Quantification of Left Ventricular Volumes and Ejection Fraction in Mice Using PET, Compared with MRI

Abstract

PET has become an important noninvasive imaging technique in cardiovascular research for the characterization of mouse models in vivo. This modality offers unique insight into biochemical changes on a molecular level, with excellent sensitivity. However, morphologic and functional changes may be of equal importance for a thorough assessment of left ventricular (LV) pathophysiology. Although echocardiography and MRI are widely considered the imaging techniques of choice for the assessment of these parameters, their use with PET considerably increases study complexity and decreases cost-and time-efficiency. In this study, a novel method for the additional quantification of LV volumes and ejection fraction (EF) from PET was evaluated using cardiac MRI as the reference method. Methods: The radiolabeled glucose derivative 18 F-FDG was injected into 33 mice (6 mice with previous permanent occlusion of the left anterior descending artery [LAD], 15 mice with a temporary 30-min occlusion of the LAD, and 12 mice without previous surgery). 18 F-FDG uptake within the LV myocardium was measured using a dedicated small-animal PET scanner. After we reconstructed the images into 16 electrocardiogram (ECG)-gated frames, we determined the LV cavity volumes in end-diastole (EDV) and end-systole (ESV) and the EF using a semiautomatic segmentation algorithm based on elastic surfaces. A 6.3-T cardiac MRI examination was performed in the same animals using an ECG-triggered and respiratory-gated multislice cine sequence. The MR images were segmented with a semiautomatic algorithm using commercially available software. Results: Overall, measurements from PET agreed well with those obtained by MRI. Mean EDV and ESV were slightly overestimated by PET (86 6 43 mL and 44 6 42 mL), compared with MRI (73 6 44 mL and 41 6 46 mL); mean (6SD) EF was similar (PET, 55 6 19 mL; MRI, 54 6 18 mL). Correlation between PET and MRI was excellent for EDV (0.97) and ESV (0.96) and good for EF (0.86). The slope of the regression line was nearly perfect for EDV (0.98) and EF (1.01) and slightly below 1 for ESV (0.90), indicating a good separation of abnormal and normal values with PET. The y-intercept was above zero for EDV (15 mL) and ESV (7 mL) and near to zero for EF (0.2%). Conclusion: The quantification of LV volumes and EF in mice with PET is both efficient and accurate. This method allows for combined molecular and functional imaging of the left ventricle within a single scan, obviating additional sophisticated MRI in many cases.

Imaging Reveals the Connection Between Spontaneous Coronary Plaque Ruptures, Atherothrombosis, and Myocardial Infarctions in HypoE/SRBI−/− Mice

“…Quantification of segmental tracer uptake and volumes of the left ventricle were performed using a contour-detection algorithm developed in-house and validated against MRI (13). Here, the left ventricle was segmented into 8 segments per short-axis plane, with 7 planes per heart, resulting in 56 segments.…”

Measuring right ventricular function in the normal and hypertensive mouse hearts using admittance-derived pressure-volume loops

“…Cardiopulmonary status, including right ventricular function, pulmonary vascular function, and right ventricular-pulmonary vascular interactions, is an important facet of health and disease. Recently, different methods for assessing left ventricular function, systemic vascular function, and the efficiency of left ventricular-systemic vascular hemodynamic interactions in mice in situ have been described (13,16,17,39,41,47,53,54,64). However, the feasibility and utility of these techniques in the right ventricle and pulmonary vasculature of mice have not been established.…”

Isochronous Assessment of Cardiac Metabolism and Function in Mice Using Hybrid PET/MRI

“…The explanation of a lower resolution as the main reason for the underestimation of LV volumes and overestimation of EF is supported when the results are compared with the results of the high-resolution scanner. However, between high-resolution PET and MR images, there are remaining discrepancies in EDV and ESV that were not observed in a previous study using a similar setup and the same contourfinding algorithm (18).…”

“…Even though most of the destruction of myocardium and subsequent structural changes have already taken place in the time between the surgery and first imaging study, as has been shown by Lutgens et al (22), residual changes may have taken place between the combined PET/MRI and the dedicated PET acquisitions. Second, the software used for MRI contour detection in the study by Stegger et al (18) was not accessible for this study, and contours were traced manually instead, leading to additional systematic deviances on the MRI side. Thus, the high-resolution PET images do not necessarily correlate with the MR images exactly as has been observed before.…”

“…Hence, the system with the PET insert can have an offset and axis flips with respect to the MRI system and a rotation caused by a possible misalignment of the axes of symmetry of the 2 scanners. Coregistration was achieved using an additional combined measurement of a rod phantom filled with 18 F. The 3D PET image dataset of the phantom was manually realigned to the MRI slices using appropriate software (AMIDE (17)), and the transformation matrix M tra was stored. The mice were scanned in 2 groups at different times, with a demounting and remounting of the insert taking place in between.…”