MALDI imaging mass spectrometry for direct tissue analysis: a new frontier for molecular histology.
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ABSTRACT:
SUBMITTER: Walch A
PROVIDER: S-EPMC2522327 | biostudies-other | 2008 Sep
REPOSITORIES: biostudies-other
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Project description:MALDI Imaging Mass Spectrometry is a molecular analytical technology capable of simultaneously measuring multiple analytes directly from intact tissue sections. Histological features within the sample can be correlated with molecular species without the need for target-specific reagents such as antibodies. Several studies have demonstrated the strength of the technology for uncovering new markers that correlate with disease severity as well as prognosis and therapeutic response. This review describes technological aspects of imaging mass spectrometry together with applications in cancer research.
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Project description:Matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) combines information-rich chemical detection with spatial localization of analytes. For a given instrumental platform and analyte class, the data acquired can represent a compromise between analyte extraction and spatial information. Here, we introduce an improvement to the spatial resolution achievable with MALDI MSI conducted with standard mass spectrometric systems that also reduces analyte migration during matrix application. Tissue is placed directly on a stretchable membrane that, when stretched, fragments the tissue into micrometer-sized pieces. Scanning electron microscopy analysis shows that this process produces fairly homogeneous distributions of small tissue fragments separated and surrounded by areas of hydrophobic membrane surface. MALDI matrix is then applied by either a robotic microspotter or an artist's airbrush. Rat spinal cord samples imaged with an instrumental resolution of 50-250 μm demonstrate lipid distributions with a 5-fold high spatial resolution (a 25-fold increase in pixel density) after stretching compared to tissues that were not stretched.
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Project description:Matrix assisted laser desorption ionization imaging mass spectrometry (MALDI IMS) has the ability to provide an enormous amount of information on the abundances and spatial distributions of molecules within biological tissues. The rapid progress in the development of this technology significantly improves our ability to analyze smaller and smaller areas and features within tissues. The mammalian eye has evolved over millions of years to become an essential asset for survival, providing important sensory input of an organism's surroundings. The highly complex sensory retina of the eye is comprised of numerous cell types organized into specific layers with varying dimensions, the thinnest of which is the 10 ?m retinal pigment epithelium (RPE). This single cell layer and the photoreceptor layer contain the complex biochemical machinery required to convert photons of light into electrical signals that are transported to the brain by axons of retinal ganglion cells. Diseases of the retina, including age-related macular degeneration (AMD), retinitis pigmentosa, and diabetic retinopathy, occur when the functions of these cells are interrupted by molecular processes that are not fully understood. In this report, we demonstrate the use of high spatial resolution MALDI IMS and FT-ICR tandem mass spectrometry in the Abca4(-/-) knockout mouse model of Stargardt disease, a juvenile onset form of macular degeneration. The spatial distributions and identity of lipid and retinoid metabolites are shown to be unique to specific retinal cell layers.
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Project description:PURPOSE:A new method accessing proteins from extracellular matrix by imaging mass spectrometry (ECM IMS) has been recently reported. ECM IMS is evaluated for use in exploring breast tissue pathologies. EXPERIMENTAL DESIGN:A tissue microarray (TMA) is analyzed that has 176 cores of biopsies and lumpectomies spanning breast pathologies of inflammation, hyperplasia, fibroadenoma, invasive ductal carcinoma, and invasive lobular carcinoma and normal adjacent to tumor (NAT). NAT is compared to subtypes by area under the receiver operating curve (ROC) >0.7. A lumpectomy is also characterized for collagen organization by microscopy and stromal protein distribution by IMS. LC-based high-resolution accurate mass (HRAM) proteomics is used to identify proteins from the lumpectomy. RESULTS:TMA analysis shows distinct spectral signatures reflecting a heterogeneous tissue microenvironment. Ninety-four peaks show an ROC > 0.7 compared to NAT; NAT has overall higher intensities. Lumpectomy analysis by IMS visualizes a complex central tumor region with distal tumor regions. A total of 39 stromal proteins are identified by HRAM LC-based proteomics. Accurate mass matches between image data and LC-based proteomics demonstrate a heterogeneous collagen type environment in the central tumor. CONCLUSIONS:Data portray the heterogeneous stromal microenvironment of breast pathologies, including alteration of multiple collagen-type patterns. ECM IMS is a promising new tool for investigating the stromal microenvironment of breast tissue including cancer.
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Project description:A novel MALDI-FTICR imaging mass spectrometry (MALDI-IMS) workflow is described for on-tissue detection, spatial localization, and structural confirmation of low abundance bioactive ceramides and other sphingolipids. Increasingly, altered or elevated levels of sphingolipids, sphingolipid metabolites, and sphingolipid metabolizing enzymes have been associated with a variety of disorders such as diabetes, obesity, lysosomal storage disorders, and cancer. Ceramide, which serves as a metabolic hub in sphingolipid metabolism, has been linked to cancer signaling pathways and to metabolic regulation with involvement in autophagy, cell-cycle arrest, senescence, and apoptosis. Using kidney tissues from a new Farber disease mouse model in which ceramides of all acyl chain lengths and other sphingolipid metabolites accumulate in tissues, specific ceramides and sphingomyelins were identified by on-tissue isolation and fragmentation, coupled with an on-tissue digestion by ceramidase or sphingomyelinase. Multiple glycosphingolipid species were also detected. The newly generated library of sphingolipid ions was then applied to MALDI-IMS of human lung cancer tissues. Multiple tumor specific ceramide and sphingomyelin species were detected and confirmed by on-tissue enzyme digests and structural confirmation. High-resolution MALDI-IMS in combination with novel on-tissue ceramidase and sphingomyelinase enzyme digestions makes it now possible to rapidly visualize the distribution of bioactive ceramides and sphingomyelin in tissues.
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Project description:Utilization of MALDI-MS (matrix-assisted laser desorption/ionization mass spectrometry) for tissue imaging is a relatively new proteomic technique that simultaneously maps the spatial distribution of multiple proteins directly within a single frozen tissue section. Here, we report the development of a methodology to apply MALDI tissue imaging to chick heart tissue sections acquired from fixed and paraffin-embedded samples. This protocol produces molecular images that can be related to the high-quality histological tissue sections. Perfused term chick hearts were fixed in acidic ethanol and embedded in paraffin wax. Tissue sections (15 microm) were collected onto conductive slides, deparaffinized with xylene, and transitioned into water with graded ethanol washes and allowed to air dry. In separate experiments, three different MALDI matrices were applied to chick heart tissue sections through repeated cycles from a glass nebulizer. Tissue sections were then analyzed by MALDI mass spectrometry using a raster step-size of 75-100 microm, and molecular images for specific m/z ratios reconstituted. MALDI tissue imaging revealed spatially resolved protein signals within single heart sections that are specific to structures or regions of the heart, for example, vessels, valves, endocardium, myocardium, or septa. Moreover, no prior knowledge of protein expression is required as is the case for immunohistochemistry and in situ hybridization methodologies. The ability to simultaneously localize a large number of unique protein signals within a single tissue section, with good preservation of histological features, provides cardiovascular researchers a new tool to give insight into the molecular mechanisms underlying normal and pathological conditions.
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