Quantitative Dynamic Contrast-Enhanced Perfusion MRI - A Phantom and in Vivo Study

Quantitative Dynamic Contrast-Enhanced Perfusion MRI - A Phantom and in Vivo Study The quantification of tissue perfusion with magnetic resonance imaging (MRI) is of great medical value for tumor diagnosis, treatment planning and therapy control. The aim of this work was to evaluate the feasibility as well as to find limitations and improvements of perfusion quantification using dynamic contrast-enhanced (DCE) MRI in combination with pharmacokinetic modeling. In the first part, a multimodal perfusion phantom mimicking human physiology at capillary level and simulating intra- and extravascular space was developed. This enables the application of a dual compartment model leading to perfusion parameters of which among others the Plasma Flow PF shows reproducible values both within a series of measurements (PF = (91 ± 7) ml/100 ml/min) and in the repetition after one week (PF = (91 ± 26) ml/100 ml/min). A reliable comparison not only between MRI and DCE computer tomography (CT) (PF = (94 ± 53) ml/100 ml/min), but also to the alternative MRI perfusion technique Arterial Spin Labeling (ASL) (PF = (99 ± 36) ml/100 ml/min) is applicable. Fast temporal resolution through a high sampling rate, indispensable for exact modeling, was achieved by the implementation of parallel imaging and led to a significant reduction of the intra measurement deviation by 30%. In the second part, an in vivo perfusion study of rectal carcinomas showed that the bilateral selection of the arterial input function and the use of dual compartment models have a significant influence on the quantification of perfusion parameters with deviations of the PF of up to 30 ml/100 ml/min. The importance of tissue ROI selection in heterogeneous tumors has been shown, as the parameters within a tumor differ by up to 36%. The combination of the findings of the phantom and the patient study reveals new and promising strategies for quantifying DCE-MRI in the future

Mapping the Impact and Plasticity of Cortical-Cardiovascular Interactions in Vascular Disease Using Structural and Functional MRI

There is growing interest in the role of vascular disease in accelerating age-related decline in cerebrovascular structural and functional integrity. Since an increased number of older adults are surviving chronic diseases, of which cardiovascular disease (CVD) is prevalent, there is an urgent need to understand relationships between cardiovascular dysfunction and brain health. It is unclear if CVD puts the brains of older adults, already experiencing natural brain aging, at greater risk for degeneration. In this thesis, the role of CVD in accelerating brain aging is explored. Because physical activity is known to provide neuroprotective benefits to brains of older adults, the role of physical activity in mediating disease effects were also explored. Using novel neuroimaging techniques, measures of gray matter volume and cerebrovascular hemodynamics were compared between groups of coronary artery disease patients and age-matched controls, to describe regional effects of CVD on the brain. In a sub-set of patients, imaging measures were repeated after completion of a 6-month exercise training, part of a cardiac rehabilitation program, to examine exercise effects. Differences in cerebrovascular hemodynamics were measured as changes in resting cerebral blood flow (CBF) and changes in cerebrovascular reactivity (CVR) to hypercapnia (6% CO2) using a non-invasive perfusion magnetic resonance imaging technique, arterial spin labelling (ASL). We found decreased brain volume, CBF and CVR in several regions of the brains of coronary artery disease patients compared to age-matched healthy controls. The reductions in CBF and CVR were independent of underlying brain atrophy, suggesting that changes in cerebrovascular function could precede changes in brain structure. In addition, increase in brain volume and CBF were observed in some regions of the brain after exercise training, indicating that cardiac rehabilitation programs may have neurorehabiliation effects as well. Since, CBF measured with ASL is not the [gold] standard measure of functional brain activity, we examined the regional correlation of ASL-CBF to glucose consumption rates (CMRglc) measured with positron emission tomography (PET), a widely acceptable marker of brain functional activity. Simultaneous measurements of ASL-CBF and PET-CMRglc were performed in a separate study in a group of older adults with no neurological impairment. Across brain regions, ASL-CBF correlated well with PET-CMRglc, but variations in regional coupling were found and demonstrate the role of certain brain regions in maintaining higher level of functional organization compared to other regions. In general, the results of the thesis demonstrate the impact of CVD on brain health, and the neurorehabiliation capacity of cardiac rehabilitation. The work presented also highlights the ability of novel non-invasive neuroimaging techniques in detecting and monitoring subtle but robust changes in the aging human brain

Neuroimaging Evidence of Major Morpho-Anatomical and Functional Abnormalities in the BTBR T+TF/J Mouse Model of Autism

BTBR T+tf/J (BTBR) mice display prominent behavioural deficits analogous to the defining symptoms of autism, a feature that has prompted a widespread use of the model in preclinical autism research. Because neuro-behavioural traits are described with respect to reference populations, multiple investigators have examined and described the behaviour of BTBR mice against that exhibited by C57BL/6J (B6), a mouse line characterised by high sociability and low self-grooming. In an attempt to probe the translational relevance of this comparison for autism research, we used Magnetic Resonance Imaging (MRI) to map in both strain multiple morpho-anatomical and functional neuroimaging readouts that have been extensively used in patient populations. Diffusion tensor tractography confirmed previous reports of callosal agenesis and lack of hippocampal commissure in BTBR mice, and revealed a concomitant rostro-caudal reorganisation of major cortical white matter bundles. Intact inter-hemispheric tracts were found in the anterior commissure, ventro-medial thalamus, and in a strain-specific white matter formation located above the third ventricle. BTBR also exhibited decreased fronto-cortical, occipital and thalamic gray matter volume and widespread reductions in cortical thickness with respect to control B6 mice. Foci of increased gray matter volume and thickness were observed in the medial prefrontal and insular cortex. Mapping of resting-state brain activity using cerebral blood volume weighted fMRI revealed reduced cortico-thalamic function together with foci of increased activity in the hypothalamus and dorsal hippocampus of BTBR mice. Collectively, our results show pronounced functional and structural abnormalities in the brain of BTBR mice with respect to control B6 mice. The large and widespread white and gray matter abnormalities observed do not appear to be representative of the neuroanatomical alterations typically observed in autistic patients. The presence of reduced fronto-cortical metabolism is of potential translational relevance, as this feature recapitulates previously-reported clinical observations

Review of Journal of Cardiovascular Magnetic Resonance 2015

There were 116 articles published in the Journal of Cardiovascular Magnetic Resonance (JCMR) in 2015, which is a 14 % increase on the 102 articles published in 2014. The quality of the submissions continues to increase. The 2015 JCMR Impact Factor (which is published in June 2016) rose to 5.75 from 4.72 for 2014 (as published in June 2015), which is the highest impact factor ever recorded for JCMR. The 2015 impact factor means that the JCMR papers that were published in 2013 and 2014 were cited on average 5.75 times in 2015. The impact factor undergoes natural variation according to citation rates of papers in the 2 years following publication, and is significantly influenced by highly cited papers such as official reports. However, the progress of the journal's impact over the last 5 years has been impressive. Our acceptance rate is <25 % and has been falling because the number of articles being submitted has been increasing. In accordance with Open-Access publishing, the JCMR articles go on-line as they are accepted with no collating of the articles into sections or special thematic issues. For this reason, the Editors have felt that it is useful once per calendar year to summarize the papers for the readership into broad areas of interest or theme, so that areas of interest can be reviewed in a single article in relation to each other and other recent JCMR articles. The papers are presented in broad themes and set in context with related literature and previously published JCMR papers to guide continuity of thought in the journal. We hope that you find the open-access system increases wider reading and citation of your papers, and that you will continue to send your quality papers to JCMR for publication

From the macro- to the microvasculature : temporal and spatial visualization using arterial spin labeling

For many cerebrovascular diseases, visualization of blood flow through the large vasculature, as well as quantitative information on tissue perfusion, is very important. Arterial Spin labelling (ASL) magnetic resonance (MR) imaging enables the visualization of arterial flow by labelling the magnetization of arterial blood using radiofrequency pulses. The labelled arterial blood acts as an endogenous tracer and allows, which can avoid the reliance on the use of contrast agents. In this doctoral thesis, several new techniques for dynamic MR angiography and perfusion imaging were developed based on ASL techniques, which include pulsed ASL, pseudo-continuous ASL (pCASL), vessel-encoded pCASL, time-encoded pCASL as well as simultaneous multi-slice pCASL. The underlying motivation of these development is to reduce the burden on patients by employing non-invasive ASL techniques as potential alternatives to X-ray digital subtraction angiography, contrast-enhanced MR angiography and perfusion imaging. In each study, the optimum ASL techniques was carefully chosen by considering the pros and cons of the technique to achieve better clinical usability, while improving robustness against potential artifacts.LUMC / Geneeskund

Absolute quantification of perfusion by dynamic susceptibility contrast MRI using Bookend and VASO steady-state CBV calibration: a comparison with pseudo-continuous ASL.

Dynamic susceptibility contrast MRI (DSC-MRI) tends to return elevated estimates of cerebral blood flow (CBF) and cerebral blood volume (CBV). In this study, subject-specific calibration factors (CFs), based on steady-state CBV measurements, were applied to rescale the absolute level of DSC-MRI CBF

Doctor of Philosophy

dissertationMagnetic resonance guided high intensity focused ultrasound (MRgHIFU) is a promising minimal invasive thermal therapy for the treatment of breast cancer. This study develops techniques for determining the tissue parameters - tissue types and perfusion rate - that influence the local temperature during HIFU thermotherapy procedures. For optimal treatment planning for each individual patient, a 3D volumetric breast tissue segmentation scheme based on the hierarchical support vector machine (SVM) algorithm was developed to automatically segment breast tissues into fat, fibroglandular tissue, skin and lesions. Compared with fuzzy c-mean and conventional SVM algorithm, the presented technique offers tissue classification performance with the highest accuracy. The consistency of the segmentation results along both the sagittal and axial orientations indicates the stability of the proposed segmentation routine. Accurate knowledge of the internal anatomy of the breast can be utilized in the ultrasound beam simulation for the treatment planning of MRgHIFU therapy. Completely noninvasive MRI techniques were developed for visualizing blood vessels and determining perfusion rate to assist in the MRgHIFU therapy. Two-point Dixon fat-water separation was achieved using a 3D dual-echo SSFP sequence for breast vessel imaging. The performances of the fat-water separation with various readout gradient designs were evaluated on a water-oil phantom, ex vivo pork sample and in vivo breast imaging. Results suggested that using a dual-echo SSFP readout with bipolar readout gradient polarity, blood vasculature could be successfully visualized through the thin-slab maximum intensity projection SSFP water-only images. For determining the perfusion rate, we presented a novel imaging pulse sequence design consisting of a single arterial spin labeling (ASL) magnetization preparation followed by Look-Locker-like image readouts. This flow quantification technique was examined through simulation, in vitro and in vivo experiments. Experimental results from a hemodialyzer when fitted with a Bloch-equation-based model provide flow measurements that are consistent with ground truth velocities. With these tissue properties, it is possible to compensate for the dissipative effects of the flowing blood and ultimately improve the efficacy of the MRgHIFU therapies. Complete noninvasiveness of these techniques allows multiple measurements before, during and after the treatment, without the limitation of washout of the injected contrast agent