Department of Physics and Astronomy, University of British Columbia, Vancouver, British Columbia, V6T 2B5, Canada.
Klinikum rechts der Isar, Nuklearmedizinische Klinik und Poliklinik, Technische Universität München, München, 81675, Germany.
Med Phys. 2017 Aug;44(8):4056-4067. doi: 10.1002/mp.12300. Epub 2017 Jul 5.
Mn is used as a contrast agent and marker for neuronal activity with magnetic resonance imaging (MRI) in rats and mice, but its accumulation is generally not assessed quantitatively. In this work, nonradioactive Mn and Mn are injected simultaneously in rats, and imaged with MRI, positron emission tomography (PET) and autoradiography (AR). Mn distributions are compared between modalities, to assess the potential and limitations on quantification of Mn with MRI, and to investigate the potential of multimodal measurement of Mn accumulation.
MRI (in vivo), PET (in vivo and post mortem), and AR (ex vivo) were acquired of rat brains, for which animals received simultaneous intraperitoneal (IP) or intracerebrovertricular (ICV)-targeted injections containing the positron-emitting radionuclide Mn and additional nonradioactive MnCl , which acts as an MRI contrast agent. Pre and postinjection MR images were fit for the longitudinal relaxation rate (R1), coregistered, and subtracted to generate R1 difference maps, which are expected to be proportional to change in Mn concentration in tissue. AR and PET images were coregistered to smoothed R1 difference maps.
Similar spatial distributions were seen across modalities, with Mn accumulation in the colliculus, near the injection site, and in the 4th ventricle. There was no Mn accumulation measurable with PET in the brain after IP injection. In areas of very highly localized and concentrated Mn accumulation in PET or AR, consistent increases of R1 were not seen with MRI. Scatter plots of corresponding voxel R1 difference and PET or AR signal intensity were generated and fit with least squares linear models within anatomical regions. Linear correlations were observed, particularly in regions away from very highly localized and concentrated Mn accumulation at the injection site and the 4th ventricle. Accounting for radioactive decay of Mn, the MnCl longitudinal relaxivity was between 4.0 and 5.1 s /mM, which is within 22% of the in vitro relaxivity.
This proof-of-concept study demonstrates that MR has strong potential for quantitative assessment of Mn accumulation in the brain, although local discrepancies from linear correlation suggest limitations to this use of MR in areas of inflammation or very high concentrations of Mn. These discrepancies also suggest that a combination of modalities may have additional utility for discriminating between different pools of Mn accumulation in tissue.
锰被用作磁共振成像（MRI）在大鼠和小鼠中神经元活动的对比剂和示踪剂，但通常不进行其积累的定量评估。在这项工作中，同时向大鼠注射非放射性锰和 64Cu 标记的锰，并通过 MRI、正电子发射断层扫描（PET）和放射自显影（AR）进行成像。比较模态之间的锰分布，以评估 MRI 定量评估锰的潜力和局限性，并研究锰积累的多模态测量的潜力。
对大鼠脑进行 MRI（体内）、PET（体内和死后）和 AR（体外）采集，动物接受同时腹腔内（IP）或脑室内（ICV）靶向注射，包含正电子发射放射性核素 64Cu 标记的锰和额外的非放射性 MnCl2，后者作为 MRI 对比剂。注射前后的 MR 图像拟合纵向弛豫率（R1），配准，并减去以生成 R1 差图谱，预计该图谱与组织中锰浓度的变化成正比。AR 和 PET 图像与平滑的 R1 差图谱配准。
模态之间观察到相似的空间分布，在丘脑中、靠近注射部位以及第四脑室中积累锰。在 IP 注射后，大脑中无法用 PET 测量到 64Cu 标记的锰积累。在 PET 或 AR 中非常高度局灶性和集中性锰积累的区域，MRI 未见一致的 R1 增加。生成了对应体素 R1 差异和 PET 或 AR 信号强度的散点图，并在解剖区域内用最小二乘线性模型拟合。观察到线性相关性，特别是在远离注射部位和第四脑室非常高度局灶性和集中性锰积累的区域。考虑到 64Cu 标记的锰的放射性衰变，MnCl2 的纵向弛豫率在 4.0 到 5.1 s /mM 之间，这与体外弛豫率相差 22%。
这项概念验证研究表明，MR 具有定量评估大脑中锰积累的强大潜力，尽管与线性相关性的局部差异表明 MR 在炎症或锰浓度非常高的区域的这种用途存在局限性。这些差异还表明，模态的组合可能对区分组织中不同的锰积累池具有额外的效用。
