Multimodal Correlative Preclinical Whole Body Imaging and Segmentation.

Segmentation of anatomical structures and particularly abdominal organs is a fundamental problem for quantitative image analysis in preclinical research. This paper presents a novel approach for whole body segmentation of small animals in a multimodal setting of MR, CT and optical imaging. The algorithm integrates multiple imaging sequences into a machine learning framework, which generates supervoxels by an efficient hierarchical agglomerative strategy and utilizes multiple SVM-kNN classifiers each constrained by a heatmap prior region to compose the segmentation.

MR Imaging-derived Oxygen-Hemoglobin Dissociation Curves and Fetal-Placental Oxygen-Hemoglobin Affinities.

Purpose To generate magnetic resonance (MR) imaging-derived, oxygen-hemoglobin dissociation curves and to map fetal-placental oxygen-hemoglobin affinity in pregnant mice noninvasively by combining blood oxygen level-dependent (BOLD) T2* and oxygen-weighted T1 contrast mechanisms under different respiration challenges. Materials and Methods All procedures were approved by the Weizmann Institutional Animal Care and Use Committee. Pregnant mice were analyzed with MR imaging at 9.

Genetic and Pharmacological Modulation of Akt1 for Improving Ovarian Graft Revascularization in a Mouse Model.

Ovarian tissue cryopreservation and transplantation is one of a few available treatments for fertility preservation in women diagnosed with cancer. Rapid revascularization is essential for reducing hypoxic damage after grafting and protecting the primordial follicles reserve. Using a mouse model of heterotopic ovarian graft transplantation, we have delineated the role of endothelial Akt1 expression using longitudinal magnetic resonance imaging follow-up to quantify angiogenic response.

In search of signaling pathways critical for ovarian graft reception: Akt1 is essential for long-term survival of ovarian grafts.

Objective: To explore the role of Akt1, a principle modulator of angiogenesis, in ovarian graft reception and to investigate whether Akt1 deficiency can alter ovarian graft reception.

Design: Experimental mouse model.

Setting: Research institute.

The hemodynamic basis for positional- and inter-fetal dependent effects in dual arterial supply of mouse pregnancies.

In mammalian pregnancy, maternal cardiovascular adaptations must match the requirements of the growing fetus(es), and respond to physiologic and pathologic conditions. Such adaptations are particularly demanding for mammals bearing large-litter pregnancies, with their inherent conflict between the interests of each individual fetus and the welfare of the entire progeny. The mouse is the most common animal model used to study development and genetics, as well as pregnancy-related diseases.

Unique in utero identification of fetuses in multifetal mouse pregnancies by placental bidirectional arterial spin labeling MRI.

Noninvasive imaging is a critical part of the study of developing embryos/fetuses, particularly in the context of alterations of gene expression in genetically modified animals. However, in litter-bearing animals, such as mice, the inability to accurately identify individual embryo/fetus in utero is a major obstacle to longitudinal, noninvasive in vivo studies. Arterial spin labeling MRI was adopted here to determine the fetal order along the uterine horns in vivo, based on the specific pattern of dual arterial blood supply within the mouse uterine horns.

Hypoxic stress and cancer: imaging the axis of evil in tumor metastasis.

Tumors emerge as a result of the sequential acquisition of genetic, epigenetic and somatic alterations promoting cell proliferation and survival. The maintenance and expansion of tumor cells rely on their ability to adapt to changes in their microenvironment, together with the acquisition of the ability to remodel their surroundings. Tumor cells interact with two types of interconnected microenvironments: the metabolic cell autonomous microenvironment and the nonautonomous cellular-molecular microenvironment comprising interactions between tumor cells and the surrounding stroma.

Novel MRI and fluorescent probes responsive to the Factor XIII transglutaminase activity.

Transglutaminases, including factor XIII and tissue transglutaminase, participate in multiple extracellular processes associated with remodeling of the extracellular matrix during wound repair, blood clotting, tumor progression and fibrosis of ischemic injuries. The aim of this work was to evaluate a novel substrate analog for transglutaminase optimized by molecular modeling calculations (DCCP16), which can serve for molecular imaging of transglutaminase activity by magnetic resonance imaging and by near-infrared imaging. Experimental data showed covalent binding of Gd-DCCP16 and DCCP16-IRIS Blue to human clots, to basement membrane components and to casein in purified systems as well as in three-dimensional multicellular spheroids.

Mice with vestibular deficiency display hyperactivity, disorientation, and signs of anxiety.

Previous studies revealed that vestibular cues are crucial for exploration in the absence of visual cues. The working hypothesis of this study was, accordingly, that mice with vestibular dysfunction would become disoriented or unable to globally explore an unfamiliar environment. In 2- and 3-month-old mutant headbanger (Hdb) mice, stereocilia of hair cells are abnormally elongated, yet maintain partial staircase arrangement, suggesting some spared vestibular function at these ages.

Magnetization transfer magic-angle-spinning z-spectroscopy of excised tissues.

NMR experiments devised to aid in analyses of tissues include magnetization transfer (MT), which can highlight the signals of biological macromolecules through cross-relaxation and/or chemical exchange processes with the bulk (1)H water resonance, and high-resolution magic-angle-spinning (HRMAS) methods, akin to those used in solid-state NMR to introduce additional spectral resolution via the averaging of spin anisotropies. This paper explores the result of combining these methodologies, and reports on MT "z-spectroscopy" between water and cell components in excised tissues under a variety of HRMAS conditions. Main features arising from the resulting (1)H "MTMAS" experiments include strong spinning sideband manifolds centered at the liquid water shift, high-resolution isotropic features coinciding with aliphatic and amide proton resonances, and a second sideband manifold arising as spinning speeds are increased.

Exploration and navigation in the blind mole rat (Spalax ehrenbergi): global calibration as a primer of spatial representation.

The aim of this study was to uncover the process of initial spatial mapping of the environment. For this, blind mole rats (Spalax ehrenbergi), were tested in an unfamiliar square arena, in order to reveal how they construct a spatial representation. The mole rats first displayed a build-up phase, in which they gradually formed a path along the perimeter while travelling slowly, frequently pausing and repeating previously travelled segments of the path.

On the border: perimeter patrolling as a transitional exploratory phase in a diurnal rodent, the fat sand rat (Psammomys obesus).

Exploration is an initial phase of constructing spatial representation. In an illuminated environment, exploration by nocturnal rodents takes the form of home-base behavior, with the rodents organizing their activity in relation to the base, repeatedly orienting and returning to it. In the dark, home base behavior in gerbils is preceded by looping exploration, in which travel paths tangle into loops that close at various locations so that the gerbils pilot from one loop to the next.

Exploration in a dark open field: a shift from directional to positional progression and a proposed model of acquiring spatial information.

Exploration in a dark open field undergoes three progressive changes: (i) an initial phase of spending equal amounts of time in various zones of the arena changes to staying in the corners, and ultimately spending most of the time in one corner; (ii) travel paths are first circular and scattered all over the arena, but gradually become anchored to one corner at which they start and end; (iii) traveled distance gradually decreases to that of the initial level seen in a lit open field. Altogether, rodents shift from a 'looping' exploration mechanism with feeble coupling with the environment, to 'home base' exploration which is firmly anchored to the environment. This shift also involves switching from momentary and sporadic to repeated returns to a specific, presumably familiar place, to which the animal navigates back from various other places.

'Looping'-an exploration mechanism in a dark open field.

The behavior of Tristram's jird (a species of gerbil) in an illuminated open field resembled that of other rodents, comprising round trips to a home base and alternating between periods of progression (locomoting) and of stopping. In this study, we compared the characteristics of exploration in a dark arena with exploration by the same individuals in a lit arena. In the dark arena, stopping episodes were brief and fewer, suggesting almost continuous locomotion by the rodents.