Improvement of the specificity of cancer detection by autofluorescence imaging in the tracheo-bronchial tree using backscattered violet light.

BACKGROUND: Autofluorescence bronchoscopy (AFB) is a highly sensitive tool for the detection of early bronchial cancers. However, its specificity remains limited due to primarily false positive results induced by hyperplasia, metaplasia and inflammation. We have investigated the potential of blue-violet backscattered light to eliminate false positive results during AFB in a clinical pilot study. METHODS: The diagnostic autofluorescence endoscopy (DAFE) system was equipped with a variable band pass filter in the imaging detection path. The backscattering properties of normal and abnormal bronchial mucosae were assessed by computing the contrast between the two tissue types for blue-violet wavelengths ranging between 410 and 490 nm in 12 patients undergoing routine DAFE examination. In a second study including 6 patients we used a variable long pass (LP) filter to determine the spectral design of the emission filter dedicated to the detection of this blue-violet light with the DAFE system. RESULTS: (Pre-)neoplastic mucosa showed a clear wavelength dependence of the backscattering properties of blue-violet light while the reflectivity of normal, metaplastic and hyperplastic autofluorescence positive mucosa was wavelength independent. CONCLUSIONS: Our results showed that the detection of blue-violet light has the potential to reduce the number of false positive results in AFB. In addition we determined the spectral design of the emission filter dedicated to the detection of this blue-violet light with the DAFE system.

Breast cancer and melanoma cell line identification by FTIR imaging after formalin-fixation and paraffin-embedding.

Over the past few decades, Fourier transform infrared (FTIR) spectroscopy coupled to microscopy has been recognized as an emerging and potentially powerful tool in cancer research and diagnosis. For this purpose, histological analyses performed by pathologists are mostly carried out on biopsied tissue that undergoes the formalin-fixation and paraffin-embedding (FFPE) procedure. This processing method ensures an optimal and permanent preservation of the samples, making FFPE-archived tissue an extremely valuable source for retrospective studies. Nevertheless, as highlighted by previous studies, this fixation procedure significantly changes the principal constituents of cells, resulting in important effects on their infrared (IR) spectrum. Despite the chemical and spectral influence of FFPE processing, some studies demonstrate that FTIR imaging allows precise identification of the different cell types present in biopsied tissue, indicating that the FFPE process preserves spectral differences between distinct cell types. In this study, we investigated whether this is also the case for closely related cell lines. We analyzed spectra from 8 cancerous epithelial cell lines: 4 breast cancer cell lines and 4 melanoma cell lines. For each cell line, we harvested cells at subconfluence and divided them into two sets. We first tested the "original" capability of FTIR imaging to identify these closely related cell lines on cells just dried on BaF2 slides. We then repeated the test after submitting the cells to the FFPE procedure. Our results show that the IR spectra of FFPE processed cancerous cell lines undergo small but significant changes due to the treatment. The spectral modifications were interpreted as a potential decrease in the phospholipid content and protein denaturation, in line with the scientific literature on the topic. Nevertheless, unsupervised analyses showed that spectral proximities and distances between closely related cell lines were mostly, but not entirely, conserved after FFPE processing. Finally, PLS-DA statistical analyses highlighted that closely related cell lines are still successfully identified and efficiently distinguished by FTIR spectroscopy after FFPE treatment. This last result paves the way towards identification and characterization of cellular subtypes on FFPE tissue sections by FTIR imaging, indicating that this analysis technique could become a potential useful tool in cancer research.

Modelling plant species distribution in alpine grasslands using airborne imaging spectroscopy.

Remote sensing using airborne imaging spectroscopy (AIS) is known to retrieve fundamental optical properties of ecosystems. However, the value of these properties for predicting plant species distribution remains unclear. Here, we assess whether such data can add value to topographic variables for predicting plant distributions in French and Swiss alpine grasslands. We fitted statistical models with high spectral and spatial resolution reflectance data and tested four optical indices sensitive to leaf chlorophyll content, leaf water content and leaf area index. We found moderate added-value of AIS data for predicting alpine plant species distribution. Contrary to expectations, differences between species distribution models (SDMs) were not linked to their local abundance or phylogenetic/functional similarity. Moreover, spectral signatures of species were found to be partly site-specific. We discuss current limits of AIS-based SDMs, highlighting issues of scale and informational content of AIS data.

Evaluating effects of spectral training data distribution on continuous field mapping performance

Continuous field mapping has to address two conflicting remote sensing requirements when collecting training data. On one hand, continuous field mapping trains fractional land cover and thus favours mixed training pixels. On the other hand, the spectral signature has to be preferably distinct and thus favours pure training pixels. The aim of this study was to evaluate the sensitivity of training data distribution along fractional and spectral gradients on the resulting mapping performance. We derived four continuous fields (tree, shrubherb, bare, water) from aerial photographs as response variables and processed corresponding spectral signatures from multitemporal Landsat 5 TM data as explanatory variables. Subsequent controlled experiments along fractional cover gradients were then based on generalised linear models. Resulting fractional and spectral distribution differed between single continuous fields, but could be satisfactorily trained and mapped. Pixels with fractional or without respective cover were much more critical than pure full cover pixels. Error distribution of continuous field models was non-uniform with respect to horizontal and vertical spatial distribution of target fields. We conclude that a sampling for continuous field training data should be based on extent and densities in the fractional and spectral, rather than the real spatial space. Consequently, adequate training plots are most probably not systematically distributed in the real spatial space, but cover the gradient and covariate structure of the fractional and spectral space well. (C) 2009 International Society for Photogrammetry and Remote Sensing, Inc. (ISPRS). Published by Elsevier B.V. All rights reserved.

An infrared spectral signature of human lymphocyte subpopulations from peripheral blood.

Metastatic melanomas are frequently refractory to most adjuvant therapies such as chemotherapies and radiotherapies. Recently, immunotherapies have shown good results in the treatment of some metastatic melanomas. Immune cell infiltration in the tumor has been associated with successful immunotherapy. More generally, tumor infiltrating lymphocytes (TILs) in the primary tumor and in metastases of melanoma patients have been demonstrated to correlate positively with favorable clinical outcomes. Altogether, these findings suggest the importance of being able to identify, quantify and characterize immune infiltration at the tumor site for a better diagnostic and treatment choice. In this paper, we used Fourier Transform Infrared (FTIR) imaging to identify and quantify different subpopulations of T cells: the cytotoxic T cells (CD8+), the helper T cells (CD4+) and the regulatory T cells (T reg). As a proof of concept, we investigated pure populations isolated from human peripheral blood from 6 healthy donors. These subpopulations were isolated from blood samples by magnetic labeling and purities were assessed by Fluorescence Activated Cell Sorting (FACS). The results presented here show that Fourier Transform Infrared (FTIR) imaging followed by supervised Partial Least Square Discriminant Analysis (PLS-DA) allows an accurate identification of CD4+ T cells and CD8+ T cells (>86%). We then developed a PLS regression allowing the quantification of T reg in a different mix of immune cells (e.g. Peripheral Blood Mononuclear Cells (PBMCs)). Altogether, these results demonstrate the sensitivity of infrared imaging to detect the low biological variability observed in T cell subpopulations.

Combining T2-preparation with spectral and spatial selectivity for improved coronary MRA

Cardiovascular disease is the leading cause of death worldwide. Within this subset, coronary artery disease (CAD) is the most prevalent. Magnetic resonance angiography (MRA) is an emerging technique that provides a safe, non-invasive way of assessing CAD progression. To generate contrast between tissues, MR images are weighted according to the magnetic properties of those tissues. In cardiac MRI, T2 contrast, which is governed by the rate of transverse signal loss, is often created through the use of a T2-Preparation module. T2-Preparation, or T2-Prep, is a magnetization preparation scheme used to improve blood/myocardium contrast in cardiac MRI. T2-Prep methods generally use a non-selective +90°, 180°, 180°, -90° train of radiofrequency (RF) pulses (or variant thereof), to tip magnetization into the transverse plane, allow it to evolve, and then to restore it to the longitudinal plane. A key feature in this process is the combination of a +90° and -90° RF pulse. By changing either one of these, a mismatch occurs between signal excitation and restoration. This feature can be exploited to provide additional spectral or spatial selectivity. In this work, both of these possibilities are explored. The first - spectral selectivity - has been examined as a method of improving fat saturation in coronary MRA. The second - spatial selectivity - has been examined as a means of reducing imaging time by decreasing the field of view, and as a method of reducing artefacts originating from the tissues surrounding the heart. Two additional applications, parallel imaging and self-navigation, are also presented. This thesis is thus composed of four sections. The first, "A Fat Signal Suppression for Coronary MRA at 3T using a Water-Selective Adiabatic T2-Preparation Technique", was originally published in the journal Magnetic Resonance in Medicine (MRM) with co-authors Ruud B. van Heeswijk and Matthias Stuber. The second, "Combined T2-Preparation and 2D Pencil Beam Inner Volume Selection", again with co-authors Ruud van Heeswijk and Matthias Stuber, was also published in the journal MRM. The third, "A cylindrical, inner volume selecting 2D-T2-Prep improves GRAPPA-accelerated image quality in MRA of the right coronary artery", written with co-authors Jerome Yerly and Matthias Stuber, has been submitted to the "Journal of Cardiovascular Magnetic Resonance", and the fourth, "Combined respiratory self-navigation and 'pencil-beam' 2D-T2 -Prep for free-breathing, whole-heart coronary MRA", with co¬authors Jerome Chaptinel, Giulia Ginami, Gabriele Bonanno, Simone Coppo, Ruud van Heeswijk, Davide Piccini, and Matthias Stuber, is undergoing internal review prior to submission to the journal MRM. -- Les maladies cardiovasculaires sont la cause principale de décès dans le monde : parmi celles-ci, les maladies coronariennes sont les plus répandues. L'angiographie par résonance magnétique (ARM) est une technique émergente qui fournit une manière sûre, non invasive d'évaluer la progression de la coronaropathie. Pour obtenir un contraste entre les tissus, les images d'IRM sont pondérées en fonction des propriétés magnétiques de ces tissus. En IRM cardiaque, le contraste en T2, qui est lié à la décroissance du signal transversal, est souvent créé grâce à l'utilisàtion d'un module de préparation T2. La préparation T2, ou T2-Prep, est un système de préparation de l'aimantation qui est utilisé pour améliorer le contraste entre le sang et le myocarde lors d'une IRM cardiaque. Les méthodes de T2-Prep utilisent généralement une série non-sélective d'impulsions de radiofréquence (RF), typiquement [+ 90°, 180°, 180°, -90°] ou une variante, qui bascule l'aimantation dans le plan transversal, lui permet d'évoluer, puis la restaure dans le plan longitudinal. Un élément clé de ce processus est la combinaison des impulsions RF de +90° et -90°. En changeant l'une ou l'autre des impulsions, un décalage se produit entre l'excitation du signal et de la restauration. Cette fonction peut être exploitée pour fournir une sélectivité spectrale ou spatiale. Dans cette thèse, les deux possibilités sont explorées. La première - la sélectivité spectrale - a été examinée comme une méthode d'améliorer la saturation de la graisse dans l'IRM coronarienne. La deuxième - la sélectivité spatiale - a été étudiée comme un moyen de réduire le temps d'imagerie en diminuant le champ de vue, et comme une méthode de réduction des artefacts provenant des tissus entourant le coeur. Deux applications supplémentaires, l'imagerie parallèle et la self-navigation, sont également présentées. Cette thèse est ainsi composée de quatre sections. La première, "A Fat Signal Suppression for Coronary MRA at 3T using a Water-Selective Adiabatic T2-Preparation Technique", a été publiée dans la revue médicale Magnetic Resonance .in Medicine (MRM) avec les co-auteurs Ruud B. van Heeswijk et Matthias Stuber. La deuxième, Combined T2-Preparation and 2D Pencil Beam Inner Volume Selection", encore une fois avec les co-auteurs Ruud van Heeswijk et Matthias Stuber, a également été publiée dans le journal MRM. La troisième, "A cylindrical, inner volume selecting 2D-T2-Prep improves GRAPPA- accelerated image quality in MRA of the right coronary artery", écrite avec les co-auteurs Jérôme Yerly et Matthias Stuber, a été présentée au "Journal of Cardiovascular Magnetic Resonance", et la quatrième, "Combined respiratory self-navigation and 'pencil-beam' 2D-T2 -Prep for free-breathing, whole-heart coronary MRA", avec les co-auteurs Jérôme Chaptinel, Giulia Ginami, Gabriele Bonanno , Simone Coppo, Ruud van Heeswijk, Davide Piccini, et Matthias Stuber, subit un examen interne avant la soumission à la revue MRM.

PET Molecular Imaging of Hypoxia in Ischemic Stroke: An Update.

Hypoxia, a condition of insufficient oxygen availability to support metabolism, occurs when the vascular supply is interrupted, as in stroke. The identification of the hypoxic and viable tissue in stroke as compared with irreversible lesions (necrosis) has relevant implications for the treatment of ischemic stroke. Traditionally, imaging by positron emission tomography (PET), using 15O-based radiotracers, allowed the measurement of perfusion and oxygen extraction in stroke, providing important insights in its pathophysiology. However, these multitracer evaluations are of limited applicability in clinical settings. More recently, specific tracers have been developed, which accumulate with an inverse relationship to oxygen concentration and thus allow visualizing the hypoxic tissue non invasively. These belong to two main groups: nitroimidazoles, and among these the 18F-Fluoroimidazole (18F-FMISO) is the most widely used, and the copper-based tracers, represented mainly by Cu-ATSM. While these tracers have been at first developed and tested in order to image hypoxia in tumors, they have also shown promising results in stroke models and preliminary clinical studies in patients with cardiovascular disorders, allowing the detection of hypoxic tissue and the prediction of the extent of subsequent ischemia and clinical outcome. These tracers have therefore the potential to select an appropriate subgroup of patients who could benefit from a hypoxia-directed treatment and provide prognosis relevant imaging. The molecular imaging of hypoxia made important progress over the last decade and has a potential for integration into the diagnostic and therapeutic workup of patients with ischemic stroke.

High-resolution magnetic resonance imaging quantitatively detects individual pancreatic islets.

OBJECTIVE-We studied whether manganese-enhanced high-field magnetic resonance (MR) imaging (MEHFMRI) could quantitatively detect individual islets in situ and in vivo and evaluate changes in a model of experimental diabetes.RESEARCH DESIGN AND METHODS-Whole pancreata from untreated (n = 3), MnCl(2) and glucose-injected mice (n = 6), and mice injected with either streptozotocin (STZ; n = 4) or citrate buffer (n = 4) were imaged ex vivo for unambiguous evaluation of islets. Exteriorized pancreata of MnCl(2) and glucose-injected mice (n = 6) were imaged in vivo to directly visualize the gland and minimize movements. In all cases, MR images were acquired in a 14.1 Testa scanner and correlated with the corresponding (immuno)histological sections.RESULTS-In ex vivo experiments, MEHFMRI distinguished different pancreatic tissues and evaluated the relative abundance of islets in the pancreata of normoglycemic mice. MEHFMRI also detected a significant decrease in the numerical and volume density of islets in STZ-injected mice. However, in the latter measurements the loss of beta-cells was undervalued under the conditions tested. The experiments on the externalized pancreata confirmed that MEHFMRI could visualize native individual islets in living, anesthetized mice.CONCLUSIONS-Data show that MEHFMRI quantitatively visualizes individual islets in the intact mouse pancreas, both ex vivo and in vivo. Diabetes 60:2853-2860, 2011

Imagerie des BPCO [Imaging of COPD].

Standard chest radiographs have been shown to be insensitive for the diagnosis of morphologic abnormalities of airways. Computed tomography is the most sensitive and specific investigation to diagnose emphysema. However, as emphysema may be missed on computed tomography, this investigation cannot be used to definitely rule out the diagnosis. Computed tomography may contribute to the investigation of bronchiolitis, and it is now considered as the gold standard for establishing the diagnosis of bronchiectasis. Imaging may contribute to identify complications such as bronchopulmonary infection, pulmonary hypertension, pneumothorax, cancer of the lung, compressive bullae, and pulmonary embolism.

Determination of displacement, stress- and strain-distribution in the human heart: a FE-model on the basis of MR imaging.

The determination of characteristic cardiac parameters, such as displacement, stress and strain distribution are essential for an understanding of the mechanics of the heart. The calculation of these parameters has been limited until recently by the use of idealised mathematical representations of biventricular geometries and by applying simple material laws. On the basis of 20 short axis heart slices and in consideration of linear and nonlinear material behaviour we have developed a FE model with about 100,000 degrees of freedom. Marching Cubes and Phong's incremental shading technique were used to visualise the three dimensional geometry. In a quasistatic FE analysis continuous distribution of regional stress and strain corresponding to the endsystolic state were calculated. Substantial regional variation of the Von Mises stress and the total strain energy were observed at all levels of the heart model. The results of both the linear elastic model and the model with a nonlinear material description (Mooney-Rivlin) were compared. While the stress distribution and peak stress values were found to be comparable, the displacement vectors obtained with the nonlinear model were generally higher in comparison with the linear elastic case indicating the need to include nonlinear effects.

Stem cell transplantation in brain tumors: a new field for molecular imaging?

Neural stem cells have been proposed as a new and promising treatment modality in various pathologies of the central nervous system, including malignant brain tumors. However, the underlying mechanism by which neural stem cells target tumor areas remains elusive. Monitoring of these cells is currently done by use of various modes of molecular imaging, such as optical imaging, magnetic resonance imaging and positron emission tomography, which is a novel technology for visualizing metabolism and signal transduction to gene expression. In this new context, the microenvironment of (malignant) brain tumors and the blood-brain barrier gains increased interest. The authors of this review give a unique overview of the current molecular-imaging techniques used in different therapeutic experimental brain tumor models in relation to neural stem cells. Such methods for molecular imaging of gene-engineered neural stem/progenitor cells are currently used to trace the location and temporal level of expression of therapeutic and endogenous genes in malignant brain tumors, closing the gap between in vitro and in vivo integrative biology of disease in neural stem cell transplantation.