| 1. |
- Hansson, Nils Henrik, et al.
(författare)
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Evaluation of ECG-gated [(11)C]acetate PET for measuring left ventricular volumes, mass, and myocardial external efficiency
- 2016
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Ingår i: Journal of Nuclear Cardiology. - : Springer Science and Business Media LLC. - 1071-3581 .- 1532-6551. ; 23:4, s. 670-9
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Noninvasive estimation of myocardial external efficiency (MEE) requires measurements of left ventricular (LV) oxygen consumption with [(11)C]acetate PET in addition to LV stroke volume and mass with cardiovascular magnetic resonance (CMR). Measuring LV geometry directly from ECG-gated [(11)C]acetate PET might enable MEE evaluation from a single PET scan. Therefore, we sought to establish the accuracy of measuring LV volumes, mass, and MEE directly from ECG-gated [(11)C]acetate PET.METHODS: Thirty-five subjects with aortic valve stenosis underwent ECG-gated [(11)C]acetate PET and CMR. List mode PET data were rebinned into 16-bin ECG-gated uptake images before measuring LV volumes and mass using commercial software and compared to CMR. Dynamic datasets were used for calculation of mean LV oxygen consumption and MEE.RESULTS: LV mass, volumes, and ejection fraction measured by CMR and PET correlated strongly (r = 0.86-0.92, P < .001 for all), but were underestimated by PET (P < .001 for all except ESV P = .79). PET-based MEE, corrected for bias, correlated fairly with PET/CMR-based MEE (r = 0.60, P < .001, bias -3 ± 21%, P = .56). PET-based MEE bias was strongly associated with LV wall thickness.CONCLUSIONS: Although analysis-related improvements in accuracy are recommended, LV geometry estimated from ECG-gated [(11)C]acetate PET correlate excellently with CMR and can indeed be used to evaluate MEE.
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| 2. |
- Harms, Hendrik Johannes, et al.
(författare)
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Automatic Extraction of Myocardial Mass and Volume Using Parametric Images from Dynamic Nongated PET
- 2016
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Ingår i: Journal of Nuclear Medicine. - : Society of Nuclear Medicine. - 0161-5505 .- 1535-5667 .- 2159-662X. ; 57:9, s. 1382-1387
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Tidskriftsartikel (refereegranskat)abstract
- Dynamic cardiac PET is used to quantify molecular processes in vivo. However, measurements of left ventricular (LV) mass and volume require electrocardiogram-gated PET data. The aim of this study was to explore the feasibility of measuring LV geometry using nongated dynamic cardiac PET. Methods: Thirty-five patients with aortic-valve stenosis and 10 healthy controls underwent a 27-min C-11-acetate PET/CT scan and cardiac MRI (CMR). The controls were scanned twice to assess repeatability. Parametric images of uptake rate K-1 and the blood pool were generated from nongated dynamic data. Using software-based structure recognition, the LV wall was automatically segmented from K-1 images to derive functional assessments of LV mass (m(LV)) and wall thickness. End systolic and end-diastolic volumes were calculated using blood pool images and applied to obtain stroke volume and LV ejection fraction (LVEF). PET measurements were compared with CMR. Results: High, linear correlations were found for LV mass (r = 0.95), end-systolic volume (r = 0.93), and end-diastolic volume (r = 0.90), and slightly lower correlations were found for stroke volume (r = 0.74), LVEF (r = 0.81), and thickness (r = 0.78). Bland Altman analyses showed significant differences for m(LV) and thickness only and an overestimation for LVEF at lower values. Intra- and interobserver correlations were greater than 0.95 for all PET measurements. PET repeatability accuracy in the controls was comparable to CMR. Conclusion: LV mass and volume are accurately and automatically generated from dynamic C-11-acetate PET without electrocardiogram gating. This method can be incorporated in a standard routine without any additional workload and can, in theory, be extended to other PET tracers.
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| 3. |
- Lillethorup, Thea Pinholt, et al.
(författare)
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In vivo quantification of glial activation in minipigs overexpressing human α-synuclein
- 2018
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Ingår i: Synapse. - : Wiley. - 0887-4476. ; 72:12
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Tidskriftsartikel (refereegranskat)abstract
- Parkinson’s disease is characterized by a progressive loss of substantia nigra (SN) dopaminergic neurons and the formation of Lewy bodies containing accumulated alpha-synuclein (α-syn). The pathology of Parkinson’s disease is associated with neuroinflammatory microglial activation, which may contribute to the ongoing neurodegeneration. This study investigates the in vivo microglial and dopaminergic response to overexpression of α-syn. We used positron emission tomography (PET) and the 18 kDa translocator protein radioligand, [11C](R)PK11195, to image brain microglial activation and (+)-α-[11C]dihydrotetrabenazine ([11C]DTBZ), to measure vesicular monoamine transporter 2 (VMAT2) availability in Göttingen minipigs following injection with recombinant adeno-associated virus (rAAV) vectors expressing either mutant A53T α-syn or green fluorescent protein (GFP) into the SN (4 rAAV-α-syn, 4 rAAV-GFP, 5 non-injected control minipigs). We performed motor symptom assessment and immunohistochemical examination of tyrosine hydroxylase (TH) and transgene expression. Expression of GFP and α-syn was observed at the SN injection site and in the striatum. We observed no motor symptoms or changes in striatal [11C]DTBZ binding potential in vivo or striatal or SN TH staining in vitro between the groups. The mean [11C](R)PK11195 total volume of distribution was significantly higher in the basal ganglia and cortical areas of the α-syn group than the control animals. We conclude that mutant α-syn expression in the SN resulted in microglial activation in multiple sub- and cortical regions, while it did not affect TH stains or VMAT2 availability. Our data suggest that microglial activation constitutes an early response to accumulation of α-syn in the absence of dopamine neuron degeneration.
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| 4. |
- Scott, J., et al.
(författare)
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Prospective cohort study of early biosignatures of response to lithium in bipolar-I-disorders: overview of the H2020-funded R-LiNK initiative
- 2019
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Ingår i: International Journal of Bipolar Disorders. - : Springer Science and Business Media LLC. - 2194-7511. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Lithium is recommended as a first line treatment for bipolar disorders. However, only 30% of patients show an optimal outcome and variability in lithium response and tolerability is poorly understood. It remains difficult for clinicians to reliably predict which patients will benefit without recourse to a lengthy treatment trial. Greater precision in the early identification of individuals who are likely to respond to lithium is a significant unmet clinical need. Structure The H2020-funded Response to Lithium Network (R-LiNK; ) will undertake a prospective cohort study of over 300 individuals with bipolar-I-disorder who have agreed to commence a trial of lithium treatment following a recommendation by their treating clinician. The study aims to examine the early prediction of lithium response, non-response and tolerability by combining systematic clinical syndrome subtyping with examination of multi-modal biomarkers (or biosignatures), including omics, neuroimaging, and actigraphy, etc. Individuals will be followed up for 24 months and an independent panel will assess and classify each participants' response to lithium according to predefined criteria that consider evidence of relapse, recurrence, remission, changes in illness activity or treatment failure (e.g. stopping lithium; new prescriptions of other mood stabilizers) and exposure to lithium. Novel elements of this study include the recruitment of a large, multinational, clinically representative sample specifically for the purpose of studying candidate biomarkers and biosignatures; the application of lithium-7 magnetic resonance imaging to explore the distribution of lithium in the brain; development of a digital phenotype (using actigraphy and ecological momentary assessment) to monitor daily variability in symptoms; and economic modelling of the cost-effectiveness of introducing biomarker tests for the customisation of lithium treatment into clinical practice. Also, study participants with sub-optimal medication adherence will be offered brief interventions (which can be delivered via a clinician or smartphone app) to enhance treatment engagement and to minimize confounding of lithium non-response with non-adherence. Conclusions The paper outlines the rationale, design and methodology of the first study being undertaken by the newly established R-LiNK collaboration and describes how the project may help to refine the clinical response phenotype and could translate into the personalization of lithium treatment.
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| 5. |
- Sejr-Hansen, Martin, et al.
(författare)
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Comparison of Quantitative Flow Ratio and Instantaneous Wave-Free Ratio for Immediate Assessment of Non-Culprit Lesions in Patients With ST-Segment Elevation Myocardial Infarction An iSTEMI Substudy
- 2018
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Ingår i: Journal of the American College of Cardiology. - : Elsevier. - 0735-1097 .- 1558-3597. ; 72:13, s. B248-B249
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- BACKGROUND: Quantitative flow ratio (QFR) is an angiography-based approach for in-procedure functional evaluation of coronary artery lesions. We evaluated the diagnostic performance of QFR with instantaneous wave-free ratio (iFR) in non-culprit lesions (NCLs) in patients with ST-segment elevation myocardial infarction (STEMI) and with staged fractional flow reserve (FFR) as reference standard.METHODS: This is a post-hoc analysis of the iSTEMI study. All NCLs were assessed with iFR in the acute setting and with iFR and FFR at staged (median 19 days) follow-up. QFR (Medis Medical Imaging bv., The Netherlands) was computed for all analyzable NCLs in a core lab by an investigator blinded to iFR and FFR results. Diagnostic cut-off values were 0.80 for QFR, 0.89 for iFR, and 0.80 for FFR.RESULTS: A total of 156 NCLs in 120 patients were included in the iSTEMI study. Paired iFR and FFR data were available for 146 NCls in 112 patients. Of these, QFR analysis was feasible in 103 (71 %) lesions assessed in the acute setting. Mean acute QFR was 0.800.13, acute iFR was 0.860.12, and staged FFR was 0.800.11. With staged FFR as reference standard, diagnostic accuracy was 84% (95%CI: 76-90) for acute QFR and 73% (95%CI: 66-83) for acute iFR (p¼0.09), area under the receiver operating curve (AUC) was 0.89 (95%CI: 0.82-0.95) vs. 0.77 (95%CI: 0.68-0.87) (p¼0.02), sensitivity was 83% (95%CI: 69-92) vs. 85% (95%CI: 73-92) (p¼0.79), specificity was 84% (95%CI: 72-92) vs. 64% (95%CI: 53-75) (p¼0.11), positive predictive value was 81% (95%CI: 57-82) vs. 70% (95%CI: 57-82)(p¼0.06), and negative predictive value was 86% (95%CI: 76-95) vs. 84% (95%CI: 69-91)(p¼0.37), for acute QFR and acute iFR, respectively.CONCLUSION: The diagnostic performance of acute QFR in post hocevaluation of NCLs in STEMI patients was at least similar to acuteassessment by iFR with staged procedure FFR as reference. QFR couldprovide an easy, safe and cost-effective solution to evaluate NCLs inthe acute phase, thus potentially reducing the number of unnecessaryfollow-up procedures.CATEGORIES IMAGING: Physiologic Lesion Assessment.
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| 6. |
- Sejr-Hansen, Martin, et al.
(författare)
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Quantitative flow ratio for immediate assessment of nonculprit lesions in patients with ST-segment elevation myocardial infarction—An iSTEMI substudy
- 2019
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Ingår i: Catheterization and Cardiovascular Interventions. - : Wiley. - 1522-1946 .- 1522-726X. ; 94:5, s. 686-692
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: We evaluated the diagnostic performance of quantitative flow ratio (QFR) assessment of nonculprit lesions (NCLs) based on acute setting angiograms obtained in patients with ST-segment elevation myocardial infarction (STEMI) with QFR, fractional flow reserve (FFR), and instantaneous wave-free ratio (iFR) in the staged setting as reference. Background: QFR is an angiography-based approach for the functional evaluation of coronary artery lesions. Methods: This was a post-hoc analysis of the iSTEMI study. NCLs were assessed with iFR in the acute setting and with iFR and FFR at staged (median 13 days) follow-up. Acute and staged QFR values were computed in a core laboratory based on the coronary angiography recordings. Diagnostic cut-off values were ≤0.80 for QFR and FFR, and ≤0.89 for iFR. Results: Staged iFR and FFR data were available for 146 NCLs in 112 patients in the iSTEMI study. Among these, QFR analysis was feasible in 103 (71%) lesions assessed in the acute setting with a mean QFR value of 0.82 (IQR: 0.73–0.91). Staged QFR, FFR, and iFR were 0.80 (IQR: 0.70–0.90), 0.81 (IQR: 0.71–0.88), and 0.91 (IQR: 0.87–0.96), respectively. Classification agreement of acute and staged QFR was 93% (95%Cl: 87–99). The classification agreement of acute QFR was 84% (95%CI: 76–90) using staged FFR as reference and 74% (95%CI: 65–83) using staged iFR as reference. Conclusions: Acute QFR showed a very good diagnostic performance with staged QFR as reference, a good diagnostic performance with staged FFR as reference, and a moderate diagnostic performance with staged iFR as reference.
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| 7. |
- Thim, Troels, et al.
(författare)
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Agreement between iFR and FFR in staged follow-up evaluation of non-culprit stenoses after ST-segment elevation myocardial infarction (iSTEMI substudy)
- 2017
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Ingår i: Journal of the American College of Cardiology. - : Elsevier. - 0735-1097 .- 1558-3597. ; 70:18, s. B91-B91
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- BACKGROUND: Classification agreement between instantaneous wave-free ratio (iFR) and fractional flow reserve (FFR) is approximately 80% in stable patients. It was recently shown that FFR guidance, as compared to iFR guidance, was associated with a higher risk of subsequent revascularization among patients with non- ST-segment elevation myocardial infarction. The classification agreement, and the impact of time interval, between iFR and FFR in the assessment of non-culprit lesions after recent ST-segment elevation myocardial infarction (STEMI) has not been described.METHODS: The iSTEMI study assessed agreement between iFR across non-culprit stenoses at the index procedure in patients with STEMI versus iFR and FFR at a follow-up angiography. The interval between STEMI and follow-up evaluation was at the discretion of the treating physicians. In this substudy, classification agreement between follow-up iFR and follow-up FFR was evaluated within groups defined according to follow-up time point after STEMI, i.e., <5days, 5-15days, and16 days. iFR<0.90 and FFR0.80 were considered hemodynamically significant.RESULTS: Among 120 patients with 157 non-culprit stenoses, follow-up iFR and FFR was available in 112 patients with 146 non-culprit stenoses. Median follow-up interval was 16 days (IQR 5-32 days). The overall classification agreement was 84%. With follow-up<5days after STEMI, there was classification agreement between iFR and FFR was in 27 of 35 (77%) non-culprit stenoses. With follow-up 5-15 after STEMI, there was classification agreement in 33 of 38 (86%) non-culprit stenoses. With follow-up 16 days after STEMI, there was classification agreement in 63 of 73 (86%) non-culprit stenoses. The observed differences in these proportions over time after STEMI were not statistically significant (<5versus5days, p¼0.19).CONCLUSION: Overall, classification agreement between iFR and FFR in the assessment of non-culprit lesions after STEMI was comparable to that observed in stable patients. Time interval between STEMI and follow-up evaluation may impact agreement between follow-up iFR and follow-up FFR, although the observed differences were not statistically significant.
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| 8. |
- Thim, Troels, et al.
(författare)
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Nonculprit Stenosis Evaluation Using Instantaneous Wave-Free Ratio in Patients With ST-Segment Elevation Myocardial Infarction
- 2017
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Ingår i: JACC. - New York, USA : Elsevier. - 1936-8798 .- 1876-7605. ; 10:24, s. 2528-2535
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: The aim of this study was to examine the level of agreement between acute instantaneous wave-free ratio (iFR) measured across nonculprit stenoses in patients with ST-segment elevation myocardial infarction (STEMI) and iFR measured at a staged follow-up procedure.BACKGROUND: Acute full revascularization of nonculprit stenoses in STEMI is debated and currently guided by angiography. Acute functional assessment of nonculprit stenoses may be considered.METHODS: Immediately after successful primary culprit intervention for STEMI, nonculprit coronary stenoses were evaluated with iFR and left untreated. Follow-up evaluation with iFR was performed at a later stage. iFR <0.90 was considered hemodynamically significant.RESULTS: One hundred twenty patients with 157 nonculprit lesions were included. Median acute iFR was 0.89 (interquartile range: 0.82 to 0.94; n = 156), and median follow-up iFR was 0.91 (interquartile range [IQR]: 0.86 to 0.96; n = 147). Classification agreement was 78% between acute and follow-up iFR. The negative predictive value of acute iFR was 89%. Median time from acute to follow-up evaluation was 16 days (IQR: 5 to 32 days). With follow-up within 5 days after STEMI, no difference was observed between acute and follow-up iFR, and classification agreement was 89%. With follow-up ≥16 days after STEMI, acute iFR was lower than follow-up iFR, and classification agreement was 70%.CONCLUSIONS: Acute iFR evaluation appeared valid for ruling out significant nonculprit stenoses in patients with STEMI undergoing primary percutaneous coronary intervention. The time interval from acute to follow-up iFR influenced classification agreement, suggesting that inherent physiological disarrangements during STEMI may contribute to classification disagreement.
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