Tissue imaging using MALDI-MS: a new frontier of histopathology proteomics

Modern pathology is an amalgam of many disciplines, such as microbiology, biochemistry and immunology, which historically have been intermingled with the practice of clinical medicine. For centuries, the pre-eminent pathological tool, at least in the context of patients, was a post-mortem examination. With the advent of optical microscopes, morphology became a predominant means of developing tissue classification. A further paradigm shift occurred in the attempt to understand the nature and origin of disease; the recognition that, ultimately, it is the derangement in the structure and function of genes and proteins that causes human disease. More recent progress in pathology has led to the use of genomics and molecular technologies, including DNA sequencing, microarray analysis, PCR, in situ hybridization and proteomics. Today, the newest frontier appears to be histopathology proteomics, which adds the mass spectrometer to the arsenal of tools for the direct analysis of tissue biopsies and molecular diagnosis. Typically called MALDI imaging, this technique takes mass spectral snapshots of intact tissue slices, revealing how proteins and peptides are spatially distributed within a given sample. In this review, MALDI imaging technology is presented as well as applications of such technology in cancer or neurodegenerative diseases.     

Molecular histology of arteries: mass spectrometry imaging as a novel ex vivo tool to investigate atherosclerosis

Atherosclerosis is usually the underlying cause of a fatal event such as myocardial infarction or ictus. The atherome plaque develops silently and asymptomatically within the arterial intima layer. In this context, the possibility to analyze the molecular content of arterial tissue while preserving each molecule’s specific localization is of great interest as it may reveal further insights into the physiopathological changes taking place. Mass spectrometry imaging (MSI) enables the spatially resolved molecular analysis of proteins, peptides, metabolites, lipids and drugs directly in tissue, with a resolution sufficient to reveal molecular features specific to distinct arterial structures. MSI represents a novel ex vivo imaging tool still underexplored in cardiovascular diseases. This review focuses on the MSI technique applied to cardiovascular disease and covers the main contributions to date, ongoing efforts, the main challenges and current limitations of MSI.     

Infrared imaging microscopy of bone: Illustrations from a mouse model of Fabry disease

Bone is a complex tissue whose composition and properties vary with age, sex, diet, tissue type, health and disease. In this review, we demonstrate how infrared spectroscopy and infrared spectroscopic imaging can be applied to the study of these variations. A specific example of mice with Fabry disease (a lipid storage disease) is presented in which it is demonstrated that the bones of these young animals, while showing typical spatial variation in mineral content, mineral crystal size, and collagen maturity, do not differ from the bones of age- and sex-matched wild type animals.     

2-Arylimidazo[2,1-b]benzothiazoles: a new family of amyloid binding agents with potential for PET and SPECT imaging of Alzheimer's brain

We designed and synthesized a small series of 2-aryl-imidazo[2,1-b]benzothiazole, representing a combination of motifs from the two most potent amyloid imaging agents, PIB and IMPY. The binding affinity of the new compounds ranged from 6 to 133 nM. Among the best compounds, 3b (K_i = 6 nM) can be labeled with ¹¹CH₃ for PET imaging whereas 3j (K_i = 10.9 nM) can be labeled with ¹²³I for SPECT imaging.     

Improvement of the contrast in cancer detection by autofluorescence bronchoscopy using a narrowband spectral violet excitation: A preliminary study

Autofluorescence (AF) bronchoscopy is a useful tool for early cancer detection. However, the mechanisms involved in this diagnosis procedure are poorly understood. We present a clinical autofluorescence imaging study to assess the depth of the principal contrast mechanisms within the bronchial tissue comparing a narrowband (superficial) and broadband (penetrating) violet excitation. Knowledge of this parameter is crucial for the optimization of the spectral and optical design of clinical diagnostic AF imaging devices. An intensity contrast improvement was observed with the narrowband excitation, suggesting that the heme absorption plays a key role in the AF contrast mechanism.