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- Kero, Tanja
(författare)
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Methodological aspects of quantitative cardiac molecular imaging
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The objective of this research was to facilitate the use of quantitative cardiac molecular imaging by developing and validating methods and applications. More specifically:we determined the optimal tracer kinetic model for analysis of 11C-PIB and evaluated the performance of two simpler measures, retention index (RI) and standardized uptake value (SUV), in the quantification of cardiac 11C-PIB uptake in amyloidosis. An irreversible two-tissue (2Tirr) model best described the 11C-PIB uptake in cardiac amyloidosis. RI and SUV showed high correlation with quantitative results from this kinetic model and also a better discrimination between amyloidosis patients and controls than a 2Tirr model with population averaged metabolite correction. RI and SUV are furthermore more feasible for use in clinical routine and therefore the preferred measure to use in PET diagnosis of cardiac amyloidosis. We also tested the feasibility of a semiautomatic software to analyze RI and visualize cardiac uptake of 11C-PIB in amyloidosis. The RI values were comparable with RI based on manual segmentation, showing significantly higher 11C-PIB RI in amyloidosis patients than in healthy volunteers. A fast and accurate semiautomatic analysis process is thus feasible to use for PET in cardiac amyloidosis instead of the laborious manual analyses that were used so far.Furthermore, we assessed the quantitative accuracy of cardiac perfusion measurements with 15O-water PET in a digital time-of-flight PET-MR scanner. A high correlation and agreement between PET-MR based and PET-CT based MBF was found; cardiac perfusion measurements with 15O-water can therefore be performed accurately with the fully integrated Signa PET-MR scanner. Finally, we assessed the quantitative accuracy of cardiac perfusion measurements using dynamic contrast-enhanced MRI with simultaneous 15O-water PET as reference at rest and during adenosine-induced hyperemia with a fully integrated PET-MR scanner. The correlations between global and regional MRI- and PET-based MBF values were good and the biases were negliable for both global and regional MBF comparisons, but the limits of agreement were wide for both global and regional MBF, with larger variability for high MBF-values indicating that MRI-based quantitative MBF measurement based on widely available acquisition protocols is not yet ready for clinical introduction.
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| 2. |
- Trägårdh, Elin
(författare)
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Adjuncts to the Conventional 12-Lead ECG: Assessment of High-Frequency QRS Components and Additional Leads
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The standard 12-lead electrocardiogram (ECG) is one of the most commonly used methods for diagnosing heart disease. Standard ECG is not always optimal, however, and new ECG methods can provide additional information. Analysis of high-frequency QRS components (HF-QRS) has been shown to increase the diagnostic performance of the ECG. Since the amplitudes of the HF-QRS are low compared with those visible in the standard ECG, analysis of HF-QRS requires a low noise level, a sampling rate of at least 1000 Hz, and multibeat signal averaging. Methods for analyzing HF-QRS have been developed in collaboration with the Department of Electroscience at the Faculty of Engineering, Lund University. Another method for increasing the diagnostic performance of the ECG is to add electrodes to provide leads that see parts of the heart not covered by conventional leads. This could be particularly interesting in diagnosing conditions such as acute myocardial infarction (MI), for example, for which it is important to initiate reperfusion treatment as soon as possible. The overall objectives of the thesis are to investigate whether analysis of HF-QRS has the ability to provide information not available from the standard ECG and to investigate whether information from additional ECG leads can improve the diagnosis of acute MI. In Study I, patients with ischemic heart disease had significantly lower HF-QRS compared with normal individuals. There was substantial interindividual variability, however, which probably limits the clinical usefulness of this method. The study also showed that HF-QRS are not related to sex or age. In Study II, we investigated whether the amplitude of HF-QRS correlates to the left ventricular mass. This has been shown to be the case in previous studies in rabbits. Our study, however, showed that analysis of HF-QRS is no better than analysis of standard 12-lead ECG for determination of left ventricular mass. In Study III, patients with intraventricular conduction delay had lower HF-QRS in leads with a positive electrode facing the area of the heart with the conduction delay. In areas of the heart with normal conduction velocity, the amplitudes of HF-QRS were normal or almost normal. These findings support the theory that HF-QRS relate to the conduction velocity of the heart. In Study IV, we investigated whether additional leads can improve the diagnosis of acute MI. The accuracy of the conventional 12-lead ECG is poor for finding acute MI when certain coronary arteries are involved. Conventional 12-lead ECG was compared with 16-lead ECG (12-lead ECG plus 4 additional electrodes) as well as with 24-lead ECG (12-lead ECG plus the inverted leads of these 12 leads). The sensitivity for detecting acute MI increased when using the 16-lead or 24-lead ECG compared with the 12-lead ECG. The specificity, however, decreased slightly. If the aim is to increase sensitivity for detecting MI, clinicians should be advised to use the 24-lead ECG, since no additional electrodes are required.
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| 3. |
- Vyakaranam, Achyut Ram
(författare)
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Nuclear medicine imaging and treatment in pheochromocytoma, paraganglioma, and role of the new tracer 11C-hydroxy ephedrine in diabetes mellitus
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Carbon-11 hydroxy ephedrine (11C-HED) is a norepinephrine analog which binds to the norepinephrine receptor present in adrenal medulla, lung, liver and pancreas. 11C-HED-positron emission tomography with concomitant computed tomography (PET/CT) can image these organs. Pheochromocytoma (PCC) and Paraganglioma (PGL) are rare, chromaffin cell tumors, which may mimic other diseases and can be difficult to diagnose because of vague and uncharacteristic symptoms. The diagnosis of PCC/PGL is reached either by detection of excessive catecholamines or metanephrines in plasma or urine, or may be detected incidentally on computed tomography (CT)/magnetic resonance imaging (MRI) as an “incidentaloma”. Also, these tumors are most heritable endocrine neoplasms, and can metastasize in up to 20% of patients. Better post-operative surveillance, re-staging on evidence of recurrent disease, biochemical recurrence and therapy monitoring is needed in these patients to improve care. Also, in inoperable cases and metastatic disease of neuroendocrine tumors (NETs), peptide receptor radiotherapy (PRRT) with 177Lu-DOTATATE has emerged as a promising nuclear medicine therapy. Recent studies have shown a connection between sympathetic nervous system and diabetes mellitus both type 1(T1D) and type 2(T2D), which are a global health burden. However, underlying pathophysiology of both types are not well understood. The aims of this thesis was, in Paper I to establish the role of 11C-HED PET/CT in complex clinical scenarios to diagnose or rule out primary tumors of PCC/PGL (n=102). In Paper II, to determine the outcome of treatment with 177Lu-DOTATATE in PCC/PGL (n=22), in Paper III to assess the additional clinical benefit of 11C-HED PET/CT in in patients with metastatic PCC/PGL in comparison to morphological imaging, CT/MRI and other available imaging (n=74), in Paper IV to establish 11C-HED PET/CT for non-invasive imaging of the pancreatic sympathetic innervation in individuals with T2D (n=25) and non-diabetics (n=64).We demonstrate that 11C-HED PET/CT is a valuable diagnostic tool to diagnose or rule out pheochromocytoma and paraganglioma. Also, it is excellent in surveilling metastatic disease post-surgery, monitoring therapy with parameters such as standardized uptake value (SUV) and total catecholamine transporter tumor volume (TCTTV) and provides additional benefit in complex clinical scenarios. Upon treatment with 177Lu-DOTATATE patients with PCC/PGL had a favorable outcome with low toxicity. There was focal accumulation of 11C-HED in the sympathetic innervation of the pancreas and CT helped in delineation and further segmentation. In conclusion, we showed the role of new radiotracer 11C-HED and theragnostic option, PRRT with 177Lu-DOTATATE successfully better nuclear medicine diagnosis and therapy in pheochromocytoma, paraganglioma and diabetes mellitus.
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