Does cerebral blood flow decline in healthy aging? A PET study with partial-volume correction.

UNLABELLED: It remains a matter of controversy as to whether cerebral perfusion declines with healthy aging. In vivo imaging with PET permits quantitative evaluation of brain physiology; however, previous PET studies have inconsistently reported aging reductions in cerebral blood flow (CBF), oxygen metabolism, and glucose metabolism. In part, this may be because of a lack of correction for the dilution effect of age-related cerebral volume loss on PET measurements. METHODS: CBF PET scans were obtained using [15O]H2O in 27 healthy individuals (age range, 19-76 y) and corrected for partial-volume effects from cerebral atrophy using an MR-based algorithm. RESULTS: There was a significant difference (P = 0.01) in mean cortical CBF between young/midlife (age range, 19-46 y; mean +/- SD, 56+/-10 mL/100 mL/min) and elderly (age range, 60-76 y; mean +/- SD, 49+/-2.6 mL/100 mL/min) subgroups before correcting for partial-volume effects. However, this group difference resolved after partial-volume correction (young/midlife: mean +/- SD, 62+/-10 mL/100 mL/min; elderly: mean +/- SD, 61+/-4.8 mL/100 mL/min; P = 0.66). When all subjects were considered, a mild but significant inverse correlation between age and cortical CBF measurements was present in the uncorrected but not the corrected data. CONCLUSION: This study suggests that CBF may not decline with age in healthy individuals and that failure to correct for the dilution effect of age-related cerebral atrophy may confound interpretation of previous PET studies that have shown aging reductions in physiologic measurements.

PET imaging of serotonin type 2A receptors in late-life neuropsychiatric disorders.

OBJECTIVE: To determine whether there are abnormalities in the in vivo status of the serotonin type 2A (5-HT2A) receptor in late-life depression and Alzheimer's disease, the authors used positron emission tomography (PET) to assess patients with these two conditions and healthy subjects. METHOD: PET was performed by using [18F]altanserin to evaluate 5-HT2A receptor binding in 11 elderly patients with depression (four men, seven women; mean age = 65.0 years, SD = 5.5); nine Alzheimer's disease patients, including three with concurrent depression (two men, seven women; mean age = 69.7 years, SD = 5.0); and 10 age-matched healthy subjects (four men, six women; mean age = 69.8 years, SD = 5.0). Partial-volume correction of regional specific binding estimates was performed by using a method based on magnetic resonance imaging. RESULTS: No significant abnormalities in [18F]altanserin binding (binding potential) were observed in the patients with late-life depression, and no effect of depression on binding potential was present within the Alzheimer's disease group. However, the patients with Alzheimer's disease had significantly lower binding than the normal subjects in several brain regions, including the anterior cingulate, prefrontal cortex, and sensorimotor cortex. CONCLUSIONS: These results suggest that the 5-HT2A receptor is differentially affected in late-life depression and Alzheimer's disease, a finding that has implications for the etiological basis of mood and cognitive features of neuropsychiatric disorders of late life.

Comparative evaluation of MR-based partial-volume correction schemes for PET.

UNLABELLED: Because of limitations of spatial resolution, quantitative PET measurements of cerebral blood flow, glucose metabolism and neuroreceptor binding are influenced by partial-volume averaging among neighboring tissues with differing tracer concentrations. METHODS: Two MR-based approaches to partial-volume correction of PET images were compared using simulations and a multicompartment phantom. The two-compartment method corrects PET data for the diluting effects of cerebrospinal fluid (CSF) spaces. The more complex three-compartment method also accounts for the effect of partial-volume averaging between gray and white matter. The effects of the most significant sources of error on MR-based partial-volume correction, including misregistration, resolution mismatch, segmentation errors and white matter heterogeneity, were evaluated. We also examined the relative usefulness of both approaches in PET studies of aging and neurodegenerative disease. RESULTS: Although the three-compartment method was highly accurate (with 100% gray matter recovery achieved in simulations), it was also more sensitive to all errors tested, particularly image segmentation and PET-MR registration. CONCLUSION: Based on these data, we conclude that the two-compartment approach is better suited for comparative PET studies, whereas the three-compartment algorithm is capable of greater accuracy for absolute quantitative measures.

Reduced binding of [18F]altanserin to serotonin type 2A receptors in aging: persistence of effect after partial volume correction.

The serotonin (5-HT) neurotransmitter system, which has a widespread distribution in the central nervous system, has been implicated in regulating mood and many human behaviors. There is evidence from postmortem human studies and limited information from prior in vivo studies to support a decline in 5-HT2A receptor density with aging. We examined nine elderly (ages 61-76) and nine young (ages 18-29) healthy individuals with positron emission tomography (PET) and [18F]altanserin, a ligand with high affinity for the 5-HT2A binding site. The PET data were corrected for differences in brain tissue volume between the young and elderly subjects using a magnetic resonance (MR) imaging-based partial volume correction method. Highly significant and widespread cortical reductions in 5-HT2A specific binding were demonstrated in the elderly group relative to young controls. Regional losses averaged 61% before and 57% following correction for effects of cerebral atrophy. This finding, which is consistent with prior postmortem and in vivo studies, has both etiological and potential therapeutic implications for behavioral changes commonly observed in the elderly, including geriatric depression.