Oligoclonal Band Straightening Based on Optimized Hierarchical Warping for Multiple Sclerosis Diagnosis.

The detection of immunoglobulin G (IgG) oligoclonal bands (OCB) in cerebrospinal fluid (CSF) by isoelectric focusing (IEF) is a valuable tool for the diagnosis of multiple sclerosis. Over the last decade, the results of our clinical research have suggested that tears are a non-invasive alternative to CSF. However, since tear samples have a lower IgG concentration than CSF, a sensitive OCB detection is therefore required. We are developing the first automatic tool for IEF analysis, with a view to speeding up the current visual inspection method, removing user variability, reducing misinterpretation, and facilitating OCB quantification and follow-up studies. The removal of band distortion is a key image enhancement step in increasing the reliability of automatic OCB detection. Here, we describe a novel, fully automatic band-straightening algorithm. The algorithm is based on a correlation directional warping function, estimated using an energy minimization procedure. The approach was optimized via an innovative coupling of a hierarchy of image resolutions to a hierarchy of transformation, in which band misalignment is corrected at successively finer scales. The algorithm's performance was assessed in terms of the bands' standard deviation before and after straightening, using a synthetic dataset and a set of 200 lanes of CSF, tear, serum and control samples on which experts had manually delineated the bands. The number of distorted bands was divided by almost 16 for the synthetic lanes and by 7 for the test dataset of real lanes. This method can be applied effectively to different sample types. It can realign minimal contrast bands and is robust for non-uniform deformations.

Toward an automatic tool for oligoclonal band detection in cerebrospinal fluid and tears for multiple sclerosis diagnosis: lane segmentation based on a ribbon univariate open active contour.

The latest revision of multiple sclerosis diagnosis guidelines emphasizes the role of oligoclonal band detection in isoelectric focusing images of cerebrospinal fluid. Recent studies suggest tears as a promising noninvasive alternative to cerebrospinal fluid. We are developing the first automatic method for isoelectric focusing image analysis and oligoclonal band detection in cerebrospinal fluid and tear samples. The automatic analysis would provide an accurate, fast analysis and would reduce the expert-dependent variability and errors of the current visual analysis. In this paper, we describe a new effective model for the fully automated segmentation of highly distorted lanes in isoelectric focusing images. This approach is a new formulation of the classic parametric active contour problem, in which an open active contour is constrained to move from the top to the bottom of the image, and the x-axis coordinate is expressed as a function of the y-axis coordinate. The left and right edges of the lane evolved together in a ribbon-like shape so that the full width of the lane was captured reliably. The segmentation algorithm was implemented using a multiresolution approach in which the scale factor and the active contour control points were progressively increased. The lane segmentation algorithm was tested on a database of 51 isoelectric focusing images containing 419 analyzable lanes. The new model gave robust results for highly curved lanes, weak edges, and low-contrast lanes. A total of 98.8% of the lanes were perfectly segmented, and the remaining 1.2% had only minor errors. The computation time (1 s per membrane) is negligible. This method precisely defines the region of interest in each lane and thus is a major step toward the first fully automatic tool for oligoclonal band detection in isoelectric focusing images. Graphical abstract.

A story of oedemas.

The Waldmann's disease is a primitive intestinal lymphangectasia. This exsudative enteropathy initiates a protein leakage by the digestive tract. Clinically, this syndrome is characterised by oedemas and biologically by hypoprotidemia and loss of lymphocytes T CD4+, which increases a risk for infections. Here, we describe a patient's case for whom the protein loss was aggravated by a nephrotic syndrome.

Three-dimensional (3D) culture of adult murine colon as an in vitro model of cryptosporidiosis: Proof of concept.

Cryptosporidium parvum is a major cause of diarrheal illness and was recently potentially associated with digestive carcinogenesis. Despite its impact on human health, Cryptosporidium pathogenesis remains poorly known, mainly due to the lack of a long-term culture method for this parasite. Thus, the aim of the present study was to develop a three-dimensional (3D) culture model from adult murine colon allowing biological investigations of the host-parasite interactions in an in vivo-like environment and, in particular, the development of parasite-induced neoplasia. Colonic explants were cultured and preserved ex vivo for 35 days and co-culturing was performed with C. parvum. Strikingly, the resulting system allowed the reproduction of neoplastic lesions in vitro at 27 days post-infection (PI), providing new evidence of the role of the parasite in the induction of carcinogenesis. This promising model could facilitate the study of host-pathogen interactions and the investigation of the process involved in Cryptosporidium-induced cell transformation.

[Comparison of immunochromatographic tests Actim(®) Prom and Amnioquick(®) Duo for the rapid detection of premature rupture of membranes]. / Comparaison des tests immunochromatographiques Actim(®) Prom et Amnioquick(®) Duo pour le dépistage rapide de la rupture prématurée des membranes.

Premature rupture of membranes (PRM) affects 5 to 15% of pregnancies, leading to prematurity and neonatal infection. PRM can be identified by through various amniotic fluid proteins in vaginal secretions. The aim of this study is to compare two immunochromatographic tests based on the detection of insulin-like growth factor binding protein (IGFBP-1) and alpha-foeto protein (AFP) for one of the two tests in cervico-vaginal secretions. Two tests, Actim(®) Prom and Amnioquick(®) Duo were performed on 80 pregnant women with suspected PRM. Amnioquick(®) Duo allows the simultaneous detection of IGFBP-1 and AFP with an automated incubation and reading. The number of positive results is similar (Khi-deux = 0.173, p = 0.6773) for IGFBP-1 between the two tests and there is a good agreement (K = 0.621), with a proportion of negative results of 86%. The number of positive results for AFP is more important in comparison to IGFBP-1. Results positive/positive (Actim(®) Prom/Amnioquick(®)) for IGFBP-1 seems to be related to the time when tests have been performed, that is to say in the last weeks of pregnancy. In conclusion, both tests have similar performance, but there is a risk of false positive results with AFP, this can be explained by the presence of non-visible blood in samples. An automated incubation and reading allows a good reproducibility. Moreover, the computer data storage improve the post-analytical quality.

Prostate contours delineation using interactive directional active contours model and parametric shape prior model.

Prostate contours delineation on Magnetic Resonance (MR) images is a challenging and important task in medical imaging with applications of guiding biopsy, surgery and therapy. While a fully automated method is highly desired for this application, it can be a very difficult task due to the structure and surrounding tissues of the prostate gland. Traditional active contours-based delineation algorithms are typically quite successful for piecewise constant images. Nevertheless, when MR images have diffuse edges or multiple similar objects (e.g. bladder close to prostate) within close proximity, such approaches have proven to be unsuccessful. In order to mitigate these problems, we proposed a new framework for bi-stage contours delineation algorithm based on directional active contours (DAC) incorporating prior knowledge of the prostate shape. We first explicitly addressed the prostate contour delineation problem based on fast globally DAC that incorporates both statistical and parametric shape prior model. In doing so, we were able to exploit the global aspects of contour delineation problem by incorporating a user feedback in contours delineation process where it is shown that only a small amount of user input can sometimes resolve ambiguous scenarios raised by DAC. In addition, once the prostate contours have been delineated, a cost functional is designed to incorporate both user feedback interaction and the parametric shape prior model. Using data from publicly available prostate MR datasets, which includes several challenging clinical datasets, we highlighted the effectiveness and the capability of the proposed algorithm. Besides, the algorithm has been compared with several state-of-the-art methods.

Study of proximal femoral bone perfusion with 3D T1 dynamic contrast-enhanced MRI: a feasibility study.

OBJECTIVE: The objective of this study was to compare measurements of semi-quantitative and pharmacokinetic parameters in areas of red (RBM) and yellow bone marrow (YBM) of the hip, using an in-house high-resolution DCE T1 sequence, and to assess intra- and inter-observer reproducibility of these measurements. METHODS: The right hips of 21 adult patients under 50 years of age were studied. Spatial resolution was 1.8 × 1.8 × 1.8 mm(3), and temporal resolution was 13.5 seconds. Two musculoskeletal radiologists independently processed DCE images and measured semi-quantitative and pharmacokinetic parameters in areas of YBM and RBM. Signal-to-noise (SNR) and contrast-to-noise (CNR) ratios were calculated. Intra- and inter-observer reproducibility was assessed. RESULTS: Area under the curve (AUC) and initial slope (IS) were significantly greater for RBM than for YBM (p < 0.05). K(trans) and kep were also significantly greater for RBM (p < 0.05). There was no significant difference in time to peak between the regions (p < 0.05). SNR, CNR, and intra- and inter-observer reproducibility were all good. CONCLUSIONS: DCE study of the whole hip is feasible with high spatial resolution using a 3D T1 sequence. Measures were possible even in low vascularized areas of the femoral head. K(trans), kep, AUC, and IS values were significantly different between red and yellow marrow, whereas TTP values were not. KEY POINTS: High-spatial-resolution dynamic contrast-enhanced MRI of hip structures is feasible. Intra- and inter-observer reproducibility is good. Red and yellow bone marrow have different perfusion patterns.

Carpal pseudoerosions: a plain X-ray interpretation pitfall.

OBJECTIVE: To examine in detail images of pseudoerosion of the wrist and hand on plain radiographs. MATERIAL AND METHODS: The study was conducted with 28 cadaver wrists. During a single imaging session three techniques-plain radiography, tomosynthesis, and computed tomography-were used to visualize the wrist and hand specimens. For each technique, 20 radio-ulno-carpo-metacarpal sites known to present bone erosions in rheumatoid arthritis were analyzed by two radiologists using a standard system to score the cortical bone: normal, pseudoerosion, true erosion, or other pathology. Cohen's concordance analysis was performed to determine inter-observer and intra-observer (for the senior radiologist) agreement by site and by technique. Serial sections of two cadaver specimens were examined to determine the anatomical correlation of the pseudoerosions. RESULTS: On the plain radiographs, the radiologists scored many images as pseudoerosion (7.3%), particularly in the distal ulnar portion of the capitate, the distal radial portion of the hamate, the proximal ulnar portion of the base of the third metacarpal, the proximal radial portion of the base of the fourth metacarpal, the distal ulnar portion of the hamate, and the proximal portion of the base of the fifth metacarpal. The computed tomography scan revealed that none of these doubtful images corresponded to true erosions. The anatomical correlation study showed that these images could probably be attributed to ligament insertions, thinner lamina, and enhanced cortical bone transparency. CONCLUSION: Knowledge of the anatomical carpal localizations where pseudoerosions commonly occur is a necessary prerequisite for analysis of plain radiographs performed to diagnose or monitor rheumatoid arthritis.

BioSigPlot: an opensource tool for the visualization of multi-channel biomedical signals with Matlab.

This paper presents a Matlab-based software (MathWorks inc.) called BioSigPlot for the visualization of multi-channel biomedical signals, particularly for the EEG. This tool is designed for researchers on both engineering and medicine who have to collaborate to visualize and analyze signals. It aims to provide a highly customizable interface for signal processing experimentation in order to plot several kinds of signals while integrating the common tools for physician. The main advantages compared to other existing programs are the multi-dataset displaying, the synchronization with video and the online processing. On top of that, this program uses object oriented programming, so that the interface can be controlled by both graphic controls and command lines. It can be used as EEGlab plug-in but, since it is not limited to EEG, it would be distributed separately. BioSigPlot is distributed free of charge (http://biosigplot.sourceforge.net), under the terms of GNU Public License for non-commercial use and open source development.

Assessment of reduced field of view in diffusion tensor imaging of the lumbar nerve roots at 3 T.

OBJECTIVES: To assess the value of reduced field of view (rFOV) imaging in diffusion tensor imaging (DTI) and tractography of the lumbar nerve roots at 3 T from the perspective of future clinical trials. METHODS: DTI images of the lumbar nerves were obtained in eight healthy volunteers, with and without the rFOV technique. Non-coplanar excitation and refocusing pulses associated with outer volume suppression (OVS) were used to achieve rFOV imaging. Tractography was performed. A visual evaluation of image quality was made by two observers, both senior musculoskeletal radiologists. Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) were measured in L5 and S1 roots. RESULTS: rFOV images of the L5 and S1 roots were assessed as being superior to full FOV (fFOV) images. Image quality was rated as good to excellent by both observers. Interobserver agreement was good. No significant difference was found in FA and ADC measurements of the L5 or S1 roots. On the contrary, only poor-quality images could be obtained with fFOV imaging as major artefacts were present. CONCLUSION: The rFOV approach was essential to achieve high-quality DTI imaging of lumbar nerve roots on 3-T MRI. KEY POINTS: • Diffusion tensor 3-T MR imaging of lumbar nerve roots creates severe artefacts. • A reduced field of view drastically reduces artefacts, thereby improving image quality. • Good-quality tractography images can even be obtained with rFOV imaging. • rFOV DTI is better than fFOV DTI for clinical studies.

Angiographic regression patterns after intravitreal ranibizumab injections for neovascular age-related macular degeneration.

BACKGROUND AND OBJECTIVE: To investigate the relation between visual gain, injection frequency, and the angiographic regression patterns after intravitreal ranibizumab on an as-needed basis in exudative age-related macular degeneration (AMD). PATIENTS AND METHODS: Fifty-nine treatment-naïve patients (68 eyes) were retrospectively analyzed. All patients received three consecutive monthly injections (induction phase) of ranibizumab (0.5 mg/0.05 mL). Based on fluorescein angiography (FA), the choroidal neovascularization (CNV) was judged to present either complete regression (pattern 1), partial regression (pattern 2), stabilization of the lesion size without leakage (pattern 3), stabilization of the lesion size with persistence of leakage (pattern 4), or increased angiographic size (pattern 5). RESULTS: Mean visual acuity (VA) significantly improved from 48 to 54.3 letters at 1 year after a mean of 5.5 injections (P < .001). Multiple linear regression revealed baseline VA as a predictor of visual gain and the angiographic pattern as a predictor of number of injections. Analysis of variance revealed a significant interaction (F-test [1.67] = 25, P < .001) between the number of injections at 12 months and the regression patterns, as evaluated by FA 1 month after the induction phase. Eyes showing complete CNV regression needed significantly fewer injections than eyes without any angiographic sign of CNV regression (3.4 injections in pattern 1 vs 5.6 injections in pattern 3 [P = .03], and 7 injections in pattern 4 [P < .001], 4.4 injections in pattern 2 vs 7 injections in pattern 4 [P < .001]). CONCLUSION: FA may represent a useful tool to adapt the rhythm of visits and intravitreal anti-vascular endothelial growth factor injections in exudative AMD.

Comparison of surface plasmon resonance transferrin quantification with a common immunoturbidimetric method.

OBJECTIVES: The variation in the results from different clinical laboratories testing the same patient sample using classical methods for serum transferrin determination can affect interpretation. We developed a surface plasmon resonance (SPR) method for serum transferrin assay that may aid standardization. DESIGN AND METHODS: Quantification of transferrin was performed by direct analysis on a Biacore system (GE Healthcare). We assessed analytical performance of this new assay and compared it to a common immunoturbidimetric method (Beckman Coulter). RESULTS: Intra-run coefficients of variation (CV) were up to 1.10% and inter-day CVs were up to 2.10%. The comparison of this new SPR assay (Biacore) with a classical immunoturbidimetric method (Beckman Coulter) showed a good correlation (r=0.959), and the Bland and Altman plot with no global significant difference. CONCLUSIONS: According excellent achievement of SPR transferrin determination, we suggest its use as an independent method for comparison different immunoassays. This could be an important tool to help clinical laboratories to deliver standardized values, essential for the decision to investigate genetic hereditary hemochromatosis.

Tear analysis in clinically isolated syndrome as new multiple sclerosis criterion.

In clinically isolated syndrome (CIS), the detection of oligoclonal bands (OCBs) in cerebrospinal fluid (CSF) is critical for space dissemination validation when magnetic resonance imaging (MRI) diagnostic criteria are not fulfilled. However, lumbar puncture for CSF collection is considered relatively invasive. Previous studies have demonstrated applicability of OCB detection in tears to the diagnosis of multiple sclerosis (MS). The objective of the present study was to assess concordance between OCB detection in tears and in CSF. We have prospectively included patients with CIS and compared results of CSF and tear OCB detection by isoelectric focusing (IEF). Tears were collected using a Schirmer strip. We included 82 patients. For 69 of them, samples were analysable. OCBs were detected in CSF for 63.8% and in tears for 42% of patients. All patients with tear OCBs had CSF OCBs. We suggest that tear OCB detection may replace CSF OCB detection as a diagnostic tool in patients with CIS. This would circumvent the practice of invasive lumbar punctures currently used in MS diagnosis.

Factors of accuracy of transient elastography (fibroscan) for the diagnosis of liver fibrosis in chronic hepatitis C.

UNLABELLED: The purpose of this study was to assess the influence of success rate and interquartile range on the accuracy of transient elastography for the diagnostic of fibrosis in hepatitis C virus infection. Two-hundred fifty-four consecutive patients had liver stiffness measurements and liver biopsy of at least 15 mm. Discordances of at least two stages between transient elastography and histological assessment were observed in 28 cases (11%). Factors of discordance were assessed by comparing the 28 misclassified cases with the 226 others. In multivariate analysis, fibrosis stage (F0-F2 versus F3-F4) and the ratio interquartile range/median value of liver stiffness measurement (IQR/M) were associated with discordances (P or= 0.21, discordances of at least two stages of fibrosis were respectively observed in 10 of 135 cases (7.4%) versus 18 of 119 cases (15.1%) (P or= 0.21 versus IQR/M < 0.21, for the diagnosis of liver fibrosis F >or= 2, F >or= 3, F = 4, areas under the receiver operating characteristic curve (AUROCs) were 0.80 (95% confidence interval [CI], 0.73-0.89) versus 0.81 (95% CI, 0.70-0.90), (P = NS); 0.80 (95% CI, 0.72-0.88) versus 0.89 (95% CI, 0.83-0.95) (P = 0.04); and 0.86 (95% CI, 0.77-0.94) versus 0.95 (95% CI, 0.92-0.99) (P = NS). No association was found between success rate and discordance. CONCLUSION: IQR/M is a factor of overestimation of liver fibrosis, and the most discriminant cutoff value is 0.21. Success rate is not a factor of accuracy for the diagnosis of hepatic fibrosis.

Routine practice HCV infection screening with saliva samples: multicentric study in an intravenous drug user population.

OBJECTIVE: The purpose of this randomized multicentric study was to evaluate the diagnostic contribution of screening for HCV infection on saliva samples in day-to-day practice in the intravenous drug-user (IVDU) population. METHODS: Between January and May 2004, 274 presumably HCV-negative IVDU were screened for HCV infection in 15 centers in France (median age 29 years). After centralized randomization, screening tests were performed on blood samples (arm A) or saliva samples (arm B). Screening tests were performed in 78 subjects (28%) had never been screened before and in 196 subjects (72%) who had had a negative HCV screening test on average 12 months prior to the beginning of the study. In the event of a positive saliva test for anti-HCV Ab, a serum test for anti-HCV Ab was performed. In the event of a positive serum test for anti-HCV Ab, PCR was performed on serum to measure HCV-RNA. RESULTS: Fourteen individuals were positive for HCV RNA (7 in each arm). Six of these cases had not been detected before. In eight cases, the median time between the last negative screening test and study inclusion was 11 months (range 6-94 months). CONCLUSIONS: Viremia tests were positive in 5% percent of the target population, although one-third of the individuals in arm A (blood samples) were not tested. The saliva test may be a useful alternative in the event of refusal of a blood test or when poor venous conditions compromise venous puncture. A confirmatory blood test still remains difficult to obtain in nearly half of patients.

An analysis of the biochemical diagnosis of 66 pheochromocytomas.

OBJECTIVES: The aims of this study were to determine the performance of each variable, to define the optimal diagnostic thresholds and to determine the relative value of assaying chromogranin A (CgA). DESIGN: Prospective study. METHODS: Two groups of patients were studied: a control group of 71 patients and a group of 63 patients with a histologically-proven pheochromocytoma (52 pheochromocytomas and 14 paragangliomas). Fourteen of the patients had a family history of the disease. Eleven variables were assayed in each patient, i.e. the plasma and urinary concentrations of amines and their derivatives, and the CgA serum concentration. RESULTS: The study of the control group showed that all the serum assays gave false positive results (from 6 to 23%), as did four of the six urinary assays (from 2.9 to 12.3%). The areas under the receiver operating characteristic curves varied from 0.689 to 0.992. The variables relating to the epinephrine pathway were significantly less expressed in the hereditary diseases than in the sporadic cases. The diagnostic thresholds of the three most efficient variables have been raised. CONCLUSIONS: Plasma determinations of metanephrines are now an easy and convenient tool for the diagnosis of pheochromocytoma. However, in our study the best specificity was obtained with the urinary tests rather than with the plasma assays while the highest sensitivities were for the normetanephrine assays. The assay of CgA was highly efficient in diagnosing pheochromocytomas in the absence of renal insufficiency. By combining it with fractionated metanephrine assays, the sensitivities of the latter were increased.

Clinical evaluation of nine free thyroxine assays: persistent problems in particular populations.

Over the past decade, numerous papers have addressed the various methodological problems encountered with free thyroxine (FT4) assays. We evaluated the clinical performance of nine FT4 assays in five centres, using a panel of 310 sera: 156 from euthyroid controls; 27 from hyperthyroid patients; 34 from untreated hypothyroidism; 22 from patients with renal failure; 30 from women in the last trimester of pregnancy; 23 from patients on thyroid substitutive therapy; and 18 from patients treated with amiodarone. Only three methods showed a Gaussian distribution of FT4 concentrations. Reference ranges were calculated using the 2.5th and 97.5th percentiles. A significant difference was observed between FT4 values in men and women. The areas under the receiver operating characteristic (ROC) curves ranged from 0.996 to 1 for hyperthyroidism and from 0.973 to 1 for hypothyroidism. In sera from patients with renal failure and from pregnant women, method-dependent biases were observed and confirmed with dilution experiments. In conclusion, current FT4 assays show good performance regarding the diagnosis of overt dysthyroidism. Nevertheless, FT4 measurements are still vulnerable to method-dependent artefacts in particular populations such as patients with renal failure and pregnant women.