Wei Fang

Heterogeneity in Lung 18 FDG Uptake in Pulmonary Arterial Hypertension Potential of Dynamic 18 FDG Positron Emission Tomography With Kinetic Analysis as a Bridging Biomarker for Pulmonary Vascular Remodeling Targeted Treatments

Background— Pulmonary arterial hypertension (PAH) is a disease of progressive vascular remodeling, characterized by dysregulated growth of pulmonary vascular cells and inflammation. A prevailing view is that abnormal cellular metabolism, notably aerobic glycolysis that increases glucose demand, underlies the pathogenesis of PAH. Increased lung glucose uptake has been reported in animal models. Few data exist from patients with PAH. Methods and Results— Dynamic positron emission tomography imaging with fluorine-18–labeled 2-fluoro-2-deoxyglucose (18FDG) ligand with kinetic analysis demonstrated increased mean lung parenchymal uptake in 20 patients with PAH, 18 with idiopathic PAH (IPAH) (FDG score: 3.27±1.22), and 2 patients with connective tissue disease (5.07 and 7.11) compared with controls (2.02±0.71; P<0.05). Further compartment analysis confirmed increased lung glucose metabolism in IPAH. Lung 18FDG uptake and metabolism varied within the IPAH population and within the lungs of individual patients, consistent with the recognized heterogeneity of vascular pathology in this disease. The monocrotaline rat PAH model also showed increased lung 18FDG uptake, which was reduced along with improvements in vascular pathology after treatment with dicholoroacetate and 2 tyrosine kinase inhibitors, imatinib and sunitinib. Hyperproliferative pulmonary vascular fibroblasts isolated from IPAH patients exhibited upregulated glycolytic gene expression, along with increased cellular 18FDG uptake; both were reduced by dicholoroacetate and imatinib. Conclusions— Some patients with IPAH exhibit increased lung 18FDG uptake. 18FDG positron emission tomography imaging is a tool to investigate the molecular pathology of PAH and its response to treatment.

Comparison of 18F-FDG uptake by right ventricular myocardium in idiopathic pulmonary arterial hypertension and pulmonary arterial hypertension associated with congenital heart disease.

This study measured glucose uptake in the right ventricle (RV) of patients with pulmonary hypertension and investigated the relationship to hemodynamics and survival. Myocardial 18F-fluorodeoxy-glucose (FDG) uptake was measured using single-photon positron emission tomography (SPECT) in 24 patients with idiopathic pulmonary arterial hypertension (IPAH) and 43 patients with congenital heart disease (CHD). In both IPAH and CHD-PAH, RV FDG uptake (RV/LV ratio) was associated with pulmonary vascular resistance (PVR). A second SPECT scan was performed in nine patients after 6 months treatment with sildenafil. PVR decreased from 1683±426 to 1207±383 dyn s−1 cm−5 (P < 0.05) and cardiac index improved from 2.2±0.2 to 2.8±0.5 L/min/m2 (P < 0.01). RV/LV FDG uptake decreased from 1.28±0.32 before treatment to 0.99±0.23 (P < 0.05). Survival in the IPAH group with a baseline RV/LV FDG uptake greater than the median value of 1.20 was significantly lower than that of the group with RV/LV FDG uptake below 1.20 (log-rank test, P < 0.05). In contrast, baseline RV/LV FDG was of little informative value in CHD. FDG uptake by the RV reflects the severity of PVR in PAH. Increased RV FDG uptake is a marker of poor prognosis in IPAH and is reduced in patients receiving effective therapy. It could prove useful in the early clinical assessment of novel therapies for PAH.

Evaluation of right ventricular volume and ejection fraction by gated (18)F-FDG PET in patients with pulmonary hypertension: comparison with cardiac MRI and CT.

BackgroundRight ventricular (RV) function is a powerful predictor of survival in patients with pulmonary hypertension (PH), but noninvasively assessing RV function remains a challenge. The aim of this study was to prospectively compare gated 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) myocardial imaging (gated PET), cardiac magnetic resonance (CMR), and cardiac computed tomography (CCT) for the assessment of RV volume and ejection fraction in patients with PH.MethodsTwenty-three consecutive patients aged more than 16xa0years diagnosed with PH were included. All patients underwent gated PET, CMR, and CCT within 7xa0days. Right ventricular end-diastolic volume (RVEDV), right ventricular end-systolic volume (RVESV), and right ventricular ejection fraction (RVEF) were calculated by three imaging modalities. RV 18F-FDG uptake was determined as RV-corrected standardized uptake value (SUV), and the ratio of RV to left ventricular (LV)-corrected SUV (Corrected SUV R/L).ResultsGated PET showed a moderate correlation (rxa0=xa00.680, Pxa0<xa0.001) for RVEDV, good correlation for RVESV (rxa0=xa00.757, Pxa0<xa0.001) and RVEF (rxa0=xa00.788, Pxa0<xa0.001) with CMR, and good correlation for RVEDV (rxa0=xa00.767, Pxa0<xa0.001), RVESV (rxa0=xa00.837, Pxa0<xa0.001), and RVEF (rxa0=xa00.730, Pxa0<xa0.001) with CCT. Bland-Altman analysis revealed systematic underestimation of RVEDV and RVESV and overestimation of RVEF with gated PET compared with CMR and CCT. The correlation between RVESV (rxa0=xa00.863, Pxa0<xa0.001), RVESV (rxa0=xa00.903, Pxa0<xa0.001), and RVEF (rxa0=xa00.853, Pxa0<xa0.001) of CMR and those of CCT was excellent; Bland-Altman analysis showed only a slight systematic variation between CMR and CCT. There were statistically significant negative correlations between RV-corrected SUV and RVEF-CMR (rxa0=xa0−0.543, Pxa0<xa0.01), Corrected SUV R/L and RVEF-CMR (rxa0=xa0−0.521, Pxa0<xa0.05), RV-corrected SUV and RVEF-CCT (rxa0=xa0−0.429, Pxa0<xa0.05), Corrected SUV R/L and RVEF-CCT (rxa0=xa0−0.580, Pxa0<xa0.01), respectively.ConclusionGated PET had moderate-to-high correlation with CMR and CCT in the assessments of RV volume and ejection fraction. It is an available method for simultaneous assessing of RV function and myocardial glucose metabolism in patients with PH.

Avoiding full corrections in dynamic SPECT images impacts the performance of SPECT myocardial blood flow quantitation

IntroductionThis study investigated the performance of SPECT myocardial blood flow (MBF) quantitation lacking full physical corrections (All Corr) in dynamic SPECT (DySPECT) images.MethodsEleven healthy normal volunteers (HVT) and twenty-four patients with angiography-documented CAD were assessed. All Corr in 99mTc-sestamibi DySPECT encompassed noise reduction (NR), resolution recovery (RR), and corrections for scatter (SC) and attenuation (AC), otherwise no correction (NC) or only partial corrections. The performance was evaluated by quality index (R2) and blood-pool spillover index (FBV) in kinetic modeling, and by rest flow (RMBF) and stress flow (SMBF) compared with those of All Corr.ResultsIn HVT group, NC diminished 2-fold flow uniformity with the most degraded quality (15%-18% reduced R2) and elevated spillover effect (45%-50% increased FBV). Consistently higher RMBF and SMBF were discovered in both groups (HVT 1.54/2.31 higher; CAD 1.60/1.72; all Pxa0<xa0.0001). Bland-Altman analysis revealed positive flow bias (HVT 0.9-2.6xa0mL/min/g; CAD 0.7-1.3) with wide ranges of 95% CI of agreement (HVT NC −1.9-7.1; NR −0.4-4.4; NRxa0+xa0SC −1.1-4.3; NRxa0+xa0SCxa0+xa0RR −0.7-2.5) (CAD NC −1.2-3.8; NR −1.0-2.8; NRxa0+xa0SC −1.0-2.5; NRxa0+xa0SCxa0+xa0RR −1.1-2.6).ConclusionsUncorrected physical interference in DySPECT images can extensively impact the performance of MBF quantitation. Full physical corrections should be considered to warrant this tool for clinical utilization.

The characterization and prognostic significance of right ventricular glucose metabolism in non-ischemic dilated cardiomyopathy

AimsIn dilated cardiomyopathy (DCM), there are limited data on right ventricular (RV) glucose metabolism assessed by [18F]fludeoxyglucose positron emission tomography (18F-FDG PET) imaging. We aimed to characterize RV glucose metabolism and investigate the prognostic significance of RV FDG uptake in DCM.Methods and Results18F-FDG PET imaging and cardiac magnetic resonance imaging (MRI) were performed in 63 consecutive DCM patients within an interval of 3-7xa0days. There was a significant correlation between RVEF and RV FDG uptake whether corrected RV standard uptake value (cRVSUV) (rxa0=xa0−0.571, Pxa0<xa0.001) or the relative RV FDG uptake determined as the ratio of RV to left ventricular (LV) corrected SUV (cR/L) (rxa0=xa0−0.405, Pxa0<xa0.001) was used. During a median follow-up period of 804xa0days, 15 patients (23.8%) reached the primary endpoint of all-cause mortality or heart transplantation. On univariate Cox analysis, cRVSUVxa0>xa07.01 and cR/Lxa0>xa00.795 were significantly associated with the overall survival (hazard ratio [HR] 5.415, 95% confidence interval [CI] 1.945-15.078, Pxa0<xa0.001; HR 6.422, 95% CI 2.250-18.332, Pxa0<xa0.001). Patients with increased RV FDG uptake had a worse outcome (cRVSUVxa0>xa07.01 vs cRVSUVxa0≤xa07.01, log-rank 13.085, Pxa0<xa0.001; cR/Lxa0>xa00.795 vs cR/Lxa0≤xa00.795, log-rank 15.695, Pxa0<xa0.001). On multivariate analysis, cR/Lxa0>xa00.795 remained a significant independent predictor of the endpoint (HR 5.001, 95% CI 1.641-15.239, Pxa0=xa0.004), while cRVSUVxa0>xa07.01 showed no significance (HR 2.611; 95% CI 0.797-8.558; Pxa0=xa0.113).ConclusionsIncreased RV FDG uptake was associated with RV dysfunction and may be a prognostic predictor of all-cause mortality or heart transplantation in patients with DCM.

Quantitative assessment of right ventricular glucose metabolism in idiopathic pulmonary arterial hypertension patients: a longitudinal study

AIMSnRight ventricular (RV) glucose metabolism disorder in pulmonary arterial hypertension (PAH) has been studied using (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) imaging with inconsistent results. We aimed to quantitatively assess RV glucose metabolism and further identify its role of monitoring RV function in idiopathic PAH (IPAH) patients in a longitudinal study.nnnMETHODS AND RESULTSnTwenty-seven treatment-naïve IPAH patients and 21 healthy control subjects performed FDG-PET dynamic scan for quantification of the rate of myocardium glucose utilization (rMGU) and echocardiography for assessment of cardiac function. Right heart catheterization was conducted for IPAH patients for haemodynamic measurement. A subgroup of 14 patients repeated FDG-PET and echocardiography after 6-month treatment. RV rMGU was significantly increased compared with controls; while the rMGU in left ventricle showed no difference. RV rMGU was significantly correlated with pulmonary artery pressure, pulmonary vascular resistance, RV Tei index, and right atrial area, and negatively correlated with RV ejection fraction (RVEF) and tricuspid annular plane systolic excursion. Six of 14 patients with increased RV rMGU after 6-month treatment showed no change in RVEF, 6-min walk distance (6MWD), and RV Tei index; however, the other 8 patients with decreased RV rMGU demonstrated significantly increased RVEF and 6MWD and decreased RV Tei index. Notably, the change in RV rMGU of 14 patients was significantly correlated with the change in 6MWD and RV Tei index.nnnCONCLUSIONnIncreased RV rMGU of IPAH correlates with RV dysfunction and RV pressure overload. The change in RV glucose metabolism may help monitor RV function after treatment.

Comparison of CZT SPECT and conventional SPECT for assessment of contractile function, mechanical synchrony and myocardial scar in patients with heart failure

AimThe aim of this study was to compare CZT-SPECT (CZT SPECT) to conventional SPECT (C-SPECT) in the assessment of left ventricular myocardial scar, contractile function, and mechanical synchrony in patients with heart failure (HF).MethodsFifty-nine patients with HF who were referred for myocardial perfusion/metabolism imaging were enrolled. All patients underwent resting 99mTc-MIBI gated myocardial perfusion imaging using a CZT SPECT camera and a C-SPECT camera, respectively, and 18F-FDG PET myocardial metabolism imaging within three days. Summed rest score (SRS) and total perfusion defect (TPD) (as indices of perfusion abnormality), left ventricular (LV), end diastolic volume (EDV), end systolic volume (ESV), and ejection fraction (EF) (as indices of LV systolic function), and histogram band width (BW) and standard deviation (SD) (as indices of mechanical synchrony) were analyzed by automated software while the perfusion/metabolism patterns were analyzed visually.ResultsThere was a good correlation between CZT SPECT and C-SPECT for SRS and TPD. CZT SPECT tended to underestimate SRS and TPD compared to C-SPECT. CZT-SPECT and C-SPECT showed excellent agreement in assessing the perfusion/metabolism pattern though a small proportion of normal segments (6.6%) identified by CZT/PET exhibited mismatch pattern on C-SPECT/PET. CZT SPECT also showed excellent correlation with C-SPECT in measuring EDV, ESV, and EF. Finally, BW and SD measured by CZT SPECT correlated well with C-SPECT but CZT SPECT tended to overestimate BW and SD compared to C-SPECT.ConclusionCZT SPECT provided comparable data to C-SPECT for measuring LV scar, function and synchrony at a considerable reduction in imaging time. CZT SPECT holds a promise for comprehensive evaluation of myocardial performance in patients with HF.

Relationship of myocardial hibernation, scar, and angiographic collateral flow in ischemic cardiomyopathy with coronary chronic total occlusion.

BackgroundThe relationship between myocardial viability and angiographic collateral flow is not fully elucidated in ischemic cardiomyopathy (ICM) with coronary artery chronic total occlusion (CTO). We aimed to clarify the relationship between myocardial hibernation, myocardial scar, and angiographic collateral flow in these patients.Methods and ResultsSeventy-one consecutive ICM patients with 122 CTOs and 652 dysfunctional segments within CTO territories were retrospectively analyzed. Myocardial hibernation (perfusion-metabolism mismatch) and the extent of 18F-fluorodeoxyglucose (FDG) abnormalities were assessed using 99mTc-sestamibi and 18F–FDG imaging. Myocardial scar was evaluated by late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) imaging. Collateral flow observed on coronary angiography was assessed using Rentrop classification. In these patients, neither the extent nor frequency of myocardial hibernation or scar was related to the status of collateral flow. Moreover, the matching rate in determining myocardial viability was poor between any 2 imaging indices. The extent of 18F-FDG abnormalities was linearly related to the extent of LGE rather than myocardial hibernation. Of note, nearly one-third (30.4%) of segments with transmural scar still had hibernating tissue. Hibernation and non-transmural scar had higher sensitivity (63.0% and 66.7%) than collateral flow (37.0%) in predicting global functional improvement.ConclusionsAngiographic collateral cannot accurately predict myocardial viability, and has lower sensitivity in prediction of functional improvement in CTO territories in ICM patients. Hence, assessment of myocardial viability with non-invasive imaging modalities is of importance. Moreover, due to the lack of correlation between myocardial hibernation and scar, these two indices are complementary but not interchangeable.