MRI Based Techniques in Diagnosing Alzheimer’s Disease

ABSTRACT

With an aging population comes associated health complications. Senior Citizens aged 65 years and older have many health deficits but the most feared is Alzheimer’s disease. Alzheimer’s Disease is a neurodegenerative brain disorder.

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A brain disorder of this kind causes significant alterations to normal brain functions as well as structural. Magnetic Resonance Imaging, also known as MRI, is a diagnostic imaging modality that is used to diagnose and stage this disease as well as multiple other age-specific brain disorders. Utilization of current techniques and advancing new clinical research coupled with other diagnostic imaging modalities has helped increase early detection of Alzheimer’s disease thus, aiding in the prognosis and treatment. MRI-based techniques are being combined with functional and resting MRI studies, positron emission tomography and the use of chemical compounds and contrast agents to enhance visualization of brain atrophy before a patient begins to exhibit any symptoms. Advanced imaging has moved into a central position in the research and diagnosing of Alzheimer’s disease. Researchers also hope to perfect MRI techniques so that it can enhance the physicians’ ability to measure brain atrophy and diagnose Alzheimer’s with greater accuracy.. It has been recently found that combining advanced imaging modalities together to perform specific testing would more accurately diagnose Alzheimer’s with the combination of their results. Early detection of this disease is vital to the prognosis of this disease and will aid in implementing therapeutic treatments preserving as much of the patient’s independence as possible.

MRI-Based Techniques in Diagnosing Alzheimer’s disease

The population of people is aging rapidly and with that comes associated health complications (Korolev, 2014). There are many diseases associated with aging, however, the most feared disease would be Alzheimer’s disease. This disease is the most prominent public health problem that senior citizens are faced with (Jack, 2012). It is the fifth leading cause of death in adults and is estimated to be affecting over 5 million Americans (Korolev, 2014). Alzheimer’s disease is caused by changes in the brain integrity and neuro-activity as a progression of a mild cognitive impairment, MCI. (Bayram, Caldwell & Banks, 2018). Alzheimer’s Disease is a neurodegenerative brain disorder. A brain disorder of this kind causes significant alterations to normal brain functions as well as structural (Korolev, 2014). Dementia, a clinical syndrome that diminishes intellectual function of an individual, affects one-in-nine people aged 65 years and older with the leading cause of it being Alzheimer’s disease (Korolev, 2014). Looking at the disease at a cellular level, the disease targets particular cells such as the cortical neurons and the pyramidal cells. Disruption in these cells causes a progressive loss of cortical neurons, which transversely impacts cognitive functions of the individual (Korolev, 2014). The first symptoms of Alzheimer’s disease exhibit in the region of the brain known as the hippocampus. The atrophy located in this region of the brain is established best on an MRI examination and is what physicians use as the base criteria for diagnosing a patient with the disease (Bayram, Caldwell & Banks, 2018). Researchers are currently working to extend their techniques to better understand brain disorders such as Alzheimer’s (O’Connor, 2018). Dmitry Yablonskiy, a PhD and professor of radiology at Mallinckrodt Institute of Radiology, stated in a news release there are now MRI scans that can detect brain atrophy even before people begin to show symptoms of the disease.

Magnetic Resonance Imaging, also known as MRI, is a diagnostic imaging modality that uses strong magnetic fields coupled with radio waves to produce an image (Korolev, 2014). An antenna in the scanner machine detects the signals generated from the body, a computer then processes those radio frequencies and a three-dimensional image of the internal structures of the body is created (Ferris & Goergen, 2017). MRI non-invasively differentiates between various brain tissue components like gray matter, white matter and cerebral fluid then produces images by measuring the energy that is being released by the protons in those various tissues (Korolev, 2014). Brain and brain stem MRI scans focus on the smaller abnormalities and structures, which make it more effective in diagnosing brain disorders (Harkin, 2017). To improve the diagnostic accuracy of the MRI scan a contrast agent is sometimes used. Contrast is injected directly into the patient intravenously to better visualize the focus points of the exam (Harkin, 2017). One in three MRI scans are produced using a contrast agent that is gadolinium based (Ferris & Goergen, 2017). Gadolinium based contrast media is used because of its complex molecules and arrangement of atoms held together by chemical bonds giving it the ability to enhance the visualization of certain tissues, which improves the quality of the MRI images for the radiologist. Thus, aiding in a more accurate report on whether or not there is an abnormality present (Ferris & Goergen, 2017).

MRI has been a tool utilized in studying brain atrophy in patients with Alzheimer’s disease, mainly because of its ability to show the loss of brain mass associated with Alzheimer’s disease and other dementias (Marshall, 2018). The earliest detection of atrophy in the medial temporal lobe and hippocampus of the brain can be seen on a MRI scan when the hippocampus, the curved like structure found deep within the brain is disproportionately diminished in size (Marshall, 2018). When this is seen on the captured images it means that the patient has progressed from a form of mild cognitive impairment, MCI, to Alzheimer’s (Korolev, 2014). Patients who undergo MRI also show signs of enlarged lateral ventricles adjacent to the medial temporal lobes. (Korolev, 2014) These findings however are not common deficits of Alzheimer’s butt for other dementias. When coupling MRI scanning with other forms of diagnostic techniques it helps narrow down the diagnosis by revealing deficits distinct to Alzheimer’s (Marshall, 2018).

Functional MRI, or fMRI, is a technique that measures blood-oxygen-level-dependent activity, also known as hemodynamic activity. Different application techniques are used in fMRI such as resting and functional, which evaluate the brain’s intrinsic activity while being externally stimulated. This will show the patients decreased activity and connectivity in the brain, such as communication in the regions involving memory and the processing of information (Korolev, 2014). Basically, in a functional assessment the patient is asked to perform activities of daily living and the patient’s’ ability to successfully complete those tasks help determine the stage at which the Alzheimer’s has progressed (Marshall, 2018). A treatment plan based on those findings can help in preserving as much of the patient’s independence as possible (Marshall, 2018).

Positron Emission Tomography, also known as PET, is a nuclear imaging technique provides images of the brain activity based on blood flow, oxygen consumption and glucose use (Marshall, 2018). One of the techniques used with PET uses a radioactive tracer called fluorodeoxyglucose to measure the brain’s metabolism (Korolev, 2014). This specific exam is called an FDG-PET. The hypo metabolism of parts of the brain is the earliest sign of Alzheimer’s disease in a patient (Korolev, 2014). FDG-PET has also been a great asset in determining between different forms of dementia such as but limited to Alzheimer’s, MCI, frontotemporal dementia (Korolev, 2014). Researchers are optimistic about this techniques future in diagnosing Alzheimer’s (Dalli, 2018). Recent advancement in PET scanning is the implementation of in-vivo PET-based amyloidal imaging. During this examination amyloid plaques are sought out by a radioactive ligand called carbon-11-based amyloid labeling compound which then binds to these plaques. Alzheimer’s patients would have an increased showing of this in the parietal, temporal, and frontal regions of the brain (Korolev, 2014).

A study that was recently published in the Journal of American Medical Association, JAMA, was conducted using a new MRI-based PET method with over 700 participants, 90-95 % of all involved cases were successful in the diagnosing of Alzheimer’s (Dalli, 2018). This method used two protein markers known to be linked with Alzheimer’s, which spread throughout the brain years before a patient shows any symptoms of the disease. The two proteins are beta-amyloid and tau (Walter, 2018). The bio-marker consisting of the tau protein is injected into the patient and the MRI-based PET scan is then performed. ” If the patient has tau in certain parts of the brain, the marker will detect it,” said Hansson, a researcher at the Clinical Memory Research Unit at Lund University in Sweden ,in a recently published article by Kristen Dalli (2018). Rik Ossenkoppele, a colleague and fellow senior researcher of Dr. Hansson at Lund University, explained that “it is when tau begins to spread that the neurons start dying and the patient experiences the first problems with the disease… if we scan a patient with memory difficulties and he or she proves to have a lot of tau in the brain, we know with a high degree of certainty that it is a case of Alzheimer’s” (Walter, 2018). Kristen Dalli wrote in an Alzheimer’s News report what researcher Oskar Hansson said about it during a press release, ‘The method works very well, I believe it will be applied clinically all over the world in only a few years” (2018). So far, this technique is being used only in research studies. Experts anticipate PET scans with similar tracer compounds will be in general use within the next several years. These tests may help doctors diagnose the disease before symptoms appear, as well as assess new treatments (Marshall, 2018). A new clinical approach to diagnosing Alzheimer’s is still in its preclinical trial infancy and is known as simultaneous PET-MRI scanning. This new application will combine fMRI and PET and shows great potential in paving a new path for molecular imaging (Judenhofer et al., 2008).

New diagnosis’s are being made every 68 seconds in the United States and it is estimated that 65 million people are expected to be diagnosed by 2030 (Korolev, 2014). Fortunately, the diagnostic capability of brain scans is improving (Marshall, 2018). Diagnostically, advanced imaging has moved into a central position in research and diagnosing (Johnson, Sperling & Klunk, 2012). Researchers also hope to perfect MRI techniques so that it can enhance the physicians’ ability to measure brain atrophy and diagnose Alzheimer’s with greater accuracy (Marshall, 2018). It has been recently found that combining these modalities together to perform specific testing would more accurately diagnose Alzheimer’s with the combination of their results. The challenge of the future will be efficiently combining imaging techniques to facilitate a diagnosis as well as staging and developing effective therapies (Johnson, Sperling & Klunk, 2012). If widely embraced, the advances of MRI and the combination of testing would greatly expand the application of imaging to improve clinical diagnosis of Alzheimer’s (Jack, 2012). The slowing, delaying and prevention of this disease is clearly the most important goal for the future of understanding of Alzheimer’s disease (Johnson, Sperling & Klunk, 2012).

References

  1. Bayram, E., Caldwell, J., & Banks, S. (n.d). Current understanding of magnetic resonance imaging biomakers and memory in Alzheimer’s disease, Alzheimer’s & Dementia; Translational Research & Clinical Interventions, 4,395-413.
  2. doi:10.1016/j.trci.2018.04.007
  3. Dalli, K. (2018, September 21). New brain imaging technique may help doctors more accurately diagnose Alzheimer’s. Alzheimer’s News. Retrieved from https://www.consumeraffairs.com/news/new-brain-imaging-technique-may-help- doctors-more-accurately-diagnose-alzheimers-092118.html
  4. Ferris, N., Dr., & Goergen, S., Prof. (2017). Gadolinium Contrast Medium (MRI Contrast agents). The Royal Australian and New Zealand College of Radiologists. Retrieved July 26, 2017.
  5. Harkin, M. (2017, March 29). Head MRI: Purpose, Prepartation and Procedure. Retrieved from https://www.healthline.com/health/head-mri
  6. Jack, C. (2012, May 1). Alzheimer Disease; New Conceprts on Its Neurobiology and the Clinical Role Imaging Will Play. Radiology, 263(2), doi:10.1148/radiolo.12110433
  7. Johnson, K. A., Fox, N. C., Sperling, R. A., & Klunk, W. E. (2012). Brain imaging in Alzheimer disease. Cold Spring Harbor perspectives in medicine, 2(4), a006213.
  8. Judenhofer, M. S., Wehrl, H. F., Newport, D. F., Catana, C., Siegel, S. B., Becker, M., . . . Pichler, B. J. (2008). Simultaneous PET-MRI: A new approach for functional and morphological imaging. Nature Medicine,14, 459-465. doi:10.1038/nm1700
  9. Korolev, I. 0. (2014). Alzheimer’s Disease: A Clinical and Basic Science Review. Medical Student Research Journal,4(Fall), 24-33. doi:10.3402/msrj.v3i0.201333
  10. Marshall, G. A. (2018). Alzheimer’s Disease: A guide to coping, treatment, and caregiving. Boston, MA: Harvard Health Publishing.
  11. O’Connor, M. (2018, September 25). Unused MRI information offers insights into brain conditions. Proceedings of the National Academy of Sciences.
  12. Walter, K. (2018, September 19). New Brain Scan Provides More Accurate Alzheimer’s Diagnosis. R&D Magazine. Retrieved from https://www.rdmag.com/article/2018/09/new-brain-scan-provides-more-accurate- alzheimers-diagnosis
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