Radboud University, Nijmegen
Made by: Georgia Graat
SUMMARY MINOR TRANSLATIONAL
NEUROSCIENCE PART 2
Elective minor year 3 – Biomedical Sciences
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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
- Diffusion is different for intra- and extracellular media
- Diffusion might be different in different directions
- When the nuclei don’t move (no diffusion) you would imagine the nuclei getting out
- When the nuclei do move (diffusion) you would imagine the nuclei getting out of
• 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.
of phase by the first pulse, but back in phase by the second pulse
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
- If any of the three gradient directions show signal loss compared to the T2 image →
- If all three gradient directions show minimal or no signal loss compared to the T2
- Images with gradients in many different directions. Determine direction and strength
- Information on fiber direction and brain connectivity
- Images with gradients in many different directions. Construct an image with the
- Information on less diffusion spots in the brain
- Is not based on the T2 image and shows the level of diffusion: white = high diffusion
normal diffusion → mid-gray value
image → diffusion restriction (no diffusion) → white value • Diffusion tensor imaging (DTI)
of diffusion in each of the voxels (diffusion tensor)
• Diffusion weighted imaging (DWI)
average signals.
• Apparent Diffusion Coefficient (ADC) image
fMRI • T2* is the observed value of T2, reflecting true T2 as well as magnetic field inhomogeneities within voxels
- T2* is smaller than T2 and causes the nuclei to dephase quicker
- Oxyhemoglobin → no unpaired electrons → diamagnetic → not magnetic → strong
▪ 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
signal on T2 weighted image 2 / 4
Made by: Georgia Graat
- 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
- 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.
- Nuclei can only be excited if they are parallel to the magnetic field (in the ground
- When TR is short, not all nuclei will have returned to the ground state and the signal
- T1 image is a very short T2 time where all nuclei are still in phase, but a medium T1
state)
will be small
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.
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Made by: Georgia Graat
- Neural induction
- Polarity and segmentation
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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.
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