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- Dahlqvist Leinhard, Olof
(författare)
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Quantitative Magnetic Resonance in Diffuse Neurological and Liver Disease
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: Magnetic resonance (MR) imaging is one of the most important diagnostic tools in modern medicine. Compared to other imaging modalities, it provides superior soft tissue contrast of all parts of the body and it is considered to be safe for patients. Today almost all MR is performed in a nonquantitative manner, only comparing neighboring tissue in the search for pathology. It is possible to quantify MR-signals and relate them to their physical entities, but time consuming and complicated calibration procedures have prevented this being used in a practical manner for clinical routines. The aim of this work is to develop and improve quantification methods in MRspectroscopy (MRS) and MR-imaging (MRI). The techniques are intended to be applied to diffuse diseases, where conventional imaging methods are unable to perform accurate staging or to reveal metabolic changes associated with disease development.Methods: Proton (1H) MRS was used to characterize the white matter in the brain of multiple sclerosis (MS) patients. Phosphorus (31P) MRS was used to evaluate the energy metabolism in patients with diffuse liver disease. A new quantitative MRI (qMRI) method was invented for accurate, rapid and simultaneous quantification of B1, T1, T2, and proton density. A method for automatic assessment of visceral adipose tissue volume based on an in- and out-ofphase imaging protocol was developed. Finally, a method for quantification of the hepatobiliary uptake of liver specific T1 enhancing contrast agents was demonstrated on healthy subjects.Results: The 1H MRS investigations of white matter in MS-patients revealed a significant correlation between tissue concentrations of Glutamate and Creatine on the one hand and the disease progression rate on the other, as measured using the MSSS. High accuracy, both in vitro and in vivo, of the measured MR-parameters from the qMRI method was observed. 31P MRS showed lower concentrations of phosphodiesters, and a higher metabolic charge in patients with cirrhosis, compared to patients with mild fibrosis and to controls. The adipose tissue quantification method agreed with estimates obtained using manual segmentation, and enabled measurements which were insensitive to partial volume effects. The hepatobiliary uptake of Gd-EOB-DTPA and Gd-BOPTA was significantly correlated in healthy subjects.Conclusion: In this work, new methods for accurate quantification of MR parameters in diffuse diseases in the liver and the brain were demonstrated. Several applications were shown where quantitative MR improves the interpretation of observed signal changes in MRI and MRS in relation to underlying differences in physiology and pathophysiology.
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| 2. |
- Dahlqvist, Peter
(författare)
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Late Ordovician-Early Silurian facies development and stratigraphy of Jämtland, central Sweden
- 2005
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis is based on studies of Lower Palaeozoic sedimentary successions within the central Scandinavian Caledonides. These deposits have been transported by considerable nappe displacement (several kilometres), and are today relatively isolated from the nearest coeval outcrops (Dalarna 250 km, Oslo Region 350 km). As a consequence, and due to the previously limited biostratigraphical control the investigated area have received little attention the last decades. Therefore, a detailed investigation, using several untried geological tools was performed. During the study it became clear that the strata reflected substantial changes in depositional environment and complexity in lateral facies relationship during the Late Ordovician?Early Silurian. This was a time characterised by global environmental changes such as glacio-eustasy and climate change, in particular during the end-Ordovician (Hirnantian) glaciation. Facies and sequence stratigraphical analysis of two key units (the Ede Quartzite and the Kyrkås Quartzite) and their preceding and succeeding units resulted in reinterpretations and refinement of the stratigraphy. The new data implied that the successions could be linked to known Hirnantian sea-level fluctuations. This correlation was subsequently supported, and our understanding of the timing of changes was improved, by biostratigraphical evidence (conodonts, graptolites, and brachiopods). This revealed a ca 5 myr stratigraphical gap, within the Ede Quartzite, spanning the Ordovician?Silurian boundary. It is concluded that the interaction of allocyclic changes (sea level and climate) were the overriding controls on deposition during the Late Ordovician?Early Silurian in the Jämtland basin. The contrasting sedimentary architecture of the Ede Quartzite to the west and the partly coeval Kyrkås Quartzite to the east remained enigmatic. Provenance studies (radiometric dating of zircons) tentatively indicate different dominating source areas, but further studies are needed to solve their relationship.
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| 3. |
- Forsgren, Mikael
(författare)
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The Non-Invasive Liver Biopsy : Determining Hepatic Function in Diffuse and Focal LiverDisease
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The liver is one of the largest organs within the human body and it handles many vital tasks such as nutrient processing, toxin removal, and synthesis of important proteins. The number of people suffering from chronic liver disease is on the rise, likely due to the present ‘western’ lifestyle. As disease develops in the liver there are pathophysiological manifestations within the liver parenchyma that are both common and important to monitor. These manifestations include inflammation, fatty infiltration (steatosis), excessive scar tissue formation (fibrosis and cirrhosis), and iron loading. Importantly, as the disease progresses there is concurrent loss of liver function. Furthermore, postoperative liver function insufficiency is an important concern when planning surgical treatment of the liver, because it is associated with both morbidity and mortality. Liver function can also be hampered due to drug-induced injuries, an important aspect to consider in drug-development.Currently, an invasive liver needle biopsy is required to determine the aetiology and to stage or grade the pathophysiological manifestations. There are important limitations with the biopsy, which include, risk of serious complications, mortality, morbidity, inter- and intra-observer variability, sampling error, and sampling variability. Cleary, it would be beneficial to be able investigate the pathophysiological manifestations accurately, non-invasively, and on regional level.Current available laboratory liver function blood panels are typically insufficient and often only indicate damage at a late stage. Thus, it would be beneficial to have access to biomarkers that are both sensitive and responds to early changes in liver function in both clinical settings and for the pharmaceutical industry and regulatory agencies.The main aim of this thesis was to develop and evaluate methods that can be used for a ‘non-invasive liver biopsy’ using magnetic resonance (MR). We also aimed to develop sensitive methods for measure liver function based on gadoxetate-enhanced MR imaging (MRI).The presented work is primarily based on a prospective study on c. 100 patients suffering from chronic liver disease of varying aetiologies recruited due to elevated liver enzyme levels, without clear signs of decompensated cirrhosis. Our results show that the commonly used liver fat cut-off for diagnosing steatosis should be lowered from 5% to 3% when using MR proton-density fat fraction (PDFF). We also show that MR elastography (MRE) is superior in staging fibrosis.Finally we presented a framework for quantifying liver function based on gadoxetate-enhanced MRI. The method is based on clinical images and a clinical approved contrast agent (gadoxetate). The framework consists of; state-of the-art image reconstruction and correction methods, a mathematical model, and a precise model parametrization method. The model was developed and validated on healthy subjects. Thereafter the model was found applicable on the chronic liver disease cohort as well as validated using gadoxetate levels in biopsy samples and blood samples. The liver function parameters correlated with clinical markers for liver function and liver fibrosis (used as a surrogate marker for liver function).In summary, it should be possible to perform a non-invasive liver biopsy using: MRI-PDFF for liver fat and iron loading, MRE for liver fibrosis and possibly also inflammation, and measure liver function using the presented framework for analysing gadoxetate-enhanced MRI. With the exception of an MREtransducer no additional hardware is required on the MR scanner. The liver function method is likely to be useful both in a clinical setting and in pharmaceutical trials.
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| 4. |
- West, Janne
(författare)
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Quantitative Magnetic Resonance Imaging of the Brain : Applications for Tissue Segmentation and Multiple Sclerosis
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Magnetic resonance imaging (MRI) is a sensitive technique for assessing white matter (WM) lesions in multiple sclerosis (MS), but there is a low correlation between MRI findings and clinical disability. Because of this, other pathological changes are of interest, including changes in normal appearing white matter (NAWM) and diffusely abnormal white matter (DAWM). Even so, the mechanisms leading to permanent disability in MS remain unclear.In contrast to conventional MRI, quantitative MRI (qMRI) is aimed at the direct measurement of the physical tissue properties, such as the relaxation times, T1 and T2, as well as the proton density (PD). QMRI is promising for characterising and quantifying changes in MS and for brain tissue segmentation.The present work describes a novel method of qMRI for the human brain (QMAP), and a segmentation method based on this. The developed methods were validated in control subjects and MR phantoms. Furthermore, an application in diseased human brain was demonstrated in MS patients. In all, 50 healthy controls and 35 MS patients were scanned with qMRI in a total of 225 acquisitions.One major finding of this work was that qMRI was able to detect and quantify changes in the MS disease that were not visible using conventional MRI. In particular, it was found that DAWM appears to constitute an intermediate between focal white matter (WM) lesions and NAWM. These changes may be caused by pathological processes that are not entirely attributable to Wallerian degeneration.This study showed that the QMAP method had high accuracy and relatively high precision, within a clinically acceptable time. This work also demonstrated that qMRI could be used for brain tissue segmentation and volume estimation of the whole brain, using pre-defined tissue characteristics. The results showed that brain tissue segmentation had high repeatability, which was somewhat lower when different geometries were acquired or different field strengths used. In particular, small differences were found between 1.5 T and 3.0 T in deep brain structures, the cerebellum and the brain stem.This work leads the way for early clinical applications of qMRI, and the challenge for the years to come is to understand the connection between qMRI properties of the brain and underlying biology.
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