Photo-hyperpolarized 13C MRI

光超极化 13C MRI

• 批准号: 10366910
• 负责人: Ashok Ajoy
• 金额: $ 38.56万
• 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/10366910
• 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; 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; Magnetic nanoparticles; Methodology; Methods; Natural regeneration; Nitrogen; Noise; Nuclear; Optics; Particle Size; Play; Relaxation; Research; Research Personnel; Resolution; Role; Scheme; Signal Transduction; Speed; Structure; Study models; Surface; Techniques; Technology; Temperature; Time; Tissue imaging; Tissues; attenuation; base; biomaterial compatibility; biomedical imaging; cellular imaging; clinical imaging; contrast imaging; cost; fluorescence imaging; high resolution imaging; imager; imaging agent; imaging modality; imaging probe; immune imaging; in vivo; innovation; light scattering; magnetic field; microwave electromagnetic radiation; molecular marker; multidisciplinary; nanodiamond; nanoparticle; nanosized; new technology; novel; optical imaging; particle; portability; pre-clinical; 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.

摘要在深层组织（> 1 cm）环境中的高分辨率成像可以解决大量的眼底问题， 在阐明疾病起源和发展机制方面的精神和应用问题。当荧光- CENE成像是用于生物分子标记物的细胞成像的主力技术，其遭受 光散射和组织深度>1 mm处的像差失真。在光谱的另一端， 磁共振成像（MRI）是一种成熟的和广泛使用的临床前和临床成像 这种方法对组织深度没有实际限制，但分辨率低。在这 项目我们将创新一类新的超极化13 C纳米粒子探针，可以作为有效的深度 MRI中的组织标记。我们的中心思想是通过（i）光学超极化， 可以在低磁场下进行的Larization;（ii）13 C相干时间的显着延长。 具体来说，我们建议开发基于荧光纳米金刚石（FND）的MRI探针， 氮空位（NV）中心。与NV相关的电子自旋可以是光学“超极化”的， 该极化被有效地转移到金刚石13 C核自旋，导致NMR信号增强- 在临床MRI的领域中，与13 C热极化相比，与此同时， 实施有效的去耦方案，我们提出了显着扩展13 C自旋相干，能够 对他们进行第二次长时间的审问后者产生巨大的信号增益， 103倍。结合由于超极化和自旋相干扩展而产生的增益， 信号增益106，并且将使得能够显著提高空间分辨率。而且由于 极化是光学产生的，这种13 C光MRI（PMRI），可以在低场进行，在低得多的 成本与传统MRI基础设施。在我们的方法中，自旋极化是光学再生的， 重复采集MRI数据并进行纵向研究。此外，FND颗粒固有地 它们具有生物相容性，并且它们的表面适合于一组通用的靶向配体。在此基础上，我们建议 开发可靶向的荧光纳米颗粒MRI探针， 在深层组织（>1 cm）环境中优于20 um。除了是明亮的MRI试剂，这些颗粒还 明亮的荧光为组织病理学中的试剂生物分布的交叉检查提供了选择 分析.为了实现这一新技术的前景，我们建议进一步发展超声波， 和MR成像方法，以及通过优化纳米颗粒的超极化率， 通过合成和加工发展改变其结构。我们的目标是转让PMRI技术 我们证明了从微米尺寸的颗粒到纳米尺寸的FND适用于体内MRI。的一部分所 技术演示，我们将构建一个简单的原型PMRI成像设置在工作台上（低场） 以及在组织体模中成像FND，表征分辨率和成像深度的可实现度量。