Alteration of Hippocampal Perfusion as an Early Indicator of Alzheimer's Disease

Evaluation with Arterial Spin Labeling MRI

Thomas Liu, Ph.D.

University of California, San Diego

Funded in February, 2002: $100000 for 4 years
LAY SUMMARY . BIOGRAPHY . HYPOTHESIS . FINDINGS . SELECTED PUBLICATIONS .

LAY SUMMARY

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A Potential New Indicator for Detecting Early Alzheimer’s Disease

While a decade ago diagnosing Alzheimer’s disease primarily helped a patient and family prepare for the patient’s inevitable cognitive deterioration, today early diagnosis allows for use of promising therapeutic approaches to slow cognitive decline. This makes early diagnosis key. Past research using two invasive imaging techniques, PET and fMRI, suggest that people with early Alzheimer’s disease have decreased blood flow to a part of the brain involved in forming memories, the hippocampus. The UCSF researchers hypothesize that a non-invasive technique, a form of MRI called arterial spin labeling (ASL), can be used to measure blood flow to the hippocampus at rest and during memory tasks. ASL relies on water already present in the blood, and, unlike PET and fMRI, does not require radioactive labeling to produce a scan. The researchers will compare ASL scans of people with mild cognitive impairment to those of healthy controls at rest and while performing memory tasks.  If ASL proves to be a reliable diagnostic tool, its ease of administration could make it an important advance in diagnosing Alzheimer’s disease early, when treatment is most likely to be effective.

INVESTIGATOR BIOGRAPHIES

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Thomas Liu, Ph.D.

Assistant Professor of Radiology, University of California, San Diego

HYPOTHESIS

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Hypothesis: 
The proposed research will test the hypothesis that resting hippocampal perfusion levels and task-related functional increases in hippocampal perfusion, as measured by arterial spin labeling (ASL) magnetic resonance imaging (MRI), can serve as early indicators of Alzheimer's disease (AD).

Goals: 
Alzheimer's Disease (AD) initially attacks structures in the medial temporal lobe, such as the hippocampus and the entorhinal cortex, that are critical to proper memory function. The overall objective of this proposal is to determine if measures of cerebral blood flow (perfusion) in the hippocampus as measured with arterial spin labeling magnetic resonance imaging can aid in the early diagnosis of AD. The two specific aims are: 1) Measurement of resting hippocampal perfusion: This aim will examine the effect of AD on the resting level of perfusion in the hippocampal region. 2) Measurement of functional changes in hippocampal perfusion:  This aim will examine the effect of AD on functional changes in hippocampal perfusion during a memory encoding task

Methods: 
The proposed pilot study will involve 10 patients exhibiting signs of mild AD or mild cognitive impairment and 10 age-matched control subjects. For measurements of baseline perfusion, the subjects will be asked to remain motionless in the MRI scanner with their eyes closed. Functional perfusion changes will be assessed during a memory encoding task in which the subject will view alternating blocks of novel color outdoor scenes and familiar scenes.  Arterial spin labeling imaging data will be acquired on a 3 Tesla MRI scanner.  Levels of resting and functional perfusion in the hippocampal region will be compared across groups.

 

FINDINGS

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In the course of this study, we found that the available methods for measuring perfusion in the hippocampus did not work well in older adults.  We therefore developed new methods to improve the quality of our perfusion measurements (Restom et al. 2006a,b). To test these methods, we then compared perfusion in the hippocampus between healthy young and elderly adults (Restom 2006c, Bangen 2006).  We found that, although the older adults start off with lower levels of hippocampal perfusion, when asked to perform a memory task they try to get to nearly the same level of perfusion as the young subjects .  Now that we have tested our methods in healthy subjects, we are acquiring perfusion data in subjects with mild cognitive impairment.  Our preliminary results suggest that the subjects with mild cognitive impairment show less of a perfusion increase than the older healthy subjects.

 

SELECTED PUBLICATIONS

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Restom K., Behzadi, Y., and Liu, T.T.  Physiological noise reduction for arterial spin labeling fMRI.  NeuroImage, 2006 Jul 1; 31(3):1104-15.

Liu T. T., Stark C. E. L., Wong E. C., and Buxton R. B. (2001)."Quantitative imaging of hippocampal perfusion during a memory encoding task." Proceedings of the 9th Meeting Intl. Soc. Mag. Reson. Med., p. 1285.

Restom K., Bangen K.J., Perthen J.E., Bondi M.W., and Liu T.T. “Physiological Noise Correction is Critical for Quantitative Perfusion fMRI of the Hippocampus in Elderly Adults.”  12th Annual Meeting, Organization for Human Brain Mapping, Florence, 2006b, p. 428.

Restom K., Bangen K.J., Perthen J.E., Bondi M.W., and Liu T.T. “Quantitative Hippocampal Perfusion Response to a Memory Encoding Task: A Comparison Between Healthy Young and Elderly Adults.”  14th Meeting, International Society for Magnetic Resonance in Medicine, Seattle, 2006c, p. 377.

Bangen K.J., Restom K., Liu T.T., Jak A.J., Han S.D., Fleisher A.S., Salmon D.P., Thal L.J., and Bondi M.W. “Hippocampal perfusion during picture encoding: A comparison between younger and older adults.”  12th Annual Meeting, Organization for Human Brain Mapping, Florence, 2006, p. 263.