Taking pictures of your brain - MRIs and Alzheimer's Disease

Currently, the only confirmation of Alzheimer's Disease is made post-mortem; by looking at the brain after death. Additionally, current therapies seem to work best when Alzheimer's is not in an advanced stage. Therefore, early, accurate diagnoses of Alzheimer's is crucial to the welfare and caregiving of patients.

Although there are other possibilities, neuroimaging is arguably the best candidate for early detection of Alzheimer's. 'Imaging' is just a fancy way of saying 'let me take a picture'. Neuroimaging, therefore, is the ability to take a picture of your nervous system. In this case, we're talking about the brain.

Since this isn't my area of expertise, I was thrilled that my friend and fellow graduate student, Ms. Joey Contreras (@JoeyAnnette) agreed to answer some basic questions about neuroimaging in Alzheimer's Disease. Joey is doing her grad work in a lab that is well-renowned for terrific work in neuroimaging in Alzheimer's and other disorders. 

1.    What is an MRI?

MRI stands for Magnetic Resonance Imaging. An MRI scanner uses magnetic fields and radio waves to be able to form images of structures within the body, like the brain. This technique is really helpful in medical imaging research because it’s a non-invasive, safe procedure that does not require exposure to any radiation (like positron emission tomography, PET). 

When MRI is applied to the investigation of brain disorders we call this “neuroimaging” and it’s often the tool of choice because you can visualize and differentiate between different types of brain tissue. The two major types of brain tissue are called grey matter and white matter. 

Grey matter (GM), which is normally a pinkish grey color in a living brain, is the part that contains all the cell bodies, dendrites, and axon terminals of neurons (highlighted with red arrow). The other major tissue in the brain is referred to as white matter (WM). White matter is named because of its whitish color, which is made up of axons connecting different parts of grey matter to each other (shown by the blue arrow). Basically, these axons are like the major highways for information to travel in the brain. The green arrow denotes cerebral spinal fluid (CSF), which acts as a cushion, protecting the brain and spine from injury.

            During Alzheimer’s disease (AD) the brain experiences major damage in the form of overall loss of grey matter as well as loss of or abnormal WM. Additionally, abnormalities in GM and WM have been found to be correlated with cognitive decline (a major indicator of disease progression with Alzheimer’s disease). In this regard, its important to get a comprehensive picture of exactly what changes are occurring as the disease progresses and even before diagnosis occurs, this is where getting a good picture of brain can help.  

To speak on this a little more, the problem with Alzheimer’s disease is that by the time you start to notice cognitive decline (noticeable memory loss) years of underlying abnormal neuropathology may already have occurred.  Using neuroimaging techniques, we may be able to detect a problem even before the patient does if they come in early enough.

2. What is an fMRI

Similar to MRI, fMRI stands for functional magnetic resonance imaging. This type of imaging is unique in that it measures brain activity by detecting changes in blood flow in different areas of the brain. This technique takes advantage of the fact that when an area of the brain is in use, blood flow to that region will be greater.  This is what’s essentially called a BOLD (blood-oxygen-level dependent) signal.  

The advantage of fMRI over MRI is that fMRI can monitor brain activity and detect functional differences in brain regions when the brain in engaged in a task (ie, memory task, motor task, etc) or disengaged (at rest).  In terms of diagnosing Alzheimer’s disease, there is no single test that can be used. As a result, a medical evaluation which includes past and current medical standing, mental status, physical and neurological exams, blood tests, and of course brain imaging data (fMRI, MRI etc) go into establishing a diagnosis.

            Often times when MRI is used to aid in diagnosing AD.  It does so by looking for similar patterns such as a reduction in grey matter (indicated by red circle in top image, and arrows in bottom image ), resulting in enlarged ventricles (indicated by red arrows in top image) and overall dramatic volumetric loss in medial temporal lobes.

In terms of helping diagnosis AD, fMRI is a bit less straightforward. However, there is a lot of evidence to suggest the carriers of the e4 allele of the apolipoprotien E (APOE) gene (associated with increased risk for late-onset AD) correlate strongly with functional brain activation patterns in older adults despite normal cognitive abilities (Bookheimer et al, 2000),. This would suggest that fMRI can help elucidate changes in the brain that would otherwise be undetectable in a high-risk population for AD (for more in depth review on this look for Rishacher et al, 2013)

3. What are the problems with the field that have hampered progress in diagnosing AD?

            Imaging studies involving neurodegenerative diseases and dementias such as AD are very informative regarding structural and functional changes in  the brain which are underlie the observed clinical symptoms such as cognitive decline. They play an important role in aiding and supplementing additional data for making an accurate diagnosis as well as ruling out other diagnoses. Further studies with advanced MRI and fMRI techniques will likely provide even more information about pathology associated with AD. 

However the problem now is that these techniques are still relatively new in a young field (neuroscience). As a result there is a lot more room for improvement and accuracy. For instance, resolution is something that the field of neuroimaging still struggles with immensely. Think of it in terms of TV screens. When the TV first came the image was pixelated and fuzzy. This is very true for MRI and fMRI but instead of pixels we have something called voxels. 

Voxels are essentially a 3D pixel and the smaller the voxel the more accurate the picture. As time progresses we, as a field, are getting better at this going from a 5 mm³ voxel to current 1 mm³ voxels or smaller. Better resolution means more accurate representation of brain tissue in both time and space, which is incredibly important if we want to make accurate diagnostic boundaries.  We also need to do a better job in terms of identifying and using appropriate statistical methods that will allow us to analyze and integrate large imaging data sets and different types of imaging data.

4.    How do you see the field of neuroimaging contributing to the diagnosis/treatment of Alzheimer’s in the future

  Neuroimaging has major potential. In the last 10 years we have seen exponential growth in this area as well as the emergence of a new field called brain connectomics. Brain connectomics is the marriage of network science theory with neuroimaging.

 Basically, this field uses information from MRI, fMRI and other imaging sequences (which I can go into at another time) and analyze it in a new way, helping to predict how information flows and model anatomical and functional pathways in the brain.  

The field of neuroimaging and brain connectomics holds promise in two ways. First, it will be able to identify early pathological changes that may otherwise have been undetectable. Second, we could also use fMRI to assess the effects of various treatments (e.q. get a baseline assessment of functional brain changes and comparing that to how that same brain might change or improve with treatment). 

This would allow us to better monitor and personalize treatments for patients.  Basically this field has the potential to better predict cognitive impairment, even before the onset of clinical symptoms, creating promising biomarkers for understanding AD.

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Thanks, Joey!! 

Joey's work:

The goal of my project is to identify and characterize the subtle changes that occur in both structural and functional connectivity in the brain during the early prodromal to clinical stages of Alzheimer’s disease (AD). Recent evidence indicates that cognitive alterations as well as anatomical abnormalities in AD begin manifesting years before they can be detected by traditional methods. In order to assess the brain from a systems perspective, I have begun to use brain connectomics (a very powerful methodology that relies on network science). This allows me to assess and understand how brain networks are affected at different stages of neurodegeneration.