We welcome Dr. Jan Grimm as our next guest speaker for our seminar program. He is a physician-scientist from Memorial Sloan Kettering Cancer Center.
Imaging with the Speed and Sound of Light
Abstract: Besides working on novel approaches for cancer therapy using on chip microfluidic assyas, where we grow tumors with vessels on a chip, my lab is developing and exploring novel imaging applications based on imaging suprarelativistic particles and the sound of light. Cerenkov luminescence is the dim blue-light produced by charged subatomic particles traveling faster than the speed of a light through a dielectric medium such as tissue. These particles can originate from various sources, most prominently though from the decay of radioisotopes. Cerenkov Luminescence Imaging (CLI) is an emerging modality that fuses nuclear and optical imaging as well as radiotherapy. Highly sensitive optical equipment to detect the low amount of photons emitted compared to other optical imaging modalities. However, it offers several compelling advantages. CLI utilizes clinical approved tracers, thus avoiding significant hurdles for approval of the imaging agent. By reverting to PET of the very same agent an internal standard is provided that allows for quantification as well as true multimodality imaging from the same imaging label. CLI allows for preoperative PET scanning and intraoperative imaging of tumors. Clinical Cerenkov is a feasible molecular imaging modality that seamlessly integrates with existing clinical SPECT, PET, and nuclear medicine procedures. At MSKCC we have imaged more than 60 patients in a prototype Cerenkov imaging suite. Overall, Cerenkov imaging provides a paradigm shift, providing the first truly multimodal imaging system, merging optical and nuclear imaging and transgressing conventional borders between imaging systems, thus allowing for completely new imaging approaches and applications (e.g. intraoperative imaging) with a fast-track into the clinic. Optoacoustic imaging on the other hand utilizes pulsed light excitation of mostly intrinsic absorbers detected with ultrasound. We have a 2d generation prototype optoacoustic system (RSOM; raster-scanning optoacoustic ultrasound) that utilizes the intrinsic optical properties of hemoglobin to provide images of the entire tumor vasculature and surrounding skin non-invasively and can also be used to detect other absorbers as well. The animal is illuminated by nanosecond pulses of laser light. This light is both scattered and absorbed by chromophores such as hemoglobin as it transmits through tissue causing transient localized heating effects resulting in generation of an ultrasonic pulse. A single element ultrabroadband transducer (50MHz center frequency) detects the frequency composition and amplitude of the pulse. Information derived from a raster-scan of an area of interest is reconstructed to form an image denoting structure and composition of vasculature while information on local blood oxygenation can be derived by utilizing a multispectral approach to differentiate Hb vs HbO2. We currently use this system to interrogate tumor vascularity and antivascular therapy, in conjunction with the above mentioned chip system, offering the range from in vitro to in vivo.
Bio: Dr. Jan Grimm has experience in clinical radiology, nuclear medicine, and basic science. I trained in both Europe and the United States. He did a body imaging fellowship and nuclear medicine residency at MSK. In that time Jan gained extensive experience in tumor imaging using MRI, CT, and PET/CT. His main interests are body imaging, particularly lymph node imaging and prostate imaging, as well as prostate cancer biology. Dr. Grimm's lab has developed a new method to identify tumor-positive lymph nodes. They are also creating new imaging approaches (Cerenkov imaging) and therapies based on nanoparticles.