BERKELEY, CA (UroToday.com) - The development, in the late 1990’s, of practically useful molecular imaging techniques based on mass spectrometry (MS), represented a significant advance for biological tissue analysis.1, 2
The current strong interest in molecular imaging by MS is due to the enormous amount of detailed chemical information provided. More recently, an exciting new version of the imaging MS experiment (DESI imaging) has been developed which requires no prior sample preparation and in which imaging is done in the ambient environment. One can spray a tissue section with charged aqueous droplets, record mass spectra as the spray is moved across the surface, and plot the data in the form of a 2D image of any compound of interest in the tissue. The DESI experiment gives information that allows diseased and healthy tissue to be discriminated; it even allows grades of some tumors to be assigned. Imaging MS is at an exciting crossroads as it transitions from instrumentation research to applications, especially clinical applications. It is reasonable to expect that these diagnostic experiments will soon be implemented in pathology laboratories within hospital surgical suites.
Prior to the development of molecular imaging MS methods, traditional chemical analysis of biological tissue by MS was performed by extensive (and tedious) sample preparation and chromatographic separation. The first of the ambient ionization techniques, desorption electrospray ionization (DESI) was introduced by our group in 2004.3, 4 The advent of DESI added to the imaging MS revolution by providing a means to analyze samples with little to no sample preparation, without the need for matrix application and in the open environment. Ions in DESI are produced through a ‘droplet pickup’ mechanism, where initial micron-sized charged droplets moving at more than 100 m/s impact a sample surface, wetting it and allowing analytes to dissolve.5 Subsequent droplet collisions at the surface produce analyte-containing secondary droplets from which ion formation occurs.5 The later stages of the process are very similar to those that occur in solution analysis using the very well known technique of electrospray ionization (ESI).
In the last six years, we have worked to expand the utility of imaging by DESI-MS. This was made possible by collaborations with clinicians willing to pursue this line of research. To date we have shown that diagnosis of animal and human genitourinary cancers in bladder, kidney, prostate and germ tissue can be achieved on the basis of the lipid profiles of thin tissue sections as measured by imaging DESI-MS.6-10 Moreover, different grades of human gliomas can be discriminated on the basis of the DESI-MS lipid profiles acquired during imaging.11 In this recent study of kidney cancer, we used DESI-MS imaging to interrogate the lipid profiles of 11 sample pairs of human papillary renal cell carcinoma (RCC) and adjacent normal tissue and 9 sample pairs of clear cell RCC and adjacent normal tissue.8 DESI-MS in conjunction with multivariate statistical analysis, allowed successful discrimination of each type of tumor when compared with paired normal tissue. It also allowed the distinction between papillary and clear cell RCC, both from each other and from the combined normal tissues.8
Surgery remains the most important and usually first treatment modality for the majority of solid tumors. While maximum surgical excision with the goal of gross total tumor resection is desirable, in practice, delineation of resection margins is very difficult because tumors can closely resemble or often infiltrate normal tissue. Intra-operatively acquired molecular images could provide surgeons with the information needed to perform real-time, image-guided surgery. Ambient ionization techniques, such as DESI, have characteristic ease and speed of execution, and we believe this approach will allow in situ analysis of tissue to assist in intraoperative surgical decision-making. Note that the required invasive nature of these imaging methods is successfully juxtaposed against this necessary characteristic of surgery. As the possibility of these clinical applications increases, larger more diverse sample populations will be necessary for validation and with these come increasing demands of data reduction and data processing. With all opportunities come challenges but it seems likely that these will be overcome and imaging MS has the potential to be widely used in biomedicine.
- Chughtai, K.; Heeren, R. M. A., Mass Spectrometric Imaging for Biomedical Tissue Analysis. Chem. Rev. 2010, 110, (5), 3237-3277.
- van Hove, E. R. A.; Smith, D. F.; Heeren, R. M. A., A concise review of mass spectrometry imaging. J. Chromatogr. A 2010, 1217, (25), 3946-3954.
- Takats, Z.; Wiseman, J. M.; Gologan, B.; Cooks, R. G., Mass spectrometry sampling under ambient conditions with desorption electrospray ionization. Science 2004, 306, (5695), 471-473.
- Wiseman, J. M.; Ifa, D. R.; Song, Q.; Cooks, R. G., Tissue Imaging at Atmospheric Pressure using Desorption Electrospray Ionization (DESI) Mass Spectrometry. Angew. Chem. Int. Edit. 2006, 45, (43), 7188-7192.
- Costa, A. B.; Cooks, R. G., Simulated splashes: Elucidating the mechanism of desorption electrospray ionization mass spectrometry. Chem. Phys. Lett. 2008, 464, (1-3), 1-8.
- Dill, A. L.; Ifa, D. R.; Manicke, N. E.; Costa, A. B.; Ramos-Vara, J. A.; Knapp, D. W.; Cooks, R. G., Lipid Profiles of Canine Invasive Transitional Cell Carcinoma of the Urinary Bladder and Adjacent Normal Tissue by Desorption Electrospray Ionization Imaging Mass Spectrometry. Anal. Chem. 2009, 81, (21), 8758-8764.
- Dill, A. L.; Eberlin, L. S.; Costa, A. B.; Zheng, C.; Ifa, D. R.; Cheng, L.; Masterson, T. A.; Koch, M. O.; Vitek, O.; Cooks, R. G., Multivariate Statistical Classification of Human Bladder Carcinomas using Ambient Ionization Imaging Mass Spectrometry. Chem.--Eur. J. 2010, in press.
- Dill, A.; Eberlin, L.; Zheng, C.; Costa, A.; Ifa, D.; Cheng, L.; Masterson, T.; Koch, M.; Vitek, O.; Cooks, R., Multivariate statistical differentiation of renal cell carcinomas based on lipidomic analysis by ambient ionization imaging mass spectrometry. Anal. Bioanal. Chem. 2010, 398, (7), 2969-2978.
- Eberlin, L. S.; Dill, A. L.; Costa, A. B.; Ifa, D. R.; Cheng, L.; Masterson, T.; Koch, M.; Ratliff, T. L.; Cooks, R. G., Cholesterol Sulfate Imaging in Human Prostate Cancer Tissue by Desorption Electrospray Ionization Mass Spectrometry. Anal. Chem. 2010, 82, (9), 3430-3434.
- Masterson, T. A.; Dill, A. L.; Eberlin, L. S.; Mattarozzi, M.; Cheng, L.; Koch, M. O.; Bianchi, F.; Cooks, R. G., Distinctive Glycerophospholipid Profiles of Human Seminoma and Adjacent Normal Tissues by Desorption Electrospray Ionization Imaging Mass Spectrometry. J. Am. Soc. Mass. Spectrom. 2010, Submitted.
- Eberlin, L. S.; Dill, A. L.; Golby, A. J.; Ligon, K. L.; Wiseman, J. M.; Cooks, R. G.; Agar, N. Y. R., Discrimination of Human Astrocytoma Subtypes by Lipid Analysis Using Desorption Electrospray Ionization Imaging Mass Spectrometry. Angew. Chem. Int. Edit. 2010, 49, (34), 5953-5956.
Allison L. Dill, Livia S. Eberlin, R. Graham Cooks, Timothy A. Masterson, and Michael O. Koch as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.