Cone Beam Micro-CT System for Small Animal Imaging and Performance Evaluation

A prototype cone-beam micro-CT system for small animal imaging has been developed by our group recently, which consists of a microfocus X-ray source, a three-dimensional programmable stage with object holder, and a flat-panel X-ray detector. It has a large field of view (FOV), which can acquire the whole body imaging of a normal-size mouse in a single scan which usually takes about several minutes or tens of minutes. FDK method is adopted for 3D reconstruction with Graphics Processing Unit (GPU) acceleration. In order to reconstruct images with high spatial resolution and low artifacts, raw data preprocessing and geometry calibration are implemented before reconstruction. A method which utilizes a wire phantom to estimate the residual horizontal offset of the detector is proposed, and 1D point spread function is used to assess the performance of geometric calibration quantitatively. System spatial resolution, image uniformity and noise, and low contrast resolution have been studied. Mouse images with and without contrast agent are illuminated in this paper. Experimental results show that the system is suitable for small animal imaging and is adequate to provide high-resolution anatomic information for bioluminescence tomography to build a dual modality system

In-vivo Optical Tomography of Small Scattering Specimens: time-lapse 3D imaging of the head eversion process in Drosophila melanogaster

5 fig.Even though in vivo imaging approaches have witnessed several new and important developments, specimens that exhibit high light scattering properties such as Drosophila melanogaster pupae are still not easily accessible with current optical imaging techniques, obtaining images only from subsurface features. This means that in order to obtain 3D volumetric information these specimens need to be studied either after fixation and a chemical clearing process, through an imaging window - thus perturbing physiological development -, or during early stages of development when the scattering contribution is negligible. In this paper we showcase how Optical Projection Tomography may be used to obtain volumetric images of the head eversion process in vivo in Drosophila melanogaster pupae, both in control and headless mutant specimens. Additionally, we demonstrate the use of Helical Optical Projection Tomography (hOPT) as a tool for high throughput 4D-imaging of several specimens simultaneously.This work was supported in part by Project ‘‘THALES – BSRC ‘Alexander Fleming’ – Development and employment of Minos-based genetic and functional genomic technologies in model organisms (MINOS)’’ – MIS: 376898, the Fellowship for Young International Scientist of the Chinese Academy of Sciences Grant No. 2010Y2GA03 and the NSFC-NIH Biomedical collaborative research program 81261120414. A. Arranz acknowledges support from Marie Curie Intra-European Fellowship Program FP7-PEOPLE-2010-IEF. J. Ripoll acknowledges support from EC FP7 CIG grant HIGH-THROUGHPUT TOMO, and Spanish MINECO grant MESO-IMAGING FIS2013-41802-R. The authors would like to thank Dr. S. Oehler for the help with the GFP-expressing flies, and G. Livadaras and G. Zacharakis for help with the Drosophila stocks

Helical Optical Projection Tomography

A new technique termed Helical Optical Projection Tomography (hOPT) has been developed with the aim to overcome some of the limitations of current 3D optical imaging techniques. hOPT is based on Optical Projection Tomography (OPT) with the major difference that there is a translation of the sample in the vertical direction during the image acquisition process, requiring a new approach to image reconstruction. Contrary to OPT, hOPT makes possible to obtain 3D-optical images of intact long samples without imposing limits on the sample length. This has been tested using hOPT to image long murine tissue samples such as spinal cords and large intestines. Moreover, 3D-reconstructed images of the colon of DSS-treated mice, a model for Inflammatory Bowel Disease, allowed the identification of the structural alterations. Finally, the geometry of the hOPT device facilitates the addition of a Selective Plane Illumination Microscopy (SPIM) arm, providing the possibility of delivering high resolution images of selected areas together with complete volumetric informationThis work was partially supported by EC FP7 collaborative grant FMT-XCT and the Bill and Melinda Gates foundation. A.A. wishes to acknowledge support from Marie Curie IEF-2010-275137. J.R. wishes to acknowledge support from EC FP7 IMI project PREDICT-TB, and the EC FP7 CIG grant HIGH-THROUGHPUT TOMO. D.D., S.Z. and J.T. acknowledge support from the National Basic Research Program of China (973 Program) under Grant 2011CB707700, the Fellowship for Young International Scientists of the Chinese Academy of Sciences under Grant 2010Y2GA03, the National Natural Science Foundation of China under Grant 81101084 and Instrument Developing Project of the Chinese Academy of Sciences under Grant No. YZ201164Publicad

Automated identification and quantification of myocardial inflammatory infiltration in digital histological images to diagnose myocarditis

This study aims to develop a new computational pathology approach that automates the identification and quantification of myocardial inflammatory infiltration in digital HE-stained images to provide a quantitative histological diagnosis of myocarditis.898 HE-stained whole slide images (WSIs) of myocardium from 154 heart transplant patients diagnosed with myocarditis or dilated cardiomyopathy (DCM) were included in this study. An automated DL-based computational pathology approach was developed to identify nuclei and detect myocardial inflammatory infiltration, enabling the quantification of the lymphocyte nuclear density (LND) on myocardial WSIs. A cutoff value based on the quantification of LND was proposed to determine if the myocardial inflammatory infiltration was present. The performance of our approach was evaluated with a five-fold cross-validation experiment, tested with an internal test set from the myocarditis group, and confirmed by an external test from a double-blind trial group. An LND of 1.02/mm2 could distinguish WSIs with myocarditis from those without. The accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) in the five-fold cross-validation experiment were 0.899 plus or minus 0.035, 0.971 plus or minus 0.017, 0.728 plus or minus 0.073 and 0.849 plus or minus 0.044, respectively. For the internal test set, the accuracy, sensitivity, specificity, and AUC were 0.887, 0.971, 0.737, and 0.854, respectively. The accuracy, sensitivity, specificity, and AUC for the external test set reached 0.853, 0.846, 0.858, and 0.852, respectively. Our new approach provides accurate and reliable quantification of the LND of myocardial WSIs, facilitating automated quantitative diagnosis of myocarditis with HE-stained images.Comment: 21 pages,5 figures,6 Tables, 25 reference

Vertically scanned laser sheet microscopy

Laser sheet microscopy is a widely used imaging technique for imaging the three-dimensional distribution of a fluorescence signal in fixed tissue or small organisms. In laser sheet microscopy, the stripe artifacts caused by high absorption or high scattering structures are very common, greatly affecting image quality. To solve this problem, we report here a two-step procedure which consists of continuously acquiring laser sheet images while vertically displacing the sample, and then using the variational stationary noise remover (VSNR) method to further reduce the remaining stripes. Images from a cleared murine colon acquired with a vertical scan are compared with common stitching procedures demonstrating that vertically scanned light sheet microscopy greatly improves the performance of current light sheet microscopy approaches without the need for complex changes to the imaging setup and allows imaging of elongated samples, extending the field of view in the vertical direction.This work was supported in part by the Bill and Melinda Gates Foundation, the National Basic Research Program of China (973 Program) under Grant No. 2011CB707700, the National Natural Science Foundation of China under Grant No. 81227901, 81027002, 61231004, and 81101095, the Fellowship for Young International Scientists of the Chinese Academy of Sciences under Grant No. 2010Y2GA03, and the Instrument Developing Project of the Chinese Academy of Sciences under Grant No. YZ201164. A. Arranz acknowledges support from the Marie Curie Intra-European Fellowship program IEF-2010-275137. J.R. acknowledges support from EC FP7 IMI project PREDICT-TB, the EC FP7 CIG grant HIGHTHROUGHPUT TOMO, and the Spanish MINECO project grant FIS2013-41802-R MESO-IMAGING

The Antimicrobial Peptide Mastoparan X Protects Against Enterohemorrhagic Escherichia coli O157:H7 Infection, Inhibits Inflammation, and Enhances the Intestinal Epithelial Barrier

Escherichia coli can cause intestinal diseases in humans and livestock, destroy the intestinal barrier, exacerbate systemic inflammation, and seriously threaten human health and animal husbandry development. The aim of this study was to investigate whether the antimicrobial peptide mastoparan X (MPX) was effective against E. coli infection. BALB/c mice infected with E. coli by intraperitoneal injection, which represents a sepsis model. In this study, MPX exhibited no toxicity in IPEC-J2 cells and notably suppressed the levels of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), myeloperoxidase (MPO), and lactate dehydrogenase (LDH) released by E. coli. In addition, MPX improved the expression of ZO-1, occludin, and claudin and enhanced the wound healing of IPEC-J2 cells. The therapeutic effect of MPX was evaluated in a murine model, revealing that it protected mice from lethal E. coli infection. Furthermore, MPX increased the length of villi and reduced the infiltration of inflammatory cells into the jejunum. SEM and TEM analyses showed that MPX effectively ameliorated the jejunum damage caused by E. coli and increased the number and length of microvilli. In addition, MPX decreased the expression of IL-2, IL-6, TNF-α, p-p38, and p-p65 in the jejunum and colon. Moreover, MPX increased the expression of ZO-1, occludin, and MUC2 in the jejunum and colon, improved the function of the intestinal barrier, and promoted the absorption of nutrients. This study suggests that MPX is an effective therapeutic agent for E. coli infection and other intestinal diseases, laying the foundation for the development of new drugs for bacterial infections

Reconstruction of fluorescence molecular tomography with a cosinoidal level set method

Abstract Background Implicit shape-based reconstruction method in fluorescence molecular tomography (FMT) is capable of achieving higher image clarity than image-based reconstruction method. However, the implicit shape method suffers from a low convergence speed and performs unstably due to the utilization of gradient-based optimization methods. Moreover, the implicit shape method requires priori information about the number of targets. Methods A shape-based reconstruction scheme of FMT with a cosinoidal level set method is proposed in this paper. The Heaviside function in the classical implicit shape method is replaced with a cosine function, and then the reconstruction can be accomplished with the Levenberg–Marquardt method rather than gradient-based methods. As a result, the priori information about the number of targets is not required anymore and the choice of step length is avoided. Results Numerical simulations and phantom experiments were carried out to validate the proposed method. Results of the proposed method show higher contrast to noise ratios and Pearson correlations than the implicit shape method and image-based reconstruction method. Moreover, the number of iterations required in the proposed method is much less than the implicit shape method. Conclusions The proposed method performs more stably, provides a faster convergence speed than the implicit shape method, and achieves higher image clarity than the image-based reconstruction method

Image Restoration for Fluorescence Planar Imaging with Diffusion Model

Fluorescence planar imaging (FPI) is failure to capture high resolution images of deep fluorochromes due to photon diffusion. This paper presents an image restoration method to deal with this kind of blurring. The scheme of this method is conceived based on a reconstruction method in fluorescence molecular tomography (FMT) with diffusion model. A new unknown parameter is defined through introducing the first mean value theorem for definite integrals. System matrix converting this unknown parameter to the blurry image is constructed with the elements of depth conversion matrices related to a chosen plane named focal plane. Results of phantom and mouse experiments show that the proposed method is capable of reducing the blurring of FPI image caused by photon diffusion when the depth of focal plane is chosen within a proper interval around the true depth of fluorochrome. This method will be helpful to the estimation of the size of deep fluorochrome

The effect of periodic resistance training on obese patients with type 2 diabetic nephropathy

Abstract Resistance training is an exercise against resistance designed to train the endurance and strength of muscle. To observe the effect of intervention of periodic resistance training on obese patients with type 2 diabetic nephropathy. A total of 60 obese patients with type 2 diabetic nephropathy were randomized into resistance training group and aerobic exercise group (30 patients each group) for observing the changes of blood glucose, body weight, blood lipid, insulin resistance, serum creatinine (Scr), urinary microalbumin, urinary albumin excretion rate (UAER) calculated by urinary creatinine, and glomerular filtration rate (GFR) after 12 weeks of intervention, and relevant significance as well. The number of patients with hypoglycemia during the intervention was also recorded. After 12 weeks of intervention, the weight, Body mass index (BMI), Waist, Triglyceride (TG), Cholesterol (TC), Low-density lipoprotein cholesterol (LDL), Fasting glucose (FBG), Fasting insulin (FINS), Glycosylated hemoglobin (HbA1c) and urine Albumin–Creatinine Ratio (uACR) were decreased and GFR was increased in both groups (P  0.05). Periodic resistance training can not only control the weight, blood sugar and blood lipid of obese patients with type 2 diabetic nephropathy, but also improve the urinary albumin excretion rate and glomerular filtration rate of early obese patients with type 2 diabetic nephropathy, and delay the progression of diabetic nephropathy. It is an effective non-drug intervention