MALDI MS Tissue Imaging and Profiling

New Tissue Imaging Lab at the University of Victoria

"With $620,000 in federal funding, the University of Victoria’s Genome B.C. Proteomics Centre at the Vancouver Island Tech Park is now home to the only MALDI imaging equipment in Canada."

UVic lab gets new body mapping tool. in BCLocalNews.com

Imaging Mass Spectrometry in Wikipedia

An entry for "MALDI imaging" was added to Wikipedia last June. Having received the benefit of the initial author's initiative, and several editorial contributions by others, the brief entry is looking pretty good and will no doubt be a help to many.

MALDI imaging in Wikipedia

Tissue Imaging Jobs

Sheffield University's Department of Animal and Plant Sciences have posted two projects on FindAPhD requiring the use of imaging mass spectrometry. One project ("Control of the cell cycle and dormancy in potato tubers") will use tissue imaging with transgenic potatoes to map biochemical changes associated with the transition from dormancy to growth. Another project ("The biochemistry of meristem differentiation") will use tissue imaging to explore the link between tobacco plant stem cell function, the cell cycle, and metabolism.

Tissue imaging jobs at FindAPhD

Applying PCA to IMS Data

A group of researchers from Katholieke Universiteit Leuven have demonstrated the application of principal component analysis (PCA) to imaging mass spec data.

At the 2007 Pacific Symposium on Biocomputing (January 3-7, Maui), the group presented the paper "Prospective Exploration of Biochemical Tissue Composition via Imaging Mass Spectrometry Guided by Principal Component Analysis." The authors note in the paper that there are typically thousands of ion images collected to compose each complete imaging mass spectrometry image data set, and that the volume of data can complicate unassisted scouting projects where the object is to find meaningful variations without the benefit of a priori knowledge of the identity or m/z values of relevant analytes.

"This is why we employ multivariate data analysis methods, such as the principal component analysis discussed in this paper, to perform a preliminary exploration of the data tensor in order to identify spatial and mass trends that merit further investigation."

In a prospective evaluation on rat spinal cord imaging mass spectrometry data, PCA found markers that differentiate white matter tissue from gray matter tissue, and dorsal tissue from ventral tissue, based differences in cellular protein composition between these tissue types.

"In summary, the PCA-results tell us that in this particular IMS data set the chemical composition is dominated by the difference between grey matter nerve tissue and white matter, and two quantitative ion markers for these areas are observed at m/z 5484 and 8564. In addition to that, a ventral/dorsal difference was measured which can be related to known ventral/dorsal differences in the spinal cord."

Raf Van de Plas, Fabian Ojeda, Maarten Dewil, Ludo Van Den Bosch, Bart De Moor, and Etienne Waelkens. "Prospective Exploration of Biochemical Tissue Composition via Imaging Mass Spectrometry Guided by Principal Component Analysis." (944 KB pdf)

Plant Oligosaccharide Analysis by Imaging MALDI

Researchers at the University of York, Syngenta, and Sheffield Hallam University are exploring the use of imaging mass spectrometry to analyze water-soluble oligosaccharides in the stems of wheat. From their paper in the January 2007 issue of New Phytologist,

"A range of oligosaccharides up to Hex₁₁ were observed. Water-soluble oligosaccharides were ionized as potassiated molecules, and found to be located in the stem pith that is retained predominantly around the inner stem wall."

"Imaging MALDI analyses provided spatial information on endogenous oligosaccharides present in wheat stems. The technique was found to offer comparable sensitivities for oligosaccharide detection to those of our established LC-MS method, and has potential for broad application in studying the in situ localization of other compound types in plant material."

Sarah Robinson, Karen Warburton, Mark Seymour, Malcolm Clench, Jane Thomas-Oates (2007)    
Localization of water-soluble carbohydrates in wheat stems using imaging matrix-assisted laser desorption ionization mass spectrometry . New Phytologist 173 (2), 438–444. doi:10.1111/j.1469-8137.2006.01934.x

Protein Discovery Offers Tissue Imaging "By-the-Slice"

Site sponsor Protein Discovery put out a news release this morning announcing their new "Tissue Imaging By-the-Slice" service. According to the release, the new service "reads and delivers tissue imaging MALDI mass spectrometry data from a customer-supplied tissue sample for just $1200."

"The MALDI tissue images contain protein patterns specific to disease states and patient prognosis," said Richard Caprioli PhD, a pioneering researcher in the field of tissue imaging MALDI mass spectrometry. "Data acquisition requires people and facilities, but, once acquired, the data can be interrogated by multiple software platforms at the user's facilities and discretion. Protein Discovery's service means that more groups can look into the value of this technology for use in their research programs," he added.

Protein Discovery's latest newsletter has more information about tissue imaging by-the-slice.

Imaging Mass Spectrometry for Whole-Body Analysis

Part of the difficulty of using whole body autoradiography (WBA) to visualize drug distribution is that it typically takes a long time to develop a radiolabeled version of the compound under study. Then you can track the compound, but not its metabolites. Then, because long half-life compounds like ¹⁴C and ³H produce the best images, you have expensive disposal issues.

Imaging mass spectrometry may offer an attractive alternative. By comparison to WBA, IMS is non-radioactive, requires no separate compound synthesis development, images both drugs and metabolites, and offers the additional ability to correlate protein expression changes with compound distribution.

In the September 15 Analytical Chemistry, Sheerin Khatib-Shahidi et al. compared whole body imaging by imaging mass spectrometry to WBA:

"IMS analysis of tissues from 8 mg/kg olanzapine dosed rats revealed temporal distribution of the drug and metabolites that correlate to previous quantitative whole-body autoradiography studies. This technology will significantly help advance the analysis of novel therapeutics and may provide deeper insight into therapeutic and toxicological processes, revealing at the molecular level the cause of efficacy or side effects..."

Direct molecular analysis of whole-body animal tissue sections by imaging MALDI mass spectrometry.

Khatib-Shahidi S, Andersson M, Herman JL, Gillespie TA, Caprioli RM

Anal Chem. 2006 Sep 15; 78(18): 6448-56

NACB Practice Guidelines

The National Academy of Clinical Biochemistry publishes guidelines on many clinical biochemistry methods, including "The Use of MALDI-TOF Mass Spectrometry Profiling to Diagnose Cancer."

"Mass spectrometry is considered to be particularly well suited to serve as a diagnostic or biomarker discovery tool in cancer, given emerging evidence that during cancer development, cancer cells and/or the surrounding microenvironment generate proteins and peptides of different type and in different concentrations than normal cells. These abnormal tissue distributions can be analyzed by imaging-based mass spectrometry and the patterns compared with controls to identify cancer-specific changes that may prove to be clinically useful."

Table 1 of the document cites these works by investigators who have used tissue imaging to identify cancer markers:

Glioma:

• Imaging mass spectrometry: a new technology for the analysis of protein expression in mammalian tissues. Stoeckli M, Chaurand P, Hallahan DE, Caprioli RM. Nat Med. 2001 Apr ; 7(4): 493-6

Lung:

• Proteomic patterns of tumour subsets in non-small-cell lung cancer. Yanagisawa K, Shyr Y, Xu BJ, Massion PP, Larsen PH, White BC, Roberts JR, Edgerton M, Gonzalez A, Nadaf S, Moore JH, Caprioli RM, Carbone DP. Lancet. 2003 Aug 9; 362(9382): 433-9

Download the National Academy of Clinical Biochemistry's "The Use of MALDI-TOF Mass Spectrometry Profiling to Diagnose Cancer" (123 KB pdf).

Softer ionization. Thicker, wetter slices.

A poster on MassTech's web site presents work by researchers from MassTech and from NIH on an atmospheric pressure MALDI imaging mass spectrometer.

"...it is a softer ionization technique compared with vacuum MALDI and it can be used for thicker tissue slices without drying. AP-MALDI also enables the use of volatile matrices such as DHA (2,6-dihydroxyacetophenone). AP-MALDI-source coupled with ion-trap, QTOF or FT-ICR instruments provides MS/MS possibility for tissue imaging." 

 

Download Atmospheric Pressure MALDI Imaging Mass Spectrometry poster (168KB pdf)

Imaging Mass Spec Talent at FACSS

Don't miss MALDI Tissue Imaging presentations by Pierre Chaurand, Stacy Sherrod, Werner Ens, Jonathan Sweedler, Akos Vertes, and John McLean at this year's Federation of Analytical Chemistry and Spectroscopy Societies meeting, Sept. 24-28 in Lake Buena Vista, Florida. Pay by September 4 to get the advance registration rate.

The 33rd FACSS: Lake Buena Vista, FL
September 24 - 28, 2006