An innovative dual-modality 3D fluorescence/3D ultrasound tomography system was demonstrated in this research. The system includes an electron-multiplying charge-coupled device (EMCCD), a 660 nm wavelength fiber-coupling laser, and a 10-15 MHz frequency customized single-element ultrasound transducer on a 3D rotating scanning device. We combined multiple ultrasound images from different sections to obtain a whole-body 3D mesh of mice, which provide anatomical information. In this study, we demonstrated the accuracy of this system through a 4T1 tumor-bearing nude mice experiment.
We demonstrate dual modality of free-space fluorescence diffuse optical tomography (FDOT) and handheld ultrasound (US) imaging to reveal both functional and structural information in small animals. FDOT is a noninvasive method for examining the fluorophore inside an object from the light distribution of the surface. In FDOT, a 660-nm continuous wave diode laser was used as an excitation source and an electron-multiplying charge-coupled device (EMCCD) was used for fluorescence data acquisition. Both the laser and EMCCD were mounted on a 360-deg rotation gantry for the transmission optical data collection. The structural information is obtained from a 6- to 17-MHz handheld US linear transducer by single-side access and conducts in the reconstruction as soft priors. The rotation ranges from 0 deg to 360 deg; different rotation degrees, object positions, and parameters were determined for comparison. Both phantom and tissue phantom results demonstrate that fluorophore distribution can be recovered accurately and quantitatively using this imaging system. Finally, an animal study confirms that the system can extract a dual-modality image, validating its feasibility for further in vivo experiments. In all experiments, the error and standard deviation decrease as the rotation degree is increased and the error was reduced to 10% when the rotation degree was increased over 135 deg.
Fluorescence diffuse optical tomography (FDOT) has been widely used for in vivo small animal studies and the illposed problem in reconstruction can be eased by utilizing structural a priori obtained from an anatomic imaging modality. In this study, a multispectral fluorescence tomography (FT) is used, which has shown the ability to detect subtle shifts in the ICG absorption spectrum in our previous study. The imaging system is in trans-illumination mode with a swept-wavelength laser and a CCD on a rotation gantry and the structural image from the X-ray computed tomography is used to guide and constrain the FT reconstruction algorithm. In this work, a phantom with two inclusions filled with different fluorophores is utilized to evaluate whether the spectral information obtained using sweptwavelength laser can distinguish these two inclusions. The images are captured from 8 different views with three different wavelengths.
In this study, a novel imaging modality, free space guided fluorescence diffuse optical tomography (FDOT), was perform to reconstruct the fluorophore distribution by incorporate structural priors into optical image inversion schemes. The dual modality imaging system used a rotation gantry combined with an electron-multiplying charge-coupled device (EMCCD) and a laser source in trans-illumination mode. The fluorescence data was collected from 360° range. The structural information of the object were obtained by an ultrasound linear array transducer. To validate the performance of the system, phantoms and bio tissue experiment were conducted. The results show that the imaging system achieves accurate and has the potential for further in vivo study.
The strong scattering and absorption of light in biological tissue makes it challenging to model the propagation of light, especially in deep tissue. This is especially true in fluorescent tomography, which aims to recover the internal fluorescence source distribution from the measured light intensities on the surface of the tissue. The inherently ill-posed and underdetermined nature of the inverse problem along with strong tissue scattering makes Fluorescence Tomography (FT) extremely challenging. Previously, multispectral detection fluorescent tomography (FT) has been shown to improve the image quality of FT by incorporating the spectral filtering of biological tissue to provide depth information to overcome the inherent absorption and scattering limitations. We investigate whether multi-wavelength fluorescent tomography can be used to distinguish the signals from multiple fluorophores with overlapping fluorescence spectrums using a unique near-infrared (NIR) swept laser. In this work, a small feasibility study was performed to see whether multi-wavelength FT can be used to detect subtle shifts in the absorption spectrum due to differences in fluorophore microenvironment.
X-ray luminescence computed tomography (XLCT) is a novel molecular imaging modality that reconstructs the optical
distribution of x-ray-excited phosphor particles with prior informational of anatomical CT image. The prior information
improves the accuracy of image reconstruction. The system can also present anatomical CT image. The optical system
based on a high sensitive charge coupled device (CCD) is perpendicular with a CT system. In the XLCT system, the xray
was adopted to excite the phosphor of the sample and CCD camera was utilized to acquire luminescence emitted
from the sample in 360 degrees projection free-space. In this study, the fluorescence diffuse optical tomography
(FDOT)-like algorithm was used for image reconstruction, the structural prior information was incorporated in the
reconstruction by adding a penalty term to the minimization function. The phosphor used in this study is Gd2O2S:Tb. For
the simulation and experiments, the data was collected from 16 projections. The cylinder phantom was 40 mm in
diameter and contains 8 mm diameter inclusion; the phosphor in the in vivo study was 5 mm in diameter at a depth of 3
mm. Both the errors were no more than 5%. Based on the results from these simulation and experimental studies, the
novel XLCT method has demonstrated the feasibility for in vivo animal model studies.
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