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| 2. |
- Blystad, Ida, 1972-
(författare)
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Clinical Applications of Synthetic MRI of the Brain
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Magnetic Resonance Imaging (MRI) has a high soft-tissue contrast with a high sensitivity for detecting pathological changes in the brain. Conventional MRI is a time-consuming method with multiple scans that relies on the visual assessment of the neuroradiologist. Synthetic MRI uses one scan to produce conventional images, but also quantitative maps based on relaxometry, that can be used to quantitatively analyse tissue properties and pathological changes. The studies presented here apply the use of synthetic MRI of the brain in different clinical settings.In the first study, synthetic MR images were compared to conventional MR images in 22 patients. The contrast, the contrast-to-noise ratio, and the diagnostic quality were assessed. Image quality was perceived to be inferior in the synthetic images, but synthetic images agreed with the clinical diagnoses to the same extent as the conventional images.Patients with early multiple sclerosis were analysed in the second study. In patients with multiple sclerosis, contrast-enhancing white matter lesions are a sign of active disease and can indicate a need for a change in therapy. Gadolinium-based contrast agents are used to detect active lesions, but concern has been raised regarding the long-term effects of repeated use of gadolinium. In this study, relaxometry was used to evaluate whether pre-contrast injection tissue-relaxation rates and proton density can identify active lesions without gadolinium. The findings suggest that active lesions often have relaxation times and proton density that differ from non-enhancing lesions, but with some overlap. This makes it difficult to replace gadolinium-based contrast agent injection with synthetic MRI in the monitoring of MS patients.Malignant gliomas are primary brain tumours with contrast enhancement due to a defective blood-brain barrier. However, they also grow in an infiltrative, diffuse manner, making it difficult to clearly delineate them from surrounding normal brain tissue in the diagnostic workup, at surgery, and during follow-up. The contrast-enhancing part of the tumour is easily visualised, but not the diffuse infiltration. In studies three and four, synthetic MRI was used to analyse the peritumoral area of malignant gliomas, and revealed quantitative findings regarding peritumoral relaxation changes and non-visible contrast enhancement suggestive of non-visible infiltrative tumour growth.In conclusion, synthetic MRI provides quantitative information about the brain tissue and this could improve the diagnosis and treatment for patients.
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| 3. |
- Blystad, Ida, et al.
(författare)
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Synthetic MRI of the brain in a clinical setting
- 2012
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Ingår i: Acta Radiologica. - : Sage Publications. - 0284-1851 .- 1600-0455. ; 53:10, s. 1158-1163
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:Conventional magnetic resonance imaging (MRI) has relatively long scan times for routine examinations, and the signal intensity of the images is related to the specific MR scanner settings. Due to scanner imperfections and automatic optimizations, it is impossible to compare images in terms of absolute image intensity. Synthetic MRI, a method to generate conventional images based on MR quantification, potentially both decreases examination time and enables quantitative measurements.PURPOSE:To evaluate synthetic MRI of the brain in a clinical setting by assessment of the contrast, the contrast-to-noise ratio (CNR), and the diagnostic quality compared with conventional MR images.MATERIAL AND METHODS:Twenty-two patients had synthetic imaging added to their clinical MR examination. In each patient, 12 regions of interest were placed in the brain images to measure contrast and CNR. Furthermore, general image quality, probable diagnosis, and lesion conspicuity were investigated.RESULTS:Synthetic T1-weighted turbo spin echo and T2-weighted turbo spin echo images had higher contrast but also a higher level of noise, resulting in a similar CNR compared with conventional images. Synthetic T2-weighted FLAIR images had lower contrast and a higher level of noise, which led to a lower CNR. Synthetic images were generally assessed to be of inferior image quality, but agreed with the clinical diagnosis to the same extent as the conventional images. Lesion conspicuity was higher in the synthetic T1-weighted images, which also had a better agreement with the clinical diagnoses than the conventional T1-weighted images.CONCLUSION:Synthetic MR can potentially shorten the MR examination time. Even though the image quality is perceived to be inferior, synthetic images agreed with the clinical diagnosis to the same extent as the conventional images in this study.
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| 5. |
- Dahlqvist Leinhard, Olof, et al.
(författare)
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Is Increased Normal White Matter Glutamate Concentration a Precursor of Gliosis and Disease Progression in Multiple Sclerosis?
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Background: The multiple sclerosis (MS) severity scale (MSSS) is a new scoring procedure to clinically characterize the rate of disease progression in MS, rather than the disability of the patient. The latter is often characterized using the expanded disability status score (EDSS). The progress rate of the disease, magnetic resonance imaging (MRI)-based measures of ‘black hole lesions’, and atrophy have all been shown to be predicted well by MSSS. In this study we investigated possible relationships between brain metabolite concentrations, measured using proton (1H) magnetic resonance spectroscopy (MRS), and MSSS. Purpose: Our aims were to quantitatively investigate the metabolite concentrations in normal appearing white matter (NAWM) in MS-patients, and also to investigate possible correlations between disease subtype, EDSS and MSSS and metabolite concentrations. To minimize the interference from lesion contamination in the MRS measurement, a refined novel analysis procedure had to be developed in order to correct for partial volume effects in tissues near plaques. Materials and Methods: Forty eight patients with Clinically Definite MS (CDMS), and 18 normal control subjects (NC) were included retrospectively from several MRS studies. T1, T2, and proton density MRI, and four white matter 1H MRS single voxel PRESS (Point-REsolved SpectroScopy) spectra were acquired in each subject using echo time 35 ms and repetition time 6000 ms on a 1.5 T MR-scanner. A total of 108 examinations were acquired from patients and 18 from NC. Absolutely quantified NAWM metabolite concentrations were determined using a mixed linear model (MLM) analysis that included the degree of T2 lesion contamination in each voxel. The T2 lesion contamination of the MRS voxels was also used as an estimate of ‘lesion load’ at each exam. The corrected metabolite concentrations were then correlated with clinical measures of the patients’ status, including EDSS and MSSS. Results: The axonal marker N-acetyl aspartate (NAA) did not correlate with either EDSS or MSSS. The glial cell markers creatine and myo-inositol correlated positively with EDSS. Creatine and glutamate correlated positively with MSSS. The ‘estimated lesion load’ correlated positively not only with EDSS, but also with the number of bouts since disease onset. Importantly, it did not correlate with MSSS. Conclusion: The most interesting findings were the unchanged concentrations of NAA, and the concomitant increase of creatine and myo-inositol during the course of disease progression in MSpatients. These not only indicated a constant axonal density, but also that a simultaneous development of gliosis occurred. These processes are most likely linked to demyelination, as well as development of white matter atrophy, a process in which the demyelinated volume is replaced by the surrounding tissue leading to a net loss of white matter. As a consequence of this process, axons in NAWM are probably damaged, which leads to a higher concentration of glia cells relative to the axonal volume. The positive correlation that was found between MSSS, and the glutamate and creatine concentrations in NAWM, in combination with a complete lack of correlation between lesion load and MSSS, suggests that altered glutamate metabolism, and subsequent demyelination and gliosis, is an important pathophysiological mechanism in MS.
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| 7. |
- Tisell, Anders, et al.
(författare)
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Increased Concentrations of Glutamate and Glutamine in Normal Appearing White Matter of Patients with Multiple Sclerosis and Normal MR Imaging Brain Scans
- 2013
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:4
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Tidskriftsartikel (refereegranskat)abstract
- In Multiple Sclerosis (MS) the relationship between disease process in normal-appearing white matter (NAWM) and the development of white matter lesions is not well understood. In this study we used single voxel proton ‘Quantitative Magnetic Resonance Spectroscopy’ (qMRS) to characterize the NAWM and thalamus both in atypical ‘Clinically Definite MS’ (CDMS) patients, MRIneg (N = 15) with very few lesions (two or fewer lesions), and in typical CDMS patients, MRIpos (N = 20) with lesions, in comparison with healthy control subjects (N = 20). In addition, the metabolite concentrations were also correlated with extent of brain atrophy measured using Brain Parenchymal Fraction (BPF) and severity of the disease measured using ‘Multiple Sclerosis Severity Score’ (MSSS). Elevated concentrations of glutamate and glutamine (Glx) were observed in both MS groups (MRIneg 8.12 mM, p<0.001 and MRIpos 7.96 mM p<0.001) compared to controls, 6.76 mM. Linear regressions of Glx and total creatine (tCr) with MSSS were 0.16±0.06 mM/MSSS (p = 0.02) for Glx and 0.06±0.03 mM/MSSS (p = 0.04) for tCr, respectively. Moreover, linear regressions of tCr and myo-Inositol (mIns) with BPF were −6.22±1.63 mM/BPF (p<0.001) for tCr and −7.71±2.43 mM/BPF (p = 0.003) for mIns. Furthermore, the MRIpos patients had lower N-acetylaspartate and N-acetylaspartate-glutamate (tNA) and elevated mIns concentrations in NAWM compared to both controls (tNA: p = 0.04 mIns p<0.001) and MRIneg (tNA: p = 0.03 , mIns: p = 0.002). The results suggest that Glx may be an important marker for pathology in non-lesional white matter in MS. Moreover, Glx is related to the severity of MS independent of number of lesions in the patient. In contrast, increased glial density indicated by increased mIns and decreased neuronal density indicated by the decreased tNA, were only observed in NAWM of typical CDMS patients with white matter lesions.
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| 8. |
- Tisell, Anders
(författare)
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The Non-Invasive Brain Biopsy : Implementation and Application of Quantitative Magnetic Resonance Spectroscopy on Healthy and Diseased Human Brain
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: In this thesis, one of the major objectives was to implement a method for (absolute) quantitative magnetic resonance spectroscopy (qMRS) of the human brain, intended for clinical use. The implemented method was based on standard spatially selective MRS sequences. The tissue water was used as an internal reference, which was calibrated using whole brain quantitative magnetic resonance imaging (qMRI). The second objective was to apply the method in clinical neuroimaging investigation, of different disease processes in the human brain.Materials and Methods: In total, 158 subjects were included and 507 MRS measurements (330 in white matter and 177 in the thalamus) were acquired.In a cross-sectional study of multiple sclerosis (MS), 35 ‘clinically definite MS’ (CDMS) patients were included, of which 15 were atypical CDMS patients with a very low number of white matter lesions (two or fewer), and 20 were typical CDMS patients with white matter lesions (three or more) were included. The metabolite concentrations in normal appearing white matter (NAWM) and the thalamus were assessed using the qMRS method developed in this thesis, and the brain parenchymal fraction (BPF) was calculated from the qMRI data. A cohort of 27 CDMS patients were then treated with Natalizumab and examined both at baseline, and after one year of treatment. Both qMRS and CSF samples for the purpose of assessing intrathecal inflammation were obtained. In addition, the frontal deep white matter (FDWM) and the thalamus were investigated in 20 idiopathic normal pressure hydrocephalus (iNPH) patients using qMRS. Finally, the left thalamus of 14 Kleine-Levin Syndrome (KLS) patients were examined using both qMRS and functional MRI (fMRI) of neurological activation of the left thalamus during a working memory test. Moreover, 63 healthy subjects were included as controls for this work.Results: A quantitative MRS method based on water referencing was successfully developed, implemented, and evaluated at 1.5 T. Both healthy subjects and MS patients showed a positive correlation between the concentrations of total Creatine (tCr) and myo Inositol (mIns) and age, and also a negative correlation with BPF were observed. Glutamate and Glutamine (Glx) levels were elevated for all MS patient groups compared to healthy controls. In contrast, lower concentrations of total N-acetyl aspartate and N-acetyl aspartate glutamate (tNA) and higher mIns concentrations in NAWM were only observed in MS patients that had developed white matter lesions. Moreover, the change in concentrations of tCr and total Choline (tCho) in MS patients during Natalizumab-treatment were positively correlated with markers of intrathecal inflammation. The iNPH patients had lower tNA and N-acetyl aspartate (NAA) concentrations in the thalamus compared to the controls. In addition, the NAA concentrations in the left thalamus were inversely correlated to the fMRI activation in the left thalamus during the working memory test in KLS patients.Discussion: The calculated calibration factors were in good agreement with the results found in the literature, indicating that the calibration factors were accurate.The observed elevated Glx concentration in MS could be due to increased concentrations of glutamate (Glu), which is neurotoxic at high concentrations, thus the elevated Glx could be linked to the clinically observed neurodegeneration in MS both in patients that have developed lesions and in atypical patients that do not develop any (or extremely few) lesions.Both tCr and mIns can be used as glia markers, thus the correlations of tCr and mIns concentrations with both age and BPF indicates that the local glia cell density, or tissue fraction, increases with age and atrophy. Moreover, the higher mIns concentrations in the NAWM of MS patients with a substantial white matter lesion load indicate that the glia tissue amount in NAWM is increased in MS patients that develop lesions. NAA is neuronal-specific, thus the lower tNA concentrations indicate that the neurone concentration is lower in the NAWM of MS patients that develop MS lesions. The lack of correlation between tNA with age and BPF in combination with the presence of correlation between tCr and mIns with both age and BPF, might be explained using a model for neurodegeneration. In which, there is a higher neurone loss compared to the glia loss. However, the lost tissue is compensated by compression of the tissue, which keeps the density of neurones more or less constant and the density of glia increased.The low concentration levels of the neuronal marker NAA in the thalamus of the iNPH patients indicates that the basal ganglia-thalamic-subcortical frontal circuits are damage or at least strongly modulated in the thalamus.The correlation between strong activation in left thalamus during a working memory test with the neuronal marker NAA indicate that the KLS patients that have low neuronal concentration also needed to utilise the working memory circuitry more heavily in order to perform the task as healthy subjects.Conclusion: It is possible to use qMRI for accurate and robust determination of qMRS in clinical practice, even at 1.5 T field strength. The tGlx concentration may be an important marker for pathology in the nonlesional white matter of MS-patients. The increased glia and loss of neurones in the NAWM are associated with the formation of white matter lesions.
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| 10. |
- West, Janne, et al.
(författare)
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Normal Appearing and Diffusely Abnormal White Matter in Patients with Multiple Sclerosis, Assessed with Quantitative MR : Optimization for clinical usage
- 2014
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Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 9:4, s. e95161-
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Magnetic Resonance Imaging is a sensitive technique for detecting white matter (WM) MS lesions, but the relation with clinical disability is low. Because of this, changes in both ‘normal appearing white matter’ (NAWM) and ‘diffusely abnormal white matter’ (DAWM) have been of interest in recent years. MR techniques, including quantitative magnetic resonance imaging (qMRI) and quantitative magnetic resonance spectroscopy (qMRS), have been developed in order to detect and quantify such changes.In this study, a combination of qMRI and qMRS was used to investigate NAWM and DAWM in typical MS patients and in MS patients with low number of WM lesions. Patient data were compared to ‘normal white matter’ (NWM) in healthy controls.Methods: QMRI and qMRS measurements were performed on a 1.5T Philips MR-scanner. 35 patients with clinically definite MS and 20 healthy controls were included. Fifteen of the patients showed few WM lesions (‘MRIneg‘) and 20 showed radiologically typical findings (‘MRIpos’). QMRI properties were determined in ROIs of NAWM, DAWM and WM lesions in the MS groups and of NWM in controls. Descriptive statistical analysis and comparisons were performed. Correlations were calculated between qMRI measurements and (1) clinical parameters and (2) WM metabolite concentrations. Regression analyses were performed with brain parenchyma fraction and MSSS.Results: NAWM in the MRIneg group was significantly different from NAWM in the MRIpos group and NWM. In addition, R1 and R2 of NAWM in the MRIpos group correlated negatively with EDSS and MSSS. DAWM was significantly different from NWM, but similar in the two MS groups. N-acetyl aspartate correlated negatively with R1 and R2 in MRIneg. Finally, R2 of DAWM was associated with BPF.Conclusions: Changes in NAWM and DAWM are independent pathological entities in the disease. Combined qMRI and qMRS measurements of NAWM and DAWM provide important markers for disease status.
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