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BEST IN PHYSICS (IMAGING): 3D Cherenkov Sheet Molecular Imaging Provides 100 μm Whole Body Spatial Resolution

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P Bruza

P Bruza1*, J Feng2 , D Gladstone1,3,4 , L Jarvis3,4 , B Pogue1,3 , (1) Thayer School of Engineering, Dartmouth College, Hanover, NH, (2) Beijing University of Technology, Beijing, China, (3) Geisel School of Medicine, Dartmouth College, Lebanon, New Hampshire, (4) Norris Cotton Cancer Center, Lebanon, NH


TH-AB-708-12 (Thursday, August 3, 2017) 7:30 AM - 9:30 AM Room: 708

Purpose: To test the spatial and temporal imaging resolution limits for 3D fluorescence intensity and lifetime kinetics from a whole body of a small animal, excited by thin MV linac photon sheets inducing Cherenkov excitation light.

Methods: Scanned thin sheet of radiation from a medical linear accelerator was used to produce a series of 2D sheets of Cherenkov light within tissue. These Cherenkov radiation in turn excited the fluorescence of molecular probes distributed along the sheet planes. Analogous to light sheet microscopy, a series of luminescence images was taken for varied depths of the Cherenkov light sheet in sample. The fluorescence was imaged by a gated, intensified camera positioned perpendicularly to the sheet plane. Precise knowledge of the light sheet position within the object allowed an iterative 3D reconstruction of the 3D fluorophore distribution. Since the X-ray beam fluence was modulated with a megahertz frequency, the temporal deconvolution can enable the separation of the prompt Cherenkov radiation background from a fluorescence signal without the need of spectral decomposition. Moreover, the temporal deconvolution can yield the spatial distribution of fluorescence lifetime across the whole field of view.

Results: The phantom imaging and reconstruction recovered a 6 mm weakly phosphorescent object (25 μM PtG4) 30 mm deep inside an 1% intralipid tissue-mimicking phantom. The simulation results demonstrated a feasibility of recovering a 2D fluorescence lifetime kinetics image from a high quality image (signal-to-noise ratio >1000). The culminating preliminary in-vivo experiment recovered a 3D distribution of PtG4 molecular probe inside a 5 mm subcutaneous tumor.

Conclusion: The scanned-sheet tomographic technique can reconstruct a 3D fluorescence intensity and lifetime distribution with sub-millimeter resolution in 10-30 millimeter depths. Phantom and in vivo results demonstrate that this method can produce perhaps the highest resolution fluorecsence imaging tool possible for whole body imaging at low tracer concentration.

Funding Support, Disclosures, and Conflict of Interest: US National Institute of Health (NIH) (R01CA109558); US Army CDMRP Breast Cancer Research Program Breakthrough Award (BC150584). B. Pogue is founder and president of DoseOptics LLC developing Cherenkov imaging systems, however this work was not supported by DoseOptics in any way.

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