Diagnostic digital pathology implementation: Learning from the digital health experience.

Digital Pathology (also referred to as Telepathology and Whole Slide Imaging) is the process of producing high resolution digital images from tissue sections on glass slides. These glass slides are normally examined under a microscope by a pathologist as part of the diagnostic process. The emergence of digital pathology now means that digital images are stored on secure servers and can be viewed on computer monitors; enabling pathologists to work remotely and to collaborate with other colleagues when second opinions are needed.

Elevated myeloperoxidase activity in white matter in multiple sclerosis.

Recent studies have revealed extensive axonal damage in patients with progressive multiple sclerosis (MS). Axonal damage can be caused by a plethora of factors including the release of proteolytic enzymes and cytotoxic oxidants by activated immune cells and glia within the lesion. Macrophages and microglia are known to express myeloperoxidase (MPO) and generate reactive oxygen species during myelin phagocytosis in the white matter.

Elevated matrix metalloproteinase-9 and degradation of perineuronal nets in cerebrocortical multiple sclerosis plaques.

Matrix metalloproteinases (MMPs) degrade extracellular matrix; MMP activity, particularly of MMP-9, is elevated in the white matter in multiple sclerosis (MS) patients. The cerebral cortical extracellular matrix includes perineuronal nets (PNs) that surround parvalbumin-positive neurons (PV-positive neurons) and are important for their function. We measured active and total MMP-9 levels in postmortem homogenates of demyelinated and nondemyelinated cerebral cortical regions from 9MS and 7 control cases and assessed Wisteria floribunda agglutin (WFA)-positive PNs in paraffin sections from 15 MS and 6 controls and PV-positive neurons in sections from 26 MS and 6 controls.

Loss of Perineuronal Net in ME7 Prion Disease.

Microglial activation and behavioral abnormalities occur before neuronal loss in experimental murine prion disease; the behavioral changes coincide with a reduction in synaptic plasticity. Because synaptic plasticity depends on an intact perineuronal net (PN), a specialized extracellular matrix that surrounds parvalbumin (PV)-positive GABAergic (gamma-aminobutyric acid [GABA]) inhibitory interneurons, we investigated the temporal relationships between microglial activation and loss of PN and PV-positive neurons in ME7 murine prion disease. Anesthetized C57Bl/6J mice received bilateral intracerebral microinjections of ME7-infected or normal brain homogenate into the dorsal hippocampus.

Elevated activity and microglial expression of myeloperoxidase in demyelinated cerebral cortex in multiple sclerosis.

Recent studies have revealed extensive cortical demyelination in patients with progressive multiple sclerosis (MS). Demyelination in gray matter lesions is associated with activation of microglia. Macrophages and microglia are known to express myeloperoxidase (MPO) and generate reactive oxygen species during myelin phagocytosis in the white matter.

An integrated, temporal study of the behavioural, electrophysiological and neuropathological consequences of murine prion disease.

We have conducted an integrated study of ME7 prion disease by examining the electrophysiological and neuropathological features of hippocampal slices from behaviourally characterised C57Bl/6J mice 12, 14, 16, 18, 20 and 24 weeks after intracerebral micro-injection of ME7 or normal brain homogenate. We describe the pathogenesis of ME7 as a three-stage process. STAGE ONE: PrPSc deposition, synaptic pathology and abnormal synaptic plasticity.

Absence of detectable IL-1beta production in murine prion disease: a model of chronic neurodegeneration.

Murine prion disease is accompanied by a modified inflammatory response characterized by early but prolonged microglial activation and T-lymphocyte recruitment. In this model, we look at the profile of cytokine production, particularly IL-1beta. Mice inoculated with prion-infected brain homogenate show typical signs of prion disease.

Central nervous system inflammation and prion disease pathogenesis.

The study of inflammation in the prion diseases is relatively new. Indeed, for a number of years the accepted dogma was that the prion diseases lacked an inflammatory response in the brain (1-3). This persists in spite of a number of studies showing that the pathological hallmarks of the prion diseases (PrPSc deposition, astrocytosis, vacuolation, and neuronal loss) are associated with the presence of activated microglia (4-7).

What levels of agreement can be expected between histopathologists assigning cases to discrete nominal categories? A study of the diagnosis of hyperplastic and adenomatous colorectal polyps.

Aims: To assess the levels of agreement between histopathologists for a two-class nominal categorization process--the discrimination between hyperplastic and adenomatous colorectal polyps.

Methods: Fifty hyperplastic and 50 adenomatous polyps received consecutively in the laboratory were categorized by nine histopathologists, and the level of agreement between all observers and the original diagnosis was assessed using kappa statistics.

Results: For the eight observers with 11 months or more experience in histopathology, there was a high level of agreement with kappa statistics ranging from 0.

Non-nuclear histone H1 is upregulated in neurones and astrocytes in prion and Alzheimer's diseases but not in acute neurodegeneration.

A non-nuclear isoform of histone H1 is constitutively expressed in neurones. This protein is the major lipopolysaccharide (LPS)-binding protein in the brain. Since the major systemic LPS-binding protein is released in the liver and is an acute phase reactant, we were interested to learn whether this novel CNS histone showed altered expression following neuronal injury.

Inflammatory response and retinal ganglion cell degeneration following intraocular injection of ME7.

Scrapie is a prion disease which occurs naturally in sheep and which can be transmitted experimentally to rodents. After intracerebral injection of ME7 into mouse, an atypical inflammatory response, characterized by T-lymphocytes and activated microglia is present early in the course of the disease. In the present work, we have investigated the relationship between this inflammatory response, astrocytosis and neuronal loss along the visual pathway after intraocular injection (intraocular) of ME7 in C57BL/6J mice.

The acute inflammatory response in CNS following injection of prion brain homogenate or normal brain homogenate.

The neuropathological hallmarks of end-stage prion disease are vacuolation, neuronal loss, astrocytosis and deposition of PrPSc amyloid. We have also shown that there is an inflammatory response in the brains of scrapie-affected mice from 8 weeks post-injection. In this study we have investigated the acute CNS response to the intracerebral injection of scrapie-affected brain homogenate.

Evidence for an early inflammatory response in the central nervous system of mice with scrapie.

In Alzheimer's disease, the most prevalent of the neurodegenerative diseases, inflammation of the CNS contributes to the pathology and is a target for therapy. In contrast, the group of neurodegenerative conditions known as the Prion Diseases have been widely reported as lacking any inflammatory elements despite the many similarities between the pathologies of Alzheimer's Disease and Prion Diseases We have found evidence for an inflammatory component in mouse scrapie, characterized by microglial activation and T-lymphocyte recruitment, which appears long before any clinical signs of the disease and spreads along well-defined anatomical pathways. These observations emphasize the potential value of murine scrapie as a model for studying the inflammatory pathology of other neurodegenerative diseases.