Research ArticleCARDIAC IMAGING

Accurate needle-free assessment of myocardial oxygenation for ischemic heart disease in canines using magnetic resonance imaging

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Science Translational Medicine  29 May 2019:
Vol. 11, Issue 494, eaat4407
DOI: 10.1126/scitranslmed.aat4407
  • Fig. 1 Repeat stimulations and image averaging for enhancing myocardial BOLD response.

    (A) Prospective control of PaCO2. The image (left) shows the system (computer-controlled gas control, input for source gases, and disposable breathing circuit) used for prospectively modulating PaCO2. The graph (right) shows the trace of achieved PaCO2 during the scans. Light blue trace represents the targeted PETCO2, and dark blue points denote the actual PETCO2 values. Representative results in a healthy dog during repeated intermittent hypercapnia (four stimulations) are presented in (B) to (D). (B) Representative segmental BOLD response in AHA segments 1 through 6 in a healthy dog during the first four blocks of intermittent hypercapnia (four stimulations). (C) Spatial distribution of the BOLD response in the midventricular myocardium after one hypercapnic stimulation (single pair, left) and mean BOLD response after four hypercapnic stimulations (four pairs, middle). The 13N-ammonia PET response (MPR, right) was acquired simultaneously with BOLD-CMR. (D) Corresponding location of the AHA segments in a bullseye plot. Representative results in a dog with LAD coronary stenosis during repeated intermittent hypercapnia (four stimulations) are presented in (E) to (G). (E) Representative segmental BOLD response across AHA segments 1 through 6 during four blocks of intermittent hypercapnia (four stimulations) from an animal with LAD coronary stenosis. (F) Spatial maps of the BOLD response in the midventricular myocardium after one hypercapnic stimulation (left) and mean BOLD response after four hypercapnic stimulations (middle). The 13N-ammonia PET response (MPR, right) was acquired simultaneously with BOLD-CMR. (G) Corresponding location of the AHA segments in a bullseye plot. The LAD territory highlighted with a blue shade indicates the presence of coronary stenosis.

  • Fig. 2 Theoretical basis for objective assessment of myocardial BOLD response.

    Numerically simulated BOLD response according to the number of stimulations required to establish statistical significance (color-coded P values). For a given BOLD response, the number of stimulations required for reliable assessment (P < 0.05) of a change from baseline condition lies at the right of the white dotted line. For example, to reliably detect a BOLD response with a peak BOLD signal response of 10%, greater than three measurements are needed. The color bar on the right provides the scale for P values.

  • Fig. 3 Cardiac fMRI framework integrating MRI, hypercapnic stimulation, and statistical analysis.

    (A) Data acquisition framework: The approach used to acquire 3D MRI under periodic changes in PaCO2 (normocapnic and hypercapnic conditions), preceded by a short delay (stabilization period) to ensure that the acquisitions are only triggered once the desired PaCO2 values are reached. Acq, acquisition. (B) Time-efficient, free-breathing, confounder-corrected whole-heart T2 mapping. Left: The timing diagram shows a T2 preparation scheme composed of composite adiabatic RF pulses and spoiled GRE readout, used to minimize B1 and B0 artifacts at 3 T. An SR preparation was added to eliminate the signal dependence on heart rate between segmented readouts, and navigator (NAV) pulses were added to monitor the respiratory motion during acquisition. Right: The centric-encoding scheme with hybrid trajectory to ensure optimal T2 weighting. Bottom: motion-correction algorithm and T2 mapping. Respiratory motion was corrected using a previously described algorithm (36). The details of the pulse sequence development are provided in the “MRI pulse sequence development” section in the Supplementary Materials. (C) 3D myocardial BOLD response: 3D T2 maps (basal, midventricular, and apical) acquired during normocapnia and hypercapnia (single stimulation block). For reference, results from 2D imaging obtained from a midventricular slice are also shown (left column). BOLD response was computed as ((hypercapnic myocardial T2)/(normocapnia myocardial T2)) × 100%. (D) Statistical framework: A schematic of the statistical framework using repeated-measures one-way ANOVA to discriminate between registered images of myocardial segments that are or are not statistically responsive, based on the hypothesis testing outlined in text, after each repeat hypercapnic/normocapnic stimulation. The polar maps on the lower row show the AHA segmentation with P values assigned on the statistical test.

  • Fig. 4 Application of cardiac fMRI approach for reliable identification of healthy myocardium.

    (A) Myocardial statistical parametric mapping (SPM). Long- and short-axis volume rendered views of the heart with intensities denoting segmental P values derived from the statistical framework from a typical healthy dog. Bottom: polar maps of P values. (B) Myocardial SPM versus 13N-ammonia PET in a representative case. The graph (left) shows the mean and SD of P values across all segments for the case in (A) as a function of number of stimulation blocks (one through four). The image (right) shows the corresponding 13N-ammonia PET MPR. (C) Myocardial SPM versus 13N-ammonia PET MPR. Graphs show the average P values across all dogs (n = 8) and all myocardial segments after one and four stimulations (left) and the mean and scatter of MPR across all animals in response to hypercapnia (right). P values were derived from repeated-measures one-way ANOVA and P < 0.05 was used for statistical significance.

  • Fig. 5 Cardiac fMRI-based SPM for identification of myocardial segments affected by clinically relevant coronary stenosis.

    (A) Myocardial SPM under coronary stenosis. Representative images of long- and short-axis volume rendered views of the heart with intensities denoting segmental P values derived from the statistical framework from one dog with clinically important coronary stenosis. Bottom: polar maps of P values for the AHA segments. (B) Myocardial SPM versus 13N-ammonia PET for a representative case. Left: mean and SD of P values across affected and remote segments for the case in (A) as a function of number of stimulation blocks (one through four). Right: the corresponding 13N-ammonia PET MPR. (C) Myocardial SPM versus 13N-ammonia PET MPR for all cases (dogs, n = 7). Left: average response across all animals in the affected and remote myocardial segments after one and four stimulations. Right: mean and scatter of PET MPR across all animals in the remote and affected segments after hypercapnia. (D) Sensitivity, specificity, and accuracy determined after each stimulation with PET serving as the ground truth. P values were derived from repeated-measures one-way ANOVA and P < 0.05 was used for statistical significance.

Supplementary Materials

  • stm.sciencemag.org/cgi/content/full/11/494/eaat4407/DC1

    Materials and Methods

    Fig. S1. Schematic of the cardiac fMRI approach.

    Fig. S2. Imaging study protocol.

    Fig. S3. Computer simulations and ex vivo experiments.

    Table S1. Physiological parameters during normocapnia and hypercapnia.

    Data file S1. Individual subject-level data.

    References (38, 39)

  • The PDF file includes:

    • Materials and Methods
    • Fig. S1. Schematic of the cardiac fMRI approach.
    • Fig. S2. Imaging study protocol.
    • Fig. S3. Computer simulations and ex vivo experiments.
    • Table S1. Physiological parameters during normocapnia and hypercapnia.
    • References (38, 39)

    [Download PDF]

    Other Supplementary Material for this manuscript includes the following:

    • Data file S1 (Microsoft Excel format). Individual subject-level data.

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