Quantitative Magnetic Resonance Imaging of Tissue Microvasculature and Microstructure in Selected Clinical Applications

This thesis is based on four papers and aims to establish perfusion and diffusion measurements with magnetic resonance imaging (MRI) in selected clinical applications. While structural imaging provides invaluable geometric and anatomical information, new disease relevant information can be obtained from measures of physiological processes inferred from advanced modelling. This study is motivated by clinical questions pertaining to diagnosis and treatment effects in particular patient groups where inflammatory processes are involved in the disease. Paper 1 investigates acquisition parameters in dynamic contrast enhanced (DCE)-MRI of the temporomandibular joint (TMJ) with possible involvement of juvenile idiopathic arthritis. High level elastic motion correction should be applied to DCE data from the TMJ, and the DCE data should be acquired with a sample rate of at least 4 s. Paper 2 investigates choices of arterial input functions (AIFs) in dynamic susceptibility contrast (DSC)-MRI in brain metastases. AIF shapes differed across patients. Relative cerebral blood volume estimates differentiated better between perfusion in white matter and grey matter when scan-specific AIFs were used than when patient-specific AIFs and population-based AIFs were used. Paper 3 investigates DSC-MRI perfusion parameters in relation to outcome after stereotactic radiosurgery (SRS) in brain metastases. Low perfusion prior to SRS may be related to unfavourable outcome. Paper 4 applies free water (FW) corrected diffusion MRI to characterise glioma. Fractional anisotropy maps of the tumour region were significantly impacted by FW correction. The estimated FW maps may also contribute to a better description of the tumour. Although there are challenges related to post-processing of MRI data, it was shown that the advanced MRI methods applied can add to a more accurate description of the TMJ and of brain lesions.Doktorgradsavhandlin

Dynamic Susceptibility Contrast MRI May Contribute in Prediction of Stereotactic Radiosurgery Outcome in Brain Metastases

Background Following stereotactic radiosurgery (SRS), predicting treatment response is not possible at an early stage using structural imaging alone. Hence, the current study aims at investigating whether dynamic susceptibility contrast (DSC)-MRI estimated prior to SRS can provide predictive biomarkers in response to SRS treatment and characterize vascular characteristics of pseudo-progression. Methods In this retrospective study, perfusion-weighted DSC-MRI image data acquired with a temporal resolution of 1.45 seconds were collected from 41 patients suffering from brain metastases. Outcome was defined based on lesion volume changes in time (determined on structural images) or death. Motion correction and manual lesion delineation were performed prior to semi-automated, voxel-wise perfusion analysis. Statistical testing was performed using linear regression and a significance threshold at P = .05. Age, sex, primary cancers (pulmonary cancer and melanoma), lesion volume, and dichotomized survival time were added as covariates in the linear regression models (ANOVA). Results Relative cerebral blood volume (rCBV) and relative cerebral blood flow (rCBF) were found to be significantly lower prior to SRS treatment in patients with increasing lesion volume or early death post-SRS (P ≤ .01). Conclusion Unfavorable treatment outcome may be linked to low perfusion prior to SRS. Pseudo-progression may be preceded by a transient rCBF increase post-SRS. However, results should be verified in different or larger patient material.publishedVersio

Effects of Multi-Shell Free Water Correction on Glioma Characterization.

Diffusion MRI is a useful tool to investigate the microstructure of brain tumors. However, the presence of fast diffusing isotropic signals originating from non-restricted edematous fluids, within and surrounding tumors, may obscure estimation of the underlying tissue characteristics, complicating the radiological interpretation and quantitative evaluation of diffusion MRI. A multi-shell regularized free water (FW) elimination model was therefore applied to separate free water from tissue-related diffusion components from the diffusion MRI of 26 treatment-naïve glioma patients. We then investigated the diagnostic value of the derived measures of FW maps as well as FW-corrected tensor-derived maps of fractional anisotropy (FA). Presumed necrotic tumor regions display greater mean and variance of FW content than other parts of the tumor. On average, the area under the receiver operating characteristic (ROC) for the classification of necrotic and enhancing tumor volumes increased by 5% in corrected data compared to non-corrected data. FW elimination shifts the FA distribution in non-enhancing tumor parts toward higher values and significantly increases its entropy (p ≤ 0.003), whereas skewness is decreased (p ≤ 0.004). Kurtosis is significantly decreased (p < 0.001) in high-grade tumors. In conclusion, eliminating FW contributions improved quantitative estimations of FA, which helps to disentangle the cancer heterogeneity

Effects of Multi-Shell Free Water Correction on Glioma Characterization.

Diffusion MRI is a useful tool to investigate the microstructure of brain tumors. However, the presence of fast diffusing isotropic signals originating from non-restricted edematous fluids, within and surrounding tumors, may obscure estimation of the underlying tissue characteristics, complicating the radiological interpretation and quantitative evaluation of diffusion MRI. A multi-shell regularized free water (FW) elimination model was therefore applied to separate free water from tissue-related diffusion components from the diffusion MRI of 26 treatment-naïve glioma patients. We then investigated the diagnostic value of the derived measures of FW maps as well as FW-corrected tensor-derived maps of fractional anisotropy (FA). Presumed necrotic tumor regions display greater mean and variance of FW content than other parts of the tumor. On average, the area under the receiver operating characteristic (ROC) for the classification of necrotic and enhancing tumor volumes increased by 5% in corrected data compared to non-corrected data. FW elimination shifts the FA distribution in non-enhancing tumor parts toward higher values and significantly increases its entropy (p ≤ 0.003), whereas skewness is decreased (p ≤ 0.004). Kurtosis is significantly decreased (p < 0.001) in high-grade tumors. In conclusion, eliminating FW contributions improved quantitative estimations of FA, which helps to disentangle the cancer heterogeneity

Effects of fleas on nest success of Arctic barnacle geese:experimentally testing the mechanism

Parasites have detrimental effects on their hosts' fitness. Therefore, behavioural adaptations have evolved to avoid parasites or, when an individual is already in contact with a parasite, prevent or minimize infections. Such anti-parasite behaviours can be very effective, but can also be costly for the host. Specifically, ectoparasites can elicit strong host anti-parasite behaviours and interactions between fleas (Siphonaptera) and their hosts are one of the best studied. In altricial bird species, nest fleas can negatively affect both parent and offspring fitness components. However, knowledge on the effects of fleas on precocial bird species is scarce. Research on geese in the Canadian Arctic indicated that fleas have a negative impact on reproductive success. One possible hypothesis is that fleas may affect female incubation behaviour. Breeding females with many fleas in their nest may increase the frequency and/or duration of incubation breaks and could even totally desert their nest. The aim of our study was to 1) determine if a similar negative relationship existed between flea abundance and reproductive success in our study colony of Arctic breeding barnacle geese Branta leucopsis and 2) experimentally quantify if such effects could be explained by a negative effect of nest fleas on female behaviour. We compared host anti-parasite and incubation behaviour between experimentally flea-reduced and control nests using wildlife cameras and temperature loggers. We found that flea abundance was negatively associated with hatching success. We found little experimental support, however, for changes in behaviour of the breeding female as a possible mechanism to explain this effect

Cluster Lenses

Clusters of galaxies are the most recently assembled, massive, bound structures in the Universe. As predicted by General Relativity, given their masses, clusters strongly deform space-time in their vicinity. Clusters act as some of the most powerful gravitational lenses in the Universe. Light rays traversing through clusters from distant sources are hence deflected, and the resulting images of these distant objects therefore appear distorted and magnified. Lensing by clusters occurs in two regimes, each with unique observational signatures. The strong lensing regime is characterized by effects readily seen by eye, namely, the production of giant arcs, multiple-images, and arclets. The weak lensing regime is characterized by small deformations in the shapes of background galaxies only detectable statistically. Cluster lenses have been exploited successfully to address several important current questions in cosmology: (i) the study of the lens(es) - understanding cluster mass distributions and issues pertaining to cluster formation and evolution, as well as constraining the nature of dark matter; (ii) the study of the lensed objects - probing the properties of the background lensed galaxy population - which is statistically at higher redshifts and of lower intrinsic luminosity thus enabling the probing of galaxy formation at the earliest times right up to the Dark Ages; and (iii) the study of the geometry of the Universe - as the strength of lensing depends on the ratios of angular diameter distances between the lens, source and observer, lens deflections are sensitive to the value of cosmological parameters and offer a powerful geometric tool to probe Dark Energy. In this review, we present the basics of cluster lensing and provide a current status report of the field.Comment: About 120 pages - Published in Open Access at: http://www.springerlink.com/content/j183018170485723/ . arXiv admin note: text overlap with arXiv:astro-ph/0504478 and arXiv:1003.3674 by other author

Quantitative Magnetic Resonance Imaging of Tissue Microvasculature and Microstructure in Selected Clinical Applications

This thesis is based on four papers and aims to establish perfusion and diffusion measurements with magnetic resonance imaging (MRI) in selected clinical applications. While structural imaging provides invaluable geometric and anatomical information, new disease relevant information can be obtained from measures of physiological processes inferred from advanced modelling. This study is motivated by clinical questions pertaining to diagnosis and treatment effects in particular patient groups where inflammatory processes are involved in the disease. Paper 1 investigates acquisition parameters in dynamic contrast enhanced (DCE)-MRI of the temporomandibular joint (TMJ) with possible involvement of juvenile idiopathic arthritis. High level elastic motion correction should be applied to DCE data from the TMJ, and the DCE data should be acquired with a sample rate of at least 4 s. Paper 2 investigates choices of arterial input functions (AIFs) in dynamic susceptibility contrast (DSC)-MRI in brain metastases. AIF shapes differed across patients. Relative cerebral blood volume estimates differentiated better between perfusion in white matter and grey matter when scan-specific AIFs were used than when patient-specific AIFs and population-based AIFs were used. Paper 3 investigates DSC-MRI perfusion parameters in relation to outcome after stereotactic radiosurgery (SRS) in brain metastases. Low perfusion prior to SRS may be related to unfavourable outcome. Paper 4 applies free water (FW) corrected diffusion MRI to characterise glioma. Fractional anisotropy maps of the tumour region were significantly impacted by FW correction. The estimated FW maps may also contribute to a better description of the tumour. Although there are challenges related to post-processing of MRI data, it was shown that the advanced MRI methods applied can add to a more accurate description of the TMJ and of brain lesions

Dynamic Susceptibility Contrast MRI May Contribute in Prediction of Stereotactic Radiosurgery Outcome in Brain Metastases

Background Following stereotactic radiosurgery (SRS), predicting treatment response is not possible at an early stage using structural imaging alone. Hence, the current study aims at investigating whether dynamic susceptibility contrast (DSC)-MRI estimated prior to SRS can provide predictive biomarkers in response to SRS treatment and characterize vascular characteristics of pseudo-progression. Methods In this retrospective study, perfusion-weighted DSC-MRI image data acquired with a temporal resolution of 1.45 seconds were collected from 41 patients suffering from brain metastases. Outcome was defined based on lesion volume changes in time (determined on structural images) or death. Motion correction and manual lesion delineation were performed prior to semi-automated, voxel-wise perfusion analysis. Statistical testing was performed using linear regression and a significance threshold at P = .05. Age, sex, primary cancers (pulmonary cancer and melanoma), lesion volume, and dichotomized survival time were added as covariates in the linear regression models (ANOVA). Results Relative cerebral blood volume (rCBV) and relative cerebral blood flow (rCBF) were found to be significantly lower prior to SRS treatment in patients with increasing lesion volume or early death post-SRS (P ≤ .01). Conclusion Unfavorable treatment outcome may be linked to low perfusion prior to SRS. Pseudo-progression may be preceded by a transient rCBF increase post-SRS. However, results should be verified in different or larger patient material

Effects of Multi-Shell Free Water Correction on Glioma Characterization

Diffusion MRI is a useful tool to investigate the microstructure of brain tumors. However, the presence of fast diffusing isotropic signals originating from non-restricted edematous fluids, within and surrounding tumors, may obscure estimation of the underlying tissue characteristics, complicating the radiological interpretation and quantitative evaluation of diffusion MRI. A multi-shell regularized free water (FW) elimination model was therefore applied to separate free water from tissue-related diffusion components from the diffusion MRI of 26 treatment-naïve glioma patients. We then investigated the diagnostic value of the derived measures of FW maps as well as FW-corrected tensor-derived maps of fractional anisotropy (FA). Presumed necrotic tumor regions display greater mean and variance of FW content than other parts of the tumor. On average, the area under the receiver operating characteristic (ROC) for the classification of necrotic and enhancing tumor volumes increased by 5% in corrected data compared to non-corrected data. FW elimination shifts the FA distribution in non-enhancing tumor parts toward higher values and significantly increases its entropy (p ≤ 0.003), whereas skewness is decreased (p ≤ 0.004). Kurtosis is significantly decreased (p < 0.001) in high-grade tumors. In conclusion, eliminating FW contributions improved quantitative estimations of FA, which helps to disentangle the cancer heterogeneity

Effects of motion correction, sampling rate and parametric modelling in dynamic contrast enhanced MRI of the temporomandibular joint in children affected with juvenile idiopathic arthritis

The temporomandibular joint (TMJ) is typically involved in 45–87% of children with Juvenile Idiopathic Arthritis (JIA). Accurate diagnosis of JIA is difficult as various clinical tests, including MRI, disagree. The purpose of this study is to optimize the methodological aspects of Dynamic Contrast Enhanced (DCE) MRI of the TMJ in children. In this cross-sectional study, including data from 73 JIA affected children, aged 6–15 years, effects of motion correction, sampling rate and parametric modelling on DCE-MRI data is investigated. Consensus among three radiologists determined the regions of interest. Quantitative perfusion parameters were estimated using four perfusion models; the Adiabatic Approximation to Tissue Homogeneity (AATH), Distributed Capillary Adiabatic Tissue Homogeneity (DCATH), Gamma Capillary Transit Time (GCTT) and Two Compartment Exchange (2CXM) models. Effects of motion correction were evaluated by a sum of least squares between corrected raw data and the GCTT model. The effect of systematically down sampling the raw data was tested. The sum of least squares was computed across all pharmacokinetic models. Relative difference perfusion parameters between the left and right TMJ were used for an unsupervised k-means based stratification of the data based on a principal component analysis, as well as for a supervised random forest classification. Diagnostic sensitivity and specificity were computed relative to structural image scorings. Paired sample t-tests, as well as ANOVA tests, were used (significant threshold: p < 0.05) with Tukeys post hoc test. High-level elastic motion correction provides the best least square fit to the GCTT model (percental improvement: 72–84%). A 4 s sampling rate captures more of the potentially disease relevant signal variations. The various parametric models all leave comparable residues (relative standard deviation: 3.4%). In further evaluation of DCE-MRI as a potential diagnostic tool for JIA a high-level elastic motion correction scheme should be adopted, with a sampling rate of at least 4 s. Results suggest that DCE-MRI data can be a valuable part in JIA diagnostics in the TMJ