Photo-hyperpolarized 13C MRI

总结。在深部组织(&gt；1厘米)环境中的高分辨率成像可以解决一系列基础- 阐明疾病发生和发展机制中的心理和应用问题。而荧光灯- Cence成像是生物分子标记细胞成像的主要技术，但它存在以下问题 光散射和组织深度的像差失真&gt；1 mm。在光谱的另一端，MAG- 磁共振成像(Mri)是一种广泛应用的临床前和临床成像技术。 这种方法对组织深度没有实际限制，但分辨率较低。在这 我们将创新一类新型的超极化13C纳米粒子探测器，它可以作为高效的深度探测器 磁共振成像中的组织标志物。我们的中心思想是通过(I)光学超载来显著增强~(13)C核磁共振信号。 可以在低磁场下进行的放大，以及(Ii)13C相干时间的显著延长。 具体地说，我们建议开发基于荧光纳米钻石(FND)的磁共振探针 氮空位(NV)中心。与NV相关的电子自旋可以在光学上“超极化”， 这种极化有效地转移到钻石的13C核自旋，导致核磁共振信号增强- 临床磁共振成像领域中超过三个数量级的热极化与13C的热极化。同时，由 通过实现有效的去耦合方案，我们提出了显著扩展~(13)C自旋相干性的方案 对他们进行第二长时间的审问。后者产生了巨大的信号增益，是 又是103倍。将超极化和自旋相干扩展产生的增益组合在一起 对于核磁共振，信号增益约为106，并将显著提高空间分辨率。此外，由于 偏振是光学产生的，这种13C光磁共振成像(PMRI)可以在低得多的低场下进行 成本与传统核磁共振基础设施相比。在我们的方法中，自旋极化是光学再生的，允许 重复获取MRI数据，并进行纵向研究。此外，FND粒子本身就是 生物相容，其表面可与多种靶向配体结合。在此基础上，我们建议 开发可高保真、高分辨率成像的靶向荧光纳米核磁共振探针 在深层组织(&gt；1厘米)环境中优于20微米。除了是明亮的核磁共振成像试剂外，这些颗粒还 明亮的荧光为组织病理学中药物生物分布的交叉检查提供了一种选择 分析。为了实现这一新技术的前景，我们提出了进一步开发超音速电机的建议。 大型化和磁共振成像方法，以及通过优化提高纳米粒子的超极化率- 通过合成和加工开发来优化它们的结构。我们的目标是将PMRI技术 我们演示了适用于体内磁共振成像的微米级颗粒到纳米级FND。作为该计划的一部分 技术演示，我们将在台式(低场)上构建一个简单的PMRI成像设备原型 以及组织模体中的图像FND，以表征分辨率和成像深度的可实现度量。

Summary. High resolution imaging in deep tissue (> 1 cm) environments can address a swathe of funda- mental and applied problems in the elucidation of mechanisms of disease origin and progression. While fluores- cence imaging is a workhorse technique for the cellular imaging of biological molecular markers, it suffers from light scattering, and aberration distortions at tissue depths >1 mm. On the opposite end of the spectrum, mag- netic resonance imaging (MRI) is a well-established and broadly employed pre-clinical and clinical imaging method that has no practical limitations with respect to tissue depth, but it suffers from low resolution. In this project we will innovate a new class of hyperpolarized 13C nanoparticle probes that can serve as efficient deep tissue markers in MRI. Our central idea is to dramatically boost 13C NMR signal by means of (i) optical hyperpo- larization that can be carried out at low magnetic fields and (ii) significant extension of 13C coherence times. Specifically, we propose to develop MRI probes based on fluorescent nanodiamonds (FNDs) endowed with nitrogen-vacancy (NV) centers. The electronic spins associated with NVs can be optically “hyperpolarized” and that polarization to be effectively transferred to the diamond 13C nuclear spins, resulting in NMR signal enhance- ment over three orders of magnitude vs. 13C thermal polarization at the fields of clinical MRI. In conjunction, by implementing effective decoupling schemes we propose significantly extend the 13C spin coherences to be able to interrogate them for second-long periods. The latter yields enormous signal gains, a multiplicative factor of another 103- fold. Combining the gains due to hyperpolarization and spin coherence extensions permits a total signal gain of ca. 106 for MRI, and will enable a significant improvement in spatial resolution. Moreover, since the polarization is optically generated, this 13C photo-MRI (PMRI), can be carried out at low-field at a much lower cost vs. conventional MRI infrastructure. In our method the spin polarization is regenerated optically, allowing for acquiring MRI data repeatedly and enabling longitudinal studies. Furthermore, the FND particles are inherently biocompatible, and their surfaces are amenable to a versatile set of targeting ligands. With this basis, we propose to develop targetable fluorescent nanoparticle MRI probes that can be imaged with high fidelity with resolution better than 20 um in deep tissue (>1 cm) settings. In addition to being bright MRI agents, the particles are also bright fluorescent providing an option for a cross-examination of the agent biodistribution in histopathological analysis. In order to realize the prospects of this novel technology, we propose to further develop the hyperpo- larization and MR imaging methodologies, as well as boost hyperpolarizability of nanosized particles by optimiz- ing their structure through synthesis and processing developments. We aim at transferring the PMRI technology we demonstrated for micron-sized particles to the nanosized FND suitable for in vivo MRI. As a part of the technology demonstration, we will construct a simple prototype PMRI imaging set-up on the benchtop (low-field) and image FNDs in tissue phantoms, characterizing achievable metrics of resolution and imaging depth.