A microcomputed tomography guided fluorescence tomography system for small animal molecular imaging.
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ABSTRACT:
SUBMITTER: Kepshire D
PROVIDER: S-EPMC2678792 | biostudies-other | 2009 Apr
REPOSITORIES: biostudies-other
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Project description:UNLABELLED:Spatial and temporal coregistration of nuclear and optical images can enable the fusion of the information from these complementary molecular imaging modalities. A critical challenge is in integrating the optical and nuclear imaging hardware. Flexible fiber-based fluorescence-mediated tomography (FMT) systems provide a viable solution. The various bore sizes of small-animal nuclear imaging systems can potentially accommodate the FMT fiber imaging arrays. In addition, FMT imaging facilitates coregistration of the nuclear and optical contrasts in time. Herein, we combine a fiber-based FMT system with a preclinical SPECT/CT platform. Feasibility of in vivo imaging is demonstrated by tracking a monomolecular multimodal imaging agent (MOMIA) during transport from the forepaw to the axillary lymph node region of a rat. METHODS:The fiber-based, video-rate FMT imaging system is composed of 12 sources (785- and 830-nm laser diodes) and 13 detectors. To maintain high temporal sampling, the system simultaneously acquires ratio-metric data at each detector. A 3-dimensional finite element model derived from CT projections provides anatomically based light propagation modeling. Injection of a MOMIA intradermally into the forepaw of rats provided spatially and temporally coregistered nuclear and optical contrasts. FMT data were acquired concurrently with SPECT and CT data. The incorporation of SPECT data as a priori information in the reconstruction of FMT data integrated both optical and nuclear contrasts. RESULTS:Accurate depth localization of phantoms with different thicknesses was accomplished with an average center-of-mass error of 4.1 ± 2.1 mm between FMT and SPECT measurements. During in vivo tests, fluorescence and radioactivity from the MOMIA were colocalized in spatially coincident regions with an average center-of-mass error of 2.68 ± 1.0 mm between FMT and SPECT for axillary lymph node localization. Intravital imaging with surgical exposure of the lymph node validated the localization of the optical contrast. CONCLUSION:The feasibility of integrating a fiber-based, video-rate FMT system with a commercial preclinical SPECT/CT platform was established. These coregistered FMT and SPECT/CT results with MOMIAs may facilitate the development of the next generation of preclinical and clinical multimodal optical-nuclear platforms for a broad array of imaging applications and help elucidate the underlying biologic processes relevant to cancer diagnosis and therapy monitoring.
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Project description:The work presented herein describes the system design and performance evaluation of a miniaturized near-infrared fluorescence (NIRF) frequency-domain photon migration (FDPM) system with non-contact excitation and homodyne detection capability for small animal fluorescence tomography. The FDPM system was developed specifically for incorporation into a Siemens micro positron emission tomography/computed tomography (microPET/CT) commercial scanner for hybrid small animal imaging, but could be adapted to other systems. Operating at 100 MHz, the system noise was minimized and the associated amplitude and phase errors were characterized to be ±0.7% and ±0.3°, respectively. To demonstrate the tomographic ability, a commercial mouse-shaped phantom with 50 µM IRDye800CW and ⁶⁸Ga containing inclusion was used to associate PET and NIRF tomography. Three-dimensional mesh generation and anatomical referencing was accomplished through CT. A third-order simplified spherical harmonics approximation (SP₃) algorithm, for efficient prediction of light propagation in small animals, was tailored to incorporate the FDPM approach. Finally, the PET-NIRF target co-localization accuracy was analyzed in vivo with a dual-labeled imaging agent targeting orthotopic growth of human prostate cancer. The obtained results validate the integration of time-dependent fluorescence tomography system within a commercial microPET/CT scanner for multimodality small animal imaging.
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Project description:In this study, several key optimization steps are outlined for a non-contact, time-correlated single photon counting small animal optical tomography system, using simultaneous collection of both fluorescence and transmittance data. The system is presented for time-domain image reconstruction in vivo, illustrating the sensitivity from single photon counting and the calibration steps needed to accurately process the data. In particular, laser time- and amplitude-referencing, detector and filter calibrations, and collection of a suitable instrument response function are all presented in the context of time-domain fluorescence tomography and a fully automated workflow is described. Preliminary phantom time-domain reconstructed images demonstrate the fidelity of the workflow for fluorescence tomography based on signal from multiple time gates.
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Project description:BACKGROUND:MR-guided focused ultrasound or high-intensity focused ultrasound (MRgFUS/MRgHIFU) is a non-invasive therapeutic modality with many potential applications in areas such as cancer therapy, drug delivery, and blood-brain barrier opening. However, the large financial costs involved in developing preclinical MRgFUS systems represent a barrier to research groups interested in developing new techniques and applications. We aim to mitigate these challenges by detailing a validated, open-source preclinical MRgFUS system capable of delivering thermal and mechanical FUS in a quantifiable and repeatable manner under real-time MRI guidance. METHODS:A hardware and software package was developed that includes closed-loop feedback controlled thermometry code and CAD drawings for a therapy table designed for a preclinical MRI scanner. For thermal treatments, the modular software uses a proportional integral derivative controller to maintain a precise focal temperature rise in the target given input from MR phase images obtained concurrently. The software computes the required voltage output and transmits it to a FUS transducer that is embedded in the delivery table within the magnet bore. The delivery table holds the FUS transducer, a small animal and its monitoring equipment, and a transmit/receive RF coil. The transducer is coupled to the animal via a water bath and is translatable in two dimensions from outside the magnet. The transducer is driven by a waveform generator and amplifier controlled by real-time software in Matlab. MR acoustic radiation force imaging is also implemented to confirm the position of the focus for mechanical and thermal treatments. RESULTS:The system was validated in tissue-mimicking phantoms and in vivo during murine tumor hyperthermia treatments. Sonications were successfully controlled over a range of temperatures and thermal doses for up to 20 min with minimal temperature overshoot. MR thermometry was validated with an optical temperature probe, and focus visualization was achieved with acoustic radiation force imaging. CONCLUSIONS:We developed an MRgFUS platform for small-animal treatments that robustly delivers accurate, precise, and controllable sonications over extended time periods. This system is an open source and could increase the availability of low-cost small-animal systems to interdisciplinary researchers seeking to develop new MRgFUS applications and technology.
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Project description:The combination of early diagnosis and complete surgical resection offers the greatest prospect of curative cancer treatment. An iodine-124/fluorescein-based dual-modality labeling reagent, 124I-Green, constitutes a generic tool for one-step installation of a positron emission tomography (PET) and a fluorescent reporter to any cancer-specific antibody. The resulting antibody conjugate would allow both cancer PET imaging and intraoperative fluorescence-guided surgery. 124I-Green was synthesized in excellent radiochemical yields of 92 ± 5% (n = 4) determined by HPLC with an improved one-pot three-component radioiodination reaction. The A5B7 carcinoembryonic antigen (CEA)-specific antibody was conjugated to 124I-Green. High tumor uptake of the dual-labeled A5B7 of 20.21 ± 2.70, 13.31 ± 0.73, and 10.64 ± 1.86%ID/g was observed in CEA-expressing SW1222 xenograft mouse model (n = 3) at 24, 48, and 72 h post intravenous injection, respectively. The xenografts were clearly visualized by both PET/CT and ex vivo fluorescence imaging. These encouraging results warrant the further translational development of 124I-Green for cancer PET imaging and fluorescence-guided surgery.
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Project description:A new concept for cancer screening has been preliminarily investigated. A cancer targeting agent loaded with a near-infrared (NIR) dye was topically applied on the tissue to highlight cancer-suspect locations and guide optical coherence tomography (OCT) imaging, which was used to further investigate tissue morphology at the micron scale. A pilot study on ApcMin mice has been performed to preliminarily test this new cancer screening approach. As a cancer-targeting agent, poly(epsilon-caprolactone) microparticles (PCLMPs), labeled with a NIR dye and functionalized with an RGD (argenine-glycine-aspartic acid) peptide, were used. This agent recognizes the α(ν)β(3) integrin receptor (ABIR), which is over-expressed by epithelial cancer cells. The contrast agent was administered topically in vivo in mouse colon. After incubation, the animals were sacrificed and fluorescence-guided high resolution optical coherence tomography (OCT) imaging was used to visualize colon morphology. The preliminary results show preferential staining of the abnormal tissue, as indicated by both microscopy and laser-induced fluorescence imaging, and OCT's capability to differentiate between normal mucosal areas, early dysplasia, and adenocarcinoma. Although very preliminary, the results of this study suggest that fluorescence-guided OCT imaging might be a suitable approach for cancer screening. If successful, this approach could be used by clinicians to more reliably diagnose early stage cancers in vivo.
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Project description:Cancer is a major threat to human health. Diagnosis and treatment using precision medicine is expected to be an effective method for preventing the initiation and progression of cancer. Although anatomical and functional imaging techniques such as radiography, computed tomography (CT), magnetic resonance imaging (MRI) and positron emission tomography (PET) have played an important role for accurate preoperative diagnostics, for the most part these techniques cannot be applied intraoperatively. Optical molecular imaging is a promising technique that provides a high degree of sensitivity and specificity in tumor margin detection. Furthermore, existing clinical applications have proven that optical molecular imaging is a powerful intraoperative tool for guiding surgeons performing precision procedures, thus enabling radical resection and improved survival rates. However, detection depth limitation exists in optical molecular imaging methods and further breakthroughs from optical to multi-modality intraoperative imaging methods are needed to develop more extensive and comprehensive intraoperative applications. Here, we review the current intraoperative optical molecular imaging technologies, focusing on contrast agents and surgical navigation systems, and then discuss the future prospects of multi-modality imaging technology for intraoperative imaging-guided cancer surgery.
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