[18F]Flutemetamol amyloid-beta PET imaging compared with [11C]PIB across the spectrum of Alzheimer’s disease

Purpose

The aim was to identify the amyloid beta (Aβ) deposition by positron emission tomography (PET) imaging with the ¹⁸F-labeled Pittsburgh compound B (PIB) derivative [¹⁸F]flutemetamol (FMM) across a spectrum of Alzheimer’s disease (AD) and to compare Aβ deposition between [¹⁸F]FMM and [¹¹C]PIB PET imaging.

Methods

The study included 36 patients with AD, 68 subjects with mild cognitive impairment (MCI), 41 older healthy controls (HC) (aged ≥56), 11 young HC (aged ≤45), and 10 transitional HC (aged 46–55). All 166 subjects underwent 30-min static [¹⁸F]FMM PET 85 min after injection, 60-min dynamic [¹¹C]PIB PET, and cognitive testing. [¹⁸F]FMM scans were assessed visually, and standardized uptake value ratios (SUVR) were defined quantitatively in regions of interest identified on coregistered MRI (cerebellar cortex as a reference region). The PIB distribution volume ratios (DVR) were determined in the same regions.

Results

Of 36 AD patients, 35 had positive scans, while 36 of 41 older HC subjects had negative scans. [¹⁸F]FMM scans had a sensitivity of 97.2 % and specificity of 85.3 % in distinguishing AD patients from older HC subjects, and a specificity of 100 % for young and transitional HC subjects. The [¹¹C]PIB scan had the same results. Interreader agreement was excellent (kappa score?=?0.81). The cortical FMM SUVR in AD patients was significantly greater than in older HC subjects (1.76?±?0.23 vs 1.30?±?0.26, p?<?0.01). Of the MCI patients, 68 had a bimodal distribution of SUVR, and 29 of them (42.6 %) had positive scans. Cortical FMM SUVR values were strongly correlated with PIB DVR (r?=?0.94, n?=?145, p?<?0.001).

Conclusion

[¹⁸F]FMM PET imaging detects Aβ deposition in patients along the continuum from normal cognitive status to dementia of AD and discriminates AD patients from HC subjects, similar to [¹¹C]PIB PET.     

Test-retest reproducibility of 18F-MPPF PET in healthy humans: a reliability study.

The aim of this study was to assess the reliability of 2'-methoxyphenyl-(N-2'-pyridinyl)-p-18F-fluoro-benzamidoethylpiperazine (18F-MPPF) PET binding parameter's quantification via a test-retest study over a long-term period. METHODS: Ten healthy volunteers underwent 2 dynamic 18F-MPPF PET scans in an interval of 6 mo. As a methodologic control, 10 simulated datasets, including interindividual functional and anatomic variabilities, were also used to assess the measurement variations in the absence of intraindividual variability. Indices of tracer binding were computed using 2 different models: (a) the simplified reference tissue model (SRTM) and (b) the Logan graphical model. The SRTM allows computing the binding potential (BP) index and plasma-to-brain transport constants (R1, k2). The Logan model evaluates the distribution volume (DV). For both methods, cerebellum was taken as the reference region. From both models, binding indices were calculated with time-activity curves extracted from regions of interest, on one hand, and for each voxel to perform parametric images on the other hand. RESULTS: Reliability indices--that is, bias, variability, and intraclass correlation (ICC)--indicated a good reproducibility: the BP percentage change in mean between test and retest is close to 1% in rich regions and 2% in poor regions. The typical error is around 7%. Mean ICC is over 0.70. The DV percentage change in the mean is +/-2.5%, with a typical error close to 6% and an ICC over 0.60. CONCLUSION: Our results show a good reliability, with a reasonable level of intraindividual biologic variability that allows crossover studies with 18F-MPPF in which small percentage changes are expected between test and retest measurements, in group studies and for single subject assessment.     

^18F-AV45PET/CT显像视觉分析及SUVR对不同认知障碍患者的辅助诊断价值

目的 探讨^18F-AV45 PET/CT脑显像中视觉分析、标准摄取值比值(SUVR)对不同认知障碍患者大脑内β-淀粉样蛋白(Aβ)沉积情况的评估以及临床辅助诊断价值.方法 自2018年12月至2019年7月共纳入47例(名)受试者,包括5名[男3名、女2名,年龄(58±13)岁]健康人对照(NC)、8例[男2例、女6例,年龄(66±10)岁]阿尔茨海默病(AD)患者和34例[男16例、女18例,年龄(70±7)岁]轻度认知障碍(MCI)患者.对所有纳入者行^18F-AV45 PET/CT检查,进行视觉分析,并计算SUVR.对视觉分析和SUVR的诊断效率采用McNemar检验比较,一致性采用Kappa检验分析;组间比较采用单因素方差分析及Welch检验.另外,通过受试者工作特征(ROC)曲线分析获得SUVR的最佳界值.结果 SUVR和视觉分析评估的全部受试Aβ沉积阳性率分别是46.81%(22/47)和38.30% (18/47),差异无统计学意义(x^2=33.15,P>0.05),一致性较好(Kappa=0.83).以临床诊断为“金标准”,视觉分析与SUVR均可鉴别AD和NC:灵敏度分别为7/8和8/8,特异性均为5/5 (x^2=9.48,P>0.05),一致性较好(Kappa=0.84).SUVR定量分析可以鉴别AD与NC组、AD与MCI组,组间SUVR差异有统计学意义(F值:3.99~8.79,均P<0.01),无法鉴别NC与MCI组(均P>0.05).ROC曲线分析示,楔前叶SUVR> 1.08对AD与NC的鉴别诊断效能最高;侧颞叶SUVR> 1.06是鉴别AD与MCI的最佳界值.结论 在^18F-AV45 PET/CT显像中,视觉分析与SUVR定性判断大脑Aβ沉积能力一致,而SUVR定量分析可以辅助鉴别AD与NC、AD与MCI.     

Use of reference tissue models for quantification of histamine H1 receptors in human brain by using positron emission tomography and [11C]doxepin

The aim of the present study is to evaluate the validity of the simplified reference tissue model (SRTM) and of Logan graphical analysis with reference tissue (LGAR) for quantification of histamine H1 receptors (H1Rs) by using positron emission tomography (PET) with [11C]doxepin. These model-based analytic methods (SRTM and LGAR) are compared to Logan graphical analysis (LGA) and to the one-tissue model (1TM), using complete datasets obtained from 5 healthy volunteers. Since HIR concentration in the cerebellum can be regarded as negligibly small, the cerebellum was selected as the reference tissue in the present study. The comparison of binding potential (BP) values estimated by LGAR and 1TM showed good agreement; on the other hand, SRTM turned out to be unstable concerning parameter estimation in several regions of the brain. By including the results of noise analysis, LGAR became a reliable method for parameter estimation of [11C]doxepin data in the cortical regions.     

一体化PET/MR结合统计参数图辅助^11C-PIB显像的半定量分析及其临床应用

目的 研究一体化PET/MR结合统计参数图(SPM)辅助^11C-匹兹堡化合物B(PIB)用于β-淀粉样蛋白(Aβ)PET显像半定量分析的准确性,探索其用于认知障碍的诊断及鉴别诊断的可行性.方法 回顾分析2018年1月至2019年9月在华中科技大学同济医学院附属协和医院PET中心进行^11C-PIB PET/MR扫描,临床最终确诊的13例阿尔茨海默病(AD)患者[男4例,女9例;年龄(59.2±5.8)岁]和10例血管性认知障碍(VCD)患者[男9例,女1例;年龄(59.5±11.5)岁].结合三维T1加权成像(3D T1WI)对^11C-PIB PET图像分别进行脑区手动勾画和SPM辅助半自动分割,获得8个关键脑区(大脑白质、纹状体、丘脑、后扣带回、额叶皮质、后顶叶皮质、颞叶外侧皮质和枕叶皮质)与小脑皮质的标准摄取值比值(SUVR).对2种方法所获结果进行Pearson相关分析;采用两独立样本t检验、配对t检验分析数据.结果 AD组与VCD组患者的年龄和简易精神状态检查量表(MMSE)评分[(19.7±4.7)和(21.7±3.8)分]差异均无统计学意义(t值:0.095和1.098,均P>0.05).除丘脑外(r=0.179,P=0.413),分割法和勾画法在其余7个关键脑区获得的SUVR均有良好的相关性(r值:0.678~0.893,均P<0.05).AD组8个关键脑区的SUVR均明显高于VCD组(1.519~2.055与1.105~1.618;t值:2.799~11.582,均P相似文献   

Optimal scanning time window for 18F-FP-(+)-DTBZ (18F-AV-133) summed uptake measurements

¹⁸F-9-fluoropropyl-(+)-dihydrotetrabenazine (¹⁸F-AV-133) is a novel positron emission tomography tracer for imaging the vesicular monoamine transporter II in dopaminergic neuron degeneration, which might be indicative for Parkinson's disease (PD) and other parkinsonism. Studies were performed to optimize the imaging time window for calculating standardized uptake value ratio (SUVR) with correlation to distribution volume ratio (DVR) and in differentiating PD from normal controls (NCs).

Methods

Thirteen ¹⁸F-AV-133 positron emission tomography studies were conducted on four NCs (age, 62.3±4.9 years) and nine PD patients (age, 60.8±6.0 years) with Hoehn and Yahr stages 2 to 3. Dynamic images were acquired within 180 min (0–30, 50–140 and 160–180 min) and were rearranged into 14 of 10-min scans. The contralateral striatum was defined as the opposite striatum to the predominantly affected limbs. Volumes of interest (VOIs) of bilateral putamen, caudate nuclei and occipital cortex (OC; as the reference region) were delineated from individual magnetic resonance imaging. SUVRs of striatum to OC were computed from 14 dynamic image sets. The DVRs were computed from Logan graphic analysis by using OC as the input. The performance of SUVR was evaluated based on the correlation of SUVR at each time window to DVR, as well as the Cohen effect size (group mean SUVR difference between PD and NC/standard deviation).

Results

¹⁸F-AV-133 uptake decreased in PD subjects at bilateral striatum especially at contralateral side with posterior putamen predominant as compared with NC. Consistent higher correlations of SUVRs to DVR for all VOIs were observed at later time window and reached to its maximal value of 0.9917 at 90–100 min. The group mean SUVR differences between NC and PD subjects increased and reached relatively stable values after 90 min. The effect sizes for all VOIs were stable across different time window and with the largest value around 90~120 min.

Conclusion

The scanning time of 90–100 min for ¹⁸F-AV-133 is considered as the optimal time window for summed uptake measurements in terms of SUVRs' correlation to DVRs, differential power, stability and clinical feasibility across and between NC and PD patients.     

人脑前扣带回皮质喙部在^11C—PIB PET诊断阿尔茨海默病型痴呆中的价值

目的研究人脑前扣带回皮质喙部（rACC）与[N-甲基-^11C]2-[4′-（甲氨基）苯基]-6-羟基苯并噻唑（^11C—PIB）的黏附能力（BP）对阿尔茨海默病型痴呆（DAT）的诊断价值。方法受试对象为美国华盛顿大学医学院通过广告方式招募，按临床痴呆评定量表（CDR）评定的健康受试者（CDR=0）和痴呆患者（CDR〉0），分别为129名和40例（其中有rACC PIB BP数据的健康受试者和DAT患者分别为120名和34例。所有169例受试者均有其他被研究脑局部的PIB BP数据）。脑MRI用于脑局部精确定位。^11C—PIB经肘静脉注射后行PET脑显像。用软件融合MRI和PET图像。用Logan分析软件计算BP。和其他脑局部比较，分析rACC部位PIB BP特点。采用SPSS11．5软件对数据进行线性相关分析、t检验或方差分析。结果有rACC PIB BP数据的健康受试者（CDR=0）和痴呆患者（CDR〉0）分别为120例和34例，而所有169例受试者均有其他脑部位的PIB BP数据。rACC PIB BP和CDR呈直线相关（BP为0．2865±0．442，CDR为0．143±0．290，r=0．545，P〈0．01）。CDR=0．5和1的2组人群中rACC PIB BP值差异无统计学意义（0．6719±0．1545和0．8933±0．0880，t=-1．245，P〉0．05），但CDR=0和〉0的2组人群中差异有统计学意义（0．1589±0．0219和0．7370±0．1125，t=-7．998，P〈0．01）。rACC PIB BP的阈值为0．4592，用该阈值诊断DAT的灵敏度为67．65％（23／34），特异性为88．33％（106／120）。DAT患者和健康人群之间BP有交叉在已被研究的脑局部中，DAT患者楔前回、rACC和额前回各自的PIB BP均值及这3个脑局部各自在DAT患者组和HC组间的PIB BP均值之差都高居前3位。结论rACC PIB BP有鉴别诊断DAT的价值，rACC、楔前回、额前回均是用PIB BP诊断DAT的较敏感脑部区域。     

Reference region selection and the association between the rate of amyloid accumulation over time and the baseline amyloid burden

Relative quantitative analysis of amyloid plaque burden in Alzheimer’s disease (AD) patients can be reported as standardized uptake value ratio (SUVR) from positron emission tomography (PET). Here, the SUVR is the ratio of the mean amyloid radioligand retention in a composite (COMP) neocortical volume of interest (VOI) to that in a reference VOI, such as the cerebellum, brainstem (BST)/pons, or white matter (WM). Some longitudinal PET investigations show that the rate of amyloid accumulation to follow-up has an inverted U relationship with baseline amyloid SUVR relative to cerebellar or brainstem/pons reference VOIs. The corresponding association with SUVR relative to WM is unknown. To test the possible benefits of WM normalization, we analyzed [¹⁸F]-AV45 PET data from 404 subjects in the AD Neuroimaging Initiative (ADNI) database at baseline and 2-year follow-up (144 cognitively normal controls, 225 patients with mild cognitive impairment, and 35 AD patients). Reference regions included subcortical WM as well as conventional cerebellar gray matter (CBL), and BST. We tested associations between each subject’s inter-session change (?) of SUVR and their baseline SUVR by applying linear, logarithmic, and quadratic regression analyses. Unscaled standardized uptake values (SUVs) were correlated between VOIs at baseline and follow-up, and within VOIs in the longitudinal run. The association between ?SUVR and baseline SUVR relative to WM reference was best described by an inverted U-shaped function. Correlation analyses demonstrated a high regional and temporal correlation between COMP and WM VOI SUVs. For WM normalization, we confirm that the rate of amyloid accumulation over time follows an inverted U-shaped function of baseline amyloid burden. Reference region selection, however, has substantial effects on SUVR results. This reflects the extent of covariance between SUVs in the COMP VOI and those in the various reference VOIs. We speculate that PET labeling of amyloid deposition within target regions is partially confounded by effects of longitudinal changes of cerebral blood flow (CBF) on tracer delivery. Indeed, CBF may be the leading factor influencing longitudinal SUV changes. We suggest that SUVR relative to WM may be more robust to changes in CBF, and thus fitter for sensitive detection of amyloid accumulation in intervention studies.     

Visual assessment versus quantitative assessment of 11C-PIB PET and 18F-FDG PET for detection of Alzheimer's disease.

Amyloid-beta (Abeta) imaging with N-methyl-(11)C-2-(4'-methylamino-phenyl)-6-hydroxy-benzothiazole ((11)C-6-OH-BTA-1; also known as (11)C-PIB) shows a robust increase in cortical binding in Alzheimer's disease (AD). The aim of this study was to explore the clinical potential of Abeta imaging for the diagnosis of AD by comparison of the accuracy of visual reading of (11)C-PIB images with quantitative analysis and (18)F-FDG. METHODS: Fifteen AD patients (age, 71.1 +/- 11.3 y [mean +/- SD]; mini-mental state examination [MMSE], 18.9 +/- 9.3 [mean +/- SD]) and 25 healthy control (HC) subjects (age, 71.9 +/- 6.82 y; MMSE >or= 28) underwent 90-min dynamic (11)C-PIB PET and 20-min static (18)F-FDG PET. (11)C-PIB images, generated from data acquired between 40 and 70 min after injection, and (18)F-FDG images were rated separately by 2 readers as normal, possible AD, or probable AD. Quantitative analyses used the distribution volume ratio (DVR) of frontal cortex, parietotemporal cortex, posterior cingulate, and caudate nucleus for (11)C-PIB and standardized uptake value ratio (SUVR) of parietotemporal cortex and posterior cingulate for (18)F-FDG, using cerebellar cortex as the reference region. Receiver-operating-characteristic (ROC) analysis was performed to compare the accuracy of quantitative measures. To determine the effect of age on diagnostic accuracy, the median age of the AD subjects (74 y) was chosen to separate the cohort into younger (64.4 +/- 5.8 y) and older (78.6 +/- 4.1 y) groups. RESULTS: Visual agreement between readers was excellent for (11)C-PIB (kappa = 0.90) and good for (18)F-FDG (kappa = 0.56). (11)C-PIB was more accurate than (18)F-FDG both on visual reading (accuracy, 90% vs. 70%, P = 0.05) and ROC analysis (95% vs. 83%, P = 0.02). Accuracy declined more with (18)F-FDG than with (11)C-PIB in the older group. CONCLUSION: Visual analysis of (11)C-PIB images appears more accurate than visual reading of (18)F-FDG for identification of AD and has accuracy similar to quantitative analysis of a 90-min dynamic scan. The accuracy of (11)C-PIB PET is limited by cortical binding in some healthy elderly subjects, consistent with postmortem studies of cerebral Abeta. Longitudinal follow-up is required to determine if this represents detection of preclinical AD.     

Comparison of 11C-PiB and 18F-florbetaben for Aβ imaging in ageing and Alzheimer’s disease

Purpose

Amyloid imaging with ¹⁸F-labelled radiotracers will allow widespread use of this technique, facilitating research, diagnosis and therapeutic development for Alzheimer’s disease (AD). The purpose of this analysis was to compare data on cortical Aβ deposition in subjects who had undergone both ¹¹C-PiB (PiB) and ¹⁸F-florbetaben (FBB) PET imaging.

Methods

We identified ten healthy elderly controls (HC) and ten patients with AD who had undergone PET imaging after intravenous injection of 370?MBq of PiB and 300?MBq of FBB under separate research protocols. PiB and FBB images were coregistered so that placement of regions of interest was identical on both scans and standard uptake value ratios (SUVR) using the cerebellar cortex as reference region were calculated between 40 and 70?min and between 90 and 110?min after injection for PiB and FBB, respectively.

Results

Significantly higher SUVR values (p?r?=?0.97, p?d 3.3 for PiB and 3.0 for FBB).

Conclusion

FBB, while having a narrower dynamic range than PiB, clearly distinguished HC from AD patients, with a comparable effect size. FBB seems a suitable ¹⁸F radiotracer for imaging AD pathology in vivo.     

Perfusion-like template and standardized normalization-based brain image analysis using 18F-florbetapir (AV-45/Amyvid) PET

Purpose

Amyloid positron emission tomography (PET) is an important noninvasive method for detecting amyloid burden in Alzheimer’s disease (AD) patients. As amyloid PET images have limited anatomical information, magnetic resonance (MR) imaging is usually acquired to perform reliable spatial normalization needed for large-scale analysis. This work proposed and evaluated the performance of new MR-free spatial normalization methods using a perfusion-like template for amyloid PET imaging.

Methods

Amyloid PET and MR images were collected in 35 subjects (cohort 1: 8 AD patients and 6 controls; cohort 2: 15 AD patients and 6 controls). Three ligand-related templates (AD, control, mixed group) and a perfusion-like template (pAV-45) from early time frames of amyloid PET images were constructed from cohort 1. The variations of ¹⁸F-AV-45 standardized uptake value ratios (SUVRs) among AD patients, controls, and all subjects were tested with repeated two-way (template × brain region) analysis of variance (ANOVA) in cohort 2. ¹⁸F-AV-45 SUVRs by region of interest analysis and voxelwise analysis between MR-based and MR-free approaches were compared and correlated to clinical and image parameters. Effect size (group mean SUVR difference between AD and control/standard deviation) was also evaluated for each template method.

Results

Significantly different ¹⁸F-AV-45 SUVRs between MR-free spatial normalization and MR-based reference images were found among AD patients, controls, and all subjects by the effect of template and brain regions. The highest correlation (r=0.991) of ¹⁸F-AV-45 SUVR to MR-based reference was found in the pAV-45 group. The SUVR percentage difference to MR-based reference showed the least variation and bias (control: ?1.31±3.47 %; AD: ?0.36±2.50 %) in the pAV-45 group as well. The voxelwise analysis showed the smallest t statistic value in pAV-45 followed by mixed, control, and AD groups when compared to MR-based reference images. Moreover, an overall larger effect size but compatible to that of MR-based reference result was observed in the pAV-45 group as compared to those of the other MR-free template.

Conclusion

The novel MR-free template based on the early-phase perfusion images pAV-45 approach for amyloid imaging showed significantly better performance in quantitation accuracy, effect size, and stability when compared with other MR-free PET templates and thus has potential for large-scale clinical applications.     

视觉定性评估法与半定量分析法在18F-florbetabenβ-淀粉样蛋白显像中的准确性比较

目的比较视觉定性评估法和半定量分析法用于¹⁸F-氟比他班(FBB)β-淀粉样蛋白(Aβ)显像诊断阿尔茨海默病(AD)的准确性并探讨其临床应用价值。方法前瞻性纳入2019年1月至2019年10月间解放军总医院临床诊断为可能的轻/中度AD患者17例[男8例,女9例,年龄(74.1±8.5)岁]和认知功能正常志愿者(NC)17名[男9名,女8名,年龄(64.5±6.3)岁]。所有受试者均行动态¹⁸F-FBB PET/CT脑显像。采用视觉定性评估法和半定量分析法分析PET脑显像结果。采用两样本t检验比较2种方法所得标准摄取值比值(SUVR)差异;2种方法与临床结果的一致性采用Kappa检验分析;采用受试者工作特征(ROC)曲线确定诊断AD的SUVR最佳界值。结果视觉定性评估诊断AD的灵敏度、特异性和准确性分别为14/17、16/17和88.2%(30/34)。NC组和AD组全脑SUVR分别为1.09±0.85和1.75±0.25,复合皮质SUVR分别为1.16±0.57和1.89±0.15,差异均有统计学意义(t值:-10.263和-10.789,均P<0.001)。半定量分析法诊断AD的SUVR最佳界值为1.47,灵敏度、特异性和准确性分别为15/17、16/17和91.2%(31/34)。视觉定性评估法和半定量分析法与临床诊断结果的一致性都较好(Kappa值:0.765和0.824,均P<0.001)。结论视觉定性评估法和半定量分析法用于¹⁸F-FBB Aβ显像诊断AD都具有较高的准确性,但视觉定性评估法简洁清晰易掌握,在临床工作中值得进一步推广和使用。     

新型斑块显像剂18F-W372在阿尔茨海默病中的应用

目的 通过比较18F-7-甲氧基-2(6-氟-18吡啶-3-yl)咪唑[2,1-β]-8-吡啶噻唑(18F-W372)和11C-匹兹堡化合物B(11C-PIB)在AD患者和健康老年志愿者(HC)的动态影像,评价新型斑块显像剂18F-W372的临床应用价值.方法 8例AD患者,年龄(64.00±8.81)岁,男∶女=1∶7;9名HC,年龄(64.78±4.02)岁,男∶女=4∶5;2名青年志愿者,男29岁,女25岁.静脉注射18F-W372和11C-PIB后,进行40 min连续动态PET数据采集.计算每个受试者SUV以及皮质/小脑SUV比率(SUVR),获得2种示踪剂TAC.应用秩和检验及两样本t检验进行统计学处理.结果 AD患者简易智力状态检查量表(MMSE)评分低于HC,为19.13±4.05与28.89±0.78(T=36.00,P＜0.01).AD与HC受试者年龄(H=28.50,P＞0.05)及受教育程度(H=35.50,P＞0.05)差异无统计学意义.18F-W372能够快速通过血脑屏障并迅速廓清.AD患者在皮质区域出现18F-W372摄取,而青年志愿者仅有少量摄取.给药40 min内,18F-W372和11C-PIB在AD患者皮质/小脑SUVR进行性增加,但后者更加明显.两者均出现白质区放射性浓聚,但18F-W372在白质的摄取明显高于皮质.35～40 min时,AD患者和HC11C-PIB和18F-W372皮质/小脑SUVR分别为1.48±0.22与1.06±0.04(t=5.58,P＜0.001)和1.31±0.08与1.17±0.06(t=3.78,P＜0.01).结论 18F-W372与11C-PIB具有相似分布模式,在注射18F-W372 40 min内SUVR在AD患者与HC间有差异,但视觉上病灶欠清晰.18F-W372作为斑块显像剂临床应用有待进一步深入研究.     

Reference and target region modeling of [11C]-(R)-PK11195 brain studies.

PET with [(11)C]-(R)-PK11195 is currently the modality of choice for the in vivo imaging of microglial activation in the human brain. In this work we devised a supervised clustering procedure and a new quantification methodology capable of producing binding potential (BP) estimates quantitatively comparable with those derived from plasma input with robust quantitative implementation at the pixel level. METHODS: The new methodology uses predefined kinetic classes to extract a gray matter reference tissue without specific tracer binding and devoid of spurious signals (in particular, blood pool and muscle). Kinetic classes were derived from an historical database of 12 healthy control subjects and from 3 patients with Huntington's disease. BP estimates were obtained using rank-shaping exponential spectral analysis (RS-ESA) (both plasma and reference input) and the simplified reference tissue model (SRTM). Comparison between plasma- derived BPs and those produced with the new reference methodology was performed using 6 additional healthy control subjects. Reliability of the new methodology was performed on 4 test-retest studies of patients with Alzheimer's disease. RESULTS: The new algorithm selected reference voxels in gray matter tissue avoiding regions with specific binding located, in particular, in the venous and arterial circulation. Using the new reference, BP values obtained using a plasma input and a reference input were in excellent agreement and highly correlated (r = 0.811, P < 10(-5)) when calculated with RS-ESA and less so (r = 0.507, P < 0.005) when SRTM was used. In the production of parametric maps, SRTM was used with the new reference extraction, resulting in test-retest variability (10.6%; mean ICC = 0.878) that was superior to that obtained using the previous unsupervised clustering approach (mean ICC = 0.596). CONCLUSION: Reference region modeling combined with supervised reference tissue extraction produces a robust and reproducible quantitative assessment of [(11)C]-(R)-PK11195 studies in the human brain.     

Quantification of serotonin transporters in nonhuman primates using [(123)I]ADAM and SPECT.

We reported recently a highly selective radioligand, 2-([2-([dimethylamino]methyl)phenyl]thio)-5-[(123)I]iodophenylamine (ADAM), for SPECT imaging of serotonin transporters (SERT). In this article we describe the kinetic modeling of [(123)I]ADAM and its ability to quantitatively and reproducibly measure the concentrations of SERT in the nonhuman primate brain. We also investigate simplified models of tracer behavior that do not require invasive arterial blood sampling. METHODS: Three female baboons each underwent 3 [(123)I]ADAM SPECT studies. The studies consisted of a dynamic sequence of seventy-two 5-min scans after injection of 330 +/- 50 MBq (mean +/- SD) [(123)I]ADAM. Rapid arterial blood samples were obtained and corrected for the presence of labeled metabolites. Dynamic imaging and metabolite-corrected plasma data were analyzed using graphic analysis to give the distribution volumes (DVs) of different brain regions. DV ratios (DVRs) of target to cerebellum were derived and compared against a kinetic reference tissue model and simple target-to-background ratio. RESULTS: Averaged over all 9 scans, the mean DV in the midbrain was 4.86 +/- 1.06 mL/mL and the mean DV in the cerebellum was 2.25 +/- 0.48 mL/mL. The mean test-retest repeatability of the midbrain DV was 14.5%. The reference tissue model gave a mean midbrain DVR of 2.01 +/- 0.17 and correlated strongly with the DVR calculated from the full kinetic model (correlation coefficient [R(2)] = 0.94; P < 0.001), but with much improved repeatability (test-retest, 5.4%; intersubject variability, 5.2%). Similarly, the simple ratio method gave strong correlations with the full kinetic model (R(2) = 0.89; P < 0.001) and a test-retest of 7.6%. CONCLUSION: Accurate, repeatable quantification of SERT in the nonhuman primate brain is possible using kinetic modeling of dynamic [(123)I]ADAM SPECT scans. Simplified models, which do not require arterial blood sampling, gave accurate results that correlated strongly with the full kinetic model. The test-retest reliability of the simplified reference region models was excellent. Quantification of SERT is possible using full kinetic modeling and also with simpler reference region methods.     

11C-PIB在轻度认知障碍及阿尔茨海默病诊断中的价值及其影响因素

目的研究¹¹C-匹兹堡化合物B(PIB)在轻度认知障碍(MCI)与阿尔茨海默病(AD)患者诊断中的应用价值及可能影响¹¹C-PIB结合的因素。方法回顾性分析2017年1月至2019年12月期间在陆军军医大学大坪医院行¹¹C-PIB PET显像的6例认知功能正常患者(NC)[男、女各3例,年龄(64.5±12.3)岁]、11例MCI患者[男4例,女7例,年龄(64.5±9.8)岁]和21例AD患者[男7例,女14例,年龄(68.1±9.1)岁]对¹¹C-PIB的摄取情况,采用标准摄取值比值(SUVR)法及视觉分析评估¹¹C-PIB在患者脑皮质的分布区域和结合量,并收集患者相关临床资料[包括年龄、性别、文化程度、认知障碍程度、神经心理学量表评分、血管危险因素(VRF)、载脂蛋白E(ApoE)基因等]。采用单因素方差分析或Fisher确切概率法进行组间比较,两两比较采用最小显著差异t检验,采用多元线性回归分析可能影响11C-PIB结合的因素。结果NC、MCI及AD组各脑叶组间比较SUVR差异均有统计学意义(3组各脑叶SUVR均值范围:1.16~1.26、1.19~1.35和1.40~1.61;F值:5.331~9.279,均P<0.05)。NC组与PIB阳性的MCI患者比较,后扣带回及楔前叶SUVR差异均有统计学意义(1.20±0.15与1.50±0.12,1.18±0.15与1.59±0.13;F值:6.389和10.668,t值:-2.33和-3.10,均P<0.05);PIB阳性的MCI与PIB阳性的AD比较各脑叶SUVR差异均无统计学意义(t值:-1.29~-0.51,均P>0.05)。视觉分析结果显示,AD组额叶[85.7%(18/21)]、后扣带回[85.7%(18/21)]、楔前叶[81.0%(17/21)]、颞叶[81.0%(17/21)]和枕叶[47.6%(10/21)]PIB阳性率明显高于MCI组(4/11、4/11、4/11、3/11和1/11;均P<0.05)。多元线性回归分析示认知障碍程度是影响各脑叶SUVR的独立危险因素(b值:0.377~0.536,均P<0.05),携带ApoEε4基因是影响楔前叶SUVR的独立危险因素(b=0.290,P<0.05)。结论¹¹C-PIB有助于临床对MCI及AD患者的诊断;认知障碍程度及ApoEε4基因携带是影响¹¹C-PIB结合的独立危险因素。     

Reproducibility of automated simplified voxel-based analysis of PET amyloid ligand [<Superscript>11</Superscript>C]PIB uptake using 30-min scanning data

Purpose  

Positron emission tomography (PET) with ¹¹C-labelled Pittsburgh compound B ([¹¹C]PIB) enables the quantitation of β-amyloid accumulation in the brain of patients with Alzheimer’s disease (AD). Voxel-based image analysis techniques conducted in a standard brain space provide an objective, rapid and fully automated method to analyze [¹¹C]PIB PET data. The purpose of this study was to evaluate both region- and voxel-level reproducibility of automated and simplified [¹¹C]PIB quantitation when using only 30 min of imaging data.     

Simplified quantification of nicotinic receptors with 2[18F]F-A-85380 PET

INTRODUCTION: Neuronal nicotinic acetylcholine receptors (nAChRs), widely distributed in the human brain, are implicated in various neurophysiological processes as well as being particularly affected in neurodegenerative conditions such as Alzheimer's disease. We sought to evaluate a minimally invasive method for quantification of nAChR distribution in the normal human brain, suitable for routine clinical application, using 2[(18)F]F-A-85380 and positron emission tomography (PET). METHODS: Ten normal volunteers (four females and six males, aged 63.40+/-9.22 years) underwent a dynamic 120-min PET scan after injection of 226 MBq 2[(18)F]F-A-85380 along with arterial blood sampling. Regional binding was assessed through standardized uptake value (SUV) and distribution volumes (DV) obtained using both compartmental (DV(2CM)) and graphical analysis (DV(Logan)). A simplified approach to the estimation of DV (DV(simplified)), defined as the region-to-plasma ratio at apparent steady state (90-120 min post injection), was compared with the other quantification approaches. RESULTS: DV(Logan) values were higher than DV(2CM). A strong correlation was observed between DV(simplified), DV(Logan) (r=.94) and DV(2CM) (r=.90) in cortical regions, with lower correlations in thalamus (r=.71 and .82, respectively). Standardized uptake value showed low correlation against DV(Logan) and DV(2CM). CONCLUSION: DV(simplified) determined by the ratio of tissue to metabolite-corrected plasma using a single 90- to 120-min PET acquisition appears acceptable for quantification of cortical nAChR binding with 2[(18)F]F-A-85380 and suitable for clinical application.     

Whole-body biodistribution and the influence of body activity on brain kinetic analysis of the <Superscript>11</Superscript>C-PiB PET scan

Dynamic ¹¹C-PiB PET imaging with kinetic analysis has been performed for accurate quantification of amyloid binding in patients with Alzheimer’s disease (AD). In this study, we measured the whole-body biodistribution of ¹¹C-PiB in nine subjects. We then evaluated the effect of body activity on quantitative accuracy of brain ¹¹C-PiB three-dimensional (3D) dynamic PET. Based on clinical biodistribution data, we conducted phantom experiments to estimate the effect of body activity on quantification of the brain 3D dynamic ¹¹C-PiB PET data and the error introduced by body activity using six different PET camera models. One of the PET cameras was used to acquire ¹¹C-PiB brain 3D dynamic PET data on a patient with AD. We calculated the distribution volume ratio (DVR) in two kinetic methods using both the original human time-activity-curve (TAC) data and the TAC corrected for the error caused by body activity. In the early phase, both healthy subjects and patients with AD showed a biodistribution of ¹¹C-PiB that reflected regional blood flow. In the simulated early phase of the phantom experiments, activity outside the field of view led to a maximum 6.0% overestimation of brain activity in the vertex region. Conversely, the effect of body activity on the DVR estimate was small (≤1.2%), probably because the tested kinetic methods did not rely heavily on early phase data. These results indicate that the effect of body activity on brain ¹¹C-PiB PET quantification is generally small and that it depends on the method of kinetic analysis, the region of interest, and the PET camera model used.     

Construction and evaluation of multitracer small-animal PET probabilistic atlases for voxel-based functional mapping of the rat brain.

Automated voxel-based or predefined volume-of-interest (VOI) analysis of rodent small-animal PET data is necessary for optimal use of information because the number of available resolution elements is limited. We have mapped metabolic ((18)F-FDG), dopamine transporter (DAT) (2'-(18)F-fluoroethyl(1R-2-exo-3-exe)-8-methyl-3-(4-chlorophenyl)-8-azabicyclo[3.2.1]-octane-2-carboxylate [(18)F-FECT]), and dopaminergic D(2) receptor ((11)C-raclopride) small-animal PET data onto a 3-dimensional T2-weighted MRI rat brain template oriented according to the rat brain Paxinos atlas. In this way, ligand-specific templates for sensitive analysis and accurate anatomic localization were created. Registration accuracy and test-retest and intersubject variability were investigated. Also, the feasibility of individual rat brain statistical parametric mapping (SPM) was explored for (18)F-FDG and DAT imaging of a 6-hydroxydopamine (6OHDA) model of Parkinson's disease. METHODS: Ten adult Wistar rats were scanned repetitively with multitracer small-animal PET. Registrations and affine spatial normalizations were performed using SPM2. On the MRI template, a VOI map representing the major brain structures was defined according to the stereotactic atlas of Paxinos. (18)F-FDG data were count normalized to the whole-brain uptake, whereas parametric DAT and D(2) binding index images were constructed by reference to the cerebellum. Registration accuracy was determined using random simulated misalignments and vectorial mismatching. RESULTS: Registration accuracy was between 0.24 and 0.86 mm. For (18)F-FDG uptake, intersubject variation ranged from 1.7% to 6.4%. For (11)C-raclopride and (18)F-FECT data, these values were 11.0% and 5.3%, respectively, for the caudate-putamen. Regional test-retest variability of metabolic normalized data ranged from 0.6% to 6.1%, whereas the test-retest variability of the caudate-putamen was 14.0% for (11)C-raclopride and 7.7% for (18)F-FECT. SPM analysis of 3 individual 6OHDA rats showed severe hypometabolism in the ipsilateral sensorimotor cortex (P 相似文献