| 1. |
- Eriksson, Rolf, 1979-
(författare)
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The Utility of Manganese for Magnetic Resonance Imaging of Transient Myocardial Ischemia
- 2005
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In order to improve the diagnosis of coronary artery disease, better methods for detection of myocardial perfusion defects would be useful. One of the methods used for myocardial perfusion evaluation today is magnetic resonance imaging. This method could be improved if a contrast agent that induced long-lasting contrast enhancement in the myocardium could be developed. The paramagnetic manganese(II) ion has promising properties for meeting this need, since it enters cardiomyocytes through voltage-gated calcium channels and remains inside the cells for a long time after an intravenous injection. If these properties can be utilized, manganese-enhanced MRI has potential for detecting transient periods of ischemia in a manner similar to the conventional SPECT stress test.To investigate the contrast-enhancing properties of the manganese(II) ion, a series of experiments was performed in pigs, using a manganese salt (MnCl2) and two manganese-based chelates (MnDPDP and MnHPTA) and measuring the longitudinal relaxation rates before and after contrast agent administration. This was done in normal pig myocardium at rest and during dobutamine-induced stress with several different doses of contrast agent, and in a model for coronary artery stenosis using MnCl2 administered during dobutamine stress to determine whether transient ischemia could be detected with this contrast agent.The results of these experiments showed that of the three contrast agents, MnCl2 induces the greatest increase in ΔR1, followed by MnHPTA. Using MnCl2 it was possible to produce images on which transient myocardial ischemia was visible, but only during the first 30 minutes after contrast agent injection.The stenosis model is still far from the clinical situation and several complications, including the potential toxicity of the manganese(II) ion, remain to be overcome. However, the results from this model are promising for the future development of manganese- enhanced magnetic resonance imaging of transient myocardial ischemia.
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| 2. |
- Hedström, Erik, et al.
(författare)
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Importance of perfusion in myocardial viability studies using delayed contrast-enhanced magnetic resonance imaging
- 2006
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Ingår i: Journal of Magnetic Resonance Imaging. - : Wiley. - 1053-1807 .- 1522-2586. ; 24:1, s. 77-83
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To investigate whether an extracellular gadolinium-(Gd)-based contrast agent (CA) enters nonperfused myocardium during acute coronary occlusion, and whether nonperfused myocardium presents as hyperintense in delayed contrast-enhanced (DE) MR images in the absence of CA in that region. MATERIALS AND METHODS: The left anterior descending coronary artery (LAD) was occluded for 200 minutes in six pigs. The longitudinal relaxation rate (R(1)) in blood, perfused myocardium, and nonperfused myocardium was repeatedly measured using a Look-Locker sequence before and during the first hour after administration of Gd-DTPA-BMA. RESULTS: While blood and perfused myocardium showed a major increase in R(1) after CA administration, nonperfused myocardium did not. R(1) in nonperfused myocardium was significantly lower than in blood and perfused myocardium during the first hour after CA administration. When the signal from perfused myocardium was nulled, demarcation of the hyperintense nonperfused myocardium was achieved in all of the study animals. CONCLUSION: Gd-DTPA-BMA does not enter ischemic myocardium within one hour after administration during acute coronary occlusion. The ischemic region with complete absence of CA still appears bright when the signal from perfused myocardium is nulled using inversion-recovery DE-MRI. This finding is important for understanding the basic pathophysiology of inversion-recovery viability imaging, as well as for imaging of acute coronary syndromes.
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| 3. |
- Briley-Saebo, Karen C., et al.
(författare)
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Clearance of iron oxide particles in rat liver : effect of hydrated particle size and coating material on liver metabolism
- 2006
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Ingår i: Investigative Radiology. - : Ovid Technologies (Wolters Kluwer Health). - 0020-9996 .- 1536-0210. ; 41:7, s. 560-571
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: We sought to evaluate the effect of the particle size and coating material of various iron oxide preparations on the rate of rat liver clearance. MATERIALS AND METHODS: The following iron oxide formulations were used in this study: dextran-coated ferumoxide (size = 97 nm) and ferumoxtran-10 (size = 21 nm), carboxydextran-coated SHU555A (size = 69 nm) and fractionated SHU555A (size = 12 nm), and oxidized-starch coated materials either unformulated NC100150 (size = 15 nm) or formulated NC100150 injection (size = 12 nm). All formulations were administered to 165 rats at 2 dose levels. Quantitative liver R2* values were obtained during a 63-day time period. The concentration of iron oxide particles in the liver was determined by relaxometry, and these values were used to calculate the particle half-lives in the liver. RESULTS: After the administration of a high dose of iron oxide, the half-life of iron oxide particles in rat liver was 8 days for dextran-coated materials, 10 days for carboxydextran materials, 14 days for unformulated oxidized-starch, and 29 days for formulated oxidized-starch. CONCLUSIONS: The results of the study indicate that materials with similar coating but different sizes exhibited similar rates of liver clearance. It was, therefore, concluded that the coating material significantly influences the rate of iron oxide clearance in rat liver.
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| 4. |
- Ebeling Barbier, Charlotte, et al.
(författare)
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Clinically unrecognized myocardial infarction detected at MR imaging may not be associated with atherosclerosis
- 2007
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Ingår i: Radiology. - : Radiological Society of North America (RSNA). - 0033-8419 .- 1527-1315. ; 245:1, s. 103-110
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To prospectively investigate whether there is support for the hypothesis that clinically unrecognized myocardial infarctions (UMIs) detected at magnetic resonance (MR) imaging have an atherosclerotic pathogenesis similar to that of recognized myocardial infarctions (RMIs). Materials and Methods: After ethics committee approval and informed consent were obtained, gadolinium-enhanced whole-body MR angiography and late-enhancement MR imaging were performed in 248 randomly chosen 70-year-old subjects (123 women, 125 men). Imaging included the aorta and the carotid, renal, and lower limb arteries to the ankle, but not the coronary arteries. Subjects with myocardial infarction (MI) scars at late-enhancement MR imaging were classified as having RMI (n = 11) (those with a diagnosis of MI at the hospital) or UMI (n = 49) (those without a diagnosis of MI at the hospital). The presence of 50% or higher luminal narrowing in any vessel at whole-body MR angiography was considered to represent significant atherosclerosis. Intima-media thickness of the common carotid artery was measured with ultrasonography. C-reactive protein level was measured, and coronary heart disease risk was estimated. Observers were blinded to any previous results. The chi(2) test analysis of variance, and Bonferroni correction were used for statistical analyses. Results: None of the measured parameters differed significantly between the group without MI scars and the UMI group, but parameters were significantly increased in the RMI group (P < .05) compared with those in the group without MI scars. Forty-two of 49 UMIs and nine of 11 RMIs were located within inferolateral segments of the left ventricle. Conclusion: MR imaging-detected UMIs might have a different pathogenesis from that of RMIs or may have the same pathogenesis but may manifest at an earlier stage.
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| 5. |
- Ebeling Barbier, Charlotte, et al.
(författare)
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Myocardial scars more frequent than expected - Magnetic resonance imaging detects potential risk group
- 2006
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Ingår i: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097 .- 1558-3597. ; 48:4, s. 765-771
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: The aim of this study was to investigate the prevalence of clinically recognized myocardial infarctions (RMIs) and unrecognized myocardial infarctions (UMIs) in 70-year-old subjects, assessed with magnetic resonance imaging (MRI), and to relate the findings to cardiac function and morbidity. Background: Late enhancement MRI identifies myocardial scars and thereby has the potential to detect UMI. Methods: Cardiac MRI was performed on 259 randomly chosen 70-year-old subjects. Late enhancement and cine sequences were acquired, and the ejection fraction and left ventricular (LV) mass were calculated. Late enhancement involving the subendocardial layer was considered to represent myocardial infarction (MI) scars, and their volumes were calculated. Information on cardiac morbidity and risk factors was collected from medical records and from a health examination. Subjects with MI scars, with or without a hospital diagnosis of MI were classified as RMI or UMI, respectively. Results: The images from 248 subjects (123 women, 125 men) were assessable. Myocardial infarction scars were found in 60 subjects (24.2%), in 49 of whom (19.8%) they were UMIs. The volumes of the UMIs were significantly smaller than those of the RMIs. There was an increased frequency of chest pain symptoms among the subjects with UMI or RMI compared with those without MI scars. Ejection fraction was significantly lower and LV mass significantly larger in the subjects with UMI or RMI than in those without MI scars. Conclusions: Unrecognized MI detected with MRI was more frequent than expected in 70-year-old subjects. The subjects displaying these UMIs may represent a previously unknown potential risk group for future cardiovascular events.
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| 6. |
- Ebeling Barbier, Charlotte, 1969-
(författare)
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Myocardial Scars on MRI : Their Prevalence and Possible Impact
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Myocardial infarction (MI) causes high morbidity and mortality worldwide and for effective prevention and treatment MIs have to be adequately detected.The existence of clinically unrecognized MIs (UMIs) has been known for the past hundred years, but an ultimate tool for their detection has not yet been found. Using persistent Q waves on electrocardiography as a sign of MI, it has been estimated that UMIs constitute at least ¼ of all MIs and have mortality rates similar to those of recognized MIs (RMIs). These estimates are misleading, however, since persistent Q waves do not necessarily represent MIs.The late enhancement technique in magnetic resonance imaging (LE MRI) has been developed over the past decade and accurately determines myocardial viability. The aim of this research was to investigate the prevalence and impact of UMI and RMI in a population-based sample of 70-year-olds, assessed with MRI.Cardiac function and viability were examined with MRI in 259 randomly selected 70-year-old subjects (127 women, 132 men) participating in a larger population-based study (PIVUS). Information on other parameters of cardiovascular disease was obtained and related to the findings.Three methods for segmentation of the left ventricular mass were used in the first 100 subjects; these differed in accuracy and led to differences in systolic function values. In the subsequent 159 examinations one of the segmentation methods was used.The viability images were assessable in 248 subjects (123 women, 125 men). Among these, the prevalence of UMI, 19.8%, definitely exceeded the expectations and UMIs constituted 4/5 of all MIs. The prevalence of RMI was 4.4%. MRI-detected UMIs differed from RMIs in several respects; they were smaller, frequently located inferolaterally, did not appear to be associated with atherosclerosis, and displayed increased collagen turnover. The pathogenesis of these UMIs remains to be investigated, but our observations suggest that they are caused by ischemia. Subjects with UMI showed increased cardiac morbidity, a decreased ejection fraction and an increased left ventricular mass, indicating an increased cardiovascular risk.It is thus important to detect these UMIs, and this is adequately achieved by LE MRI. However, to decide upon prevention and treatment of these UMIs we need to know more about their pathogenesis and prognosis.
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| 7. |
- Ebeling Barbier, Charlotte, et al.
(författare)
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The exactness of left ventricular segmentation in cine magnetic resonance imaging and its impact on systolic function values
- 2007
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Ingår i: Acta Radiologica. - : SAGE Publications. - 0284-1851 .- 1600-0455. ; 48:3, s. 285-291
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To evaluate the impact of exactness of the segmentation of the left ventricle (LV), using cine magnetic resonance imaging (MRI). Material and methods: Steady-state free-precession cine MRI was performed on 100 randomly selected subjects. Myocardial borders were outlined on short-axis images using three methods: method 1 was computer assisted, excluding papillary muscles from the left ventricular mass (LVM); method 2 was similar but included papillary muscles; and method 3 was manually traced including papillary muscles. LV end-systolic (ES) and end-diastolic (ED) masses and volumes, ejection fraction (EF), stroke volume (SV), and cardiac output (CO) were calculated from these measurements. The difference between the ES and ED LVM was used to estimate the exactness of the methods. Results: Method 3 was the most exact, and method 1 was the least exact. The three methods generated differing EF, SV, and CO measurements. With an ES-ED LVM difference exceeding 20 g, the mean SV measurement error was 8.83.6 ml. Conclusion: Manual tracing proved more exact than computer-assisted quantification. Exactness had an impact on EF, SV, and CO measurements, and the ES-ED LVM difference can be used to identify assessments that would benefit from more exact segmentation.
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| 8. |
- Edwards, David, et al.
(författare)
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99mTc-NC100668, an agent for imaging venous thromboembolism : The effect of anticoagulant or thrombolytic therapy on the uptake and retention of radioactivity in blood clots in vivo
- 2007
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Ingår i: Nuclear medicine communications. - : Ovid Technologies (Wolters Kluwer Health). - 0143-3636 .- 1473-5628. ; 28:1, s. 55-62
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The purpose of this study was to evaluate the uptake of Tc-NC100668 into blood clots and elucidate the potential for medications commonly used to treat thromboembolism to interfere with the uptake and retention of Tc-NC100668. METHODS: Tc-NC100668 in vivo uptake and retention in a range of blood clot of various ages (up to 4 h old) and in the presence of anticoagulants or thrombolytic therapies was measured in a rat model of deep vein thrombosis. RESULTS: Tc-NC100668 was rapidly absorbed into and retained by blood clots and was not significantly affected by the presence of unfractionated or low molecular weight heparin or thrombin inhibitor. Tissue plasminogen activator reduced the uptake of Tc-NC100668 into blood clot by a factor of 3 when adjusted to allow for changes in the weight of the blood clot. CONCLUSIONS: This study has demonstrated that the uptake and retention of Tc-NC100668 into blood clots in the rat model of deep vein thrombosis is rapid and maintained over at least a 4 h post-injection period. It has been shown that Tc-NC100668 is retained in blood clots even in the presence of therapeutic doses of those anticoagulant and thrombolytic therapies typically used to treat pulmonary embolism and venous thrombosis.
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| 9. |
- Edwards, David, 1971-
(författare)
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Pre-Clinical Evaluation of a Novel Radiotracer for the Diagnosis of DVT and Pulmonary Embolism.
- 2006
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Deep vein thrombosis (DVT) and pulmonary embolism (PE) are different aspects of a single condition, venous thrombo-embolic disease (VTE), a major cause of morbidity and mortality in the western world. Rapid diagnosis is critical, as timely medical intervention can have a substantial beneficial effect on the mortality rate. Irrespective of its presentation, VTE is a difficult disease to diagnose. Pathologies unrelated to VTE can give rise to a clinical presentation similar to DVT or PE, resulting in a false positive diagnosis. This raises the risk of a patient being treated inappropriately. Therefore, there is a need for an agent that has high specificity and sensitivity for the detection of active blood clots, which are amenable to treatment by anticoagulant and/or thrombolytic therapy. This work describes the pre-clinical efficacy studies performed on one such agent, 99mTc-NC100668. 99mTc-NC100668 is a substrate for factor XIIIa and as a potential physiological, rather than anatomical, marker of VTE it is hoped it will not give rise to the false negative and positive diagnoses that are inherent in the currently available diagnostic techniques, such as the ventilation perfusion (V/Q) scan, multidetector computer tomography or ultrasound. It is reported in this work that 99mTc-NC100668 uptake and retention in blood clot was rapid and maintained over at least a 4 hour period in a rat model of DVT. Anticoagulant and thrombolytic therapies commonly used to treat thrombosis did not seriously impair the ability of 99mTc-NC100668 to detect thrombi. No significant tissue retention, which could interfere with the ability to image thrombi in vivo, was observed. Biodistribution and plasma clot uptake studies showed that 99mTc complex of gly-NC100194, the major metabolite of 99mTc-NC100668, would be unlikely to affect adversely the clinical utility of the test substance. The in vitro uptake of 99mTc-NC100668 into forming plasma clots indicated that retention into human blood clots would be comparable with the observations made in the rat preclinical models. The uptake of 99mTc-NC100668 in vitro and in vivo was much greater than could be accounted for by physical entrapment into the forming blood clots. The reduced uptake of a biologically inactive analogue of 99mTc-NC100668 both in vitro and in vivo indicated that the blood clot uptake and retention of 99mTc-NC100668 was mediated by factor XIIIa. In conclusion, 99mTc-NC100668 might be useful in the detection of thrombo embolism.
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| 10. |
- Edwards, David, et al.
(författare)
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Tc-99m-NC100668, a new tracer for imaging venous thromboemboli : pre-clinical biodistribution and incorporation into plasma clots in vivo and in vitro
- 2006
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Ingår i: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer Science and Business Media LLC. - 1619-7070 .- 1619-7089. ; 33:11, s. 1258-1265
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Tc-99m-NC100668 is a new radiotracer being developed to aid the diagnosis of thromboembolism. The structure of NC100668 is similar to a region of human alpha(2)-antiplasmin, which is a substrate for factor XIIIa (FXIIIa). The purpose of this study was to confirm the uptake of Tc-99m-NC100668 into forming plasma clot and to establish the biodistribution of Tc-99m-NC100668 in Wistar rats. Methods: The in vitro plasma clot uptake of Tc-99m-NC100668 and other compounds with known affinities to FXIIIa was measured using a plasma clot assay. The biodistribution and blood clot uptake of radioactivity of Tc-99m-NC100668 in normal Wistar rats and those bearing experimentally induced deep vein thrombi were investigated. Results: The in vitro uptake of Tc-99m-NC100668 was greater than that for [C-14] dansyl cadaverine, a known substrate of FXIIIa in the plasma clot assay. The biodistribution of Tc-99m-NC100668 in male and female Wistar rats up to 24 h p.i. showed that radioactivity was rapidly excreted, predominantly into the urine, with very little background tissue retention. In vivo the uptake and retention of Tc-99m-NC100668 into the blood clot was greater than could be accounted for by non-specific accumulation of the radiotracer within the blood clot. Conclusion: Tc-99m-NC100668 was retained by plasma clots in vitro and blood clots in vivo. No significant tissue retention which could interfere with the ability to image thrombi in vivo was observed. This evidence suggests that Tc-99m-NC100668 might be useful in the detection of thromboembolism.
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