SUMMARY MINOR TRANSLATIONAL
NEUROSCIENCE PART 2
Elective minor year 3 – Biomedical Sciences
Radboud University, Nijmegen
Made by: Georgia Graat
,DTI and fMRI
MRI mechanism
• Hydrogen nuclei in the body are kicked by a strong magnetic field (3T)
• When the magnetic field is turned off, the kicked hydrogen nuclei return to their normal
state and emit radio waves when doing so
• An image is created that shows how strongly each voxel (square of hydrogen nuclei) emits
radio waves (hydrogen density)
Diffusion MRI
• Diffusion is created by random movement of molecules
o Diffusion is different for intra- and extracellular media
o Diffusion might be different in different directions
• In a normal MRI, one excitation pulse is used. The magnetic gradient is low at one side of the
body (e.g. feet) and high at the other side (e.g. head). This makes the nuclei spin faster at the
head side (high precession) and slower at the feet side (low precession)
• In a diffusion MRI, two excitation pulses are used, one after another in both directions.
o When the nuclei don’t move (no diffusion) you would imagine the nuclei getting out
of phase by the first pulse, but back in phase by the second pulse
o When the nuclei do move (diffusion) you would imagine the nuclei getting out of
phase by the first pulse, but also staying out of phase because they have taken a
different position before the second pulse.
• Different diffusions cause different signal strengths when compared to a baseline T2
weighted image. Three different diffusion signals: X, Y, and Z
o If any of the three gradient directions show signal loss compared to the T2 image →
normal diffusion → mid-gray value
o If all three gradient directions show minimal or no signal loss compared to the T2
image → diffusion restriction (no diffusion) → white value
• Diffusion tensor imaging (DTI)
o Images with gradients in many different directions. Determine direction and strength
of diffusion in each of the voxels (diffusion tensor)
o Information on fiber direction and brain connectivity
• Diffusion weighted imaging (DWI)
o Images with gradients in many different directions. Construct an image with the
average signals.
o Information on less diffusion spots in the brain
• Apparent Diffusion Coefficient (ADC) image
o Is not based on the T2 image and shows the level of diffusion: white = high diffusion
fMRI
• T2* is the observed value of T2, reflecting true T2 as well as magnetic field inhomogeneities
within voxels
o T2* is smaller than T2 and causes the nuclei to dephase quicker
▪ This can be compensated for, but that is not necessary for fMRI
• In fMRI, the T2* signal can be used to distinguish between oxyhemoglobin and
deoxyhemoglobin
• Utilization of NMR signal characteristics of oxy- & deoxyhemoglobin to indirectly measure
local neuronal activity based on vascular response.
• Oxy- & deoxyhemoglobin differ on the number of unpaired electrons
o Oxyhemoglobin → no unpaired electrons → diamagnetic → not magnetic → strong
signal on T2 weighted image
Made by: Georgia Graat
, o Deoxyhemoglobin → 4 unpaired electrons → paramagnetic → magnetic → weak
signal on T2 weighted image
• When part of the brain is active, increased blood volume is present due to vasoactive signals.
This causes an increase in oxyhemoglobin in that region of the brain, providing a relatively
stronger signal. (Blood Oxygen Level Dependent (BOLD) fMRI)
• Disadvantages
o Temporal resolution: inherent time delay between stimulus and fMRI signal
o Limited spatial accuracy: since this is an indirect measurement of brain activity, it
might be possible that the measured blood flow is a few millimeters away from the
increased blood flow
T1
• Signal strength is dependent on the time interval between pulses: repetition time (TR). The
longer the interval between pulses, the stronger the signal.
o Nuclei can only be excited if they are parallel to the magnetic field (in the ground
state)
o When TR is short, not all nuclei will have returned to the ground state and the signal
will be small
o T1 image is a very short T2 time where all nuclei are still in phase, but a medium T1
time
T2
• After the magnetic field is turned off, the spins dephase which decreases the signal strength
• Differences between different tissues, the contrast between these tissues depends on the
time between excitation and recording (echo time)
• T2 image is a very long T1 time where all nuclei are in their ground state again, but a medium
T2 time
Brain development
The construction of the brain and in general the development of the nervous
system is an integrated series of developmental steps, beginning with the
decision of a few early embryonic cells to become neural progenitors. These
steps follow a specific order, but are also seen simultaneously sometimes.
Since the nervous system is constructed over a period of time, behaviors
cannot be slapped together exactly at the moment they are first needed, but
arise with the developing circuitry. This takes time and if steps along the way
are not performed correctly or at the incorrect time, this might lead to
neurodevelopmental disorders.
Brain patterning thus requires certain developmental events to become one
whole organ. The process begins at molecule level, as all molecules together
form a map of the placement of all cells. This beginning at the smallest level mostly uses intrinsic
factors and transcription factors for controlling the process, mostly for regional specification and
expansion. A hallmark of development is thereafter migration to the correct place. Afferent input is
important here so contact with other regions is made throughout the areas. Extrinsic factors and
guidance cues are more important in the later stages, for brain arealization and synapse refinement.
Made by: Georgia Graat
, - Neural induction
This is the process in which the embryonic cells become neural progenitors. It all begins with the
zygote that turns into a blastocyst when the trophoblast (amnion and chorion) and inner cell mass
are clearly distinguishable. This develops into the gastrula with three germ layers, that serve as
primitive tissues from which all body organs will derive. These are the ectoderm, mesoderm and
endoderm. The ectoderm will turn into the epidermal skin layer and the whole central nervous
system!
After implantation, the neural induction will start in the blastocyst
and later gastrula. The embryo is first a flat disk that has one layer
of cells. This layer gets a primitive pit and a primitive streak at the
bottom. Right above this, but in the mesodermal layer, the
notochord can be found. The notochord is a rod of mesodermal
cells that serves as axial support. These starts giving off hormones
and other cues to the ectodermal layer. The ectodermal layer then
begins with the growth of the neural plate right above the
notochord. This is the beginning of the neural induction.
Then the neural
folding begins,
meaning the first sight of the human nervous
system is there. The thickened ectodermal layer
then starts folding inwards and the two neural
grooves beside it make it look like a pit or hole. This
folding happens inside of the mesoderm below it
and it folds down so far that eventually the neural
grooves will touch each other and the whole
ectoderm makes a tube inside the mesoderm. This is also called the neural tube that forms the brain
and spinal cord later. Right above the neural tube is the neural crest with some leftover ectoderm
within the mesoderm layer and next to the neural grooves are the somites, which will become
repetitive aspects of the body like the ribcage. The neural grooves first fold together in the middle of
the embryo, and then start closing towards the anterior and posterior neuropores. The anterior
neuropores is closed earlier, meaning things like spina bifida (no correct closing of the neural tube all
the way) are more common at the end of the spinal cord and not the brain.
- Polarity and segmentation
Neurulation is the stage of organogenesis in vertebrate embryos during which the neural tube is
transformed into the primitive structures that will later develop into the central nervous system,
which has happened right before segmentation starts. Polarity and segmentation is regional
specialization of the nervous system, which arises during development of all animals, including
humans. This means the vesicles specify to a more clear role in the system and each region gets a
certain task. A segmentation gene is also a term for a gene whose function it is to specify tissue
pattern in each repeated unit of a segmented organism.
The divide starts with 3 primary vesicles, and the order of these primary and later secondary vesicles
is really important in the good buildup and functioning of the brain. If these are not correctly formed
or not in the right time, this will lead to neurodevelopmental disorders. The 3 primary vesicles are
from cranial to caudal forebrain, midbrain and hindbrain. This starts to change and divide into several
other parts that really get their own functions and structures during development. The forebrain, or
Made by: Georgia Graat
