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，它可能很快就会让医生们 CAR-T细胞免疫疗法是否真的针对肿瘤--零辐射，而且只是 3天。这比现在的随访PET/CT要安全得多，速度也快得多。 考虑到个性化免疫治疗护理的速度很慢。MPI不使用辐射，但它甚至与 先进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、 胃肠道(GI)出血和癌症。本质上，MPI提供了核医学的敏感性 核磁共振的安全性。MPI是定量的，在体内的任何地方都很健壮，而且它不使用辐射。 MPI也是紧急诊断的理想选择，因为MPI示踪剂可以与 然后从工厂直接从冰箱注射。因此，可以进行紧急MPI扫描 使用MPI只需5分钟，比核医学扫描通常2小时的速度要快得多。 我们的目标是消除阻碍MPI临床应用的唯一技术弱点，即它的弱点 空间分辨率。我们的关键创新是将MPI的空间分辨率提高了10倍。 美维。我们的创新涉及硬件、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有10- 与MPI标准相比，分辨率和信噪比(通常)和30倍(偶尔)提高了一倍， VivoTrax。一旦我们的新示踪剂具有生物兼容性，它们将为史无前例的10 使用安全且负担得起的人体MPI扫描仪，对人体细胞在2 mm分辨率下的灵敏度，大致为 硬件成本为100,000美元--这是一个真正能够实现的进步。 我们的具体目标是：(1)开发高分辨率MPI示踪剂，供行业和 为学术界和学术界共享的高分辨率MPI开发工程工具 工业；(3)活体扫描，以证明高分辨率MPI的有效性。 生物工程与工业的伙伴关系是促进这一突破的理想机制 加州大学伯克利分校三个实验室与PI实验室外的一家初创公司合作解决MPI问题 (Magic 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).