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

Minimally invasive therapies for the brain using magnetic particles

Delivering a therapy with precision, while reducing off target effects is key to the success of any novel therapeutic intervention. This is of most relevance in the brain, where the preservation of surrounding healthy tissue is crucial in reducing the risk of cognitive impairment and improving patient prognosis. Our scientific understanding of the brain would also benefit from minimally invasive investigations of specific cell types so that they may be observed in their most natural physiological environment. Magnetic particles based techniques have the potential to deliver cellular precision in a minimally invasive manner. When inside the body, Magnetic particles can be actuated remotely using externally applied magnetic fields while their position can be detected non-invasively using MRI. The magnetic forces applied to the particles however, rapidly decline with increasing distance from the magnetic source. It is therefore critical to understand the amount of force needed for a particular application. The properties of the magnetic particle such as the size, shape and magnetic content, as well as the properties of the applied magnetic field, can then be tailored to that application. The aim of this thesis was to develop magnetic particle based techniques for precise manipulation of cells in the brain. Two different approaches were explored, utilising the versatile nature of magnetic actuation for two different applications. The first approach uses magnetic nanoparticles to mechanically stimulate a specific cell type. Magnetic particles conjugated with the antibody ACSA-1 would selectively bind to astrocytes to evoke the controlled release of ATP and induce a calcium flux which are used for communication with neighbouring cells. This approach allows for the investigation into the role of astrocytes in localised brain regions using a naturally occurring actuation process (mechanical force) without effecting their natural environment. The second approach uses a millimetre sized magnetic particle which can be navigated through the brain and ablate localised regions of cells using a magnetic resonance imaging system. The magnetic particle causes a distinct contrast in MRI images, allowing for precise detection of its location so that it may be iteratively guided along a pre-determined path to avoid eloquent brain regions. Once at the desired location, an alternating magnetic field can be applied causing the magnetic particle to heat and deliver controllable, well defined regions of cell death. The forces needed for cell stimulation are orders of magnitude less than the forces needed to guide particles through the brain. Chapters 4 and 5 use external magnets to deliver forces in the piconewton range. While stimulation was demonstrated in small animals, scaling up this technique to human proportions remains a challenge. Chapters 6 and 7 use a preclinical MRI system to generate forces in the millinewton range, allowing the particle to be moved several centimetres through the brain within a typical surgical timescale. When inside the scanner, an alternating magnetic field causes the particle to heat rapidly, enabling the potential for multiple ablations within a single surgery. For clinical translation of this technique, MRI scanners would require a dedicated propulsion gradient set and heating coil

Sub-pixel Registration In Computational Imaging And Applications To Enhancement Of Maxillofacial Ct Data

In computational imaging, data acquired by sampling the same scene or object at different times or from different orientations result in images in different coordinate systems. Registration is a crucial step in order to be able to compare, integrate and fuse the data obtained from different measurements. Tomography is the method of imaging a single plane or slice of an object. A Computed Tomography (CT) scan, also known as a CAT scan (Computed Axial Tomography scan), is a Helical Tomography, which traditionally produces a 2D image of the structures in a thin section of the body. It uses X-ray, which is ionizing radiation. Although the actual dose is typically low, repeated scans should be limited. In dentistry, implant dentistry in specific, there is a need for 3D visualization of internal anatomy. The internal visualization is mainly based on CT scanning technologies. The most important technological advancement which dramatically enhanced the clinician\u27s ability to diagnose, treat, and plan dental implants has been the CT scan. Advanced 3D modeling and visualization techniques permit highly refined and accurate assessment of the CT scan data. However, in addition to imperfections of the instrument and the imaging process, it is not uncommon to encounter other unwanted artifacts in the form of bright regions, flares and erroneous pixels due to dental bridges, metal braces, etc. Currently, removing and cleaning up the data from acquisition backscattering imperfections and unwanted artifacts is performed manually, which is as good as the experience level of the technician. On the other hand the process is error prone, since the editing process needs to be performed image by image. We address some of these issues by proposing novel registration methods and using stonecast models of patient\u27s dental imprint as reference ground truth data. Stone-cast models were originally used by dentists to make complete or partial dentures. The CT scan of such stone-cast models can be used to automatically guide the cleaning of patients\u27 CT scans from defects or unwanted artifacts, and also as an automatic segmentation system for the outliers of the CT scan data without use of stone-cast models. Segmented data is subsequently used to clean the data from artifacts using a new proposed 3D inpainting approach

Interaction of some polyoxotunstates with acetylcholinesterase

Polyoxometalates (POMs) are polyanionic oligomeric aggregates of transition metal ions, such as tungsten, molybdenum, vanadium, etc. held together by oxygen bridges, with a high density of negative charge. They are relatively stable, some even highly stable in aqueous solutions at biological pH values. In addition to applications in catalysis, separations, analysis, and as electrondense imaging agents, some of these complexes have been shown to exhibit biological activity in vitro as well as in vivo ranging from anti-cancer, antibiotic, and antiviral to antidiabetic effects. Recent investigations reported some polyoxotungstates as reversible inhibitors of acetylcholinesterase (AChE), making them potential anti-Alzheimer’s drugs. AChE is a serine hydrolase mainly found at neuromuscular junctions and cholinergic brain synapses. Its principal biological role is the termination of impulse transmission at cholinergic synapses. Reversible inhibitors of AChE mostly have therapeutic applications, while toxic effects are associated with irreversible AChE activity modulators. Reversible inhibitors play an important role in the pharmacological manipulation of the enzyme activity, and have been applied in the diagnostic and/or treatment of various diseases such as: myasthenia gravis, AD, postoperative ileus, bladder distention, glaucoma, as well as antidote to anticholinergic overdose. The effect of four new synthesized polyoxotungstates soluble in water on AChE activity was studied. AChE is purified from electric eel and commercially available. The enzyme was treated in vitro with polyoxotungstates in the concentration range from 1 × 10-7 to 1 × 10-3 mol/L at 37ºC for 15 minutes, and the incubation time was 12 min. The obtained dependence remaining enzyme activity vs. the inhibitor concentration fitted the sigmoidal function. IC50values, indicating the enzyme sensitivity toward the inhibitor and the inhibitory capacity of the analyzed compounds, were determined from the inhibition sigmoidal curves. Na10[H2W12O42] × 27H2O did not markedly reduce AChE activity at the highest investigated concentration (1 mmol/L). K7[SiV3W9O40] × 10H2O exhibited a weak inhibitory potential, causing 50% decrease in the enzyme activity at 5 × 10-4 mol/L. However, AChE sensitivity in the presence of K7[Ti2PW10O40] was several hundred times higher, reaching IC50 at 1.15 × 10-6 mol/L. Furthermore, (NH4)14[NaP5W30O110] × 31H2O demonstrated the strongest capacity to inhibit AChE. In the presence of its low concentration of 2 × 10-8 mol/L, the enzyme activity was noticeably reduced related to the control value (obtained without inhibitor), while 50% decrease in AChE activity was achieved at 3.8 × 10-7 mol/L.Fourth International Conferenceon Radiation and Applications in Various Fields of Research, RAD 2016, May 23-27, 2016, Niš, Serbi