2012 Cellular imaging at 3 T

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Cellular imaging at 3 T: Detecting
Cells in Inflammation using Active
Labeling with Super paramagnetic
Iron oxide
Azhar Hosein Faraz
Medical 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.
Imaging Immune Cells with MRI
• In Vivo Labeling of Cells with Iron Particles
Iron oxide contrast
agent
Labeled cells
Intravenous (i.v)
administration
Phagocytosis
Iron oxide-based MRI contrast agents
Iron-labeled cells
In gel
Adapted from Modo, M. et al. Mol. Imag, 2004
Effect of iron is to
cause signal loss in
MRI images
Aim of study
• To detect inflammatory cells in the mouse brain
by in vivo 3T MRI in a model of
neuroinflammation.
Methods
Normal Healthy Mouse (C57/Bl6, n=2)
MRI Pre-Scan of body
Iron Oxide (Fe) injected Intravenously (IV) to Mice
Fe
- Bone marrow
- Liver
- Spleen
Monocytes
MRI Body 24 hours Post-injection (Fe)
Inject mice with :
LPS (lipopolysaccharide) 48 hours Post-injection (Fe)

Model of Neuroinflammation
- Neurotoxic
- Over activation of microglia
MRI Body 6 days Post-injection (Fe)
MRI Brain 9 days Post-injection
(Fe)
Imaging Cells (3T cellular MRI) at Robarts
Custom-built high performance gradient
- Only lab in the world
- research imaging
experiments at clinical
magnetic strength
- pulse sequence known as,
bSSFP.
Solenoid radio frequency coil
3T clinical system
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
Image Analysis: Brain Images
• No. of Voids present in Brain MRI scan
• Mean signal intensity of each discrete region of
signal void
• Fractional signal loss in %
∆𝑠
𝑠
=
𝑆𝐼 𝑏𝑟𝑎𝑖𝑛 −𝑆𝐼 ( 𝑉𝑜𝑖𝑑)
𝑆𝐼 ( 𝑏𝑟𝑎𝑖𝑛)
× 100
• Clear canvas software used for analyze of MRI
scan images.
Results
Whole Mouse Body BSSFP Images
Before Iron Injection
Tail
Head
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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