Translocator Protein 18 kDa Tracer 18F-FDPA PET/CTA Imaging for the Evaluation of Inflammation in Vulnerable Plaques.

Inflammation induced by activated macrophages within vulnerable atherosclerotic plaques (VAPs) constitutes a significant risk factor for plaque rupture. Translocator protein (TSPO) is highly expressed in activated macrophages. This study investigated the effectiveness of TSPO radiotracers, 18F-FDPA, in detecting VAPs and quantifying plaque inflammation in rabbits. 18 New Zealand rabbits were divided into 3 groups: sham group A, VAP model group B, and evolocumab treatment group C. 18F-FDPA PET/CTA imaging was performed at 12, 16, and 24 weeks in all groups. Optical coherence tomography (OCT) was performed on the abdominal aorta at 24 weeks. The VAP was defined through OCT images, and ex vivo aorta PET imaging was also performed at 24 weeks. The SUVmax and SUVmean of 18F-FDPA were measured on the target organ, and the target-to-background ratio (TBRmax) was calculated as SUVmax/SUVblood pool. The arterial sections of the isolated abdominal aorta were analyzed by HE staining, CD68 and TSPO immunofluorescence staining, and TSPO Western blot. The results showed that at 24 weeks, the plaque TBRmax of 18F-FDPA in group B was significantly higher than in groups A and C. Immunofluorescence staining of CD68 and TSPO, as well as Western blot, confirmed the increased expression of macrophages and TSPO in the corresponding regions of group B. HE staining revealed an increased presence of the lipid core, multiple foam cells, and inflammatory cell infiltration in the area with high 18F-FDPA uptake. This indicates a correlation between 18F-FDPA uptake, inflammation severity, and VAPs. The TSPO-targeted tracer 18F-FDPA shows specific uptake in macrophage-rich regions of atherosclerotic plaques, making it a valuable tool for assessing inflammation in VAPs.

The prognostic study of mental stress-induced myocardial ischemia in coronary revascularization patients with depression/anxiety: rationale and design.

BACKGROUND: Mental stress-induced myocardial ischemia (MSIMI) frequently occurs in patients with coronary artery disease (CAD), and is even more common in patients with co-occurring CAD and depression/anxiety. MSIMI appears to be a poor prognostic factor for CAD, but existing data on depression/anxiety patients are limited. METHODS: This cohort study will consecutively screen 2,647 CAD patients between 2023 and 2025. Included subjects will need to have received coronary revascularization and also have depression and/or anxiety at baseline. This study will enroll 360 subjects who meet the criteria. Two mental stress tests will be carried out in each patient at 1 month and 1 year timelines after coronary revascularization, using Stroop color word tests. MSIMI will be assessed by 99 m-Tc-sestamibi myocardial perfusion imaging. The endothelial function will be assessed by EndoPAT. Furthermore, we will dynamically monitor patients' health and mental conditions every 3 months. The mean follow-up time will be 1 year. The primary endpoint is the major adverse cardiac events, a composite of all-cause death, cardiac death, myocardial infarction, stroke, or unplanned revascularization. Secondary endpoints will include overall health and mental conditions. The reproducibility of mental stress combined with myocardial perfusion for detecting MSIMI and comparisons between coronary stenosis and ischemic segments will also be included. CONCLUSIONS: This cohort study will provide information on MSIMI outcomes in CAD patients who also have comorbid depression/anxiety after revascularization. In addition, understanding the long-term dynamics of MSIMI and the match between coronary stenosis and ischemia will provide insight into MSIMI mechanisms. TRAIL REGISTRATION: ChiCTR2200055792, 2022.1.20, www.medresman.org.cn.

Association between quality of life and mental stress-induced myocardial ischaemia in high-risk patients after coronary revascularization.

OBJECTIVE: We sought to determine the association between mental stress-induced myocardial ischaemia (MSIMI) and quality of life (QoL) in patients with coronary artery disease (CAD) after coronary revascularization. METHODS: This cohort study involved patients with high-risk MSIMI who received coronary revascularization between Dec 2018 and Dec 2019. Patients who screened positive for depression/anxiety were enrolled in this study. Mental stress was induced by the Stroop Colour and Word Test 1 month after coronary revascularization. All participants underwent single photon emission computed tomography (SPECT) scans at rest and under mental stress. MSIMI was defined as the presence of four abnormal SPECT phenomena. QoL was assessed using the Seattle Angina Questionnaire (SAQ) prior to treatment and 1 month after coronary revascularization. RESULTS: Of the 1845 consecutive patients who received coronary revascularization, 590 (31.9%) had depression/anxiety, and 205 agreed to accept the mental stress test. During the average observation period of 33 days, 105 (51.2%) patients exhibited MSIMI. All SAQ subscales showed significant improvement, except for QoL, in the MSIMI group. The QoL score was lower (- 0.2 ± 32.7 vs. 13.1 ± 29.9, P = 0.005), and the proportion of deterioration in QoL was higher (50.5% vs. 31.9%, P = 0.010) in the MSIMI group than in the non-MSIMI group. Those with a deterioration in QoL had approximately twice the rate of MSIMI than those with an improvement in QoL (unadjusted OR: 2.019, 95% CI 1.122-3.634, P = 0.026; adjusted OR: 1.968, 95% CI 1.083-3.578, P = 0.017). CONCLUSION: Among patients with CAD who received coronary revascularization and had depression/anxiety, deterioration in QoL increased the likelihood of MSIMI. Hence, our results indicate that deterioration in QoL is a predictor of MSIMI. Trail Registration ChiCTR2200055792, retrospectively registered, 2022.1.20, www.medresman.org.cn.

Molecular responses reveal that two glutathione S-transferase CsGSTU8s contribute to detoxification of glyphosate in tea plants (Camellia sinensis).

Tea plant (Camellia sinensis) is an important economical crop that frequently suffers from various herbicides, especially glyphosate. However, the molecular responses and regulatory mechanisms of glyphosate stress in tea plants remain poorly understood. Here, we reported a transcriptome dataset and identified large number of differentially expressed genes (DEGs) under glyphosate exposure. Next, two glutathione S-transferase genes (CsGSTU8-1 and CsGSTU8-2) that upregulated significantly were screened as candidate genes. Tissue-specific expression patterns showed that both CsGSTU8-1 and CsGSTU8-2 had extremely high expression levels in the roots and were predominantly localized in the nucleus and plasma membrane based on subcellular localization. Both were significantly upregulated at different time points under various stressors, including drought, cold, salt, pathogen infections, and SA treatments. An enzymatic activity assay showed that CsGSTU8-1 catalyzes the conjugation of glutathione with 2,4-dinitrochlorobenzene (CDNB). Functional analysis in yeast verified that the two genes significantly contributed to the detoxification of glyphosate, and CsGSTU8-1 had a stronger role in detoxification than CsGSTU8-2. Taken together, these findings provide insights into the molecular responses of tea plants to glyphosate and the functions of CsGSTU8s in glyphosate detoxification, which can be used as a promising genetic resource for improving herbicide resistance in tea cultivars.

[A comparison of ventilation/perfusion single photon emission CT and CT pulmonary angiography for diagnosis of pulmonary embolism].

OBJECTIVE: To assess the diagnostic accuracy of ventilation/perfusion (V/Q) single photon emission CT (SPECT) as compared to computed tomographic pulmonary angiography (CTPA) for pulmonary embolism (PE). METHODS: In this prospective multicenter study, 111 patients in whom acute or sub-acute PE was clinically confirmed or suspected were enrolled. The patients underwent one-day method V/Q lung scan (including SPECT and planar imaging) within 3 days before and after completion of CTPA. The European Association of Nuclear Medicine (EANM) guidelines for ventilation/perfusion scintigraphy (2009) reference was used as the evaluation criteria of V/Q SPECT imaging. The refined modified prospective investigation of pulmonary embolism diagnosis (RM-PIOPED) criteria was used for evaluation of planar imaging. According to the direct and indirect signs of PE, the imaging of CTPA was evaluated. All patients were followed for at least 6 months. A diagnosis was finally made by consensus of respiratory physicians, radiologists and nuclear medicine physicians based on the clinical data, laboratory tests, imaging features and follow-up results. The difference among diagnostic methods was evaluated for significance using chi-square test. The receiver operator characteristic (ROC) curve was drawn according to the results of the 3 diagnostic tests. The area under ROC curve (AUC) was calculated and compared. P < 0.05 was considered statistically significant. RESULTS: Among the 111 patients, PE was confirmed in 80, and excluded in 31. The diagnostic sensitivity/specificity/accuracy of V/Q SPECT, planar imaging, and CTPA were 85.9%/93.5%/88.1%, 75.7%/92.9%/81.4%, and 85.5%/90.0%/86.8%, respectively. By ROC curve analysis, the AUC values of V/Q SPECT, planar imaging and CTPA were 0.898, 0.838, and 0.877, respectively; with 95% confidence intervals [CI] 0.831 to 0.966, 0.759 to 0.917, and 0.801 to 0.954, respectively. The area of the fitted smooth ROC curve was statistically significant (P < 0.05) as compared with the area under the reference line. CONCLUSION: The results indicate that SPECT V/Q imaging is superior to V/Q planar scan and CTPA in the diagnosis of PE.

Corrigendum: Myocardial Viability, Functional Status, and Collaterals of Patients With Chronically Occluded Coronary Arteries.

[This corrects the article DOI: 10.3389/fcvm.2021.754826.].

Myocardial Viability, Functional Status, and Collaterals of Patients With Chronically Occluded Coronary Arteries.

Objective: Viability and functional assessments are recommended for indication and intervention for chronic coronary total occlusion (CTO). We aimed to evaluate myocardial viability and left ventricular (LV) functional status by using cardiovascular magnetic resonance (CMR) and to investigate the relationship between them and collaterals in patients with CTO. Materials and Methods: We enrolled 194 patients with one CTO artery as detected by coronary angiography. Patients were scheduled for CMR within 1 week after coronary angiography. Results: A total of 128 CTO territories (66%) showed scar based on late gadolinium enhancement (LGE) imaging. There were 1,112 segments in CTO territory, while only 198 segments (18%) subtended by the CTO artery showed transmural scar (i.e., >50% extent on LGE). Patients with viable myocardium had higher LV ejection fraction (LVEF) (56.7 ± 13.5% vs. 48.3 ± 15.4%, p < 0.001) than those with transmural scar. Angiographically, well-developed collaterals were found in 164 patients (85%). There was no significant correlation between collaterals and the presence of myocardial scar (p = 0.680) or between collaterals and LVEF (p = 0.191). Nevertheless, more segments with transmural scar were observed in patients with poorly-developed collaterals than in those with well-developed collaterals (25 vs. 17%, p = 0.010). Conclusion: Myocardial infarction detected by CMR is widespread among patients with CMO, yet only a bit of transmural myocardial scar was observed within CTO territory. Limited number of segments with transmural scar is associated with preserved LV function. Well-developed collaterals are not related to the prevalence of myocardial scar or systolic functioning, but could be related to reduce number of non-viable segments subtended by the CTO artery.

Left ventricular mechanical dyssynchrony analzyed by Tc-99m sestamibi SPECT and F-18 FDG PET in patients with ischemic cardiomyopathy and the prognostic value.

To compare the left ventricular (LV) phase dyssynchrony parameters obtained from Tc-99m Sestamibi SPECT (GSPECT) and F-18 FDG PET(GPET), as well as the prognostic values in patients with ischemic cardiomyopathy (ICM). Consecutive ICM patients referred for myocardial viability assessment were retrospectively evaluated and were followed-up for 21 ± 5 months. Phase parameter from both GSPECT and GPET were analyzed by QGS software, including histogram bandwidth (BW), standard deviation (SD) and entropy. Independent predictor for cardiac death was analyzed by Cox regression analysis. The estimated cardiac survival curve was analyzed by and was compared with the log-rank test. Eight-eight (mean age 56 ± 10, male 94%, LVEFSPECT23 ± 10%) ICM patients were included for analysis. Moderate correlations were observed for BW (r = 0.65; p < 0.001), SD (r = 0.63; p < 0.001) and entropy (r = 0.73; p < 0.001) between GSPECT and GPET. Among all covariates, the extent of myocardial scar was significantly associated with the differences of SD (r = 0.22; p < 0.05) and entropy (r = - 0.7; p < 0.05), whereas the extent of myocardial viability was not (all p > 0.05). Entropy measured by GSPECT was the predictor for cardiac death (p = 0.037) while QRS duration was not. The cardiac survival of patients with a high entropy (≥ 59%) was significantly lower than that of patients with low entropy (< 59%) (p < 0.05). GSPECT and GPET-derived phase parameters were not interchangeable in ICM patients. Patients with LV dyssynchrony measured by gated SPECT were associated with a worse outcome.

Automated synthesis and preliminary evaluation of [18F]FDPA for cardiac inflammation imaging in rats after myocardial infarction.

A translocator protein 18 kDa targeted radiotracer, N,N-diethyl-2-(2-(4-[18F]fluorophenyl)-5,7-dimethylpyrazolo[1,5-a] pyrimidin-3-yl) acetamide ([18F]FDPA), was automated synthetized and evaluated for cardiac inflammation imaging. Various reaction conditions for an automated synthesis were systematically optimized. MicroPET/CT imaging were performed on normal rats and rats with myocardial infarction (MI). Normalized SUV ratios of [18F]FDPA to [13N]NH3 (NSRs) in different regions were calculated to normalize the uptake of [18F]FDPA to perfusion. The amount of TBAOMs and the volume/proportion of water were crucial for synthesis. After optimization, the total synthesis time was 68 min. The non-decay corrected radiochemical yields (RCYs) and molar activities were 19.9 ± 1.7% and 169.7 ± 46.5 GBq/µmol, respectively. In normal rats, [18F]FDPA showed a high and stable cardiac uptake and fast clearance from other organs. In MI rats, NSRs in the peri-infarct and infarct regions, which were infiltrated with massive inflammatory cells revealed by pathology, were higher than that in the remote region (1.20 ± 0.01 and 1.08 ± 0.10 vs. 0.89 ± 0.05, respectively). [18F]FDPA was automated synthesized with high RCYs and molar activities. It showed a high uptake in inflammation regions and offered a wide time window for cardiac imaging, indicating it could be a potential cardiac inflammation imaging agent.

The success of opening concurrent chronic total occlusion lesion to improve cardiac function trial in patients with multi-vessel disease (SOS-moral): Study protocol of a prospective multicenter study.

AIMS: The purpose of the present trial is to determine whether opening co-existing chronic total occlusions (CTOs) using percutaneous coronary interventions (PCIs) improves cardiac function in patients with multi-vessel disease (MVD). Patients with MVD are defined as having at least one additional major vessel exhibiting no less than 75% stenosis combined with the presence of a CTO artery. METHODS AND RESULTS: Patients will be prospectively recruited who meet the following criteria:Patients presenting with no necrosis of myocardial tissue in the territory of the CTO will be excluded. Recruited patients will be randomized into 2 groups: those undergoing PCI of only the non-CTO artery (non-CTO PCI group), and those undergoing PCI of the non-CTO artery concurrently with the CTO artery (CTO-PCI group). The primary outcome will be the change in cardiac function evaluated via CMR at a 12-month of follow-up appointment, which will be compared to a baseline measurement. Secondary outcomes include occurrence of major cardiac events, CMR-assessed myocardial viability in the CTO-supplied territory, and quality of life assessed by Seattle angina questionnaire, Patient Health Questionnaire 9 and Generalized Anxiety Disorder Scale-7 after 12-month follow-up. CONCLUSION: The SOS-moral trial will provide data necessary to determine whether to open concurrent CTOs among MVD patients with CMR-detected necrotic myocardial tissue.

[In vivo noninvasive detection of vulnerable atherosclerotic plaque by (99)Tc(m)-Annexin V imaging in an atherosclerotic rabbit model.].

OBJECTIVE: Apoptosis contributes to the instability of the atherosclerotic (AS) lesions. The vulnerable plaque was identified in vivo by detecting the apoptosis with radiolabeled annexin V in an atherosclerotic rabbit model. METHODS: Eight male New Zealand white rabbits on 2% cholesterol diet for 2 weeks had abdominal aortic balloon injury and fed a 2% cholesterol diet for another 15 weeks (AS group), 3 rabbits fed a normal rabbit chow for 17 weeks without balloon injury served as controls. Annexin V labeled with (99)Tc(m) was then intravenously administered and planar whole-body images were captured using a gamma camera in the left lateral position. The entire length of the abdominal aorta was explanted for ex vivo imaging with gamma camera. The aorta then was divided into several segments according to the severity of AS. The segments were separated weighted and counted in an gamma counter for the absorptive dose of annexin per gram of tissue. Histology examinations were made on specimens. RESULTS: At 2 hours post annexin V injection, clear delineation of radiolabel within the abdominal aorta could be evidenced in vivo gamma imaging. After explanation of the aorta, ex vivo imaging showed a robust uptake of radiotracer in the infradiaphragmatic aorta corresponding to the in vivo images and conforming to the macroscopic distribution of atherosclerotic lesions. The uptake of radiolabel was absent in areas without grossly visible atherosclerotic lesions. The in vivo and ex vivo images identified plaque areas were identical and corresponded histological results on the explanted specimen. The aortic specimen was divided into 18 segments on lesions. The magority of the lesions (14/18) manifested as type IV or type V lesions of AHA classification (vulnerable lesions), except segments 1 - 4, which manifested as type I or type II lesions. The thickness of fibrous cap (TFC) and the ratio of cap and lipid nuclear (RCN) were significantly reversely correlated to the unit radioactivity counts, and the correlation between RCN and the unit radioactivity counts was more significant than that between TFC and the unit radioactivity counts (r = -0.904, P < 0.01, and r = -0.8, P < 0.01). Apoptosis detection (TUNEL): annexin V intake in plaques was positively correlated to apoptotic index(r = 0.651, P = 0.012). CONCLUSION: Noninvasive Annexin V imaging could be used to detect vulnerable atherosclerotic plaques in vivo.

Relationship between collateral circulation and myocardial viability of 18F-FDG PET/CT subtended by chronic total occluded coronary arteries.

OBJECTIVE: To analyze the relationship between the collateral flow of coronary chronic total occlusion (CTO) and myocardial viability detected by 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) imaging. METHODS: A prospective analysis of 104 patients diagnosed by coronary angiography. All patients underwent resting myocardial perfusion imaging and PET/CT within 1 week. The collateral circulation was graded with Rentrop classification as no or poor collateral circulation in 16 CTO vessels, moderate collateral circulation in 34 CTO vessels, and good collateral circulation in 69 CTO vessels. Myocardial viability was determined with myocardial perfusion imaging and PET. The patterns were interpreted as mismatch, match and normal perfusion and 18F-FDG uptake. RESULTS: There was no significant correlation between the severity and extent of perfusion defect, myocardial viability and collateral circulation grade. The myocardial viability was normal in mild and moderate hypokinetic regions and decreased in severe hypokinetic and akinesis-dyskinesis regions. The presence of collateral circulation was a sensitive (89%) but not a specific (31%) sign of myocardial viability. CONCLUSIONS: In patients with CTO, collateral circulation does not seem to be an effective way for predicting myocardial viability. Further analysis of PET patterns of viable myocardium is needed to guide further revascularization and predict functional improvement and survival benefit.