82Rb Positron Emission Tomography Research Articles

TAI-GAN: A Temporally and Anatomically Informed Generative Adversarial Network for early-to-late frame conversion in dynamic cardiac PET inter-frame motion correction

Inter-frame motion in dynamic cardiac positron emission tomography (PET) using rubidium-82 (82Rb) myocardial perfusion imaging impacts myocardial blood flow (MBF) quantification and the diagnosis accuracy of coronary artery diseases. However, the high cross-frame distribution variation due to rapid tracer kinetics poses a considerable challenge for inter-frame motion correction, especially for early frames where intensity-based image registration techniques often fail. To address this issue, we propose a novel method called Temporally and Anatomically Informed Generative Adversarial Network (TAI-GAN) that utilizes an all-to-one mapping to convert early frames into those with tracer distribution similar to the last reference frame. The TAI-GAN consists of a feature-wise linear modulation layer that encodes channel-wise parameters generated from temporal information and rough cardiac segmentation masks with local shifts that serve as anatomical information. Our proposed method was evaluated on a clinical 82Rb PET dataset, and the results show that our TAI-GAN can produce converted early frames with high image quality, comparable to the real reference frames. After TAI-GAN conversion, the motion estimation accuracy and subsequent myocardial blood flow (MBF) quantification with both conventional and deep learning-based motion correction methods were improved compared to using the original frames. The code is available at https://github.com/gxq1998/TAI-GAN.

Pulmonary blood volume measured by 82Rb-PET in patients with chronic obstructive pulmonary disease: a retrospective cohort study.

In patients with chronic obstructive pulmonary disease (COPD), pulmonary vascular dysfunction and destruction are observable before the onset of detectable emphysema, but it is unknown whether this is associated with central hypovolemia. We investigated if patients with COPD have reduced pulmonary blood volume (PBV) evaluated by 82Rb-positron emission tomography (PET) at rest and during adenosine-induced hyperemia. This single-center retrospective cohort study assessed 6,301 82Rb-PET myocardial perfusion imaging (MPI) examinations performed over a 6-yr period. We compared 77 patients with COPD with 44 healthy kidney donors (controls). Cardiac output ([Formula: see text]) and mean 82Rb bolus transit time (MBTT) were used to calculate PBV. [Formula: see text] was similar at rest (COPD: 3,649 ± 120 mL vs. control: 3,891 ± 160 mL, P = 0.368) but lower in patients with COPD compared with controls during adenosine infusion (COPD: 5,432 ± 124 mL vs. control: 6,185 ± 161 mL, P < 0.050). MBTT was shorter in patients with COPD compared with controls at rest (COPD: 8.7 ± 0.28 s vs. control: 11.4 ± 0.37 s, P < 0.001) and during adenosine infusion (COPD: 9.2 ± 0.28 s vs. control: 10.2 ± 0.37 s, P < 0.014). PBV was lower in patients with COPD, even after adjustment for body surface area, sex, and age at rest [COPD: 530 (29) mL vs. 708 (38) mL, P < 0.001] and during adenosine infusion [COPD: 826 (29) mL vs. 1,044 (38) mL, P < 0.001]. In conclusion, patients with COPD show evidence of central hypovolemia, but it remains to be determined whether this has any diagnostic or prognostic impact.NEW & NOTEWORTHY The present study demonstrated that patients with chronic obstructive pulmonary disease (COPD) exhibit central hypovolemia compared with healthy controls. Pulmonary blood volume may thus be a relevant physiological and/or clinical outcome measure in future COPD studies.

Impact on cardiovascular outcome of coronary revascularization-induced changes in ischemic perfusion defect and myocardial flow reserve

PurposeWe evaluated the impact on cardiovascular outcome of coronary revascularization-induced changes in ischemic total perfusion defect (ITPD) and myocardial flow reserve (MFR) as assessed by 82Rb positron emission tomography (PET)/computed tomography (CT) imaging.MethodsThe study included 102 patients referred to 82Rb PET/CT myocardial perfusion imaging before and after coronary revascularization. All patients were followed for the occurrence of cardiovascular events (cardiac death, nonfatal myocardial infarction, repeated revascularization, and heart failure) after the second imaging study.ResultsDuring a median follow-up of 20 months, 21 events occurred. The clinical characteristics were comparable between patients with and without events. In the overall study population, after revascularization, there was a significant reduction (P < 0.001) of ITPD, while hyperemic myocardial blood flow (MBF) (P < 0.01) and MFR (P < 0.05) significantly improved. Event rate was higher in patients with ITPD (P < 0.005) or MFR (P < 0.001) worsening compared to those with unchanged or improved ITPD or MFR. At Cox univariable analysis, ITPD and MFR worsening resulted in predictors of events (both P < 0.05). Patients with worsening of both ITPD and MFR had the worst event-free survival (log-rank 32.9, P for trend < 0.001).ConclusionsIn patients with stable CAD, worsening of ITPD and MFR after revascularization procedures is associated with higher risk of cardiovascular events. Follow-up MPI with 82Rb PET/CT may improve risk stratification in patients submitted to coronary revascularization.

Coronary flow capacity and survival prediction after revascularization: physiological basis and clinical implications.

Coronary flow capacity (CFC) is associated with an observed 10-year survival probability for individual patients before and after actual revascularization for comparison to virtual hypothetical ideal complete revascularization. Stress myocardial perfusion (mL/min/g) and coronary flow reserve (CFR) per pixel were quantified in 6979 coronary artery disease (CAD) subjects using Rb-82 positron emission tomography (PET) for CFC maps of artery-specific size-severity abnormalities expressed as percent left ventricle with prospective follow-up to define survival probability per-decade as fraction of 1.0. Severely reduced CFC in 6979 subjects predicted low survival probability that improved by 42% after revascularization compared with no revascularization for comparable severity (P = .0015). For 283 pre-and-post-procedure PET pairs, severely reduced regional CFC-associated survival probability improved heterogeneously after revascularization (P < .001), more so after bypass surgery than percutaneous coronary interventions (P < .001) but normalized in only 5.7%; non-severe baseline CFC or survival probability did not improve compared with severe CFC (P = .00001). Observed CFC-associated survival probability after actual revascularization was lower than virtual ideal hypothetical complete post-revascularization survival probability due to residual CAD or failed revascularization (P < .001) unrelated to gender or microvascular dysfunction. Severely reduced CFC in 2552 post-revascularization subjects associated with low survival probability also improved after repeat revascularization compared with no repeat procedures (P = .025). Severely reduced CFC and associated observed survival probability improved after first and repeat revascularization compared with no revascularization for comparable CFC severity. Non-severe CFC showed no benefit. Discordance between observed actual and virtual hypothetical post-revascularization survival probability revealed residual CAD or failed revascularization.

Prediction of outcome by 82Rb PET/CT in patients with ischemia and nonobstructive coronary arteries

BackgroundThe purpose of this study was to assess the prognostic value of cardiac 82Rb positron emission tomography (PET)/computed tomography (CT) imaging in patients with myocardial ischemia of nonobstructive coronary arteries (INOCA). MethodsWe retrospectively evaluated 311 INOCA patients who underwent rest stress 82Rb PET/CT. Cardiac end points were cardiac death, myocardial infarction, or late coronary revascularization. A parametric survival model was also used to identify how the variables influenced time to event. ResultsDuring a median follow-up of 37 months (range 6–108), 23 (7%) cardiac events occurred. In patients with events total perfusion defect (TPD) was higher and myocardial flow reserve (MFR) lower compared to those without events (both P < .001). At multivariable Cox analysis, increased TPD (i.e., ≥ 5%) and reduced MFR (i.e., < 2) were predictors of events (both P < .001). At Weibull survival analysis, the highest probability of cardiac events and risk acceleration were observed in patients with both increased TPD and reduced MFR. Annualized event rate was higher in patients with reduced MFR compared to those with preserved MFR (P < .001). ConclusionIn patients with INOCA, the combined evaluation of myocardial perfusion and coronary vascular function by 82Rb PET/CT is able to identify those at higher risk of cardiac events.

Quantification of myocardial blood flow using dynamic myocardial CT perfusion compared with 82Rb PET

PurposeAbsolute measures of myocardial blood flow (MBF) obtained with dynamic myocardial CT perfusion (DM-CTP) are underestimated when compared with reference standards. This is to some extent explained by incomplete extraction of iodinated contrast agent (iCA) to the myocardial tissue. We aimed to establish an extraction function for iCA, use the function to calculate MBFCT and to compare this with MBF measured with 82Rb positron emission tomography (PET). Materials and methodsHealthy individuals without coronary artery disease (CAD) were examined with 82Rb PET and DM-CTP. The factors a and β of the generalized Renkin-Crone model were estimated using a non-linear least squares model. The factors providing the best fit for the data were subsequently used to calculate MBFCT. ResultsOf consecutive 91 individuals examined, 79 were eligible for analysis. The factors a and β providing the best fit of the nonlinear least-squares model to the data were a ​= ​0.614 and β ​= ​0.218 (R-squared ​= ​0.81). Conversion of the CT inflow parameter (K1) values using the derived extraction function resulted in a significant correlation between MBF measured during stress using CT and PET (P ​= ​0.039). ConclusionIn healthy individuals, flow estimates obtained with dynamic myocardial CT perfusion during stress were, after conversion to MBF using the extraction of iodinated CT contrast agent, correlated with absolute MBF quantified with 82Rb PET.

TAI-GAN: Temporally and Anatomically Informed GAN for Early-to-Late Frame Conversion in Dynamic Cardiac PET Motion Correction.

The rapid tracer kinetics of rubidium-82 (82Rb) and high variation of cross-frame distribution in dynamic cardiac positron emission tomography (PET) raise significant challenges for inter-frame motion correction, particularly for the early frames where conventional intensity-based image registration techniques are not applicable. Alternatively, a promising approach utilizes generative methods to handle the tracer distribution changes to assist existing registration methods. To improve frame-wise registration and parametric quantification, we propose a Temporally and Anatomically Informed Generative Adversarial Network (TAI-GAN) to transform the early frames into the late reference frame using an all-to-one mapping. Specifically, a feature-wise linear modulation layer encodes channel-wise parameters generated from temporal tracer kinetics information, and rough cardiac segmentations with local shifts serve as the anatomical information. We validated our proposed method on a clinical 82Rb PET dataset and found that our TAI-GAN can produce converted early frames with high image quality, comparable to the real reference frames. After TAI-GAN conversion, motion estimation accuracy and clinical myocardial blood flow (MBF) quantification were improved compared to using the original frames. Our code is published at https://github.com/gxq1998/TAI-GAN.

Abstract 9874: Correlation of Left Ventricular Strain Derived From Rb-82 ECG-Gated PET Myocardial Perfusion Imaging vs 2D Echocardiography

Introduction: Global longitudinal strain (GLS) by two-dimensional (2D) transthoracic echocardiography (TTE) is a robust index for identifying early left ventricular (LV) myocardial dysfunction. Positron emission tomography (PET) myocardial perfusion imaging (MPI) is widely used in the assessment of ischemic heart disease (IHD) but has not been used for strain analysis. Hypothesis: Longitudinal, radial, and circumferential myocardial strain measures at rest and at pharmacologic stress by Rb-82 ECG-gated PET MPI are correlated to those measured by resting 2D TTE. Methods: We developed a novel PET MPI method to track the LV myocardium throughout the cardiac cycle processed in the Emory Cardiac Toolbox, to measure LV strain from longitudinal, radial, and circumferential direction at regadenoson-stress and at rest. We retrospectively identified 80 patients who underwent Rb-82 PET MPI and also had TTE with strain analysis within 3 months. The agreement between LV strain and LVEF derived from PET MPI and resting TTE was assessed with Bland-Altman analysis, Pearson’s correlation, and the concordance correlation coefficient (CCC). Results: PET MPI derived measurements of longitudinal (Figure 1A-1B: Bland-Altman analysis; 1C-1D: Pearson’s correlations), circumferential (Figure 1E-1F: Pearson’s correlations) and radial (Figure 1G-1H: Pearson’s correlations) strain measures at rest and stress were strongly correlated to resting TTE derived GLS (p&lt;.001). LVEF showed strong correlations at stress (0.83, p&lt;.001) and rest (0.80, p&lt;.001). Inter-observer agreements of PET MPI strain measures showed high correlation between 2 independent observers for all 3 directions (p&lt;.001). Conclusions: LV strain measures by PET MPI using a novel automated technique correlated strongly with GLS by TTE. PET MPI measures are highly reproducible. Strain by PET MPI should be investigated further to establish its value in routine clinical practice.

WHY IS HEART FAILURE WITH PRESERVED EJECTION FRACTION (HFPEF) MORE COMMON IN WOMEN THAN MEN? EXPLORING ABNORMALITIES IN PULSITILE ARTERIAL LOAD AS DISTINCT FEATURE OF THE HFPEF SYNDROME IN WOMEN

WHY IS HEART FAILURE WITH PRESERVED EJECTION FRACTION (HFPEF) MORE COMMON IN WOMEN THAN MEN? EXPLORING ABNORMALITIES IN PULSITILE ARTERIAL LOAD AS DISTINCT FEATURE OF THE HFPEF SYNDROME IN WOMEN

Prognostic value of myocardial flow reserve obtained by 82-rubidium positron emission tomography in long-term follow-up after heart transplantation

BackgroundCardiac allograft vasculopathy (CAV) is a leading cause of death following heart transplantation (HTx) and non-invasive prognostic methods in long-term CAV surveillance are needed. We evaluated the prognostic value of myocardial flow reserve (MFR) obtained by 82-rubidium (82Rb) positron emission tomography (PET). MethodsRecipients undergoing dynamic rest-stress 82Rb PET between April 2013 and June 2017 were retrospectively evaluated in a single-center study. Evaluation by PET included quantitative myocardial blood flow and semiquantitative myocardial perfusion imaging. Patients were grouped by MFR (MFR ≤ 2.0 vs MFR > 2.0) and the primary outcome was all-cause mortality. ResultsA total of 50 patients (68% men, median age 57 [IQR: 43 to 68]) were included. Median time from HTx to PET was 10.0 (6.7 to 16.0) years. In 58% of patients CAV was documented prior to PET. During a median follow-up of 3.6 (2.3 to 4.3) years 12 events occurred. Survival probability by Kaplan–Meier method was significantly higher in the high-MFR group (log-rank P = .02). Revascularization (n = 1), new CAV diagnosis (n = 1), and graft failure (n = 4) were more frequent in low-MFR patients. No retransplantation occurred. ConclusionsMyocardial flow reserve appears to offer prognostic value in selected long-term HTx recipients and holds promise as a non-invasive method for CAV surveillance possibly guiding management strategy.

Relationship between ischaemia, coronary artery calcium scores, and major adverse cardiovascular events.

Positron emission tomography (PET) myocardial perfusion imaging (MPI) is often combined with coronary artery calcium (CAC) scanning, allowing for a combined anatomic and functional assessment. We evaluated the independent prognostic value of quantitative assessment of myocardial perfusion and CAC scores in patients undergoing PET. Consecutive patients who underwent Rb-82 PET with CAC scoring between 2010 and 2018, with follow-up for major adverse cardiovascular events (MACE), were identified. Perfusion was quantified automatically with total perfusion deficit (TPD). Our primary outcome was MACE including all-cause mortality, myocardial infarction (MI), admission for unstable angina, and late revascularization. Associations with MACE were assessed using multivariable Cox models adjusted for age, sex, medical history, and MPI findings including myocardial flow reserve.In total, 2507 patients were included with median age 70. During median follow-up of 3.9 years (interquartile range 2.1-6.1), 594 patients experienced at least one MACE. Increasing CAC and ischaemic TPD were associated with increased MACE, with the highest risk associated with CAC &gt; 1000 [adjusted hazard ratio (HR) 1.67, 95% CI 1.24-2.26] and ischaemic TPD &gt; 10% (adjusted HR 1.80, 95% CI 1.40-2.32). Ischaemic TPD and CAC improved overall patient classification, but ischaemic TPD improved classification of patients who experienced MACE while CAC mostly improved classification of low-risk patients. Ischaemic TPD and CAC were independently associated with MACE. Combining extent of atherosclerosis and functional measures improves the prediction of MACE risk, with CAC 0 identifying low-risk patients and regional ischaemia identifying high-risk patients in those with CAC &gt; 0.

Highlights From the Circulation Family of Journals

Highlights From the <i>Circulation</i> Family of Journals

Prognostic Relationship Between Coronary Artery Calcium Score, Perfusion Defects, and Myocardial Blood Flow Reserve in Patients With Suspected Coronary Artery Disease.

Coronary artery calcium score (CACS) is an anatomic measure of calcified atherosclerosis. Myocardial perfusion defects and reduced myocardial blood flow reserve (MBFR) are physiological measures of ischemia and coronary circulatory health. We aimed to assess the relative prognostic importance of MBFR, perfusion defects, and CACS in patients with suspected coronary artery disease. A total of 5983 consecutive patients without known history of coronary artery disease or cardiomyopathy, who underwent a CACS and 82Rb positron emission tomography myocardial perfusion imaging between 2010 and 2016, were followed for all-cause death (n=785) over median of 3 years. Prognostic value was assessed using multivariable Cox regression models, and incremental risk discrimination for imaging variables was evaluated by comparing model c-indices after adjusting for clinical risk factors (RF). Mean age was 67.1 years, 60% were female, and 83% were symptomatic. CACS was 0 in 22%, abnormal perfusion in 19%, and MBFR <2 in 53.3%. When added to RF, the model with MBFR had the best fit (c=0.78, P<0.0001). Addition of CACS to model with RF and perfusion (c=0.77) offered modest improvement in discrimination over the model with RF and perfusion (c=0.76, P=0.02). Adding CACS to a model with RF, perfusion, and MBFR did not provide incremental prognostic value (c=0.785 for both, P=0.16). CACS and MBFR both had independent prognostic value in patients with normal and abnormal myocardial perfusion imaging. Even among patients with CACS of 0, MBFR <2 was present in 37.8%, being associated with higher risk of death (hazard ratio per 0.1↓, 1.10 [1.04-1.15]; P<0.001), but perfusion defects were not. Use of anatomic testing such as CACS of 0 to avoid myocardial perfusion imaging in symptomatic patients could lead to missing microvascular dysfunction in 4 out of 10 patients, a finding associated with a high mortality risk. Higher CACS was independently associated with the risk of death but did not provide incremental prognostic value over positron emission tomography with MBFR.

Quantification of Resting Myocardial Blood Flow Using Rubidum82 Positron Emission Tomography in Regions with MRI-Confirmed Myocardial Scar.

Background: Resting myocardial blood flow (rMBF) within regions of myocardial scar as measured by positron emission tomography (PET) has not yet been assessed with the radiotracer Rubidium82 (Rb82) or correlated with scar thickness. Cardiac magnetic resonance imaging (cMRI) offers high spatial resolution and identifies myocardial scar with late gadolinium enhancement (LGE). Using Rb82 PET, we sought to characterize rMBF in regions of myocardial scar of varying thicknesses determined by cMRI. Methods/Results: Patients with a history of myocardial infarction, a resting Rb82 PET study and a cMRI were identified. On cMRI, regions of infarction, defined as >50% LGE with akinesis, were sub-categorized as 50-75% LGE or >75% LGE, corresponding with increasing transmural scar thickness. PET zones of infarct based on size and %LGE by cMRI were quantified for mean and minimum rMBF. Mean rMBF (cc/min/g) in infarct zones with >75% LGE was 0.32±0.07 with a minimum rMBF of 0.19±0.03. In infarct zones with 50-75% LGE, rMBF was 0.45±0.14 (50-75% vs. >75%, p=0.002). Conclusions: We identified rMBF within cMRI confirmed regions of myocardial scar of varying thicknesses. rMBF has an inverse relationship with the extent of LGE on cMRI, with the most severe regions (>75% LGE) having mean and minimal rMBF (cc/min/g) of 0.32±0.07 and 0.19±0.03, respectively.

The Application of Conditional Probability to Harmonize Nuclear Cardiology Test Results.

Both exercise single photon emission computed tomography (SPECT) imaging and myocardial perfusion imaging with positron emission tomography produce multiple outcome variables. These include the stress electrocardiogram (ECG), visual perfusion assessment and quantitative myocardial blood flow. Bayes' analysis using conditional probability allows the distillation of multiple test results into a single probability of disease for individual patients. This paper examines the application of conditional probability analysis to two noninvasive modalities that generate multiple outcome results: exercise ECG combined with SPECT imaging and vasodilator RB-82 positron emission tomography perfusion imaging combined with quantitative measure of absolute myocardial blood flow. In this manner, a single probability of disease incorporating all the available data is generated for an individual patient.

The Association Between Cardiovascular Autonomic Function and Changes in Kidney and Myocardial Function in Type 2 Diabetes and Healthy Controls.

BackgroundThe mechanisms linking cardiovascular autonomic neuropathy, diabetic kidney disease and cardiovascular mortality in type 2 diabetes are widely unknown. We investigated the relationship between baseline cardiovascular autonomic function and changes in kidney and myocardial function over six years in patients with type 2 diabetes and healthy controls.Methods Post-hoc analysis of a cohort study in 24 patients with type 2 diabetes and 18 healthy controls. Baseline determinants were cardiovascular autonomic reflex tests (heart rate response to: standing (30:15); deep breathing (E:I); and the Valsalva test) and time- and frequency-domain heart rate variability indices. Outcomes were changes in estimated glomerular filtration rate (eGFR), albuminuria, myocardial flow reserve (MFR) measured by cardiac 82Rb Positron emission tomography computed tomography (PET/CT), and coronary artery calcium score (CACS).ResultsMean age at inclusion was 61 ± 10 years and 36% were female. Mean follow up time was 6 ± 0 years. A lower response in heart rate to the Valsalva test (corresponding to weaker autonomic function) was associated with a larger decline in eGFR (p=0.04), but not significantly after adjustment for sex, baseline age, smoking status, systolic blood pressure, heart rate, HbA1c, body mass index and baseline eGFR (p=0.12). A higher baseline response in heart rate to standing (30:15) was associated with a larger decline in myocardial flow reserve in the unadjusted analysis (p=0.02) and after adjustment (p=0.02). A higher response in heart rate to the Valsalva maneuver was associated with a larger increase in CACS (p = 0.02), but the association became insignificant after adjustment (p = 0.16).ConclusionA lower response in heart rate to the Valsalva test was associated with a larger decline in kidney function, indicating that autonomic dysfunction may predict future loss of kidney function. However, we did not find any association between lower values in cardiovascular autonomic function at baseline and a worsening in albuminuria, myocardial function, or atherosclerotic burden.

Incremental value of 18F-FDG cardiac PET imaging over dobutamine stress echocardiography in predicting myocardial ischemia in patients with suspected coronary artery disease

BackgroundTo assess the incremental value of 18F-fluorodeoxyglucose (FDG) cardiac positron emission tomography (PET) over dobutamine stress echocardiography (DSE) in predicting myocardial ischemia in patients with suspected coronary artery disease (CAD). MethodsForty-one patients with suspected CAD underwent within 7 days apart rest-stress cardiac PET with 82Rb and DSE followed by cardiac 18F-FDG PET imaging. 18F-FDG images were scored on a 0 (no discernible uptake) to 2 (intense uptake) scale. Logistic regression analysis was performed to identify predictors of stress-induced ischemia. The incremental value of 18F-FDG PET over DSE in detecting ischemia at 82Rb PET cardiac imaging was assessed by the likelihood ratio chi-square and net reclassification index. ResultsOn 82Rb-PET imaging, myocardial ischemia (ischemic total perfusion defect ≥ 5%) was detected in 20 (49%) patients. Inducible ischemia was found in 22 (54%) patients on DSE (biphasic or worsening response pattern in ≥ 1 segment) and in 21 (51%) patients on 18F-FDG PET (uptake score of 2 in ≥ 1 segment). 18F-FDG PET resulted as statistically significant predictor of ischemia on 82Rb-PET. The addition of 18F-FDG PET to DSE increased the likelihood of ischemia on 82Rb-PET (P < .05). 18F-FDG PET was able to reclassify the probability of stress-induced myocardial ischemia on both patient and vessel analyses. Conclusion18F-FDG PET performed after dobutamine stress test may provide incremental value to DSE in the evaluation of myocardial ischemia. These results suggest that stress-induced myocardial ischemia can be imaged directly using 18F-FDG PET after dobutamine stress test.

Abstract 9057: Anti-inflammatory Effect of Biologic Therapy in Patients With Psoriatic Disease: A Prospective Cohort Fdg-pet Study

Introduction: Psoriatic arthritis (PsA) and cutaneous psoriasis (PsO) are linked with an increased risk of adverse cardiovascular events. Hypothesis: Central vascular inflammation (VI) as measured on F-18-fluorodeoxyglucose (FDG) positron emission tomography (PET) in the ascending aorta will improve in patients following therapy with biologic agents compared to PsO patients receiving non-biologic therapy and controls. We also postulate that in patients responding to biologics, there will be an improvement in coronary microvascular dysfunction as measured by myocardial blood flow reserve (MFR) determined by rubidium-82 (82Rb) PET. Methods: We studied 3 patient cohorts (patients with PsA and/or PsO started on biologic agents, patients with PsO managed on non-biologic therapy, and patients with non-inflammatory arthritis). The primary outcome of our study was the change in VI, estimated as the target-to-background ratio by FDG PET in the most diseased segment of the ascending aorta at baseline compared to 6-month follow-up (TBRmax). We also performed 82Rb PET studies at baseline and 6-month follow-up to determine any changes on left ventricular MFR. Results: 34 participants were enrolled in the study (11 PsA and/or PsO patients on biologic agents, 13 patients in PsO group managed on non-biologic therapy, and 10 in the non-inflammatory control group). A significant drop in the thoracic aorta uptake was observed in the biologic-treated group (change in TBRmax: -0.46±0.55) when compared to the the PsO group treated with non-biologic therapy (change in TBRmax: 0.23±0.67). The group with imaging evidence of a response to biologic agents (i.e. TBRmax drop greater than median value) maintained MFR (change in MFR of 0.05±0.19) when compared to the group with a response on TBRmax that was below the median, which had a drop in MFR (-2.9±0.8) (P=0.03). Conclusions: VI in the thoracic aorta decreased compared to psoriasis patients treated with non-systemic therapies and controls. Psoriasis patients treated with biologics who demonstrated a significant response on FDG PET imaging, maintained their MFR compared to non-responders. There is a positive impact of immune therapies on VI and microvascular disease in patients with chronic inflammation.

ANTI-INFLAMMATORY EFFECT OF BIOLOGIC THERAPY IN PATIENTS WITH PSORIATIC DISEASE COMPARED WITH TREATMENT WITH NON-BIOLOGIC DMARDS: A PROSPECTIVE COHORT FDG-PET STUDY

<h3>BACKGROUND</h3> Psoriatic arthritis (PsA) and cutaneous psoriasis (PsO) are linked with an increased risk of adverse cardiovascular events. We hypothesized that central vascular inflammation on F-18-fluorodeoxyglucose (FDG) positron emission tomography (PET) in the ascending aorta would improve in these patients following therapy with biologic agents compared to PsO patients receiving non-biologic therapy and non-inflammatory control patients. We also postulated that in patients responding to biologics, there would an improvement in coronary microvascular dysfunction as measured by myocardial blood flow reserve (MFR) determined by rubidium-82 (82Rb) PET. <h3>METHODS AND RESULTS</h3> We studied 3 patient cohorts (patients with PsA and/or PsO started on biologic agents, patients with PsO managed on non-biologic therapy, and control patients with non-inflammatory arthritis). The primary outcome of our study was the change in vascular inflammation, estimated as the target-to-background ratio (TBR) by FDG PET in the most diseased segment of the ascending aorta at baseline compared to 6-month follow-up (TBRmax). We also performed 82Rb PET studies at baseline and 6-month follow-up to determine any changes on left ventricular MFR. A total of 34 participants were enrolled in the study (11 PsA and/or PsO patients on biologic agents, 13 patients in PsO group managed on non-biologic therapy, and 10 in the non-inflammatory control group). The majority (64.7%) of participants were men and the median age was 62 years (IQR: 48, 69). A significant drop in the thoracic aorta uptake was observed in the biologic-treated group (thoracic aorta change in TBRmax: -0.46±0.55) when compared to the change in the thoracic aorta FDG uptake of the PsO group treated with non-biologic therapy (thoracic aorta change in TBRmax: 0.23±0.67). Furthermore, the group with imaging evidence of a response to biologic agents (i.e. TBRmax drop > median value of 7%) maintained MFR (3.40±1.23 MFR to 3.5±1.2 MFR over 6 months) when compared to the group with a below median response on TBRmax which had a drop in MFR (2.9±0.8 MFR to 2.2±0.6 over 6 months) (P=0.03). <h3>CONCLUSION</h3> In a cohort of psoriasis patients treated with biologics, the FDG uptake in the thoracic aorta decreased over the study period compared to psoriasis patients treated with non-systemic therapies as well as controls. Additionally, psoriasis patients treated with biologics who demonstrated a significant anti-inflammatory response on FDG PET imaging, maintained their MFR compared to non-responders. This study supports the notion that there is a positive impact of immune therapies on vascular inflammation and microvascular disease in patients with chronic inflammation.

Multiparametric cardiac 18F-FDG PET in humans: pilot comparison of FDG delivery rate with 82Rb myocardial blood flow

Myocardial blood flow (MBF) and flow reserve are usually quantified in the clinic with positron emission tomography (PET) using a perfusion-specific radiotracer (e.g. 82Rb-chloride). However, the clinical accessibility of existing perfusion tracers remains limited. Meanwhile, 18F-fluorodeoxyglucose (FDG) is a commonly used radiotracer for PET metabolic imaging without similar limitations. In this paper, we explore the potential of 18F-FDG for myocardial perfusion imaging by comparing the myocardial FDG delivery rate K 1 with MBF as determined by dynamic 82Rb PET in fourteen human subjects with heart disease. Two sets of FDG K 1 were derived from one-hour dynamic FDG scans. One was the original FDG K 1 estimates and the other was the corresponding K 1 values that were linearly normalized for blood glucose levels. A generalized Renkin-Crone model was used to fit FDG K 1 with Rb MBF, which then allowed for a nonlinear extraction fraction correction for converting FDG K 1 to MBF. The linear correlation between FDG-derived MBF and Rb MBF was moderate (r = 0.79) before the glucose normalization and became much improved (r > 0.9) after glucose normalization. The extraction fraction of FDG was also similar to that of Rb-chloride in the myocardium. The results from this pilot study suggest that dynamic cardiac FDG-PET with tracer kinetic modeling has the potential to provide MBF in addition to its conventional use for metabolic imaging.