Perfusion MRI Studies of Patients with Alzheimer's Disease

Andrew J. Greenshields, BS; Jacobo Mintzer, MD; Dario Mirski, MD; Heather Lawrence, BA; Andrew M. Speer, MD; Ziad Nahas, MD; Daryl E. Bohning, PhD; Mark S. George MD

Functional Neuroimaging Division, Departments of Psychiatry, Radiology and Neurology

Abstract

PET and SPECT studies have shown that persons with AlzheimerÕs Disease (AD) have decreased perfusion and metabolic activity in the medial temporal lobe and hippocampus. PET and SPECT involve injection of radiotracers and have relatively poor spatial resolution (5-10 mm). We wondered if a new mode of functional neuroimaging pioneered in our lab, perfusion MRI, might be able to detect AD pathological changes, and perhaps, with the higher spatial resolution of MRI (1-2 mm), even earlier in the disease course. With several new medications showing potential for slowing AD progression, earlier detection would provide a significant treatment advantage. We scanned 9 AD patients (mean age 77.6, MMSE 13.0) and 7 age and sex matched healthy controls (mean age 72.4, MMSE 29.0). All subjects had a high-resolution 3-D volumetric MRI scan. Three axial perfusion scans were then taken in the Anterior-Posterior Commissure (AC-PC) plane, and 24mm above and 12mm below. Volumetric and perfusion data are in final analysis stages. Two AD subjects were not able to tolerate the MRI environment without sedation (mean age 86, MMSE 2.5) and movement artifact caused their scans to be uninterpretable. The scanning sequences were well tolerated by most mildly demented patients and healthy controls. Final volumetric and perfusion data will be presented by group (AD and Controls) and correlations will be examined with disease severity. It appears possible to use fMRI to investigate AD brain changes, although this technique may not be suitable for some highly demented, agitated patients.

Patients and Methods

We recruited, rated and scanned a group of AD patients (n=9, mean age 77.6, MMSE 13.0) and a group of age and sex matched healthy controls (n=7, mean age 72.4, MMSE 29.0). All subjects were objectively rated for cognitive function, depression and anxiety and had a high-resolution 3-D volumetric MRI scan. Three axial perfusion scans were then taken in the Anterior-Posterior Commissure (AC-PC) plane, and 24mm above and 12mm below. Two AD patients became extremely agitated during the scanning sequence and the perfusion data is uninterpretable due to movement artifact. One perfusion scan of an AD patient was not performed according to the protocol and will not be used. The 3-D volumetric scans were analysed, in blinded fashion, using MEDx software produced by Picker. The scans were oriented in the AC-PC plane and sliced coronally at 1mm intervals. The volume was measured by manually tracing the outline of the temporal lobe, progressing anterior to posterior, starting with the appearance of the temporal pole and ending with the last slice in which the corpus callosum was visible. These landmarks were chosen because they provided unambiguous features that were consistent between subjects

Results

The volumetric data of all but two subjects has been processed and the results are summarised in table 1 (see below). 
	                                AD Patient       	Control
Maximum Volume	                  37688	                  60106
Minimum Volume	                  81894                	  95387
Mean                            	59733               	78109
Standard Deviation	             14815	             13466
Table 1. All measurements are given in mm3 Graph 1 shows the temporal lobe volume plotted against Mini Mental Status Exam (MMSE) scores and indicates a clear trend towards decreasing volume with increasing dementia (as evidenced by the low MMSE).

References

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