Biomedical Engineering Reference
In-Depth Information
single point with a cursor on the generated imaging. Selected ions for different
compounds are displayed as pseudocolor imaging in which the color intensity
correspond to ion signal abundance. The different compounds are separated based
on mass scan results (MS and/or MS/MS).
Klerk et al. [
142
] reported a new method to deal with extremely large image
hyperspectral datasets. Authors introduced the use of a data format capable of
efficiently storing sparse datasets for multivariate analysis. Recent work has also
demonstrated the feasibility to generate three-dimensional (3D) molecular images
composed of two spatial dimension using MALDI-MS [
59,
143
] and MALDI-MS/
MS imaging technology [
144
] and coregistration of these image volumes to other
imaging modalities such as magnetic resonance imaging (MRI) [
145
] . Norris et al.
[
146
] presented a data processing workflow that they had used to successfully increase
the amount of useful information that could be derived from mass spectrometry
profiling and imaging of biological specimens.
4
Applications to Small Molecular Drug Discovery
and Development
The MALDI-TOF-IMS has been applied to tissue imaging of pharmaceuticals and
their metabolites for supporting drug discovery and development. Drug distribution
is commonly studied by using radiolabeled compounds and autoradiography.
MALDI-TOF-IMS allows for the study of drug distribution using nonradiolabeled
compounds and offers the potential to simultaneously study drug and metabolites.
The IMS assay has been applied to the analysis of animal organ tissue, skin,
whole body, human and animal cancer tissue, and drug formulation. It was also used
for MS imaging study on mammalian cell [
147
] , single neurons [
148,
149
] , bacteria
[
150
], and MS imaging of features smaller than the size of laser beam [
151
] .
4.1
Application to Animal Tissue
4.1.1
Brain
Astemizole [
152
] examined the spatial distribution of astemizole and its metabolites
in rat brain slices with and without perfusion with saline solution. The Sprague-
Dawley rats were treated orally with the drug at 100 mg/kg in 0.4 % methylcellu-
lose. Matrix solution (DHB, 10 ml) coated by 15-20 coats over the entire surface
of tissue sections by a glass reagent sprayer. MALDI-MS/MS images showed the
distribution of astemizole and its metabolite (M-14) in rat brain slice. Astemizole
appeared to be the major drug-related component in rat brain (Fig.
2
).
Clozapine and norclozapine [
52
] were used as model compounds to investigate
fundamental parameters such as matrix and solvent effects and irradiance dependence
