Photo-hyperpolarized 13C MRI

光超极化 13C MRI

• 批准号: 10710367
• 负责人: Ashok Ajoy
• 金额: $ 33.72万
• 依托单位: ADAMAS NANOTECHNOLOGIES, INC.
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-28 至 2026-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10710367
• 关键词: Address; Adoption; Biodistribution; Biological; Biological Process; Biological Sciences; Cell Nucleus; Cells; Clinical; Contrast Media; Data; Defect; Development; Devices; Diamond; Disease; Disease Progression; Electronics; Endowment; Environment; Equilibrium; Future; High temperature of physical object; Hour; Image; Imaging Device; Imaging technology; In Situ; Infrastructure; Label; Length; Ligands; Light; Lighting; Longitudinal Studies; Magnetic Resonance Imaging; Methodology; Methods; Natural regeneration; Nitrogen; Noise; Nuclear; Optics; Particle Size; Play; Relaxation; Reproducibility; Research; Research Personnel; Resolution; Role; Scheme; Signal Transduction; Speed; Structure; Study models; Surface; Techniques; Technology; Temperature; Tissue imaging; Tissues; attenuation; biomaterial compatibility; biomedical imaging; cellular imaging; clinical imaging; contrast imaging; cost; fluorescence imaging; high resolution imaging; imager; imaging agent; imaging modality; immune imaging; improved; in vivo; innovation; light scattering; magnetic field; meter; microwave electromagnetic radiation; molecular marker; multidisciplinary; nanodiamond; nanoparticle; nanosized; new technology; novel; optical imaging; particle; portability; pre-clinical; preclinical imaging; preservation; prototype; submicron; technology development; temporal measurement; tissue phantom; tool; treatment response

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.

概括。深组织（> 1 cm）环境中的高分辨率成像可以解决一系列基本 精神和应用问题在阐明疾病起源机制和进展机制中。而荧光 - Cence Imaging是一种用于生物分子标记物细胞成像的主力技术 > 1 mm的组织深度处的光散射和像差变形。在频谱的另一端，杂志 - 网络共振成像（MRI）是一个良好的且广泛使用的临床和临床成像 对于组织深度没有实际限制的方法，但分辨率低。在这个 项目我们将创新一类新的超极化13C纳米颗粒问题，这些问题可以作为有效的深度 MRI中的组织标记。我们的核心思想是通过（i）光学超音 可以在低磁场和（ii）13C相干时间的显着延伸时间进行的射出。 具体而言，我们建议基于具有荧光纳米符号（FND）的MRI问题 氮散布（NV）中心。与NV相关的电子旋转可以在光学上“超极化”，并且 极化有效地转移到钻石13C核自旋上，导致NMR信号增强 - 在临床MRI领域的三个数量级与13C热偏振的男性。结合 实施有效的解耦方案，我们建议大大扩展13c旋转相干性 审问他们在第二个时期。后者产生巨大的信号增长，这是一个乘法因子 另一个103倍。结合由于超极化和自旋相干扩展而获得的收益，可以允许总计 信号增益Ca。 106对于MRI，将能够显着改善空间分辨率。而且，从那以后 偏振是通过光学产生的，该13c摄影-MRI（PMRI）可以在低田间以低得多的方式进行 成本与常规MRI基础设施。在我们的方法中，自旋极化是光学再生的，允许 反复获取MRI数据并实现纵向研究。此外，FND颗粒是继承的 生物相容性及其表面适合一组多功能的靶向配体。在此基础上，我们建议 出现可靶向的荧光纳米颗粒MRI问题，可以以高忠诚度成像 在深组织（> 1厘米）设置中，大于20 um。除了是明亮的MRI代理外，颗粒也是 明亮的荧光为组织病理学中的剂生物分布提供了一种选择 分析。为了实现这一新技术的前景，我们建议进一步发展 范围和MR成像方法，以及通过优化的纳米颗粒增强纳米化颗粒的超极化性 通过合成和加工发展来制定其结构。我们旨在转移PMRI技术 我们证明了适用于适合体内MRI的纳米型FND的微米大小颗粒。作为一部分 技术演示，我们将在台式（低场）上构建一个简单的原型PMRI成像设置 以及组织幻象中的图像FND，表征了可实现的分辨率和成像深度的指标。

项目成果

Optical and electronic spin properties of fluorescent micro- and nanodiamonds upon prolonged ultrahigh-temperature annealing

长时间超高温退火后荧光微米和纳米金刚石的光学和电子自旋特性

• DOI: 10.1116/6.0002797
• 发表时间: 2023
• 期刊: Journal of Vacuum Science & Technology B
• 影响因子: 1.4
• 作者: Nunn, Nicholas;Milikisiyants, Sergey;Torelli, Marco D.;Monge, Richard;Delord, Tom;Shames, Alexander I.;Meriles, Carlos A.;Ajoy, Ashok;Smirnov, Alex I.;Shenderova, Olga A.
• 通讯作者: Shenderova, Olga A.