BackgroundThe aim of this study was to develop and validate an automated method for extracting forward stroke volume (FSV) using indicator dilution theory directly from dynamic positron emission tomography (PET) studies for two different tracers and scanners.Methods35 subjects underwent a dynamic 11C-acetate PET scan on a Siemens Biograph TruePoint-64 PET/CT (scanner I). In addition, 10 subjects underwent both dynamic 15O-water PET and 11C-acetate PET scans on a GE Discovery-ST PET/CT (scanner II). The left ventricular (LV)-aortic time-activity curve (TAC) was extracted automatically from PET data using cluster analysis. The first-pass peak was isolated by automatic extrapolation of the downslope of the TAC. FSV was calculated as the injected dose divided by the product of heart rate and the area under the curve of the first-pass peak. Gold standard FSV was measured using phase-contrast cardiovascular magnetic resonance (CMR).ResultsFSVPET correlated highly with FSVCMR (r = 0.87, slope = 0.90 for scanner I, r = 0.87, slope = 1.65, and r = 0.85, slope = 1.69 for scanner II for 15O-water and 11C-acetate, respectively) although a systematic bias was observed for both scanners (p < 0.001 for all). FSV based on 11C-acetate and 15O-water correlated highly (r = 0.99, slope = 1.03) with no significant difference between FSV estimates (p = 0.14).ConclusionsFSV can be obtained automatically using dynamic PET/CT and cluster analysis. Results are almost identical for 11C-acetate and 15O-water. A scanner-dependent bias was observed, and a scanner calibration factor is required for multi-scanner studies. Generalization of the method to other tracers and scanners requires further validation.

Subjects with asymptomatic moderate-to-severe or severe primary mitral regurgitation are closely observed for signs of progression or symptoms requiring surgical intervention. The role of myocardial metabolic function in progression of mitral regurgitation is poorly understood. We used 11 C-acetate PET to noninvasively measure myocardial mechanical external efficiency (MEE), which is the energetic ratio of external cardiac work and left ventricular (LV) oxygen consumption. Methods: Forty-seven patients in surveillance with mitral regurgitation and no or minimal symptoms prospectively underwent PET, echocardiography, and cardiac MRI on the same day. PET was used to simultaneously measure cardiac output, LV mass, and oxygen consumption to establish MEE. PET findings were compared between patients and healthy volunteers (n 5 9). MEE and standard imaging indicators of regurgitation severity, LV volumes, and function were studied as predictors of time to surgical intervention. Patients were followed a median of 3.0 y (interquartile range, 2.0-3.8 y), and the endpoint was reached in 22 subjects (47%). Results: MEE in patients reaching the endpoint (23.8% 6 5.0%) was lower than in censored patients (28.5% 6 4.5%, P 5 0.002) or healthy volunteers (30.1% 6 4.9%, P 5 0.001). MEE with a cutoff lower than 25.7% was significantly associated with the outcome (hazard ratio, 7.5; 95% CI, 2.7-20.6; P , 0.0001) and retained independent significance when compared with standard imaging parameters. Conclusion: MEE independently predicted time to progression requiring valve surgery in patients with asymptomatic moderate-to-severe or severe primary mitral regurgitation. The study suggests that inefficient myocardial oxidative metabolism precedes clinically observed progression in mitral regurgitation.

Background Quantitative echocardiographic assessment of severity of primary mitral regurgitation (MR) is challenging. CMR is recommended if MR severity cannot be clearly determined, since quantitation of regurgitation as well as of left ventricular (LV) volumes and function is crucial for the indication for surgery especially in asymptomatic patients. Purpose We aimed to compare volumetric measurements obtained from transthoracic echo (TTE) and cardiovascular magnetic resonance (CMR) using ECG-gated [(11)C]acetate PET as reference for assessment of LV volumes. Methods A total of 51 asymptomatic patients with severe primary mitral regurgitation underwent TTE, CMR and PET on the same day. Mitral regurgitant volumes (RVol) were measured by TTE using proximal convergence (PISA) method and by CMR, subtracting aortic forward flow volume from LV stroke volume. LV volumes were measured by TTE, CMR and PET. Results Despite a fair correlation between regurgitant volumes measured by TTE and CMR (r=0.53, p<0.001), PISA method heavily overestimated regurgitant volumes on TTE as compared to CMR (103±60ml vs. 78±35ml, p<0.001). TTE systematically underestimated LV volumes as compared to CMR (see table) despite a good correlation (r=0.81, 0.67 and 0.76 respective for LV EDV, ESV and SV, p<0.001 for all). There was no difference in LV EF between the methods. LV volumes obtained by CMR and PET showed a strong correlation (r=0.92, 0.79 and 0.89 respective for LV EDV, ESV and SV, p<0.001 for all) and agreement (see table). Comparison of TTE, CMR and PET TTE CMR PET PET TTEvs.CMR PET CMRvs.PET F-test LV EDV, ml 145±34 241±57 234±51 <0.001 0.004 <0.001 LV ESV, ml 47±11 76±22 81±23 <0.001 0.067 <0.001L LV SV, ml 99±26 164±38 152±34 <0.001 <0.001 <0.001 LV EF, % 68±5 69±5 65±6 0.236 <0.001 <0.001 Conclusions As compared to CMR, PISA method used by TTE substantially overestimates regurgitant volumes in patients with asymptomatic primary mitral regurgitation. Conversely, LV volumes in spite of good correlation are heavily underestimated by TTE in comparison with CMR. A strong correlation and agreement between LV volumes measured by CMR and PET confirms the accuracy of the former method which is considered as a golden standard for assessment of ventricular function and volumes. Thus, even so-called quantitative echo measures should be understoas essentially semi-quantitative indicators of severity.

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