The Brain & Neuroimaging: MRI

Question 1

What is most of the body made up of and what happens when you lie under scanner magnets?

Answer 1

• Most of human body is made up of water molecules (hydrogen & oxygen atoms)
  o At centre of each hydrogen atom is an even smaller particle, called proton
  o Protons are like tiny magnets & are very sensitive to magnetic fields
• When you lie under the powerful scanner magnets, protons in body line up in the same direction, in same way that a magnet can pull the needle of a compass
• Short bursts of radio waves are then sent to certain areas of the body, knocking the protons out of alignment
  o When radio waves are turned off, the protons realign. This sends out radio signals, which are picked up by receivers.
• These signals provide info about exact location of protons in body
  o They also help to distinguish between various types of tissue in the body, as protons in different types of tissue realign at different speeds & produce distinct signals
• In same way that millions of pixels on a computer screen can create complex pictures, signals from millions of protons in body are combined to create a detailed image of inside of body

Question 2

Describe MRI and what it stands for?

Answer 2

• Magnetic resonance imaging (MRI), nuclear magnetic resonance imaging (NMRI), or magnetic resonance tomography (MRT) uses strong magnetic fields radio waves & field gradients to form images of organs in body
• MRI uses the spin of atomic nuclei of hydrogen – these have a magnetic dipole like a compass needle & thus can be detected by MRI
  o Imposed magnetic field aligns the nuclear spin - anything that is out of line generates a radio freq
  o This RF gives an image when it is Fourier transformed.
• MRI is widely used in hospitals & clinics for medical diagnosis, staging of disease & follow-up without exposing body to ionizing radiation
  o If have any type of metal in body then cannot use MRI
• MRI is designed for revealing the peculiarities of anatomical structure inside a human organism, including those in human brain
  Using MRI, doctors and scientist can grossly visualise organs & tissues

Question 3

Describe fMRI?

Answer 3

• fMRI maps image via measuring blood flow levels in human brain
  o Data captured with fMRI shows changes in metabolic functioning in brain
• Due to different ways of measuring processes in human brain, MRI & fMRI differ in terms of the resulting picture
• MRI measures the hydrogen nuclei
  o Captured data allows MRI to create a spatial image of finest resolution of human brain
• fMRI measures oxygen levels flowing into brain & calculates differences in tissue with respect to time
• fMRI is a more recent technique – only beginning to gain popularity – still a research tool
  fMRI noninvasively measures brain activity changes deep inside brain

Question 4

Give some information on fMRI?

Answer 4

• Non-invasive
• Used to show where something is happening in response to a stimulus
• Brain, like any other organ in body requires steady supply of oxygen to metabolise glucose to provide energy
  o This oxygen is supplied by component of blood called haemoglobin
• Magnetic properties of haemoglobin depend on amount of oxygen it carried
  o This dependency gave rise to method for measuring activation using MRI –> known as fMRI
• Measuring oxygen use

Question 5

Describe metabolism & blood flow in the brain?

Answer 5

• The biochemical reactions that transmit neural information via action potentials & neurotransmitters, all require energy
• This energy is provided in form of ATP, which in turn is produced from glucose by oxidative phosphorylation & Kreb’s cycle

Question 6

Describe ATP, Oxygen and Haemoglobin?

Answer 6

• As ATP is hydrolysed to ADP, energy is given up, which can be used to drive biochemical reactions that require free energy
• Production of ATP from ADP by oxidative phosphorylation is governed by demand, so energy reserves are kept constant
  o Rate of reaction depends mainly on level of ADP present
  o Means rate of O2 consumption by oxidative phosphorylation is a good measure of rate of use of energy in that area
• Oxygen required by metabolism is supplied in blood. Since oxygen is not very soluble in water, blood contains a protein that oxygen can bind to, called haemoglobin
  o Important part of haemoglobin molecule is an iron atom (gives blood its colour) bound in an organic structure
  o When an oxygen molecule binds to haemoglobin it is called oxyhaemoglobin
  o When no oxygen is bound it is called deoxyhaemoglobin
• To keep up with high energy demand of brain, oxygen delivery & blood flow to this organ is quite large.
• Although brain’s weight is only 2% of body’s, its oxygen consumption rate is 20% of body’s & blood flow 15%
• Blood flow to grey matter, which is a synapse rich area, is ~10x that to white matter per unit volume
• Regulation of regional blood flow is poorly understood, but it is known that localised neural activity results in rapid selective increase in blood flow to that area

Question 7

Describe BOLD Contrast in MR Images & what does BOLD stand for?

Answer 7

Blood Oxygen Level Dependent
* Since regional blood flow is closely related to neural activity, measurement of rCBF (regional cerebral blood flow) is useful in studying brain function
* Can measure blood perfusion with MRI
* Another, more sensitive, contrast mechanism which depends on the blood oxygenation level, known as blood oxygen level dependent (BOLD) contrast
* Deoxyhaemoglobin is a paramagnetic molecule whereas oxyhaemoglobin is diamagnetic
* Presence of deoxyhaemoglobin in a BV causes a susceptibility difference between vessel & its surrounding tissue
o Such susceptibility differences cause dephasing of MR proton signal, leading to reduction in value of T2*
o In a T2* weighted imaging experiment, presence of deoxyhaemoglobin in BVs causes darkening of image in those voxels (like pixels) containing vessels
o Since oxyhaemoglobin is diamagnetic & does not produce same dephasing, changes in oxygenation of blood can be observed as the signal changes in T2* weighted images
 T2* just the arbitrary name given to signals coming out of this process

Question 8

Describe BOLD - blood oxygen level dependent?

Answer 8

• Brain requires homeostatic level of oxidation all time so therefore it is requiring more blood flow even at rest than e.g. a muscle cell
  o When this homeostatic level falls, get problems
• Get cell death when there is ischaemia (lack of blood)
• On neural activation, O2 consumption ↑ & level of deoxyhaemoglobin in blood also ↑ & MR signal ↓
  o However, what is observed is an ↑in signal, implying a ↓ in deoxyhaemoglobin
   Relative huge increase in oxygenation in particular area to a particular area as it is being activated more than other areas of brain
• This is because upon neural activity, as well as slight ↑in oxygen extraction from blood, there is a much larger ↑in cerebral blood flow (arterial flow ↑), bringing with it more oxyhaemoglobin
  o Thus, bulk effect upon neural activity is a regional ↓in paramagnetic deoxyhaemoglobin (regional ↓in venous return – venous return especially in brain is dependent on gravity so goes back down slowly meanwhile heart is pumping blood to keep homeostatic level of oxygenation in brain normal), and an ↑in MR signal

Question 9

Describe PET, NIRS & BOLD?

Answer 9

• Study of these mechanisms w/ BOLD is helped by results from PET & near-IR spectroscopy (NIRS) studies
• PET has shown that changes in cerebral blood flow & cerebral blood volume upon activation, are not accompanied by any significant ↑in tissue oxygen consumption
  o Just flow increases, not consumption
  o Heart sends more blood to brain because brain calls for it since it is being activated
• NIRS can measure changes in concentrations of oxy- & deoxyhaemoglobin, by looking at absorbency at different frequencies
  o Such studies have shown an ↑in oxyhaemoglobin & a ↓deoxyhaemoglobin upon activation
   ↑in total amount of haemoglobin is also observed, reflecting ↑ in blood volume upon activation
• Time course for BOLD signal changes is delayed from onset of neural activity by a few seconds, & is smooth, representing changes in blood flow that technique detects
  o Termed the ‘haemodynamic response’ to the stimulus
  o There have also been observations of an initial small ‘dip’ in signal before & after the larger ↑in signal, possibly reflecting a transient imbalance between metabolic activity & blood flow
• On activation, O2 is extracted by cells (neurons), thereby ↑level of deoxyhaemoglobin in blood
  o Compensated for by an ↑in blood flow in vicinity of active cells, leading to a net ↑in oxyhaemoglobin