Background Superparamagnetic particles of iron oxide (SPIO) are part of a novel and exciting class of ‘smart’ magnetic resonance imaging (MRI) contrast agents that are taken up by inflammatory cells. Ultrasmall SPIO (USPIO; ~30 nm diameter) can be used to assess cellular tissue inflammation and SPIO (80-150 nm) have the potential to be used to label cells ex vivo for in vivo cell tracking studies. Objectives The aims of the thesis were therefore (i) to develop and validate quantitative MRI methodology for assessing SPIO uptake within tissues, (ii) to demonstrate USPIO accumulation within the aortic wall and its implications in patients with abdominal aortic aneurysms (AAA), and (iii) to develop and apply a Good Manufacturing Practice (GMP) compliant method of SPIO cell labelling in healthy volunteers. Methods Patients with asymptomatic AAA >4.0 cm in diameter were recruited. Imaging sequences were optimised in eight patients using a 3 tesla MRI scanner. Data were analysed using the decay constant for multi echo T2* weighted (T2*W) sequences (T2*) or its inverse (R2*) and the repeatability of these measurements was established. A further twenty-nine patients underwent MRI scanning before and 24- 36 hours after administration of USPIO. T2 and multi echo T2*W sequences were performed and ultrasound-based growth rate data were collected. Operative aortic wall tissue samples were obtained from patients undergoing open surgical aneurysm repair. A GMP compliant protocol was developed for labelling cells with SPIO for clinical cell tracking studies. The effects of SPIO-labelling on cell viability and function were assessed in vitro. A phased-dosing protocol was used to establish the safety of intravenous administration of SPIO-labelled cells in healthy volunteers. The feasibility of imaging cells at a target site in vivo following local or systemic administration was assessed. Tracking of SPIO-labelled cells to a target site was investigated by inducing an iatrogenic inflammatory focus in the skin of the anterior thigh of healthy volunteers, following which autologous SPIO-labelled cells were administered and their accumulation was assessed using MRI scanning and histology of skin biopsies. Results Robust and semi-quantitative data acquisition and image analysis methodology was developed for the assessment of SPIO accumulation in tissues. In patients with AAA, histological analysis of aortic wall tissue samples confirmed USPIO accumulation in areas of cellular inflammation. USPIO-enhanced MRI detected aortic wall inflammation and mural USPIO uptake was associated with a 3-fold higher aneurysm expansion rate. Human mononuclear cells were labelled with SPIO under GMP compliant conditions without affecting cell viability or function. Both local and intravenous administration of SPIO-labelled cells was safe and cells were detectable in vitro and in vivo using a clinical MRI scanner. SPIO-labelled cells tracked to a focal iatrogenic inflammatory focus following intravenous administration in humans and were detectable on MRI scanning and histological examination of skin biopsies. Conclusions SPIO contrast agents have an extensive range of potential clinical applications. USPIO uptake in the wall of AAA appears to identify cellular inflammation and predict accelerated aneurysm expansion. This is therefore a promising investigative tool for stratifying the risk of disease progression in patients with AAA, and may also be considered as a biomarker for response to novel pharmacological agents. The ability to label cells for non-invasive cell tracking studies would facilitate the further development of novel cell-based therapies and would enable assessment of dynamic inflammatory processes through inflammatory cell tracking.

No description available.

Yes / Appendicitis is the most common cause of acute abdominal pain requiring surgical intervention in paediatric patients. Ultrasound is generally the diagnostic imaging modality of choice, followed by CT, where paediatric appendicitis is suspected. However, high operator dependency and diagnostic restrictions related to anatomical and clinical presentation may limit consistency of application. This paper explores whether MRI is a viable alternative to ultrasound as the primary imaging modality. Method: A systematic review of the literature was undertaken. A search of Medline, Cinahl, PubMed Central and Google Scholar was undertaken supplemented by a review of reference lists, author searching and review of NICE evidence base for existing guidelines. Included studies were assessed for bias using the QUADAS-2 quality assessment tool and data were extracted systematically using a purposefully designed electronic data extraction proforma. Results: Seven studies were included in final review. The age range of participants extended from 0 to 19 years. Only one study with a patient age range of 0e14 used sedation. Sensitivity estimates from the included studies ranged from 92% to 100% while specificity ranged from 89% to 100%. A significant variation in the number and type of sequences was noted between the studies. Conclusion: MRI offers high sensitivity and specificity comparable to contrast enhanced CT and greater than ultrasound as reported in the literature. Where accessibility is not a restriction, MRI is a viable alternative to ultrasound in the assessment and diagnosis of paediatric appendicitis. Clinical practice recommendations have been provided to facilitate the translation of evidence into practice.

Background: Hip fractures are a major health problem in Canada, and two main contributors to hip fracture are weak bone strength and fall. Weak muscles also negatively affect bone strength and increase the likelihood of falling. Advanced imaging techniques, such as magnetic resonance imaging (MRI), offer in vivo measurement of bone strength and muscle area at the proximal femur. However, it is not known if MRI-based measurements of bone and muscle properties are repeatable (i.e. precise). Methods: The femoral neck and shaft of 14 healthy participants were scanned three times, using a 1.5T MRI with repositioning between scans. Boundaries of the femoral neck, shaft and four muscle groups were delineated semi-automatically. Geometrical and strength properties of bone and area of muscle groups were determined based on segmented images. The short-term precision errors (root mean square coefficient of variation; CVrms%) between the repeated measures were calculated accordingly. Results: MRI-based measures of bone geometry and strength and muscle area at the proximal femur demonstrated in vivo precision errors < 7.6%. The average CVrms% for bone measures and muscle area were less than 4% and 2.5% respectively. Higher CVrms% (e.g. average: 4.8%) was obtained for bone strength properties. Conclusion: This is the first study to evaluate the in vivo performance of MRI on application to the proximal femur and surrounding muscles. Results demonstrate that MRI is a promising non-ionizing technique that offers precise measures of bone and muscle at the proximal femur.

The dramatic improvement in magnetic resonance imaging (MRI) scan time over the past fifteen years through gradient-based methods that sample k-space more efficiently and quickly cannot be sustained, as thresholds regarding hardware and safety limitations are already being approached. Parallel imaging methods (using multiple receiver coils to partially encode k-space) have offered some relief in the efforts and are rapidly becoming the focus of current endeavors to decrease scan time. Ideally, for some applications, phase encoding would be eliminated completely, replaced with array coil encoding instead, and the entire image formed in a single echo. The primary objective of this work was to explore that acceleration limit – to implement and investigate the methodology of single echo acquisition magnetic resonance imaging (SEA MRI). The initial evaluation of promising array coil designs is described, based on parameters determined by the ability to enable the imaging method. The analyses of field patterns, decoupling, and signal-to-noise ratio (SNR) that led to the final 64-channel array coil design are presented, and the fabrication and testing of coils designed for 4.7T and 1.5T are described. A detailed description of the obtainment of the first SEA images – 64xNreadout images, acquired in a single echo – is provided with an evaluation of those images and highly accelerated images (through parallel imaging techniques) based on SNR and artifact power. Finally, the development of methodologies for various MR applications is described: applications that would particularly benefit from the speed of the imaging method, or those to which the method or the tool (array coil) lends itself. These applications include, but are not limited to, 3D imaging (phase encode in the slice select direction), resolution-enhanced imaging, large-scale (field-of-view) microscopy, and conformal surface imaging. Finally, using the primary enablement of the method – the ability to obtain complete MR images at speeds limited only by the time it takes to acquire a single echo – is presented with a discussion of extremely high frame rate imaging. The contribution to the field of medical imaging is the first implementation, characterization, and demonstration of applications for the acquisition of MR images in a single echo.

Ischaemic stroke is a leading cause of death and disability in the developed world. Despite that considerable advances in experimental research enabled understanding of the pathophysiology of the disease and identified hundreds of potential neuroprotective drugs for treatment, no such drug has shown efficacy in humans. The failure in the translation from bench to bedside has been partially attributed to the poor quality and rigour of animal studies. Recently, it has been suggested that multicentre animal studies imitating the design of randomised clinical trials could improve the translation of experimental research. Magnetic resonance imaging (MRI) could be pivotal in such studies due to its non-invasive nature and its high sensitivity to ischaemic lesions, but its accuracy and concordance across centres has not yet been evaluated. This thesis focussed on the use of MRI for the assessment of late infarct size, the primary outcome used in stroke models. Initially, a systematic review revealed that a plethora of imaging protocols and data analysis methods are used for this purpose. Using meta-analysis techniques, it was determined that T2-weighted imaging (T2WI) was best correlated with gold standard histology for the measurement of infarctbased treatment effects. Then, geometric accuracy in six different preclinical MRI scanners was assessed using structural phantoms and automated data analysis tools developed in-house. It was found that geometric accuracy varies between scanners, particularly when centre-specific T2WI protocols are used instead of a standardised protocol, though longitudinal stability over six months is high. Finally, a simulation study suggested that the measured geometric errors and the different protocols are sufficient to render infarct volumes and related group comparisons across centres incomparable. The variability increases when both factors are taken into account and when infarct volume is expressed as a relative estimate. Data in this study were analysed using a custom-made semi-automated tool that was faster and more reliable in repeated analyses than manual analysis. Findings of this thesis support the implementation of standardised methods for the assessment and optimisation of geometric accuracy in MRI scanners, as well as image acquisition and analysis of in vivo data for the measurement of infarct size in multicentre animal studies. Tools and techniques developed as part of the thesis show great promise in the analysis of phantom and in vivo data and could be a step towards this endeavour.

Les pathologies cardiovasculaires et leurs conséquences représentent actuellement un problème de santé publique majeur dont la prise en charge pourrait être considérablement améliorée par le développement de nouvelles méthodes de diagnostic non invasives. Ce projet doctoral vise à développer des microparticules polysaccharides injectables dans la circulation sanguine permettant l’imagerie moléculaire des pathologies artérielles. Grâce à un procédé d’émulsion-réticulation, nous avons synthétisé ces microparticules qui sont d’une part fonctionnalisées avec du fucoïdane afin de pouvoir cibler la P-Sélectine qui est une molécule d’adhésion exprimée au niveau de la paroi artérielle lésée, et d’autre part, conjuguées à des agents de contraste afin d’apporter un signal en imagerie. Nous avons alors développé 2 outils d’imagerie moléculaire propres à 2 modalités classiques d’imagerie médicale. Afin de suivre les microparticules en tomographie par émission monophotonique de positons (TEMP), nous les avons radiomarquées avec du technétium 99m et pour les détecter en imagerie par résonance magnétique (IRM), nous les avons chargées avec des nanoparticules d’oxyde de fer superparamagnétiques. Nous avons ensuite validé l’efficacité de ces 2 outils d’imagerie moléculaire avec des essais précliniques en imagerie in vivo chez le petit animal sur des modèles de pathologies artérielles. Les résultats obtenus sont très encourageants et ces 2 outils d’imagerie moléculaire ont un fort potentiel clinique pour le diagnostic des pathologies artérielles. Nous avons également observé que les microparticules migrent dans la paroi artérielle dégradée au niveau des pathologies étudiées. Cette propriété singulière pourrait s’avérer très intéressante pour les futurs travaux qui consisteront à utiliser ce support pour véhiculer des molécules thérapeutiques au cœur des différentes pathologies artérielles. / Cardiovascular diseases and their consequences constitute nowadays a major health issue. Their treatment could be substantially improved with the development of new non invasive diagnostic techniques. The aim of this doctoral project is to develop injectable into blood stream polysaccharide microparticles that would permit molecular imaging of arterial pathologies. From an emulsion- crosslinking process, we synthesized these microparticles which are on the one hand functionalized with fucoidan to target P-Selectin which is expressed at damaged arterial wall, and on the other hand combined with contrast agents to bring an imaging signal. We developed 2 molecular imaging tools dedicated to 2 classical medical imaging modalities. In order to track the microparticles by single photon emission computed tomography, we radiolabeled them with technetium 99m and to detect them by MRI, we loaded them with superparamagnetic nanoparticles of iron oxide. We then have validated the efficiency of these 2 molecular imaging tools with preclinical studies of in vivo small animal imaging of arterial disease models. The obtained results are very promising and these 2 molecular imaging tools have a strong clinical potential for the diagnosis of arterial pathologies. We also have observed that the microparticles tend to migrate though the damaged arterial wall. This specific property could turn out to be very interesting for future works which will consist in using this technology to convey therapeutic molecules directly into the core of the arterial pathologies.

No description available.

For many decades the Boston University School of Medicine Department of Anatomy and Neurobiology has housed an unprovenienced collection of fetal specimens. At least ten percent of the 137 fetal specimens were lost due to drying out and other damage. The specimens were stored for many decades in individual fluid filled containers. There is no reliable information regarding the medical or curation histories of the human fetal specimens. Furthermore, there is concern that the fixative may have led some internal structures to shrink more than others. At issue was to determine whether the specimens had maintained or lost their relationships, and size amongst internal structures. In normal fetal development the cerebellum, the femur, and the foot all follow mostly positive linear growth with age. Therefore, the purpose of the present study was to assess whether these specimens demonstrate anatomical correlations that one might find within in utero fetuses. This prospective correlation study used MRI images of the cerebellum and femur as well as anthropometric measurements of each foot and mass to seek to answer this question. A blind, random sample of twenty-five specimens was selected from forty-eight specimens roughly grouped by size. The Boston University Institutional Review Board was notified and, assigned waiver status to the application because the specimens were unprovenienced fixed tissue. All specimens were magnetic resonance scanned at the Center for Biomedical Imaging at the Boston University School of Medicine using a 3.0T whole body scanner (Achieva, Philips Healthcare, Best, The Netherlands). All scans were acquired using the 8-channel high-resolution head coil made by Invivo for the Achieva 3T scanner. This study found that the measurements taken from the images, and the feet had good intra-rater reliability because paired t-tests did not show significant differences between the measurements (alpha (α) < 0.05, all p-values were > 0.17, t-values were less than t-critical, and R2 < 0.02). Pearson's correlation coefficient testing revealed strong positive correlation between all the mean measures comparing these three structures: transverse cerebellar diameter (TCD), femur length, and foot length (α < 0.05, r - values were > 0.91, p < 0.001, and R2 > 0.82). Leading us to conclude that the dimensions of the soft tissues - TCD; and bone tissues - femur and foot of the lower extremities were unlikely to have changed significantly in decades of storage.

Η απεικόνιση μαγνητικού συντονισμού (MRI) βασίζεται στο φυσικό φαινόμενο του πυρηνικού μαγνητικού συντονισμού (NMR). Ενώ το φαινόμενο αυτό είναι γνωστό από το 1950, η πρώτη μαγνητική τομογραφία σε άνθρωπο διενεργήθηκε μόλις το 1977. Η δεκαετία του '80 ήταν η δεκαετία που τα συστήματα MRI άρχισαν να εξελίσσονται ταχύτατα και η εξέλιξη αυτή συνεχίζεται ακόμη και σήμερα. Στις μέρες μας, τα σύγχρονα συστήματα MRI κάνουν πολύ περισσότερα από απλή απεικόνιση, με τη μαγνητική τομογραφία διάχυσης, τη φασματοσκοπία και τη λειτουργική μαγνητική τομογραφία να αποτελούν νέες και πολλά υποσχόμενες εφαρμογές. Τα συστήματα MRI δεν χρησιμοποιούν ιοντίζουσα ακτινοβολία, αλλά μαγνητικά πεδία και ηλεκτρομαγνητικά κύματα στην περιοχή των ραδιοσυχνοτήτων. Αυτός είναι πιθανώς ο λόγος για τον οποίο τα συστήματα MRI δεν είχαν τύχει τόσης προσοχής όπως τα συστήματα υπολογιστικής τομογραφίας, όσον αφορά τους κανονισμούς που διέπουν την ασφάλεια της χρήσης τους για χρήση σε εξετάσεις ασθενών. Ωστόσο, δεδομένου ότι η απεικόνιση χρησιμοποιείται για τη διάγνωση και μια λανθασμένη διάγνωση μπορεί να οδηγήσει σε λανθασμένη θεραπεία ή την απουσία θεραπείας, τα οποία με τη σειρά τους μπορεί να οδηγήσουν σε μη αναστρέψιμη βλάβη για την υγεία των ασθενών ή ακόμα και στο θάνατο, η Αμερικανική Ένωση Φυσικών Ιατρικής (AAPM) είχε προτείνει μεθόδους για τον έλεγχο της ποιότητας εικόνας από τις αρχές της δεκαετίας του 1990. Το Αμερικανικό Κολλέγιο Ακτινολογίας (ACR), είχε επίσης συμβάλει στην προσπάθεια αυτή από την αρχή της νέας χιλιετίας, προτείνοντας μεθόδους ελέγχου της ποιότητας εικόνας για τη δημιουργία ενός προγράμματος πιστοποίησης για τις εγκαταστάσεις MRI. Το 2010 η AAPM δημοσίευσε μια έκθεση (AAPM report No. 100) με τίτλο «Έλεγχοι αποδοχής και διαδικασίες διασφάλισης ποιότητας για εγκαταστάσεις απεικόνισης μαγνητικής τομογραφίας», το οποίο περιγράφει τις διαδικασίες για τον έλεγχο της απόδοσης των μαγνητικών τομογράφων, αλλά και τις διαδικασίες που αφορούν άλλα ζητήματα ασφάλειας για τους ασθενείς και το προσωπικό. Στην Ελλάδα μέχρι πρόσφατα, οι εγκαταστάσεις MRI - σε αντίθεση με τους υπολογιστικούς τομογράφους και όλα τα άλλα ακτινολογικά συστήματα - ήταν εκτός της εποπτείας της Ελληνικής Επιτροπής Ατομικής Ενέργειας (Ε.Ε.Α.Ε.) και της Ένωσης Φυσικών Ιατρικής Ελλάδος (Ε.Φ.Ι.Ε.). Ωστόσο, από τις αρχές του 2013, η E.E.A.E. έχει προτείνει ένα πρόγραμμα διαπίστευσης (με βάση την έκθεση AAPM Νο. 100) που πρέπει να εφαρμόζεται σε όλες τις καινούριες εγκαταστάσεις MRI. Αυτό το πρόγραμμα πιστοποίησης σταδιακά θα εφαρμοστεί και σε παλαιότερες εγκαταστάσεις. Ο στόχος είναι μέσα σε 5 χρόνια το πολύ, όλες οι εγκαταστάσεις MRI να είναι διαπιστευμένες όπως ισχύει εδώ και πολλά χρόνια για τις εγκαταστάσεις υπολογιστικής τομογραφίας. Ο σκοπός αυτής της διπλωματικής εργασίας είναι να συνοψίσει το βασικό θεωρητικό υπόβαθρο πάνω στο οποίο στηρίζεται η απεικόνιση μαγνητικού συντονισμού, για να βοηθήσει τους Φυσικούς Ιατρικής οι οποίοι δεν έχουν εξειδικευτεί στα συστήματα αυτά, να κατανοήσουν τις αρχές της λειτουργίας τους, ιδίως εκείνες που σχετίζονται με τον τρόπο δημιουργίας των διαγνωστικών εικόνων. Στο επόμενο κεφάλαιο, παρουσιάζεται η AAPM report No. 100 (μεταφρασμένη στα Ελληνικά), προκειμένου να θέσει τις βάσεις για την κατανόηση των διαδικασιών που χρησιμοποιούνται για τους ποιοτικούς ελέγχους (QC), αλλά και άλλα θέματα που αφορούν στην ασφάλεια λειτουργίας των συστημάτων MRI. Στο τελευταίο κεφάλαιο, παρουσιάζεται η εφαρμογή αυτών των διαδικασιών σε μια υπάρχουσα εγκατάσταση MRI, ως ένα παράδειγμα του τρόπου με τον οποίο εκτελούνται οι διαδικασίες QC και του τρόπου με τον οποίο οι εικόνες που προκύπτουν αξιολογούνται προκειμένου να εξαχθούν μετρήσιμες ποσότητες. Αυτές οι ποσότητες χρησιμοποιούνται ως δείκτες απόδοσης και ο Φυσικός Ιατρικής συγκρίνοντάς τις με καθορισμένα όρια, μπορεί να διαπιστώσει εάν το ελεγχόμενο σύστημα MRI πληροί τα καθορισμένα κριτήρια (κάτι που υποδηλώνει μια ικανοποιητική λειτουργία και ποιότητα απεικόνισης) ή εάν υπάρχουν ένα ή περισσότερα προβλήματα που οδηγούν σε μη αποδεκτή ποιότητα απεικόνισης και ως εκ τούτου απαιτούνται διορθωτικές ενέργειες. Στην τελευταία περίπτωση, ο έλεγχος που ανέδειξε το πρόβλημα θα πρέπει να επαναλαμβάνεται μετά από την όποια επισκευή, προκειμένου να διαπιστωθεί εάν το σύστημα MRI είναι κατάλληλο να χρησιμοποιηθεί για διάγνωση. / Magnetic Resonance Imaging (MRI) is based on the physical phenomenon of Nuclear Magnetic Resonance (NMR). While this phenomenon has been known since the 1950s, the first MRI scan was performed on a human being just in 1977. The 80’s was the decade that MRI systems started to evolve rapidly and this evolution still goes on. Nowadays, modern MRI systems do so much more than simple imaging, with diffusion MRI, MRI spectroscopy and functional MRI being the new promising applications. MRI scanners do not use ionizing radiation but magnetic fields and electromagnetic waves in the range of radiofrequencies. This is probably the reason why the MRI scanners did not attract so mach attention as CT scanners did, in terms of regulations regarding the safety of their use for patient scanning. However, since imaging is used for diagnosis and a wrong diagnosis can result to a wrong therapy or no therapy at all, which in turn may result to irreversible damage in the patient health or even to death, the American Association of Physicists in Medicine (AAPM) had proposed methods for testing the image quality from the early 1990s , . The American College of Radiology (ACR) has also contributed to this effort in the beginning of the new millennium, proposing image quality control methods to establish an accreditation program for MRI facilities , . In 2010 the AAPM published a report (AAPM REPORT NO. 100) with title “Acceptance Testing and Quality Assurance Procedures for Magnetic Resonance Imaging Facilities”, which describes procedures for testing the performance of MRI scanners, but also procedures concerning other safety issues for the patients and the personnel. In Greece until recently, MRI facilities – in contrast to CT scanners and all the other radiological equipment - were beyond the supervision of the Greek Atomic Energy Commission (Ε.Ε.Α.Ε.) and the Greek Association of Physicist in Medicine (Ε.Φ.Ι.Ε.). However, from the beginning of 2013, E.E.A.E. has proposed an accreditation program (based on the AAPM report No. 100) to be applied in all new MRI facilities. This accreditation program will progressively applied in older MRI facilities as well. The goal is within 5 years at most, all MRI facilities be accredited in the same way that CT scanners are. The purpose of this MSc thesis was to review the basics of MRI theory, to help Medical Physicists which are not experts in MRI, understand the principles of its operation, especially those related to the production of diagnostic images. In the next chapter the AAPM No. 100 report is presented (translated in Greek), in order to set the foundations for understanding the procedures used for quality control (QC) purposes but also other MRI operation safety issues. In the last chapter, an application of these procedures to an existing MRI installation is presented, as an example of the way that QC procedures are performed and the way that the resulting images are evaluated to result to measurable quantities. These quantities are used as performance indices and when compared to established limits, may inform the Medical Physicist whether the tested MRI systems satisfies the established criteria indicating an acceptable performance or whether one or more problems exist that result to suboptimal image quality and therefore corrective actions should be taken. In the latter case the failed test should be repeated after the field service engineers have corrected the problem, in order to ascertain that the MRI system is eligible to be used for medical diagnosis.