Cerenkov luminescence imaging (CLI) is an emerging cost effective modality that uses conventional small animal
optical imaging systems and clinically available radionuclide probes for light emission. CLI has shown good correlation
with PET for organs of high uptake such as kidney, spleen, thymus and subcutaneous tumors in mouse models. However,
CLI has limitations for deep tissue quantitative imaging since the blue-weighted spectral characteristics of Cerenkov
radiation attenuates highly by mammalian tissue. Large organs such as the liver have also shown higher signal due to the
contribution of emission of light from a greater thickness of tissue. In this study, we developed a simple model that
estimates the effective tissue attenuation coefficient in order to correct the CLI signal intensity with a priori estimated
depth and thickness of specific organs. We used several thin slices of ham to build a phantom with realistic attenuation.
We placed radionuclide sources inside the phantom at different tissue depths and imaged it using an IVIS Spectrum
(Perkin-Elmer, Waltham, MA, USA) and Inveon microPET (Preclinical Solutions Siemens, Knoxville, TN). We also
performed CLI and PET of mouse models and applied the proposed attenuation model to correct CLI measurements.
Using calibration factors obtained from phantom study that converts the corrected CLI measurements to %ID/g, we
obtained an average difference of less that 10% for spleen and less than 35% for liver compared to conventional PET
measurements. Hence, the proposed model has a capability of correcting the CLI signal to provide comparable
measurements with PET data.
Adam de la Zerda, Moritz Kircher, Jesse Jokerst, Cristina Zavaleta, Paul Kempen, Erik Mittra, Ken Pitter, Ruimin Huang, Carl Campos, Frezghi Habte, Robert Sinclair, Cameron Brennan, Ingo Mellinghoff, Eric Holland, Sanjiv Gambhir
The difficulty in delineating brain tumor margins is a major obstacle in the path toward better
outcomes for patients with brain tumors. Current imaging methods are often limited by
inadequate sensitivity, specificity and spatial resolution. Here we show that a unique triplemodality
magnetic resonance imaging - photoacoustic imaging - Raman imaging nanoparticle
(termed here MPR nanoparticles), can accurately help delineate the margins of brain tumors in
living mice both preoperatively and intraoperatively. The MPRs were detected by all three
modalities with at least a picomolar sensitivity both in vitro and in living mice. Intravenous
injection of MPRs into glioblastoma-bearing mice led to MPR accumulation and retention by the
tumors, with no MPR accumulation in the surrounding healthy tissue, allowing for a noninvasive
tumor delineation using all three modalities through the intact skull. Raman imaging allowed for
guidance of intraoperative tumor resection, and a histological correlation validated that Raman
imaging was accurately delineating the brain tumor margins. This new triple-modality–
nanoparticle approach has promise for enabling more accurate brain tumor imaging and
resection.
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