Superparamagnetic nanoparticle-enhanced MRI of Alzheimer's disease plaques and activated microglia in 3X transgenic mouse brains: Contrast optimization
Superparamagnetic nanoparticle-enhanced MRI of Alzheimer's disease plaques and activated microglia in 3X transgenic mouse brains: Contrast optimization
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DOI：
10.1002/jmri.25563
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发表时间：
2017-08-01
影响因子：
4.4
通讯作者：
Sillerud, Laurel O.
中科院分区：
文献类型：
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作者：
Tafoya, Marissa A.;Madi, Saaussan;Sillerud, Laurel O.
目的优化抗体偶联超顺磁性纳米颗粒的磁共振成像（MRI）技术，用于检测阿尔茨海默病3X转基因小鼠模型中的淀粉样蛋白斑块和活化的小胶质细胞。材料与方法分别饲喂100ppm白藜芦醇饲料和100ppm白藜芦醇饲料。从注射了抗淀粉样蛋白靶向超顺磁性氧化铁纳米颗粒或抗iba -1共轭fept纳米颗粒的动物中选择4个大脑，切除，用福尔马林固定，并放置在Fomblin中进行体外MRI (11.7T)，使用多层多回波，多重梯度回波，快速采集弛豫增强和敏感性加权成像（SWI）。A斑块和神经炎症区表现为低信号区，其数量、位置和z评分作为序列类型和回声时间的函数进行测量。结果磁共振造影是由于斑块附近组织水的横向弛豫时间缩短所致。对这种效应的理论分析表明，回声时间是斑块对比度的主要决定因素，并用于优化z评分。回声时间在4 ~ 25 msec范围内，检测到病变的z -评分在21 ~ 34之间，其中SWI的z -评分最高，检测到的病变数量也最多。对整个斑块和激活的小胶质细胞分布的3D计算表明，白藜芦醇处理导致斑块密度减少约24倍，小胶质细胞激活减少约4倍。结论优化后的抗体偶联超顺磁性纳米颗粒MRI可显示A斑块和活化小胶质细胞的三维分布，并可测量药物治疗对3X Tg模型的影响。证据等级：1技术功效：2期。的原因。成像2017;46:574 - 588
PurposeTo optimize magnetic resonance imaging (MRI) of antibody-conjugated superparamagnetic nanoparticles for detecting amyloid- plaques and activated microglia in a 3X transgenic mouse model of Alzheimer's disease.Materials and MethodsTen 3X Tg mice were fed either chow or chow containing 100ppm resveratrol. Four brains, selected from animals injected with either anti-amyloid targeted superparamagnetic iron oxide nanoparticles, or anti-Iba-1-conjugated FePt-nanoparticles, were excised, fixed with formalin, and placed in Fomblin for ex vivo MRI (11.7T) using multislice-multiecho, multiple gradient echo, rapid acquisition with relaxation enhancement, and susceptibility-weighted imaging (SWI). A plaques and areas of neuroinflammation appeared as hypointense regions whose number, location, and Z-score were measured as a function of sequence type and echo time.ResultsThe MR contrast was due to the shortening of the transverse relaxation time of the plaque-adjacent tissue water. A theoretical analysis of this effect showed that the echo time was the primary determinant of plaque contrast and was used to optimize Z-scores. The Z-scores of the detected lesions varied from 21 to 34 as the echo times varied from 4 to 25 msec, with SWI providing the highest Z-score and number of detected lesions. Computation of the entire plaque and activated microglial distributions in 3D showed that resveratrol treatment led to a reduction of approximate to 24-fold of A plaque density and approximate to 4-fold in microglial activation.ConclusionOptimized MRI of antibody-conjugated superparamagnetic nanoparticles served to reveal the 3D distributions of both A plaques and activated microglia and to measure the effects of drug treatments in this 3X Tg model. Level of Evidence: 1 Technical Efficacy: Stage 2 J. MAGN. RESON. IMAGING 2017;46:574-588