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MSACL 2020 US : Basu

MSACL 2020 US Abstract

Topic: Imaging

Podium Presentation in the Ether on Wednesday at 9:00 (Chair: Peggi Angel / Anna Krieger)

A Rapid MALDI Mass Spectrometry Imaging Method to Complement the Frozen Section Procedure in Surgical Pathology

Sankha Basu (Presenter)
Brigham and Women’s Hospital, Harvard Medical School

Presenter Bio(s): I am currently the Assistant Director of Clinical Chemistry and Mass Spectrometry at the Brigham and Women’s Hospital (BWH) and Instructor of Pathology at Harvard Medical School. After completing my undergraduate studies in Biology and Chemical Engineering at MIT, I obtained my M.D. and Ph.D. (Pharmacology) degrees from the University of Pennsylvania School of Medicine, where I performed my thesis research in the laboratory of Dr. Ian Blair. Following this, I came to BWH, where I completed a residency in Clinical Pathology, a clinical fellowship in Medical Microbiology and a post-doctoral research fellowship under the supervision of Dr. Nathalie Agar, before joining the Pathology faculty in 2019. My clinical and research interests include mass spectrometry-based applications in the clinical laboratory.

Authors: Sankha S. Basu (1), Michael S. Regan (2), Elizabeth C. Randall (3), Walid M. Abdelmoula (2), Amanda R. Clark (2), Begoña Gimenez-Cassina Lopez (2), Dale S. Cornett (4), Andreas Haase (5), Sandro Santagata (1,6), and Nathalie Y.R. Agar (2,3,7)
(1) Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts 02115, United States (2) Department of Neurosurgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts 02115, United States (3) Department of Radiology, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts 02115, United States (4) Bruker Daltonics, Billerica, MA 01821, United States (5) Bruker Daltonik, Bremen, Germany (6) Ludwig Center at Harvard, Harvard Medical School, Boston, Massachusetts 02115, United States (7) Department of Cancer Biology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, United States

Abstract

Introduction: The frozen section procedure (FSP) is a century-old technique used by surgeons and pathologists for intraoperative tissue analysis. The procedure involves tissue excision, specimen transport, cryo-sectioning, and histopathological assessment. Although the FSP remains the standard method for intraoperative tissue assessment due to its fast turnaround time, it is largely limited to hematoxylin and eosin (H&E) staining only. Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) has emerged as a promising analytical technique capable of providing spatially-resolved biochemical characterization of tissue specimens. However, extensive pre-analytical steps, combined with long acquisition times have limited its clinical translation. Here, we present a rapid MALDI MSI method for tissue assessment, providing a method which can be utilized in the frozen section room.

Methods: To improve MALDI MSI turnaround time, we shortened or eliminated the three most time-consuming steps, namely, matrix application, acquisition set-up, and data acquisition. We effectively eliminated matrix application time by mounting tissue sections on indium tin oxide (ITO) slides with pre-coated matrix. Next, we used a templated ITO slide with a pre-selected region for analysis, eliminating the need for high resolution scanning, image registration, and region of interest selection. Finally, to reduce data acquisition time, we used a high frequency laser and optimized the firing pattern to provide the highest quality ion images. The optimized method was applied to tissue specimens and compared with conventional MALDI MSI approaches. Finally, we used high dimensional data visualization and automated multi-modal integration to align MSI and H&E stained images.

Results: After optimization, we were able to image tissue specimens with a total preparation and run time of less than five minutes, with data quality comparable to conventional MALDI MSI methods. We then applied this “streamlined” method to cryo-sectioned brains from healthy mice which highlighted the major landmarks of the mouse brain. We also used the technique in a patient derived xenograft (PDX) model of glioblastoma, as well as surgically resected human breast and brain specimens, each demonstrating unique metabolomic signatures. We then used t-distributed stochastic neighbor embedding (t-SNE) algorithm to reduce the high dimensional data, which was then spatially projected onto the tissue specimens to reveal molecularly defined structures not apparent histologically, thereby enhancing the diagnostic power of the frozen section procedure.

Conclusions: We present a MALDI MSI method that can be completed in under five minutes including preparation and run time. This can serve as a complementary tool to histopathology during the frozen section procedure to help surgeons and pathologists provide improved diagnostic capabilities.


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