Gated Positron Emission Tomography Research Articles

The feasibility of 18F-FDG gated positron emission tomography (PET) for left ventricular dyssynchrony assessment in comparison with 99mTc-MIBI gated single-photon emission computed tomography (SPECT) among patients with prior myocardial infarction

Phase analysis by 99mTc-MIBI gated single-photon emission computed tomography (GSPECT) has been considered to be an adequate method in the validation of left ventricular (LV) dyssynchrony. Compared with GSPECT, prior myocardial infarction patients with myocardial perfusion defects but myocardial viability usually show preserved uptake of 18F-FDG, and extensive myocardium is detected by 18F-FDG gated positron emission tomography (GPET). Thus, theoretically, it should be more accurate. The aim of this study was to investigate the feasibility of GPET for LV dyssynchrony assessment in comparison with GSPECT among infarction patients. A total of 146 patients with infarction underwent 2 consecutive days of GSPECT and GPET examinations. Quantitative gated SPECT-derived LV phase analysis was applied to GPET and GSPECT data to assess the presence of LV dyssynchrony via histogram bandwidth (BW) and phase standard deviation (SD). The correlation and agreement of BW and SD between GSPECT and GPET were examined. Factors (i.e., total perfusion defect, scar and mismatch) related to the discrepancies of LV dyssynchrony (i.e., BW and SD) in GPET and GSPECT were assessed by univariate and multivariate regression analysis. A moderate correlation between GPET and GSPECT was found in the measurements of BW (r=0.554) and SD (r=0.537). Bland-Altman analysis revealed that GPET overestimated both BW and SD (20.5° and 9.5°, respectively). In addition, the BW and SD measured by GPET were still overestimated after subgroup analysis. Between GPET and GSPECT, multivariate regression analysis revealed that total perfusion defects were related to the difference in BW measurement (P<0.001), and mismatch was associated with the difference in SD measurement (P<0.01). In patients with infarction, GPET moderately correlated with GSPECT in assessing LV dyssynchrony. GPET overestimated both BW and SD, so these analyses should not be interchangeable in individual patients.

Left Ventricular Remodeling Results in Homogenization of Myocardial Work Distribution.

The interaction between regional left ventricular (LV) myocardial work and metabolism in remodeled hearts has not yet been well established. Our aim was to investigate the effect of inhomogeneous LV work distribution on regional metabolism and remodeling in our animal model with reversible dyssynchrony due to pacing. In 12 sheep, 8 weeks of right atrial and right ventricular free wall (DDD) pacing lead to LV dilatation, a thinned septum, and thickened lateral wall. Left bundle branch block-like dyssynchrony caused by DDD pacing could be acutely reverted by right atrial pacing (AAI) only. Invasive hemodynamics and echocardiography were used to assess regional work by stress-strain loop area and compared with regional glucose metabolism measured by 18F-fluorodeoxyglucose positron emission tomography with and without improved spatial resolution by motion and anatomy correction on gated reconstructions. Glucose metabolism by positron emission tomography with anatomic correction on gated positron emission tomography reconstruction showed a different regional distribution than with clinical reconstructions and correlated best and significantly with regional myocardial work. At baseline, work was homogeneously distributed with normal conduction (AAI pacing), whereas during dyssynchrony (DDD pacing), the lateral wall was more loaded, and the septum was unloaded. After 8 weeks of remodeling under DDD pacing, however, an almost homogeneous work distribution was found with DDD pacing, whereas with AAI pacing, the thin septum showed exaggerated loading and the lateral walls a low load. Our experimental observations were confirmed in 5 patient responders to cardiac resynchronization therapy. Regional LV glucose metabolism closely correlates with regional work. Our data indicate that regionally different LV remodeling after exposure to inhomogeneous loading conditions, such as during LV dyssynchrony, is an adaptive process that helps to equilibrate work distribution. Correction of the inhomogeneous loading conditions, such as during cardiac resynchronization therapy, then triggers a reverse LV remodeling through the same mechanism.

The impact of respiratory gated positron emission tomography on clinical staging and management of patients with lung cancer

Respiratory motion artefacts during positron emission tomography (PET) deteriorate image quality, potentially introducing diagnostic uncertainties. The objective of this study was to determine the impact of optimal respiratory gating on clinical staging and management of patients with primary lung cancer. From our fast-track outpatient diagnostic program, 55 patients with primary lung cancer, who underwent whole body [(18)F]-fluorodeoxyglucose (FDG) PET, were included. Respiratory gating was performed on bed positions covering the thorax and abdomen. Independent reading was conducted by two nuclear medicine physicians. The observers scored the number and anatomical location of the lesions, lymph node basins and the presence of distant metastasis in non-gated and gated images. A tumor (T), lymph node (N), and metastasis (M) stage was assigned to each patient according to the 7th revision of the TNM classification. Staging accuracy was determined using histopathological data and follow-up CT imaging. In addition, a management plan was created for each patient based on non-gated and gated images by an experienced pulmonologist. For nuclear medicine physician 1 and 2, respiratory gating resulted in detection of more lesions in five and eight patients (9% and 15%) respectively. However, this did not result in any migration in T or M-stage. Migration in N-stage was observed in four and seven patients (7% and 13%) for nuclear medicine physician 1 and 2 respectively. Staging accuracy was slightly improved when respiratory gating was performed. Furthermore, there was substantial agreement in patient management between non-gated and gated images. Respiratory gating improved staging accuracy, mainly in assessment of lymph node involvement. However, the effect on patient management was limited due to the presence of already advanced disease stage in many patients. These findings suggest that the expected impact of respiratory gating will be solely on management of patients with early disease.

Respiratory gated PET/CT of the liver: A novel method and its impact on the detection of colorectal liver metastases

PurposeTo evaluate the diagnostic performance of a new method for respiratory gated positron emission tomography (rgPET/CT) for colorectal liver metastases (CRLM), secondly, to assess its additional value to standard PET/CT (PET/CT). Materials and methodsForty-three patients scheduled for resection of suspected CRLM were prospectively included from September 2011 to January 2013. None of the patients had previously undergone treatment for their CRLM. All patients underwent PET/CT and rgPET/CT in the same session. For rgPET/CT an in-house developed electronic circuit was used which displayed a color-coded countdown for the patient. The patients held their breath according to the countdown and only the data from the inspiration breath-hold period was used for image reconstruction. Two independent and blinded readers evaluated both PET/CT and rgPET/CT separately. The reference standard was histopathological confirmation for 73 out of 131 CRLM and follow-up otherwise. ResultsReference standard identified 131 CRLM in 39/43 patients. Nine patients accounted for 25 mucinous CRLM. The overall per-lesion sensitivity for detection of CRLM was for PET/CT 60.0%, for rgPET/CT 63.1%, and for standard+rgPET/CT 67.7%, respectively. Standard+rgPET/CT was overall significantly more sensitive for CRLM compared to PET/CT (p=0.002) and rgPET/CT (p=0.031). The overall positive predictive value (PPV) for detection of CRLM was for PET/CT 97.5%, for rgPET/CT 95.3%, and for standard+rgPET/CT 93.6%, respectively. ConclusionCombination of PET/CT and rgPET/CT improved the sensitivity significantly for CRLM. However, high patient compliance is mandatory to achieve optimal performance and further improvements are needed to overcome these limitations. The diagnostic performance of the evaluated new method for rgPET/CT was comparable to earlier reported technically more complex and expensive methods.

Evaluation of respiratory and cardiac motion correction schemes in dual gated PET/CT cardiac imaging.

Cardiac imaging suffers from both respiratory and cardiac motion. One of the proposed solutions involves double gated acquisitions. Although such an approach may lead to both respiratory and cardiac motion compensation there are issues associated with (a) the combination of data from cardiac and respiratory motion bins, and (b) poor statistical quality images as a result of using only part of the acquired data. The main objective of this work was to evaluate different schemes of combining binned data in order to identify the best strategy to reconstruct motion free cardiac images from dual gated positron emission tomography (PET) acquisitions. A digital phantom study as well as seven human studies were used in this evaluation. PET data were acquired in list mode (LM). A real-time position management system and an electrocardiogram device were used to provide the respiratory and cardiac motion triggers registered within the LM file. Acquired data were subsequently binned considering four and six cardiac gates, or the diastole only in combination with eight respiratory amplitude gates. PET images were corrected for attenuation, but no randoms nor scatter corrections were included. Reconstructed images from each of the bins considered above were subsequently used in combination with an affine or an elastic registration algorithm to derive transformation parameters allowing the combination of all acquired data in a particular position in the cardiac and respiratory cycles. Images were assessed in terms of signal-to-noise ratio (SNR), contrast, image profile, coefficient-of-variation (COV), and relative difference of the recovered activity concentration. Regardless of the considered motion compensation strategy, the nonrigid motion model performed better than the affine model, leading to higher SNR and contrast combined with a lower COV. Nevertheless, when compensating for respiration only, no statistically significant differences were observed in the performance of the two motion models considered. Superior image SNR and contrast were seen using the affine respiratory motion model in combination with the diastole cardiac bin in comparison to the use of the whole cardiac cycle. In contrast, when simultaneously correcting for cardiac beating and respiration, the elastic respiratory motion model outperformed the affine model. In this context, four cardiac bins associated with eight respiratory amplitude bins seemed to be adequate. Considering the compensation of respiratory motion effects only, both affine and elastic based approaches led to an accurate resizing and positioning of the myocardium. The use of the diastolic phase combined with an affine model based respiratory motion correction may therefore be a simple approach leading to significant quality improvements in cardiac PET imaging. However, the best performance was obtained with the combined correction for both cardiac and respiratory movements considering all the dual-gated bins independently through the use of an elastic model based motion compensation.

Enhanced [18F]fluorodeoxyglucose accumulation in the right ventricular free wall predicts long-term prognosis of patients with pulmonary hypertension: a preliminary observational study

We have previously demonstrated that [(18)F]fluorodeoxyglucose (FDG) accumulation is increased in the right ventricular (RV) free wall of patients with pulmonary hypertension (PH), and that this accumulation is ameliorated after the treatment with epoprostenol associated with improvement of haemodynamic overload. The aim of this study was to examine whether enhanced RV FDG accumulation by gated positron emission tomography (PET) has a prognostic impact in patients with PH. We examined the prognostic impact of the RV standardized uptake value (SUV) of FDG-PET corrected for the partial volume effect (cRV-SUV) in 27 patients with PH who underwent gated FDG-PET from March 2001 to June 2004. During the follow-up period of 69 ± 49 (mean ± SD) months, among the 27 patients, 15 showed clinical worsening (CW) and 11 died. FDG-PET examination showed that cRV-SUV was significantly higher in the CW group compared with the non-CW group (10.1 vs. 7.6, P = 0.02). Univariate Cox hazard analysis showed that cRV-SUV was significantly correlated with the time to CW (hazard ratio 1.25, 95% confidence interval 1.04-1.51, P = 0.02), which remained significant even after adjustment of World Health Organization functional class. Kaplan-Meier analysis showed that the patients with cRV-SUV ≥8.3 had poor prognosis compared with those with cRV-SUV <8.3 (log-rank P = 0.005 for time to CW and P = 0.07 for mortality). These results indicate that enhanced FDG accumulation in the RV free wall may be a novel prognostic factor in patients with PH.

Electrocardiographically gated 11C-hydroxyephedrine PET for the simultaneous assessment of cardiac sympathetic and contractile functions

Application of the electrocardiographically (ECG) gated positron emission tomography (PET) technique with (11)C-hydroxyephedrine (HED) would allow the simultaneous assessment of cardiac sympathetic and contractile functions. However, there are uncertainties regarding the diagnostic accuracy of left ventricular (LV) volume measurements using ECG-gated HED-PET. The purpose of this study was to clarify the minimal requirement of count statistics to measure LV volumes with ECG-gated HED-PET and to investigate the reliability of the measurements. Five healthy volunteers and 11 patients with heart failure underwent a 40-min list-mode PET scan after an injection of HED (197 ± 35 MBq). The list-mode data were histogrammed into multiple sets of acquisition periods at 0.5, 1.0, 2.0, 4.0, 6.0, 8.0, 12.0 Mcount/bin and reconstructed into corresponding gated images using an iterative algorithm. The LV end-diastolic volume (LVEDV), the LV end-systolic volume (LVESV), and the LV ejection fraction (LVEF) were calculated in each acquisition period. These values were compared with those obtained by cardiac magnetic resonance imaging (MRI). Possible effects of HED retention on the accuracy of the volume measurements were investigated. Collecting less than 4.0 Mcount/bin resulted in noisy cardiac images. The lower counts resulted in underestimation in the volume measurements. Reasonably accurate volume measurements required equal to or greater than 6.0 Mcount/bin. This corresponded to 7.0 ± 1.9 min (range, 4.0-10.3 min) for the acquisition period. Volumetric results using the 6.0 Mcount/bin data highly correlated with cardiac MRI (LVEDV: r = 0.85, p < 0.0001; LVESV: r = 0.89, p < 0.0001; LVEF: r = 0.77, p < 0.01). The HED retention did not affect the volumetric results compared to the MRI volumetry. The volumetric accuracy with ECG-gated HED-PET was affected by the count statistics rather than the HED retention. LV volume measurements were feasible with 10-min acquisition period for most of the patients. This technique allows the simultaneous assessment of cardiac sympathetic and contractile functions without the need for an additional injection or scanning time, thus reducing overall costs for diagnostic imaging.

Enhanced [18F]fluorodeoxyglucose accumulation in the right ventricular free wall predicts long-term prognosis of patients with pulmonary hypertension

Background: We have previously demonstrated that [18F]fluorodeoxyglucose (FDG) accumulation evaluated by ECG gated positron emission tomography (PET) is increased in the right ventricular (RV) free wall of patients with pulmonary hypertension (PH) and that this accumulation is ameliorated after medical therapy associated with hemodynamic improvement. However, it remains to be examined whether RV FDG accumulation has a prognostic significance in patients with PH. Methods and results: From March 2001 to June 2004, we performed gated FDG-PET in 27 patients with PH, including 18 with pulmonary arterial hypertension and 9 with chronic thromboembolic pulmonary hypertension. We examined baseline clinical parameters, invasive hemodynamic data, imaging data with cardiac MR, electron beam CT and FDG-PET quantified by calculating standardized uptake value (SUV) and corrected for partial volume effect based on the RV free wall thickness, the composite primary endpoint defined as all-cause mortality, lung transplantation, hospitalization for progression of PH and deterioration of NYHA functional class and/or >15% reduction in 6-min walk distance (6MWD) from baseline, and all-cause mortality as the second endpoint. During the mean follow-up period of 66 months, 15 patients reached the composite primary endpoint, including all-cause mortality in 4, lung transplantation in 1, hospitalization for PH progression in 9, deterioration of NYHA functional class and/or >15% reduction in 6MWD from baseline in 1 and death in 11 (41%). In FDG-PET measurements, corrected RV free wall SUV was significantly increased in the endpoint group compared with the no endpoint group (10.1±2.7 vs. 7.6±2.2, P=0.02). Univariate COX hazard analysis showed that the corrected RV SUV of FDG was significantly correlated with the composite endpoint (hazard ratio 1.25, 95% confidence interval 1.04-1.51, P=0.04). This relationship remained significant even after adjustment for NYHA functional class or 6MWD. In Kaplan-Meier analysis for the composite primary endpoint, patients with a corrected RV SUV of FDGSUV ≥8.5 had a significantly poor prognosis compared with those with <8.5 (log-rank P=0.005 for the composite endpoint, P=0.07 for all-cause mortality). Furthermore, the corrected RV SUV of FDG at 3months after epoprostenol treatment could predict survival in patients with PAH better than the reduction in pulmonary vascular resistance by ≥30% (log-rank P=0.02, P=0.34, respectively). Conclusions: These results indicate that enhanced FDG accumulation in the RV is a useful prognostic factor in patients with PH.

Preclinical evaluation of carbon-11 and fluorine-18 sulfonamide derivatives for in vivo radiolabeling of erythrocytes.

BackgroundTo date, few PET tracers for in vivo labeling of red blood cells (RBCs) are available. In this study, we report the radiosynthesis and in vitro and in vivo evaluation of 11C and 18F sulfonamide derivatives targeting carbonic anhydrase II (CA II), a metallo-enzyme expressed in RBCs, as potential blood pool tracers. A proof-of-concept in vivo imaging study was performed to demonstrate the feasibility to assess cardiac function and volumes using electrocardiogram (ECG)-gated positron emission tomography (PET) acquisition in comparison with cine magnetic resonance imaging (cMRI) in rats and a pig model of myocardial infarction.MethodsThe inhibition constants (Ki) of CA II were determined in vitro for the different compounds by assaying CA-catalyzed CO2 hydration activity. Binding to human RBCs was estimated after in vitro incubation of the compounds with whole blood. Biodistribution studies were performed to evaluate tracer kinetics in NMRI mice. ECG-gated PET acquisition was performed in Wistar rats at rest and during pharmacological stress by infusing dobutamine at 10 μg/kg/min and in a pig model of myocardial infarction. Left ventricular ejection fraction (LVEF) and volumes were compared with values from cMRI.ResultsThe Ki of the investigated compounds for human CA II was found to be in the range of 8 to 422 nM. The fraction of radioactivity associated with RBCs was found to be ≥90% at 10- and 60-min incubation of tracers with heparinized human blood at room temperature for all tracers studied. Biodistribution studies in mice indicated that 30% to 67% of the injected dose was retained in the blood pool at 60 min post injection. A rapid and sustained tracer uptake in the heart region with an average standardized uptake value of 2.5 was observed from micro-PET images. The LVEF values obtained after pharmacological stress in rats closely matched between the cMRI and micro-PET values, whereas at rest, a larger variation between LVEF values obtained by both techniques was observed. In the pig model, a good agreement was observed between PET and MRI for quantification of left ventricular volumes and ejection fraction.ConclusionsThe 11C and 18F sulfonamide derivatives can be used for efficient in vivo radiolabeling of RBCs, and proof-of-concept in vivo imaging studies have shown the feasibility and potential of these novel tracers to assess cardiac function.

Prognostic Impact of Enhanced [18F]Fluorodeoxyglucose Accumulation in the Right Ventricular Free Wall in Patients with Pulmonary Hypertension

We have previously demonstrated that [18F]fluorodeoxyglucose (FDG) accumulation evaluated by gated positron emission tomography (PET) is increased in the right ventricular (RV) free wall of patients with pulmonary hypertension (PH). However, it remains to be examined whether RV FDG accumulation has a prognostic significance in patients with PH.

Association of left ventricular mechanical dyssynchrony with survival benefit from revascularization: a study of gated positron emission tomography in patients with ischemic LV dysfunction and narrow QRS

LV mechanical dyssynchrony (LVMD) is a risk marker in narrow QRS cardiomyopathy, but its association with treatment outcome is not well defined. We determined the incremental prognostic value of LVMD in ischemic cardiomyopathy, and assessed its interaction with scar, myocardium in jeopardy and subsequent revascularization. Stress and rest (82)Rb gated PET were performed in 486 consecutive patients (66 ± 11 years of age, 82 % men, LV ejection fraction 26 ± 6 %) with ischemic cardiomyopathy and QRS <120 ms. LVMD was determined as the standard deviation (SD) of the regional time to minimum volume on phase analysis of the gated PET scan. A propensity score was determined to adjust for nonrandomized referral after imaging to coronary artery bypass grafting (CABG). In a Cox proportional hazards model used to determine the association between measures of LVMD and survival time, CABG was included as a time-dependent covariate and the use of an implantable cardiac defibrillator (ICD) after imaging was modeled as a stratification factor. Over 1.9 ± 1.4 years, 96 patients (20 %) underwent CABG and 108 (22 %) died. LVMD was a predictor of mortality (HR 1.16. 95 % CI 1.03;1.30, per 10° increase in phase SD, p = 0.02) after adjusting for baseline covariates, prior ICD use, the use of postimaging CABG, and other imaging data. There was a significant interaction between phase SD and CABG. Nested Cox models showed that LVMD carried prognostic information incremental to clinical variables, ejection fraction and CABG. LVMD is an independent predictor of all-cause mortality in ischemic cardiomyopathy, and may identify patients with a differential survival benefit from CABG versus medical therapy.

Effect of stress testing on left ventricular mechanical synchrony by phase analysis of gated positron emission tomography in patients with normal myocardial perfusion

There are limited data on whether differences exist in left ventricular (LV) mechanical dyssynchrony indices derived from stress versus rest gated positron emission tomography (PET) in patients with normal myocardial perfusion imaging (MPI). Stress/rest (82)Rb gated PET was performed in consecutive patients with normal MPI between 2006 and 2010. Patients were divided into two groups: group 1 [LV ejection fraction (EF) ≥ 55% and QRS < 120 ms] and group 2 (LVEF ≤35%). Images were acquired on a dedicated PET scanner prior to and on a hybrid PET/CT system after November 2008. LV dyssynchrony indices [phase standard deviation (SD)° and SD (ms)] were derived from stress and rest gated images. There were 91 patients in group 1 (age 61 ± 13, LVEF 66 ± 8%, normal QRS) and 126 in group 2 (age 66 ± 12, LVEF 25 ± 7%). The stress derived LVEF were significantly higher than rest for either group (p < 0.0001). Patients with cardiomyopathy had significantly higher dyssynchrony indices compared to those with normal LVEF (rest SD° 49.2 ± 21.5° vs 16.8 ± 7.8° and stress SD° 42.5 ± 19.4° vs 12.4 ± 3.7°, respectively, p < 0.0001 for both). The dyssynchrony indices derived from rest gated images were significantly higher than those derived from stress in both groups (p < 0.001 by unpaired and paired t test) and irrespective of the type of PET scanner utilized. Finally, 20/87 (23%) patients with normal LVEF and 27/66 (41%) of those with cardiomyopathy but without dyssynchrony based on stress indices were recategorized as having significant dyssynchrony given their resting indices. LV mechanical dyssynchrony indices by phase analysis are smaller when derived from peak stress versus rest gated PET imaging in patients with normal MPI, irrespective of the resting LVEF.

Acipimox-enhanced 18F-fluorodeoxyglucose positron emission tomography for characterizing and predicting early remodeling in the rat infarct model

The rat myocardial infarction (MI) model is widely used to study left ventricular (LV) remodeling. In this study, acipimox-enhanced (18)F-Fluorodeoxyglucose (FDG) gated-positron emission tomography (PET) was assessed for characterizing and predicting early remodeling in the rat infarct model. Nineteen Wistar rats had surgical occlusion of the left anterior descending coronary artery and 7 were sham-operated. PET was scheduled 48 h and 2 weeks later for quantifying MI area and LV function. Segments with <50% of FDG uptake had histological evidence of MI (74 ± 9% decrease in parietal thickness, fibrosis development). At 48 h, MI area was large (>35% of LV) in 6 rats, moderate (15-35% of LV) in 8 rats, limited (<15% of LV) in 5 rats and absent in the 7 sham rats. LV remodeling, assessed through the 2 weeks increase in end-diastolic volume, increased between rats with limited, moderate and large MI (+72 ± 25, +109 ± 56, +190 ± 69 μl, respectively, P = 0.007). This 3-groups classification allowed predicting 44% of the 2 weeks increase in end-diastolic volume, and additional 34% were predicted by heart rate at 48 h. The acipimox-enhanced FDG gated-PET technique provides efficient characterization and prediction of early remodeling in the rat infarct model.

Abstract 8091: Left Ventricular Mechanical Dyssynchrony to Distinguish Hibernating versus Scarred Myocardium in Patients with Cardiomyopathy Undergoing Gated Positron Emission Tomography

Background: We sought to determine whether left ventricular (LV) mechanical dyssynchrony can differentiate predominately hibernating versus scarred myocardium in patients with ischemic cardiomyopathy (ICM) on gated positron emission tomography (PET). Methods and Results: Stress/rest rubidium-82 gated PET with 18 FDG scan performed on consecutive patients with ICM and LV ejection fraction (EF) ≤35% were analyzed. Of 254 patients (age 65±11 years, QRS 108±10 ms, and LVEF 25±6), 25 (10%) had normal rest perfusion, and 229 had a fixed resting perfusion defect (77 (34%) with ≥ 50% hibernating defect (82±21% hibernation) (Group 1) and 152 (66%) with &gt;50% scar (8±12% hibernation) (Group2)). Patients in Group 1 had smaller fixed PDS, more ischemia, and similar LVEF and volumes to those in Group 2. Dyssynchrony indices were derived using Corridor 4DM software (figure 1). Phase SD was lowest in patients with normal perfusion, higher in Group 1, and highest in Group 2 (Figure 2). Using ROC analysis, a phase SD ms cut-off of 120 ms had a 75% specificity to distinguish predominately scarred versus hibernating myocardium (AUC 0.60 [0.52-0.68], P=0.015). By linear regression analysis, phase SD≥120 ms (beta =0.13 [95%CI 0.01;0.25]), implantable cardiac defibrillator (0.23 [0.096;0.36]), beta blockers (-0.17[-0.31;-0.025]), fixed PDS (0.046[0.013;0.079] per 10% increase), and reversible PDS (-0.036[-0.067;-0.005] per 10% increase) were independently associated with predicting scar verus hibernation. Conclusion: PET LV dyssynchrony analysis can potentially distinguish predominately hibernating from scarred myocardium.

Left ventricular dyssynchrony assessment by phase analysis from gated PET-FDG scans

BackgroundThe outcome of patients with severe ischaemic left ventricular (LV) dysfunction is determined by the extent of myocardial viability and the presence of LV dyssynchrony. We aimed at assessing both parameters from the same imaging method, i.e. gated positron emission tomography (PET) F18-fluorodeoxyglucose (FDG) scans. MethodsPhase analysis from Emory Cardiac Toolbox was applied on gated PET-FDG scans to assess histogram bandwidth and standard deviation (SD) as a measure of LV dyssynchrony in 30 heart failure patients (mean ejection fraction: 30.2% ± 13.8%) referred for the evaluation of myocardial viability. Cut-off values from single-photon emission computed tomography myocardial perfusion imaging (SPECT-MPI) best predicting cardiac resynchronization therapy (CRT) response served as standard of reference (bandwidth < 135°; phase SD < 43°). Severe LV dyssynchrony was diagnosed if both SPECT-MPI values were above these limits. Intraclass correlation and clinical agreement in detection of severe LV dyssynchrony by PET vs SPECT were assessed. ResultsThere was a significant correlation between PET-FDG and SPECT-MPI for bandwidth (r = 0.88, P < .001) and phase SD (r = 0.88, P < .001) resulting in an excellent clinical agreement between the two methods of 93%. ConclusionsAccurate LV dyssynchrony assessment by phase analysis of gated PET-FDG scans is feasible, allowing assessing myocardial viability and severe LV dyssynchrony in one scan.

Joint Reconstruction of Image and Motion in Gated Positron Emission Tomography

We present a novel intrinsic method for joint reconstruction of both image and motion in positron emission tomography (PET). Intrinsic motion compensation methods exclusively work on the measured data, without any external motion measurements. Most of these methods separate image from motion estimation: They use deformable image registration/optical flow techniques in order to estimate the motion from individually reconstructed gates. Then, the image is estimated based on this motion information. With these methods, a main problem lies in the motion estimation step, which is based on the noisy gated frames. The more noise is present, the more inaccurate the image registration becomes. As we show both visually and quantitatively, joint reconstruction using a simple deformation field motion model can compete with state-of-the-art image registration methods which use robust multilevel B-spline motion models.

Image-Derived Input Function from Cardiac Gated Maximum a Posteriori Reconstructed PET Images in Mice

The purpose of this study was to determine if accurate image-derived input functions (IDIF) can be measured from cardiac gated positron emission tomography (PET) images reconstructed using ordered subset expectation maximization-maximum a posteriori (OSEM-MAP) without further correction. IDIFs from the left ventricle were measured from cardiac gated PET images reconstructed using OSEM-MAP with computed tomography (CT)-based attenuation correction for five C57/BL6 mice. The accuracy of the IDIF was tested against blood samples using Bland-Altman analysis. Image-derived blood radioactivity concentration values were not significantly different from sampled blood values at two late time points as determined by a paired t test (P = 0.97). Bland-Altman analysis revealed a mean difference of 0.06 μCi/ml (1%). Using kinetic analysis, the mean myocardial 2-deoxy-2-[(18)F]fluoro-D-glucose uptake rate constant based on the IDIF was comparable to values reported in the literature based on physical blood sampling. Accurate IDIFs can be obtained non-invasively. Although reconstruction times are increased, no further spillover corrections are necessary for IDIFs derived from gated, OSEM-MAP reconstructed images with attenuation correction.

Transient left ventricular dysfunction syndrome: Patho-physiological bases through nuclear medicine imaging

Takotsubo cardiomyopathy (TTC) is a novel heart disease, mimicking acute myocardial infarction. The term "transient left ventricular dysfunction syndrome" (TLVDS) seems to be more appropriate since variant forms of TTC sparing apical segments (mid-ventricular ballooning syndrome (MVBS) and inverted TTC) have been described. Patho-physiological bases of TLVDS remain poorly understood and its optimal management is until now empirical. Our aim was to characterize patho-physiological mechanisms of TLVDS by means of nuclear medicine procedures and to discuss the clinical usefulness of isotopic imaging for a non-invasive diagnosis of TLVDS. During the sub acute phase, eighteen patients with TLVDS (13 TTC and 5 MVBS) underwent myocardial (99m)Tc-tetrofosmin or (201)Thallium Gated Single Photon Emission Computed Tomography (G-SPECT) (n=11), (123)I-mIBG SPECT (n=8) and (18)F-FDG Gated Positron Emission Tomography (G-PET) (n=15), assessing respectively LV perfusion, sympathetic innervation and glucose metabolism. Hypocontractile LV segments were characterized by normal perfusion but reduced uptake of (18)F-FDG and (123)I-mIBG. Topography and extent of metabolic defects and innervation abnormalities were largely overlapping. Follow-up (123)I-mIBG SPECT and (18)F-FDG G-PET were performed in selected patients showing rapid normalization of LV motion and progressive improvement of both glucose metabolism and sympathetic innervation. With the hypothesis of neurogenic stunned myocardium as the central causative mechanism of TLVDS, (123)I-mIBG SPECT seems to be the most specific diagnostic technique. Sympathetic function and glucose metabolism seem to be strictly correlated in the hypocontractile LV segments. Finally, our results underline the role of nuclear imaging in the setting of patho-physiological mechanisms of TLVDS.

Dual cardiac–respiratory gated PET: implementation and results from a feasibility study

Spatial resolution in myocardial imaging is impaired by both cardiac and respiratory motion owing to motional blurring. We investigated the feasibility of a dual cardiac-respiratory gated positron emission tomography (PET) acquisition using a clinical PET/computer tomography (CT) scanner. We describe its implementation and present results on the respiratory motion observed. The correlation between diaphragmatic excursion measured by real-time magnetic resonance imaging (MRI) and the expansion of the chest measured with an elastic belt was studied in six subjects. PET list mode acquisitions were then performed in 12 patients, six of them injected with 13N-ammonia and six with 18F-FDG. In parallel, the ECG and respiratory signals of the patients were recorded and the list mode file correspondingly sorted using a dual gated approach. Respiratory motion of the heart was quantified by measuring the displacement between the inspiratory and expiratory images in the diastolic phase by means of intensity-based non-rigid image registration. The correlation between diaphragmatic excursion and expansion of the chest was excellent (R2=0.91), validating the ability of the elastic belt to provide an adequate respiratory trigger. Respiratory signals corresponding to the chest expansion showed a large inter-patient variability, requiring adapted algorithms in order to define suitable respiratory gates. Dual gated PET series were successfully acquired for both groups of patients, showing better resolved myocardial walls. The average respiratory motion of the heart measured by PET was 4.8 mm, with its largest component in the craniocaudal direction. Moreover, a deformation of the heart with respiration was observed, with the inferior wall moving significantly more than the anterior. Dual gated cardiac PET studies were performed successfully and showed better resolved myocardial walls as compared with ungated acquisitions. The respiratory motion of the heart presented a significant elastic component and was of the same magnitude as the spatial resolution of current PET cameras.

Myocardial blood flow and oxygen consumption in patients with Friedreich's ataxia prior to the onset of cardiomyopathy

We tested the hypothesis, in patients with Friedreich's ataxia and no overt structural heart disease, that impairment of cardiac oxidative metabolism may be compensated for either by increased rest myocardial blood flow or more efficient oxygen consumption in performance of external work. Friedreich's ataxia is characterized by a mutant frataxin gene, which causes mitochondrial iron overload and impaired energy production. Further, it is frequently associated with cardiomyopathy. Studies using magnetic resonance spectroscopy, however, suggest impaired cardiac energetics even in the absence of structural heart disease. Positron emission tomography measured rest myocardial blood flow (N-13-ammonia method) and myocardial oxygen consumption (11-C-acetate, Kmono) in Friedreich's ataxia patients (n=8; 31+/-5 years, mean+/-SD, four women) and healthy controls (n=8; 30+/-7 years, five women) matched for stroke work index and age. Stroke work index and power were determined by electrocardiogram gated positron emission tomography N-13-ammonia using modified Simpson's rule to compute left ventricular volumes. Neither stroke work index nor rest myocardial blood flow differed significantly between the groups. Although myocardial oxygen consumption was lower in Friedreich's ataxia (P<0.001), Kmono/rest myocardial blood flow, an index of myocardial oxygen extraction, did not differ between the groups. Power/Kmono, an index of the efficiency of myocardial oxygen consumption, was greater in Friedreich's ataxia (P<0.04). Rest myocardial blood flow normalized to rate pressure product was lower in Friedreich's ataxia (P<0.05). Prior to the onset of cardiomyopathy, selected patients with Friedreich's ataxia may compensate for impaired cardiac energetics through more efficient oxygen consumption rather than increased rest myocardial blood flow. The data illustrate a more general mechanism pertaining to metabolic regulation of myocardial blood flow and myocardial oxygen consumption.