title: Connecting imaging mass spectrometry and magnetic resonance imaging-based anatomical atlases for automated anatomical interpretation and differential analysis.
abstract: Imaging mass spectrometry (IMS) is a molecular imaging technology that can measure thousands of biomolecules concurrently without prior tagging, making it particularly suitable for exploratory research. However, the data size and dimensionality often makes thorough extraction of relevant information impractical. To help guide and accelerate IMS data analysis, we recently developed a framework that integrates IMS measurements with anatomical atlases, opening up opportunities for anatomy-driven exploration of IMS data. One example is the automated anatomical interpretation of ion images, where empirically measured ion distributions are automatically decomposed into their underlying anatomical structures. While offering significant potential, IMS-atlas integration has thus far been restricted to the Allen Mouse Brain Atlas (AMBA) and mouse brain samples. Here, we expand the applicability of this framework by extending towards new animal species and a new set of anatomical atlases retrieved from the Scalable Brain Atlas (SBA). Furthermore, as many SBA atlases are based on magnetic resonance imaging (MRI) data, a new registration pipeline was developed that enables direct non-rigid IMS-to-MRI registration. These developments are demonstrated on protein-focused FTICR IMS measurements from coronal brain sections of a Parkinson's disease (PD) rat model. The measurements are integrated with an MRI-based rat brain atlas from the SBA. The new rat-focused IMS-atlas integration is used to perform automated anatomical interpretation and to find differential ions between healthy and diseased tissue. IMS-atlas integration can serve as an important accelerator in IMS data exploration, and with these new developments it can now be applied to a wider variety of animal species and modalities. This article is part of a Special Issue entitled: MALDI Imaging, edited by Dr. Corinna Henkel and Prof. Peter Hoffmann.
authors.affiliation: Delft Center for Systems and Control (DCSC), Delft University of Technology, Mekelweg 2, 2628 CD Delft, the Netherlands. Electronic address: n.verbeeck@tudelft.nl.
authors.forename: Nico
authors.initials: N
authors.lastname: Verbeeck
authors.affiliation: Mass Spectrometry Research Center (MSRC), Vanderbilt University, 465 21st Ave. South, 9160 Medical Research Building III, Nashville, TN 37240, USA; Department of Biochemistry, Vanderbilt University, 607 Light Hall, Nashville, TN 37205, USA; Department of Chemistry, Vanderbilt University, 7330 Stevenson Center Station B 351822, Nashville, TN 37235, USA. Electronic address: jeff.spraggins@vanderbilt.edu.
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Spraggins
authors.affiliation: Program in Neuroscience, Vanderbilt University, U-1205 Medical Research Building III, 465 21st Ave. South, Nashville, TN 37232, USA. Electronic address: monika.murphy@vanderbilt.edu.
authors.forename: Monika J M
authors.initials: MJM
authors.lastname: Murphy
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, 1211 Medical Center Dr. Nashville, TN 37232, USA. Electronic address: huidong.wang@vanderbilt.edu.
authors.forename: Hui-Dong
authors.initials: HD
authors.lastname: Wang
authors.affiliation: Program in Neuroscience, Vanderbilt University, U-1205 Medical Research Building III, 465 21st Ave. South, Nashville, TN 37232, USA; Department of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, 1211 Medical Center Dr. Nashville, TN 37232, USA; Department of Pharmacology, Vanderbilt University, Nashville, 460B Preston Research Building, Nashville, TN 37232, USA. Electronic address: ariel.deutch@vanderbilt.edu.
authors.forename: Ariel Y
authors.initials: AY
authors.lastname: Deutch
authors.affiliation: Mass Spectrometry Research Center (MSRC), Vanderbilt University, 465 21st Ave. South, 9160 Medical Research Building III, Nashville, TN 37240, USA; Department of Biochemistry, Vanderbilt University, 607 Light Hall, Nashville, TN 37205, USA; Department of Chemistry, Vanderbilt University, 7330 Stevenson Center Station B 351822, Nashville, TN 37235, USA; Department of Medicine, Vanderbilt University Medical Center, 1161 21st Ave. South, D-3100 Medical Center North, Nashville, TN 37232, USA. Electronic address: richard.m.caprioli@vanderbilt.edu.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Caprioli
authors.affiliation: Delft Center for Systems and Control (DCSC), Delft University of Technology, Mekelweg 2, 2628 CD Delft, the Netherlands; Mass Spectrometry Research Center (MSRC), Vanderbilt University, 465 21st Ave. South, 9160 Medical Research Building III, Nashville, TN 37240, USA; Department of Biochemistry, Vanderbilt University, 607 Light Hall, Nashville, TN 37205, USA. Electronic address: raf.vandeplas@tudelft.nl.
authors.forename: Raf
authors.initials: R
authors.lastname: Van de Plas
mesh_terms: D000818:Animals; D001921:Brain / Q000033:anatomy & histology* / Q000378:metabolism / Q000473:pathology; D007091:Image Processing, Computer-Assisted / Q000379:methods; D021621:Imaging, Three-Dimensional / Q000379:methods; D007477:Ions / Q000378:metabolism; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D013058:Mass Spectrometry / Q000379:methods*; D051379:Mice; D010300:Parkinson Disease / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D007477:Ions
keywords: Anatomical atlas; FTICR MS; Imaging mass spectrometry; MRI; Rat brain