Myocardial Blood Flow Research Articles

Computed tomography myocardial perfusion imaging to detect myocardial ischemia in patients with anxiety and obstructive coronary heart disease post-exposure to mental stressors

This study aims to measure myocardial blood flow (MBF) using dynamic CT- myocardial perfusion imaging (CT-MPI) combined with mental stressors in patients with obstructive coronary artery disease (OCAD) and in patients with anxiety and no obstructive coronary artery disease (ANOCAD). A total of 30 patients with OCAD with 30 patients with ANOCAD were included in this analysis. Using the 17-segment model, the rest and stress phase MBF of major coronary arteries in participants were recorded respectively. Compared with ANOCAD patients, OCAD patients were more likely to have localized reduction of MBF (p < 0.05). For patients with ANOCAD, both global MBF and MBF of the main coronary arteries in the stress phase were lower than those in the rest phase (all p < 0.05), but there was no significant difference in MBF among the main coronary arteries in the rest or stress phase (p = 0.25, p = 0.15). For patients with OCAD, the MBF of the target area was lower than that of the non-target area in both the rest and stress phase, and the MBF of the target area in the stress phase was lower than that in the rest phase (all p < 0.05). However, there was no significant difference in MBF between the rest or stress phase in the non-target area (p = 0.73). Under mental stress, the decrease in MBF in ANOCAD patients was diffuse, while the decrease in MBF in OCAD patients was localized. Dynamic CT-MPI combined with mental stressors can be used to detect MBF changes in anxiety patients.

Value of Dynamic Computed Tomography Myocardial Perfusion in CAD: A Systematic Review and Meta-analysis.

Dynamic stress computed tomography (CT) perfusion is a non-invasive method for quantifying myocardial ischemia by assessing myocardial blood flow (MBF). In this meta-analysis, we evaluated the diagnostic accuracy of dynamic CT perfusion for the detection of significant coronary artery disease (CAD) across various CT scanners, obese patients, and its prognostic value. We systematically searched PubMed, Embase, Web of Science, and Cochrane library for published studies evaluating the accuracy of CT myocardial perfusion in diagnosing functional significant ischemia by invasive fractional flow reserve. The diagnostic performance of dynamic CT perfusion in detecting ischemia was evaluated using a summary receiver operating characteristic (sROC) curve. A total of 23 studies underwent meta- analysis. In myocardial region without ischemia, MBF was measured at 1.44 ml/min/g (95% confidence interval [CI]: 1.13-1.75), while in region with ischemia, it was 0.94 ml/min/g (95% CI: 0.80-1.08) (p<0.001). On the patient-based analysis, the area under the sROC curve of CT-MBF was 0.93, with a sensitivity of 0.84 and specificity of 0.88. Differences in CT type (dual source vs. single source), and body mass index (BMI) did not significantly affect the diagnostic performance. The pooled hazard ratio of dynamic CT perfusion for predicting adverse events was 4.98 (95%CI: 2.08-11.93, p=<0.001, I2=61%, p for heterogeneity = 0.07). Dynamic CT perfusion has high diagnostic performance in the quantitative assessment of ischemia and detection of functional myocardial ischemia as defined by invasive FFR, and may be useful in risk stratification of CAD patients.

Abstract PO3-19-04: The CROWN STUDY: A multicenter prospective cohort study of cardiovascular outcomes in premenopausal women with hormone receptor positive breast cancer treated with ovarian suppression and an aromatase inhibitor

Abstract Background: Treatment for premenopausal women with high or intermediate risk hormone receptor (HR)+ breast cancer (BC) includes the concurrent use of ovarian function suppression (OFS) and an aromatase inhibitor (AI) to induce near complete estrogen deprivation (NCED). The long-term cardiovascular (CV) sequela for women treated with NCED is unknown. Premature menopause in non-cancer populations is associated with CV disease. The CROWN study (CaRdiac Outcomes With Near complete estrogen deprivation) will use sophisticated imaging assessments of cardiac dysfunction to understand the evolution of CV injury, as well as biomarker and demographic correlates, with the goal of developing tools to assess and mitigate CV risk. Methods: This is a NIH funded prospective cohort study conducted at 3 regional NCI-supported Cancer Centers (Atrium Health Wake Forest Baptist, Virginia Commonwealth and Duke) that will include premenopausal women, age ≤ 55, with Stage I-III BC following completion of planned chemotherapy, surgery and radiation with an ECOG 0-1. HR+ BC patients will receive an AI and OFS. Women with HR- BC are included as comparators. CV imaging and biomarkers will be obtained at baseline, 1 year and 2 years (Table 1). These assessments will include serial cardiac magnetic resonance (CMR) and coronary computed tomography angiography (CCTA) imaging as well as laboratory measurements, including exploratory biomarkers. The primary objective is to determine the 24-month difference in stress myocardial blood flow as measured by adenosine CMR imaging in both groups. We will correlate CMR imaging with CCTA to provide complementary detail of coronary plaque changes. The study will also assess the relevance of pre-existing risk factors on study outcomes, including an emphasis on racial disparities, and dynamic change in modifiable and treatment related risk factors. We plan to enroll 90 women, 67 in the NCED group and 23 in the HR-group, allowing for a 10% drop out rate. There are two primary types of statistical analyses. The first includes testing hypotheses between group (NCED vs HR-) and within group (longitudinal changes within the NCED group). The second analyses, involve developing predictive equations utilizing a stepwise linear regression approach to determine if patient demographics, clinical parameters and serum biomarkers are associated with cardiovascular changes over time. A total of 17 patients are enrolled as of 07/2023. NCT05309655 Study Procedures XX- XX Citation Format: Susan Dent, Emily Douglas, Sarah Hatcher, Katherine Ansley, Carolyn Park, Nathaniel O'Connell, Mary Hackney, Ralph D'Agostino, Rani Bansal, Renee Avecilla, Monica Brown, Kacey Clayton-Stiglbauer, Igor Klem, Jennifer Jordan, Alexandra Thomas. The CROWN STUDY: A multicenter prospective cohort study of cardiovascular outcomes in premenopausal women with hormone receptor positive breast cancer treated with ovarian suppression and an aromatase inhibitor [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-19-04.

Myocardial Blood Flow in Newly Diagnosed Breast Cancer Patients at Rest and During Exercise

Heart depends critically on continuous supply of blood, but it is unknown whether cancer, without any treatments, affects myocardial blood flow (MBF) at rest or during exercise. This study therefore aimed at measuring MBF in cancer patients and control subjects and it was hypothesized that MBF is affected by cancer. The study included recently-diagnosed breast cancer patients (n=18) who had not started their oncologic treatments and age-matched female control participants (n=32). Controls were women referred to cardiac diagnostic testing but who were by this testing judged to be free of obstructive coronary artery disease. MBF was quantified with [15O]H2O positron emission tomography (PET) at rest in both groups and additionally during 10-min supine bicycling exercise in the breast cancer patients. Furthermore, cardiac morphological changes were analyzed with a breast cancer mice-model four weeks after the inoculation of 13TC mammary tumor cells. Respective mice without tumors served as controls. Resting heart rate (HR) and rate pressure product (RPP) correlated positively with resting MBF, but were similar in both groups resulting also in similar resting MBF in cancer patients and controls. MBF increased significantly from rest during exercise in breast cancer patients (p&lt;0.0001) and exercising MBF correlated positively with the histologic grade of cancer (r=0.54, p=0.021). However, cancer grade did not associate with exercise intensity measures such as HR, RPP or HR percentage from age-predicted maximal HR. In the mouse model, the breast cancer did not affect heart weight, cardiomyocyte size, myocardial capillary density, or capillary-to-myocyte size ratio. In conclusion, resting MBF in humans or myocardial capillarity in mice appear not to be affected by breast cancer. However, the more severe is the histologic grade of cancer, the higher is the MBF during exercise in patients with breast cancer, independently of the intensity of the exercise suggesting dysregulation of myocardial blood supply with cancer. This novel finding requires further investigations. This study was financially supported by Academy of Finland and Hospital District of South-West Finland. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

CORRELATION BETWEEN RETINAL MICROCIRCULATION, ECHOCARDIOGRAPHIC PARAMETERS AND MYOCARDIAL CORONARY FLOW RESERVE

Objective: Arterial hypertension causes cardiac functional and structural alterations. In hypertensive patients without flow-limiting epicardial coronary artery disease, we investigated the possible relationship between retinal microcirculation, positron emission tomography myocardial blood flow (MBF) and echocardiographic parameters of left ventricular (LV) performance, including mechano-energetic efficiency indexed for myocardial mass (MEEi) Design and method: Nineteen hypertensive patients (mean age 65 ± 11, 10 F) without flow-limiting epicardial coronary artery disease underwent patients wall-to-lumen ratio (WLR) and the cross-sectional area of the vascular wall (WCSA) of retinal arterioles by an Adaptive Optics (AO) retinal camera, echocardiography, including MEEi computation, and cardiac 13NH3 positron emission tomography (13NH3 PET) with assessment of myocardial coronary flow reserve (CFR). A positive 13NH3 PET was defined as a ratio of stress (regadenoson) myocardial blood flow (MBF)/mass and resting MBF/mass lower than 2. Results: No significant differences of demographic parameters were observed between patients with positive (n=6) vs negative (n=13) 13NH3 PET. In all patients WLR was significantly related to BMI (0,50, p=0.02), age (r=0.49, p=0.03)and LVMi (r=0.48, p=0.03) at univariate analysis. A negative correlation was also observed between WLR and total CFR (-0.64, p=0.003) and MMEi (-0.35, p=0.13). The relationship between WLR and CFR remained significant after adjustment for age and BMI (r=-0.49, p=0.047). Conclusions: In hypertensive patients without flow-limiting epicardial coronary artery disease, retinal WLR could reflect the presence of structural alterations in coronary microcirculation, possibly contributing to an impairment of CFR and to early LV dysfunction, as detected by low values of MEEi.

The Regulatory Role of microRNA-21 in Coronary Microcirculation in Metabolic Syndrome

Coronary vasculature is essential to supply oxygen and nutrients to the heart and maintain normal cardiac function. Obstruction of large vessels of coronaries (atherosclerosis) is well studied, but coronary microvascular dysfunction (CMD), which is associated with diabetic cardiomyopathy, Takotsubo cardiomyopathy, Ischemia with the non-obstructive coronary artery (INOCA), and HFpEF, is understudied. CMD is characterized by impaired endothelial-dependent vasodilation, but detailed mechanisms have yet to be elucidated. The anti-fibrotic role of microRNA-21 (miR-21) is reported in the HFrEF induced by ischemia/reperfusion or pressure overload, but how miR-21 regulates CMD is not entirely understood. Our recent study shows miR-21 ablation ameliorated impaired vasodilation in isolated coronaries of mice fed on high fat and high sugar (HFHS) diet. In this study, we examined the coronary flow reserve (CFR), the relationship between myocardial blood flow (MBF) and cardiac work (doppler) under hyperemia, cardiac function (echocardiography and exercise exertion test), fibrosis and gene expression of miR-21 knockout and wild-type (WT) mice fed on chow or HFHS diet. Our preliminary data show that MBF and CFR were decreased, cardiac index, stroke volume, and running distance were reduced, and the E/E’ ratio was increased in WT mice fed on the HFHS diet compared to the WT mice fed on the chow diet. The perivascular fibrosis was increased in the WT mice fed on the HFHS diet compared to WT mice on the chow diet. The ablation of miR-21 reversed all these changes in the mice treated with HFHS, suggesting miR-21 deficiency ameliorated CMD in metabolic syndrome. Moreover, we used endothelial-specific miR-21 knockout to study the endothelial miR-21 function. Interestingly, the endothelial mi-R21 KO phenocopied the global knockouts, suggesting the benefit of miR-21 deficiency to coronary microvascular function in metabolic syndrome is from endothelial cells. The study provides the potential therapeutic strategy to target vascular endothelial cells with miR-21 antagomir for CMD in metabolic syndromes. AHA 970663,1R56HL165207,1 R01 HL165207-01A1 to LY and 1 F31 HL156726-01A1 to CJ. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

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.

Personalized coronary and myocardial blood flow models incorporating CT perfusion imaging and synthetic vascular trees

Computational simulations of coronary artery blood flow, using anatomical models based on clinical imaging, are an emerging non-invasive tool for personalized treatment planning. However, current simulations contend with two related challenges – incomplete anatomies in image-based models due to the exclusion of arteries smaller than the imaging resolution, and the lack of personalized flow distributions informed by patient-specific imaging. We introduce a data-enabled, personalized and multi-scale flow simulation framework spanning large coronary arteries to myocardial microvasculature. It includes image-based coronary anatomies combined with synthetic vasculature for arteries below the imaging resolution, myocardial blood flow simulated using Darcy models, and systemic circulation represented as lumped-parameter networks. We propose an optimization-based method to personalize multiscale coronary flow simulations by assimilating clinical CT myocardial perfusion imaging and cardiac function measurements to yield patient-specific flow distributions and model parameters. Using this proof-of-concept study on a cohort of six patients, we reveal substantial differences in flow distributions and clinical diagnosis metrics between the proposed personalized framework and empirical methods based purely on anatomy; these errors cannot be predicted a priori. This suggests virtual treatment planning tools would benefit from increased personalization informed by emerging imaging methods.

Cardiomyocyte Ketone Metabolism Regulates Myocardial Hyperemia

Myocardial perfusion is inextricably coupled to metabolism, with increases in physiologic cardiac demand promoting coronary vasodilation. Despite its wide acceptance, the hypothesis that cardiomyocyte metabolism autoregulates myocardial perfusion lacks mechanistic detail; however, clinical and preclinical studies suggest a signaling role for intermediary metabolites in the vasodilatory response. In particular, the ketone body precursor, β-hydroxybutyrate (3-OHB), enhances myocardial blood flow in humans, but the mechanism by which it does so remains unclear. Here, we determined the extent to which 3-OHB influences myocardial hyperemia in mice. Intravenous 3-OHB infusion (0.5 g/kg) in adult mice (12–24 wks) raised circulating 3-OHB levels (0.5 ± 0.1 to 5.1 ± 0.6 mM; p=0.005) and increased myocardial perfusion (18.6 ± 4.4 to 50.9 ± 10.4 mL/min/g; p=0.024), as measured by myocardial contrast echocardiography. Enhanced perfusion induced by 3-OHB occurred in the absence of changes in cardiac output or systolic performance. Next, to determine if 3-OHB directly dilates the coronary vasculature, we exposed pressurized (80 mmHg), small-diameter (100–260 μm) coronary arteries from mice (C57/Bl6J and 6N) to 3-OHB (0.1–5 mM) but found no significant changes in diameter. Based on these results, we tested whether cardiomyocyte metabolism of 3-OHB is required for the vasodilatory response. We deleted β-hydroxybutyrate dehydrogenase (BDH1) selectively in cardiomyocytes using Bdh1fl/fl mice crossed with tamoxifen-inducible Cre recombinase mice (csBDH1−/−). Although 3-OHB robustly enhanced myocardial perfusion (6.9 ± 1.4 to 21.3 ± 5.6 mL/min/g; p=0.031) at sustained cardiac workloads and peripheral vascular resistance in Cre-negative littermate (control) mice, csBDH1−/− mice completely lacked the 3-OHB-induced hyperemic response (8.0 ± 2.5 to 6.3 ± 2.8 mL/min/g; p&gt;0.999). Together, these data indicate that 3-OHB evokes workload-independent enhancement of myocardial perfusion through a mechanism that requires cardiomyocyte metabolism of 3-OHB. Our results support the general concept that acute changes in metabolic substrate availability may influence oxygen delivery to cardiomyocytes via a cardiomyocyte-vascular signaling nexus. R01HL163818, R01HL142710, R01HL163003, P30GM127607, P30GM127607-05S1, Jewish Heritage Fund for Excellence (JHFE), S10OD025178. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Artificial Intelligence–Enabled Quantitative Coronary Plaque and Hemodynamic Analysis for Predicting Acute Coronary Syndrome

BackgroundA lesion-level risk prediction for acute coronary syndrome (ACS) needs better characterization. ObjectivesThis study sought to investigate the additive value of artificial intelligence–enabled quantitative coronary plaque and hemodynamic analysis (AI-QCPHA). MethodsAmong ACS patients who underwent coronary computed tomography angiography (CTA) from 1 month to 3 years before the ACS event, culprit and nonculprit lesions on coronary CTA were adjudicated based on invasive coronary angiography. The primary endpoint was the predictability of the risk models for ACS culprit lesions. The reference model included the Coronary Artery Disease Reporting and Data System, a standardized classification for stenosis severity, and high-risk plaque, defined as lesions with ≥2 adverse plaque characteristics. The new prediction model was the reference model plus AI-QCPHA features, selected by hierarchical clustering and information gain in the derivation cohort. The model performance was assessed in the validation cohort. ResultsAmong 351 patients (age: 65.9 ± 11.7 years) with 2,088 nonculprit and 363 culprit lesions, the median interval from coronary CTA to ACS event was 375 days (Q1-Q3: 95-645 days), and 223 patients (63.5%) presented with myocardial infarction. In the derivation cohort (n = 243), the best AI-QCPHA features were fractional flow reserve across the lesion, plaque burden, total plaque volume, low-attenuation plaque volume, and averaged percent total myocardial blood flow. The addition of AI-QCPHA features showed higher predictability than the reference model in the validation cohort (n = 108) (AUC: 0.84 vs 0.78; P < 0.001). The additive value of AI-QCPHA features was consistent across different timepoints from coronary CTA. ConclusionsAI-enabled plaque and hemodynamic quantification enhanced the predictability for ACS culprit lesions over the conventional coronary CTA analysis. (Exploring the Mechanism of Plaque Rupture in Acute Coronary Syndrome Using Coronary Computed Tomography Angiography and Computational Fluid Dynamics II [EMERALD-II]; NCT03591328)

Association of Hypertensive Disorders of Pregnancy With Coronary Microvascular Dysfunction 8 to 10 Years After Delivery.

Hypertensive disorders of pregnancy (HDP) are associated with subsequent adverse cardiac remodeling and cardiovascular disease. The role of myocardial microvascular disease among individuals with HDP and left ventricular (LV) remodeling as a potential link to cardiovascular disease is unknown. We aimed to determine whether individuals with HDP history have coronary microvascular dysfunction measured by coronary flow reserve 8 to 10 years after delivery and whether microvascular dysfunction correlates with LV remodeling. Individuals with pregnancies delivered from 2008 to 2010 underwent burst-replenishment myocardial contrast echocardiography (2017-2020) to quantify myocardial perfusion at rest and during dobutamine stress. Video intensity versus time data were used to derive β, the rate of rise of video intensity, a correlate for myocardial blood flow. Coronary flow reserve was calculated as the ratio of β at peak stress to β at rest, averaged across LV myocardial regions of interest. We studied 91 individuals (aged 38±6 and 9.1±0.9 years postdelivery) and 19 with a history of HDP. Individuals with coronary microvascular dysfunction (coronary flow reserve <2.0; n=13) had a higher proportion of HDP (46.2% versus 16.7%; P=0.026) and higher prepregnancy body mass index, baseline heart rate, and hemoglobin A1c compared with those without microvascular dysfunction. The association of coronary flow reserve and HDP was attenuated after adjusting for cardiometabolic factors (P=0.133). In exploratory subgroup analyses, individuals with both LV remodeling (relative wall thickness >0.42) and HDP (n=12) had the highest proportion of microvascular dysfunction (41.7% versus +HDP-LV remodeling [n=7] 14.3%; -HDP+LV remodeling [n=26] 7.7%; P=0.0498). In this small study, HDP history is associated with coronary microvascular dysfunction 1 decade after delivery, findings that may, in part, be driven by metabolic factors including obesity and diabetes. Microvascular dysfunction may contribute to cardiovascular disease among individuals with a history of HDP.

Arterial Input Function (AIF) Correction Using AIF Plus Tissue Inputs with a Bi-LSTM Network.

Background: The arterial input function (AIF) is vital for myocardial blood flow quantification in cardiac MRI to indicate the input time-concentration curve of a contrast agent. Inaccurate AIFs can significantly affect perfusion quantification. Purpose: When only saturated and biased AIFs are measured, this work investigates multiple ways of leveraging tissue curve information, including using AIF + tissue curves as inputs and optimizing the loss function for deep neural network training. Methods: Simulated data were generated using a 12-parameter AIF mathematical model for the AIF. Tissue curves were created from true AIFs combined with compartment-model parameters from a random distribution. Using Bloch simulations, a dictionary was constructed for a saturation-recovery 3D radial stack-of-stars sequence, accounting for deviations such as flip angle, T2* effects, and residual longitudinal magnetization after the saturation. A preliminary simulation study established the optimal tissue curve number using a bidirectional long short-term memory (Bi-LSTM) network with just AIF loss. Further optimization of the loss function involves comparing just AIF loss, AIF with compartment-model-based parameter loss, and AIF with compartment-model tissue loss. The optimized network was examined with both simulation and hybrid data, which included in vivo 3D stack-of-star datasets for testing. The AIF peak value accuracy and ktrans results were assessed. Results: Increasing the number of tissue curves can be beneficial when added tissue curves can provide extra information. Using just the AIF loss outperforms the other two proposed losses, including adding either a compartment-model-based tissue loss or a compartment-model parameter loss to the AIF loss. With the simulated data, the Bi-LSTM network reduced the AIF peak error from -23.6 ± 24.4% of the AIF using the dictionary method to 0.2 ± 7.2% (AIF input only) and 0.3 ± 2.5% (AIF + ten tissue curve inputs) of the network AIF. The corresponding ktrans error was reduced from -13.5 ± 8.8% to -0.6 ± 6.6% and 0.3 ± 2.1%. With the hybrid data (simulated data for training; in vivo data for testing), the AIF peak error was 15.0 ± 5.3% and the corresponding ktrans error was 20.7 ± 11.6% for the AIF using the dictionary method. The hybrid data revealed that using the AIF + tissue inputs reduced errors, with peak error (1.3 ± 11.1%) and ktrans error (-2.4 ± 6.7%). Conclusions: Integrating tissue curves with AIF curves into network inputs improves the precision of AI-driven AIF corrections. This result was seen both with simulated data and with applying the network trained only on simulated data to a limited in vivo test dataset.

Splenic switch-off in [15O]H2O-positron emission tomography myocardial perfusion imaging using parametric blood flow images

BackgroundEvaluation of sufficient adenosine response constitutes a significant challenge in myocardial perfusion imaging (MPI). Splenic switch-off in MPI studies denotes a visually (qualitatively) reduced splenic radiotracer signal during adenosine stress and is considered indicative of sufficient cardiac vasodilation. In this study, we examined semi-quantitative and quantitative approaches to splenic switch-off assessment using [15O]H2O-PET with either summed activity images or calculated parametric splenic blood flow images. MethodsCohort 1: 90 clinical patients undergoing [15O]H2O MPI in whom adenosine response was considered clinically adequate were identified to characterize the corresponding splenic switch-off. Spleen stress/rest-ratio (SSR-ratio) was calculated as spleen stress signal intensity/spleen rest signal intensity on both summed activity and parametric blood flow images.Cohort 2: Twenty-five patients with repeat MPI due to suspected insufficient adenosine response were identified to observe if splenic switch-off on the initial MPI could predict the outcome of the repeat MPI.Cohort 3: Fifty-four patients who were considered adenosine responders on MPI and who had a coronary angiogram (CAG) follow-up within 3 months after MPI served as a separate validation group. ResultsSplenic switch-off was present in most patients with a clinically sufficient adenosine response (Cohort 1), illustrated by both visual (74.4%–86.7%), semi-quantitative (summed activity images) (85.6%), and quantitative (parametric blood flow images) (92.2%) evaluation, which corresponds to the distribution in patients with sufficient adenosine response and follow-up CAG (Cohort 3). In patients suspected of insufficient adenosine response on the initial MPI (Cohort 2), the repeat MPI only yielded different myocardial blood flow (MBF) results if the initial SSR-ratio was >0.90 on splenic parametric blood flow images. Conclusionquantitative splenic switch-off assessment on parametric blood flow images was superior to the semi-quantitative splenic switch-off approach. Patients with a suspected insufficient initial adenosine response and SSR-ratio >0.90 can benefit from a repeat MPI. Thus, the integration of quantitative splenic switch-off using parametric blood flow images in the evaluation of adenosine response may support future clinical decision-making.

Association of cardiac mechanical dyssynchrony indices with data of dynamic single-photon emission computed tomography of the myocardium: the role of the time interval between the stress test and recording

Introduction. According to ECG-synchronized myocardial perfusion imaging (MPI) mechanical dyssynchrony (MD) is a sensitive marker of impaired myocardial perfusion. However, its direct comparison with indicators of myocardial blood flow reserve (MFR) according to single-photon emission computed tomography (SPECT) was not carried out. Traditional MPI protocols imply a long gap between stress test and image acquisition, during which stress-induced changes may pass. It is potentially possible to reduce the time interval down to 5 minutes.Aim: To investigate the relationship between early and delayed MD indices and the data of MFR by means of SPECT.Material and Methods. The study included 20 patients with suspected coronary heart disease, preserved left ventricular ejection fraction (&gt; 55%) and without obstructive coronary artery lesions (&lt; 50%) according to multislice computed coronary angiography. All patients underwent dynamic SPECT (dSPECT) according to a two-day rest/stress protocol. Gated MPI was performed 60 minutes after radiopharmaceutical administration. Myocardial blood flow and reserve, as well as phase histogram standard deviation (PSD, degree) and phase histogram bandwidth (HBW, degree) from 5 minutes after radiopharmaceutical administration were obtained from the dSPECT data by postprocessing. Perfusion data as well as MD indices (PSD, HBW) were obtained from delayed images. Based on dSPECT data, patients were divided into 2 groups: with preserved (MFR ≥ 2.0) and reduced (MFR &lt; 2.0) myocardial blood flow reserve.Results. Correlation analysis showed that MD indices on stress test in early scan had a stronger association with MFR (PSD ρ = –0.68, p &lt; 0.001; HBW ρ = –0.68, p = 0.001) compared to those in delayed scan (PSD ρ = –0.38, p = 0.019; HBW ρ = –0.44, p = 0.005). According to multivariate regression analysis, PSD on stress test at early scan was the only independent predictor of reduced MFR (OR 1.29 (1.1; 1.53)). Stress PSD &gt; 22° obtained at early scanning had a sensitivity of 81% and specificity of 87% (AUC = 0.86, p &lt; 0.001) in predicting of reduced MFR.Conclusion. Left ventricular mechanical dyssynchrony indices obtained by early post-stress gated MPI have a stronger association with myocardial blood flow reserve indices.

Comparing various AI approaches to traditional quantitative assessment of the myocardial perfusion in [82Rb] PET for MACE prediction

Assessing the individual risk of Major Adverse Cardiac Events (MACE) is of major importance as cardiovascular diseases remain the leading cause of death worldwide. Quantitative Myocardial Perfusion Imaging (MPI) parameters such as stress Myocardial Blood Flow (sMBF) or Myocardial Flow Reserve (MFR) constitutes the gold standard for prognosis assessment. We propose a systematic investigation of the value of Artificial Intelligence (AI) to leverage [82\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$^{82}$$\\end{document}Rb] Silicon PhotoMultiplier (SiPM) PET MPI for MACE prediction. We establish a general pipeline for AI model validation to assess and compare the performance of global (i.e. average of the entire MPI signal), regional (17 segments), radiomics and Convolutional Neural Network (CNN) models leveraging various MPI signals on a dataset of 234 patients. Results showed that all regional AI models significantly outperformed the global model (p<0.001\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$p<0.001$$\\end{document}), where the best AUC of 73.9% (CI 72.5–75.3) was obtained with a CNN model. A regional AI model based on MBF averages from 17 segments fed to a Logistic Regression (LR) constituted an excellent trade-off between model simplicity and performance, achieving an AUC of 73.4% (CI 72.3–74.7). A radiomics model based on intensity features revealed that the global average was the least important feature when compared to other aggregations of the MPI signal over the myocardium. We conclude that AI models can allow better personalized prognosis assessment for MACE.

Microvascular resistance reserve before and after PCI: A serial FFR and [15O] H2O PET study

Background and aimsMicrovascular Resistance Reserve (MRR) has recently been introduced as a microvasculature-specific index and hypothesized to be independent of coronary stenosis. The aim of this study was to investigate the change of MRR after percutaneous coronary intervention (PCI). MethodsIn this post-hoc analysis from the PACIFC trials, symptomatic patients underwent [15O]H2O positron emission tomography (PET) and invasive fractional flow reserve (FFR) before and after revascularization. Coronary flow reserve (CFR) from PET and invasive FFR were used to calculate MRR. ResultsAmong 52 patients (87 % male, age 59.4 ± 9.4 years), 61 vessels with a median FFR of 0.71 (95 % confidence interval: 0.55 to 0.74) and a mean MRR of 3.80 ± 1.23 were included. Following PCI, FFR, hyperemic myocardial blood flow (hMBF) and CFR increased significantly (all p-values ≤0.001). MRR remained unchanged after PCI (3.80 ± 1.23 before PCI versus 3.60 ± 0.97 after PCI; p=0.23). In vessels with a pre-PCI, FFR ≤0.70 pre- and post-PCI MRR were 3.90 ± 1.30 and 3.73 ± 1.14 (p=0.56), respectively. Similar findings were observed for vessels with a FFR between 0.71 and 0.80 (pre-PCI MRR 3.70 ± 1.17 vs. post PCI MRR 3.48 ± 0.76, p=0.19). ConclusionsOur study indicates that MRR, assessed using a hybrid approach of PET and invasive FFR, is independent of the severity of epicardial stenosis. These findings suggest that MRR is a microvasculature-specific parameter.

Prognostic value of a novel artificial intelligence-based coronary CTA-derived ischemia algorithm among patients with normal or abnormal myocardial perfusion

BackgroundAmong patients with obstructive coronary artery disease (CAD) on coronary computed tomography angiography (CTA), downstream positron emission tomography (PET) perfusion imaging can be performed to assess the presence of myocardial ischemia. A novel artificial-intelligence-guided quantitative computed tomography ischemia algorithm (AI-QCTischemia) aims to predict ischemia directly from coronary CTA images. We aimed to study the prognostic value of AI-QCTischemia among patients with obstructive CAD on coronary CTA and normal or abnormal downstream PET perfusion. MethodsAI-QCTischemia was calculated by blinded analysts among patients from the retrospective coronary CTA cohort at Turku University Hospital, Finland, with obstructive CAD on initial visual reading (diameter stenosis ≥50%) being referred for downstream 15O-H2O-PET adenosine stress perfusion imaging. All coronary arteries with their side branches were assessed by AI-QCTischemia. Absolute stress myocardial blood flow ≤2.3 ​ml/g/min in ≥2 adjacent segments was considered abnormal. The primary endpoint was death, myocardial infarction, or unstable angina pectoris. The median follow-up was 6.2 [IQR 4.4–8.3] years. Results662 of 768 (86%) patients had conclusive AI-QCTischemia result. In patients with normal 15O-H2O-PET perfusion, an abnormal AI-QCTischemia result (n ​= ​147/331) vs. normal AI-QCTischemia result (n ​= ​184/331) was associated with a significantly higher crude and adjusted rates of the primary endpoint (adjusted HR 2.47, 95% CI 1.17–5.21, p ​= ​0.018). This did not pertain to patients with abnormal 15O-H2O-PET perfusion (abnormal AI-QCTischemia result (n ​= ​269/331) vs. normal AI-QCTischemia result (n ​= ​62/331); adjusted HR 1.09, 95% CI 0.58–2.02, p ​= ​0.794) (p-interaction ​= ​0.039). ConclusionAmong patients with obstructive CAD on coronary CTA referred for downstream 15O-H2O-PET perfusion imaging, AI-QCTischemia showed incremental prognostic value among patients with preserved perfusion by 15O-H2O-PET imaging, but not among those with reduced perfusion.

Study of Attenuation Correction Using a Cardiac Dynamic Phantom: Synchronized Time-Phase-Gated Attenuation Correction Method.

In cardiac nuclear medicine examinations, absorption in the body is the main factor in the degradation of the image quality. The Chang and external source methods were used to correct for absorption in the body. However, fundamental studies on attenuation correction for electrocardiogram (ECG)-synchronized CT imaging have not been performed. Therefore, we developed and improved an ECG-synchronized cardiac dynamic phantom and investigated the synchronized time-phase-gated attenuation correction (STPGAC) method using ECG-synchronized SPECT and CT images of the same time phase. Methods: As a basic study, SPECT was performed using synchronized time-phase-gated (STPG) SPECT and non-phase-gated (NPG) SPECT. The attenuation-corrected images were, first, CT images with the same time phase as the ECG waveform of the gated SPECT acquisition (with CT images with the ECG waveform of the CT acquisition as the reference); second, CT images with asynchronous ECG; third, CT images of the 75% region; and fourth, CT images of the 40% region. Results: In the analysis of cardiac function in the phantom experiment, left ventricle ejection fraction (heart rate, 11.5%-13.4%; myocardial wall, 49.8%-55.7%) in the CT images was compared with that in the STPGAC method (heart rate, 11.5%-13.3%; myocardial wall, 49.6%-55.5%), which was closer in value to that of the STPGAC method. In the phantom polar map segment analyses, none of the images showed variability (F (10,10) < 0.5, P = 0.05). All images were correlated (r = 0.824-1.00). Conclusion: In this study, we investigated the STPGAC method using a SPECT/CT system. The STPGAC method showed similar values of cardiac function analysis to the CT images, suggesting that the STPGAC method accurately reconstructed the distribution of blood flow in the myocardial region. However, the target area for attenuation correction of the heart region was smaller than that of the whole body, and changing the gated SPECT conditions and attenuation-corrected images did not affect myocardial blood flow analysis.

Coronary Microvascular Dysfunction in Acute Cholestasis-Induced Liver Injury.

Previous studies have shown cardiac abnormalities in acute liver injury, suggesting a potential role in the associated high mortality. We designed an experimental study exploring the short-term effects of acute cholestasis-induced liver injury on cardiac function and structure in a rodent bile duct ligation (BDL) model to elucidate the potential interplay. Thirty-seven male Sprague-Dawley rats were subjected to BDL surgery (n = 28) or served as sham-operated (n = 9) controls. Transthoracic echocardiography, Doppler evaluation of the left anterior descending coronary artery, and myocardial contrast echocardiography were performed at rest and during adenosine and dobutamine stress 5 days after BDL. Immunohistochemical staining of myocardial tissue samples for hypoxia and inflammation as well as serum analysis were performed. BDL animals exhibited acute liver injury with elevated transaminases, bilirubin, and total circulating bile acids (TBA) 5 days after BDL (TBA control: 0.81 ± 2.54 µmol/L vs. BDL: 127.52 ± 57.03 µmol/L; p < 0.001). Concurrently, cardiac function was significantly impaired, characterized by reduced cardiac output (CO) and global longitudinal strain (GLS) in the echocardiography at rest and under pharmacological stress (CO rest control: 120.6 ± 24.3 mL/min vs. BDL 102.5 ± 16.6 mL/min, p = 0.041; GLS rest control: -24.05 ± 3.8% vs. BDL: -18.5 ± 5.1%, p = 0.01). Myocardial perfusion analysis revealed a reduced myocardial blood flow at rest and a decreased coronary flow velocity reserve (CFVR) under dobutamine stress in the BDL animals (CFVR control: 2.1 ± 0.6 vs. BDL: 1.7 ± 0.5 p = 0.047). Immunofluorescence staining indicated myocardial hypoxia and increased neutrophil infiltration. In summary, acute cholestasis-induced liver injury can lead to impaired cardiac function mediated by coronary microvascular dysfunction, suggesting that major adverse cardiac events may contribute to the mortality of acute liver failure. This may be due to endothelial dysfunction and direct bile acid signaling.

Impact of sex on myocardial perfusion following percutaneous coronary intervention of chronic total coronary occlusions

ObjectivesWe sought to investigate the impact of sex on myocardial perfusion changes following chronic total coronary occlusion (CTO) percutaneous coronary intervention (PCI) as measured by [15O]H2O positron-emission tomography (PET) perfusion imaging. BackgroundCTO PCI has been associated with an increase in myocardial perfusion, yet females are less likely to undergo revascularization. As such, data on the impact of sex on myocardial perfusion following CTO PCI is scarce. MethodsA total of 212 patients were prospectively enrolled and underwent CTO PCI combined with [15O]H2O PET perfusion imaging prior to and 3 months after PCI. Hyperemic myocardial blood flow (hMBF, mL·min−1·g−1) and coronary flow reserve (CFR) allocated to the CTO territory were quantitatively assessed. ResultsThis study comprised 34 (16 %) females and 178 (84 %) males. HMBF at baseline did not differ between sexes. Females showed a higher increase in hMBF than males (Δ1.34 ± 0.67 vs. Δ1.06 ± 0.74, p = 0.044), whereas post-PCI hMBF was comparable (2.59 ± 0.85 in females vs. 2.28 ± 0.84 in males, p = 0.052). Female sex was independently associated with a higher increase in hMBF after correction for clinical covariates. CFR increase after revascularization was similar in females and males (Δ1.47 ± 0.99 vs. Δ1.30 ± 1.14, p = 0.711). ConclusionsThe present study demonstrates a greater recovery of stress perfusion in females compared to males as measured by serial [15O]H2O PET imaging. In addition, a comparable increase in CFR was found in females and males. These results emphasize the benefit of performing CTO PCI in both sexes. Clinical perspectiveWhat is new?•CTO PCI has been associated with an increase in myocardial perfusion, yet females are less likely to undergo revascularization.•We found a greater recovery of stress perfusion in females compared to males after CTO PCI as measured by serial [15O]H2O PET imaging, whereas coronary flow reserve was comparable between sexes.•The present study adds to the limited body of evidence on the impact of sex on myocardial perfusion following CTO PCI.What are the clinical implications?•Our findings suggest that recovery of myocardial perfusion following CTO PCI is achievable in both female and male patients.•These results underscore the need to adhere to current guidelines for optimal CTO management in both sexes.•Future studies with standardized preprocedural imaging are warranted to increase our understanding of the impact of sex on changes in myocardial perfusion following CTO PCI.