Glucose metabolism and gray-matter concentration in apolipoprotein E ε4 positive normal subjects.

Apolipoprotein E (ApoE) ε4 is known as a genetic risk factor for Alzheimer's disease (AD). This study investigated the prevalence of imaging abnormalities suggestive of AD in cognitively normal ApoE ε4 carriers using (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) and voxel-based morphometry (VBM). Forty-five cognitive normal ApoE ε4 allele carriers and 45 noncarriers underwent both FDG positron emission tomography and magnetic resonance imaging (MRI). A total of 90 normal database sets were generated for the individual 45 ε4 carriers and 45 noncarriers. Mean z-scores in the predefined AD-specific regions of interest (ROI) were calculated for each ε4 carrier and noncarrier using the individually defined normal database. The prevalence of AD-like hypometabolism and atrophy in the ε4 carriers was 8.9% and 17.7%, respectively, and did not differ significantly from those in the noncarriers (8.9%, 8.8%). The majority of ε4 carriers showed preserved FDG uptake or gray matter concentration.

Posterior cingulate atrophy and metabolic decline in early stage Alzheimer's disease.

To test the hypothesis that Alzheimer's disease (AD) patients with posterior cingulate/precuneus (PCP) atrophy would be a distinct disease form in view of metabolic decline. Eighty-one AD patients underwent (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) and structural magnetic resonance imaging (MRI). Positron emission tomography and voxel-based morphometry (VBM) Z-score maps were generated for the individual patients using age-specific normal databases. The patients were classified into 3 groups based on atrophic patterns (no-Hipp-PCP, atrophy in neither hippocampus nor PCP; Hipp, hippocampal atrophy; PCP, PCP atrophy). There were 16 patients classified as no-Hipp-PCP, 55 as Hipp, and 10 as PCP. The Mini Mental State Examination (MMSE) score was similar among the groups. The greater FDG decline than atrophy was observed in all groups, including the no-Hipp-PCP. The PCP group was younger, and was associated with a greater degree of FDG decline in PCP than the others. There are diverse atrophic patterns in a spectrum of AD. In particular, a subset of patients show PCP atrophy, which is associated with greater metabolic burden.

Effect of an age-mismatched and sex-mismatched normal database on the diagnostic performance of ¹8F-FDG PET for Alzheimer's disease: the Ishikawa Brain Imaging Study.

OBJECTIVES: ¹8F-FDG PET with voxel-based statistical image analysis plays an important role in the diagnosis of Alzheimer's disease (AD). However, the effect of an age-matched and sex-matched or mismatched normal database (NDB) on the diagnostic performance of ¹8F-FDG PET has not yet been investigated systematically. The aim of this study was to determine whether an age-matched and sex-matched NDB is necessary for the detection of AD using ¹8F-FDG PET. METHODS: We generated 11 NDB sets for ¹8F-FDG PET, including six age-specific NDB sets consisting of participants ranging in age from 20 to 70 years, one age-non-specific NDB set, one age-matched NDB set, two sex-specific NDB sets, each consisting of 20 men or 20 women, and one sex-matched NDB set. The average z-scores in predefined AD-specific regions of interest of the PET images were calculated using those NDB sets and a receiver-operating characteristic analysis was carried out to assess the diagnostic performance of ¹8F-FDG PET to discriminate 46 patients with AD from 50 normal controls. RESULTS: There was no significant difference in each area under the receiver-operating characteristic curve using either age-matched/mismatched NDB sets or sex-matched/mismatched NDB sets. CONCLUSION: The diagnostic performance of ¹8F-FDG PET was rather insensitive to differences in age or sex in the NDB, indicating that exact age-matched or sex-matched NDB may not be essential for discriminating patients with AD from normal participants using ¹8F-FDG PET.

Iodine-123 metaiodobenzylguanidine imaging and carbon-11 hydroxyephedrine positron emission tomography compared in patients with left ventricular dysfunction.

BACKGROUND: Although both (123)I-metaiodobenzylguanidine ((123)I-MIBG) imaging and (11)C-hydroxyephedrine ((11)C-HED) positron emission tomography (PET) are used for assessing cardiac sympathetic innervation, their relationship remains unknown. The aims were to determine whether (123)I-MIBG parameters such as heart-to-mediastinum ratio (H/M) are associated with quantitative measures by (11)C-HED PET and to compare image quality, defect size, and location between (123)I-MIBG single-photon emission computed tomography (SPECT) and (11)C-HED PET. METHODS AND RESULTS: Twenty-one patients (mean left ventricular ejection fraction, 39 ± 15%) underwent (123)I-MIBG imaging and (11)C-HED PET. Early (15-minute), late (3-hour) H/M, and washout rate (WR) were calculated for (123)I-MIBG. Myocardial retention and WR was calculated for (11)C-HED. Using a polar map approach, defect was defined as the area with relative activity <60% of the maximum. Both the early (r=0.76) and late (r=0.84) (123)I-MIBG H/M were correlated with (11)C-HED retention. (123)I-MIBG WR was correlated with (11)C-HED WR (r=0.57). Defect size could not be measured in 3 patients because of poor quality (123)I-MIBG SPECT, whereas (11)C-HED defect was measurable in all patients. Although defect size measured by early or late (123)I-MIBG SPECT was closely correlated with that by (11)C-HED PET (early: r=0.94; late: r=0.88), the late (123)I-MIBG overestimated defect size particularly in the inferior and septal regions. CONCLUSIONS: (123)I-MIBG H/M gives a reliable estimate of cardiac sympathetic innervation as measured by (11)C-HED PET. Furthermore, despite the close correlation in defect size, (11)C-HED PET appears to be more suitable for assessing regional abnormalities than does (123)I-MIBG SPECT.

Effect of sample size for normal database on diagnostic performance of brain FDG PET for the detection of Alzheimer's disease using automated image analysis.

OBJECTIVE: To investigate the relationship between the sample size for a normal database (NDB) and diagnostic performance of FDG PET using three-dimensional stereotactic surface projection for the detection of Alzheimer's disease. METHODS: We generated nine NDB sets consisting of 4, 6, 8, 10, 20, 30, 40, 50 and 60 normal subjects. In order to assess the diagnostic performance using these NDBs to distinguish Alzheimer's disease patients from normal subjects, we recruited 52 patients with probable Alzheimer's disease (25 males, 27 females; mean age, 66.8+/-8.1 years) and 50 normal subjects (24 males, 26 females; mean age, 65.7+/-9.4 years). A receiver operating characteristic (ROC) analysis was performed for comparison of diagnostic accuracy among NDB sets. RESULTS: Small NDBs (n< or =10) yielded poor quality of mean and SD images as compared with large NDBs (n> or =20). The ROC curves of the smaller group varied inconsistently, whereas those of the larger group were nearly superimposable. The area under the ROC curve (AUC) of the NDBs with sample size 6 (0.911) or 8 (0.929) was significantly smaller than that of the largest NDB (n=60, 0.956). The AUCs of the larger group did not fall below 0.950, whereas AUCs of the smaller subgroup never exceeded 0.950. CONCLUSIONS: Our data indicate that the sample size for an NDB affects the diagnostic performance of FDG PET using automated statistical approach, and that inclusion of at least 10 subjects is recommended, and 20 seems to be preferable for generating NDBs, although even a small NDB may provide clinically relevant results.

Comparison of 18F-FDG PET and optimized voxel-based morphometry for detection of Alzheimer's disease: aging effect on diagnostic performance.

UNLABELLED: The aim of this study was to compare optimized voxel-based morphometry (VBM) and (18)F-FDG PET for discrimination between patients with Alzheimer's disease (AD) and healthy subjects in relation to age. METHODS: The study population consisted of 2 groups; the first group (27 AD patients and 40 control subjects) was used to determine the locations of significant abnormalities for both PET and VBM using statistical parametric mapping, and the second group (34 AD patients and 50 control subjects) was used to compare the diagnostic performance of PET and VBM. In the second group, a z-score map for PET or VBM of each subject was obtained by comparison with the mean and SD of PET or gray-matter MR images of the control subjects. Receiver-operating-characteristic (ROC) curve analysis was then performed to compare the diagnostic performance between PET and VBM. Furthermore, group 2 was divided into the early- and late-onset subgroups, and ROC analysis was performed for each subgroup. RESULTS: In the first group, VBM revealed a significant decrease in gray-matter concentration in the hippocampus complex in AD, whereas PET showed a significant reduction in (18)F-FDG uptake in the posterior cingulate and parietotemporal lobe. The diagnostic performance of PET (0.988 +/- 0.008; mean +/- SE), as measured by the area under the ROC curve, was higher than that of VBM with (0.782 +/- 0.059) or without (0.832 +/- 0.049) modulation. PET yielded a sensitivity, specificity, and overall accuracy of 100%, 92%, and 95%, respectively, whereas for VBM the sensitivity, specificity, and accuracy were 74%, 92%, and 85%. Modulation for the VBM did not improve these values (56%, 94%, and 79%, respectively). When the early- and late-onset subjects were analyzed separately, the superiority of (18)F-FDG PET was significant only in the early-onset subgroup. CONCLUSION: The present study indicates that the detection of metabolic alteration by (18)F-FDG PET yields a better diagnostic performance for the discrimination between AD patients and healthy control subjects than does the morphologic approach by VBM, particularly in the early-onset subjects.

Partial volume effect-corrected FDG PET and grey matter volume loss in patients with mild Alzheimer's disease.

PURPOSE: Although( 18)F-fluorodeoxyglucose (FDG) PET is an established imaging technique to assess brain glucose utilisation, accurate measurement of tracer concentration is confounded by the presence of partial volume effect (PVE) due to the limited spatial resolution of PET, which is particularly true in atrophic brains such as those encountered in patients with Alzheimer's disease (AD). Our aim was to investigate the effects of PVE correction on FDG PET in conjunction with voxel-based morphometry (VBM) in patients with mild AD. METHODS: Thirty-nine AD patients and 73 controls underwent FDG PET and MRI. The PVE-corrected grey matter PET images were obtained using an MRI-based three-compartment method. Additionally, the results of PET were compared with grey matter loss detected by VBM. RESULTS: Before PVE correction, reduced FDG uptake was observed in posterior cingulate gyri (PCG) and parieto-temporal lobes (PTL) in AD patients, which persisted after PVE correction. Notably, PVE correction revealed relatively preserved FDG uptake in hippocampal areas, despite the grey matter loss in medial temporal lobe (MTL) revealed by VBM. CONCLUSION: FDG uptake in PCG and PTL is reduced in AD regardless of whether or not PVE correction is applied, supporting the notion that the reduced FDG uptake in these areas is not the result of atrophy. Furthermore, FDG uptake by grey matter tissue in the MTL, including hippocampal areas, is relatively preserved, suggesting that compensatory mechanisms may play a role in patients with mild AD.

Rapid scanning protocol for brain (18)F-FDG PET: a validation study.

UNLABELLED: Although (18)F-FDG PET is an established technique to assess brain glucose use, a shorter imaging time is preferable for patient convenience and increased throughput. The aim of this study was to validate a brain (18)F-FDG PET protocol more rapid than the conventional protocol. METHODS: For comparison of normalized metabolic activities, brain (18)F-FDG PET was performed on 60 healthy subjects and 25 patients with probable Alzheimer's disease (AD), and an additional 20 healthy subjects served as a control group to assess diagnostic performance between the conventional and rapid scanning protocols. Conventional scans were acquired for a total of 20 min (a 10-min emission and a 10-min transmission). Immediately after conventional scanning, rapid scanning was performed for a total of 4 min (a 3-min emission and a 1-min transmission). PET images were anatomically standardized using NEUROSTAT, with pixel values normalized to the individual global value. Two database sets, from the 2 protocols, were compared by regional values and pixel-by-pixel analysis. A receiver-operating-characteristic analysis was performed for comparison of diagnostic accuracy between the 2 protocols. A kinetic simulation study was also performed to examine the possible difference due to the time lag between the protocols. RESULTS: Although small differences in normalized activity were found in several regions in the healthy subjects between the 2 protocols, no significant difference was found in any region in the patient group. The coefficients of variation of the normalized activity were 20%-30% larger in the rapidly scanned images, but the mean z images and their coefficient-of-variation images did not differ. The kinetic simulation study suggested that the differences were caused by the time lag between the 2 protocols. No significant differences were found in area under the receiver-operating-characteristic curves, and the diagnostic accuracies for the detection of AD were virtually equal between the 2 protocols. CONCLUSION: The rapid scanning protocol used in the present study could provide results nearly equivalent to data from the conventional protocol. Thus, it is feasible to use this rapid protocol to detect AD, without losing diagnostic accuracy.