New Advances in Susceptibility Weighted MRI to Determine Physiological Parameters

Die Magnetresonanztomographie bietet die Möglichkeit der Bestimmung des Blutoxygenierungsgrades kleiner venöser Gefäße und damit lokaler Hirnareale mit Hilfe einer Multiecho-Gradientenecho-Sequenz. Mit dieser Sequenz kann der Signalzerfall in einem Voxel, welches von einer einzelnen Vene bzw. von Blutkapillaren durchzogen ist, bestimmt werden. Der Signalzerfall ist charakteristisch für die von der Vene oder den Kapillaren erzeugten Feldinhomogenitäten, so dass sich Aussagen über den Blutoxygenierungsgrad und Blutvolumenanteil treffen lassen. Durch Fitten simulierter Signalverläufe an gemessene Phantom- und Probandendaten konnte gezeigt werden, dass es mit der hier vorgestellten Methode möglich ist, den venösen Blutoxygenierungsgrad zu quantifizieren. Weiterhin konnte eine durch gezielte Modulation des zerebralen Blutflusses hervorgerufene Änderung der Blutoxygenierung in vivo nachgewiesen werden. Die Erweiterung des Modells eines einzelnen Gefäßes auf ein Gefäßnetzwerk diente als Grundlage zur theoretischen Beschreibung der Blutkapillaren, die das Hirngewebe durchziehen und mit Sauerstoff versorgen. Dieses Netzwerkmodel konnte in Phantomexperimenten verifiziert werden. Dagegen zeigte sich bei einer Probandenmessung, dass es nicht möglich ist einzig anhand des gemessenen Signalverlaufs valide Werte für die Blutoxygenierung und den Blutvolumenanteil eindeutig zu bestimmen. Die hohe Korrelation zwischen beiden Parametern bewirkt, dass mehrere Paare von Oxygenierungs- und Volumenwerten passende Signalkurven liefern. Eine unabhängige Quantifizierung oder Abschätzung des venösen Blutvolumens kann hier helfen eindeutige Oxygenierungswerte zu erhalten. Im Rahmen der vorliegenden Dissertation konnte das Signalverhalten von suszeptibilitätssensitiven Messungen in der Magnetresonanztomographie genauer untersucht und eine Methode zur nicht-invasiven Bestimmung der venösen Blutoxygenierung an einzelnen Gefäßen entwickelt werden. Erste in vivo Ergebnisse des Gefäßnetzwerkes verdeutlichen, dass für eine genaue Quantifizierung der Blutoxygenierung weitere Parameter, wie das Blutvolumen, unabhängig bestimmt werden müssen. Dennoch ist es möglich, die Methode am einzelnen Blutgefäß zur besseren Charakterisierung von Pathologien sowie physiologischen Änderungen, z.B. bei der funktionellen Magnetresonanztomographie, einzusetzen.Magnetic resonance imaging allows to determine the blood oxygenation level of small venous vessels or the blood capillary network by evaluating the magnetic resonance signal acquired with multi-echo gradient-echo sequences. The signal formation of a voxel traversed by a vein or interspersed with capillaries shows a characteristic decay or modulation as a function of time from which the blood oxygenation and blood volume fraction can be derived. It could be demonstrated in phantom measurements that the signal of a single vessel traversed voxel correctly matched the calculations of numerical signal simulation. By fitting the signal simulation to in vivo measurements of cerebral venous vessels, vessel size and venous blood oxygenation was determined quantitatively. Furthermore, it was possible to detect and to quantify a physiologically induced change in cerebral venous blood oxygenation. To describe the signal of the blood capillary network in normal brain matter, an extension of the single vessel model to a vessel network was applied. This network model was also validated in phantom experiments. As a result of these investigations it was found that the two parameters describing the network, the blood volume fraction and blood oxygenation level, are correlated to each other and can not be separated without additional information by simply fitting the signal simulation to the measurement. This finding was of special importance in the initial in vivo measurements conducted in the present work. Where, independent blood volume determination may help to further validate the quantified blood oxygenation level. In the present work a non-invasive method was developed to quantify cerebral blood oxygenation levels in single veins. This was possible by investigating the signal evolution of susceptibility sensitive magnetic resonance imaging. The initial result of the vessel network signal reveals, that for obtaining a valid blood oxygenation level, the volume fraction has to be further determined by an independent measurement. Nevertheless, is has been demonstrated that the quantification of the blood oxygenation level in single venous vessels is possible and can be applied in clinical diagnosis for better characterization of cerebral pathologies or in physiological investigations, like in functional magnetic resonance imaging

Investigating the effect of flow compensation and quantitative susceptibility mapping method on the accuracy of venous susceptibility measurement

Quantitative susceptibility mapping (QSM) is a promising non-invasive method for obtaining information relating to oxygen metabolism. However, the optimal acquisition sequence and QSM reconstruction method for reliable venous susceptibility measurements are unknown. Full flow compensation is generally recommended to correct for the influence of venous blood flow, although the effect of flow compensation on the accuracy of venous susceptibility values has not been systematically evaluated. In this study, we investigated the effect of different acquisition sequences, including different flow compensation schemes, and different QSM reconstruction methods on venous susceptibilities. Ten healthy subjects were scanned with five or six distinct QSM sequence designs using monopolar readout gradients and different flow compensation schemes. All data sets were processed using six different QSM pipelines and venous blood susceptibility was evaluated in whole-brain segmentations of the venous vasculature and single veins. The quality of vein segmentations and the accuracy of venous susceptibility values were analyzed and compared between all combinations of sequences and reconstruction methods. The influence of the QSM reconstruction method on average venous susceptibility values was found to be 2.7–11.6 times greater than the influence of the acquisition sequence, including flow compensation. The majority of the investigated QSM reconstruction methods tended to underestimate venous susceptibility values in the vein segmentations that were obtained. In summary, we found that multi-echo gradient-echo acquisition sequences without full flow compensation yielded venous susceptibility values comparable to sequences with full flow compensation. However, the QSM reconstruction method had a great influence on susceptibility values and thus needs to be selected carefully for accurate venous QSM

Inferring Geodesic Cerebrovascular Graphs: Image Processing, Topological Alignment and Biomarkers Extraction

A vectorial representation of the vascular network that embodies quantitative features - location, direction, scale, and bifurcations - has many potential neuro-vascular applications. Patient-specific models support computer-assisted surgical procedures in neurovascular interventions, while analyses on multiple subjects are essential for group-level studies on which clinical prediction and therapeutic inference ultimately depend. This first motivated the development of a variety of methods to segment the cerebrovascular system. Nonetheless, a number of limitations, ranging from data-driven inhomogeneities, the anatomical intra- and inter-subject variability, the lack of exhaustive ground-truth, the need for operator-dependent processing pipelines, and the highly non-linear vascular domain, still make the automatic inference of the cerebrovascular topology an open problem. In this thesis, brain vessels’ topology is inferred by focusing on their connectedness. With a novel framework, the brain vasculature is recovered from 3D angiographies by solving a connectivity-optimised anisotropic level-set over a voxel-wise tensor field representing the orientation of the underlying vasculature. Assuming vessels joining by minimal paths, a connectivity paradigm is formulated to automatically determine the vascular topology as an over-connected geodesic graph. Ultimately, deep-brain vascular structures are extracted with geodesic minimum spanning trees. The inferred topologies are then aligned with similar ones for labelling and propagating information over a non-linear vectorial domain, where the branching pattern of a set of vessels transcends a subject-specific quantized grid. Using a multi-source embedding of a vascular graph, the pairwise registration of topologies is performed with the state-of-the-art graph matching techniques employed in computer vision. Functional biomarkers are determined over the neurovascular graphs with two complementary approaches. Efficient approximations of blood flow and pressure drop account for autoregulation and compensation mechanisms in the whole network in presence of perturbations, using lumped-parameters analog-equivalents from clinical angiographies. Also, a localised NURBS-based parametrisation of bifurcations is introduced to model fluid-solid interactions by means of hemodynamic simulations using an isogeometric analysis framework, where both geometry and solution profile at the interface share the same homogeneous domain. Experimental results on synthetic and clinical angiographies validated the proposed formulations. Perspectives and future works are discussed for the group-wise alignment of cerebrovascular topologies over a population, towards defining cerebrovascular atlases, and for further topological optimisation strategies and risk prediction models for therapeutic inference. Most of the algorithms presented in this work are available as part of the open-source package VTrails

Characterization of alar ligament on 3.0T MRI: a cross-sectional study in IIUM Medical Centre, Kuantan

INTRODUCTION: The main purpose of the study is to compare the normal anatomy of alar ligament on MRI between male and female. The specific objectives are to assess the prevalence of alar ligament visualized on MRI, to describe its characteristics in term of its course, shape and signal homogeneity and to find differences in alar ligament signal intensity between male and female. This study also aims to determine the association between the heights of respondents with alar ligament signal intensity and dimensions. MATERIALS & METHODS: 50 healthy volunteers were studied on 3.0T MR scanner Siemens Magnetom Spectra using 2-mm proton density, T2 and fat-suppression sequences. Alar ligament is depicted in 3 planes and the visualization and variability of the ligament courses, shapes and signal intensity characteristics were determined. The alar ligament dimensions were also measured. RESULTS: Alar ligament was best depicted in coronal plane, followed by sagittal and axial planes. The orientations were laterally ascending in most of the subjects (60%), predominantly oval in shaped (54%) and 67% showed inhomogenous signal. No significant difference of alar ligament signal intensity between male and female respondents. No significant association was found between the heights of the respondents with alar ligament signal intensity and dimensions. CONCLUSION: Employing a 3.0T MR scanner, the alar ligament is best portrayed on coronal plane, followed by sagittal and axial planes. However, tremendous variability of alar ligament as depicted in our data shows that caution needs to be exercised when evaluating alar ligament, especially during circumstances of injury

Case series of breast fillers and how things may go wrong: radiology point of view

INTRODUCTION: Breast augmentation is a procedure opted by women to overcome sagging breast due to breastfeeding or aging as well as small breast size. Recent years have shown the emergence of a variety of injectable materials on market as breast fillers. These injectable breast fillers have swiftly gained popularity among women, considering the minimal invasiveness of the procedure, nullifying the need for terrifying surgery. Little do they know that the procedure may pose detrimental complications, while visualization of breast parenchyma infiltrated by these fillers is also deemed substandard; posing diagnostic challenges. We present a case series of three patients with prior history of hyaluronic acid and collagen breast injections. REPORT: The first patient is a 37-year-old lady who presented to casualty with worsening shortness of breath, non-productive cough, central chest pain; associated with fever and chills for 2-weeks duration. The second patient is a 34-year-old lady who complained of cough, fever and haemoptysis; associated with shortness of breath for 1-week duration. CT in these cases revealed non thrombotic wedge-shaped peripheral air-space densities. The third patient is a 37‐year‐old female with right breast pain, swelling and redness for 2- weeks duration. Previous collagen breast injection performed 1 year ago had impeded sonographic visualization of the breast parenchyma. MRI breasts showed multiple non- enhancing round and oval shaped lesions exhibiting fat intensity. CONCLUSION: Radiologists should be familiar with the potential risks and hazards as well as limitations of imaging posed by breast fillers such that MRI is required as problem-solving tool

The pathophysiology of CADASIL: studies in a Scottish cohort

Since identification that mutations in NOTCH3 are responsible for cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL) in the early 1990s, there has been extensive characterisation of the clinical and radiological features of the disease. However therapeutic interventions remain elusive, partly due to a limited understanding of the vascular pathophysiology and how it leads to the development of strokes, cognitive decline and disability. The apparent rarity and heterogenous natural history of CADASIL potentially make conducting any longitudinal or therapeutic trials difficult. The role of disease biomarkers is therefore of some interest. This thesis focuses on vascular function in CADASIL and how it may relate to clinical and radiological markers of disease. Establishing the prevalence of CADASIL in the West of Scotland was important to assess the impact of the disease, and how feasible a trial would be. A mutation prevalence of 10.7 per 100,000 was demonstrated, suggesting significant under diagnosis of the disease across much of Scotland. Cerebral hypoperfusion is thought to be important in CADASIL, and it has been shown that vascular abnormalities precede the development of brain pathology in mouse models. Investigation of vascular function in patients, both in the brain and systemically, requires less invasive measures. Arterial spin labelling magnetic resonance imaging (MRI) and transcranial Doppler ultrasound (TCD) can both be used to obtain non-invasive and quantifiable indices of vascular function. Monitoring patients with MRI whilst they receive different concentrations of inspired oxygen and carbon dioxide can provide information on brain function, and I reviewed the practicalities of this technique in order to guide the design of the studies in this thesis. 22 CADASIL patients were recruited to a longitudinal study. Testing included peripheral vascular assessment, assessment of disability, neurological dysfunction, mood and cognition. A CO2 reactivity challenge during both TCD and arterial spin labelling MRI, and detailed MRI sequences were obtained. I was able to demonstrate that vasoreactivity was associated with the number of lacunes and brain atrophy, as were carotid intima-media thickness, vessel stiffness, and age. Patients with greater disability, higher depressive symptoms and poorer processing speed showed a tendency to worse cerebral vasoreactivity but numbers were small. This observation suggests vasoreactivity may have potential as a therapeutic target, or a biomarker. I then wished to establish if arterial spin labelling MRI was useful for assessing change in cerebral blood flow in CADASIL patients. Cortical grey matter showed the highest blood flow, mean (SD), 55 (10) ml/100g/min and blood flow was significantly lower within hyperintensities (19 (4) ml/100g/min; p <0.001). Over one year, blood flow in both grey matter (mean -7 (10) %; p = 0.028) and deep white matter (-8 (13) %; p = 0.036) declined significantly. Cerebrovascular reactivity did not change over one year. I then investigated whether baseline vascular markers were able to predict change in radiological or neuropsychological measures of disease. Changes in brain volume, lacunes, microbleeds and normalised subcortical hyperintensity volume (increase of 0.8%) were shown over one year. Baseline vascular parameters were not able to predict these changes, or those in neuropsychological testing. NOTCH3 is found throughout the body and a systemic vasculopathy has been seen particularly affecting resistance vessels. Gluteal biopsies were obtained from 20 CADASIL patients, and ex vivo myography investigated the response to vasoactive agents. Evidence of impairment in both vasodilation and vasoconstriction was shown. The addition of antioxidants improved endothelium-dependent relaxation, indicating a role for oxidative stress in CADASIL pathology. Myography measures were not related to in vivo measures in the sub-group of patients who had taken part in both studies. The small vessels affected in CADASIL are unable to be imaged by conventional MR imaging so I aimed to establish which vessels might be responsible for lacunes with use of a microangiographic template overlaid onto brain images registered to a standard brain template. This showed most lacunes are small and associated with tertiary arterioles. On the basis of this thesis, it is concluded that vascular dysfunction plays an important role in the pathophysiology of CADASIL, and further assessment of vascular measures in longitudinal studies is needed. Arterial spin labelling MRI should be used as it is a reliable, non-invasive modality that can measure change over one year. Furthermore conventional cardiovascular risk factor prevention should be undertaken in CADASIL patients to delay the deleterious effects of the disease