Automated discrimination between very early Alzheimer disease and controls using an easy Z-score imaging system for multicenter brain perfusion single-photon emission tomography

BACKGROUND AND PURPOSE: In Alzheimer disease (AD), a peculiar regional cerebral blood flow (rCBF) abnormality has been reported in the posterior cingulate gyri and precunei, even at a very early stage. We performed a multicenter brain perfusion single-photon emission tomography (SPECT) study to evaluate the discrimination ability of an easy Z-score imaging system (eZIS) with a common normal data base between patients with very early AD at the stage of mild cognitive impairment and age-matched healthy controls. MATERIALS AND METHODS: For a multicenter study, SPECT images of 40 patients with AD and 40 healthy volunteers were acquired from 4 gamma camera systems in 4 different institutions. Systematic differences of SPECT images between gamma cameras were corrected by using conversion maps calculated from the SPECT images of the same brain phantom. Receiver operating characteristic (ROC) analysis was performed to discriminate patients and controls by using a Z-score in the volume of interest (VOI), which had been defined as a region related to AD in subjects other than those in a multicenter study. RESULTS: Bilateral posterior cingulate gyri, precunei, and parietal cortices were defined as a VOI showing rCBF reduction in very early AD. A new indicator of rCBF abnormality in the VOI provided 86% accuracy for distinction of AD and healthy controls in the multicenter study. The area under the ROC curve was 0.934. CONCLUSION: Because an eZIS can use a common normal data base by converting site-specific SPECT data to the core data, the eZIS was useful for automated diagnosis of very early AD in routine studies in multiple institutions.     

Superiority of 3-dimensional stereotactic surface projection analysis over visual inspection in discrimination of patients with very early Alzheimer's disease from controls using brain perfusion SPECT.

In Alzheimer's disease (AD), regional cerebral blood flow (rCBF) in the posterior cingulate gyri and precunei has been reported to decrease even at a very early stage. It may be helpful to use statistical image analysis to distinguish slight decreases in rCBF in this area. We compared a 3-dimensional stereotactic surface projection (3D-SSP) technique with visual inspection in the discrimination of patients with very early AD from age-matched controls using brain perfusion SPECT. METHODS: SPECT was obtained in 38 patients with probable AD at a very early stage and after a mean interval of 15 mo and in 76 age-matched healthy volunteers. We randomly divided these subjects into 2 groups. The first group was used to identify the areas with significant decreases of rCBF in patients compared with healthy control subjects based on the voxel-based analysis using 3D-SSP. The second group was used to compare the discrimination ability between patients and control subjects by 3D-SSP with that by visual inspection. In the second group, a Z-score map for a SPECT image of a subject was obtained by comparison with mean and SD SPECT images of control subjects for each voxel after anatomic standardization and voxel normalization to reference regions. Receiver operating characteristic (ROC) curves for a Z-score discriminating patients with AD from control subjects were analyzed in areas with significant decreases of rCBF identified in the first group. For visual inspection, 6 physicians graded the rCBF decrease on SPECT images for ROC curves. They inspected the images twice at an interval of >2 wk, and intra- and interobserver reliabilities were determined. RESULTS: Visual inspection showed fair-to-excellent intra- and interobserver reliabilities. The 3D-SSP demonstrated an accuracy of 86.2% for discriminating patients with AD from control subjects when analyzing the posterior cingulate gyri and precunei with global mean normalization. In contrast, visual inspection did not show an accuracy of >74.0% for this discrimination. CONCLUSION: The ability of 3D-SSP to discriminate patients with very early AD from control subjects is superior to that of visual inspection. It is clinically useful and reliable to adopt the use of 3D-SSP as an adjunct to visual interpretation.     

Influence of smoothing process on statistical brain function image analysis

Spatial smoothing performed after spatial normalization on the easy Z-score Imaging System (eZIS) is considered to affect signal size. The purpose of this study was to analyze quantitatively the influence of the smoothing process on eZIS using the voxel of interest (VOI) method. A normal database (NDB) was established using (99m)Tc-Hexamethylpropyleneamine oxime (HMPAO) brain perfusion SPECT images of thirty healthy volunteers. Then the NDB was smoothed with various Gaussian kernels (2, 4, 8, 12, 16 mm). Artificial lesions with known volumes and reduction of tracer uptake were made on one of the healthy volunteer images, and eZIS analysis was performed on the NDB of the same Gaussian kernel, respectively. The signal size of small-sized lesions was expanded 5.1 times to the true signal size of a 12 mm Gaussian kernel. On the other hand, the medium lesion size, which was approximately the same size as the posterior cingulate gyrus, was expanded 2.9 times to true signal size. Estimation of the false positive area using the extraction estimation method at lesion size medium indicated the lowest value at 8, 12 mm Gaussian kernel smoothing. The smoothing procedure at 8-12 mm Gaussian kernel is effective to detect a focal abnormality in the brain SPECT of Alzheimer's disease.     

Effect of linearization correction on statistical parametric mapping (SPM): A99mTc-HMPAO brain perfusion SPECT study in mild Alzheimer’s disease

OBJECTIVE: Statistical parametric mapping (SPM) was employed to investigate the regional decline in cerebral blood flow (rCBF) as measured by 99mTc-hexamethyl propylene amine oxime (HMPAO) single photon emission computed tomography (SPECT) in mild Alzheimer's disease (AD). However, the role of the post reconstruction image processing on the interpretation of SPM, which detects rCBF pattern, has not been precisely studied. We performed 99mTc-HMPAO SPECT in mild AD patients and analyzed the effect of linearization correction for washout of the tracer on the detectability of abnormal perfusion. METHODS: Eleven mild AD (NINCDS-ADRDA, male/female, 5/6; mean+/-SD age, 70.6+/-6.2 years; mean+/-SD mini-mental state examination score, 23.9+/-3.41; clinical dementia rating score, 1) and eleven normal control subjects (male/female, 4/7; mean+/-SD age, 66.8+/-8.4 years) were enrolled in this study. 99mTc-HMPAO SPECT was performed with a four-head rotating gamma camera. We employed linearization uncorrected (LU) and linearization corrected (LC) images for the patients and controls. The pattern of hypoperfusion in mild AD on LU and LC images was detected by SPM99 applying the same image standardization and analytical parameters. A statistical inter image-group analysis (LU vs. LC) was also performed. RESULTS: Clear differences were observed between the interpretation of SPM with LU and LC images. Significant hypoperfusion in mild AD was found on the LU images in the left posterior cingulate gyrus, right precuneus, left hippocampus, left uncus, and left superior temporal gyrus (cluster level, corrected p < 0.005). With the LC images, significant hypoperfusion in AD was found only in the bilateral posterior cingulate gyrus and left precuneus (cluster level, corrected p < 0.005). A pattern of greater rCBF distribution at the high flow cortices and low flow cortices was observed on LC and LU images, respectively, in the case of both controls and mild AD patients. CONCLUSION: Hippocampal hypoperfusion could be detected by means of SPM in the LU images but not in the LC images. The results of SPM may vary in 99mTc-HMPAO SPECT with or without linearization correction, which should be carefully evaluated when interpreting the pattern of rCBF changes in mild Alzheimer's disease.     

Functional interactions between entorhinal cortex and posterior cingulate cortex at the very early stage of Alzheimer's disease using brain perfusion single-photon emission computed tomography

OBJECTIVE: The cause of the reduced regional cerebral blood flow (rCBF) in the posterior cingulate cortex in the early stage of Alzheimer's disease has not been clarified. In Alzheimer's disease, the posterior cingulate cortex itself shows little neuropathologic degeneration, and a hypothesis explaining such a discrepancy is that the functional impairment in the posterior cingulate cortex reflects remote effects caused by degeneration in distant but connected areas, such as the entorhinal cortex. To test the hypothesis, we investigated the functional connectivity between the entorhinal cortex and posterior cingulate cortex. METHODS: Sixty-one patients with probable Alzheimer's disease at a very early stage and 61 age-matched healthy controls underwent both brain structural magnetic resonance imaging (MRI) and single-photon emission computed tomography (SPECT). Voxel-based morphometry was performed on MRI data to identify clusters of significantly reduced grey matter concentration in patients with Alzheimer's disease relative to controls, which were set as volumes of interest (VOIs) for correlation analyses of SPECT images. We then used adjusted rCBF values in the VOIs as covariates of interest in statistical parametric mapping. RESULTS: Voxel-based morphometry demonstrated a significant reduction in grey matter concentration in the bilateral entorhinal cortex in Alzheimer's disease. A positive correlation between rCBF in the entorhinal cortex as VOI and that in the limbic and paralimbic systems, including the posterior cingulate cortex, anterior cingulate cortex, lingual gyri and left middle temporal gyrus (P<0.001), was observed in Alzheimer's disease. Control subjects also showed a similar correlation in the limbic and paralimbic systems, but not in the posterior cingulate cortex. CONCLUSION: These results indicate that rCBF changes in the posterior cingulate cortex may be closely related to those in the entorhinal cortex in patients with Alzheimer's disease, thereby supporting the 'remote effect' hypothesis.     

Longitudinal evaluation of both morphologic and functional changes in the same individuals with Alzheimer's disease.

Morphologic and functional imaging studies have not always given concordant results about brain areas showing atrophic changes and reduced flow or metabolism in Alzheimer's disease (AD). The aim of this study was to determine the initial abnormality and the longitudinal changes in both morphologic and functional measurements for the same individuals with AD. METHODS: We investigated 15 patients with mild AD and 25 age-matched healthy volunteers. The AD patients underwent both MRI and SPECT 3 times at intervals of approximately 1 y. The gray matter volume, as segmented from MRI, and the regional cerebral blood flow (rCBF), as measured by SPECT, of AD patients were compared with those of healthy volunteers using statistical parametric mapping, which is a voxel-based analysis in stereotactic space. RESULTS: Considerable discordance between areas of regional atrophy and areas of decreased rCBF was observed. The medial temporal areas showed a faster and more extensive reduction of gray matter volume than of rCBF. In comparison with the value at the baseline study, rCBF in the posterior cingulate gyrus and precuneus and the associative parietal cortex was extensively decreased. In contrast, the extent of significant decrease in this area continued to be much narrower for gray matter volume than for rCBF, even in the follow-up studies. Frontal areas, including the anterior cingulate gyrus and the orbitofrontal areas, showed a progressive reduction in both rCBF and gray matter volume. The reduction in rCBF was in a more posterior part of the associative temporal cortex than was the reduction in gray matter volume. CONCLUSION: These results indicate a distinct discordance between morphologic and functional changes in a longitudinal study of AD. Functional changes may be caused partly by remote effects from the morphologically involved areas with decreased connectivity and partly by a compensatory response by neuronal plasticity.     

Predicting human performance by channelized Hotelling observer in discriminating between Alzheimer’s dementia and controls using statistically processed brain perfusion SPECT

OBJECTIVE: We compared the diagnostic accuracy achieved by a human observer (nuclear medicine physician) and a channelized Hotelling (CH) observer on the basis of receiver-operating characteristics (ROC) curve for the differential diagnosis of Alzheimer's disease (AD) from SPECT images. METHODS: The I-123-IMP brain perfusion SPECT images of 42 subjects (21 AD patients and 21 healthy controls) were used for an interpretation study and those of 10 healthy subjects were for a normal database. SPECT images were processed into four types: original SPECT images, three-dimensional stereotactic surface projection (3DSSP) images derived from them, Z-scores of SPECT images, and Z-scores of 3DSSP images. Five nuclear medicine physicians evaluated the test dataset sequentially as to whether the presented images were those of AD patients, which were rated using five categories of certainty: definitely, possibly, equivocally, possibly not, and definitely not. The test statistics (lambda) of the dataset generated by the CH observer were rated for ROC analysis. The areas under the ROC curves (Az) for the four image types interpreted by the human and CH observers were estimated and compared. RESULTS: Among the four image types, the best performance based on Az obtained by both the CH and human observers was observed for the Z-score of 3DSSP images, and the lowest was for the original SPECT images. CONCLUSIONS: The performance of the CH observer was similar to that of the human observers, and both were dependent on the image type. This indicates that the CH observer may predict human performance in discriminating Alzheimer's dementia and can be useful for comparing and optimizing image processing methods of brain perfusion SPECT without human observers.     

Effects of partial volume correction on discrimination between very early Alzheimer’s dementia and controls using brain perfusion SPECT

We assessed the accuracy of brain perfusion single-photon emission computed tomography (SPECT) in discriminating between patients with probable Alzheimers disease (AD) at the very early stage and age-matched controls before and after partial volume correction (PVC). Three-dimensional MRI was used for PVC. We randomly divided the subjects into two groups. The first group, comprising 30 patients and 30 healthy volunteers, was used to identify the brain area with the most significant decrease in regional cerebral blood flow (rCBF) in patients compared with normal controls based on the voxel-based analysis of a group comparison. The second group, comprising 31 patients and 31 healthy volunteers, was used to study the improvement in diagnostic accuracy provided by PVC. A Z score map for a SPECT image of a subject was obtained by comparison with mean and standard deviation SPECT images of the healthy volunteers for each voxel after anatomical standardization and voxel normalization to global mean or cerebellar values using the following equation: Z score = ([control mean]–[individual value] )/(control SD). Analysis of receiver operating characteristics curves for a Z score discriminating AD and controls in the posterior cingulate gyrus, where a significant decrease in rCBF was identified in the first group, showed that the PVC significantly enhanced the accuracy of the SPECT diagnosis of very early AD from 73.9% to 83.7% with global mean normalization. The PVC mildly enhanced the accuracy from 73.1% to 76.3% with cerebellar normalization. This result suggests that early diagnosis of AD requires PVC in a SPECT study.     

Donepezil hydrochloride preserves regional cerebral blood flow in patients with Alzheimer's disease.

The aim of this SPECT study was to investigate the effects of donepezil on regional cerebral blood flow (rCBF) in patients with mild to moderate Alzheimer's disease (AD) using statistical parametric mapping. METHODS: rCBF was noninvasively measured using (99m)Tc-ethyl cysteinate dimer in 35 AD patients with a Mini-Mental State Examination score > 16 on initial evaluation. Baseline and follow-up SPECT studies with a mean interval of 12 mo were performed on these patients. We used the adjusted rCBF images in the relative flow distribution (normalization of global cerebral blood flow for each patient to 50 mL/100 g/min with proportional scaling) to compare these groups through statistical parametric mapping. RESULTS: In the follow-up study, the adjusted rCBF was significantly preserved in the right and left anterior cingulate gyri, right middle temporal gyrus, right inferior parietal lobules, and prefrontal cortex of donepezil-treated AD patients, compared with placebo-treated AD patients. CONCLUSION: Treatment with donepezil for 1 y appears to reduce the decline in rCBF, suggesting preservation of functional brain activity.     

Cerebral blood flow and metabolic abnormalities in Alzheimer’s disease

In this review I summarize observations of PET and SPECT studies about cerebral blood flow and metabolic abnormalities in Alzheimer's disease. In very early AD flow or metabolism reduces first in the posterior cingulate gyrus and precuneus. This reduction may arise from functional deafferentation caused by primary neural degeneration in the remote area of the entorhinal cortex that is the first to be pathologically affected in AD. Then medial temporal structures and parietotemporal association cortex show flow or metabolic reduction as disease processes. The reason why flow or metabolism in medial temporal structures shows delay in starting to reduce in spite of the earliest pathological affection remains to be elucidated. It is likely that anterior cingulate gyrus is functionally involved, since attention is the first non-memory domain to be affected, before deficits in language and visuospatial functions. However few reports have described involvement in the anterior cingulate gyrus. Relationship between cerebral blood flow or metabolism and apolipoprotein E genotype has been investigated. Especially, the APOE epsilon4 allele has been reported to increase risk and to lower onset age as a function of the inherited dose of the epsilon4 allele. Reduction of flow or metabolism in the posterior cingulate gyrus and precuneus has been reported even in presymptomatic nondemented subjects who were cognitively normal and had at least a single epsilon4 allele. On the contrary the relation of epsilon4 allele to the progression rate of AD has been controversial from neuroimaging approaches. PET and SPECT imaging has become to be quite useful for assessing therapeutical effects of newly introduced treatment for AD. Recent investigations observed significant regional flow increase after donepezil hydrochloride treatment. Most of these observations have been made by applying computer assisted analysis of three-dimensional stereotactic surface projection or statistical parametric mapping instead of a conventional regions of interest technique.     

Longitudinal evaluation of early Alzheimer's disease using brain perfusion SPECT.

The aim of this SPECT study was to determine the initial abnormality and longitudinal changes in regional cerebral blood flow (rCBF) in early Alzheimer's disease (AD) using statistical parametric mapping (SPM). METHODS: rCBF was noninvasively measured using (99m)Tc-ethyl cysteinate dimer SPECT in 32 patients complaining of mild cognitive impairment, with a Mini-Mental State Examination score more than 24 at the initial study, and 45 age-matched healthy volunteers. All patients satisfied the diagnostic criteria of AD during the follow-up period of at least 2 y. Follow-up SPECT studies were performed on the patients at a mean interval of 15 mo. We used the raw data (absolute rCBF parametric maps) and the adjusted rCBF images of relative flow distribution (normalization of global cerebral blood flow [CBF] for each subject to 50 mL/100 g/min with proportional scaling) to compare these groups with SPM. RESULTS: In the baseline study, the adjusted rCBF was significantly and bilaterally decreased in the posterior cingulate gyri and precunei of patients compared with healthy volunteers. In the follow-up study, selected reduction of the adjusted rCBF was observed in the left hippocampus and parahippocampal gyrus. These areas showed the most prominent reduction in absolute rCBF on each occasion. Moreover, further decline of the absolute rCBF was longitudinally observed in extensive areas of the cerebral association cortex. CONCLUSION: SPM analysis showed the characteristic early-AD rCBF pattern of selective decrease and longitudinal decline, which may be overlooked by a conventional region-of-interest technique with observer a priori choice and hypothesis. This alteration in rCBF may closely relate to the pathophysiologic process of this disease.     

Comparison of SPM and NEUROSTAT in voxelwise statistical analysis of brain SPECT and MRI at the early stage of Alzheimer’s disease

Objective  Neuroimaging plays a major role in the early diagnosis of Alzheimer’s disease (AD). Recent advances in voxelwise statistical analysis after anatomic standardization of images have made this early diagnosis easier and more objective than visual inspection. We present comparative observations of NEUROSTAT, statistical parametric mapping (SPM) 99, and SPM2 in the early diagnosis of AD using brain perfusion single-photon emission computed tomography (SPECT) and magnetic resonance imaging (MRI). Methods  We performed voxel-by-voxel statistical group analysis for brain perfusion SPECT and gray matter images segmented from MRI between 61 patients with very early AD and 82 age-matched healthy volunteers. Anatomic standardization was performed using NEUROSTAT, SPM99, and SPM2 using both original and common templates. Results  The location of significant reduction of regional cerebral blood flow (rCBF) for SPECT and gray matter concentration for MRI were identical among these three methods irrespective of the templates used. When using the original template, the significance of peak rCBF reduction in the posterior cingulate gyri was higher in SPM99 and SPM2 than that in NEUROSTAT. On the other hand, when using the common template, the significance of peak rCBF reduction in the posterior cingulate gyri was higher in NEUROSTAT and SPM2 than that in SPM99. NEUROSTAT showed almost the equal significance of peak rCBF reduction between the used templates. Almost the equal significance of reduction in gray matter concentration was observed in the parahippocampal gyri among the three methods. Conclusions  NEUROSTAT, SPM99, and SPM2 showed identical location of significant reductions in rCBF and gray matter concentration in very early AD patients. Used templates for anatomic standardization are relevant to the results of voxelwise statistical analysis in SPM, less prominently in SPM2 than in SPM99, whereas irrelevant in NEUROSTAT.     

脑SPECT诊断早期阿茨海默氏病的初步探讨

目的：本文旨在初步探讨脑ＳＰＥＣＴ在诊断早期阿茨海默氏病中的价值。材料和方法：采用Ｍａｙｂｅｒｇ氏的断面划分感兴趣区的方法，使用放射性药物９９ｍ锝──六甲基丙叉二胺肟（９９ｍＴｃ－ＨＭＰＡＯ），比较１８例早期阿茨海默氏病患者及１１名正常老年人脑ＳＰＥＣＴ的血流灌注显像特点。结果：早期阿茨海默氏病患者脑ＳＰＥＣＴ可见不同程度的弥漫性大脑皮质血流灌注减低，左颞叶、扣带回、左额叶的血流灌注减低与正常老年人相比有显著差异（Ｐ＜０．０５），而皮质下血流灌注则未受影响。结论：早期阿茨海默氏病患者大脑半球血流灌注为左右非对称性减低，脑ＳＰＥＣＴ的血流灌注显像有助于诊断早期阿茨海默氏病。     

Gender difference in brain perfusion 99mTc-ECD SPECT in aged healthy volunteers after correction for partial volume effects

BACKGROUND: Previous reports have yielded controversial results concerning gender differences in regional cerebral blood flow (rCBF). To elucidate this issue, we compared 99mTc ethyl cysteinate dimer single photon emission computed tomography (SPECT) images for brain perfusion between aged-matched healthy men and women after correction for partial volume effects (PVEs). METHODS: Brain perfusion SPECT in the resting state was performed on 40 healthy, right-handed subjects, 20 men and 20 women, with an age range of 58-86 years, who did not differ sociodemographically. PVE correction was performed using grey matter volume measured by magnetic resonance imaging. Statistical parametric mapping was used for the analysis of the adjusted rCBF images of relative flow distribution. RESULTS: The PVE correction revealed that women had higher rCBF in left inferior frontal gyrus, bilateral middle temporal gyri, and left superior temporal gyrus. Men had higher rCBF in left superior frontal gyrus, right medial frontal gyrus, right superior parietal lobule, right postcentral gyrus, right cerebellum, right middle frontal gyrus, right fusiform gyrus, and right precuneus. CONCLUSION: Significant gender differences in rCBF existed in these healthy volunteers. The PVE correction of SPECT images revealed gender differences that were consistent with the universal findings of better performance on verbal tasks in women and on visuospatial tasks in men.     

强迫症患者局部脑血流变化的SPM和ROI分析

目的 用^99Tc^m－双半胱乙酯（ECD）SPECT显像研究强迫症（OCD）患者的局部脑血流（rCBF)变化。方法 受检才为14例OCD患者（OCD组）和23例年龄相匹配的健康志愿者（CN组）。^99Tc^m-ECD脑SPECT显像后，用统计参数地图（SPM）和感兴趣区（ROI）两种方法分析OCD组和CN组的rCBF分布差别（rCBF增高区和降低区）。P值设为0.01。结果 SPM分析显示OCD患者双侧壳核、颞上回和楔前叶，右侧眶回、额上回和额中回，左侧颞枕叶、顶上小叶和小脑蚓部的rCBF降低；同时，左侧额下回和扣带回后部有小范围的rCBF升高。ROI分析显示OCD患者右侧大脑颞前叶、顶颞叶和左侧大脑颞枕叶的脑血流分数明显低于正常大脑的相应皮层（P＜0．01）。基底节的rCBF无明显差异。结论 研究结果支持OCD患者的额纹状体环路病变假说，SPM是分析rCBF变化的有力工具。     

Posterior cingulate hypoperfusion in Alzheimer's disease, senile dementia of Alzheimer type, and other dementias evaluated by three-dimensional stereotactic surface projections using Tc-99m HMPAO SPECT

Hypoperfusion in the posterior cingulate cortex is thought to be useful for the early diagnosis of dementia of Alzheimer type (DAT). In the present study, we compared the incidence of posterior cingulate hypoperfusion in patients with Alzheimer's disease (AD), patients with senile dementia of Alzheimer type (SDAT), and patients with other types of dementia, as evaluated by three-dimensional stereotactic surface projection (3D-SSP) imaging. The subjects were 20 AD patients, 20 SDAT patients, 13 frontotemporal dementia patients, and 3 other types of dementia patients. A SPECT study was performed 5 minutes after the injection of 740 MBq technetium-99m hexamethylpropylene amine oxime. 3D-SSP images were obtained with global normalization to perform the statistical analysis. The normal database of 3D-SSP consisted of 15 healthy volunteers. Hypoperfusion was considered to be significant when the Z-score was over 2.5. Posterior cingulate hypoperfusion was observed in 13 of 20 AD patients (65%), in 5 of 20 SDAT patients (25%), but in none of other type of dementia patients. Posterior cingulate hypoperfusion was considered to be a finding specific to DAT, and this finding was thought to be useful to diagnose DAT patients, especially for AD patients. However, it was considered to be difficult to diagnose early-stage SDAT patients.     

Diagnostic performance of Tc-99m HMPAO SPECT for early and late onset Alzheimer’s disease: a clinical evaluation of linearization correction

Objective  This study examined the influence of linearization correction (LC) on brain perfusion single-photon emission computed tomography (SPECT) for the diagnosis of Alzheimer’s disease (AD). Methods  The early onset group (<65 years old) consisted of 10 patients with AD, and the late onset group (≥65 years old) of 13 patients with AD. Age-matched controls included seven younger and seven older normal volunteers. Tc-99m hexamethyl propyleneamine oxine (HMPAO) SPECT images were reconstructed with or without LC [LC (+) or LC (−)] and a statistical analysis was performed using a three-dimensional stereotactic surface projection (3D-SSP). In addition, a fully automatic diagnostic system was developed, which calculated the proportion of the number of abnormal pixels in the superior and inferior parietal lobule, as well as in the precuneus and posterior cingulate gyrus. Results  The areas under the receiver-operating characteristic curve (AUCs) of the early onset group for conventional axial SPECT images, SPECT + 3D-SSP images and the fully automatic diagnostic system were 0.71, 0.88, and 0.92 in LC (−) and 0.67, 0.85, and 0.91 in LC (+), respectively. The AUCs of the late onset group were 0.50, 0.61, and 0.79 in LC (−) and 0.49, 0.67, and 0.85 in LC (+), respectively. Conclusion  LC on Tc-99m HMPAO SPECT did not significantly influence the diagnostic performance for differentiating between AD and normal controls in either early or late onset AD. Further examination with individuals suffering from very mild dementia is, therefore, expected to elucidate the effect of LC on minimally hypoperfused areas.     

Direct comparison study between FDG-PET and IMP-SPECT for diagnosing Alzheimer's disease using 3D-SSP analysis in the same patients

Purpose The purpose of this study was to evaluate and compare the diagnostic ability of 2-[¹⁸F]-fluoro-2-deoxy-d-glucose (FDG) positron emission tomography (PET) and N-isopropyl-p-¹²³I iodoamphetamine single photon emission computed tomography (IMP-SPECT) using three-dimensional stereotactic surface projections (3D-SSP) in patients with moderate Alzheimer's disease (AD). Materials and methods FDG-PET and IMP-SPECT were performed within 3 months in 14 patients with probable moderate AD. Z-score maps of FDG-PET and IMP-SPECT images of a patient were obtained by comparison with data obtained from control subjects. Four expert physicians evaluated and graded the glucose hypometabolism and regional cerebral blood flow (rCBF), focusing in particular on the posterior cingulate gyri/precunei and parietotemporal regions, and determined the reliability for AD. Receiver operating characteristic (ROC) curves were applied to the results for clarification. To evaluate the correlation between two modalities, the regions of interest (ROIs) were set in the posterior cingulate gyri/precunei and parietotemporal region on 3D-SSP images, and mean Z-values were calculated. Conclusion No significant difference was observed in the area under the ROC curve (AUC) between FDG-PET and IMP-SPECT images (FDG-PET 0.95, IMP-SPECT 0.94). However, a significant difference (P < 0.05) was observed in the AUC for the posterior cingulate gyri/precuneus (FDG-PET 0.94, IMP-SPECT 0.81). The sensitivity and specificity of each modality were 86%, and 97% for FDG-PET and 70% and 100% for IMP-SPECT. We could find no significant difference between FDG-PET and IMP-SPECT in terms of diagnosing moderate AD using 3D-SSP. There was a high correlation between the two modalities in the parietotemporal region (Spearman's r = 0.82, P < 0.001). The correlation in the posterior cingulate gyri/precunei region was lower than that in the parietotemporal region (Spearman's r = 0.63, P < 0.016).     

A region-of-interest template for three-dimensional stereotactic surface projection images: initial application to the analysis of Alzheimer's disease and mild cognitive impairment

OBJECTIVE: To construct a region-of-interest (ROI) template for Z-score images of three-dimensional stereotactic surface projections (3-D SSP) and to assess whether the ROI template can be a useful tool for evaluation of brain perfusion abnormalities of neurological disorders. MATERIALS AND METHODS: We constructed the ROI template for Z-score images of 3-D SSP based on the standardized magnetic resonance imaging data of 10 healthy volunteers. We assigned a total of 26 ROIs to Z-score images and superimposed it on Z-score images constructed from the brain perfusion SPECT data of 15 patients with Alzheimer's disease and 10 patients with mild cognitive impairment (MCI) who developed Alzheimer's disease within the following 2 years. We then obtained the mean Z-scores of each ROI and examined them to determine whether the hypoperfusion typical of Alzheimer's disease had been demonstrated quantitatively. We also visually inspected the Z-score image of each patient in both groups to determine whether the areas with the highest Z-scores were demonstrated within the ROIs of regions typical of Alzheimer's disease. RESULTS: In the patients with Alzheimer's disease, our ROI template quantitatively demonstrated hypoperfusion in regions typical of the disease and the Z-scores were very high. In the MCI patients, the mean Z-scores of the ROI in the posterior cingulated gyrus were the highest among all regions. Visual inspection of the Z-score images of each patient in both groups confirmed that the areas with the highest Z-scores were demonstrated within the ROIs in regions typical of Alzheimer's disease in all cases. CONCLUSION: Use of 3-D SSP methods and our ROI template enables automated quantitative evaluation of brain function images over the entire brain surface. In addition, the ROI template may facilitate visual interpretation of functional images of individual patients with neurological disorders.     

Brain SPET abnormalities in Alzheimer's disease before and after atrophy correction

The aim of this study was to determine which brain structures show the greatest influence of partial volume effects (PVE) in single-photon emission tomography (SPET) studies on Alzheimer's disease (AD). Brain perfusion SPET was performed in 30 patients with probable AD and 62 age-matched healthy volunteers. SPET images were corrected for PVE using grey matter volume segmented from magnetic resonance images. The most prominent changes after PVE correction were observed in the medial temporal structures. The PVE correction revealed a selective decrease in regional cerebral blood flow (rCBF) in the parahippocampal gyrus of AD without rCBF decreases in the hippocampus, which had been observed before correction. This correction seems to be essential in order to achieve accurate measurements of rCBF in SPET, which has limited spatial resolution.