15th European Molecular Imaging Meeting
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NEUROIMAGING: in vivo and ex vivo Imaging Modalities from Preclinical to Clinical Applications

Session chair: Hervé Boutin (Manchester, UK); Philipp Böhm-Sturm (Berlin, Germany)
 
Shortcut: ES 03
Date: Tuesday, 25 August, 2020, 12:00 p.m. - 1:30 p.m.
Session type: Educational Session

Contents

Abstract/Video opens by clicking at the talk title.

12:00 p.m. SG03-00

Welcome to the vEMIM 2020 NeuroImaging Educational Session

Herve Boutin1, Philipp Boehm-Sturm2

1 University of Manchester, Faculty of Biology, Medicine and Health, School of Biological Sciences, Division of Neurosciences and Experimental Psychology, Manchester, United Kingdom
2 Charité - Universitätsmedizin Berlin, Center for Stroke Research Berlin and Department of Experimental Neurology, Berlin, Germany

Learning Objective

We would like to welcome you to the vEMIM 2020 NeuroImaging Educational Session. We have gathered a range of experts in molecular neuroimaging who will cover a broad range of techniques from in vivo to ex vivo from functional to structural imaging.

Content

Our selected experts will cover imaging modalities used for neurosciences from basic physic principles to preclinical and clinical applications.
We encourage you to interact with the speakers and ask questions through the the virtual plateform.
We will also welcome feedback about the content of this session, the length and variety of the presentation to further improve in the coming years.

Relevant Publications

Keywords: MRI, PET, autoradiography, optical, mass spectrometry
12:10 p.m. ES03-01

Imaging modalities applied to neuroscience

Laetitia Lemoine1

1 Karolinska Institutet, NVS/clinical Geriatrics Division, Stockholm, Sweden

Learning Objective

- Being able to choose the most suitable imaging modality for a given research question.

- Getting an overview of brain in vivo imaging techniques in comparision to in vitro and ex vivo data.

Content

Preclinical experimentation using MicroPET and MicroCT is an essential tool during the characterization of new PET tracers but also to understand the in vivo brain pathophysiological mechanism and changes using different animal models of neurodegenerative diseases in comparison to wild type animal. This lecture will first provide a brief introduction about MicroPET and MicroCT principles, illustrated with a panel of examples about their use in several animal models. These in vivo imaging techniques can hem complemented by in vitro and ex vivo autoradiography in order to visualize the brain distribution of different radiotracers for PET imaging. The lecture will also present the practical autoradiography procedures that are used to characterize the binding properties of novel PET tracers targeting amyloid plaques, tau deposits, and reactive astrocytes, with examples in animal models and in postmortem human brain tissues from different neurodegenerative diseases. In combination with immunohistochemistry techniques, autoradiography allows to determine what pathological hallmarks the PET tracers are binding to. These in vitro and in vivo imaging techniques are also important tools for the preclinical testing of new drugs, before they can be moved to testing in clinical trials.Finally, the lecture will discuss the usefulness of these translational imaging studies in understanding the complex pathophysiology of neurodegenerative disease, and towards developing more specific PET tracers that may be used for early diagnosis and to test novel therapeutic targets.

Relevant Publications

- Mathis CA, 2017, Small-molecule PET Tracers for Imaging Proteinopathies, Semin Nucl Med. 2017 Sep;47(5):553-575. doi: 10.1053/j.semnuclmed.2017.06.003. Epub 2017 Jul 13.

- Rodriguez-Vieitez E, Ni R, 2015, Astrocytosis precedes amyloid plaque deposition in Alzheimer APPswe transgenic mouse brain: a correlative positron emission tomography and in vitro imaging study, Eur J Nucl Med Mol Imaging. 2015 Jun;42(7):1119-32. doi: 10.1007/s00259-015-3047-0. Epub 2015 Apr 17.

- Lemoine L, 2015, Visualization of regional tau deposits using (3)H-THK5117 in Alzheimer brain tissue, Acta Neuropathol Commun. 2015 Jul 2;3:40. doi: 10.1186/s40478-015-0220-4.

Keywords: microCT, microPET, autoradiography
12:10 p.m. ES03-02

Mass spectrometry imaging of post-mortem brain

John Fletcher1, Ibrahim Kaya1

1 University of Gothenburg, Gothenburg, Sweden

Learning Objective

Appraoches and beenfits of different imaging MS approaches for post-mortem brain imaging.

Content

Imaging mass spectrometry combines the chemical specificity of mass spectrometry with the ability to provide precise chemical localisation. There are a wide range of different approaches to performing imaging mass spectrometry and each approach has different strengths and weaknesses often associated with achievable spatial resolution and sensitivity to different chemicals.

The technique is often applied to slices of tissue, but also single cells, and has become increasingly used in pre-clinical studies with advances in clinical measurements also being made.

This presentation will describe the application of secondary ion mass spectrometry (SIMS), desorption electrospray ionisation (DESI) mass spectroetry and matrix assisted laser desorption ionisation (MALDI) mass spectrometry and showcase the information that these techniques can provide.

Relevant Publications

Mass spectrometry imaging and integration with other imaging modalities for greater molecular understanding of biological tissues
TP Siegel, G Hamm, J Bunch, J Cappell, JS Fletcher… - Molecular Imaging and Biology, 2018

Brain region‐specific amyloid plaque‐associated myelin lipid loss, APOE deposition and disruption of the myelin sheath in familial Alzheimer’s disease mice
I Kaya, E Jennische, S Lange, A Tarik Baykal… - Journal of Neurochemistry, 2020

MALDI imaging of Alzheimer's model mouse brain
Keywords: Imaging mass spectrometry
12:30 p.m. ES03-03

Imaging protein aggregation, neuroinflammation and neurodegeneration (part 1)

Sylvie Chalon1

1 UMR Inserm U1253 iBrain, UFR de Médecine, Tours Cedex 01, France

Learning Objective

An up-to-date on the interests to explore by PET imaging several molecular targets such as abnormal aggregated proteins and markers of neuroinflammation in the context of neurodegenerative disorders.
An up-to-date on the main imaging probes (tracers) already available or to be developed for this exploration.

Content

Neurodegenerative diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS) and Huntington disease (HD) share several pathological features such as abnormal protein aggregation and neuroinflammation. In vivo PET imaging of these processes is therefore highly valuable for improvement of the early and differential diagnosis, follow up and treatment evaluation. This exploration requires the choice of the relevant molecular target and the availability of specific radiotracer of each target. PET imaging of misfolded proteins characteristics of AD, i.e. Aβ and hyperphosphorylated tau, is to date achievable whereas no tool is yet available for α-synuclein aggregates which is the main feature of synucleinopathies (including PD, dementia with Lewy body and multiple system atrophy), and TDP43 present in ALS. Brain neuroinflammation can already be explored using radioligands of the mitochondrial marker of microglial activation 18kDa translocator protein (TSPO), although more specific targets are searched at the same time. Through the presentation of various PET studies in animal models and humans, the interests and limits of this imaging modality will be discussed.

Relevant Publications

Keywords: PET imaging, Animal model, Parkinson's disease, Alzheimer's disease, Radiotracers
12:40 p.m. ES03-04

Imaging protein aggregation, neuroinflammation and neurodegeneration (part 2)

Elena Rodriguez-Vieitez1

1 Karolinska Institutet, Div. Clinical Geriatrics, Stockholm, Sweden

Learning Objective

Understand how positron emission tomography (PET) imaging can specifically target and quantify different molecular and neuropathological changes in neurodegenerative diseases, with a special focus on Alzheimer's disease.

Appreciate the utility of multi-tracer PET and multi-modal MRI/PET imaging studies to visualize associations between neuroinflammation, amyloid, tau and neurodegeneration in the human brain

Content

The neuropathological hallmarks of Alzheimer’s disease (AD) are the abnormal aggregation of amyloid-β and hyperphosphorylated tau proteins. In addition, there is increasing evidence for the central role of the brain’s innate immune system (glial cells, including astrocytes and microglia) in the pathogenesis of AD and other neurodegenerative diseases. In particular, glial cells undergo dynamic phenotypic changes, namely glial activation and neuroflammation, along disease progression. While we have gained substantial knowledge about neuroinflammation from cellular and animal models, much is still unknow about the in vivo relationships between neuroinflammation and protein aggregation in the human brain, and whether neuroinflammation and protein aggregation may interact to cause subsequent neurodegeneration. Recent advances in positron emission tomography (PET), a molecular imaging technique that can specifically target those different biological changes in the brain, offer hope towards visualizing the in vivo relationships between neuroinflammation and other pathological changes in the brain.

This lecture will present recent advances in PET imaging of astrocytosis using novel tracers (e.g. 11C-deuterium-L-deprenyl and 11C-BU99008), as applied in multi-tracer PET imaging studies to quantify dynamic relationships between astrocytosis, amyloid-β, tau and neurodegeneration [1-3]. Traditional imaging biomarkers of neurodegeneration include metabolism as measured by 18F-fluorodeoxyglucose (FDG) PET and cortical thinning as measured by magnetic resonance imaging (MRI). More recently, novel PET tracers have been designed to measure synaptic dysfunction by targeting the synaptic vesicle protein 2A (SV2A), a promising novel marker of neurodegeneration. In Parkinson’s disease (PD), specific deficits in presynaptic dopaminergic neuronal function can be visualized using the PET tracer 18F-DOPA. Finally, recent developments in multi-modal MRI/PET imaging will be described to illustrate how these studies contribute to understanding the in vivo relationships between brain structure, pathology and function, with potential clinical applications.

Relevant Publications

AcknowledgmentMulti-tracer PET imaging studies described in this lecture were made possible with support and guidance from Prof. Agneta Nordberg at Karolinska Institutet, Sweden. I gratefully acknowledge financial support from the Swedish Alzheimer Foundation (Alzheimerfonden), Åke Wiberg Foundation, Swedish Dementia Association (Demensfonden), Erik and Edith Fernström Foundation, Stiftelsen för Gamla Tjänarinnor, Stohnes Foundation, and Karolinska Institutet Foundation, Sweden.
References
[1] Jagust W. Imaging the evolution and pathophysiology of Alzheimer disease. Nat Rev Neurosci 2018;19:687-700.
[2] Leuzy A, Chiotis K, Lemoine L, et al. Tau PET imaging in neurodegenerative tauopathies-still a challenge. Mol Psychiatry 2019;24:1112-1134.
[3] Rodriguez-Vieitez E, Saint-Aubert L, Carter SF, et al. Diverging longitudinal changes in astrocytosis and amyloid PET in autosomal dominant Alzheimer's disease. Brain 2016;139:922-936.
Keywords: amyloid, glial cells, neuroinflammation, tau, positron emission tomography
1:00 p.m. ES03-05

Brain imaging in clinical neurology

Ahmed Khalil1, 2, 3

1 Charité – Universitätsmedizin Berlin, Center for Stroke Research Berlin, Berlin, Berlin, Germany
2 Berlin Institute of Health, Berlin, Germany
3 Max Planck Institute for Human Cognitive and Brain Sciences, Department of Neurology, Leipzig, Germany

Learning Objective

Upon completion of this educational activity, the participants should be able to:

  1. List the imaging modalities commonly used in clinical routine at a typical neurology department 
  2. Describe the fundamental physical principles behind CT, MRI, and PET
  3. Describe the broad types of clinical scenarios in which each of these techniques is commonly used
  4. Explain what kind of information is provided by each of these techniques, and provide examples of their complementary nature in clinical practice.

Content

Imaging plays an indispensable role in diagnosis, disease monitoring and guiding of therapeutic decisions in clinical neurology. This presentation will provide an overview of the commonly used neuroimaging modalities in clinical practice, with a focus on the tomographic techniques (computed tomography, magnetic resonance imaging and positron emission tomography). The presentation will cover the fundamental physical principles behind each technique, discuss their relative merits and drawbacks in specific clinical scenarios, and outline their typical use cases.

Relevant Publications

Keywords: MRI, PET, CT, neuroimaging, neuroradiology