Ten-Fold Resolution Boost for Magnetic Particle Imaging with Applications to Rapid, Non-Invasive Imaging of CAR-T Cell Therapies, Stroke, GI Bleeds and Pulmonary Embolisms

摘要 磁粒子成像（MPI）是一种新的示踪成像技术，很快就可以让MD告诉 CAR-T细胞免疫疗法是否真的靶向肿瘤-零辐射， 3天这比目前的后续PET/CT更安全，更快， 慢到允许个性化免疫治疗护理。MPI不使用辐射，但它甚至匹配 先进的核医学扫描的灵敏度。MPI可能很快就会彻底改变早期诊断， 危及生命的中风、创伤性脑损伤、心血管疾病、肺栓塞（PE）， 胃肠道（GI）出血和癌症。本质上，MPI提供了核医学的灵敏度 MRI的安全性。MPI是定量的，在身体的任何地方都是稳定的，它不使用辐射。 MPI也是紧急诊断的理想选择，因为MPI示踪剂可以与靶向剂结合， 然后直接从冰箱中注入。因此，可以进行紧急MPI扫描 MPI扫描仅需5分钟，比核医学扫描通常需要的2小时快得多。 我们的目标是消除阻碍MPI临床采用的唯一技术弱点， 空间分辨率我们的主要创新是将MPI的空间分辨率提高10倍， 月经。我们的创新跨越硬件、脉冲序列、重建算法和纳米级 创新的高分辨率MPI示踪剂的物理和化学。我们的初步实验显示，10- 与MPI标准相比，分辨率和SNR提高了1倍（常规）和30倍（偶尔）， VivoTrax一旦我们的新示踪剂具有生物相容性，它们将为前所未有的10- 使用安全且负担得起的人体MPI扫描仪，在2 mm分辨率下对人体细胞的灵敏度约为 100，000美元的硬件成本--这是一个真正的优势。 我们的具体目标是（1）开发高分辨率MPI示踪剂， （2）开发高分辨率MPI的工程工具，供学术界和 工业;和（3）体内扫描，以证明高分辨率MPI的功效。 这种生物工程与工业的伙伴关系是促进这一突破的理想机制， 由加州大学伯克利分校的三个实验室和PI实验室的一家初创公司合作完成的MPI解决方案 （Magnetic Insight）

Abstract Magnetic Particle Imaging (MPI) is a new tracer imaging technology that could soon allow MDs to tell whether a CAR-T cell immunotherapy is actually targeting a tumor— with zero radiation, and in just 3 days. This is much safer and much faster than today’s practice of a followup PET/CT, which is too slow to allow for personalized immunotherapy care. MPI uses no radiation and yet it matches even the sensitivity of advanced nuclear medicine scans. MPI could soon revolutionize the early diagnosis of life-threatening Strokes, Traumatic Brain Injuries, Cardiovascular disease, Pulmonary Embolisms (PE), Gastrointestinal (GI) Bleeds and Cancer. In essence, MPI offers the the sensitivity of Nuclear Medicine with the safety of MRI. MPI is quantitative and robust everywhere in the body and it uses no radiation. MPI also is ideal for emergency diagnoses because MPI tracers can be bound to a targeting agent in the factory and then injected directly from the refrigerator. Hence, emergency MPI scans can be done in just 5 minutes with MPI, much faster than the 2 hours typical for nuclear medicine scans. We aim to remove the only technical weakness holding back MPI from clinical adoption, its weak spatial resolution. Our key innovation is to improve the spatial resolution of MPI by 10-fold in each di- mension. Our innovations span hardware, pulse sequences, reconstruction algorithms and the nanoscale physics and chemistry of innovative high-resolution MPI tracers. Our preliminary experiments show 10- fold (routinely) and 30-fold (occasionally) boost in resolution and SNR compared to the MPI standard, VivoTrax. Once our new tracers are made biocompatible they will pave the way for unprecedented 10- cell sensitivity at 2mm resolution in humans with a safe and affordable human MPI scanner, at roughly $100,000 hardware costs—a truly enabling advance. Our Specific Aims are to (1) Develop high-resolution MPI tracers shared between Industry and Academia; (2) Develop Engineering Tools for High Resolution MPI shared between academia and industry; and (3) In vivo scanning to prove the efficacy of high-resolution MPI. This Bioengineering Partnership with Industry is the ideal mechanism to foster this breakthrough in MPI resolution by a collaboration between three labs at UC Berkeley and a startup out of the PI’s lab (Magnetic Insight).