Proceedings of a Workshop on Statistics on Networks (CD-ROM) (2007) / Chapter Skim
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Dynamics and Resilience of Blood Flow in Cortical Microvessels--David Kleinfeld, University of California at San Diego
Dynamics and Resilience of Blood Flow in Cortical Microvessels--David Kleinfeld, University of California at San Diego
Pages 292-316
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From page 292... ...
It's interesting, because as you look at this problem from a physics or math point of view, you see highly interconnected networks; and the first thing you think about is percolation networks. You can add defects to these networks, and they should keep working until some critical junction occurs, and then they will stop flowing.
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From page 293... ...
The point is that the redundancy actually begins to break down, and if a block is made in the main trunk of the middle cerebral artery, which has been a favorite model system of the neurology community, large swathes of your brain will start to die off. FIGURE 1 We are now going to look in finer scale at the region marked with the "X" in Figure 1, which is fed by the branches of these major cerebral arteries, and discuss what's known from the past.
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From page 294... ...
These images are from rats in which the entire vasculature was filled with latex, then you chew away the tissue and cover the latex with gold and look with a scanning electronic microscope. They give you beautiful pictures, but they are quantitatively useless, because you can't see deep into the tissue.
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From page 295... ...
What we could do is home in, going down from the surface to look and make a little map of individual vessels. In the previous talk, Eve Marder showed these nice reconstructions of neurons that were made by making many individual planes and then reconstructed.
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From page 296... ...
We put large dextrose in, big sugar molecules that are coated with dye, so the blood plasma glows bright and fluoresces. Particular red blood cells eschew the dye, so they are dark objects; we are imaging dark objects on a bright background.
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From page 297... ...
It's very hard to find long swatches of time where the speed is uniform, or if this is a case where the red blood cells are moving, all of a sudden they stall and stop within the capillary. They will sit there for tens of seconds, or even more interesting, if nature very politely decided that capillaries should meet at Ts, what's a better present to somebody who is doing scanning.
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From page 298... ...
We can then compute the spectral power density of this time series. This is shown on the top plot of Figure 6, and what you see is that most of the variation lives at this very low frequency that comes in at about 0.1 Hertz.
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From page 299... ...
These little boxes mark the time stamp of when we actually went in and simulated the animal. In this case, we are recording from the vibursa area of the rat cortex, and we are tweaking the vibrissae at a level where we get about one spike per tweak, which is the normal physiological level of spiking.
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From page 300... ...
The trick is these terrible molecules called photosensitizers that make a free radical when you shine light on them. Within a couple of milliseconds these free radicals will actually damage the nearest piece of tissue.
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From page 301... ...
I could actually activate the molecule on the surface, but once I get below the vessels, lensing due to the vessel and scattering through the issue will drop the intensity below threshold. I could then gradually build up a clot at this point and see that the flow, which was now all moving downward on the time scale of the block, would rapidly rearrange itself.
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From page 302... ...
As a matter of fact, the flow is almost completely stopped at this point, so the key result is already shown here, that we make a block, and we immediately get this rapid reversal in flow. More so, the point is that the speed in the reverse vessel is very much on the same order, which means the rate of perfusion is on the same order as the initial flow.
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From page 303... ...
The point is that the rearrangement is well within physiological means to keep the neurons viable, and there is a set of histology that I'm not showing here that is also consistent in showing that neurons and glia stay viable.
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From page 304... ...
Here we appeal to a technique that, as I mentioned earlier, has been in the neurology literature for a long time. That is putting a very fine filament through the carotids, and then up into the middle cerebral artery, and blocking this main artery itself.
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From page 305... ...
That is lower than physiological levels. If we make a blockage and look at vessels that fit parallel regions, there is virtually no change.
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From page 307... ...
From here to here is a few hundred microns for the next sort of primary downstream vessels. By the time we get to secondary and tertiary vessels we are talking about 500 microns, and there, I think statistically, you would be even sensitive to this effect.
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From page 308... ...
That means I have to go nonlinear, so to speak, and I need to have an interaction, which is only effective at the focus of the lens. FIGURE 15 Just like we use nonlinear interactions to do our imaging, which means that we only get appreciable absorption at the focus, I can also come in with very, very short 100 femtosecond pulses, and I could only cause damage right at the focus of the lens.
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From page 309... ...
But at modest energies you actually cause an aneurysm to form. At more intermediate energies you get something very interesting: we cause a little cavitation bubble to form inside an arterial.
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From page 310... ...
The key difference here is that I made a blockage at this point in this less connected network that lies well below the surface. When I look downstream, again I get a reversal of flow, but the magnitude of these changes is about an order of magnitude smaller than what I have gotten on the surface.
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From page 311... ...
I have caused dye to leave, but I'm looking at the motion of the red blood cells at the same time, and that motion is unchanged as shown in Figure 19. So, at least on these types of timescales of 311
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From page 312... ...
Even if we try to dilute the blood, Figure 20 shows that there is virtually no change in the immediate downstream flow, and this region is stalled out. If I look a little bit downstream, things are also fairly stalled out.
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From page 313... ...
We actually have a way to reconstruct big swatches of the vascular.
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From page 314... ...
If you look at the surface -- just so far we have looked at a couple of networks -- they are really dominated by these kind of little triads, the smallest possible loops that you could put together with these sort of three nodes. If you look at the subsurface networks you see very few of these threes, so what we hope to do over the next year is put together these dynamics and the topology in a hard way.
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From page 315... ...
The National Academies more recent perturbation-based experiments were done in collaboration with Patrick Lyden's laboratory at UCSD and involved Beth Triedman, Nozomi Nishimura, Chris Schaffer and Phil Tsai. Beth and Phil, along with Pablo Blinder, Ben Migliori and Andy Shih, are continuing this collaborative effort.
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From page 316... ...
2006. "Targeted insult to subsurface cortical blood vessels using ultrashort laser pulses: Three models of stroke." Nature Methods 3(2)
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