Browsing by Subject "Magnetic Resonance Imaging"

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    Expanding the clinical spectrum of hereditary fibrosing poikiloderma with tendon contractures, myopathy and pulmonary fibrosis due to FAM111B mutations
    (2015) Mercier, Sandra; Küry, Sébastien; Salort-Campana, Emmanuelle; Magot, Armelle; Agbim, Uchenna; Besnard, Thomas; Bodak, Nathalie; Bou-Hanna, Chantal; Bréhéret, Flora; Brunelle, Perrine; Caillon, Florence; Chabrol, Brigitte; Cormier-Daire, Valérie; David, Albert; Eymard, Bruno; Faivre, Laurence; Figarella-Branger, Dominique; Fleurence, Emmanuelle; Ganapathi, Mythily; Gherardi, Romain; Goldenberg, Alice; Hamel, Antoine; Igual, Jeanine; Irvine, Alan D; Israël-Biet, Dominique; Kannengiesser, Caroline; Laboisse, Christian; Le Caignec, Cédric; Mahé, Jean-Yves; Mallet, Stéphanie; MacGowan, Stuart; McAleer, Maeve A; McLean, Irwin; Méni, Cécile; Munnich, Arnold; Mussini, Jean-Marie; Nagy, Peter L; Odel, Jeffrey; O’Regan, Grainne M; Péréon, Yann; Perrier, Julie; Piard, Juliette; Puzenat, Eve; Sampson, Jacinda B; Smith, Frances; Soufir, Nadem; Tanji, Kurenai; Thauvin, Christel; Ulane, Christina; Watson, Rosemarie M; Khumalo, Nonhlanhla P; Mayosi, Bongani M; Barbarot, Sébastien; Bézieau, Stéphane
    BackgroundHereditary Fibrosing Poikiloderma (HFP) with tendon contractures, myopathy and pulmonary fibrosis (POIKTMP [MIM 615704]) is a very recently described entity of syndromic inherited poikiloderma. Previously by using whole exome sequencing in five families, we identified the causative gene, FAM111B (NM_198947.3), the function of which is still unknown. Our objective in this study was to better define the specific features of POIKTMP through a larger series of patients.MethodsClinical and molecular data of two families and eight independent sporadic cases, including six new cases, were collected.ResultsKey features consist of: (i) early-onset poikiloderma, hypotrichosis and hypohidrosis; (ii) multiple contractures, in particular triceps surae muscle contractures; (iii) diffuse progressive muscular weakness; (iv) pulmonary fibrosis in adulthood and (v) other features including exocrine pancreatic insufficiency, liver impairment and growth retardation. Muscle magnetic resonance imaging was informative and showed muscle atrophy and fatty infiltration. Histological examination of skeletal muscle revealed extensive fibroadipose tissue infiltration. Microscopy of the skin showed a scleroderma-like aspect with fibrosis and alterations of the elastic network. FAM111B gene analysis identified five different missense variants (two recurrent mutations were found respectively in three and four independent families). All the mutations were predicted to localize in the trypsin-like cysteine/serine peptidase domain of the protein. We suggest gain-of-function or dominant-negative mutations resulting in FAM111B enzymatic activity changes.ConclusionsHFP with tendon contractures, myopathy and pulmonary fibrosis, is a multisystemic disorder due to autosomal dominant FAM111B mutations. Future functional studies will help in understanding the specific pathological process of this fibrosing disorder.
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    Long-Term Left Ventricular Remodelling in Rat Model of Nonreperfused Myocardial Infarction: Sequential MR Imaging Using a 3T Clinical Scanner
    (2012) Saleh, Muhammad G; Sharp, Sarah-Kate; Alhamud, Alkathafi; Spottiswoode, Bruce S; van der Kouwe, André J W; Davies, Neil H; Franz, Thomas; Meintjes, Ernesta M
    Purpose. To evaluate whether 3T clinical MRI with a small-animal coil and gradient-echo (GE) sequence could be used to characterize long-term left ventricular remodelling (LVR) following nonreperfused myocardial infarction (MI) using semi-automatic segmentation software (SASS) in a rat model. Materials and Methods. 5 healthy rats were used to validate left ventricular mass (LVM) measured by MRI with postmortem values. 5 sham and 7 infarcted rats were scanned at 2 and 4 weeks after surgery to allow for functional and structural analysis of the heart. Measurements included ejection fraction (EF), end-diastolic volume (EDV), end-systolic volume (ESV), and LVM. Changes in different regions of the heart were quantified using wall thickness analyses. Results. LVM validation in healthy rats demonstrated high correlation between MR and postmortem values. Functional assessment at 4 weeks after MI revealed considerable reduction in EF, increases in ESV, EDV, and LVM, and contractile dysfunction in infarcted and noninfarcted regions. Conclusion. Clinical 3T MRI with a small animal coil and GE sequence generated images in a rat heart with adequate signal-to-noise ratio (SNR) for successful semiautomatic segmentation to accurately and rapidly evaluate long-term LVR after MI.
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    Numerical and experimental modeling of atherosclerosis related to MRI
    (1998) Bernsdorf, Stefan; Sayers, A
    This thesis was motivated by the idea of employing non-invasive investigations of atherosclerosis using Magnetic Resonance Imaging (MRI). MRI has the advantage of being able to detect atheroma in blood vessels with no risk to the patient but is still limited in its application to large blood vessels by the low geometrical resolution obtainable. The capability of MRI to measure velocities as well leads to the idea of correlating atheroma dimensions with measured velocities downstream of the blockage. This thesis makes a first step towards obtaining results that can be applied in investigations of atherosclerosis employing MRI. The fluid dynamics of arterial blood flow, the medical procedure of diagnosing and treating atherosclerotic diseases, and the physical principle of MRI are investigated to find out "if' and "how" the correlation between a blockage and the resulting downstream velocities can contribute to the diagnosis of atheroma. Parallel to this background research, experimental and numerical modeling of atheroma is carried out. These two approaches use identical geometrical and fluid parameters to enable a direct validation of the results. An experimental test-rig is designed. Experiments with different types of blockages are performed. The measured flow parameters are pressure and velocity profiles in a crosssection of the modeled artery. A commercial software package is employed for the numerical simulation of blockages with similar geometries to those used in the experiments. The pressure and absolute velocities are again the derived parameters. Both approaches are validated with analytical results obtainable for flow without any blockages. Blockages are then inserted and the results are compared and analyzed for their potential to contribute to the medical application. The results obtained with the two models give good correspondence. The transitional length of the laminar pipe flow corresponds very well to the expectations. A laminar velocity profile is completely built up before the fluid enters a blockage. Blockages with a small flow area cause a high peak velocity and a large wake. Blockages that slightly reduce the flow area have only a small influence on the flow. The length of a blockage has only a secondary influence on the downstream velocity distribution, while the influence of the surface roughness of the blockage is small. The peak velocities and pressure loss caused by the different blockages give good correlation. The prediction of the diameter of the blockage from peak velocities measured with MRI is an improvement on that which is possible from the theory only. In particular, the results obtained in this thesis show that the true maximum velocities are significantly lower than those obtained with theoretical predictions. The change in the velocity profiles, due to angioplasty, is shown in a simplified form with the models. Typical values of reduced areas before and after such surgery, where the atheroma is squeezed against the arterial walls, are analysed. The influence of the post-surgery blockage on the flow is very small, while the pre-surgery blockage shows a dominant influence. A prominent wake exists downstream of a highly reduced flow area, and high velocities occur. A wake is a potential risk area for atherosclerosis, as low shear rates and high turbulence intensities are possible. The blockage with the less reduced area has almost no influence on the flow, and a wake is hardly formed. The influence of different shapes of atheroma, while having a similar reduced area, is also demonstrated. The perfectly symmetrical blockage has less negative influence on the flow than one which is highly asymmetrical. The asymmetrical blockage causes a larger wake and higher maximum velocities.