Bio-imaging

T2-family acidic endoribonucleases are represented in all genomes. A physiological role for RNase T2 has yet to be defined for metazoa. RNASET2 mutation in humans is linked with a leukoencephalopathy that arises in infancy characterized by cortical cysts and multifocal white matter lesions. We now show localization of RNASET2 within lysosomes. Further, we demonstrate that loss of rnaset2 in mutant zebrafish results in accumulation of undigested rRNA within lysosomes within neurons of the brain. Further, by using high field intensity magnetic resonance microimaging, we reveal white matter lesions in these animals comparable to those observed in RNASET2deficient infants. This correlates with accumulation of Amyloid precursor protein and astrocytes at sites of neurodegeneration. Thus we conclude that familial cystic leukoencephalopathy is a lysosomal storage disorder in which rRNA is the best candidate for the noxious storage material.

Non-invasive measures of well-known pathological hallmarks of multiple sclerosis (MS) such as demyelination, inflammation and axonal injury would serve as useful markers to monitor disease progression and evaluate potential therapies. To this end, in vivo localized proton magnetic resonance spectroscopy ((1)H-MRS) provides a powerful means to monitor metabolic changes in the brain and may be sensitive to these pathological hallmarks. In our study, we used the cuprizone mouse model to study pathological features of MS, such as inflammation, de- and remyelination, in a highly reproducible manner. C57BL/6J mice were challenged with a 0.2% cuprizone diet for 6-weeks to induce demyelination, thereafter mice were put on a cuprizone free diet for another 6 weeks to induce spontaneous remyelination. We employed in vivo(1)H-MRS to longitudinally monitor metabolic changes in the corpus callosum of cuprizone-fed mice during the demyelination (week 4 and 6) and spontaneous remyelination (week 1...

Alzheimer's disease (AD) is the most common form of dementia in the elderly with no effective treatment or definitive antemortem diagnostic test. The neuropathologic features of AD include the occurrence of amyloid β (Aβ) containing plaques, neurofibrillary tangles, decreased synaptic density, and loss of neurons. In AD, the deposition of Aβ peptide in the cerebral vessel walls, known as cerebral amyloid angiopathy (CAA) is frequently observed, leading to blood flow abnormalities. However, its contribution to the onset and progression of dementia is unknown. The evidence for blood flow disturbance during AD comes mainly from postmortem studies. Direct non-invasive in vivo methods to probe blood flow disturbance during AD are highly challenging. A previous study [1] has shown that magnetic resonance angiography (MRA) is a useful method to identify changes of vascular function in APP23 mice model of AD. In this study we optimized high resolution MRA at 9.4T in combination with strong gradients to monitor morphological changes in cerebral arteries in APP Tg2576 transgenic mice which is one of the most widely used mouse model of AD. Our preliminary data showed significant morphological changes in large and medium sized arteries in APP Tg2576 mice.

The enzyme, β -galactosidase (E.C.3.2.1.23) has been used for dairy industry for removing lactose from milk and milk by-products. In this study, three strains namely L. plantarum NCIMB 1193, L. plantarum DSM 20246 and L. plantarum E081 were used for β -galactosidase release by sonication method. The peak of the total enzyme activity was found to be corresponding to late logarithmic or early stationary phase of all strains. As a disruption method sonication was used for the release of β -galactosidase. Meanwhile, the sonication time was optimized for each strain. The peak of the enzyme activity was observed between 210 seconds and 270 seconds of sonication period. It was also found that sonication did not decrease the viability of L.plantarum NCIMB 1193 significantly. Liquid nitrogen cell disruption method was also used to compare the results with those obtained by sonication method. For characterization β -galactosidase, cell-free crude extract of sonicated cell culture of L.plantan...

Resting-state functional MRI (rsfMRI) is a widely implemented technique used to investigate large-scale topology in the human brain during health and disease. Studies in mice provide additional advantages, including the possibility to flexibly modulate the brain by pharmacological or genetic manipulations in combination with high-throughput functional connectivity (FC) investigations. Pharmacological modulations that target specific neurotransmitter systems, partly mimicking the effect of pathological events, could allow discriminating the effect of specific systems on functional network disruptions. The current study investigated the effect of cholinergic and serotonergic antagonists on large-scale brain networks in mice. The cholinergic system is involved in cognitive functions and is impaired in, e.g., Alzheimer's disease, while the serotonergic system is involved in emotional and introspective functions and is impaired in, e.g., Alzheimer's disease, depression and autism...

Detrimental inflammatory responses in the central nervous system are a hallmark of various brain injuries and diseases. With this study we provide evidence that lentiviral vector-mediated expression of the immune-modulating cytokine interleukin 13 (IL-13) induces an alternative activation program in both microglia and macrophages conferring protection against severe oligodendrocyte loss and demyelination in the cuprizone mouse model for multiple sclerosis (MS). First, IL-13 mediated modulation of cuprizone induced lesions was monitored using T2 -weighted magnetic resonance imaging and magnetization transfer imaging, and further correlated with quantitative histological analyses for inflammatory cell influx, oligodendrocyte death, and demyelination. Second, following IL-13 immune gene therapy in cuprizone-treated eGFP(+) bone marrow chimeric mice, we provide evidence that IL-13 directs the polarization of both brain-resident microglia and infiltrating macrophages towards an alternati...

Glutamate is the principal excitatory neurotransmitter in the brain and is at the base of a wide variety of neuropathologies, including epilepsy, autism, Fragile X, and obsessive compulsive disorder. Glutamate has also become the target for novel drugs in treatment and in fundamental research settings. However, much remains unknown on the working mechanisms of these drugs and the effects of chronic administration on the glutamatergic system. This study investigated the chronic effects of two glutamate-modulating drugs with imaging techniques to further clarify their working mechanisms for future research opportunities. Animals were exposed to saline (1 ml/kg), (5S,10R)-(1)-5-Methyl-10,11-dihydro-5H-dibenzo [a,d]cyclohepten-5,10-imine (MK-801) (0.3 mg/kg), or ebselen (10 mg/kg) for 7 consecutive days. At the sixth injection, animals underwent a positron emission tomography (PET)/ computed tomography (CT) with (3-(6-methyl-pyridin-2ylethynyl)-cyclohex-2-enone-O-11C-methyl-oxime) (ABP-688) to visualize the metabotropic G protein-coupled glutamate receptor 5 (mGluR5). After the seventh injection, animals underwent a magnetic resonance spectroscopy (MRS) scan to visualize glutamate and glutamine content. Afterward, results were verified by mGluR5 immunohistochemistry (IHC). PET/CT analysis revealed that animals receiving chronic MK-801 or ebselen had a significant (P , 0.05) higher binding potential (2.90 6 0.47 and 2.87 6 0.46, respectively) when compared with saline (1.97 6 0.39) in the caudate putamen. This was confirmed by mGluR5 IHC, with 60.83% 6 6.30% of the area being highlighted for ebselen and 57.14% 6 9.23% for MK-801 versus 50.21% 6 5.71% for the saline group. MRS displayed significant changes on the glutamine level when comparing chronic ebselen (2.20 6 0.40 mmol/g) to control (2.72 6 0.34 mmol/g). Therefore, although no direct effects on glutamate were visualized, the changes in glutamine suggest changes in the total glutamate-glutamine pool. This highlights the potential of both drugs to modulate glutamatergic pathologies.

BackgroundThe critical‐period theory of menopausal hormone therapy (mHT) suggests that if menopausal hormone therapy begins shortly after menopause, it may have beneficial effects on brain structure and cognitive health. We investigated white matter integrity with diffusion tensor MRI (DTI) 3 years after the end of mHT trial in recently menopausal women who were randomized shortly after menopause.MethodParticipants of this study were enrolled in the Kronos Early Estrogen Prevention Study (aged 42–56 years; 5–36 months past menopause). Participants received the following treatments: 0.45 mg/d oral conjugated equine estrogen (oCEE, n=19); 50 μg/d transdermal 17β‐estradiol (tE2, n=22); or placebo (n=33) for 4 years. Oral progesterone (200 mg/d) was given to hormone therapy groups for 12 days each month. DTI was performed 3 years after the end of 4 years of hormone therapy (n=75), which corresponded to 7 years after randomization. Voxel‐based analysis was performed on DTI to evaluate fr...

While aging remains one of the most significant risk factors for development of Alzheimer disease (AD), increasing evidence strongly points to the potential roles of cerebrovascular and white matter abnormalities in the disease development. A better understanding of the manner in which these abnormalities contribute to disease progression can be achieved by in vivo characterization of AD related pathologies. To this end, MR based techniques serve as effective non-invasive tools to longitudinally monitor changes in AD brain. In this thesis, a variety of MR based techniques were optimized and employed to longitudinally monitor the AD progression in transgenic mouse models of the disease at 9.4T and 17.6T. In Chapter 2, age-dependent blood flow alterations were examined in a Tg2576 mouse model of Alzheimer's disease using MR angiography at 17.6T. AD is linked to abnormalities in the vascular system. In Chapter 3, in vivo T2 changes were longitudinally monitored in the corpus callos...

Glutamate is the principal excitatory neurotransmitter in the brain and is at the base of a wide variety of neuropathologies, including epilepsy, autism, Fragile X, and obsessive compulsive disorder. Glutamate has also become the target for novel drugs in treatment and in fundamental research settings. However, much remains unknown on the working mechanisms of these drugs and the effects of chronic administration on the glutamatergic system. This study investigated the chronic effects of two glutamate-modulating drugs with imaging techniques to further clarify their working mechanisms for future research opportunities. Animals were exposed to saline (1 ml/kg), (5S,10R)-(1)-5-Methyl-10,11-dihydro-5H-dibenzo [a,d]cyclohepten-5,10-imine (MK-801) (0.3 mg/kg), or ebselen (10 mg/kg) for 7 consecutive days. At the sixth injection, animals underwent a positron emission tomography (PET)/ computed tomography (CT) with (3-(6-methyl-pyridin-2ylethynyl)-cyclohex-2-enone-O-11C-methyl-oxime) (ABP-688) to visualize the metabotropic G protein-coupled glutamate receptor 5 (mGluR5). After the seventh injection, animals underwent a magnetic resonance spectroscopy (MRS) scan to visualize glutamate and glutamine content. Afterward, results were verified by mGluR5 immunohistochemistry (IHC). PET/CT analysis revealed that animals receiving chronic MK-801 or ebselen had a significant (P , 0.05) higher binding potential (2.90 6 0.47 and 2.87 6 0.46, respectively) when compared with saline (1.97 6 0.39) in the caudate putamen. This was confirmed by mGluR5 IHC, with 60.83% 6 6.30% of the area being highlighted for ebselen and 57.14% 6 9.23% for MK-801 versus 50.21% 6 5.71% for the saline group. MRS displayed significant changes on the glutamine level when comparing chronic ebselen (2.20 6 0.40 mmol/g) to control (2.72 6 0.34 mmol/g). Therefore, although no direct effects on glutamate were visualized, the changes in glutamine suggest changes in the total glutamate-glutamine pool. This highlights the potential of both drugs to modulate glutamatergic pathologies.

The benefit of small animal imaging is directly linked to the validity and reliability of the collected data. If the data (regardless of the modality used) are not reproducible and/or reliable, then the outcome of the data is rather questionable. Therefore, standardization of the use of small animal imaging equipment, as well as of animal handling in general, is of paramount importance. In a recent paper, guidance for efficient small animal imaging quality control was offered and discussed, among others, the use of phantoms in setting up a quality control program (Osborne et al. 2016). The same phantoms can be used to standardize image quality parameters for multicenter studies or multi-scanners within center studies. In animal experiments, the additional complexity due to animal handling needs to be addressed to ensure standardized imaging procedures. In this review, we will address the current status of standardization in preclinical imaging, as well as potential benefits from increased levels of standardization.

Non-rigid 3D shape retrieval has become an important research topic in content-based 3D object retrieval. The aim of this track is to measure and compare the performance of non-rigid 3D shape retrieval methods implemented by different participants around the world. The track is based on a new non-rigid 3D shape benchmark, which contains 600 watertight triangle meshes that are equally classified into 30 categories. In this track, 25 runs have been submitted by 9 groups and their retrieval accuracies were evaluated using 6 commonly-utilized measures.

In this paper a specific method is presented to facilitate the semi-automatic segmentation of liver metastases in CT images. Accurate and reliable segmentation of tumors is e.g. essential for the follow-up of cancer treatment. The core of the algorithm is a level set function. The initialization is provided by a spiral-scanning technique based on dynamic programming. The level set evolves according to a speed image that is the result of a statistical pixel classification algorithm with supervised learning. This method is tested on CT images of the abdomen and compared with manual delineations of liver tumors. The results show that the accuracy of the method does not reach that of the manual segmentation. The average overlap error is 34.6% and the average volume difference is 17.8%. The average, the rms and the maximum surface are respectively 2.0, 2.7 and 10.1 mm.

Intra-patient registration of lung CT scans acquired at a different time points or inspiration levels is a valuable examination tool to study multiple lung images. It allows to study ventilation or other functional information of the lungs. In this paper, two 3D lung registration methods are presented. The first method, splineMIRIT, uses voxel based non rigid image registration. It is based on mutual information as similarity measure, a B-spline mesh to model the deformation and B-spline image interpolation. The second method, Robust Tree Registration (RTR), extends the first by including robust 3D registration of the vessel trees found in both images. The tree is represented by intrinsic matrices containing the geodesic or Euclidean distance between each pair of detected bifurcations. This representation is independent of the reference frame. Marginalization of point pair probabilities based on the intrinsic matrices provides soft assign correspondences between the two trees. This global correspondence model is combined with local bifurcation similarity models, based on the local gray value distribution. Finally, hard correspondences are deducted from the model. The correspondences between bifurcations are added to splineMIRIT as an additional similarity measure. The method is validated on the EMPIRE10 data set. Both algorithms perform well. Comparing splineMIRIT and RTR shows that on average the results slightly improve when the robust tree registration is added, leading to a 15 th and 13 th place, respectively, in the "Grand Challenges in Medical Image Analysis" workshop of MICCAI 2010.

In this article, we present a new 3D non-rigid surface registration algorithm for unstructured point clouds. The algorithm has very low data requirements and can easily be adapted to use additional information other than vertex positions such as texture information or prior knowledge about local deformations. It is robust to noise, outliers and to some extent to missing data. The mathematical theory is based on probability density estimation. Furthermore, we use the mean shift formula for fast computation. The algorithm is able to use different regularisation models for the deformation. Quantitative and qualitative experiments are conducted on artificial surfaces and on real 3D face data.

This document gives a short overview of 3D face recognition methods invariant for expression variations and describes in more detail a method using point cloud kernel correlation. This method is also evaluated using 2 frequently used databases.

Matching 3D faces for recognition is a challenging task caused by the presence of expression variations, missing data, and outliers. In this paper the meshSIFT algorithm and its use for 3D face recognition is presented. This algorithm consists of four major components. First, salient points on the 3D facial surface are detected as mean curvature extrema in scale space. Second, orientations are assigned to each of these salient points. Third, the neighbourhood of each salient point is described in a feature vector consisting of concatenated histograms of shape indices and slant angles. Fourth, the feature vectors of two 3D facial surfaces are reliably matched by comparing the angles in feature space. This results in an algorithm which is robust to expression variations, missing data and outliers.