Positron emission tomography

正电子发射断层扫描
  • 文章类型: Journal Article
    背景:转移性分化型甲状腺癌(DTC)代表一组分子异质性癌症,具有不同的放射性碘(RAI)和[18F]-氟脱氧葡萄糖(FDG)摄取模式,可能与所谓的“翻转”现象的去分化程度相关。然而,RAI和FDG摄取模式是否与分子状态或转移部位相关尚不清楚.材料和方法:回顾性分析2008年至2022年期间接受放射性131碘全身扫描(WBS)和FDG-PET成像的转移性DTC患者(n=46)。纳入标准包括1年内可获得的FDG-PET和WBS研究。两名失明的放射科医生解释了甲状腺外部位包括肺在内的碘或FDG摄取的研究,淋巴结,还有骨头.病例按BRAFV600E突变状态分层,组织学,以及肿瘤基因型和组织学的组合。数据采用McNemar卡方检验。结果:肺转移FDG摄取明显高于碘摄取(WBS:52%,FDG:84%,p=0.04),但淋巴结或骨转移没有发现显着差异。肺转移FDG摄取在乳头状模式亚组中明显更普遍(WBS:37%,FDG:89%,p=0.02)比卵泡模式子队列(WBS:75%,FDG:75%,p=1.00)。同样,具有肺转移的BRAFV600E+肿瘤也表现出FDG摄取的优势(WBS:29%,FDG:93%,p=0.02)比BRAFV600E-肿瘤(WBS:83%,FDG:83%,p=1.00)伴肺转移。乳头状组织学在肺转移中具有较高的FDG摄取(WBS:39%,FDG:89%,p=0.03)与卵泡组织学相比(WBS:69%,FDG:77%,p=1.00)。乳头状型疾病患者,BRAFV600E+突变,与滤泡型疾病相比,或乳头状组织学在所有转移部位的两种摄取方式之间的一致性降低,BRAFV600E-突变,或卵泡组织学。无论分子状态或组织学如何,所有患者的淋巴结摄取均呈低一致性。结论:FDG-PET和放射性碘摄取的模式取决于分子状态和转移部位,具有乳头状组织学或BRAFV600E突变的患者在远处转移中表现为FDG摄取增加。扩大队列的进一步研究可以确定哪些患者可以从特定的成像模式中受益,以识别和监测转移。
    Background: Metastatic differentiated thyroid cancer (DTC) represents a molecularly heterogeneous group of cancers with varying radioactive iodine (RAI) and [18F]-fluorodeoxyglucose (FDG) uptake patterns potentially correlated with the degree of de-differentiation through the so-called \"flip-flop\" phenomenon. However, it is unknown if RAI and FDG uptake patterns correlate with molecular status or metastatic site. Materials and Methods: A retrospective analysis of metastatic DTC patients (n = 46) with radioactive 131-iodine whole body scan (WBS) and FDG-PET imaging between 2008 and 2022 was performed. The inclusion criteria included accessible FDG-PET and WBS studies within 1 year of each other. Studies were interpreted by two blinded radiologists for iodine or FDG uptake in extrathyroidal sites including lungs, lymph nodes, and bone. Cases were stratified by BRAF V600E mutation status, histology, and a combination of tumor genotype and histology. The data were analyzed by McNemar\'s Chi-square test. Results: Lung metastasis FDG uptake was significantly more common than iodine uptake (WBS: 52%, FDG: 84%, p = 0.04), but no significant differences were found for lymph or bone metastases. Lung metastasis FDG uptake was significantly more prevalent in the papillary pattern sub-cohort (WBS: 37%, FDG: 89%, p = 0.02) than the follicular pattern sub-cohort (WBS: 75%, FDG: 75%, p = 1.00). Similarly, BRAF V600E+ tumors with lung metastases also demonstrated a preponderance of FDG uptake (WBS: 29%, FDG: 93%, p = 0.02) than BRAF V600E- tumors (WBS: 83%, FDG: 83%, p = 1.00) with lung metastases. Papillary histology featured higher FDG uptake in lung metastasis (WBS: 39%, FDG: 89%, p = 0.03) compared with follicular histology (WBS: 69%, FDG: 77%, p = 1.00). Patients with papillary pattern disease, BRAF V600E+ mutation, or papillary histology had reduced agreement between both modalities in uptake at all metastatic sites compared with those with follicular pattern disease, BRAF V600E- mutation, or follicular histology. Low agreement in lymph node uptake was observed in all patients irrespective of molecular status or histology. Conclusions: The pattern of FDG-PET and radioiodine uptake is dependent on molecular status and metastatic site, with those with papillary histology or BRAF V600E+ mutation featuring increased FDG uptake in distant metastasis. Further study with an expanded cohort may identify which patients may benefit from specific imaging modalities to recognize and surveil metastases.
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  • 文章类型: Journal Article
    胃泌素释放肽受体(GRPR),在许多实体瘤中过度表达,是一个很有前途的成像标记和治疗靶点。大多数报道的GRPR靶向放射性配体含有C末端酰胺。根据报道的强效拮抗剂D-Phe-Gln-Trp-Ala-Val-Gly-His-Leu-NHOH,我们合成了C末端异羟肟酸盐衍生的[68Ga]Ga-LW02075([68Ga]Ga-DOTA-pABzA-DIG-D-Phe-Gln-Trp-Ala-Val-Gly-His-Leu-NHOH)和[68Ga]Ga-LW02050([68Ga]-DOTA-Pip-D-NHal-Phe-并将它们与密切相关和临床验证的[68Ga]Ga-SB3([68Ga]Ga-DOTA-pABzA-DIG-D-Phe-Gln-Trp-Ala-Val-Gly-His-Leu-NHEt)进行了比较。Ga-SB3、Ga-LW02075和Ga-LW02050的结合亲和力(Ki)分别为1.20±0.31、1.39±0.54和8.53±1.52nM,分别。通过钙释放测定证实Ga-LW02075和Ga-LW02050都是GRPR拮抗剂。影像学研究表明,在PET图像中,[68Ga]Ga-SB3和[68Ga]Ga-LW02050注射后1小时,PC-3前列腺癌肿瘤异种移植物清晰可见。但不是[68Ga]Ga-LW02075。注射后1小时进行的离体生物分布研究表明,[68Ga]Ga-LW02050的肿瘤摄取与[68Ga]Ga-SB3相当(5.38±1.00vs.6.98±1.36%内径/g),然后是[68Ga]Ga-LW02075(3.97±1.71%ID/g)。[68Ga]Ga-SB3的胰腺摄取最高(37.3±6.90%ID/g),其次是[68Ga]Ga-LW02075(17.8±5.24%ID/g),而[68Ga]Ga-LW02050的胰腺摄取仅为0.53±0.11%ID/g。我们的数据表明[68Ga]Ga-LW02050是一种有前途的PET示踪剂,可用于检测表达GRPR的癌症病变。
    Gastrin-releasing peptide receptor (GRPR), overexpressed in many solid tumors, is a promising imaging marker and therapeutic target. Most reported GRPR-targeted radioligands contain a C-terminal amide. Based on the reported potent antagonist D-Phe-Gln-Trp-Ala-Val-Gly-His-Leu-NHOH, we synthesized C-terminal hydroxamate-derived [68Ga]Ga-LW02075 ([68Ga]Ga-DOTA-pABzA-DIG-D-Phe-Gln-Trp-Ala-Val-Gly-His-Leu-NHOH) and [68Ga]Ga-LW02050 ([68Ga]Ga-DOTA-Pip-D-Phe-Gln-Trp-Ala-Val-Gly-His-Leu-NHOH), and compared them with the closely related and clinically validated [68Ga]Ga-SB3 ([68Ga]Ga-DOTA-pABzA-DIG-D-Phe-Gln-Trp-Ala-Val-Gly-His-Leu-NHEt). Binding affinities (Ki) of Ga-SB3, Ga-LW02075, and Ga-LW02050 were 1.20 ± 0.31, 1.39 ± 0.54, and 8.53 ± 1.52 nM, respectively. Both Ga-LW02075 and Ga-LW02050 were confirmed to be GRPR antagonists by calcium release assay. Imaging studies showed that PC-3 prostate cancer tumor xenografts were clearly visualized at 1 h post injection by [68Ga]Ga-SB3 and [68Ga]Ga-LW02050 in PET images, but not by [68Ga]Ga-LW02075. Ex vivo biodistribution studies conducted at 1 h post injection showed that the tumor uptake of [68Ga]Ga-LW02050 was comparable to that of [68Ga]Ga-SB3 (5.38 ± 1.00 vs. 6.98 ± 1.36 %ID/g), followed by [68Ga]Ga-LW02075 (3.97 ± 1.71 %ID/g). [68Ga]Ga-SB3 had the highest pancreas uptake (37.3 ± 6.90 %ID/g) followed by [68Ga]Ga-LW02075 (17.8 ± 5.24 %ID/g), while the pancreas uptake of [68Ga]Ga-LW02050 was only 0.53 ± 0.11 %ID/g. Our data suggest that [68Ga]Ga-LW02050 is a promising PET tracer for detecting GRPR-expressing cancer lesions.
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  • 文章类型: Journal Article
    目的:本研究旨在解决传统图形分析方法所需的长扫描持续时间的问题,比如洛根图及其变体,可逆平衡(RE)洛根图,用于示踪动力学的动态PET成像。
方法:我们提出了一个相对的RELogan模型,该模型建立在Logan图及其变体的原理上,以显着减少扫描时间,而不会损害示踪剂动力学分析的准确性。该模型得到了理论证据和实验验证的支持,包括两个计算机模拟和一个临床数据分析。
主要结果:所提出的模型证明了变量x与RELogan图的斜率DV_T之间存在显着的线性关系,以及相对RELogan图的变量x\'和斜率DV_T\'。x\'与x的线性拟合的皮尔逊相关系数(r)等于模拟数据中的0.9849和临床数据中的0.9912。同样,在模拟数据中,DV_T\'与DV_T线性拟合的r值等于0.9989和0.9988,和0.9954的临床数据。
意义:这些结果证明了该模型具有保持强线性关系并产生与传统RELogan图相当的参数图像的能力,但具有扫描持续时间较短的相当大的优势。这种创新对于提高临床环境中PET成像的效率和可行性具有重要的潜力。
    OBJECTIVE: This study aims to address the issue of long scan durations required by traditional graphical analysis methods, such as the Logan plot and its variant, the reversible equilibrium (RE) Logan plot, for dynamic PET imaging of tracer kinetics. Approach: We propose a relative RE Logan model that builds on the principles of the Logan plot and its variant to significantly reduce scan time without compromising the accuracy of tracer kinetics analysis. The model is supported by theoretical evidence and experimental validations, including two computer simulations and one clinical data analysis. Main results: The proposed model demonstrates a significant linear relationship between the variable x and the slope DV_T of the RE Logan plot, and the variable x\' and the slope DV_T\' of the relative RE Logan plot. The Pearson correlation coefficients (r) of the linear fitting of the x\' to the x equal 0.9849 in the simulated data and 0.9912 in the clinical data. Similarly, the r value for the linear fitting of DV_T\' to DV_T equal 0.9989 and 0.9988 in the simulated data, and 0.9954 in the clinical data. Significance: These results demonstrate the model\'s capability to maintain strong linear relationships and produce parametric images comparable to those of the traditional RE Logan plot, but with the considerable advantage of shorter scan durations. This innovation holds significant potential for enhancing the efficiency and feasibility of PET imaging in clinical settings.
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  • 文章类型: Journal Article
    [18F]FDGPET/CT无创地证实了疑似肾移植受者(KTRs)的急性肾移植排斥反应(AR)。然而,基于活检的班夫与基于PET/CT的急性炎症评分尚不清楚,怀疑AR后一年[18F]FDGPET/CT的预后表现也是如此。
    从2012年到2019年,对105例接受了每种原因移植活检的成人KTR进行了114[18F]FDG-PET/CT。序数逻辑回归评估了组织学炎症程度与平均标准化[18F]FDG摄取值(mSUVmean)之间的相关性。在每个原因活检后一年评估肾脏同种异体移植物的功能结果,并与mSUVmean相关。
    发现mSUVmean与急性Banff评分之间存在显着相关性,调整后的R2为0.25。“总i”亚组之间的mSUVmean显着不同,得分为3分,为2.30±0.710分1.68±0.24。移植物在一年时的功能和存活率与mSUVmean无统计学关系。
    [18F]FDG-PET/CT可能有助于无创性评估可疑AR的KTRs中肾脏移植炎症的严重程度,但它不能预测一年的移植结果。
    UNASSIGNED: [18F]FDG PET/CT noninvasively disproves acute kidney allograft rejection (AR) in kidney transplant recipients (KTRs) with suspected AR. However, the correlation of biopsy-based Banff vs. PET/CT-based scores of acute inflammation remains unknown, as does the prognostic performance of [18F]FDG PET/CT at one year post suspected AR.
    UNASSIGNED: From 2012 to 2019, 114 [18F]FDG-PET/CTs were prospectively performed in 105 adult KTRs who underwent per cause transplant biopsies. Ordinal logistic regression assessed the correlation between the extent of histological inflammation and the mean standardized [18F]FDG uptake values (mSUVmean). Functional outcomes of kidney allografts were evaluated at one year post per cause biopsy and correlated to mSUVmean.
    UNASSIGNED: A significant correlation between mSUVmean and acute Banff score was found, with an adjusted R 2 of 0.25. The mSUVmean was significantly different between subgroups of \"total i\", with 2.30 ± 0.71 in score 3 vs. 1.68 ± 0.24 in score 0. Neither the function nor the survival of the graft at one year was statistically related to mSUVmean.
    UNASSIGNED: [18F]FDG-PET/CT may help noninvasively assess the severity of kidney allograft inflammation in KTRs with suspected AR, but it does not predict graft outcomes at one year.
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  • 文章类型: Journal Article
    目标:尽管数据匮乏,大多数指南都主张用皮质类固醇治疗心脏结节病.然而,疾病表现和对治疗的反应存在异质性,这可能使治疗具有挑战性。因此,鉴定疾病表型以允许定制治疗的能力是非常期望的。这篇综述将试图概述心脏结节病的疾病表型以及FDG-PET成像在识别这些表型以优化疾病诊断和治疗管理中的作用。
    结果:FDGPET可以识别心脏结节病,并且越来越多地用于监测免疫抑制治疗的治疗反应,跟踪停止皮质类固醇治疗后的治疗反应,并评估疾病复发。使用FDGPET成像的现代定量技术可以允许更好的表型疾病表征和更准确地跟踪对免疫抑制的反应的能力。目前FDGPET在心脏结节病诊断中具有重要作用。然而,它还为我们提供了对心脏结节病疾病表型的见解,以更好地了解潜在的疾病过程,并且将来可能使我们能够相应地定制治疗方法。
    OBJECTIVE: Despite the scarcity of data, most guidelines have advocated for the treatment of cardiac sarcoidosis with corticosteroids. However, there is heterogeneity in disease presentation and response to treatment, which can make treatment challenging. The ability to identify disease phenotypes to allow for tailored therapy is therefore highly desirable. This review will seek to outline the disease phenotypes of cardiac sarcoidosis and the role that FDG-PET imaging can play in identifying these phenotypes to optimize disease diagnosis and treatment management.
    RESULTS: FDG PET can identify cardiac sarcoidosis and is being increasingly used to monitor therapeutic response to immunosuppressive therapy, to follow treatment response after discontinuation of corticosteroid therapy, and to evaluate for disease relapse. Modern quantitative techniques using FDG PET imaging may allow for even better phenotypic disease characterization and the ability to track the response to immunosuppression more accurately. FDG PET currently plays an important role in cardiac sarcoidosis diagnosis. However, it also affords us the opportunity to offer insights into cardiac sarcoidosis disease phenotypes to better understand the underlying disease process and in the future may allows us to tailor therapies accordingly.
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  • 文章类型: Journal Article
    胶质瘤的随访成像对于寻找残留或复发并将其与非肿瘤组织区分开来至关重要。在这种情况下,正电子发射断层扫描(PET)-磁共振成像(MRI)是解决问题的工具。与作为金标准的PET-MRI相比,我们研究了双点对比(DPC)增强MRI在区分肿瘤与非肿瘤组织中的作用。
    机构伦理委员会批准了这项研究,并获得了纳入研究的所有患者的同意.作为我们研究所PET-MRI研究的一部分,我们前瞻性地对神经胶质瘤病例进行了即时和75分钟延迟对比MRI检查。使用即时和75分钟延迟的对比图像获得了缩小的图像。将颜色编码的减影图像与PET-MRI图像进行比较。将具有灰度反演的75分钟延迟对比MRI和扩散加权成像(DWI)图像与PET衰减校正图像进行比较。
    我们在研究中纳入了23例用不同放射性示踪剂完成的PETMRI病例。总的来说,我们发现PET-DPC在(20/20〜100%)增强肿瘤中具有相关性。在两种情况下(多巴和氟脱氧葡萄糖),因为它们是非增强性低级别胶质瘤,而另一个是具有固有T1高强度的黑色素瘤,因此无法使用DPC技术.DWI-PET在17/19(~89.4%)病例中具有相关性,14/18(〜77.7%)例出血后,灌注加权成像(PWI)-PET动态敏感性对比(DSC)/ASL相关。
    DPCMRI在区分肿瘤和非肿瘤组织方面与PETMRI显示出良好的相关性。DPCMRI可以在没有PET的外围医院中作为PETMRI的潜在替代方案。然而,DPC技术在低级别非增强胶质瘤中受到限制.
    UNASSIGNED: Follow-up imaging of gliomas is crucial to look for residual or recurrence and to differentiate them from nontumoral tissue. Positron emission tomography (PET)-magnetic resonance imaging (MRI) is the problem-solving tool in such cases. We investigated the role of dual point contrast (DPC)-enhanced MRI to discriminate tumoral from the nontumoral tissue compared to PET-MRI taken as the gold standard.
    UNASSIGNED: The institutional ethics committee approved the study, and consent was obtained from all the patients included in the study. We prospectively did immediate and 75-min delayed contrast MRI in glioma cases who came for follow-up as a part of PET-MRI study in our institute. Subtracted images were obtained using immediate and 75-min delayed contrast images. Color-coded subtracted images were compared with PET-MRI images. 75-min delayed contrast MRI and diffusion-weighted imaging (DWI) images with Gray Scale inversion were compared with PET attenuation-corrected images.
    UNASSIGNED: We included 23 PET MRI cases done with different radiotracers in our study. Overall, we found PET-DPC correlation in (20/20 ~ 100%) cases of enhancing tumors. In two cases (DOPA and fluorodeoxyglucose), since they were nonenhancing low-grade gliomas and the other one was melanoma with intrinsic T1 hyperintensity and the DPC technique could not be used. DWI-PET correlated in 17/19 (~89.4%) cases, and perfusion-weighted imaging (PWI)-PET dynamic susceptibility contrast (DSC)/ASL correlated in 14/18 (~77.7%) cases after cases with hemorrhage were excluded.
    UNASSIGNED: DPC MRI showed a good correlation with PET MRI in discriminating tumoral from the nontumoral tissue. DPC MRI can act as a potential alternative to PET MRI in peripheral hospitals where PET is not available. However, the DPC technique is limited in low-grade nonenhancing gliomas.
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  • 文章类型: Journal Article
    背景:基于空间范围的淀粉样β(Aβ)在整个新皮质中扩散的程度的测量可能比传统的Aβ-正电子发射断层扫描(PET)测量的Aβ水平更敏感,以检测早期Aβ沉积在临床前阿尔茨海默病(AD)中,并提高对Aβ与tau增殖和认知能力下降的相关性的理解。
    方法:使用来自哈佛衰老大脑研究的261名认知未受损的老年人的匹兹堡复合B(PIB)-PET扫描来测量Aβ水平(LVL;新皮质PIBDVR)和空间范围(EXT),计算为PIB+的新皮层的比例。
    结果:EXT能够较早地检测Aβ沉积物,纵向证实在5年内达到传统的基于LVL的Aβ+阈值。与LVL相比,EXT改善了认知下降(临床前阿尔茨海默认知组合)和tau增殖(flortaucipir-PET)的预测。
    结论:这些发现表明,EXT可能对Aβ在临床前AD中的作用比对水平更敏感,并改善了个体在AD预防试验中的靶向性。
    结论:Aβ空间范围(EXT)以匹兹堡化合物B升高的新皮层的百分比进行测量。AβEXT将Aβ的检测提高到低于传统的PET阈值。早期区域Aβ矿床具有空间异质性。认知和tau与AβEXT的关系比Aβ水平更紧密。新皮质tau发作与达到广泛的新皮质Aβ一致。
    BACKGROUND: Spatial extent-based measures of how far amyloid beta (Aβ) has spread throughout the neocortex may be more sensitive than traditional Aβ-positron emission tomography (PET) measures of Aβ level for detecting early Aβ deposits in preclinical Alzheimer\'s disease (AD) and improve understanding of Aβ\'s association with tau proliferation and cognitive decline.
    METHODS: Pittsburgh Compound-B (PIB)-PET scans from 261 cognitively unimpaired older adults from the Harvard Aging Brain Study were used to measure Aβ level (LVL; neocortical PIB DVR) and spatial extent (EXT), calculated as the proportion of the neocortex that is PIB+.
    RESULTS: EXT enabled earlier detection of Aβ deposits longitudinally confirmed to reach a traditional LVL-based threshold for Aβ+ within 5 years. EXT improved prediction of cognitive decline (Preclinical Alzheimer Cognitive Composite) and tau proliferation (flortaucipir-PET) over LVL.
    CONCLUSIONS: These findings indicate EXT may be more sensitive to Aβ\'s role in preclinical AD than level and improve targeting of individuals for AD prevention trials.
    CONCLUSIONS: Aβ spatial extent (EXT) was measured as the percentage of the neocortex with elevated Pittsburgh Compound-B. Aβ EXT improved detection of Aβ below traditional PET thresholds. Early regional Aβ deposits were spatially heterogeneous. Cognition and tau were more closely tied to Aβ EXT than Aβ level. Neocortical tau onset aligned with reaching widespread neocortical Aβ.
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  • 文章类型: Journal Article
    嵌合抗原受体(CAR)T细胞治疗的发展领域,虽然很有希望,需要更全面的成像方法来提高治疗效果并跟踪患者和离体细胞运输。这篇综述探讨了PET成像在CAR-T细胞运输中的应用及其治疗效果的优化。使用各种放射性示踪剂的PET成像的应用在提供宿主内的CAR-T细胞相互作用的评估方面是有希望的。从而促进改善患者预后的策略。随着这项技术的进步,预计将采用进一步的创新策略来简化对免疫治疗效果的评估.
    The evolving field of chimeric antigen receptor (CAR) T-cell therapy, though promising, necessitates more comprehensive imaging methods to enhance therapeutic effectiveness and track cell trafficking in patients and ex vivo. This review examines the application of PET imaging in CAR T-cell trafficking and optimizing their therapeutic impact. The application of PET imaging using various radiotracers is promising in providing evaluation of CAR T-cell interaction within the host, thereby facilitating strategies for improved patient outcomes. As this technology progresses, further innovative strategies to streamline assessments of immunotherapeutic effectiveness are anticipated.
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  • 文章类型: Journal Article
    血管炎症是心血管疾病的主要原因,特别是动脉粥样硬化疾病,早期发现血管炎症可能是最终降低残余心血管发病率和死亡率的关键。本文讨论了非侵入性成像技术评估血管炎症的临床应用进展。关注冠状动脉粥样硬化。包括多种模式的讨论:计算机断层扫描(CT)成像(审查的主要重点),心脏磁共振,超声,和正电子发射断层扫描成像。该综述涵盖了新技术的最新进展,例如冠状动脉炎症的新型CT生物标志物(例如,血管周围脂肪衰减指数),用于正电子发射断层扫描-CT成像的新型炎症特异性示踪剂,和其他人。探索了每种模式的优点和局限性,强调多模态成像的潜力和人工智能图像解释的使用,以提高对冠状动脉疾病等常见疾病的诊断和预后潜力。
    Vascular inflammation is a major contributor to cardiovascular disease, particularly atherosclerotic disease, and early detection of vascular inflammation may be key to the ultimate reduction of residual cardiovascular morbidity and mortality. This review paper discusses the progress toward the clinical utility of noninvasive imaging techniques for assessing vascular inflammation, with a focus on coronary atherosclerosis. A discussion of multiple modalities is included: computed tomography (CT) imaging (the major focus of the review), cardiac magnetic resonance, ultrasound, and positron emission tomography imaging. The review covers recent progress in new technologies such as the novel CT biomarkers of coronary inflammation (eg, the perivascular fat attenuation index), new inflammation-specific tracers for positron emission tomography-CT imaging, and others. The strengths and limitations of each modality are explored, highlighting the potential for multi-modality imaging and the use of artificial intelligence image interpretation to improve both diagnostic and prognostic potential for common conditions such as coronary artery disease.
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  • 文章类型: Journal Article
    虽然已知免疫功能在阿尔茨海默病(AD)中起机械作用,外周循环中的免疫蛋白是否会影响淀粉样蛋白-β(Aβ)的进展速率-AD的主要特征-尚不清楚。在巴尔的摩衰老的纵向研究中,我们定量了血浆中的942种免疫蛋白,并鉴定了32种(包括CAT[过氧化氢酶],CD36[CD36抗原],和KRT19[角蛋白19])与用正电子发射断层扫描(PET)测量的皮质Aβ积累率相关。候选蛋白子集的纵向变化也预测了Aβ的进展,以及一种蛋白质的中晚期(20年)轨迹,CAT,在社区动脉粥样硬化风险(ARIC)研究中,与晚期Aβ阳性状态相关。影响CAT血浆水平的遗传变异,CD36和KRT19预测的Aβ积累率,包括两个样本孟德尔随机化确定的AβPET水平的因果关系。除了与tauPET和血浆AD生物标志物变化相关外,以及人类小胶质细胞亚型和神经血管细胞在AD脑组织中的表达模式,我们发现31%的候选蛋白与ARIC中(20岁)或晚期(8岁)痴呆风险相关.我们的发现揭示了与纵向Aβ积累相关的血浆蛋白,并鉴定可能有助于AD病理生理学进展的特异性外周免疫介质。
    While immune function is known to play a mechanistic role in Alzheimer\'s disease (AD), whether immune proteins in peripheral circulation influence the rate of amyloid-β (Aβ) progression - a central feature of AD - remains unknown. In the Baltimore Longitudinal Study of Aging, we quantified 942 immunological proteins in plasma and identified 32 (including CAT [catalase], CD36 [CD36 antigen], and KRT19 [keratin 19]) associated with rates of cortical Aβ accumulation measured with positron emission tomography (PET). Longitudinal changes in a subset of candidate proteins also predicted Aβ progression, and the mid- to late-life (20-year) trajectory of one protein, CAT, was associated with late-life Aβ-positive status in the Atherosclerosis Risk in Communities (ARIC) study. Genetic variation that influenced plasma levels of CAT, CD36 and KRT19 predicted rates of Aβ accumulation, including causal relationships with Aβ PET levels identified with two-sample Mendelian randomization. In addition to associations with tau PET and plasma AD biomarker changes, as well as expression patterns in human microglia subtypes and neurovascular cells in AD brain tissue, we showed that 31 % of candidate proteins were related to mid-life (20-year) or late-life (8-year) dementia risk in ARIC. Our findings reveal plasma proteins associated with longitudinal Aβ accumulation, and identify specific peripheral immune mediators that may contribute to the progression of AD pathophysiology.
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