Center for In Vivo Microscopy, Box 3302, Duke University Medical Center, Durham, North Carolina 27710, USA.
Med Phys. 2010 Jan;37(1):54-62. doi: 10.1118/1.3264619.
Quantitative in vivo imaging of lung perfusion in rodents can provide critical information for preclinical studies. However, the combined challenges of high temporal and spatial resolution have made routine quantitative perfusion imaging difficult in small animals. The purpose of this work is to demonstrate 4D micro-CT for perfusion imaging in rodents at heartbeat temporal resolution and isotropic spatial resolution.
We have recently developed a dual tube/detector micro-CT scanner that is well suited to capture first pass kinetics of a bolus of contrast agent used to compute perfusion information. Our approach is based on the paradigm that similar time density curves can be reproduced in a number of consecutive, small volume injections of iodinated contrast agent at a series of different angles. This reproducibility is ensured by the high-level integration of the imaging components of our system with a microinjector, a mechanical ventilator, and monitoring applications. Sampling is controlled through a biological pulse sequence implemented in LABVIEW. Image reconstruction is based on a simultaneous algebraic reconstruction technique implemented on a graphic processor unit. The capabilities of 4D micro-CT imaging are demonstrated in studies on lung perfusion in rats.
We report 4D micro-CT imaging in the rat lung with a heartbeat temporal resolution (approximately 150 ms) and isotropic 3D reconstruction with a voxel size of 88 microm based on sampling using 16 injections of 50 microL each. The total volume of contrast agent injected during the experiments (0.8 mL) was less than 10% of the total blood volume in a rat. This volume was not injected in a single bolus, but in multiple injections separated by at least 2 min interval to allow for clearance and adaptation. We assessed the reproducibility of the time density curves with multiple injections and found that these are very similar. The average time density curves for the first eight and last eight injections are slightly different, i.e., for the last eight injections, both the maximum of the average time density curves and its area under the curve are decreased by 3.8% and 7.2%, respectively, relative to the average time density curves based on the first eight injections. The radiation dose associated with our 4D micro-CT imaging is 0.16 Gy and is therefore in the range of a typical micro-CT dose.
4D micro-CT-based perfusion imaging demonstrated here has immediate application in a wide range of preclinical studies such as tumor perfusion, angiogenesis, and renal function. Although our imaging system is in many ways unique, we believe that our approach based on the multiple injection paradigm can be used with the newly developed flat-panel slip-ring-based micro-CT to increase their temporal resolution in dynamic perfusion studies.
对啮齿动物的肺部灌注进行定量活体成像，可以为临床前研究提供关键信息。然而，由于需要高时间分辨率和高空间分辨率，常规的小动物定量灌注成像一直具有挑战性。本研究旨在展示适用于啮齿动物的具有心跳时间分辨率和各向同性空间分辨率的 4D 微 CT 灌注成像。
我们最近开发了一种双管/探测器微 CT 扫描仪，非常适合捕获对比剂团注的首过动力学，从而计算灌注信息。我们的方法基于这样的设想，即通过在一系列不同角度下进行多次小体积碘造影剂连续注射，可以重现相似的时间密度曲线。通过将我们系统的成像组件与微注射器、机械呼吸机和监测应用程序高度集成，可以确保这种可重复性。采样通过在 LABVIEW 中实现的生物脉冲序列进行控制。图像重建基于在图形处理器单元上实现的同时代数重建技术。在大鼠肺部灌注的研究中展示了 4D 微 CT 成像的能力。
我们报告了在大鼠肺部进行的 4D 微 CT 成像，具有心跳时间分辨率（约 150 毫秒）和基于使用 16 次 50μL 注射进行采样的各向同性 3D 重建，体素大小为 88μm。实验中注射的造影剂总体积（0.8 毫升）小于大鼠总血量的 10%。这些造影剂不是一次性注入，而是分多次注入，每次注射间隔至少 2 分钟，以便清除和适应。我们评估了多次注射的时间密度曲线的可重复性，发现它们非常相似。前 8 次和后 8 次注射的平均时间密度曲线略有不同，即对于后 8 次注射，平均时间密度曲线的最大值及其曲线下面积分别降低了 3.8%和 7.2%，相对于基于前 8 次注射的平均时间密度曲线。我们的 4D 微 CT 成像的辐射剂量为 0.16Gy，因此处于典型微 CT 剂量范围内。
这里展示的基于 4D 微 CT 的灌注成像具有广泛的临床前研究应用，例如肿瘤灌注、血管生成和肾功能。尽管我们的成像系统在许多方面是独特的，但我们相信，我们基于多次注射范例的方法可以与新开发的基于平板滑环的微 CT 一起使用，以提高它们在动态灌注研究中的时间分辨率。
