Towards a novel small animal quantitative perfusion MRI reference standard

建立新型小动物定量灌注 MRI 参考标准

• 批准号: 446292030
• 负责人: Dr. Philipp Backhaus
• 金额: --
• 依托单位: Klinik für Nuklearmedizin
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2020
• 资助国家: 德国
• 起止时间: 2019-12-31 至 2022-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/446292030?language=en
• 关键词: Towards; novel; small; animal; quantitative

Perfusion MRI is a clinically important imaging technique in the management of e.g. stroke, cardiac ischemia or tumors. Absolute quantification of perfusion parameters is highly desirable to take treatment decisions most objectively. Small animal perfusion MRI falls far behind from clinical scanning in terms of quantification. This insufficiency limits the translation of preclinical perfusion experiments into clinical studies. The lack of quantification mainly derives from the inability to precisely measure the dynamic arterial blood concentration - the so-called arterial input function (AIF) – a critical prerequisite for quantitative perfusion MRI. Especially in mice, given the image resolution, e.g. intracranial arterial vessels are typically too small to measure signals from pure blood. In previous preliminary work, we developed a novel technique for measuring AIFs in small animals: The animals’ blood is shunted and lead through an extracorporeal circulation to generate an artificial perfused blood reservoir that can be positioned inside the imaging plane. We could demonstrate the potential of the novel setup to gather AIFs in perfusion MRI in mice with previously unmet quality and quantitative robustness. Moreover, the setup allows to simultaneously measure radiotracer blood concentrations allowing unique multimodal validation approaches. In this project, we aim (1) to demonstrate that our experimental setup can serve as a quantitative ground truth to evaluate conventional methods of AIF measurements. (2) We will establish a specific reference dataset of AIFs and perfusion parameters serving as a quantitative standard for future studies. (3) We will compare the quantitative potential of the two most common perfusion MRI methods: dynamic contrast-enhanced (DCE) and dynamic susceptibility contrast (DSC)-MRI. (4) We will validate the quantitative potential of recently published rapid MR imaging techniques of perfusion MRI.To fulfill these objectives, we perform DCE and DSC perfusion MRI using our novel extracorporeal circulation setup in mouse brains bearing intracranial glioblastoma, a frequent preclinical and clinical scenario to study perfusion. We will target our objectives by extensive multimodal validation of the MR-derived contrast agent concentration and perfusion parameters including: (1) A co-Injected radioactive labelled variant of a standard Gadolinium contrast agent will be simultaneously measured to validate the whole dynamic range of the AIF. (2) Laser-ablation ionizing coupled plasma mass spectrometry (LA-ICP-MS) will serve to evaluate contrast agent concentration in tissue. (3) [99mTc]-labeled radiotracers will be co-injected for quantitatively mapping cerebral blood volume and flow by SPECT/CT and autoradiography.We thereby expect a significant advance for quantitative preclinical perfusion MRI to catch up with the quantitative abilities of clinical scanning finally improving preclinical and translational studies.

灌注MRI是治疗中风、心脏缺血或肿瘤等临床重要的成像技术。灌注参数的绝对量化对于最客观地做出治疗决策是非常期望的。在定量方面，小动物灌注MRI福尔斯远远落后于临床扫描。这一不足限制了临床前灌注实验向临床研究的转化。定量的缺乏主要源于无法精确测量动态动脉血浓度-所谓的动脉输入功能（AIF）-定量灌注MRI的关键先决条件。特别是在小鼠中，考虑到图像分辨率，例如颅内动脉血管通常太小而无法测量来自纯血液的信号。在之前的初步工作中，我们开发了一种用于测量小动物AIF的新技术：动物的血液被分流并通过体外循环来产生可以定位在成像平面内的人工灌注血液储存器。我们可以证明新设置在小鼠灌注MRI中收集AIF的潜力，具有以前未满足的质量和定量稳健性。此外，该设置允许同时测量放射性示踪剂血液浓度，从而实现独特的多模式验证方法。在这个项目中，我们的目标是（1）证明我们的实验装置可以作为一个定量的地面真理，以评估传统的AIF测量方法。(2)我们将建立AIF和灌注参数的特定参考数据集，作为未来研究的定量标准。(3)我们将比较两种最常见的灌注MRI方法的定量潜力：动态对比增强（DCE）和动态磁化率对比（DSC）-MRI。(4)我们将验证最近发表的快速MR成像技术的灌注MRI.To实现这些目标的定量潜力，我们进行DCE和DSC灌注MRI使用我们的新的体外循环设置在小鼠大脑轴承颅内胶质母细胞瘤，一个频繁的临床前和临床研究灌注的情况。我们将通过对MR衍生造影剂浓度和灌注参数进行广泛的多模式验证来实现我们的目标，包括：（1）同时测量标准钆造影剂的共注射放射性标记变体，以验证AIF的整个动态范围。(2)激光消融电离耦合等离子体质谱法（LA-ICP-MS）将用于评价组织中的造影剂浓度。(3)[99 mTc]标记的放射性示踪剂将被共同注射用于通过SPECT/CT和放射自显影来定量地映射脑血容量和流量。因此，我们期望定量临床前灌注MRI的显著进步能够赶上临床扫描的定量能力，最终改善临床前和转化研究。