Brown adipose tissue (BAT), widely known as a "good fat" plays pivotal roles for thermogenesis in mammals. This special tissue is closely related to metabolism and energy expenditure, and its dysfunction is one important contributor for obesity and diabetes. Contrary to previous belief, recent PET/CT imaging studies indicated the BAT depots are still present in human adults. PET imaging clearly shows that BAT has considerably high uptake of (18)F-FDG under certain conditions. In this video report, we demonstrate that Cerenkov luminescence imaging (CLI) with (18)F-FDG can be used to optically image BAT in small animals. BAT activation is observed after intraperitoneal injection of norepinephrine (NE) and cold treatment, and depression of BAT is induced by long anesthesia. Using multiple-filter Cerenkov luminescence imaging, spectral unmixing and 3D imaging reconstruction are demonstrated. Our results suggest that CLI with (18)F-FDG is a practical technique for imaging BAT in small animals, and this technique can be used as a cheap, fast, and alternative imaging tool for BAT research.
This protocol outlines the steps required to longitudinally monitor a bioluminescent bacterial infection using composite 3D diffuse light imaging tomography with integrated ?CT (DLIT-?CT) and the subsequent use of this data to generate a four dimensional (4D) movie of the infection cycle. To develop the 4D infection movies and to validate the DLIT-?CT imaging for bacterial infection studies using an IVIS Spectrum CT, we used infection with bioluminescent C. rodentium, which causes self-limiting colitis in mice. In this protocol, we outline the infection of mice with bioluminescent C. rodentium and non-invasive monitoring of colonization by daily DLIT-?CT imaging and bacterial enumeration from feces for 8 days. The use of the IVIS Spectrum CT facilitates seamless co-registration of optical and ?CT scans using a single imaging platform. The low dose ?CT modality enables the imaging of mice at multiple time points during infection, providing detailed anatomical localization of bioluminescent bacterial foci in 3D without causing artifacts from the cumulative radiation. Importantly, the 4D movies of infected mice provide a powerful analytical tool to monitor bacterial colonization dynamics in vivo.
The objective of this study was to quantitatively compare tumor imaging by magnetic resonance imaging (MRI) and molecular bioluminescence imaging (BLI) and test the feasibility of monitoring the effect of MRI-guided laser ablation on tumor viability by 2-dimensional BLI and 3-dimensional diffuse luminescence tomography (3D DLIT) in an orthotopic rat model of hepatocellular carcinoma.
A novel approach is presented for obtaining fast robust three-dimensional (3-D) reconstructions of bioluminescent reporters buried deep inside animal subjects from multispectral images of surface bioluminescent photon densities. The proposed method iteratively acts upon the equations relating the multispectral data to the luminescent distribution with high computational efficiency to provide robust 3-D reconstructions. Unlike existing algebraic reconstruction techniques, the proposed method is designed to use adaptive projections that iteratively guide the updates to the solution with improved speed and robustness. Contrary to least-squares reconstruction methods, the proposed technique does not require parameter selection or optimization for optimal performance. Additionally, optimized schemes for thresholding, sampling, and ordering of the bioluminescence tomographic data used by the proposed method are presented. The performance of the proposed approach in reconstructing the shape, volume, flux, and depth of luminescent inclusions is evaluated in a multitude of phantom-based and dual-modality in vivo studies in which calibrated sources are implanted in animal subjects and imaged in a dual-modality optical/computed tomography platform. Statistical analysis of the errors in the depth and flux of the reconstructed inclusions and the convergence time of the proposed method is used to demonstrate its unbiased performance, low error variance, and computational efficiency.
There is an undisputed need for employment and improvement of robust technology for real-time analyses of therapeutic delivery and responses in clinical translation of gene and cell therapies. Over the past decade, optical imaging has become the in vivo imaging modality of choice for many preclinical laboratories due to its efficiency, practicality and affordability, while more recently, the clinical potential for this technology is becoming apparent. This review provides an update on the current state of the art in in vivo optical imaging and discusses this rapidly improving technology in the context of it representing a translation enabler or indeed a future clinical imaging modality in its own right.
Brown adipose tissue (BAT), a specialized tissue for thermogenesis, plays important roles for metabolism and energy expenditure. Recent studies validated BATs presence in human adults, making it an important re-emerging target for various pathologies. During this validation, PET images with (18)F-FDG showed significant uptake of (18)F-FDG by BAT under certain conditions. Here, we demonstrated that Cerenkov luminescence imaging (CLI) using (18)F-FDG could be utilized for in vivo optical imaging of BAT in mice.
Quite recently Cerenkov luminescence imaging (CLI) has been introduced as a novel pre-clinical imaging for the in vivo imaging of small animals such as mice. The CLI method is based on the detection of Cerenkov radiation (CR) generated by beta particles as they travel into the animal tissues with an energy such that Cerenkov emission condition is satisfied. This paper describes an image reconstruction method called multi spectral diffuse Cerenkov luminescence tomography (msCLT) in order to obtain 3D images from the detection of CR. The multispectral approach is based on a set of 2D planar images acquired using a number of narrow bandpass filters, and the distinctive information content at each wavelength is used in the 3D image reconstruction process. The proposed msCLT method was tested both in vitro and in vivo using 32P-ATP and all the images were acquired by using the IVIS 200 small animal optical imager (Caliper Life Sciences, Alameda USA). Source depth estimation and spatial resolution measurements were performed using a small capillary source placed between several slices of chicken breast. The theoretical Cerenkov emission spectrum and optical properties of chicken breast were used in the modelling of photon propagation. In vivo imaging was performed by injecting control nude mice with 10 MBq of 32P-ATP and the 3D tracer bio-distribution was reconstructed. Whole body MRI was acquired to provide an anatomical localization of the Cerenkov emission. The spatial resolution obtained from the msCLT reconstructed images of the capillary source showed that the FWHM is about 1.5 mm for a 6 mm depth. Co-registered MRI images showed that the Cerenkov emission regions matches fairly well with anatomical regions, such as the brain, heart and abdomen. Ex vivo imaging of the different organs such as intestine, brain, heart and ribs further confirms these findings. We conclude that in vivo 3D bio-distribution of a pure beta-minus emitting radiopharmaceutical such as 32P-ATP can be obtained using the msCLT reconstruction approach.
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