Haemodynamics Flashcards
What is ATP?
Adenosine triphosphate
The principle energy source for neural activity
How does neuronal firing get its energy?
When neurons fire the ionic gradients within the neuron are reduced by the release of synaptic neurotransmitters so a source of energy is required to re-establish the gradient. This is supplied by the conversion of andenosine triphospate (ATP) to adenosine diphosphate (ADP). By reversing the ATP-ADP reaction we get energy and replenished ATP supplies
Glucose and oxygen needed for ATP synthesis?
Yes - need constant diffusion of these cos need ATP to do most things - meet demands of neural activity.
Glucose is transported from vascular network into brain cells
Glucoses produces 2 ATP and pyruvate
Pyruvate enters TCA cycle where ADP is recycled into ATP (if no oxygen, pyruvate is reduced to lactate)
End products are diffused into blood stream
What is ATP used for presynaptically?
On 4 types of ATPase:
Sodium-calcium pump - forces sodium out which are generating the AP and powers calcium removal;
Calcium-ATPase - in plasma membrane which lowers calcium concentration;
Vascular ATPase - energizes vesicle transmitter uptake;
Motor proteins which move mitochondria and vesicles around the cell.
What is ATP used for postsynaptically?
More than presynaptic as primarily used to pump ions to mediate synaptic currents and has a smaller usage on returning calcium to intracellular stores and on mitochondrial trafficking
Use of ATP in astrocytes
Largely on extruding sodium to maintain the resting potential and to remove the ions driving glutamate uptake and the conversion of glutamate into glutamine.
Energy budget for ATP
Majority of rat ATP consumption supports neural activity - maintaining resting potential, reversing ion entry post AP, reversing glutamate evoked sodium and calcium flux. In humans, we have less dense neurons so more used up in synapses - maintaining resting potentials, housekeeping and restoring postsynaptic concentration gradients are more likely the highest demands of ATP
3 key haemodynamic changes associated with ATP demands
Blood flow - more activity in the area
Vasodilation - change in width of vessels
Blood oxygenation changes
Both of these changes support blood oxygenation - might tell us about oxygenation or can use it in combination with oxygen changes
First study to link blood flow and neural responses
Balance board - robust physiological change associated with cellular activity - linked vasodilation
Vasodilation
When there’s a somatosensory event or neural response we see various changes at vessel level to allow vessels to more effectively meet the demands of the surrounding tissue (blood based changes).
No imaging has the spatial resolution adequate to see this in humans so can explore it in slice work
Imaging haemodynamics using optical techniques
Allows us to measure blood flow and velocity following peripheral sensory stimulation or neural activation. The amount of wavelengths of light absorbed change based on how much oxygen is bound - so shine light of a specific wavelength that will be preferentially absorbed by one speed of haemoglobin compared to the other
What are laser Doppler techniques?
Doppler shift = frequency change imparted on waves as a source moves
When light is shined on tissue, the photons are reflected, absorbed, and scattered.
Scattering = random direction independent of blood flow and volume.
So doppler shift is induced by moving RBC and can monitor it to give us a measure of glow at the surface of the brain.
More red blood cells = more Doppler shifted photons.
Laser Doppler perfusion monitoring
Laser light illuminates area of tissue
Photons are scattered by static (scatter back) and dynamic particles (ie red blood cells which impart Doppler shift on the photon)
Light returned to the unit is now a mixture of of frequency and Doppler shifted frequencies
When light is received by photomultipliers the signal is effectively low pass filtered so only the difference signal remains
Limitations of LDF
No objective measures - difficult to establish a baseline so just subjective measures, making it difficult to compare across studies. Also means difficulty in localising the depth of the measurement.
Tissue penetration of light differs based on wavelength (green = least, infrared = best).
Surrogate measure of neural activity cos looking at blood flow.
Motion artefact noise so moving the arm will change the signal.
Strengths to LDF
Non invasive measure of flow and velocity for peripheral activity.
Sensitive to high frequency perfusion changes.
Measurable in real time.
Green vs red light
Green light is more readily absorbed by tissue so can penetrate more shallowly and is sensitive to changes in blood flow during vasodilation, allowing us to extract aspects of velocity.
Red light = not sensitive to these changes cos it penetrates the middle of the vessel where blood flow moves quickly.
Functional near infrared spectroscopy (fNIRS)
Inject high intensity light into the head to see how it diffuses across detectors to have an idea of what’s happening across the length of those lasers.
Light is scattered in all directions and a portion of this is absorbed by chromophores in the tissue.
Different chromophores are sensitive to specific wavelengths of NIR - estimate proportion of these chromophores by measuring wavelength absorption.
By changing the wavelengths of light shone we can probe different parts of the periphery.
Different chromophores include …
Oxy and deoxyH are chromophores with very different absorption profiles.
Can calculate the ratio of oxyHb to deoxyHb by shining appropriate wavelengths of light on the head and measuring the intensity of the exiting light
More photons absorbed = more chromophores = higher absorption.
Shining wavelengths of NIR light tuned to absorption profiles of oxyHb and deoxyHb we can measure blood oxygenation.
Recording fNIRS
There’s various injector and detector pairs across the head. NIR light is delivered to and collected from fiber optic bundles.
Need a delicate balance between:
Comfort
Resistance to participant movement
And reduction of cross talk (to diff detectors they’re not paired with).
Strengths of fNIRS
Great biochemical specificity
Hugh temporal resolution
Ease of transport
Great to use in kids
Can improve spatial resolution of EEG/fMRI
Limitations of fNIRS
Questions about BOLD as a measure of neural activity
Assessment of haemoglobin species may differ within a single machine (but can be compensated for in analysis stage)
Limited penetration depth to the cortex
