USGEB Meeting 2011, Zurich «Imaging Life»

Seeing Cells in Action with photoactivatable fluorescent Proteins - Jennifer Lippincott-Schwartz

• Photo-activated light microscopy → Super-resolution
• Autophagy → self-destruction of cell
• correlative imaging PALM/TEM → map molecules on Electron microscopy images
• 3D imaging possible
  • wave from photon is propagated through two objectives
  • interference makes it possible to extract 3D position

• Brain glucose level is linear to plasma glucose
• Brain glucose content mapped using ¹H NMR
• Spectroscopy can be used to emasuera concentration of biochemical compounds
  • Concentration > 1 MM
  • water soluble
• → quantitative tool

• Analysis of activation patterns of brain regions of observed and experienced pain → localized in one single part of the brain

• distribution of cells in Nucleus → Super-resolution
• Merging of several images together

• AFM imaging

• PET is quantitative, but had only a resolutin in the mm-range

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• Translational molecular imaging
• Molecular labeling with different compounds
• Makes personalized treatment possible, but needs testing for treatment with specific FDG-marker

• Since markers have short half life, repeated studies are possible
• ¹¹C has 20min half life
• Enzymes can be used, even Cocaine, Heroin and Nicotine. Can even be done without the pharmacological effect, since the markers can be labeled (which destroys the effect?)
• For antidepressants, a combination of Pindolol and SSRI was shown to improve onset of action. 70% of 5-HT1A - Receptor has to be occupied by Pindolol.

• Development and characterization of new tracers for PET imaging

• Near infrared imaging of tumors in vivo, follows by ex vivo imaging of the whole organ and tissue sectioning
• Activation of Affibodies could be detected.

• Plays a role in Alzheimer research
• Expression of Reelin changes over aging
• Similarities between human and mouse plaques

• Neocortex has several layers of neurons until the white matter
• Depth penetration into Neocortex around 800 um, into living tissue!
• Single action potentials through imaging combined wit electrical recording
• Two-photon imaging with 'swinging objective' to cover full ROI
• Tradeoff between time resolution and size of Neuron population which can be imaged
• Plasticity effect in the brain (due to trimming of whiskers)
• Imaging in awake and behaving mice an be done with animals which are trained to tolerate head fixation