As people age, it is common for their brain white matter to change. These changes often appear as bright white spots on T2-weighted MR scans. These areas or spots of hyperintensity (i.e., white matter hyperintensities {WMH}) are also called leukoaraiosis (LA). Researchers are still investigating the exact nature and pathology of these abnormalities but our understanding of them is increasing. They most often seem to start around the lateral ventricles and spread from there, although it is possible to have punctate WMH throughout the brain white matter (i.e., WMH that are not connected to other regions). WMH on brain MRIs represent rarefaction of the white matter, including swelling, demyelination, and damage, although the exact nature and combination of the white matter changes is not known. These WMH can interfere with normal cognitive functioning, including processing speed, attention, inhibition, as well as global executive functioning (although these claims are still being investigated).
Other damage to white matter includes lacunes, which are little holes in the brain, much like the holes in Swiss cheese. They are caused by mini infarcts, or strokes, or other processes. Most of the time they are due to “silent strokes”, or strokes that are small enough that the person does not have any noticeable stroke symptoms. These lacunes can have similar impact on cognition as WMH. Both WMH and lacunes are related to vascular risk factors, such as hyper- or hypo-tension, diabetes, etc.
Moral reasoning is the ability a person has to reason in and through social, ethical, and emotional situations. One component of moral reasoning is moral behavior, which is the intentional and voluntary acting in a prosocial manner (Walker, 2004). Moral behavior and reasoning are the foundation for “many human social and cultural institutions such as family structures, legal and political government systems that affect the lives of virtually every person” (Eslinger, Flaherty-Craig, & Benton, 2004, p. 100). Often situations in life are morally ambiguous and involve a choice between two actions that both have consequences that may or may not be in opposition to each other. Some researchers, such as Lawrence Kohlberg, believe that people will reason through these situations at varying levels or stages, with some in a very concrete and egotistic manner and others in an abstract and universal manner.
Lawrence Kohlberg was the first researcher to come up with a major testable theory of moral development. He formulated six stages of development, with most adults reaching stage four, a few five, and very few stage six. The first two stages are at the pre-conventional level (typically self-centered and concrete reasoning), stages three and four are at the conventional level (recognition of social norms and laws), and the last two stages at the post-conventional level (recognition of universal rights and responsibilities). While Kohlberg’s theory of moral development is a stage model, the progression through the stages is not necessarily viewed as invariant. This means that people reach them at different rates and do not always reason at a particular stage with any given dilemma. There is significant variability within and between people in moral reasoning abilities. Most research focuses on between-person variability.
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I just ran across a site that has a few medical imaging software packages. One of them is MedINRIA.
“MedINRIA aims at providing to clinicians state-of-the-art algorithms dedicated to medical image processing and visualization. Efforts have been made to simplify the user interface, while keeping high-level algorithms. Each application is called a module, and can be loaded dynamically from a single main window. MedINRIA is available for Microsoft Windows XP/Vista, Linux Fedora Core, MacOSX, and is fully multithreaded.”
Link to a description and download.
I have not tried the software yet – my MRI analysis software is FSL – but this software looks promising. Plus it runs natively on Windows, Linux (Fedora Core), and Mac OS X (FSL only runs natively in OS X and Linux – it’s a little tricky to run in Windows). Not that running in Windows is necessarily a perk – our preferred MRI processing workstation is a Mac – but many people are using Windows. If I get around to installing the software, I’ll post a review of it later. I’m always looking to user-friendly ways to analyze MRI data. Best of all, like FSL, it is free. It is based, in part, on the open-source and excellent ITK and VTK packages.
Angelo Mosso was an Italian physiologist, interested in many things but among them, blood flow and blood pressure in humans. He was born in Turin in 1846 to a father who was a carpenter by trade. Showing great promise in school, Mosso was able to attend the University of Turin and study the natural sciences. Always the consummate and prodigious researcher, over the course of his career he published more than 200 articles and books. Mosso’s work helped lay the foundation for many important (and modern) neuroscientific research methods, such as fMRI and the polygraph.
Mosso demonstrated in the late 1800s an increase in brain blood vessel pulsation as people thought about things. He interpreted this to mean that blood flow increased to the brain when people had thoughts. This particular study was one of the first (documented) functional neuroimaging (of sorts) studies. Both fMRI and PET are based on the idea that increased blood flow to the brain is associated with changes in cognition. It’s doubtful that he could have imagined how influential this research would be.
Visit this site for a longer biography of Mosso.
I learned something new this week. Modern MRI scanners produce high-strength magnetic fields (typically 1.5T up to about 20T – scanners for use with humans max out at about 7T right now {those are very rare though, 1.5T and 3T are more common). To produce these fields the scanners need to have strong electric currents. In order to handle large currents, scanners use superconductors cooled with liquid helium. In cases of serious malfunction or emergency the MRI scanner can be quenched, which releases all of the liquid helium. The helium turns into a gaseous state rapidly and expands to fill the room. The quench will make a loud sound like a jet engine or a pop. If the room is small enough, all of the air can be pushed out as the helium expands and increases the pressure. Most MRI rooms have fail-safe systems that release the helium outside, which prevents the occupants from suffocating.
Image from here.
For my research, I’ve been spending time processing brain MRIs and measuring the volume of the brain and lateral ventricles. Here is an image of one of the brains (visualization by FSLView 3.0, with ventricles measured by ITK-Snap). The image is slightly messy because the brain did not extract perfectly (separating brain from non-brain). Also, portions of the ventricles are missing (especially the occipital and temporal horns) due to imperfect MRI resolution and processing. The ventricles are viewed through a cut-away of the 3D-rendered brain.
Note: You MAY NOT use this image without express written consent from me.
I attended an interesting lecture this week. The professor who spoke talked about Diffusion Tensor Imaging (DTI) as well as about a newer technology they are trying to help develop – High Angular Resolution Diffusion Imaging (HARDI). DTI is based on tensor mathematics and physics. The tensor in DTI is basically a 3×3 matrix (x, y, and z planes) of numbers that represent the diffusion per voxel in the brain. A voxel is a volumetric pixel – a 3D portion of the brain in MR imaging. The highest resolution we can typically get with clinical MR scanners is a cubic mm voxel. So with DTI we have a tensor, a matrix, that describes the diffusion of water molecules within each voxel in the brain. Diffusion in a jar of water or in the ventricles of the brain tends to be fast and spherical. It is less spherical in the gray matter and even less so in the white matter. In fact, the diffusion of water is highly directional in white matter (the myelinated axons of neurons). This means that the water molecules tend to diffuse somewhat parallel to the length of the axon. The movements of these water molecules are picked up by the MR scanner (which is technically “focusing” on the hydrogen atoms in water).
The diffusion per voxel can be quantified by measures of fractional anisotropy (how directional is the movement), Mean Diffusivity (total diffusion within the voxel), and by the eigenvalues of the matrix (basically how far the molecules moved in the direction of the eigenvector).
Back to HARDI. HARDI improves upon DTI by allowing for more directions of the white matter fibers to be separated out than is possible with DTI. There are some areas of the brain where there are a lot of crossing fibers and these areas show up as dark spots on DTI (which looks like a hole in the brain). With HARDI, you can see that the fibers are just more complex than is possible to calculate with DTI.
Both of these methods are useful for measuring the overall integrity (and potentially connectivity) of the white matter in the brain.
Technology Review has an interesting article about “new” 3D brain imaging software being developed at Thomas Jefferson University Hospital in Philadelphia, PA (I put “new” in quotation marks because there are other similar programs out there; they might not be as polished but some are even open source). Their software fuses MRI, fMRI, and DTI together to create a fairly comprehensive view of the brain: “The fusion of these different images produces a 3-D display that surgeons can manipulate: they can navigate through the images at different orientations, virtually slice the brain in different sections, and zoom in on specific sections.”
The software looks like it is aimed more at neurosurgeons than researchers (i.e., it probably isn’t free like a lot of MRI image processing software). It does produce amazing images (view the images here) and looks like it could be a very useful tool for at least a qualitative approach to brain imaging.
The software is focused a lot on DTI (diffusion tensor imaging) and how the white matter fibers in the brain interact with lesions or tumors. I think that one researcher’s word of caution is important:
“Bruce Fischl, an assistant in neuroscience at Massachusetts General Hospital, says that the idea is ‘interesting’ but cautions that there are a number of levels of ambiguity when talking about connectivity in imaging. ‘Just because you live next to the Mass Pike doesn’t mean that there is an exit,’ he says.”
In other words, don’t get too caught up in the fact that fibers are right by a tumor, they may not really have anything to do with the part of the brain the tumor is most affecting.
In any case, I think that the idea behind this software is amazing. The graphics renderings are impressive (but they are just the pretty pictures – the rendering details may be beneficial in clinical surgery settings but they are not particularly useful in research situations, other than producing nice pictures to go in your publication). This software is very similar to something that I envisioned using a few years ago and I’m glad to see it being developed.
Image credit: Song Lai, Thomas Jefferson University Hospital (borrowed via technologyreview.com)
For a simply fabulous introduction to magnetic resonance imaging (MRI) visit Dr. Hornak’s site: http://www.cis.rit.edu/htbooks/mri/
It provides a basic but very in-depth overview of MR imaging, including the statistics and physics behind the images. It’s probably the best freely-available resource about MRI on the web.
The positron emission tomography (PET) scan measures blood flow in the brain. This is accomplished by injecting a person or animal with a radioactive isotope (i.e. an unstable atom, usually a variation of oxygen that has a short-half life); this isotope will quickly decay. Founded on the assumption that blood flow will increase in areas of the brain that are in heavy use (such as when a person is viewing an object or reading words or some other cognitive-intensive function), a fair portion of the injected isotopes will end up in the active part of the brain. As the isotopes decay, a positron (a small particle with the exact opposite charge as an electron) is released. This positron will collide with an electron and they will annihilate each other, sending two gamma ray particles in exactly opposite directions. These gamma rays are picked up by the PET scanner, which then determines where they came from in the brain. Since blood should concentrate where the brain is activated, there should be higher levels of isotopes there and this will show up on the scanner in the form of increased levels of gamma rays. The test is usually run twice (once as the control condition and once as the experimental). The difference between the two conditions is measured and any difference should show what area(s) of the brain was (or were) activated.
A PET scan is similar to an fMRI in that both measure blood flow in the brain, which is an indirect measure of brain activity. However, there are advantages and disadvantages to both functional brain imaging methods. PET scans are advantageous in that a person does not have to remain as still as he or she would for the fMRI. Tiny movements can obscure and ruin fMRI data but small movements do not affect PET scans. So, for example, with a PET scan study a researcher could have someone read out loud lists of words but the simple jaw movements would ruin the fMRI data (although this is changing to some degree as image processing becomes more sophisticated; researchers also can modify the task slightly to reduce movement artifacts in fMR images). This is really the main advantage of PET over fMRI.
PET scanning is disadvantaged compared to fMRI because the resolution of the scans is lower. PET scans can measure changes in blood flow in the brain in an area of about 5-10 cubic millimeters. fMRI can resolve down to 3 cubic millimeters and even lower as the machines become more powerful. PET scanning is also much more expensive than fMRI since it takes a special machine, radioactive isotopes, and multiple trials to get a scan. fMRI’s can be done at many hospitals around the world with little or no extra cost because of the prevalence of MRI scanners. Another disadvantage PET’s have are needing radioactive isotopes to work. This isotope can be given only a few times before it is unsafe.
While PET scans were and are better in some situations than fMRI’s, they have many disadvantages overall. With higher cost, lower spatial resolution, and need for isotopes, the disadvantages of PET scans seem to outweigh the advantages.
Image by Muffet.
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