fMRI: Biological Basis and Experiment Design Lecture 3

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fMRI Biological Basis and Experiment
DesignLecture 3

• Cell metabolism
• Vascular architecture
• Blood flow regulation

Harrison, Harel et al., Cerebral Cortex 12225
(2002)
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Oxidative vs. anaerobic metabolism
mitochondrion
http//personal.nbnet.nb.ca/trevgall/biology/
Nucleus
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Fox and Raichle

• Surprise finding suggests that neuronal activity
  elicits anaerobic metabolism

CBF
CMRO2
OEF
Fox and Raichle, 1986 ? CBF gtgt ? CMRO2
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The Magistretti Hypothesis

• Astrocytes anaerobically metabolize glucose to
  lactate
• Neurons aerobically metabolize lactate/pyruvate

Magistretti (2000) Brain Research 886108
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Neurons and astrocytes are cells
Astrocyte
Neuron
32 ATP
32 ATP
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Magistretti hypothesis an explanation for Fox
and Raichle
Astrocyte
glucose
Neuron
2 LAC 2 ATP
32 ATP
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Metabolism in astrocytes and neurons
Attwell Laughlin (2001). JCBFM 21 1133-1145.
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Evidence for compartmentalization of metabolism

• Kasischke, K. A., Vishwasrao, H. D., Fisher, P.
  J., Zipfel, W. R. Webb, W. W. (2004). Neural
  activity triggers neuronal oxidative metabolism
  followed by astrocytic glycolysis. Science, 305,
  99-103.

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Brains are not muscles
Pediatric patient (with fungal infection of liver)
Adult (showing scar tissue following hernia
repair)
18-FDG PET images from Abouzied et al. (2005). J.
Nuc. Med. Tech. 33(3)145
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Neurovascular coupling why energy budgets and
oxidative metabolism matter
Astrocyte Inc Ca, uptake of glutamate --gt
(release of NO, EET), increased glucose
metabolism (non-oxydative)?
Interneuron - inc Caeven w/o spikes -
release of NO, EETs --gt dilation -
release of NPY, SOM(?) --gt contstriction -
inc. glc metabolism?
Neuron - inc Ca when spiking - release of
NO, EETs - inc. glc metabolism (oxidative)?
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Harrison, Harel et al., Cerebral Cortex 12225
(2002)
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Harrison, Harel et al., Cerebral Cortex 12225
(2002)
100?m
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50?m
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On the scale of a voxel
Human temporal cortex

• Blood is supplied to and drained from the cortex
  by the pial network
• 100 500 micron diameter
• half the blood volume is in intracortical veins
  and arteries (2 gray matter vol.)
• 10 50 micron diameter
• diameter depends on depth
• half the blood volume is in the capillary
  network (2 gray matter vol.)
• 8 micron diameter
• density correlates with neural demand
• White matter is supplied by transcortical
  arteries and veins

375 ?m
Reina de la Torre et al (1998) Anatomical Record
25187
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The Plumbers and the Electricians

• There is no such thing as constant flow
• Pulse
• Vasculature is highly responsive can
  autoregulate
• The vascular network is not a fixed entity
• Flow can switch directions in small vessels and
  capillaries
• Capillaries can grow to match metabolic demand
• Bottom-up regulation is more practical than
  top-down

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Balloon Model, Part I CBF and CBV

• CBF cerebral blood flow
• increased CBF increases signal strength
• CBV cerebral blood volume
• increased venous blood volume decreases signal
  strength

Fout(t)
Fin(t)
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Filling the balloon
where ?0 is mean transit time through balloon,
resting state ?v is mean transit time through
expanded balloon v(t) is volume of balloon
Fout(t)
Fin(t)