Atrophy Correction

Typical functional maps of the normal brain at rest demonstrate fairly uniform activity in gray matter. When the images indicate an area of abnormal function, a variety of underlying causes should be considered. Diminished metabolism or blood flow is often interpreted as a pure reduction in functional activity, but may actually be due to alterations in underlying structure, such as atrophy or infarction. These defects likely reflect tissue loss rather than tissue dysfunction. One of the primary difficulties in the interpretation of SPECT or PET images in patients with dementia (Fig. 2) is the artifactual underestimate of "function" due to cerebral atrophy (38). Most functional image analysis yields activity in counts per unit volume of space, not in counts/unit volume of brain, a potentially important dimension that more fairly represents functional activity. In diseases associated with aging and neurodegeneration, reduced brain volume is the rule, and any attempt to quantitate a purely functional abnormality would ideally correct for the associated atrophy.

Several groups have applied an "atrophy correction" to their functional imaging studies of AD (39-41). Most of these studies reported a significant increase in "corrected" perfusion or metabolic rates in patients with AD compared to control subjects, although temporoparietal functional abnormalities remained significant after atrophy correction.

Reiman and colleagues (42) recently reported that PET scans showed significant metabolic reductions in homozygote apolipoprotein e4 carriers before

Fig. 2. Axial images from a 73-year-old woman with probable Alzheimer's disease. (Left) Structural MRI (T2-weighted) demonstrating posterior parietal atrophy. (Center) 99Tc-HMPAO SPECT demonstrating decreased parietal perfusion. (Right) Co-registered SPECT and MRI images superimposed showing perfusion deficits corresponding to atrophic parietal regions.

Fig. 2. Axial images from a 73-year-old woman with probable Alzheimer's disease. (Left) Structural MRI (T2-weighted) demonstrating posterior parietal atrophy. (Center) 99Tc-HMPAO SPECT demonstrating decreased parietal perfusion. (Right) Co-registered SPECT and MRI images superimposed showing perfusion deficits corresponding to atrophic parietal regions.

cognitive impairment, but did not find significant hippocampal atrophy in these asymptomatic individuals. These findings suggest that functional and structural alterations may not always occur in parallel, and that functional image abnormalities may precede significant atrophic changes.

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