Early detection of diabetes retinopathy by new algorithms for automatic recognition of vascular changes

Diabetes mellitus often results in diabetic retinopathy caused by pathological changes of the retinal vessel tree. Early detection of these changes can delay the disease. Image processing can reduce the workload of screeners and can play a central role in quality assurance tasks. Therefore we aimed at the refinement and development of image processing algorithms to improve the quality and cost effectiveness of screening and diagnosis of diabetic retinopathy. In order to support ophthalmologists in their routine and to enable the quantitative assessment of vascular changes in colour fundus photographs a multi-resolution approach was developed which segments the vessel tree efficiently and precisely into digital images of the retina. The vessel tracker aims at determining as correctly as possible the retinal vascular network captured on a digital image irrespective of its origin. In addition to the tracker, algorithms were developed to detect the optic disk, bright lesions such as cotton wools spots, and dark lesions such as haemorrhages. The following classification of veins and arteries identifies arteries in 78.4 % and veins in 66.5% correctly. This helps selecting conspicuous images from a great number of patients.     

Surface size, curvature analysis, and assessment of knee joint incongruity with MRI in vivo.

The purpose of this study was to develop an MR-based technique for quantitative analysis of joint surface size, surface curvature, and joint incongruity and to assess its reproducibility under in vivo imaging conditions. The surface areas were determined after 3D reconstruction of the joint by triangulation and the incongruity by Gaussian curvature analysis. The precision was tested by analyzing four replicated MRI datasets of human knees in 14 individuals. The algorithms were shown to produce accurate data in geometric test objects. The interscan precision was <4% (CV%) for surface area, 2.9-5.7 m(-1) (SD) for the mean principal curvature, and 4.1-7.4 m(-1) for congruence indices. Incongruity was highest in the femoropatellar joint (79.7 m(-1)) and lowest in the medial femorotibial joint (28.6 m(-1)). This technique will permit identification of the specific role of surface size, curvature, and incongruity as potential risk factors for osteoarthritis.     

Quantitative Knorpelanalyse mit der Magnetresonanztomographie (qMRI) –Neue ?ra der Arthrosediagnostik? Neue ?ra der Arthrosediagnostik?

Die Magnetresonanztomographie (MRT) stellt eine neues und vielversprechendes Verfahren in der Diagnostik und Verlaufsbeurteilung der Osteoarthrose dar. Ihr Vorteil ist, da? alle artikul?ren Gewebe direkt visualisiert werden k?nnen und einer dreidimensionalen Analyse zug?nglich werden. Die vorliegenden Arbeit gibt eine übersicht über qualitative, semiquantitative und quantitative Untersuchungen des Gelenkknorpels mit MRT. Insbesondere werden Sequenzen und dreidimensionale Bildverarbeitungsmethoden für die quantitative Analyse des Knorpelvolumens und der Knorpeldicke vorgestellt sowie deren Validit?t und Pr?zision bei gesunden Probanden und Patienten mit Osteoarthrose diskutiert. Darüber hinaus werden Ans?tze für quantitative Analysen strukturell/biochemischer Knorpelparameter und für die Analyse seines Deformationsverhaltens am Lebenden er?rtert.     

Three-dimensional analysis and visualization of regional MR signal intensity distribution of articular cartilage

The aim of this study was to develop a technique for analyzing and visualizing the regional, three-dimensional signal intensity distribution of articular cartilage in MR images, as a potential surrogate marker of structural or biochemical alterations in early osteoarthritis. Exemplary MR-images of human patellae were acquired at a resolution of 1.5 x 0.31 x 0.31 mm(3), using a gradient-echo sequence with water excitation, and by combining three data sets to secondary images of proton density. After segmentation of the cartilage outlines, these were transferred to the other images. Contiguous slices were automatically divided into sub-regions that extend from the surface to the bone interface (layers) as well as from medial to lateral (sections). The signal intensity was then calculated and projected onto a three-dimensional representation of the articular surface, either by averaging through the depth (sections) or by visualizing the signal intensity at distinct levels in depth (layers). The exemplary data indicate that the reproducibility for regional analyses is in the same range as for the entire patellar cartilage, and that the distribution patterns of proton density delineated with MRI are in agreement with the literature. In conjunction with suitable MR protocols, this post-processing technique has potential to allow for detection and quantification of early degenerative processes in cartilage, before macro-morphological lesions occur.     

A method for quantifying time dependent changes in MR signal intensity of articular cartilage as a function of tissue deformation in intact joints

A method is proposed to determine accurately the signal intensity changes of the articular cartilage from sectional MR images and its related cartilage deformation under compression in an intact joint. Image processing methods are developed to delineate and register the cartilage boundaries in consecutive MR images in order to track corresponding tissue sectors during the loading experiment. Regions of interest can then be defined and traced during the compression, making a spatial and temporal analysis of signal intensity changes possible. In addition, the cartilage deformation is calculated in the respective tissue sectors and is related to the MR signal changes. Using a fat-suppressed FLASH 3D sequence, the preliminary results showed location-dependent slight changes of the signal intensity varying from individual to individual. The quantitative analysis of the signal intensity changes as a function of cartilage deformation with magnetic resonance imaging (MRI) aims to characterize microstructural properties of the articular cartilage that may lead to a better understanding of degenerative joint disease.     

Functional analysis of articular cartilage deformation, recovery, and fluid flow following dynamic exercise in vivo

The function of articular cartilage depends on the interaction between the tissue matrix and the interstitial fluid bound to the proteoglycan molecules. Mechanical loading has been shown to be involved in both the metabolic regulation of chondrocytes and in matrix degeneration. The purpose of the present study was therefore to analyze the deformation, recovery, and fluid flow in human articular cartilage after dynamic loading in vivo. The patellae of 7 volunteers were imaged at physical rest and after performing knee bends, with a specifically optimized fat-suppressed FLASH-3D magnetic resonance (MR) sequence. To measure cartilage deformation, the total volume of the patellar cartilage was determined, employing 3D digital image analysis. Patellar cartilage deformation ranged from 2.4 to 8.6% after 50 knee bends, and from 2.4% to 8.5% after 100 knee bends. Repeated sets of dynamic exercise at intervals of 15 min did not cause further deformation. After 100 knee bends, the cartilage required more than 90 min to recover from loading. The rate of fluid flow during relaxation ranged from 1.1 to 3.5 mm³/min (0.08 to 0.22 mm³/min per square centimeter of the articular surface) and was highly correlated with the individual degree of deformation after knee bends. The data provide the first quantification of articular cartilage recovery and of the rate of fluid flow between the cartilage matrix and surrounding tissue in intact joints in vivo. Measurement in the living opens the possibility of relating interindividual variations of mechanical cartilage properties to the susceptibility of developing joint failure, to assess the load-partitioning between the fluid phase and solid cartilage matrix during load transfer, and to determine the role of mechanically induced fluid flow in the regulation of the metabolic activity of chondrocytes.     

Quantitative cartilage imaging of the human hind foot: precision and inter-subject variability.

Alterations of ankle cartilage are observed in degenerative and inflammatory joint disease, but cartilage cannot be directly visualized by radiography. The purpose of this study was therefore to analyze the feasibility and precision of quantitative cartilage imaging in the human hind foot (talocrural, talotarsal, and intertarsal joints), and to report the inter-subject variability for cartilage volume, thickness and surface areas. The feet of 16 healthy volunteers were imaged using a 3D gradient-echo magnetic resonance imaging sequence with water-excitation. After interpolation to a resolution of 1 x 0.125 x 0.125 mm3 the cartilage plates were segmented, and the cartilage volume, thickness, and surface areas determined. The precision (four repeated measurements) was examined in eight volunteers, the RMS average CV% being 2.1% to 10.9% in single joint surfaces, and < or = 3% for the cumulative values of all joints. The mean cartilage thickness ranged from 0.57+/-0.08 (navicular surface) to 0.89+/-0.19 mm (trochlear surface for tibia). In conclusion this study shows that it is feasible to quantify thin cartilage layers in the hind foot under in vivo imaging conditions, and that the precision errors are substantially smaller than the inter-subject variability in healthy subjects.     

In vivo morphometry and functional analysis of human articular cartilage with quantitative magnetic resonance imaging – from image to data, from data to theory

Analyses of form-function relationships and disease processes in human articular cartilage necessitate in vivo assessment of cartilage morphology and deformational behavior. MR imaging and advanced digital post-processing techniques have opened novel possibilities for quantitative analysis of cartilage morphology, structure, and function in health and disease. This article reviews work on three-dimensional post-processing of MR image data of articular cartilage, summarizing studies on the accuracy and precision of quantitative analyses in human joints. It presents normative values on cartilage volume, thickness, and joint surface areas in the human knee, and describes the correlation between different joints and joint surfaces as well as their association with gender, body dimensions, and age. The article summarizes ongoing work on functional adaptation of articular cartilage to mechanical loading, analyses of in situ cartilage deformation in intact joints in vivo and in vitro, and the quantitative evaluation of cartilage tissue loss in osteoarthritis. We describe evolving techniques for assessment of the structural/biochemical composition of articular cartilage, and discuss future perspectives of quantitative cartilage imaging in the context of joint mechanics, mechano-adaptation, epidemiology, and osteoarthritis research. Specifically, we show that fat-suppressed gradient echo sequences permit valid analysis of cartilage morphology, both in healthy and severely osteoarthritic joints, as well as highly reproducible measurements (CV%=1 to 3% in the knee, and 2 to 10% in the ankle). Relatively small differences in cartilage morphology exist between both limbs of the same person (～5%), but large differences between individuals (CV% ～20%). Men display only slightly thicker cartilage then women (～10%), but significantly larger joint surface areas (～25%), even when accounting for differences in body weight and height. Weight and height represent relatively poor predictors of cartilage thickness (r² <15%), but muscle cross section areas display more promising correlations (r² >40%). The level of physical exercise (sportive activity) does not account for interindividual differences in cartilage thickness. The thickness appears to decrease slightly in the elderly – in particular in women, even in the absence of osteoarthritic cartilage lesions. Strenuous physical exercises (e.g., knee bends) cause a 6% patellar cartilage deformation in young individuals, but significantly less deformation in elderly men and women (<3%). The time required for full recovery after exercise (fluid flow back into the matrix) is relatively long (～90 min). Static in situ compression of femoropatellar cartilage with 150% body weight produces large deformations after 4 h (～30% volume change), but only very little deformation during the first minutes of loading. Quantitative analyses of magnetization transfer and proton density hold promise for biochemical evaluation of articular cartilage, and are shown to be related to the deformational behavior of the cartilage. Application of these techniques to larger cohorts of patients in epidemiological and clinical studies will establish the role of quantitative cartilage imaging not only in basic research on form-function relationships of articular cartilage, but also in clinical research and management of osteoarthritis.     

Synthese von 2,2a,3,4-Tetrahydro[1,2-d]benz[b]-1,4-oxazin-2,4-dionen, 2. Mitt.

Synthesis of 2,2a,3,4,-Tetrahydro[1,2d]benz[b]-1,4-oxazine-2,4-diones, II The diasteromeric 3-amino-β-lactams 7 and 8 were obtained from the azides 5 and 6 and the phthalimido derivatives 9 and 12 . Compound 9 was synthesized directly from 2 by means of phthalimidoacetyl chloride/triethylamine, whereas 12 is accessible from 11 only by the Mitsunobu reaction. Acylation of 7 or 8 (to 13 or 14 ) is followed by hydrolysis of the ester function (to 15 or 16 ) and debenzylation to yield 17 or 18 which are lactonized to 19 or 20 by the action of DCC.     

Functional malcentering of the humeral head and asymmetric long-term stress on the glenoid: potential reasons for glenoid loosening in total shoulder arthroplasty

We tested the hypothesis that functional malcentering of the humeral head during arm elevation exists in patients with glenohumeral osteoarthritis and influences long-term glenoid loading. Twenty-eight healthy volunteers and 10 patients with primary osteoarthritis, 10 with cuff-arthropathy, and 1 with dysplastic glenoid were examined. Open magnetic resonance imaging and 3-dimensional (3D) digital postprocessing techniques were applied in various arm positions. Osteoabsorptiometry was used to determine 3D subchondral mineralization patterns of the glenoid as an indicator of integral long-term stress distribution. At 30 degrees of abduction, 5 patients demonstrated malcentering of the humeral head posteriorly; all patients with cuff arthropathy had malcentering superiorly. At 90 degrees, most patients displayed significant (P < .001) malcentering in the superior and posterior direction. The shoulders showed maximal subchondral mineralization patterns in the direction of malcentering. Most patients with glenohumeral osteoarthritis displayed functional malcentering, which might be responsible for postoperative glenoid loosening in shoulder arthroplasty if not corrected intraoperatively.