Modern Pathology Methods for Neural Investigations

Hale, Sarah; Andrews-Jones, Lydia; Jordan, William H.; Jortner, Bernard S.; Boyce, Rogely; Boyce, J. T.; Switzer, Robert C.; Butt, Mark T.; Garman, Robert H.; Jensen, Karl F.; Krinke, G.; Little, P B

doi:10.1177/0192623310394213

Cited by 10 publications

(9 citation statements)

References 24 publications

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“…Similarly, analysis of the brain was limited to a mid-sagittal section; hence, many neuroanatomical and functional areas were not examined for lesions or coronal symmetry. Although consensus on section orientation of the brain is lacking (Hale et al, 2011), coronal sectioning is particularly suited for assessment of brain symmetry, a feature that is affected in many diseases (Bronson, 2001). Recently, the Sanger MGP has adopted coronal sectioning of the brain.…”

Section: Discussionmentioning

confidence: 99%

Histopathology reveals correlative and unique phenotypes in a high throughput mouse phenotyping screen

Adissu

Estabel

Sunter

et al. 2014

Disease Models &Amp; Mechanisms

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The Mouse Genetics Project (MGP) at the Wellcome Trust Sanger Institute aims to generate and phenotype over 800 genetically modified mouse lines over the next 5 years to gain a better understanding of mammalian gene function and provide an invaluable resource to the scientific community for follow-up studies. Phenotyping includes the generation of a standardized biobank of paraffin-embedded tissues for each mouse line, but histopathology is not routinely performed. In collaboration with the Pathology Core of the Centre for Modeling Human Disease (CMHD) we report the utility of histopathology in a high-throughput primary phenotyping screen. Histopathology was assessed in an unbiased selection of 50 mouse lines with (n=30) or without (n=20) clinical phenotypes detected by the standard MGP primary phenotyping screen. Our findings revealed that histopathology added correlating morphological data in 19 of 30 lines (63.3%) in which the primary screen detected a phenotype. In addition, seven of the 50 lines (14%) presented significant histopathology findings that were not associated with or predicted by the standard primary screen. Three of these seven lines had no clinical phenotype detected by the standard primary screen. Incidental and strain-associated background lesions were present in all mutant lines with good concordance to wild-type controls. These findings demonstrate the complementary and unique contribution of histopathology to high-throughput primary phenotyping of mutant mice.

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Section: Discussionmentioning

confidence: 99%

Histopathology reveals correlative and unique phenotypes in a high throughput mouse phenotyping screen

Adissu

Estabel

Sunter

et al. 2014

Disease Models &Amp; Mechanisms

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“…The official research policy statement of the ATS/ERS in particular recommends using the disector as gold standard for the counting of 3D particles, such as cells [13]. Whereas stereological approaches have been considered time-consuming in the past [2], with the integration of automated whole slide scanners, automated section sampling, computer-assisted measurements, and automated capture and registration of physical disectors this no longer holds true today [48]; [49]. One other study compared the data obtained by design-based stereological and assumption-based ‘area profile’ counting techniques [38].…”

Section: Discussionmentioning

confidence: 99%

Cell Counting in Human Endobronchial Biopsies - Disagreement of 2D versus 3D Morphometry

et al. 2014

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QuestionInflammatory cell numbers are important endpoints in clinical studies relying on endobronchial biopsies. Assumption-based bidimensional (2D) counting methods are widely used, although theoretically design-based stereologic three-dimensional (3D) methods alone offer an unbiased quantitative tool. We assessed the method agreement between 2D and 3D counting designs in practice when applied to identical samples in parallel.Materials and MethodsBiopsies from segmental bronchi were collected from healthy non-smokers (n = 7) and smokers (n = 7), embedded and sectioned exhaustively. Systematic uniform random samples were immunohistochemically stained for macrophages (CD68) and T-lymphocytes (CD3), respectively. In identical fields of view, cell numbers per volume unit (NV) were assessed using the physical disector (3D), and profiles per area unit (NA) were counted (2D). For CD68+ cells, profiles with and without nucleus were separately recorded. In order to enable a direct comparison of the two methods, the zero-dimensional CD68+/CD3+-ratio was calculated for each approach. Method agreement was tested by Bland-Altmann analysis.ResultsIn both groups, mean CD68+/CD3+ ratios for NV and NA were significantly different (non-smokers: 0.39 and 0.68, p<0.05; smokers: 0.49 and 1.68, p<0.05). When counting only nucleated CD68+ profiles, mean ratios obtained by 2D and 3D counting were similar, but the regression-based Bland-Altmann analysis indicated a bias of the 2D ratios proportional to their magnitude. This magnitude dependent deviation differed between the two groups.Conclusions2D counts of cell and nuclear profiles introduce a variable size-dependent bias throughout the measurement range. Because the deviation between the 3D and 2D data was different in the two groups, it precludes establishing a ‘universal conversion formula’.

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“…But as CT or MRI can only provide a macroscopic view of a particular tumor and histopathology remains unclear, stereotactic biopsy still plays an important role in pre- and perioperative care in patients suffering from brain tumors - as Callovini et al [27] described. Although it is relatively safe and effective to perform [28] , conventional histology can only provide a snapshot of a small portion of the tumor and is subject to cutting-, embedding- and staining artifacts [29] , [30] . Endomicroscopic equipment might easily be integrated into a minimally invasive or endoscopic setting and provides immediate and intraoperativ histopathologic diagnosis of the entire entity at real time which might be directly followed by therapeutic neurosurgical intervention.…”

Section: Discussionmentioning

confidence: 99%

Confocal Laser Endomicroscopy for Diagnosis and Histomorphologic Imaging of Brain Tumors In Vivo

et al. 2012

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Early detection and evaluation of brain tumors during surgery is crucial for accurate resection. Currently cryosections during surgery are regularly performed. Confocal laser endomicroscopy (CLE) is a novel technique permitting in vivo histologic imaging with miniaturized endoscopic probes at excellent resolution. Aim of the current study was to evaluate CLE for in vivo diagnosis in different types and models of intracranial neoplasia. In vivo histomorphology of healthy brains and two different C6 glioma cell line allografts was evaluated in rats. One cell line expressed EYFP, the other cell line was used for staining with fluorescent dyes (fluorescein, acriflavine, FITC-dextran and Indocyanine green). To evaluate future application in patients, fresh surgical resection specimen of human intracranial tumors (n = 15) were examined (glioblastoma multiforme, meningioma, craniopharyngioma, acoustic neurinoma, brain metastasis, medulloblastoma, epidermoid tumor). Healthy brain tissue adjacent to the samples served as control. CLE yielded high-quality histomorphology of normal brain tissue and tumors. Different fluorescent agents revealed distinct aspects of tissue and cell structure (nuclear pattern, axonal pathways, hemorrhages). CLE discrimination of neoplastic from healthy brain tissue was easy to perform based on tissue and cellular architecture and resemblance with histopathology was excellent. Confocal laser endomicroscopy allows immediate in vivo imaging of normal and neoplastic brain tissue at high resolution. The technology might be transferred to scientific and clinical application in neurosurgery and neuropathology. It may become helpful to screen for tumor free margins and to improve the surgical resection of malignant brain tumors, and opens the door to in vivo molecular imaging of tumors and other neurologic disorders.

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Modern Pathology Methods for Neural Investigations

Cited by 10 publications

References 24 publications

Histopathology reveals correlative and unique phenotypes in a high throughput mouse phenotyping screen

Histopathology reveals correlative and unique phenotypes in a high throughput mouse phenotyping screen

Cell Counting in Human Endobronchial Biopsies - Disagreement of 2D versus 3D Morphometry

Confocal Laser Endomicroscopy for Diagnosis and Histomorphologic Imaging of Brain Tumors In Vivo

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