BCS Editorial: Quantifying myocardial perfusion using cardiac MRI– the future of ischaemia imaging?

In the setting of stable coronary artery disease, the demonstration of ischaemia prior to revascularisation is prognostically useful [1] and guideline mandated [2].
Objective ischaemia can be demonstrated invasively and non invasively, the latter across a range of imaging modalities. Currently, the majority of large trial data has focused on nuclear imaging, with stress echo represented to a lesser degree. Notably, the ongoing CE-MARC2 study will redress the imbalance and likely demonstrate the utility of stress cardiac MRI (CMR) in this setting [3].
CMR first pass perfusion for the assessment of ischaemia is attractive because it is non invasive, non toxic, and offers a high degree of spatial resolution when compared to PET for example. However, current clinically used assessment methods rely largely on visual assessment of the myocardial signal difference between normal and abnormal areas. In the vast majority of cases, this is sufficient, but there are situations when this is a limitation, for example in the detection of three vessel disease or abnormalities in the microcirculation.

It is in these situations where quantitative perfusion assessments may help. The gold standard for quantitative perfusion assessment is PET, enabling the assessment of myocardial blood flow (MBF) in mls per gm per minute. It is validated for both flow limiting epicardial stenoses and microvascular abnormalities. MPR is a ratio of peak blood flow at stress to that at rest. Importantly, in coronary artery disease, PET derived myocardial perfusion reserve (MPR) is linearly related to the severity of coronary artery disease and is an independent predictor of outcome [4].

There is an emerging body of work from multiple centres that CMR is also able to offer robust assessments of quantitative perfusion. The lower cost, wider availability and better spatial resolution compared to PET make this a potentially attractive prospect.
The overall technique of quantitative perfusion is similar to current techniques in that a contrast agent (usually Gadolinium) is injected peripherally during vasodilator induced stress and (usually, but not always) repeated at rest. In non quantitative assessments the passage of contrast from the ventricular blood pool through the myocardium in stress is then observed visually. In quantitative assessments, additional data is collected on blood enhancement data and then through complex mathematical processes, absolute quantification is generated, enabling definition of a transmural endo- to epi- cardial perfusion gradient in ml/g/min.

However, it is the variation in the complex mathematical processes involved in quantification that have so far limited its clinical uptake. Although a small study involving only 18 subjects, there has been a notable recent attempt to demystify this [5] and validate the measurements against PET.

Overall there have been few direct comparison studies between CMR and PET, and only one direct 3 way comparison between quantitative CMR, PET and coronary angiography in a coronary artery disease population [6]. They demonstrated in 41 patients that similar MPR values in PET and CMR give comparable sensitivities and specificities in the prediction of significant coronary artery disease (MPR PET <1.44 mls/g/min = sensitivity 82%, specificity 87%; MPR CMR <1.45mls/g/min = sensitivity 82%, specificity 81%). Notably, the absolute values had limited agreement between the two modalities, suggesting that direct comparisons of absolute values would be flawed.

There are significant limitations of CMR quantitative perfusion. There is currently only moderate inter-study reproducibility, the post processing analysis is very time consuming and there are still considerable technical factors that require standardisation and optimisation. One of the major limitations however is that there is currently no long term outcome data on the prognostic significance of pixel level measurements of myocardial blood flow as assessed by CMR.
Nevertheless, these issues can all potentially be addressed and CMR quantitative perfusion offers the future potential of being able to resolve a transmural perfusion gradient, which will be particularly valuable in identification of areas of myocardium at risk as well as providing clarity for borderline cases and offering huge research potential into the pathophysiology of a variety of cardiotoxic insults.

References

1. Shaw LJ, Berman DS, Maron DJ et al. Optimal Medical Therapy With or Without Percutaneous Coronary Intervention to Reduce Ischemic Burden. Results From the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) Trial Nuclear Substudy. Circulation 2008; 117: 1283-1291.
2. 2013 ESC guidelines on the management of stable coronary artery disease. The Task Force on the management of stable coronary artery disease of the European Society of Cardiology. Eur Heart J 2013;34:2949–3003
3. http://clinicaltrials.gov/show/NCT01664858
4. B.A. Herzog, L. Husmann, I. Valenta et al.Long-term prognostic value of 13N-ammonia myocardial perfusion positron emission tomography: added value of coronary flow reserve. J Am Coll Cardiol 2009; 54: 150–156
5. Miller CA, Naish JH, Ainslie MP et al. Voxel-wise quantification of myocardial blood flow with cardiovascular magnetic resonance: effect of variations in methodology and validation with positron emission tomography. Journal of Cardiovascular Magnetic Resonance 2014; 16:11
6. Morton G, Chiribiri A, Ishida et al. Quantification of absolute myocardial perfusion in patients with coronary artery disease. JACC 2012; 60: 1546-1555.

For those trainees who are interested in learning more about cardiac MRI, BCS offers a free online training course to all trainee BCS members via http://www.bcs.com/pages/page_box_contents.asp?navcatID=770&PageID=770. This course can also be used to demonstrate competency in core cardiac MRI.