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

磁粒子成像分辨率提高十倍，应用于 CAR-T 细胞疗法、中风、胃肠道出血和肺栓塞的快速、非侵入性成像

• 批准号: 10714021
• 负责人: STEVEN M CONOLLY
• 金额: $ 76.1万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-15 至 2028-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10714021
• 关键词: 3-Dimensional; Academia; Adoption; Aftercare; Algorithms; Back; Binding; Biomedical Engineering; Blood Vessels; CAR T cell therapy; Cardiovascular Diseases; Caring; Cell Survival; Cell physiology; Cells; Chemistry; Clinical; Clinical Trials; Collaborations; Data; Development; Dextrans; Diagnosis; Dimensions; Discipline of Nuclear Medicine; Early Diagnosis; Emergency Situation; Engineering; Ensure; Fostering; Gastrointestinal Hemorrhage; Goals; Grant; Homing; Hour; Human; Image; Imaging Device; Imaging Techniques; Imaging technology; Immunotherapy; Industrialization; Industry; Life; Lung; Magnetic Resonance Imaging; Magnetism; Malignant Neoplasms; Malignant neoplasm of gastrointestinal tract; Medical Imaging; Modeling; Multiple Partners; Noise; PET/CT scan; Patients; Perfusion; Physics; Physiologic pulse; Preclinical Testing; Process; Production; Pulmonary Embolism; RF coil; Radiation; Radiation Dose Unit; Research; Resolution; Safety; Scanning; Software Tools; Solid Neoplasm; Stroke; Time; Tracer; Traumatic Brain Injury; Tumor Volume; biomaterial compatibility; chimeric antigen receptor T cells; cost; design; experience; experimental study; follow-up; image reconstruction; imaging capabilities; improved; in vivo; innovation; insight; nanoscale; non-invasive imaging; particle; personalized immunotherapy; personalized medicine; reconstruction; scale up; single photon emission computed tomography; targeted agent; tool; tumor

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).

抽象的 磁性粒子成像（MPI）是一种新的示踪影像技术，可以很快允许MDS告诉 CAR-T细胞免疫疗法实际上是否针对肿瘤 - 零辐射，仅在 3天。这比今天的后续宠物/CT更安全，更快，这也是如此 缓慢允许个性化免疫疗法护理。 MPI不使用辐射，但它甚至与 晚期核医学扫描的敏感性。 MPI很快可能会彻底改变 威胁生命的中风，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提供了核医学的敏感性 使用MRI的安全。 MPI在体内到处都是定量且健壮的，它不使用辐射。 MPI也非常适合紧急诊断，因为MPI示踪剂可以与靶向剂约束 工厂然后直接从冰箱注射。因此，可以进行紧急MPI扫描 在使用MPI的短短5分钟内，比核医学扫描典型的2小时要快得多。 我们旨在消除唯一的技术弱点，从而使MPI从临床采用中撤下，而其薄弱 空间分辨率。我们的关键创新是将MPI的空间分辨率提高10倍 媒介。我们的创新涵盖了硬件，脉冲序列，重建算法和纳米级 创新高分辨率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 Vivotrax。一旦我们的新示踪剂成为生物相容性，他们将为前所未有的10- 在人类中，具有安全且负担得起的人MPI扫描仪的2mm分辨率的细胞敏感性，大致在 $ 100,000的硬件成本 - 真正的进步。 我们的具体目的是（1）在行业和 学术界; （2）为高分辨率MPI开发工程工具在学术界和 行业; （3）体内扫描以证明高分辨率MPI的效率。 与行业的这种生物工程合作伙伴关系是促进这一突破性的理想机制 MPI分辨率通过UC Berkeley的三个实验室与PI实验室的创业公司之间的合作解决 （磁性见解）。