fMRI: Biological Basis and Experiment Design
Lecture 3
• Cell metabolism
• Vascular architecture
• Blood flow regulation
Harrison, Harel et al., Cerebral Cortex 12:225 (2002)
Oxidative vs. anaerobic metabolism
Non-oxidative (glycolysis)
lac
http://personal.nbnet.nb.ca/trevgall/biology/
pyr
mitochondrion
TCA
glc
glc
Oxidative (16 times
more ATP)
Nucleus
Fox and Raichle
• Surprise finding suggests that neuronal activity elicits
anaerobic metabolism
CBF
CMRO2
Fox and Raichle, 1986:  CBF >>  CMRO2
OEF
The Magistretti Hypothesis
• Astrocytes anaerobically metabolize glucose to lactate
• Neurons aerobically metabolize lactate/pyruvate
Magistretti (2000) Brain Research 886:108
Neurons and astrocytes are cells
sm muscle
Capillary
Astrocyte
endothelium
pre-capillary
arteriole
endothelium
glucose
glucose
Neuron
2 LAC + 2 ATP
TCA
32 ATP
2 LAC + 2 ATP
TCA
32 ATP
Magistretti hypothesis: an explanation for Fox and Raichle
sm muscle
Capillary
Astrocyte
endothelium
pre-capillary
arteriole
endothelium
glucose
glucose
Neuron
2 LAC + 2 ATP
TCA
2 LAC + 2 ATP
TCA
32 ATP
Metabolism in astrocytes and neurons
Pellerin: put back in an
arrow that went missing
(too much disagreement
about what role lactate
plays for neurons)
Attwell & Laughlin (2001).
JCBFM 21: 1133-1145.
Continued debate about whether
(approximately) stoichiometric
coupling indicates that glucose
uptake is driven by glutamate
cycling
Continued debate about
compartmentalization of oxidative
and non-oxidative metabolism in
neurons and glia
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.
Mintun, Vlassenko, Rundle, Raichle (2004). Increased
lactate/pyruvate ratio augments blood flow in physiologically
activated human brain. PNAS, 101 (2), 659-664.
Brains are not muscles
Adult (showing scar tissue following hernia repair)
Pediatric patient (with fungal infection of liver)
18-FDG PET images from Abouzied et al. (2005). J. Nuc. Med. Tech. 33(3):145
Neurovascular coupling: why energy budgets and oxidative metabolism matter
sm muscle
Capillary
endothelium
pre-capillary autoregulation arteriole
endothelium
propagation of dilatory signals
Astrocyte: Inc
uptake of glutamate --> (release of NO, EET),
increased glucose metabolism (non-oxydative)?
Ca++,
Interneuron
- inc Ca++even w/o spikes
- release of NO, EETs …
--> dilation
- release of NPY, SOM(?)
--> contstriction
- inc. glc metabolism?
Neuron
- inc Ca++ when spiking
- release of NO, EETs …
- inc. glc metabolism (oxidative)?
Harrison, Harel et al., Cerebral Cortex 12:225 (2002)
Harrison, Harel et al., Cerebral Cortex 12:225 (2002)
100m
50m
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 251:87
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
5m
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
Fin(t)
Fout(t)
Filling the balloon
dv(t ) 1
 Fin (t )  Fout (t ) 
dt
0
where
Fin(t)
Fout (t )  Fin (t ) 
o
v
 F (t )  v(t ) 1 
 in

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)