Magnetic Particle Imaging as a Deep-Penetrating, Quantitative, Sensitive Molecular and Cellular Imaging Method with 100-nM Sensitivity
M. Cook Endowed Chair
BioEngineering and EECS
University of California, Berkeley
Magnetic Particle Imaging (MPI) is a noninvasive biomedical imaging modality that shows great promise for Molecular and Cellular Imaging. MPI is in the earliest stages of development by roughly two-dozen labs worldwide, mostly in Germany. Prof. Conolly’s lab at UC Berkeley has designed and built all the MPI scanners now in North America. Stanford has purchased the first preclinical MPI scanner produced by our startup company (Magnetic Insight, Alameda CA).
MPI’s physics advantages could usher completely noninvasive alternatives to tracer studies that currently must be performed with radioactive nuclear medicine techniques, such as
• Lung perfusion imaging to supplant Tc99m-MAA Ventilation-Perfusion studies, which subjects patients to substantial radiation dose.
• Capillary-level blood volume and perfusion using longcirculating SPIOs, which could supplant radioactive studies of brain perfusion following stroke
• MPI Cancer imaging MPI may soon provide a noninvasive screening alternative to X-ray mammography. We are also collaborating with Immunotherapy expert, Dr. Larry Fong at UCSF to track immunotherapies to tumors.
• MPI molecular & cellular imaging with cell binding and cell viability in vivo.
MPI relies on completely different physics from our conventional imaging modalities: MRI, CT, X-ray, ultrasound, and nuclear medicine. MPI offers extraordinary contrast, because human tissues produce zero MPI signal and these tissues are magnetically transparent. Moreover, the induced signal from MPI tracers, superparamagnetic iron oxide (SPIO) nanoparticles, is so strong that our homebuilt Berkeley scanner shows ~100 nM [Fe] with quantitative, positive contrast. The SPIO tracers are considered safe for human use even at 2 mM [Fe], and some are already FDA or EU safety approved. SPIO tracers are thought to be safer for chronic kidney disease (CKD) patients than current contrast agents.
The Conolly lab focuses on developing the hardware, pulse sequences, and image reconstruction algorithms for MPI. The lab has also recently performed many of the world's first MPI biomedical applications, including quantitative cell tracking, shown in the Figure above, where 3 million pre-labeled stem cells were injected into the tail vein of a rat. These cells quickly became trapped in the lung capillaries (seen on Day 1), and then the cells slowly are excreted through the liver and spleen (seen on Day 12). No other imaging modality can match this image quality in the lung; indeed, MPI cell tracking has the highest sensitivity of positive contrast, whole-animal imaging techniques.
With over 25 years of medical imaging hardware, systems, and image reconstruction expertise, Steven Conolly has developed a deep and broad knowledge of scanner physics, design, and construction. By working closely with MDs at Stanford and UCSF, he has developed appreciation for biomedical applications of innovative biomedical imaging scanners. The Conolly lab now emphasizes innovative hardware for important clinical and preclinical applications. Dr. Conolly oversaw the design and construction of 3 pre-polarized MRI scanners at Stanford University and 4 Magnetic Particle Imaging (MPI) scanners at UC Berkeley. MPI is a new imaging modality, which is ideal for sensitive and quantitative detection of iron oxide tracers placed on cellular therapies. The Conolly lab at UC Berkeley has built the world's highest spatial resolution MPI scanner (with a 7 T/m gradient selection field) and the only projection MPI scanner in the world. In addition, the lab has built the only 3D Projection-Reconstruction MPI scanner in existence.
Steven Conolly has nearly 30 US Patents in various stages of approval; GE, Siemens, and Philips have licensed more than half of my patents. In 2004, Stanford named him an Outstanding Inventor for his patents, one of only 24 people in the history of Stanford to be given this honor. At UC Berkeley, he has held several important administrative roles, including Chair of the Graduate Group in Bioengineering, which is joint program between UCSF and UC Berkeley. Dr. Conolly received his Ph.D. in Electrical Engineering from Stanford University.