d). Flux of pyruvate
through the pyruvate dehydrogenase
complex (PDC) is reflected in the 13C-
bicarbonate images (b,e), with signal
predominantly in the wall of the LV.
The [1-13C]lactate signal (c,f) appeared
with a diffuse distribution covering the
muscle and chambers. Reproduced from
[14] with permissions from the authors
and publisher.
Jonathan M. McGavock, PhD; Ildiko Lingvay, MD, MPH; Ivana Zib, MD; Tommy Tillery, BSc; Naomi Salas, BSc; Roger
Unger, MD; Benjamin D. Levine, MD; Philip Raskin, MD; Ronald G. Victor, MD; Lidia S. Szczepaniak, PhD. Cardiac
Steatosis in Diabetes Mellitus. A 1H-Magnetic Resonance Spectroscopy Study. Circulation. 2007;116:1170-1175
Myocardial Triglyceride content in Diabetes Mellitus
1H-Magnetic Resonance Spectroscopy Study

24. Jonathan M. McGavock, PhD; Ildiko Lingvay, MD, MPH; Ivana Zib, MD; Tommy Tillery, BSc; Naomi Salas,
BSc; Roger Unger, MD; Benjamin D. Levine, MD; Philip Raskin, MD; Ronald G. Victor, MD; Lidia S.
Szczepaniak, PhD. Cardiac Steatosis in Diabetes Mellitus. A 1H-Magnetic Resonance Spectroscopy Study.
Circulation. 2007;116:1170-1175
In vivo data showing hyperpolarized pyruvate, its downstream metabolites (bicarbonate, lactate, pyruvate hydrate
and alanine) and urea in the rat heart.
Each set of images corresponds to one combination of perfusion and metabolic state. Images are shown with either no flow
encoding (top row) or flow sensitization (bottom row). The images are cropped to a 27 × 27 mm2 field of view.
Reproduced from [36] with permissions from the authors and publisher.
Myocardial Triglyceride content in Diabetes Mellitus
1H-Magnetic Resonance Spectroscopy Study

25. In humans, impaired glucose tolerance is accompanied by
cardiac steatosis,
which precedes
• the onset of type 2 diabetes mellitus and
• left ventricular systolic dysfunction.
Thus, lipid overstorage in human cardiac myocytes is an
• early manifestation in the pathogenesis of type 2 diabetes
mellitus and
• is evident in the absence of heart failure.
Myocardial Triglyceride content in Diabetes Mellitus
1H-Magnetic Resonance Spectroscopy Study

26. Grigorios Korosoglou, MD, Dimitrios Oikonomou, MD, Sebastian J. Buss, MD, Angelika Bierhaus, PhD, Per
M. Humpert, MD, Nael F. Osman, PhD, Henning Steen, MD, Peter P. Nawroth, MD, Johannes Ahrens, MS,
Gitsios Gitsioudis, MD, Bernhardt Schnackenburg, PhD, and Hugo A. Katus, MD. Left Ventricular Diastolic
Function in Type 2 Diabetes Mellitus Is Associated With Myocardial Triglyceride Content But Not With Impaired
Myocardial Perfusion Reserve. J MAGNETIC RESONANCE IMAGING 2012; 35:804–811.
Left Ventricular Diastolic Function in Type 2 Diabetes Mellitus
Is Associated With Myocardial Triglyceride Content
But Not With Impaired Myocardial Perfusion Reserve
Figure 2. Type 2 diabetes mellitus
patient with normal systolic LV-
function (ejection fraction of 62%)
(a,b), but impaired diastolic
relaxation by SENC (normal peak
systolic strain in all segments of
19%, but reduced mean diastolic
strain rate of 42/s), (c,d), relative
triglyceride content of 1.1% (e–g)
and diminished mean myocardial
perfusion reserve index of 1.5 (h–j).
TYPE-2 DIABETES MELLITUS

27. Left Ventricular Diastolic Function in Type 2 Diabetes Mellitus
Is Associated With Myocardial Triglyceride Content
But Not With Impaired Myocardial Perfusion Reserve
Grigorios Korosoglou, MD, Dimitrios Oikonomou, MD, Sebastian J. Buss, MD, Angelika Bierhaus, PhD, Per
M. Humpert, MD, Nael F. Osman, PhD, Henning Steen, MD, Peter P. Nawroth, MD, Johannes Ahrens, MS,
Gitsios Gitsioudis, MD, Bernhardt Schnackenburg, PhD, and Hugo A. Katus, MD. Left Ventricular Diastolic
Function in Type 2 Diabetes Mellitus Is Associated With Myocardial Triglyceride Content But Not With Impaired
Myocardial Perfusion Reserve. J MAGNETIC RESONANCE IMAGING 2012; 35:804–811.
TYPE-2 DIABETES MELLITUS

28. Myocardial Steatosis may represent
• an early marker of diabetic heart disease,
• triggering subclinical myocardial dysfunction
• irrespective of myocardial perfusion reserve.
Left Ventricular Diastolic Function in Type 2 Diabetes Mellitus
Is Associated With Myocardial Triglyceride Content
But Not With Impaired Myocardial Perfusion Reserve
Grigorios Korosoglou, MD, Dimitrios Oikonomou, MD, Sebastian J. Buss, MD, Angelika Bierhaus, PhD, Per
M. Humpert, MD, Nael F. Osman, PhD, Henning Steen, MD, Peter P. Nawroth, MD, Johannes Ahrens, MS,
Gitsios Gitsioudis, MD, Bernhardt Schnackenburg, PhD, and Hugo A. Katus, MD. Left Ventricular Diastolic
Function in Type 2 Diabetes Mellitus Is Associated With Myocardial Triglyceride Content But Not With Impaired
Myocardial Perfusion Reserve. J MAGNETIC RESONANCE IMAGING 2012; 35:804–811.
TYPE-2 DIABETES MELLITUS

29. Foetal Metabolic Profile :
Beating Heart utilizes Carbohydrate (Glucose & Lactate) as Primary Source of
Energy
Source of Energy in HEART FAILURE
Adult Metabolic Profile :
Beating Heart utilizes Fatty Acid as Primary Source of Energy
Adult with Heart Failure  Foetal Metabolic Profile :
Beating Heart utilizes Carbohydrate (Glucose & Lactate) as Primary Source of
Energy
Hossein Ardehali, Hani N. Sabbah, Michael A. Burke, Satyam Sarma, Peter P. Liu,
John G.F. Cleland, Aldo Maggioni, Gregg C. Fonarow, E. Dale Abel,Umberto
Campia, and Mihai Gheorghiade. Targeting myocardial substrate metabolism in heart
failure: potential for new therapies. Eur J Heart Fail (2012) 14, 120–129.
HEART FAILURE

30. HEART FAILURE
Hossein Ardehali, Hani N. Sabbah, Michael A. Burke, Satyam Sarma, Peter P. Liu, John
G.F. Cleland, Aldo Maggioni, Gregg C. Fonarow, E. Dale Abel,Umberto Campia, and
Mihai Gheorghiade. Targeting myocardial substrate metabolism in heart failure: potential for
new therapies. Eur J Heart Fail (2012) 14, 120–129.
Figure 1 Cardiac metabolism and defects in heart failure. Under normal conditions,
cardiomyocytes mostly utilize free fatty acids as their primary substrate. However, with pressure
overload and heart failure, cardiomyocytes switch substrate preference to glucose. There is also
decreased activity of fatty acid b-oxidation, tricarboxylic acid (TCA) cycle enzymes, and
complexes involved in the electron transport chain (ETC) in heart failure. Red arrows show
defects in cellular metabolism in heart failure. For more details, please refer to the text.

31. HEART FAILRE
Hossein Ardehali, Hani N. Sabbah, Michael A. Burke, Satyam Sarma, Peter P. Liu, John G.F. Cleland, Aldo
Maggioni, Gregg C. Fonarow, E. Dale Abel,Umberto Campia, and Mihai Gheorghiade. Targeting myocardial
substrate metabolism in heart failure: potential for new therapies. Eur J Heart Fail (2012) 14, 120–129.
Figure 2 Insulin resistance in heart failure
leads to decreased glucose uptake by
cardiomyocytes via decreased translocation of
GLUT4 to the sarcolemma. Fewer GLUT4
transporters result in decreased glucose flux
into the myocyte. Strategies to augment
glucose metabolism in heart failure include
increasing glucose uptake and oxidation by
the cardiomyocyte. Administration of
exogenous insulin may increase GLUT4
transporter translocation. In addition, GLP-1
has been shown to increase GLUT1
translocation from intracellular vesicles to the
plasma membrane. Glucose oxidation can be
increased by blocking the inhibitory effects of
PDK on PDH. Increased PDH activity allows
for increased oxidation of pyruvate into acetyl-
CoA which can enter the citric acid cycle to
generate ATP. A-CoA, acetyl-CoA; DCA,
dichloroacetate; ER, endoplasmic reticulum;
GLP-1, glucagon-like peptide-1; GLUT4,
glucose transporter type 4; IR, insulin
receptor; MITO, mitochondria; PDH, pyruvate
dehyrdogenase; PDK, pyruvate
dehydrogenase kinase.

32. Fig. 1 Myocardial CMR spectroscopy. A 2 × 2 ×
1-cm 3 spectroscopic volume was acquired
from the interventricular septum during the
systolic phase (left upper inset) to generate an
input spectrum (left lower inset).
1H-CMR spectra were fitted and analyzed using
the LC Model software (Provencher, Ontario,
CA, USA). We quantified the total myocardial
TG resonance as well as its components –
including fatty acids (FA, lipid resonances d 0.9,
1.3, and 1.6 ppm) and unsaturated fatty acids
(UFA, lipid resonance d 2.1 and 2.3, 2.8, 5.3
ppm). TMA, trimethyl amide
Pen-An Liao, Lan-Yan Yang, Gigin Lin, Min-Hui Liu, Shang-Yueh Tsai, Tsun-Ching Chang, Chao-Hung Wang, Yu-Chun Lin,
Yu-Hsiang Juan, Yu-Chieh Huang, Jiun-Jie Wang,, Yu-Ching Lin, Pei-Ching Huang, Ming-Ting Wu , Shu-Hang Ng and
Koon-Kwan Ng. Myocardial triglyceride content at 3 T cardiovascular magnetic resonance and left ventricular systolic function: a
crosssectional study in patients hospitalized with acute heart failure. J Cardiovasc Magnetic Reson (2016) 18:9/
Myocardial triglyceride content in acute heart failure
ACUTE HEART FAILURE

33. Myocardial triglyceride content in acute heart failure
Pen-An Liao, Lan-Yan Yang, Gigin Lin, Min-Hui Liu, Shang-Yueh Tsai, Tsun-Ching Chang, Chao-Hung Wang, Yu-Chun Lin,
Yu-Hsiang Juan, Yu-Chieh Huang, Jiun-Jie Wang,, Yu-Ching Lin, Pei-Ching Huang, Ming-Ting Wu , Shu-Hang Ng and Koon-
Kwan Ng. Myocardial triglyceride content at 3 T cardiovascular magnetic resonance and left ventricular systolic function: a
crosssectional study in patients hospitalized with acute heart failure. J Cardiovasc Magnetic Reson (2016) 18:9/
ACUTE HEART FAILURE

34. As compared with controls, patients who
were discharged after hospitalization for
ACUTE HEART FAILURE had
1.Increased myocardial UFA content;
2.UFA was inversely related with LVEF, LV
mass and, to a lesser extent, LVEDV.
Myocardial triglyceride content in acute heart failure
ACUTE HEART FAILURE

35. Cardiac Metabolic Imaging
I. Conventional Cardiac Metabolic MRI
II. Hyperpolarized Cardiac Metabolic MRI

36. Hyperpolarized Cardiac Metabolic MRI / MRS
Based on DNP (Dynamic Nuclear Polarization) Technique
There were 4 approach to generate
hyperpolarization :
1. Brute Force Polarization
2. Optical Pumping of Noble Gas
3. Parahydrogen-induced Polarization (PHIP)
4. Dynamic Nuclear Polarization (DNP)
Metabolic Tracers :
• 13C : [1-13C]pyruvate; [2-13C]pyruvate.
• 15N

37. Hyperpolarized (DNP) Cardiac Metabolic MRI
Tracer :
• 13C
• N
Label :
• 13C-Pyruvate : [2-13C]pyruvate ; [1-13C]pyruvate
• 13C-Butyrate

38. The DNP process. (A) Tracer Sample (13C pyruvate in this example) is placed in a strong magnetic field with a radical
source of electrons (B). The sample is cooled to very low temperatures (C) resulting in high electron polarization.
Microwaves are used to transfer the spin polarization from electrons to the tracer (D). The tracer is rapidly melted
for injection (E).
Oliver J Rider and Damian J Tyler . Clinical Implications of Cardiac Hyperpolarized Magnetic
Resonance Imaging J Cardiovasc Magnetic Resonance 2013, 15:93
Technics of Cardiac Metabolic MRI / MRS
Hyperpolarized (DNP) Cardiac Metabolic MRI / MRS
1 K = - 272.15o C

39. Technics of Cardiac Metabolic MRI
Hyperpolarized (DNP) Cardiac Metabolic MRI / MRS
A, At thermal equilibrium, when magnetic resonance (MR)–
active nuclei are placed in a magnetic field, spins that
align parallel to the magnet field have a slightly lower
energy than spins that align antiparallel to it. The energy
advantage obtained by aligning parallel to the magnetic
field causes slightly more spins to
point in that direction; ie, it causes a net polarization,
which results in the production of MR signal. However,
thermal equilibrium polarization is extremely low (on the
order of only 0.0005%), and this translates directly into
low MR signals.
B, By forcing most spins to point in the same direction,
dynamic nuclear polarization (DNP) achieves polarization
levels of 20%, which translates into an equivalent 10 000-
fold increase in MR signal.
C, To achieve DNP, MR-active nuclei such as 13C are
mixed with a low concentration of free electrons, and the
sample is irradiated with microwaves in a high magnetic
field (3 T) and at low temperatures (1K). The
hyperpolarizer system (left) also allows sample dissolution
to temporarily maintain the high signal in solutions with a
physiological temperature and pH for injection.
Marie A. Schroeder, DPhil; Kieran Clarke, PhD; Stefan Neubauer, MD, FRCP, FMedSci; Damian J. Tyler, PhD/
Hyperpolarized Magnetic Resonance A Novel Technique for the In Vivo Assessment of Cardiovascular Disease. Circulation.
2011;124:1580-1594

40. Metabolic pathways interrogated according to 13C labelled position, blue C2 position, red C1 position. (A) [1-
13C]pyruvate spectrum showing conversion to lactate, pyruvate hydrate, alanine and bicarbonate and (B) Example
spectra acquired in the first 60s following [2-13C]pyruvate infusion in the in vivo rat heart. [2-13C]pyruvate is
observed at 207.8 ppm. Peaks from (1) [5-13C]glutamate, (2) [1-13C]citrate, (3) [1-13C]acetylcarnitine, (4) [1-
13C]pyruvate, (5) [2-13C]lactate & (6) [2-13C]alanine can be seen.
Oliver J Rider and Damian J Tyler . Clinical Implications of Cardiac Hyperpolarized Magnetic
Resonance Imaging J Cardiovasc Magnetic Resonance 2013, 15:93
Metabolic pathways interrogated according to 13C labelled position

41. Representative spectrum acquired from a rat heart in vivo after infusion of hyperpolarized [2-
13C]pyruvate. Bioscience Reports (2017) 37 BSR20160186 DOI: 10.1042/BSR20160186
This metabolic tracer has enabled in vivo assessment of first-pass TCA cycle dynamics. CAT indicates carnitine
acetyltransferase; CS, citrate synthase; ICDH, isocitrate dehydrogenase; OMC, oxoglutarate–malate carrier and
aKDH, a-ketoglutarate dehydrogenase. Reproduced from [12] with permissions from the authors and publisher.
Marie Schroeder and Christoffer Laustsen. Imaging oxygen metabolism with hyperpolarized
magnetic resonance: a novel approach for the examination of cardiac and renal function/
Bioscience Reports (2017) 37 BSR20160186
Assessment of first-pass TCA cycle dynamics

42. Figure 2. The metabolic pathways that have been studied with hyperpolarized 13C-labeled metabolic tracers and have the potential to
be diagnostic targets for cardiovascular disease. LDH indicates lactate dehydrogenase; AAT, alanine aminotransferase; CA, carbonic
anhydrase; CAT, carnitine acetyltransferase; GDH, glutamate dehydrogenase; and PDH, pyruvate dehydrogenase.
Metabolic pathways interrogated according to 13C labelled position
Marie A. Schroeder, DPhil; Kieran Clarke, PhD; Stefan Neubauer, MD, FRCP, FMedSci; Damian J. Tyler, PhD/
Hyperpolarized Magnetic Resonance A Novel Technique for the In Vivo Assessment of Cardiovascular Disease.
Circulation. 2011;124:1580-1594

43. Marie A. Schroeder, DPhil; Kieran Clarke, PhD; Stefan Neubauer, MD, FRCP, FMedSci; Damian J. Tyler, PhD/
Hyperpolarized Magnetic Resonance A Novel Technique for the In Vivo Assessment of Cardiovascular Disease.
Circulation. 2011;124:1580-1594
Figure 7. In vivo data acquired with a multislice cardiac-gated sequence showing spatial distribution of
metabolites in a short-axis view of the healthy pig heart. Bicarbonate, lactate, and pyruvate volumes were
acquired over 9 heartbeats, and the sequence was repeated for 3 time points. Data were acquired with a
surface coil, resulting in higher signal detection from the anterior wall of the myocardiumimages is 8.88.8
mm 2 in plane with a 1-cm slice thickness.
The entire scan was completed within 18 seconds. The data acquired compared with the posterior wall. The
resolution of the overlaid reconstructed with this novel pulse sequence illustrate the increasingly high spatial
and temporal resolution with which cardiac 13C metabolic images can be acquired. Furthermore, images of
pyruvate in the blood pool can be used for normalization of myocardial metabolite signals (ie, bicarbonate).
Reprinted from Lau et al with permission of the publisher. Copyright © 2010, John Wiley and Sons Inc.
Sequence of Metabolic Imaging in Normal Pig Heart

44. Figure 6. Proton images, semiquantitative gadolinium perfusion maps, and late gadolinium enhancement (LGE) images,
together with [1-13C]alanine and 13C-bicarbonate metabolic maps, obtained in a pig after a 15-minute and a 45-minute
occlusion of the left circumflex artery. The perfusion and metabolic maps have been superimposed on the proton image.
These images indicate the potential of Hyperpolarized 13C magnetic resonance imaging to demonstrate myocardial viability in
patients with ischemic heart disease. After 15 minutes of occlusion, thecombination of preserved [1-13C]alanine production
with a regional defect in 13C-bicarbonate production confirmed the presence of “stunned ” but viable myocardium (as
determined by assessment of wall motion with proton cine magnetic resonance imaging). After 45 minutes of occlusion,
defects in both the [1-13C]alanine and a region of nonviable myocardium, as indicated by perfusion imaging and LGE.
Reprinted from Golman et al/ 13C-bicarbonate metabolic maps correlated with permission of the publisher. Copyright ©
2008, John Wiley and Sons Inc.
Marie A. Schroeder, DPhil; Kieran Clarke, PhD; Stefan Neubauer, MD, FRCP, FMedSci; Damian J. Tyler, PhD/
Hyperpolarized Magnetic Resonance A Novel Technique for the In Vivo Assessment of Cardiovascular Disease.
Circulation. 2011;124:1580-1594
Myocardial Perfusion & Metabolic Imaging after LAD Occlusion
LAD Occlusion in Animal

45. Dual-gated short axis images in an animal exhibiting
infarcted myocardium following 60-min LAD occlusion.
Images are shown at baseline, 45-min post-reperfusion,
and 1-week postreperfusion of the occluded artery. The
color scale represents the image intensity, normalized by
the maximum LV pyruvate signal intensity.
Delayed enhancement revealed an enhancing
anteroseptal infarct near the apex (arrows). Anteroseptal
akinesis was present at the 45-min time point, persisting
at 1 week. Apparent PDH flux in the bicarbonate images
was reduced at 45 min, remaining suppressed at 1 week.
A defect in myocardial lactate signal was observed in the
infarct region (arrows), with elevated lactate in the peri-
infarct region. (Reproduced with permission Magn Reson
Med. 2013 Apr;69(4 ):1063–71).
Oliver J Rider and Damian J Tyler . Clinical Implications of Cardiac
Hyperpolarized Magnetic Resonance Imaging J Cardiovasc Magnetic
Resonance 2013, 15:93
Animal with LAD Occlusion
LAD Occlusion in Animal

46. Hyperpolarized [1-13C]pyruvate CMR
showing alterations to pyruvate
dehydrogenase complex (PDC) flux and
[13C]lactate production with the
pathogenesis of dilated cardiomyopathy
(DCM).
(A) Representative pyruvate (Pyr, top),
bicarbonate (Bic, middle), and lactate (Lac,
bottom) 13C CMR images taken from the same
pig and at weekly intervals during the pacing
protocol, until DCM developed.
The images displayed for each metabolite
were selected from the same, mid-papillary
slice and in the same respiratory cycle. Signal
intensity in the pyruvate image was scaled
based on 15–100% of the maximum pyruvate
signal at week 0, whereas the bicarbonate
and lactate signal intensities were scaled
based on 15–100% of the maximum
bicarbonate signal intensity at week 0.
(B) Relative changes to PDC flux with DCM in
five pigs.
(Reproduced with permission Eur J Heart Fail.
2013 February; 15(2): 130–140).
Oliver J Rider and Damian J Tyler . Clinical Implications of Cardiac
Hyperpolarized Magnetic Resonance Imaging J Cardiovasc Magnetic
Resonance 2013, 15:93
Hyperpolarized [1-13C]pyruvate CMR in
Dilated Cardiomyopathy (DCM) in Pig.
DILATED CARDIOMYOPATHY in Animal

47. Hyperpolarized [1-13C]pyruvate CMR in
Dilated Cardiomyopathy (DCM) in Pig.
DILATED CARDIOMYOPATHY in Animal

50. What Are Electromagnetic Waves?
• If electrons are moving in a wire, say a radio transmitting
antenna, they will set up changing electric fields.
• Changing electric fields set up magnetic fields. These
magnetic fields set up changing electric fields.
• Electric and magnetic fields oscillate and propagate
through space. They form an electromagnetic wave.
• visible light (and its color), ultraviolet light, infrared light,
radio waves, X-rays, or gamma ray

51. sequences
• Spin echo- Black Blood
refocussing RF pulse,
still image& excellent tissue contrast,longer time
• Gradient echo-Bright Blood
Refocussing gradients
Cine images,faster less tissue contrast
Perfusion,scar ,coronary imaging
Cine imaging-B`SSFP-Steady state freee precesssion,excellent
tissue contrast insensitive to blood accurate EF&Volumes
FLASH- FAST LOW ANGLE SHOT- abnormal perfused remain
dark,normal perfusion shows gadolinium increased intensity

52. Coronal MRI shows aorta, av, lv
(can eval for stenosis and regurg)
Spin echo “black blood”
anatomy
Gradient echo “white blood”
function & flow

53. Tissue Phase Mapping
Regional Tissue Contractility
3D Velocities: Radial, circumferential,
longitudinal
Petersen S et al, Radiology 2005

54. Delayed-enhancement short-axis
Tissue Phase Mapping
Bulls eye Plot
• Bull’s-eye plot

55. Wall thickening analysis of short-axis cine MR images
infarction left anterior descending artery.
• (a) Delayed-enhancement short-axis
Transmural hyperenhancement (arrows)
corresponds to scar tissue.
• (b) The endocardial and epicardial contours diagrammed on
the SSFP image.
Chords for measuring wall thickness are shown along the left
ventricular circumference.
• (c) Bull’s-eye plot shows the extent of wall thickening.
The smallest ring represents the apical region, and the
largest ring represents the basal region.

56. Dobutamine-Stress MR: 4-Chamber
rest 20 µg
40 µg30 µg
Nagel E et al, Circulation 1999

57. Influence of image quality
0
10
20
30
40
50
60
70
80
90
100
good / very
good
moderate
sensitivity (DSE)
specificity (DSE)
sensitivity (DSMR)
specificity (DSMR)
E. Nagel, Z Kardiol 1999

58. • High resolution anatomy
• Global / regional function
• Regional perfusion -
GdDTPA
• Viability/Oedema/Fibrosis
• Coronary Angiography
Comprehensive CMR Study

59. <10s
Perfusion
10-20 min
Infarct
[Gd]
time
“First pass” study: Time-intensity
curves
Norma
l
Ischemia/Infarct
LV Blood pool

60. Myocardial Perfusion -
Quantification
Wilke N et al. MRM
1993
• Qualitative (eyeballing)
• Semi-quantification (upslope)
→ perfusion reserve
• Absolute quantification (ml/min x g)
Rest and stress
perfusion
(i.v. Adenosine 140mg/kg x
min)

61. Regional Myocardial
Perfusion
• Sensitivity 88%
• Specificity 90%
• Diagnostic accuracy 89%
Nagel E el al. Circulation 2003
Wolff SD et al, Circulation 2004
Giang TH et al, Eur Heart J 2004

62. MR IMPACT II
(Magnetic Resonance Imaging for Myocardial Perfusion Assessment
in Coronary artery disease Trial)
A phase III multicenter, multivendor trial
comparing perfusion cardiac magnetic resonance
versus
single photon emission computed tomography
for the detection of coronary artery disease.
J. Schwitter, 1 C. Wacker, 2 N. Wilke, 3
N. Al-Saadi, 4 N. Hoebel, 5 T. Simor 6
33 centres, 1.5 Tesla, 465 patients
• Patients with chest pain undergoing coronary angiography
• CAD defined as >50% diameter stenosis in at least one
vessel with at least 2mm diameter

63. 0
0.25
0.5
0.75
1
0 0.25 0.5 0.75 1
1-Specificity
MR-IMPACT II
33 Centers – Multivendor: Dose 0.075 mmol/kg Gd-DTPA-BMA
*
Sensitivity
CardioVascular
MR Center Zurich
SPECT all
n=465
AUC: 0.65±0.03
P=0.0004
Perfusion-CMR
n=465
AUC: 0.75±0.02
gated-SPECT
n=277
AUC: 0.69±0.03
P=0.018
ungated-SPECT
n=188
AUC: 0.63±0.04
P=0.023
P=ns vs Gated

64. Delayed Enhancement
Phenomenon
Acute Myocarditis HCM: Fibrosis
Not specific for ischemic injury
M. Friedrich et al S. Petersen et al McCrohon et al Circulation 2003
DCM: Fibrosis

65. • High resolution anatomy
• Global / regional function
• Regional perfusion
• Viability/Oedema/Fibrosis
• Coronary Angiography
Comprehensive CMR Study

66. contrindications
• Pacemakers &ICDS
• Intravascular
coils,stents,filters(after
6-8wks)
• Prosthesis
• Occluder devices
• Ecg electrodes
• Cochlear implants
• Aneurysmal clips
• Foleys catheter(temp..
Sensors)

67. Thank u