Table 1 Clinical studies using oxygenation-sensitive CMR to evaluate ischemic and non-ischemic heart diseases

Studies in CAD cohorts

Wacker et al. [29]

1.5 T

T2* (ms)

N = 16 patients with single vessel CAD

• BOLD-CMR at rest and during dypiridamole stress

T2* was significantly lower in myocardial segments subtended by stenosed arteries compared to remote myocardium at rest. This difference in T2* increased during dipyridamole stress

N = 16 healthy volunteers

• Coronary angiography

Friedrich et al. [30]

1.5 T

T2* (SI)

N = 25 patients with exertional angina

• BOLD-CMR at rest and during adenosine stress

During adenosine, a mean signal intensity decrease was observed for myocardial segments related to coronary stenoses >75%. A non-significant increase was observed in the other segments. Using BOLD signal intensity increase cutoff value of 1.2%, BOLD-CMR had a sensitivity of 88% and a specificity of 47% to correctly classify severe stenoses. BOLD-CMR compared favorably with thallium SPECT

• Adenosine stress thallium SPECT

• Coronary angiography

Bernhardt et al. [33]

1.5 T

T2 (SI)

N = 46 patients with suspected CAD

• BOLD-CMR at rest and during adenosine stress

BOLD SI change was significantly lower in segments with perfusion deficits compared to patients with visually normal perfusion

• First-pass perfusion CMR at rest and during adenosine stress

Manka et al. [31]

3 T

T2* (ms)

N = 46 patients with known or suspected CAD

• BOLD-CMR at rest and during adenosine stress

BOLD CMR at rest revealed significantly lower T2* values for segments subtended by >50% stenosed vessels compared to segments subtended by non-stenosed vessels. Under adenosine T2* values increased only in normal segments

• Quantitative coronary angiography

Karamitsos et al. [32]

3 T

T2 (SI)

N = 22 patients with single or two-vessel CAD

• BOLD-CMR at rest and during adenosine stress

BOLD CMR and PET agreed on the presence or absence of ischemia in 18 of the 22 patients

N = 10 healthy volunteers

(82%) and in all normal subjects. On a per-segment analysis, 40% of myocardial segments with hypoperfusion on PET did not show deoxygenation, whereas the majority of segments with normal perfusion also had normal oxygenation.

• PET with oxygen-15 labeled water at rest and during adenosine stress

• Quantitative coronary angiography

Arnold et al. [35]

3 T

T2 (SI)

N = 25 CAD patients and N = 20 healthy volunteers (derivation arm)

• BOLD-CMR at rest and during adenosine stress

Prospective evaluation of BOLD imaging yielded an accuracy of 84%, a sensitivity of 92%, and a specificity of 72% for detecting myocardial ischemia and 86%, 92%, and 72%, respectively, for identifying significant coronary stenosis. Segment-based analysis revealed evidence of dissociation between oxygenation and perfusion (r = -0.26).

N = 60 patients with suspected CAD (prospective arm)

• First-pass perfusion CMR at rest and during adenosine stress (absolute quantification of myocardial blood flow)

• Quantitative coronary angiography

Jahnke et al. [36]

3 T

T2 (SI)

N = 50 patients with suspected or known CAD

• BOLD-CMR at rest and during adenosine stress

The ΔSI measurements differed significantly between normal myocardium, myocardium subtended by a stenosed coronary artery, and infarcted myocardium. A cutoff value of ΔSI = 2.7% resulted in a sensitivity and specificity of 85.0% and 80.5%, respectively to detect coronary artery stenosis. BOLD-ΔSI correlated significantly with the degree of coronary stenosis (r = -0.65, p < 0.001).

• First-pass perfusion CMR at rest and during adenosine stress (semi-quantitative assessment)

• Quantitative coronary angiography

Walcher et al. [37]

1.5 T

T2 (SI)

N = 36 patients with suspected CAD

• BOLD-CMR at rest and during adenosine stress

Relative BOLD SI increase was significantly lower in myocardial segments supplied by coronary arteries with an FFR ≤ 0.8 compared with segments with an FFR > 0.8

• Invasive Fractional Flow Reserve (FFR)

Studies in non-CAD cohorts

Beache et al. [39]

1.5 T

R2* (s)

N = 10 patients with hypertension

• BOLD-CMR at rest and during adenosine stress

Significantly reduced dipyridamole-induced change in the apparent transverse relaxation rate (R2*) in hypertensive patients compared to controls

N = 9 healthy volunteers

Karamitsos et al. [34]

3 T

T2 (SI)

N = 18 patients with Syndrome X

• BOLD-CMR at rest and during adenosine stress

No differences in myocardial perfusion and oxygenation between Syndrome X patients and controls

N = 14 healthy volunteers

• First-pass perfusion CMR at rest and during adenosine stress (absolute quantification of myocardial blood flow)

• Quantitative coronary angiography

Karamitsos et al. [40]

3 T

T2 (SI)

N = 27 patients with overt HCM

• BOLD-CMR at rest and during adenosine stress

MPRI was significantly reduced in HCM compared to controls and athletes, but remained normal in HCM mutation carriers without LVH. Oxygenation response was attenuated in overt HCM compared to controls and athletes. Interestingly, HCM mutation carriers without LVH also showed an impaired oxygenation response to adenosine.

N = 10 HCM mutation carriers without LVH

• First-pass perfusion CMR at rest and during adenosine stress (semi-quantitative measurement of myocardial perfusion reserve index-MPRI)

N = 11 athletes

N = 20 healthy volunteers