BACKGROUND: This study aims to assess the prognostic significance of myocardial blood flow (MBF) quantification parameters obtained through cadmium-zinc-telluride (CZT)-single-photon emission computed tomography (SPECT)...BACKGROUND: This study aims to assess the prognostic significance of myocardial blood flow (MBF) quantification parameters obtained through cadmium-zinc-telluride (CZT)-single-photon emission computed tomography (SPECT) in post-percutaneous coronary intervention (post-PCI) acute myocardial infarction (AMI) patient population. METHODS: A prospective cohort comprising 144 AMI patients who underwent primary PCI was enrolled. All participants received PCI within 12 hours of AMI diagnosis and subsequently underwent cardiac-dedicated CZT-SPECT dynamic imaging within two weeks post procedure. Quantitative MBF parameters, semiquantitative perfusion scores, and left ventricular functional parameters were collected. Major adverse cardiovascular events (MACEs) were defined as cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, heart failure, late coronary revascularization, or hospitalization due to unstable angina. RESULTS: Over a median follow-up duration of 27 months (interquartile range: 15-37), a total of 40 MACEs were observed. Stress myocardial blood flow (sMBF) (P < 0.001) and myocardial flow reserve (MFR) (P = 0.002) were significantly lower in patients with MACEs. Receiver operating characteristic analysis determined optimal prognostic thresholds: sMBF <1.39 (area under the curve [AUC]: 0.67, 95% confidence interval [CI]: 0.58-0.76, sensitivity: 46.2%, specificity: 90.0%, P < 0.001) and MFR <1.84 (AUC: 0.66, 95% CI: 0.57-0.75, sensitivity: 44.2%, specificity: 90.0%, P < 0.01). The Kaplan-Meier survival analysis demonstrated significantly diminished event-free survival in patients exhibiting impaired sMBF (log-rank = 14.67; P < 0.0001) or MFR (log-rank = 12.98; P = 0.0003). CONCLUSIONS: CZT-SPECT MBF quantification provides substantial prognostic value for post-PCI AMI patients. Importantly, stress-induced sMBF and MFR were identified as independent predictors of MACEs, demonstrating enhanced diagnostic efficacy over traditional semiquantitative perfusion parameters.
BACKGROUND: This study aims to establish lower reference values for myocardial blood flow (MBF) and myocardial flow reserve (MFR) measured by rubidium-82 (Rb) myocardial perfusion imaging (MPI) in patients at a low risk...BACKGROUND: This study aims to establish lower reference values for myocardial blood flow (MBF) and myocardial flow reserve (MFR) measured by rubidium-82 (Rb) myocardial perfusion imaging (MPI) in patients at a low risk for coronary artery disease (CAD). METHODS: This single-center study included 3320 patients with very low risk of obstructive CAD who underwent dipyridamole Rb positron emission tomography MPI. Patients were grouped by biological sex and age (≤40, 41-50, 51-60, 61-70, 71-80, and ≥81 years). Lower reference limits were derived using the Hoffmann method. RESULTS: Rest MBF increased with age in females (r = 0.104, P < 0.001) and males (r = 0.149, P < 0.001), while stress MBF and MFR decreased with age in both females (r = -0.344, P < 0.001; r = -0.440, P < 0.001) and males (r = -0.371, P < 0.001; r = -0.479, P < 0.001). Females had significantly higher rest and stress MBF and lower MFR than males (P < 0.001). MFR lower reference limits were 2.14, 2.11, 1.94, 1.77, 1.57, and 1.38 for females and 2.05, 2.32, 1.97, 1.92, 1.56, and 1.28 for males across the six age groups. Stress MBF lower reference limits were 2.46, 2.34, 2.23, 2.04, 1.84, and 1.59 mL/min/g for females and 1.85, 1.88, 1.65, 1.56, 1.33, and 1.20 mL/g/min for males across the six age groups. CONCLUSIONS: This study establishes sex- and age-specific lower reference limits for stress MBF and MFR in low-risk CAD patients. Females exhibited higher stress MBF and MFR than males, while both values declined with age in both sexes. These findings underscore the necessity of incorporating sex- and age-adjusted reference values when interpreting MBF and MFR in clinical practice.
Kounga C, Huck D, Sun A
… +11 more, Perillo A, Goldstein LB, Hainer JM, Lopez DM, Brown JM, Divakaran S, Dorbala S, Blankstein R, Woolley A, Di Carli MF, Weber B
BACKGROUND: Cardiovascular complications from coronavirus disease 2019 (COVID-19) contribute to its morbidity. COVID-19 has been associated with coronary microvascular dysfunction (CMD), yet the long-term relationship is...BACKGROUND: Cardiovascular complications from coronavirus disease 2019 (COVID-19) contribute to its morbidity. COVID-19 has been associated with coronary microvascular dysfunction (CMD), yet the long-term relationship is not well understood. We aimed to assess changes in CMD status and myocardial flow reserve (MFR among patients with prior COVID-19 infection using serial cardiac PET/CT imaging. METHODS: single-center study of 35 patients who underwent clinically indicated PET/CT before and after COVID-19 infection. They were compared with 70 historical COVID-19-negative controls matched 2:1 for age and sex, and cardiovascular risk factors. MFR less than 2 was used to define CMD. The primary outcome was the change in global MFR (ΔMFR = follow-up-baseline). Linear and conditional logistic regression were used to account for matching dependencies. RESULTS: The median interval between PET/CT studies among COVID-19 patients was 2.8 years. Most patients had mild symptoms, and 94% were immunized. Baseline perfusion abnormalities were similar between groups (13% vs 29%, P = 0.05). There was no significant difference in global ΔMFR between COVID-19 and control groups (0.07 vs -0.10, P = 0.23). CMD status remained unchanged among most participants (83% in the COVID-19 group and 60% in controls). CONCLUSIONS: Despite prior evidence of an association between COVID-19 and CMD, there were no apparent longitudinal changes in MFR and CMD status in patients with recovered COVID-19 infection. These findings suggest that mild COVID-19 infection does not confer persistent coronary microvascular dysfunction detectable by PET/CT.
BACKGROUND: Gadolinium-1,4,7,10-Tetraazacyclodecane-1,4,7,10-tetraacetic acid (Gd DOTA) and similar magnetic resonance imaging (MRI) contrast agents are suggested as markers for myocardial blood flow (MBF). Contrary to M...BACKGROUND: Gadolinium-1,4,7,10-Tetraazacyclodecane-1,4,7,10-tetraacetic acid (Gd DOTA) and similar magnetic resonance imaging (MRI) contrast agents are suggested as markers for myocardial blood flow (MBF). Contrary to MRI, the positron emission tomography (PET) signal is directly proportional to radioactivity concentration, and hence a PET-analog of Gd-DOTA could be used to assess the kinetics of DOTA-based agents without the challenges of measuring Gd concentrations with MRI. The aim of the present work was to assess the suitability of Gd-DOTA as a marker of MBF by comparing Ga-DOTA as a PET analog of Gd-DOTA to the gold standard for noninvasive measurement of MBF, O-water PET. METHODS: A total of 24 patients underwent dynamic O-water-PET during rest and pharmacological stress, followed by Ga-DOTA-PET and Gd-DOTA dynamic contrast-enhanced MRI on an integrated PET/MR scanner. Ga-DOTA-PET was analyzed using single-tissue and two-tissue irreversible compartment models. The dynamic contrast-enhanced MRI perfusion data were analyzed using a single-tissue reversible compartment model. K of Ga-DOTA was compared with O-water. Permeability-surface area product for Ga-DOTA was estimated using the Renkin-Crone equation. RESULTS: Kinetics of Ga-DOTA were well-described by a single-tissue compartment model. The permeability-surface area product of Ga-DOTA was 0.70 + 0.15 × MBF (mL/cm/min), corresponding to an extraction of around 30% at typical hyperemic MBF values. Average whole-myocardium Ga-DOTA K values ranged between 0.35 and 1.36 mL/cm/min compared to 0.68 and 4.55 mL/cm/min for O-water. Ga-DOTA and Gd-DOTA K values showed no significant differences. The correlation between Ga-DOTA MBF and O-water MBF was moderate (r = 0.66). CONCLUSIONS: Extraction of DOTA is low and depends on flow, resulting in a high variability and uncertainty of hyperemic MBF values.
Total-body positron emission tomography (PET) systems with a long axial field of view (LAFOV) are now commercially available and represent the state of the art in PET imaging. These systems provide wide anatomical covera...Total-body positron emission tomography (PET) systems with a long axial field of view (LAFOV) are now commercially available and represent the state of the art in PET imaging. These systems provide wide anatomical coverage and markedly increased detection sensitivity. Clinical studies have demonstrated enhanced image quality, superior quantification, and benefits for tracer kinetic modeling through dynamic imaging. LAFOV PET/CT allows for substantial reductions in acquisition time and radiation dose while maintaining diagnostic image quality. Full-body coverage enables dynamic whole-body imaging, which enables tracer kinetic modeling across multiple organs and the large vascular structures, offering new opportunities for studying their interactions in cardiovascular and systemic diseases. Furthermore, these systems facilitate the development of new PET methods including pharmacokinetics of new tracers. This review discusses the emerging opportunities and challenges associated with the application of LAFOV PET/CT systems in cardiovascular diseases.
Iqbal I, Liljenbäck H, Andriana P
… +16 more, Ståhle M, Virta J, Atencio Herre E, Miner MWG, Anand A, Suni A, Nammas W, Kytö V, Mansour HMA, Cleveland NA, Li XG, Srinivasarao M, Low PS, Knuuti J, Roivainen A, Saraste A
BACKGROUND: Folate receptor β (FR-β) is expressed on activated macrophages in inflammatory conditions. In order to study FR-β in inflammatory response following myocardial infarction (MI), we evaluated FR-β-targeted PET...BACKGROUND: Folate receptor β (FR-β) is expressed on activated macrophages in inflammatory conditions. In order to study FR-β in inflammatory response following myocardial infarction (MI), we evaluated FR-β-targeted PET imaging using aluminum fluoride-18-labeled NOTA-folate ([F]FOL) in a rat model of MI. METHODS: Rats underwent [F]FOL PET imaging on 3, 7, 15, and 90 days after induction of MI by permanent coronary artery ligation or sham operation. [F]FDG PET was performed a day before [F]FOL scans to localize the infarct area. A subset of rats underwent [F]FOL PET on day 7 and serial echocardiography until 90 days post-surgery. RESULTS: The [F]FOL uptake was significantly higher in the infarct area than in the myocardium of sham-operated rats on day 3 (SUV 1.97 ± 0.17 vs 0.74 ± 0.13), and remained higher on day 7 (SUV 1.35 ± 0.33 vs 0.70 ± 0.16), day 15 (SUV 1.24 ± 0.20 vs 0.59 ± 0.07), and day 90 (SUV 1.39 ± 0.25 vs 0.69 ± 0.11). Autoradiography of tissue sections confirmed tracer uptake in the infarct area, where immunofluorescence showed FR-β in CD68-positive macrophages. Uptake of [F]FOL correlated with CD68-positive macrophage density (r = 0.669, P < 0.001) and was associated with decline in left ventricular ejection fraction between days 7 and 90 post-MI (r = -0.665, P = 0.007). CONCLUSION: [F]FOL PET detects expression of FR-β, a marker of activated macrophages after MI. FR-β expression peaks early and remains elevated up to 3 months post-MI. Early FR-β expression is associated with worsening of left ventricular systolic function.
BACKGROUND: [F]flurpiridaz is a newly FDA-approved tracer for positron emission tomography myocardial perfusion imaging (PET MPI) with a long half-life and improved physical characteristics. However, its long half-life l...BACKGROUND: [F]flurpiridaz is a newly FDA-approved tracer for positron emission tomography myocardial perfusion imaging (PET MPI) with a long half-life and improved physical characteristics. However, its long half-life leads to residual rest activity. Prior trials used 30 to 60 minutes delays between rest and stress injections and proposed stress-to-rest dose ratios of 1:2 to 1:3 to mitigate the potential impact of residual rest counts on the stress myocardial perfusion images. OBJECTIVE: To evaluate the effect of stress-to-rest dose ratio and time interval between injections on residual activity. METHODS: We analyzed consecutive 115 patients who underwent PET MPI with [F]flurpiridaz. Relative residual activity was calculated as the ratio of tissue activity concentration (kBq/mL) in the first stress frame to that in the stress tissue phase. Linear regression was used to assess the association of dose ratio and injection time interval with global residual activity. The optimal dose ratio cutoff was identified. Mixed-effects models with interaction terms were used to assess whether the effect varied across vascular territories. RESULTS: A total of 115 patients underwent PET MPI. Results showed that increasing the stress-to-rest dose ratio was significantly associated with lower relative residual activity (β = -3.41; 95% confidence interval (CI): -4.72; -2.11 per 1-unit increase), while increasing the time interval between injections up to 39 minutes showed no significant association (β = 0.03 95% CI: -0.12; 0.17 per 1-minute increase) within this time window. The optimal cutoff dose ratio to achieve relative residual activity <20% ranged between 3.2 and 4.3. CONCLUSION: Increasing the stress-to-rest dose ratio between 3.2 and 4.3 effectively reduces residual activity to <20% of the stress dose across all time intervals, thereby enabling back-to-back imaging and improving protocol efficiency on digital PET systems. Further validation is warranted for older, non-digital scanners.