Software tools for 3D nuclei segmentation and quantitative analysis in multicellular aggregates.

Today, we are fully immersed into the era of 3D biology. It has been extensively demonstrated that 3D models: (a) better mimic the physiology of human tissues; (b) can effectively replace animal models; (c) often provide more reliable results than 2D ones. Accordingly, anti-cancer drug screenings and toxicology studies based on multicellular 3D biological models, the so-called "-oids" (e.g. spheroids, tumoroids, organoids), are blooming in the literature. However, the complex nature of these systems limit the manual quantitative analyses of single cells' behaviour in the culture. Accordingly, the demand for advanced software tools that are able to perform phenotypic analysis is fundamental. In this work, we describe the freely accessible tools that are currently available for biologists and researchers interested in analysing the effects of drugs/treatments on 3D multicellular -oids at a single-cell resolution level. In addition, using publicly available nuclear stained datasets we quantitatively compare the segmentation performance of 9 specific tools.

3D-Cell-Annotator: an open-source active surface tool for single-cell segmentation in 3D microscopy images.

SUMMARY: Segmentation of single cells in microscopy images is one of the major challenges in computational biology. It is the first step of most bioimage analysis tasks, and essential to create training sets for more advanced deep learning approaches. Here, we propose 3D-Cell-Annotator to solve this task using 3D active surfaces together with shape descriptors as prior information in a semi-automated fashion. The software uses the convenient 3D interface of the widely used Medical Imaging Interaction Toolkit (MITK). Results on 3D biological structures (e.g. spheroids, organoids and embryos) show that the precision of the segmentation reaches the level of a human expert. AVAILABILITY AND IMPLEMENTATION: 3D-Cell-Annotator is implemented in CUDA/C++ as a patch for the segmentation module of MITK. The 3D-Cell-Annotator enabled MITK distribution can be downloaded at: www.3D-cell-annotator.org. It works under Windows 64-bit systems and recent Linux distributions even on a consumer level laptop with a CUDA-enabled video card using recent NVIDIA drivers. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

A rare case of primary rectal adenocarcinoma metastatic to the breast.

Primary rectal adenocarcinoma metastatic to the breast is an exceedingly rare event. Its management differs from that of primary breast cancer, as illustrated by this case. A 63-year-old woman presented with a breast lump 30 months after abdominoperineal resection for rectal adenocarcinoma, stage T3N1M0 (stage III), followed by standard postoperative radiochemotherapy. The patient underwent a mammography and ultrasonography. A CT scan of the abdomen showed metastatic disease. An excisional biopsy of the breast lump was performed; morphological features were identical to the original rectal cancer. Immunohistochemical results were negative for estrogen and progesterone receptors and gross cystic disease fluid protein-15, and intensity positive for cytokeratin 20 and carcinoembryonic antigen. The patient died after treatment with palliative chemotherapy. Metastatic disease from rectal carcinoma to the breast is a marker for disseminated metastatic spread with poor prognosis.

Platelet activation by sustained exposure to low-dose plasmin.

Plasmin has been reported to activate and inhibit platelet function depending on dose and exposure temperature. The present study examines the induction of fibrinogen-dependent platelet aggregation following prolonged (60 min) platelet exposure to very low doses of plasmin (0.05 CU/ml) at either 22 or 37 degrees C. Maximum aggregation [mean +/- SD, 60 +/- 19 light transmission units (LTU); n = 43] occurred following platelet exposure to plasmin at 22 degrees C, but significant platelet aggregation (28 +/- 4 LTU, n = 3) also occurred following plasmin treatment at 37 degrees C. Plasmin-induced platelet aggregates appeared microscopically larger than aggregates of adenosine diphosphate (ADP)-activated platelets, and were less reversible. Aggregated plasmin-treated platelets also expressed more procoagulant activity than platelets aggregated with ADP, as reflected by shortening of the plasma kaolin recalcification time. Aggregation of platelets exposed to very low doses of plasmin was not accompanied by dense or alpha-granule secretion, and was unaffected by ADP antagonists or aspirin. Partial inhibition of platelet aggregation, however, was achieved with metabolic inhibitors, PGE1, and inhibitors of phosphoinositide 3-kinase or protein kinase C. Although fibrinogen was required for plasmin-treated platelet aggregation, [125I]-fibrinogen binding comprised only 58 +/- 3% (n = 3) of fibrinogen binding associated with ADP aggregated platelets. This was consistent with observed decreases in reptilase-induced fibrin clot retraction. Taken together, these data suggest that sustained exposure of platelets to very low plasmin doses leads to platelet activation and thus may contribute to thrombotic complications in vivo.

The effect of relative spectacle magnification on aniseikonia.

PURPOSE: The purpose of this article is to study the effects of modifying relative spectacle magnification to determine what effect this has on aniseikonia, binocularity, and visual comfort. METHODS: A prospective analysis of 34 aniseikonic patients was undertaken. The etiology of aniseikonia varied from physiologically occurring to induced. Aniseikonic screening included manifest refraction, keratometry, axial length, Randot stereoacuity, associated phoria, and Keystone space eikonometry. A modified pair of spectacles was fabricated on the basis of magnification principles for iseikonic lenses. Each patient was also given a control pair of conventional spectacles. A 4-week trial period was allowed for each pair of spectacles, pertinent examination measurements were repeated, and a patient survey was administered. Data were analyzed by t-test and chi-square. RESULTS: Modifying relative spectacle magnification reduced mean aniseikonic error by 1.06% (P < 0.0001). A difference was found between the control and modified spectacles for subjective reports of visual comfort, performance, and eye-strain (P < 0.05). There was no difference between the two groups for stereoacuity or cosmetic appearance of lenses. At the conclusion of the study, 93% of patients preferred the modified lenses in direct comparison. CONCLUSIONS: Our results confirm that modification of lens designs to equalize relative spectacle magnification reduces aniseikonia and improves subjective comfort and performance of anisometropic spectacles.

Development of a fiber-optic sensor for trace metal detection in aqueous environments.

The availability and speciation of a number of metals widely dispersed in the aquatic environment intimately affect the biogeochemistry of the ocean and its inhabitants. Much research has been focused on the development of analytical methodologies to elucidate better the background concentrations, variability, and contaminant effects of metal species. The purpose of this research is to investigate the viability of a fiber-optic sensor that will be a sensitive and selective probe for trace metals in natural waters.

Imaging with rotating slit apertures and rotating collimators.

The statistical quality of conventional nuclear medical imagery is limited by the small signal collected through low-efficiency conventional apertures. Coded-aperture imaging overcomes this by employing a two-step process in which the object is first efficiently detected as an "encoded" form which does not resemble the object, and then filtered (or "decoded") to form an image. We present here the imaging properties of a class of time-modulated coded apertures which, unlike most coded apertures, encode projections of the object rather than the object itself. These coded apertures can reconstruct a volume object nontomographically, tomographically (one plane focused), or three-dimensionally. We describe a new decoding algorithm that reconstructs the object from its planar projections. Results of noise calculations are given, and the noise performance of these coded-aperture systems is compared to that of conventional counterparts. A hybrid slit-pinhole system which combines the imaging advantages of a rotating slit and a pinhole is described. A new scintillation detector which accurately measures the position of an event in one dimension only is presented, and its use in our coded-aperture system is outlined. Finally, results of imaging test objects and animals are given.

Diferenciacion entre los virus de la fiebre aftosa y de la estomatitis vesicular por medio de la inoculacion de ratones

American Journal of Veterinary Research (English)