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Cellular imaging at 3 T: Detecting Cells in Inflammation
using Active Labeling with Super paramagnetic Iron oxide
Azhar Hosein FarazMedical Biophysics Western University
Robarts Research Institute Under supervision of: Dr. Paula Foster
4th April 2012
Immune Response and Inflammation
• Tissue injury caused by bacteria, trauma, chemicals, or any other phenomenon –Inflammation.
• Walling- off
• Within minutes after inflammation occurs macrophages already present in the tissues (microglia, Kupffer cells,..) begins their phagocytic action.
• The second line of defence within the first hours of inflammation begins are the large number of neutrophils that invade the inflamed area.
• In Vivo Labeling of Cells with Iron Particles
Imaging Immune Cells with MRI
Iron oxide contrast agent
Intravenous (i.v) administration Phagocytosis
Labeled cells
Iron oxide-based MRI contrast agents
Adapted from Modo, M. et al. Mol. Imag, 2004 Effect of iron is tocause signal loss inMRI images
Iron-labeled cells In gel
Aim of study
• To detect inflammatory cells in the mouse brain by in vivo 3T MRI in a model of neuroinflammation.
MRI Pre-Scan of body
Normal Healthy Mouse (C57/Bl6, n=2)
Iron Oxide (Fe) injected Intravenously (IV) to Mice
MRI Body 24 hours Post-injection (Fe)
Fe - Bone marrow- Liver - Spleen
Monocytes
Inject mice with :LPS (lipopolysaccharide) 48 hours Post-injection (Fe)
MRI Body 6 days Post-injection (Fe)
Model of Neuroinflammation- Neurotoxic
- Over activation of microglia
MRI Brain 9 days Post-injection (Fe)
Methods
3T clinical system
Solenoid radio frequency coil
Custom-built high performance gradient
Imaging Cells (3T cellular MRI) at Robarts
- Only lab in the world- research imaging
experiments at clinical magnetic strength
- pulse sequence known as, bSSFP.
Image Analysis: Body Images
• Measuring mean signal intensity of different image slices in Liver, Bone marrow, and Spleen.
• Standard deviation (SD) of Noise present in each slice.
• SNR Signal to Noise ratio Mean signal intensity / SD of Noise Present in each scan slice
• No. of Voids present in Brain MRI scan • Mean signal intensity of each discrete region of
signal void• Fractional signal loss in %
=
• Clear canvas software used for analyze of MRI scan images.
Image Analysis: Brain Images
Results
Whole Mouse Body BSSFP Images
Head Tail Sagittal view of mouse
Before Iron Injection
Post Injection Iron
• In vivo labelling of liver, spleen and bone marrow macrophages
Results: SNR
• Liver > Spleen > Bone marrow
MRI Brain • Voids present in brain
Results: FSL
• FSL is related to the amount of Iron in discrete reigns of signal void.
• Can be related to the number of iron-labeled cells.
SUMMARY
• Changes in SNR suggests that cells take up iron in the liver, spleen and bone marrow - the numbers of iron-labeled cells is different for each organ and varies in mice.
• This work indicates that pre-labeling immune cells with iron allows us to track their involvement in inflammation in the brain
• This study has been done for first time
Future directions
• To prove that signal loss in the brain is due to the accumulation of immune cells
• To determine which kind of cells are presenting in brain, using histology and experiments with transgenic mice.
• To obtain body images over a prolonged time period, to better understand the time course of cell uptake and retention of iron.
Acknowledgment
• Supervisor : Dr. Paula Foster
• Research funding : MS society
• Thanking Jonatan Snir, for imaging
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