Heart Rate-Independent 3D Myocardial Blood Oxygen Level-Dependent MRI at 3.0 T with Simultaneous 13N-Ammonia PET Validation

Abstract

Background Despite advances, blood oxygen level-dependent (BOLD) cardiac MRI for myocardial perfusion is limited by inadequate spatial coverage, imaging speed, multiple breath holds, and imaging artifacts, particularly at 3.0 T. Purpose To develop and validate a robust, contrast agent-unenhanced, free-breathing three-dimensional (3D) cardiac MRI approach for reliably examining changes in myocardial perfusion between rest and adenosine stress. Materials and Methods A heart rate-independent, free-breathing 3D T2 mapping technique at 3.0 T that can be completed within the period of adenosine stress (≤4 minutes) was developed by using computer simulations, ex vivo heart preparations, and dogs. Studies in dogs were performed with and without coronary stenosis and validated with simultaneously acquired nitrogen 13 (13N) ammonia PET perfusion in a clinical PET/MRI system. The MRI approach was also prospectively evaluated in healthy human volunteers (from January 2017 to September 2017). Myocardial BOLD responses (MBRs) between normal and ischemic myocardium were compared with mixed model analysis. Results Dogs (n = 10; weight range, 20-25 kg; mongrel dogs) and healthy human volunteers (n = 10; age range, 22-53 years; seven men) were evaluated. In healthy dogs, T2 MRI at adenosine stress was greater than at rest (mean rest vs stress, 38.7 msec ± 2.5 [standard deviation] vs 45.4 msec ± 3.3, respectively; MBR, 1.19 ± 0.08; both, P < .001). At the same conditions, mean rest versus stress PET perfusion was 1.1 mL/mg/min ± 0.11 versus 2.3 mL/mg/min ± 0.82, respectively (P < .001); myocardial perfusion reserve (MPR) was 2.4 ± 0.82 (P < .001). The BOLD response and PET MPR were positively correlated (R = 0.67; P < .001). In dogs with coronary stenosis, perfusion anomalies were detected on the basis of MBR (normal vs ischemic, 1.09 ± 0.05 vs 1.00 ± 0.04, respectively; P < .001) and MPR (normal vs ischemic, 2.7 ± 0.08 vs 1.7 ± 1.1, respectively; P < .001). Human volunteers showed increased myocardial T2 at stress (rest vs stress, 44.5 msec ± 2.6 vs 49.0 msec ± 5.5, respectively; P = .004; MBR, 1.1 msec ± 8.08). Conclusion This three-dimensional cardiac blood oxygen level-dependent (BOLD) MRI approach overcame key limitations associated with conventional cardiac BOLD MRI by enabling whole-heart coverage within the standard duration of adenosine infusion, and increased the magnitude and reliability of BOLD contrast, which may be performed without requiring breath holds. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Almeida in this issue.

Figures

Graphical abstract

Figure 1:

Pulse diagram and reconstruction scheme for the proposed three-dimensional (3D) T2 mapping technique. A, The timing diagram. Standard T2 preparation scheme was replaced by a T2 preparation scheme composed of composite adiabatic radiofrequency pulses and spoiled gradient-echo (GRE) readout (in place of the typical balanced steady-state free precession readout) to minimize B1 and B0 artifacts at 3.0 T. A centric readout trajectory was applied to ensure optimal T2 weighting. A saturation recovery (SR) pulse preparation was added to eliminate the recovery heart beats on conventional T2 maps and the signal dependence on heart rate between segmented readouts. The respiratory motion was monitored by using a pencil-beam navigator during acquisition. The sequence was designed to permit T2 mapping with three different T2 preparation times for T2 fitting. B, Motion correction algorithm used (21). Raw data with different T2-weighted values were first combined and binned on the basis of the navigator signal to generate anatomic images from different respiratory phases. The respiratory motion was estimated from the anatomic images and applied to the raw data to reconstruct motion-corrected T2 maps by using a log-transformed linear least-squares fit as previously described (21). NAV = navigator pulse, TE = echo time, T2 Prep = T2 preparation prepulse.

Figure 2:

T2 dependence on heart rate as determined from computer simulations and ex vivo studies (n = 3). A, The theoretically expected dependence of T2 on heart rate for the two-dimensional (2D) and three-dimensional (3D) T2 mapping without saturation recovery (SR; proposed without [w/o] SR) and with SR preparation (proposed) are shown as solid lines. Experimentally measured T2 values from ex vivo hearts at the different artificially modulated heart rates are also shown in A. B, Representative regions of interest (ROI) used for the analysis are identified for reference. C, A set of representative midventricular T2 maps acquired by using the different T2 mapping approaches is shown. Underestimated T2 values under elevated heart rate (100 beats per minute [bpm]) are observed on 2D T2 maps and 3D T2 maps without SR preparation (both P < .05). The effect is eliminated with the proposed 3D T2 mapping approach (P = 1). All T2 values were compared with the T2 value measured with the baseline values. All images showed consistent image quality and similar T2 distribution. * P< .05. Exp = experimental results, Sim = simulated results.

Figure 3:

Dependence of myocardial blood oxygen level−dependent (BOLD) response (MBR) sensitivity on heart rate differences between rest and vasodilator stress (n = 10). A, Representative rest and stress T2 maps of a midventricular section obtained at two-dimensional (2D) imaging and proposed three-dimensional (3D) T2 mapping methods are shown. Myocardial T2 under stress with the proposed T2 mapping approach is much higher than T2 at rest but T2 under stress is reduced in the 2D images compared with rest.B, Myocardial blood flow (MBF), derived from PET, in the same animal; MBF is higher under stress with an myocardial perfusion reserve (MPR) larger than 2 (P = .001).C, Experimentally observed relationship between loss of apparent MBR on 2D images and heart rate (HR) increases with vasodilator stress. A strong positive correlation was observed between loss of apparent MBR and change in HR (ΔHR). Data inA and B are means ± standard deviation. bpm = beats per minute.

Figure 4:

Three-dimensional (3D) T2 maps and nitrogen 13 (13N)-ammonia PET at rest and under adenosine stress in dogs without coronary stenosis. A, Representative basal, middle, and apical short-axis images from blood oxygen level−dependent (BOLD) cardiac MRI with the proposed 3D T2 mapping approach and PET perfusion images in a dog with 13N-ammonia are shown. From images acquired by using both modalities, signal elevation can be observed on the stress images compared with the corresponding rest images (P < .001). Corresponding bull’s eye plots in the same subject are shown (myocardial BOLD response [MBR],B, and PET MBR, C). Mean BOLD response of 16% and PET myocardial perfusion reserve (MPR) of 2.3 were evident in the whole heart. MBF = myocardial blood flow.

Figure 5:

Mean blood oxygen level−dependent (BOLD) response and nitrogen 13 (13N)-ammonia PET perfusion in dogs without coronary stenosis (n = 10). A, Box and whisker plot with higher mean myocardial T2 values at adenosine stress compared with rest (rest vs stress, 39.4 msec [interquartile range, 36.6–41.4 msec] vs 44.1 msec [interquartile range, 42.6–48.3 msec], respectively; P < .001).B, A similar trend is observed with 13N-ammonia PET perfusion measurements (rest vs stress, 1.1mL/mg/min [interquartile range, 1.06–1.14 mL/mg/min] vs 2.1mL/mg/min [interquartile range, 1.74–2.33 mL/mg/min], respectively; P < .001). C, Scatterplot comparing BOLD response (on the y-axis) compared with 13N-ammonia PET myocardial perfusion reserve (MPR). Each color represents segmental measurements (points) and regressed lines (lines) from one dog. Paired t test showed significant difference in myocardial BOLD responses (MBRs) and MPRs between rest and stress (both P < .001). A repeated measure correlation analysis to examine the data trends between MBR and MPR at the segmental level. The result showed a positive correlation between MBR and MPR (R = 0.67; P < .001). MBF = myocardial blood flow.

Figure 6:

Three-dimensional T2 maps and nitrogen 13 (13N)-ammonia PET at rest and under adenosine stress in a dog with left anterior descending (LAD) coronary stenosis. A, Representative basal, middle, and apical short-axis T2 maps at rest and under stress in a dog with LAD coronary stenosis. D, The corresponding quantitative myocardial blood flow (MBF) maps determined from 13N-ammonia PET. There is close correspondence in the MBF distribution and T2 maps, particularly at adenosine stress. Specifically, the normal territories on PET images showed increased T2 values on T2 maps acquired with adenosine. Conversely, the ischemic territories on PET images (anterior wall corresponding to LAD territory; white arrows on D) showed markedly diminished increase in T2 (black arrows on A) compared with normal segments. Corresponding polar maps for, B, blood oxygen level dependent (BOLD) and, E, PET are shown. Ischemic segments identified with change analysis from QPET are labeled on the polar maps (+ on B and E). Both,C, BOLD response and, F, PET myocardial perfusion reserve (MPR) showed lower values in the ischemic territories compared with the normal segments. Mixed-model analysis showed lower myocardial BOLD response (MBR; P < .001) and MPR (P < .001) on ischemic territories.

Figure 7:

Heart rate–independent three-dimensional T2 mapping at rest and at adenosine stress in healthy human participants (n= 10). A, Representative short-axis T2 maps at rest and stress in a single participant. An increased myocardial T2 corresponding to hyperemia can be observed across all sections.B, Polar map of myocardial blood oxygen level–dependent (BOLD) response (MBR) for the T2 maps corresponding to A; the polar maps show a relatively homogenous MBR greater than 1 (across all segments). C,Plots of myocardial T2 values across human subjects at rest and stress. Paired t test showed higher myocardial T2 under stress compare with rest (stress vs rest, 47.9 msec [interquartile range, 7.1 msec] vs 44.4 msec [interquartile range, 4.4 msec], respectively;P = .004.). CMR = cardiac MRI.