15th European Molecular Imaging Meeting
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Correlated Multimodal Imaging in Life Sciences - COMULIS (COST Action)

Session chair: Andreas Walter (COMULIS, Vienna, Austria)
 
Shortcut: PRO 02
Date: Tuesday, 25 August, 2020, 10:30 a.m. - 12:00 p.m.
Session type: Project Session

COMULIS (Correlated Multimodal Imaging in Life Sciences) is an EU-funded COST Action that aims at fueling urgently needed collaborations in the field of correlated multimodal imaging (CMI), promoting and disseminating its benefits through showcase pipelines, and paving the way for its technological advancement and implementation as a versatile tool in biological and preclinical research - www.comulis.eu.

Contents

Abstract/Video opens by clicking at the talk title.

10:30 a.m. SG02-01

Introduction to COMULIS

Martina Marchetti-Deschmann1

1 Vienna University of Technology, Vienna, Austria

Content

COMULIS (Correlated Multimodal Imaging in Life Sciences) is an EU-funded COST Action that aims at fueling urgently needed collaborations in the field of correlated multimodal imaging (CMI), promoting and disseminating its benefits through showcase pipelines, and paving the way for its technological advancement and implementation as a versatile tool in biological and preclinical research.

Keywords: COMULIS
10:40 a.m. Pro 02-02

Recent advances in multimodal nonlinear microscopy

Peter Friedl1, 2

1 Radboudumc, Nijmegen, Netherlands
2 MD Anderson Cancer Center, Houston, United States of America

Content

Nonlinear processes enable the generation of multimodal signals from 3D tissues with relevance for preclinical and clinical applications. Recently developed next-generation high-power lasers with low repetition rate (1-2 MHz) in the infrared range (1300-1700 nm) allow to simultaneously generate multimodal excitation of fluorophores, including 2-, 3- and 4-photon excitation, together with second and third harmonic generation. This enables up to 8-channel recoding of cell and tissue microanatomy and biology, and further improves microscopy in deep tissue regions by 50 to 100%, without the needs for multiple laser lines. Far-red intravital microscopy thus allows the coregistration of structural and molecular tissue features in healthy and disease tissues in vivo.

Keywords: Multimodal microscopy
11:00 a.m. Pro 02-03

Multi-modal imaging in preclinical heart:brain research

Adriana A. S. Tavares1

1 University of Edinburgh, Edinburgh, United Kingdom

Content

Imaging techniques have been the putative eyes of science for a number of years. From tissue imaging to in vivo multi-organ imaging, major breakthroughs have been pillared on the use of these techniques to test scientific hypothesis. In recent years there has been a huge interest in understanding how multiple organ systems work seamlessly together to maintain body function in heath and respond to insult during disease. For example, recent excitement has been generated around the identification of a brain:heart inflammation axis following myocardial infarction in humans and mice [1]. This discovery was made by using positron emission tomography (PET) imaging techniques with radiotracers targeting the 18 kDa translocator protein (TSPO). Our group has been interested in developing improved TSPO probes for PET imaging, as well as, improved quantification methods of cardiovascular function in heath and disease. We have developed 18F-LW223, a new TSPO PET radiotracer with binding to human tissue independent of the known rs6971 genetic polymorphism that limits clinical use of many second generation TSPO radiotracers [2]. Using a rat model of myocardial infarction, we were able to characterise infarct properties by ultrasound imaging (US) and tissue inflammation with PET/computed tomography (CT) imaging and 18F-LW223. Our 18F-LW223 PET data corroborates existence of an inflammatory heart:brain axis in rats post-myocardial infarction, similarly to previous observations in mice and humans. Following in vivo imaging characterisation, we explanted the heart and brain tissues to dissect the cell responses underlying the measured PET signal in vivo. By making use of immunofluorescent (IHF) techniques, we were able to demonstrate that 18F-LW223 distribution measured by PET in vivo was detecting macrophage-driven inflammation in the hypoperfused myocardium following myocardial infarction. IHF techniques have also been used to validate expression of TSPO in heart tissue following injury matched CD68 positive staining. Tissue autoradiography techniques with 18F-LW223 have also been used to gain higher resolution images of radiotracer expression in different tissue levels compared with PET data. Results from autoradiography and IHF experiments showed that post-myocardial infarction, the increase in neuroinflammaiton was primarily due to increases expression of TSPO in the lateral ventricles. This agrees with previous studies demonstrating the role of the choroid plexus in the recruitment of macrophages at distant sites [3]. In addition to using multi-modal imaging techniques, both in vivo and ex vivo, to understand the heart:brain inflammation axis following myocardial infarction; our group is keen on understanding cardiac remodelling following infarction. For this we are currently exploring the use of 18F-Fluoroproline PET imaging alongside magnetic resonance imaging (MRI) techniques to quantify collagen biosynthesis and fibrosis in the heart tissue. Our results so far have shown that 18F-trans-Fluoroproline PET imaging has a strong and negative correlation with the ejection fraction measured by cardiac MRI. This talk at the upcoming COMULIS session at EMIM2020 will cover how multi-modal imaging approaches can be valuable to understand cardiovascular inflammation and tissue remodelling following myocardial infarction; while delivering prognostic imaging biomarkers for clinical use and using imaging to support the discovery of new treatments.

Publications:

[1] Thackeray JT, Hupe HC, Wang Y, Bankstahl JP, Berding G, Ross TL, et al. Myocardial Inflammation Predicts Remodeling and Neuroinflammation After Myocardial Infarction. J Am Coll Cardiol 2018;71:263–275. doi:10.1016/j.jacc.2017.11.024.

[2] Owen DRJ, Gunn RN, Rabiner EA, Bennacef I, Fujita M, Kreisl WC, et al. Mixed-Affinity Binding in Humans with 18-kDa Translocator Protein Ligands. J Nucl Med 2011;52:24–32. doi:10.2967/jnumed.110.079459.

[3] Shechter R, Miller O, Yovel G, Rosenzweig N, London A, Ruckh J, et al. Recruitment of Beneficial M2 Macrophages to Injured Spinal Cord Is Orchestrated by Remote Brain Choroid Plexus. Immunity 2013;38:555–569. doi:10.1016/j.immuni.2013.02.012.

Keywords: Multi-modal imaging, PET, MRI, Ultrasound, Immunofluorescence
11:20 a.m. SG02-04

Mass Spectrometry - a yet not so common method for multimodal imaging

Martina Marchetti-Deschmann1

1 Vienna University of Technology, Vienna, Austria

Content

Everyone knows that an image says more than a thousand words. But as Aristotele already stated, “The whole is more than the sum of its parts”. This also means that a single modality is very often not good enough to understand all functional, structural, temporal and chemical relations underlying certain biological conditions. Imaging a specimen with two or more complementary modalities creates an informative, composite view of a sample that spans all relevant resolution ranges.

Here we present novel strategies to use MALDI Mass Spectrometry based imaging (MALDI-MSI) together with immunohistochemistry (IHC), light microscopy (LM), micro X-ray fluorescence (µ-XRF) and laser ablation inductive coupled plasma MS (LA-ICP-MS) for combined molecular and elemental imaging in biological tissues. IHC detects known proteins in tissue at high lateral resolution and LM images display morphological structures and pathological features. Such information can be supported by localized untargeted measurements of intact molecules by MALDI MSI and quantitative elemental information provide by LA-ICP-MS imaging. µ-XRF imaging can be used to examine the spatial context of elements without destroying the sample. Last but not least, Fourier-Transform Infrared (FT-IR) is a nondestructive optical method capable of detecting molecular classes in tissue.

This presentation will showcase correlated multimodal imaging using some or all of these methods in combination. Tissue resident immune cells are detected by IHC an LM after Toluidin staining and peptides relevant for certain cell types are detected by MALDI MSI and can be colocalized with macrophage and lymphocyte markers. It will be shown that high-resolution images based on optical methods can be used to increase the spatial resolution of MALDI MSI experiments. Moreover, the successful combination of LA-ICP-MS, MALDI-MSI and FT-IR analysis is presented that allowed to better understand different inflammation events occurring in lung tissue after inhaling different types of SiO2 nanoparticles.

Keywords: Mass Spectrometry, multimodal imaging