This Article Extract Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Pohost, G. M. Search for Related Content PubMed PubMed Citation Articles by Pohost, G. M.

(Circulation. 1995;92:9-10.)
© 1995 American Heart Association, Inc.

Articles

Is ³¹P-NMR Spectroscopic Imaging a Viable Approach to Assess Myocardial Viability?

Gerald M. Pohost, MD

From the Division of Cardiovascular Disease, the Center for Nuclear Magnetic Resonance Research and Development, and the Department of Radiology, University of Alabama at Birmingham.

Correspondence to Dr Pohost, 311-THT, UAB Station, Birmingham, AL 35294-0006.

Key Words: Editorials • spectroscopy • imaging

	Introduction

Top Introduction The Comprehensive Cardiac NMR... Problems With NMR SI... References

 
Thallium-201 imaging in its various forms (initial followed by 2- to 4-hour or 24-hour delayed imaging, initial followed by imaging after reinjection, or a "hybrid" approach using ²⁰¹Tl initially and ^99mTc-sestamibi later) is a reasonable clinical approach for assessment of myocardial perfusion and viability.^{1 2 3 4} However, other approaches that examine change in regional myocardial function during dobutamine infusion and evaluate metabolic myocardial integrity with exogenous administration of radioactive tracers also have been reported.^{5 6 7} Accordingly, one may justifiably wonder how nuclear magnetic resonance (NMR) spectroscopic imaging, another expensive, high-tech approach, might ever be used as a clinical tool for assessing myocardial viability, especially in this era of healthcare reform, managed care, and capitation.

Yabe et al⁸ report a new clinical approach for evaluating myocardial viability. The method uses ³¹P-NMR spectroscopic imaging (SI) to quantify the high-energy phosphates ATP and phosphocreatine (PCr). The use of ATP concentration as a standard for assessing myocardial viability is not new.⁹ What is new is the ability to estimate ATP and PCr concentrations clinically and noninvasively in asynergic segments of myocardium.

Wall motion abnormalities associated with ischemic heart disease may be related to myocardial scar in patients with previous myocardial infarction, an irreversible situation, or to transient ischemic dysfunction ("stunning")¹⁰ or persistent ischemic dysfunction ("hibernation").¹¹ Reversible or irreversible dysfunction can suggest the appropriate therapeutic strategy. With viable but dysfunctional myocardium, bypass graft surgery or catheterization laboratory intervention can lead to improved function and symptomatic state of the patient—or even extension of longevity. With nonviable myocardium, there is no need for intervention, since it will have no significant benefit. If dysfunction is so extensive that severe heart failure is present, the ability to assess viability can encourage beneficial coronary artery intervention if substantial myocardium is viable or cardiac transplantation if it is not.

	The Comprehensive Cardiac NMR Examination

Top Introduction The Comprehensive Cardiac NMR... Problems With NMR SI... References

 
To determine the importance of ³¹P-NMR SI as a clinical approach to viability assessment, the following points must be considered. First, despite the initial expense, NMR provides a versatile strategy to (1) assess cardiac morphology and function with high resolution without the need for an "acoustic window" or an expensive radiotracer, (2) determine myocardial perfusion with high resolution and without the need to use radioactive agents, and, potentially, (3) image the larger coronary arteries. The marriage of NMR SI measurement of ATP and PCr to assess viability could make magnetic resonance uniquely capable of a comprehensive cardiac examination, a "one-stop shop" that provides all the information that would be needed to diagnose, prognose, and provide appropriate therapeutic direction in patients with potential coronary artery disease (CAD). To obtain similar information, several noninvasive and cath lab imaging approaches would be required. Thus, NMR methods could become the diagnostic technology of choice for CAD in the reformed healthcare system.

	Problems With NMR SI as a Viability Assessment Approach

Top Introduction The Comprehensive Cardiac NMR... Problems With NMR SI... References

 
Several impediments presently exist for the application of ³¹P-NMR SI as a clinical approach for assessing myocardial viability. Some of these have been discussed by Yabe et al.⁸ (1) Abnormalities in PCr and ATP concentrations and PCr/ATP are not specific for ischemic damage or related loss of viability. Patients with cardiac allografts, adriamycin therapy, cardiomyopathy, and advanced age may show such abnormalities. (2) Specialized software and hardware are required additions to 1.5-tesla (T) NMR imaging systems to allow them to perform ³¹P spectroscopy and spectroscopic imaging. These additions can be costly. (3) While 1.5-T NMR systems are widely distributed, they are largely used for noncardiac studies, and very few imaging physicians are adequately prepared to perform myocardial metabolism studies. (4) The approaches reported by Yabe et al⁸ and others¹² are capable of interrogating only the left ventricular anterior wall and apex. Presently, the technology is unable to provide adequate ³¹P spectroscopic images of the posterior and diaphragmatic walls. (5) The time for acquisition of a ³¹P study is relatively lengthy (over 1 hour), making it impractical, at present, to couple with the other components of the comprehensive "one-stop" NMR examination. (6) It is difficult to distinguish between the myocardial and the blood pool peaks for inorganic phosphate (P_i). Visualization of the myocardial P_i peak would enhance the utility of ³¹P-NMR SI for assessing damage and indicate intracellular pH.¹² (7) The volume interrogated by ³¹P spectroscopy is limited at 1.5 T to 150 to 200 mL. Thus, as discussed by Yabe et al, both liver and/or chest wall skeletal muscle could contaminate the high-energy phosphate profile measured in myocardium. Liver has no PCr, whereas skeletal muscle has relatively high PCr. Thus, the PCr content depends on the position of the interrogated volume. It may be possible in the future with advancing technology to make improvements in each of these areas. While one solution is to use magnets with higher field strengths,¹³ this would be expensive. For example, volumes on the order of 8 mL have been used at 4.1 T to allow more precise selection of myocardium. Such an approach reduces standard deviation of the PCr/ATP from 1.8±1.0 to 1.8±0.3. Other less expensive strategies involve software and hardware modifications to existing systems.

The advantages of the ³¹P approach include (1) as demonstrated in the article by Yabe et al,⁸ the unique ability to noninvasively assess the concentration of important high-energy phosphates (ATP, PCr) (the only other approach is myocardial biopsy); (2) the lack of need to use expensive radiotracers; (3) the unique ability to assess myocardial energetics, coupled with the ability to assess morphology, function, perfusion, and, potentially, the extent of epicardial coronary artery disease, in a single system and in a single examination interval; (4) the totally noninvasive nature of the test; (5) the fact that NMR systems are widely distributed and can be upgraded to enable NMR spectroscopic imaging; and (6) the ability to make serial measurements without the cumulative effects of radioactive tracers.

Previous work by Yabe et al¹⁴ and by Weiss et al¹⁵ demonstrates reduction in the PCr/ATP during handgrip exercise–induced acute ischemia in patients with CAD, while Yabe et al in the present article use the concentrations of PCr and ATP, and PCr/ATP at rest, to characterize myocardial tissue in patients with chronic ischemic heart disease as viable or nonviable. The present article did not examine the serial changes in ³¹P spectra that occur during an acute ischemic insult. For example, in laboratory animals, the ³¹P myocardial spectrum may appear different during an acute ischemic insult than in myocardium long after the ischemic insult. Scar with mainly fibrous tissue and a low density of cells would naturally have lower concentrations of high-energy phosphates. By contrast, ischemic but viable myocardium loses its PCr—and, to a lesser extent, its ATP (and from laboratory animal studies, more dramatically, its PCr relative to its P_i). In fact, at higher magnetic fields, the severity of ischemic insult can be better assessed by loss of PCr relative to P_i. When viability is compromised acutely, ATP concentration falls dramatically. Thus, the appearance of the ³¹P spectrum is different during the acute ischemic insult versus long after the insult, in which irreversibly damaged myocardial cells and then myocardial scar are responsible for the ³¹P spectral pattern.

In conclusion, the article by Yabe et al⁸ describes and suggests the importance of ³¹P spectroscopic imaging methods to differentiate between viable and nonviable myocardium. The ³¹P-NMR spectroscopic imaging of ATP and PCr has great potential to be an important addition to our armamentarium for assessment of myocardial viability.

	Footnotes

 
The opinions expressed in this editorial are not necessarily those of the editor or of the American Heart Association.

	References

Top Introduction The Comprehensive Cardiac NMR... Problems With NMR SI... References

 

1. Akins CW, Pohost GM, DeSanctis RW, Block PC. Selection of angina-free patients with severe left ventricular dysfunction for myocardial revascularization. Am J Cardiol. 1980;46:695-700. [Medline] [Order article via Infotrieve]
   
2. Kiat H, Maddahi J, Yang L, van Train K, Daley N, Wong C, Berman DS. Late reversibility of thallium 201 myocardial tomography deficit: an accurate measure of myocardial viability. J Am Coll Cardiol. 1988;12:1456-1463. [Abstract]
   
3. Dilsizian V, Rocco TP, Freedman NMT, Leon MB, Bonow RO. Enhanced detection of ischemic but viable myocardium by the reinjection of thallium after stress-redistribution imaging. N Engl J Med. 1990;323:141-146. [Abstract]
   
4. Berman DS, Kiat H, Friedman J, Wang FP, van Train K, Matzer L, Maddahi J, Germano G. Separate acquisition rest thallium 201/stress Tc99m sestamibi dual isotope myocardial perfusion SPECT: a clinical validation study. J Am Coll Cardiol. 1993;22:1455-1464. [Abstract]
   
5. Smart SC, Sawada S, Ryan T, Segar D, Atherton L, Berkovitz K, Bourdillon PDV, Feigenbaum H. Low-dose dobutamine echocardiography detects reversible dysfunction after thrombolytic therapy of acute myocardial infarction. Circulation. 1993;88:405-415. [Abstract/Free Full Text]
   
6. Baer FM, Voth E, Schneider CA, Theissen P, Schicha H, Sechtem U. Comparison of low-dose dobutamine-gradient-echo magnetic resonance imaging and positron emission tomography with [¹⁸F] fluorodeoxyglucose in patients with chronic coronary artery disease: a functional and morphological approach to the detection of residual myocardial viability. Circulation. 1995;91:1006-1015. [Abstract/Free Full Text]
   
7. Brunken RC, Mody FV, Hawkins RA, Nienaber C, Phelps ME, Schelbert HR. Positron emission tomography detects metabolic viability in myocardium with persistent 24-hour single-photon emission computer tomography ²⁰¹Tl defects. Circulation. 1992;86:1357-1369. [Abstract/Free Full Text]
   
8. Yabe T, Mitsunami K, Inubushi T, Kinoshita M. Quantitative measurements of cardiac phosphorus metabolites in coronary artery disease by phosphorus-31 magnetic resonance spectroscopy. Circulation. 1995;92:15-23. [Abstract/Free Full Text]
   
9. Jennings RB, Reimer KA, Hill ML, Mayer SE. Total ischemia in dog hearts in vitro. Circ Res. 1981;49:892-900. [Free Full Text]
   
10. Bolli R. Myocardial `stunning' in man. Circulation. 1992;86:1671-1691. [Free Full Text]
    
11. Rahimtoola SH. The hibernating myocardium. Am Heart J. 1989;117:211-221. [Medline] [Order article via Infotrieve]
    
12. Evanochko WT, Pohost GM. Myocardial nuclear magnetic resonance spectroscopy: present and future perspectives. In: Zaret BL, Kaufman L, Berson AS, Dunn RA, eds. Frontiers in Cardiovascular Imaging. New York, NY: Raven Press; 1993:101-112.
    
13. Hetherington HP, Luney DJE, Vaughan JT, Pan JW, Ponder SL, Tschendel O, Twieg DB, Pohost GM. 3-D ³¹P spectroscopic imaging of the human heart at 4.1T. Magn Reson Med. 1995;33:427-431. [Medline] [Order article via Infotrieve]
    
14. Yabe T, Mitsunami K, Okada M, Morikawa S, Inabushi T, Kinoshita M. Detection of myocardial ischemia by magnetic resonance spectroscopy during handgrip exercise. Circulation. 1994;89:1709-1716. [Abstract/Free Full Text]
    
15. Weiss RG, Bottomley PA, Hardy CJ, Gerstenblith G. Regional myocardial metabolism of high energy phosphates during isometric exercise in patients with coronary artery disease. N Engl J Med. 1990;323:1593-1600.[Abstract]
    

This article has been cited by other articles:

				M. Saeed New Concepts in Characterization of Ischemically Injured Myocardium by MRI Experimental Biology and Medicine, May 1, 2001; 226(5): 367 - 376. [Abstract] [Full Text]

				P. A. Bottomley and R. G. Weiss Noninvasive Localized MR Quantification of Creatine Kinase Metabolites in Normal and Infarcted Canine Myocardium Radiology, May 1, 2001; 219(2): 411 - 418. [Abstract] [Full Text]

				G. M. Pohost and R. W. W. Biederman The Role of Cardiac MRI Stress Testing : "Make a Better Mouse Trap ... " Circulation, October 19, 1999; 100(16): 1676 - 1679. [Full Text] [PDF]

This Article Extract Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Pohost, G. M. Search for Related Content PubMed PubMed Citation Articles by Pohost, G. M.