U-SPECT-BioFluo: an integrated radionuclide, bioluminescence, and fluorescence imaging platform.
BACKGROUND
In vivo bioluminescence, fluorescence, and single-photon emission computed tomography (SPECT) imaging provide complementary information about biological processes. However, to date these signatures are evaluated separately on individual preclinical systems. In this paper, we introduce a fully integrated bioluminescence-fluorescence-SPECT platform. Next to an optimization in logistics and image fusion, this integration can help improve understanding of the optical imaging (OI) results.


METHODS
An OI module was developed for a preclinical SPECT system (U-SPECT, MILabs, Utrecht, the Netherlands). The applicability of the module for bioluminescence and fluorescence imaging was evaluated in both a phantom and in an in vivo setting using mice implanted with a 4 T1-luc + tumor. A combination of a fluorescent dye and radioactive moiety was used to directly relate the optical images of the module to the SPECT findings. Bioluminescence imaging (BLI) was compared to the localization of the fluorescence signal in the tumors.


RESULTS
Both the phantom and in vivo mouse studies showed that superficial fluorescence signals could be imaged accurately. The SPECT and bioluminescence images could be used to place the fluorescence findings in perspective, e.g. by showing tracer accumulation in non-target organs such as the liver and kidneys (SPECT) and giving a semi-quantitative read-out for tumor spread (bioluminescence).


CONCLUSIONS
We developed a fully integrated multimodal platform that provides complementary registered imaging of bioluminescent, fluorescent, and SPECT signatures in a single scanning session with a single dose of anesthesia. In our view, integration of these modalities helps to improve data interpretation of optical findings in relation to radionuclide images.
Radiation, Detection and Medical Imaging, Delft University of Technology, Mekelweg 15, Delft, 2629, JB, the Netherlands ; Interventional Molecular Imaging Laboratory, Department of Radiology, Leiden University Medical Center, Leiden, the Netherlands.
Matthias N
MN
van Oosterom
Radiation, Detection and Medical Imaging, Delft University of Technology, Mekelweg 15, Delft, 2629, JB, the Netherlands.
Rob
R
Kreuger
Interventional Molecular Imaging Laboratory, Department of Radiology, Leiden University Medical Center, Leiden, the Netherlands.
Tessa
T
Buckle
Radiation, Detection and Medical Imaging, Delft University of Technology, Mekelweg 15, Delft, 2629, JB, the Netherlands.
Wendy A
WA
Mahn
Interventional Molecular Imaging Laboratory, Department of Radiology, Leiden University Medical Center, Leiden, the Netherlands.
Anton
A
Bunschoten
Centre for Translational Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital, Harvard Medical School, Boston, USA.
Lee
L
Josephson
Interventional Molecular Imaging Laboratory, Department of Radiology, Leiden University Medical Center, Leiden, the Netherlands.
Fijs Wb
FW
van Leeuwen
Radiation, Detection and Medical Imaging, Delft University of Technology, Mekelweg 15, Delft, 2629, JB, the Netherlands ; MILABS, Utrecht, the Netherlands ; Department of Translational Neuroscience, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, the Netherlands.
Freek J
FJ
Beekman
Bioluminescence imaging; Fluorescence imaging; Multimodal molecular imaging; Nuclear medicine; SPECT; Small animal