Enhanced virtual microscopy for collaborative education

<p>Abstract</p> <p>Background</p> <p>Curricular reform efforts and a desire to use novel educational strategies that foster student collaboration are challenging the traditional microscope-based teaching of histology. Computer-based histology teaching tools and Virtual Microscopes (VM), computer-based digital slide viewers, have been shown to be effective and efficient educational strategies. We developed an open-source VM system based on the Google Maps engine to transform our histology education and introduce new teaching methods. This VM allows students and faculty to collaboratively create content, annotate slides with markers, and it is enhanced with social networking features to give the community of learners more control over the system.</p> <p>Results</p> <p>We currently have 1,037 slides in our VM system comprised of 39,386,941 individual JPEG files that take up 349 gigabytes of server storage space. Of those slides 682 are for general teaching and available to our students and the public; the remaining 355 slides are used for practical exams and have restricted access. The system has seen extensive use with 289,352 unique slide views to date. Students viewed an average of 56.3 slides per month during the histology course and accessed the system at all hours of the day. Of the 621 annotations added to 126 slides 26.2% were added by faculty and 73.8% by students. The use of the VM system reduced the amount of time faculty spent administering the course by 210 hours, but did not reduce the number of laboratory sessions or the number of required faculty. Laboratory sessions were reduced from three hours to two hours each due to the efficiencies in the workflow of the VM system.</p> <p>Conclusions</p> <p>Our virtual microscope system has been an effective solution to the challenges facing traditional histopathology laboratories and the novel needs of our revised curriculum. The web-based system allowed us to empower learners to have greater control over their content, as well as the ability to work together in collaborative groups. The VM system saved faculty time and there was no significant difference in student performance on an identical practical exam before and after its adoption. We have made the source code of our VM freely available and encourage use of the publically available slides on our website.</p

Extended Field Laser Confocal Microscopy (EFLCM): Combining automated Gigapixel image capture with in silico virtual microscopy

<p>Abstract</p> <p>Background</p> <p>Confocal laser scanning microscopy has revolutionized cell biology. However, the technique has major limitations in speed and sensitivity due to the fact that a single laser beam scans the sample, allowing only a few microseconds signal collection for each pixel. This limitation has been overcome by the introduction of parallel beam illumination techniques in combination with cold CCD camera based image capture.</p> <p>Methods</p> <p>Using the combination of microlens enhanced Nipkow spinning disc confocal illumination together with fully automated image capture and large scale <it>in silico </it>image processing we have developed a system allowing the acquisition, presentation and analysis of maximum resolution confocal panorama images of several Gigapixel size. We call the method Extended Field Laser Confocal Microscopy (EFLCM).</p> <p>Results</p> <p>We show using the EFLCM technique that it is possible to create a continuous confocal multi-colour mosaic from thousands of individually captured images. EFLCM can digitize and analyze histological slides, sections of entire rodent organ and full size embryos. It can also record hundreds of thousands cultured cells at multiple wavelength in single event or time-lapse fashion on fixed slides, in live cell imaging chambers or microtiter plates.</p> <p>Conclusion</p> <p>The observer independent image capture of EFLCM allows quantitative measurements of fluorescence intensities and morphological parameters on a large number of cells. EFLCM therefore bridges the gap between the mainly illustrative fluorescence microscopy and purely quantitative flow cytometry. EFLCM can also be used as high content analysis (HCA) instrument for automated screening processes.</p

A Web-Based Solution for Viewing Large-Sized Microscopic Images

This paper demonstrates a pure web-based solution enabling the presentation of scanned pathologic microscopic images on the web. For each slide, an entire specimen is scanned, and a high-resolution digital image (in the order of giga-pixels) is reconstructed. These huge images are then tiled into many 256 × 256-pixel blocks with different resolutions, and information about the blocks of each scanned slide is included in an extensible markup language metafile. Based on the data, a virtual microscopy system is created for viewing the scanned pathologic slides on web. The functionalities (changing viewing resolution, location adjustment, and multimedia annotation presentation) of our virtual slide viewing system are accomplished using pure hypertext markup language (HTML) and JavaScript. We show that there is no need to add plug-in components to browsers in order to handle virtual slides on the web. In a heterogeneous healthcare environment, methods using pure HTML and JavaScript to deal with pathologic content are more appropriate than using proprietary technologies supported only by specific browsers

JARID2 haploinsufficiency is associated with a clinically distinct neurodevelopmental syndrome

Purpose: JARID2, located on chromosome 6p22.3, is a regulator of histone methyltransferase complexes that is expressed in human neurons. So far, 13 individuals sharing clinical features including intellectual disability (ID) were reported with de novo heterozygous deletions in 6p22–p24 encompassing the full length JARID2 gene (OMIM 601594). However, all published individuals to date have a deletion of at least one other adjoining gene, making it difficult to determine if JARID2 is the critical gene responsible for the shared features. We aim to confirm JARID2 as a human disease gene and further elucidate the associated clinical phenotype. Methods: Chromosome microarray analysis, exome sequencing, and an online matching platform (GeneMatcher) were used to identify individuals with single-nucleotide variants or deletions involving JARID2. Results: We report 16 individuals in 15 families with a deletion or single-nucleotide variant in JARID2. Several of these variants are likely to result in haploinsufficiency due to nonsense-mediated messenger RNA (mRNA) decay. All individuals have developmental delay and/or ID and share some overlapping clinical characteristics such as facial features with those who have larger deletions involving JARID2. Conclusion: We report that JARID2 haploinsufficiency leads to a clinically distinct neurodevelopmental syndrome, thus establishing gene–disease validity for the purpose of diagnostic reporting