MS imaging methods

Today, M S imaging is perceived as a rather new - but very promising - approach, not only for the basic sciences but also for clinical diagnosis [156]. Although other MS imaging methods based on desorption electrospray-ionization (DESI) MS [157] or secondaryion mas s spectrometry (SIMS)are currently available (for a timely review, see Ref. [158]), attention here will be focused exclusively on MALDI-MS imaging. The same technique is also discussed comprehensively in Chapter 4 of this book. 

Al 1] Musgrave, et al., Ms imaging telephone security module and method, United States Patent 6.377.699, April 23, 2002... 

Han and Schey [71] used a special matrix coating method in processing the bovine lenses sections (30 10 pm) for MS imaging. The tissue sections were first sprayed with an acetonitrile-water (50 50, vol/vol) solution resulting in a tightly bound section. After drying, the tissue sections were coated with a thin layer matrix of S A at 15 mg/mL in ethanol-water (50 50, vol/vol). After it was dried, the tissue sections were finally sprayed with several cycles of SA matrix solution at 15 mg/mL in ethanol-water-formic acid (44 44 12, vol/vol/vol). 

Klerk L, Broersen A, Fletcher I, Liere R, Heeren R (2007) Extended data analysis strategies for high resolution imaging MS new method to deal with extremely large image hyperspec-tral datasets. Int 1 Mass Spectrom 260 222-236. doi 10.1016/j.ijms.2006.11.014... 

Since the first edition of this book in 2007 there has been a considerable increase in the ability to apply MALDI-MS to the analysis of lipids, and this has been clearly reflected by the numbers of reports on the subject made during the past decade (see Figure 7.1). Whilst interest in Upids has emerged for a variety of reasons, most notably their potential role(s) as markers of disease (as discussed below), another important factor here has been the steady increase in the use of MS imaging techniques in general [1]. The use of these methods, and in particular their application to the spatially resolved analysis of metabolite distribution in thin tissue slices, are discussed in Chapter 4, Section 4.7.1 of this book. 

The discussed mass spectrometry-based imaging techniques can be easily implemented for visualization and identification of the compounds separated by TLC. MS-based methods need to be appropriately arranged and optimized before the experiment, which costs a significant amount of time and additional reagents. However, their advantages, such as unambiguous identification of the compounds separated on the plate and visualization of every spot, independently from the quality of the separation itself, make them the perfect choice for detection in combination with the very simple TLC separation technology. 

Fig. 1.5. DESI imaging of a dmg in lung tissue, (a) Optical image, (b) Image of clozapine at m/z 327.1. (c) Image of desmethyldozapine at m/z 313.1. (d) Image of sodiated PC 16 0/16 0 at miz 756.4. (e) DESI-MS imaging and LC/MS/MS results. The signal response In each method was normalized to the maximum response in each experiment and plotted against the clozapine plasma concentration as determined by LC/MS. (Reprinted with permission from ref. (67).)...

Matrix-assisted laser desorption/ionization-tandem mass spectrometric method (MALDI-MS/MS) has proven to be a reliable tool for direct measurement of the disposition of small molecules in animal tissue sections. As example, MALDI-MS/MS imaging system was employed for visualizing the spatial distribution of astemizole and its primary metabolite in rat brain tissues. Astemizole is a second-generation antihistamine, a block peripheral HI receptor, which was introduced to provide comparable therapeutic benefit but was withdrawn in most countries due to toxicity risks. Astemizole was observed to be heterogeneously distributed to most parts of brain tissue slices including cortex, hippocampus, hypothalamic, thalamus, and ventricle regions while its major metabolite, desmethylastemizole, was only found around ventricle sites. We have shown that astemizole alone is likely to be responsible for the central nervous system (CNS) side effects when its exposures became elevated. 

The methods presented here describe the ability to characterize phosphatidylcholines (PCs), sphingomyelins (SPMs), phos-phatidylserines (PSs), and phosphatidylethanolamines (PEs) in the positive ion mode from rat brain tissue sections using imaging tandem MS and the creation of compound-specific images from full-scan MS and MS, while using MS for the final identification. The use of MS images for the separation of isobaric ions coupled with the ability to perform MS provides the means to identify isobaric species present in the tissue section. 

One generation of in vivo scanners now commercially available is capable of a read-out time of 20 ms but with a correspondingly limited spatial resolution (>100 p,m). These scanners are typically used in combination with functional imaging methods, like micro-PET and other nuclear imaging methods, or to make dynamic measurements. 

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