| 1. |
- Khoshnood, Ardavan
(författare)
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Prehospital Diagnosis and Oxygen Treatment in ST Elevation Myocardial Infarction
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- IntroductionPaper I: An Artificial Neural Network (ANN) was constructed to identify ST Elevation Myocardial Infarction (STEMI) and predict the need for Percutaneous Coronary Intervention (PCI). Paper II, III and IV: Studies suggest that O2 therapy may be harmful in STEMI patients. We therefore conducted the SOCCER study to evaluate the effects of O2 therapy in STEMI patients.MethodsPaper I: 560 ambulance ECGs sent to the Cardiac Care Unit (CCU), was together with the CCU physicians interpretation and decision of conducting an acute PCI or not collected, and compared with the interpretation and PCI decision of the ANN. Paper II, III, IV: Normoxic (≥94%) STEMI patients accepted for acute PCI were in the ambulance randomized to standard care with 10 L/min O2 or room air. A subset of the patients underwent echocardiography for determination of the Left Ventricular Ejection Fraction (LVEF) and the Wall Motion Score Index (WMSI). All patients had a Cardiac Magnetic Resonance Imaging (CMRI) to evaluate Myocardial area at Risk (MaR), Infarct Size (IS) and Myocardial Salvage Index (MSI).ResultsPaper I: The area under the ANN’s receiver operating characteristics curve for STEMI detection as well as predicting the need of acute PCI were very good.Paper II, III, IV: No significant differences could be shown in discussing MaR, MSI or IS between the O2 group (n=46) and the air group (n=49). Neither could any differences be shown for LVEF and WMSI at the index visit as well after six months between the O2 group (n=46) and the air group (n=41)ConclusionsPaper I: The results indicate that the number of ECGs sent to the CCU could be reduced with 2/3 as the ANN would safely identify ECGs not being STEMI.Paper II, III, IV: The results suggest that it is safe to withhold O2 therapy in normoxic, stable STEMI patients.
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| 2. |
- Latini, Francesco, M.D. 1982-
(författare)
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Significance of white matter anatomy in interpreting features and behaviour of low-grade gliomas and implications for surgical treatment
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Diffuse gliomas are extremely heterogeneous tumours characterized by slow growth but extensive infiltration. Their kinetic features reflect the complex interaction over time with the surrounding brain, influencing treatment planning and outcome. Indeed, resection of diffuse gliomas present a surgical challenge due to their invasiveness and the preferential location in eloquent regions. White matter bundles are the main eloquent limit to surgical resection, but this anatomical-functional information cannot be predicted preoperatively on the individual level. The incomplete description of the human brain connectome, the complex application of pathological/lesion model to the brain connectomic organization, and the underestimated role of white matter anatomy in radiological classification systems are among the major limitations for the comprehension of the glioma/white matter interaction. The overall aim of this thesis was to explore a new approach and new techniques to study the glioma/white matter interaction. A combination of white matter dissection and diffusion tensor tractography (DTT) was used to describe the connectomic organization of two major temporo-occipital connections, the inferior and the middle longitudinal fasciculus. This information was applied to patients with diffuse gliomas, demonstrating how white matter analysis was important to decode patient specific cognitive and language impairment. A new classification system for diffuse gliomas, the Brain-Grid, was created, merging local radiological anatomy with a DTT atlas for infiltration analysis. This standardized radiological tool provided information on subcortical extension (tumour invasiveness), speed, and preferential direction of glioma progression. Applied to a larger cohort of patients, differences were detected between diffuse gliomas subtypes. Tumour invasiveness and the preferential location, type, and extent of white matter involvement differed, impacting overall survival. Regional differences in white matter infiltration were detected among five major white matter bundles, and possible favourable morphological and diffusion features were investigated with transmission electron microscopy and DTT. Fibre diameter, myelin thickness, and the organization of the white matter fibres were different in regions with high infiltration frequency, providing a possible link to the preferential location of diffuse gliomas. Finally, the white matter connectivity, tumour-induced neuroplasticity, clinical and demographic information, preoperative assessment (neuropsychological and language evaluation) were compared with intraoperative findings during awake surgery. Neuropsychological impairment was associated with more invasive tumours and a higher risk of the intraoperative finding of eloquent tumour. The pattern of early cortical neuroplasticity seemed exhausted at the time of diagnosis, with age as a factor predicting the neuroplasticity potential. The combined use of these new techniques revealed new insights into the glioma/white matter interaction. The results provided in this thesis, describe a new way to structure the multidisciplinary perioperative management of these patients. This new information may improve the functional outcome at the individual level, resulting in prolonged survival for adults with diffuse gliomas.
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| 3. |
- Ahlander, Britt-Marie, 1954-
(författare)
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Magnetic Resonance Imaging of the Heart : Image quality, measurement accuracy and patient experience
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Non-invasive diagnostic imaging of atherosclerotic coronary artery disease (CAD) is frequently carried out with cardiovascular magnetic resonance imaging (CMR) or myocardial perfusion single photon emission computed tomography (MPS). CMR is the gold standard for the evaluation of scar after myocardial infarction and MPS the clinical gold standard for ischemia. Magnetic Resonance Imaging (MRI) is at times difficult for patients and may induce anxiety while patient experience of MPS is largely unknown.Aims: To evaluate image quality in CMR with respect to the sequences employed, the influence of atrial fibrillation, myocardial perfusion and the impact of patient information. Further, to study patient experience in relation to MRI with the goal of improving the care of these patients.Method: Four study designs have been used. In paper I, experimental cross-over, paper (II) experimental controlled clinical trial, paper (III) psychometric crosssectional study and paper (IV) prospective intervention study. A total of 475 patients ≥ 18 years with primarily cardiac problems (I-IV) except for those referred for MRI of the spine (III) were included in the four studies.Result: In patients (n=20) with atrial fibrillation, a single shot steady state free precession (SS-SSFP) sequence showed significantly better image quality than the standard segmented inversion recovery fast gradient echo (IR-FGRE) sequence (I). In first-pass perfusion imaging the gradient echo-echo planar imaging sequence (GREEPI) (n=30) had lower signal-to-noise and contrast–to-noise ratios than the steady state free precession sequence (SSFP) (n=30) but displayed a higher correlation with the MPS results, evaluated both qualitatively and quantitatively (II). The MRIAnxiety Questionnaire (MRI-AQ) was validated on patients, referred for MRI of either the spine (n=193) or the heart (n=54). The final instrument had 15 items divided in two factors regarding Anxiety and Relaxation. The instrument was found to have satisfactory psychometric properties (III). Patients who prior CMR viewed an information video scored significantly (lower) better in the factor Relaxation, than those who received standard information. Patients who underwent MPS scored lower on both factors, Anxiety and Relaxation. The extra video information had no effect on CMR image quality (IV).Conclusion: Single shot imaging in atrial fibrillation produced images with less artefact than a segmented sequence. In first-pass perfusion imaging, the sequence GRE-EPI was superior to SSFP. A questionnaire depicting anxiety during MRI showed that video information prior to imaging helped patients relax but did not result in an improvement in image quality.
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| 4. |
- Sandström, Agneta, 1959-
(författare)
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Neurocognitive and endocrine dysfunction in women with exhaustion syndrome
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Stress has emerged as one of the most important factors to consider in psychiatric diagnoses and has become a common reason for long-term sick leave (LTSL). Roughly 50% of LTSL due to psychiatric diseases are thought to be associated with work-related stress. The demarcation towards major depression is disputed, and no international consensus exists for how to diagnose and rehabilitate these individuals. The Swedish National Board of Health has suggested the term “exhaustion syndrome” to integrate these individuals into stress-related disorders. Prominent features of this syndrome are fatigue, sleeping disorders, and cognitive dysfunction. The cognitive dysfunction may be due to an interaction between personality features, environmental factors, the biological effects of stress hormones, and dysfunction in key brain areas, notably the hippocampus and prefrontal cortex. A consistent feature of chronic stress is activation of the cortisol, or hypothalamic-pituitary-adrenal, axis, which may be linked to cognitive dysfunction. Increased glucocorticoid levels, mainly cortisol in humans, are known to impair memory performance. The aim of this thesis was to investigate whether patients with exhaustion syndrome exhibit specific alterations in an extensive set of biological, psychological and immunological variables. Patients in Study 1 had significant cognitive impairment for specific tasks assumed to tap frontal lobe functioning. In Study 2 anxiety prone, worrying, pessimistic individuals with low executive drive and a persistent personality type were more likely to develop exhaustion syndrome. Decreased reactivity was found on the pituitary level after corticotropin releasing hormone (CRH) in exhaustion syndrome patients. The cortisol/adrenocorticotropic hormone response to CRH was slightly higher in patients compared to controls, indicating increased sensitivity at the adrenal cortex level. No differences were found in hippocampal volume. In Study 3, functional imaging revealed a different pattern of brain activation in working memory tests in patients with exhaustion syndrome compared to healthy individuals and patients with depression. In summary, our data suggests an intimate link between personality and wellbeing, cognitive performance and neuroendocrine dysfunction, in exhaustion syndrome. We thus find similarities with major depression but also distinct differences between the exhaustion syndrome and major depression.
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| 5. |
- Hadimeri, Ursula
(författare)
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Factors affecting the physical characteristics of arterio-venous fistula in patients with renal failure
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background and PurposeA patent access is vital for a dialysis patient. The arterio-venous fistula (AVF), the most important access for haemodialysis (HD), is frequently affected by extensive complications such as stenosis and occlusions.Study I: To investigate whether the dimensions of AVFs used for performing haemodialysis were affected by the original disease.Study II: To investigate if the diameter of the distal radiocephalic fistula could influence left ventricular variables in stable haemodialysis patients.Study III: To investigate whether a single Far Infrared (FIR) light treatment could alter blood velocity, AVF diameter or inflammatory markers.Study IV: To evaluate in what extent the renal diagnosis and radiological interventions affected the dysfunction of AVF and results of percutaneous transluminal angioplasty (PTA).Materials and methodsStudy I: The lumen diameter of the AVF was studied by ultrasound in 19 patients with autosomal dominant polycystic kidney disease (ADPKD) and in 19 control patients. The monitoring was performed along the forearm part of the vein, the maximal diameter was measured. The diameters of the two needle insertion sites were also measured.Study II: Nineteen patients were investigated with echocardiography, using M-mode recordings and measurements in the 2D image. Ultrasound and doppler ultrasound were performed. Transsonic measurements were performed after the ultrasound investigation. Measurements of the diameter of the AVF were performed in four locations. Heart variables were analysed regarding left ventricular (LV) criteria.Study III: Thirty patients with native AVF in the forearm were included. Each patient was his/her own control. Ultrasound examinations of the AVF diameter and blood flow velocity were performed before and after a single Far Infrared light (FIR) treatment.Study IV: 522 radiological investigations and endovascular treatments between January 1, 2006 and December 31, 2014 were analysed in 174 patients, retrospectively. All investigations had been performed due to clinical suspicion of impaired AVF function. All stenoses were evaluated and the number, degree, length, location and relation to anastomosis were recorded. After PTA the remaining stenoses were evaluated again and complications were recorded.ResultsStudy I: The diameter of the AVF at the maximal site in patients with ADPKD was significantly wider than that for the control patients.Study II: A larger AVF mean and maximal diameter worsened left ventricular characteristics.Study III: A single FIR treatment resulted in a significant increase in blood velocity over the AV fistula from a mean of 2.1±1.0 m/s to 2.3±1.0 m/s. The diameter of the arterialized vein became wider, i.e. 0.72±0.02 to 0.80±0.02 cm. The increase in fistula blood velocity correlated positively with baseline serum-urate and the increase in venous diameter correlated positively with the baseline plasma orosomucoid concentration.Study IV: The degree of AVF stenosis before PTA correlated significantly with the degree of remaining stenosis after intervention. Arterial stenosis was significantly more frequent among patients with diabetic nephropathy and interstitial nephritis. A shorter life span between PTAs was related to diabetic nephropathy.ConclusionsStudy I: The receiving veins of AVF in patients with ADPKD have an abnormality that causes a greater than normal dilatation in response to the arterialization.Study II: The maximal diameter of the distal AVF seems to be a sensitive marker of LV impairment in stable haemodialysis patients.Study III: A single FIR treatment increased AVF blood velocity and vein diameter. Thus, one FIR treatment can help maturation of AVF in the early postoperative course.Study IV: Repeated PTA was performed significantly more often in patients with diabetic nephropathy. Clinically significant stenosis should be dilated as soon as possible. Occlusion of the AVF should be thrombolyzed and/or dilated when diagnosed.
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| 6. |
- 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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| 7. |
- Covaciu, Lucian, 1964-
(författare)
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Intranasal Cooling for Cerebral Hypothermia Treatment
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The controlled lowering of core body temperature to 32°C to 34°C is defined as therapeutic hypothermia (TH). Therapeutic hypothermia has been shown to improve neurological outcome and survival in unconscious patients successfully resuscitated after cardiac arrest. Brain temperature is important for cerebral protection therefore methods for primarily cooling the brain have also been explored. This thesis focuses on the likelihood that intranasal cooling can induce, maintain and control cerebral hypothermia. The method uses bilaterally introduced intranasal balloons circulated with cold saline. Selective brain cooling induced with this method was effectively accomplished in pigs with normal circulation while no major disturbances in systemic circulation or physiological variables were recorded. The temperature gradients between brain and body could be maintained for at least six hours. Intranasal balloon catheters were used for therapeutic hypothermia initiation and maintenance during and after successful resuscitation in pigs. Temperature reduction was also obtained by combined intranasal cooling and intravenous ice-cold fluids with possible additional benefits in terms of physiologic stability after cardiac arrest. Rewarming was possible via the intranasal balloons. In these studies brain temperature was recorded invasively by temperature probes inserted in the brain. The fast changes in pig’s brain temperature could also be tracked by a non-invasive method. High-spatial resolution magnetic resonance spectroscopic imaging (MRSI) without internal reference showed a good association with direct invasive temperature monitoring. In addition the mapping of temperature changes during brain cooling was also possible. In awake and unsedated volunteers subjected to intranasal cooling brain temperature changes were followed by two MR techniques. Brain cooling was shown by the previously calibrated high-spatial resolution MRSI and by the phase-mapping method. Intranasal cooling reduced body temperature slightly. The volunteers remained alert during cooling, the physiological parameters stable, and no shivering was reported.
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| 8. |
- Pettersson, Olof
(författare)
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Monitoring of neuroendocrine tumor patients undergoing systemic therapies
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Monitoring of neuroendocrine tumor (NET) patients undergoing systemic therapies is troublesome as biomarkers capable of detecting tumor responses have been difficult to establish. Changes in the sum of target lesion diameters are used to evaluate the effects of therapy according to the response evaluation criteria in solid tumors (RECIST 1.1). However, as NETs tend to stabilize or increase in size when responding to therapies, monitoring based on changes in tumor diameters is often ineffective.The overall aim of these doctoral studies was to investigate novel methods for therapy monitoring in NET patients undergoing systemic therapies.In patients with pancreatic NETs (PanNETs) who underwent Peptide Receptor Radionuclide Therapy (PRRT) with 177Lu-DOTATATE at Uppsala University Hospital (n=151), we investigated if arterial-phase tumor attenuation and contrast-enhancement in the liver metastases on computed tomography (CT) changed during PRRT (Paper I).Tumor growth rate (TGR) allows for quantitative assessment of tumor dynamics expressed as percentage per month. In the same cohort as described above, TGR was calculated before and during/after PRRT (Paper II).While 68Ga-DOTA-somatotstatin analog (SSA) PET/CT is essential in the evaluation of NET patient eligibility for PRRT, temporal changes in the tumor uptake of 68Ga-DOTA-SSA have not been shown to reflect PRRT outcome. Tumor-to-blood (TBR) ratio may be closer correlated than SUV to the net influx rate (Ki). The institutional database of the University Hospital in Essen was screened for NET patients, who had undergone at least two cycles of PRRT and 68Ga-DOTA-SSA PET/CT. TBR and tumor-spleen ratio (TSR) were calculated in up to nine lesions per patient (Paper III).Data on imaging were investigated for possible associations with outcome parameters such as progression-free survival and overall survival (Papers I-III).46 PanNET patients with data on Ki-67 from at least two biopsies (Botling et al. 2019) at Uppsala University Hospital were screened for inclusion to describe TGR in PanNET patients. TGR was calculated to elucidate if changes in tumor grade may be reflected in changes in TGR. (Paper IV).In summary, the thesis investigates tools based on morphologic and functional imaging for monitoring of NET patients undergoing systemic therapies.
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| 9. |
- Bondesson, Johan, 1991
(författare)
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Geometric Modeling of Thoracic Aortic Surface Morphology - Implications for Pathophysiology and Clinical Interventions
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Vascular disease risk factors such as hypertension, hyperlipidemia and old age are all results of modern-day lifestyle, and these diseases are getting more and more common. One treatment option for vascular diseases such as aneurysms and dissections is endovascular aortic repair introduced in the early 1990s. This treatment uses tubular fabric covered metallic structures (endografts) that are implanted using a minimally invasive approach and placed to serve as an articial vessel in a damaged portion of the vasculature. To ensure that the interventions are successful, the endograft must be placed in the correct location, and designed to sustain the hostile biological, chemical, and mechanical conditions in the body for many years. This is an interaction that goes both ways, and keeping in mind that the endograft is a foreign object placed in the sensitive vascular system, it is also important that it does not disrupt the native conditions more than necessary. This thesis presents a segmentation and quantication methodology to accurately describe the complex morphology and motion of diseased blood vessels in vivo through a natural and intuitive description of their luminal surfaces. After methodology validation, a series of important clinical applications are performed, all based on non-invasive imaging. Firstly, it is shown that explicit surface curvature quantication is necessary when compared to relying solely on centerline curvature and estimation methods. Secondly, it is shown that endograft malapposition severity can be predicted from preoperative geometric analysis of thoracic aortic surfaces. Thirdly, a multiaxial dynamics analysis of cardiac induced thoracic aortic surface motion shows how thoracic endovascular aortic repair affects the deformations of the dierent portions of the thoracic aorta. Fourthly, the helical propagation pattern of type B aortic dissection is determined, and two distinct modes of chirality are revealed, i.e., achiral and right-handed chiral groups. Finally, the effects of thoracic endovascular aortic repair on helical and cross-sectional morphology of type B dissections are investigated revealing how acuity and chirality affects the alteration due to intraluminal lining with endografts. Thus, the work presented in this thesis contributes by adding knowledge about pathology and pathophysiology through better geometric description of surface conditions of diseased thoracic aortas. This gives clinicians insights to use in their treatment planning and provides more nuanced boundary conditions for endograft manufacturers. Comprehensive knowledge about diseases, better treatment planning, and better devices are all crucial in order to improve the outcomes of performed interventions and ultimately the quality of life for the treated patients.
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| 10. |
- Cronqvist, Mats
(författare)
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Results and complications of endovascular neurointerventions in intracranial aneurysms and arteriovenous malformations, evaluated by conventional angiography and diffusion-perfusion MRI
- 2005
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Aims - To describe and evaluate the efficacy and safety of intra-arterial fibrinolysis and the clinical outcome in SAH patients with thromboembolic complications during endovascular coiling of a ruptured aneurysm. (Paper I) - To describe the use and feasibility of magnetic resonance imaging (MRI), especially diffusion and perfusion imaging, in three patients treated endovascularly for various cerebrovascular disorders. (Paper II) - To evaluate treatment safety as well as complication frequency and management in endovascular coiling of ruptured and unruptured intracranial aneurysms using MR diffusion and perfusion imaging. (Paper III). - To evaluate treatment safety in patients with cerebral arteriovenous malformations and to correlate the anatomical results with regard to complications and clinical outcome using MRI, including diffusion-weighted (DWI) and perfusion imaging (PI). (Paper IV).
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