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- Bergman, Lina, 1982-
(författare)
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Cerebral biomarkers in women with preeclampsia
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Preeclampsia and eclampsia are among the most common causes of maternal and fetal mortality and morbidity worldwide. There are no reliable means to predict eclampsia or cerebral edema in women with preeclampsia and knowledge of the brain involvement in preeclampsia is still limited. S100B and neuron specific enolase (NSE) are two cerebral biomarkers of glial- and neuronal origin respectively. They are used as predictors for neurological outcome after traumatic brain injuries and cardiac arrest but have not yet been investigated in preeclampsia.This thesis is based on one longitudinal cohort study of pregnant women (n=469, Paper I and III), one cross sectional study of women with preeclampsia and women with normal pregnancies (n=53 and 58 respectively, Paper II and IV) and one experimental animal study of eclampsia (Paper V).In Paper I and III, plasma concentrations of S100B and NSE were investigated throughout pregnancy in women developing preeclampsia (n=16) and in women with normal pregnancies (n=36) in a nested case control study. Plasma concentrations were increased in women developing preeclampsia in gestational week 33 and 37 for S100B and in gestational week 37 for NSE compared to women with normal pregnancies.In Paper II and IV, increased plasma concentrations of S100B and NSE were confirmed among women with preeclampsia compared to women with normal pregnancies. Furthermore, increased plasma concentrations of S100B correlated to visual disturbances among women with preeclampsia (Paper II) and plasma concentrations of S100B and NSE remained increased among women with preeclampsia one year after delivery (Paper IV).In Paper V, an experimental rat model of preeclampsia and eclampsia demonstrated increased serum concentrations of S100B after seizures in normal pregnancy (n=5) and a tendency towards increased plasma concentrations of S100B in preeclampsia (n=5) compared to normal pregnancy (n=5) without seizures. Furthermore, after seizures, animals with magnesium sulphate treatment demonstrated increased serum concentrations of S100B and NSE compared to no treatment.In conclusion; plasma concentrations of S100B and NSE are increased in preeclampsia during late pregnancy and postpartum and S100B correlates to visual disturbances in women with preeclampsia. The findings are partly confirmed in an animal model of eclampsia.
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- Correia de Verdier, Maria, 1983-
(författare)
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Evaluation of Intracranial Arteriovenous Malformations with Magnetic Resonance Imaging
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Intracranial arteriovenous malformations (AVMs) are characterized by feeding arteries, a tangle of abnormal vessels (nidus) and draining veins. Radiological evaluation methods are used in diagnosing AVMs, treatment planning, post-treatment evaluation and monitoring stability. The general aim of our studies reviewed in this thesis was to develop and evaluate magnetic resonance imaging (MRI) techniques for the evaluation of AVMs. MethodsPaper I – In 30 patients treated with proton radiation therapy, radiation-induced MRI changes (vasogenic edema, contrast enhancement and cavitation) and their association with development of neurological symptoms and nidus obliteration were assessed. Paper II – We evaluated the effect of acquisition parameters (voxel size, number of signal averages and velocity encoding) on the accuracy and precision of phase-contrast MRI (PC-MRI)-measured flow and velocity in a small-lumen vessel phantom with constant flow. Paper III – Normal ranges and test-retest reproducibility of flow and velocity in the anterior, middle and posterior cerebral arteries were measured with PC-MRI in 30 healthy volunteers.Paper IV – We studied PC-MRI-measured flow and velocity in feeding arteries in 10 patients with AVMs and compared the values obtained with the results from paper III. We also assessed post-treatment changes in flow and velocity in three patients. Results Paper I – Radiation-induced MRI changes were found in 87% of patients after proton radiation treatment of AVMs. MRI changes were associated with neurological symptoms but not with nidus obliteration. Paper II – PC-MRI overestimated flow in a small-lumen vessel phantom. Accuracy for flow measurements improved by decreasing voxel size. Precision for both flow and velocity measurements improved by increasing voxel size. Precision for flow measurements improved by increasing the number of signal averages.Paper III – We reported normal ranges and test-retest reproducibility for PC-MRI-measured flow and velocity in the main intracranial arteries. Reproducibility was overall quite low, but higher for the middle cerebral arteries than for the anterior and posterior cerebral arteries.Paper IV – Patients with a large nidus have increased velocity measured with PC-MRI in feeding arteries compared to intracranial arteries in healthy individuals. There is a reduction in PC-MRI-measured flow and velocity after treatment. ConclusionRadiation-induced MRI changes are common after proton radiation treatment of AVMs. The accuracy and precision of PC-MRI measurements in a phantom depend on acquisition parameter settings. In patients with AVMs with a large nidus, increased velocity is observed in feeding arteries, and a decrease in flow and velocity is observed after treatment. PC-MRI can potentially be used as a clinical tool to aid treatment planning and post-treatment evaluation.
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- Nelander, Maria, 1974-
(författare)
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Preeclampsia and the Brain : Epidemiological and Magnetic Resonance Studies
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Preeclampsia is a pregnancy specific syndrome that causes substantial maternal and fetal morbidity and mortality. One major contributor to maternal deaths is eclampsia, i.e. when seizures arise in the context of preeclampsia. The pathophysiology of eclampsia is still incompletely chartered and the long-term cerebral consequences of preeclampsia are also largely unknown.This thesis consists of a register based cohort study (n=3232, study I), and a cross-sectional neuroimaging study of pregnant women with and without preeclampsia (n=78, studies II-IV).In paper I, we compared the incidence of dementia and cardiovascular disease (CVD) between women ≥65 years with a self-reported history of hypertensive pregnancy, and women with a normotensive pregnancy. No difference was found regarding dementia, but an increased risk of CVD persisted among these elderly women.In paper II, we used phosphorus magnetic resonance spectroscopy to measure cerebral magnesium levels (Mg2+). We found lower levels of Mg2+ in women with preeclampsia than in women with normal pregnancy and non-pregnant women. Further, which was novel, we showed that lower cerebral Mg2+levels correlated with visual disturbances. The findings are interesting, since magnesium sulfate is the most effective treatment and prophylaxis for eclampsia, but with a largely unknown mechanism of action.In paper III, we measured cerebral organic osmolytes with proton magnetic resonance spectroscopy and found lower levels of osmolytes in pregnancy. Cerebral osmolytes were positively correlated with a decreased plasma osmolality, indicating that there is a joint biological mechanism. The only osmolyte that differed between women with preeclampsia and healthy pregnant women was glutamate. Glutamate is an excitatory neurotransmitter, which also functions as an osmolyte. Thus, lower cerebral glutamate levels could have implications on the pathophysiology of seizures.In paper IV, cerebral perfusion and edema were assessed with magnetic resonance imaging using intravoxel incoherent motion technique. A reduced perfusion fraction was found in a part of the basal ganglia in women with preeclampsia. No difference in edema was detected.Our findings indicate Mg2+ metabolism, plasma hypoosmolality and possibly cerebral hypoperfusion to be involved in the pathophysiology of cerebral affection in preeclampsia.
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- Amini, Hashem
(författare)
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Fetal Anomalies : Surveillance and Diagnostic Accuracy of Ultrasound and Magnetic Resonance Imaging
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The aims were to investigate the accuracy of ultrasound in diagnosis of structural fetal anomalies with special focus on false positive findings (I), to evaluate the additional value of second trimester fetal MRI on pregnancy management (II-III) and to estimate the ascertainment in the Swedish Birth Defects Registry and incidence of spina bifida and cleft lip/palate (IV). Retrospectively, 328 fetal autopsies were identified where pregnancies were terminated due to ultrasonographically diagnosed fetal anomalies. In 175 (53.4 %) cases ultrasound and fetal autopsy were identical, in 124 (37.8 %) ultrasound was almost correct, in 23 (7.0 %) ultrasound diagnoses could not be verified, but fetal autopsy showed other anomalies with at least the same prognostic value and in six (1.8 %) ultrasound diagnosis could not be verified and autopsy showed no or less severe anomalies (I). Prospectively, 29 pregnancies with CNS- (II) and 63 with non-CNS-anomalies (III) were included. In the CNS study MRI provided no additional information in 18 fetuses (62 %), additional information without changing the management in 8 (28 %) and additional information altering the pregnancy management in 3 (10%). In the non-CNS study the corresponding figures were 43 (68 %), 17 (27 %) and three (5 %), respectively. MRI in the second trimester might be a clinically valuable adjunct to ultrasound for the evaluation of CNS anomalies, especially when the ultrasound is inconclusive due to maternal obesity (II) and in non-CNS anomalies in cases of diaphragmatic hernia or oligohydramnios (III). In newborns, the ascertainments of birth defects are relatively high and assessable, but in pregnancy terminations they are lower or unknown. The incidence of newborns with spina bifida has decreased because of an increased rate of pregnancy terminations (>60%). There is room for improvement concerning the reporting of anomalies from terminated pregnancies (IV).
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- Bannbers, Elin, 1984-
(författare)
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The Effect of Steroid Hormones in the Female Brain During Different Reproductive States
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Women are twice as likely as men to suffer from depression and anxiety disorders and have an increased risk of onset during periods associated with hormonal changes, such as the postpartum period and the menopausal transition. Furthermore, some women seem more sensitive to normal hormone fluctuations across the menstrual cycle, since approximately 3-5% suffers from premenstrual dysphoric disorder (PMDD). Why these disorders are so common in women has not been established but there is a probable involvement of the ovarian hormones.The aim of this thesis was to investigate the effect of the ovarian hormones on the female brain during different reproductive states using psychological tests known to affect brain activity in different ways.Paper one examined the effect of the ovarian hormones on prepulse inhibition (PPI) on the acoustic startle response (ASR) and comprised cycling women and postmenopausal women. The cycling women had lower levels of PPI compared to postmenopausal women and postmenopausal women with moderate estradiol levels had lower PPI compared to postmenopausal women with low estradiol levels.Paper two examined the effect of anticipation and affective modulation on the ASR in women with PMDD and healthy controls. Women with PMDD have an increased modulation during anticipation of affective pictures compared to healthy controls during the luteal phase of the menstrual cycle.Paper three examined brain activity during response inhibition among women with PMDD and healthy controls by the use of a Go/NoGo task and fMRI. Women with PMDD displayed a decreased activity in the left insula during follicular phase and an increased activity during the luteal phase compared to controls.Paper four comprised women in the postpartum period and non-pregnant controls to examine brain activity during response inhibition. While this study revealed decreased activity at 4 weeks postpartum compared to 48 hours postpartum we cannot ascertain the role of the ovarian steroids, since none of the significant brain areas correlated with ovarian steroid or neurosteroid serum concentrations.The results of this thesis demonstrate that the ovarian hormones, or at least various hormonal states, have a probable impact on how the female brain works.
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- Canto Moreira, Nuno
(författare)
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MRI Studies of the Fetal Brain and Cranium
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Ultrasound is the primary modality for fetal imaging, but Magnetic Resonance Imaging nowadays has a valuable complementary role as it often reveals findings that alter pregnancy management. Knowledge on some clinically relevant areas of the normal fetal development is still lacking, and this was the aim of this project. We wanted 1) to obtain reference MRI data of normal brain measurements before 24 gestation weeks (GW), 2) to study the development of the hippocampus, 3) to study the development of the ear and 4) to test the ability of MRI for evaluating the lip and palate. For this, we retrospectively analysed a database with 464 in vivo and 21 post mortem fetal MRI examinations. Study I evaluated a series of 70 normal fetuses. A table of normal brain measurements from 17 to 23 GW was built, the first in the literature that includes ages below 20 GW. Study II focused on the evolution of the hippocampus from 18 to 38 GW by evaluating 3 post mortem and 60 in vivo MRI examinations. Our results suggested this area to develop later and more asymmetrically than previously thought. Study III analysed a series of 122 normal MRI in vivo and 16 MRI post mortem. We described the development of the fetal ear in vivo for the first time in the literature, realizing that the value of MRI is limited by the size of the structures evaluated. In study IV, 60 brain-targeted MRI examinations of 55 normal fetuses and 5 fetuses with orofacial clefts were blindly reviewed by two readers, focusing on the lips and palates. Our results suggest a high accuracy of MRI in the evaluation of this area, regardless of fetal age or previous ultrasound findings. This thesis brings new knowledge on the normal development of the fetal brain and cranium.
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- Gingnell, Malin, 1982-
(författare)
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Ovarian Steroid Hormones, Emotion Processing and Mood
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- It is known that some psychiatric disorders may deteriorate in relation to the menstrual cycle. However, in some conditions, such as premenstrual dysphoric disorder (PMDD), symptomatology is triggered mainly by the variations in ovarian steroid hormones. Although symptoms induced by fluctuations in ovarian steroids often are affective, little is known about how emotion processing in women is influenced by variations, or actual levels, of ovarian steroid hormones.The general aim of this thesis was to evaluate menstrual cycle effects on reactivity in emotion generating and controlling areas in the corticolimbic system to emotional stimulation and anticipation, in healthy controls and women with PMDD. A second aim was to evaluate corticolimbic reactivity during long-term administration of exogenous ovarian steroids.In study I, III and IV effects of the menstrual cycle on emotional reactivity in women with PMDD was studied. In study I, women with PMDD in displayed higher amygdala reactivity than healthy controls to emotional faces, not in the luteal phase as was hypothesised, but in the follicular phase. No difference between menstrual cycle phases was obtained in women with PMDD, while healthy controls had an increased reactivity in the luteal phase. The results of study I was further elaborated in study III, where women with PMDD were observed to have an increased anticipatory reactivity to negative emotional stimuli. However, no differences in amygdala reactivity to emotional stimuli were obtained across the menstrual cycle. Finally, in study IV the hypothesis that amygdala reactivity increase in the luteal phase in women with PMDD is linked to social stimuli rather than generally arousing stimuli was suggested, tested and supported.In study II, re-exposure to COC induced mood symptoms de novo in women with a previous history of COC-induced adverse mood. Women treated with COC reported increased levels of mood symptoms both as compared to before treatment, and as compared to the placebo group. There was a relatively strong correlation between depressive scores before and during treatment. The effects of repeated COC administration on subjective measures and brain function were however dissociated with increased aversive experiences accompanied by reduced reactivity in the insular cortex.
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- Hansen, Tomas, 1970-
(författare)
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Assessment of Atherosclerosis by Whole-Body Magnetic Resonance Angiography.
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Atherosclerosis is a serious threat to public health and a major cause of morbidity and mortality. In this doctoral research, the feasibility of using whole-body magnetic resonance angiography (WBMRA) was studied as a principal aim both in patients and in an epidemiological setting. Secondary aims were to create a score for assessment of the degree of atherosclerosis with the use of WBMRA and to investigate the correlation between this score and various cardiovascular (CV) risk factors. WBMRA was found feasible both in atherosclerotic patients and in an elderly population from the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS). All subjects except one completed the examination without any adverse events. A large proportion (93-99%) of the vessel segments could be evaluated and the results of a smaller comparison between WBMRA and conventional invasive x-ray angiography were reasonable regarding the assessed degree of maximum stenosis or occlusion. This indicates the safety and robustness of the WBMRA method.Unsuspected significant vascular abnormalities were found in patients with atherosclerotic symptoms and significant vascular abnormalities were present in elderly subjects without any self-reported vascular disease. The prevalence rates of vascular abnormalities in the carotid, renal, and inflow and runoff arteries of the lower limbs were estimated in an elderly population. A total atherosclerotic score (TAS) reflecting the degree of luminal narrowing was created for the WBMRA method and was significantly related to Framingham risk score (FRS) and to the amount of abdominal visceral adipose tissue, interleukin-6, and leptin and was inversely significantly related to adiponectin. Studies with outcome data of the PIVUS cohort are needed for further validation of the WBMRA method and to determine whether TAS can be used as an adjunct for CV risk assessment. Meanwhile, the correlation with FRS indicates that TAS could be of value for this purpose.
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