Segmentation of Brain Immunohistochemistry Images Using Clustering of Linear Centroids and Regional Shapes

Wu, Haishan; Murray, Jacinta; Morgello, Susan

doi:10.2352/j.imagingsci.technol.(2008)52:4(040502)

Cited by 5 publications

(3 citation statements)

References 15 publications

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“…The number of areas taken depended on the type of quantitative analysis that followed. The percentage area occupied by cells immunoreactive for CD68, CD45 and HLA DP, DQ, DR was quantitated by analysis of six 0.03 mm 2 images using a proprietary automated morphometric analysis software [103] . The mean intensity of MAP2 and STAT1 staining was analyzed on one 0.03 mm 2 image, utilizing Image J software ( http://rsbweb.nih.gov/ij/ ).…”

Section: Methodsmentioning

confidence: 99%

Significant Effects of Antiretroviral Therapy on Global Gene Expression in Brain Tissues of Patients with HIV-1-Associated Neurocognitive Disorders

et al. 2011

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Antiretroviral therapy (ART) has reduced morbidity and mortality in HIV-1 infection; however HIV-1-associated neurocognitive disorders (HAND) persist despite treatment. The reasons for the limited efficacy of ART in the brain are unknown. Here we used functional genomics to determine ART effectiveness in the brain and to identify molecular signatures of HAND under ART. We performed genome-wide microarray analysis using Affymetrix U133 Plus 2.0 Arrays, real-time PCR, and immunohistochemistry in brain tissues from seven treated and eight untreated HAND patients and six uninfected controls. We also determined brain virus burdens by real-time PCR. Treated and untreated HAND brains had distinct gene expression profiles with ART transcriptomes clustering with HIV-1-negative controls. The molecular disease profile of untreated HAND showed dysregulated expression of 1470 genes at p<0.05, with activation of antiviral and immune responses and suppression of synaptic transmission and neurogenesis. The overall brain transcriptome changes in these patients were independent of histological manifestation of HIV-1 encephalitis and brain virus burdens. Depending on treatment compliance, brain transcriptomes from patients on ART had 83% to 93% fewer dysregulated genes and significantly lower dysregulation of biological pathways compared to untreated patients, with particular improvement indicated for nervous system functions. However a core of about 100 genes remained similarly dysregulated in both treated and untreated patient brain tissues. These genes participate in adaptive immune responses, and in interferon, cell cycle, and myelin pathways. Fluctuations of cellular gene expression in the brain correlated in Pearson's formula analysis with plasma but not brain virus burden. Our results define for the first time an aberrant genome-wide brain transcriptome of untreated HAND and they suggest that antiretroviral treatment can be broadly effective in reducing pathophysiological changes in the brain associated with HAND. Aberrantly expressed transcripts common to untreated and treated HAND may contribute to neurocognitive changes defying ART.

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Section: Methodsmentioning

confidence: 99%

Significant Effects of Antiretroviral Therapy on Global Gene Expression in Brain Tissues of Patients with HIV-1-Associated Neurocognitive Disorders

et al. 2011

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“…Six successive fields at ×40 magnification (total area of analysis, 0.03 mm 2 ) were taken from each tissue core with a Coolpix 950 digital camera attached to the microscope by a Coolpix MDC lens. The percentage of tissue area occupied by antibody-positive cells was determined by an automated system developed at the Mount Sinai School of Medicine (Wu et al 2008). Two cores were analyzed for each antibody in each anatomical region from each patient, for a total of 12 images.…”

Section: Methodsmentioning

confidence: 99%

Impact of opiate addiction on neuroinflammation in HIV

et al. 2012

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To investigate the independent and interactive effects of opiate addiction and HIV on neuroinflammation, we measured microglial/macrophage activation and astrogliosis in multiple regions of human brain. Samples of thalamus, frontal gray matter, and frontal white matter were obtained from 46 individuals categorized as: HIV negatives, HIV-negative opiate addicts, HIV positives, HIV-positive opiate addicts, HIV encephalitis (HIVE), and HIVE opiate addicts. Activated brain microglia/macrophages and astrocytosis were quantified by morphometric analysis of immunohistochemical stains for CD68, HLA-D, CD163, and GFAP. The effects of HIV grouping, opiate addiction, and their interaction on expression of the markers were examined in a series of two-way ANOVAs. In opiate addicts, there was generally higher baseline expression of CD68 and HLA-D in HIV negatives, and lower expression in HIV and HIVE, compared to individuals without opiate abuse. Thus, for these markers, and for GFAP in frontal gray, opiates were associated with attenuated HIV effect. In contrast, for CD163, opiates did not significantly alter responses to HIV, and HIV effects were variably absent in individuals without opiate abuse. The divergent impact that opiate addiction displays on these markers may suggest a generally immunosuppressive role in the CNS, with decreased HIV-associated activation of markers CD68 and HLA-D that potentially reflect neurotoxic pathways, and preservation of CD163, thought to be an indicator of neuroprotective scavenger systems. These results suggest a complex impact of opiates on neuroinflammation in baseline and virally stimulated states.

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“…With the PTShift function, a user can manually adjust the colour shift values while viewing and monitoring the reconstructed image until a visually satisfactory image appears. Although minor transverse chromatic aberration is acceptable to most pathologists when viewing diagnostic specimens, it may significantly affect the quantitative results of the image segmentation and analysis algorithms that are based on the vector clusters (Wu et al ., 2008). In this short communication, we describe an algorithm for restoration of images having transverse chromatic aberrations due to imperfect microscope lenses.…”

Section: Introductionmentioning

confidence: 99%

Restoration of distorted colour microscopic images from transverse chromatic aberration of imperfect lenses

Murray

Morgello

et al. 2010

Journal of Microscopy

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Summary An algorithm is presented for restoration of colour microscopic images with distortions from imperfect microscope lenses having transverse chromatic aberrations, resulting in a magnification that slightly varies with wavelengths or colours. The differential of each colour component image is computed as the difference between the component image and its slightly magnified version. The absolute values in the differential component images are generally higher at the edges where greater discontinuities occur. The two cross-correlation functions of the absolute differentials between red and green colours and between red and blue colours are then computed. The maximum in the two cross-correlation functions were sought, respectively, and the cross-correlation delays were then calculated. The two cross-correlation delays were used to determine dispersions and to realign the three colour components. Results of real microscopic images are provided. The restored image and the original are compared both visually and quantitatively in terms of the estimated entropies measured for the degree of concentrations using vector distributions.

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Segmentation of Brain Immunohistochemistry Images Using Clustering of Linear Centroids and Regional Shapes

Cited by 5 publications

References 15 publications

Significant Effects of Antiretroviral Therapy on Global Gene Expression in Brain Tissues of Patients with HIV-1-Associated Neurocognitive Disorders

Significant Effects of Antiretroviral Therapy on Global Gene Expression in Brain Tissues of Patients with HIV-1-Associated Neurocognitive Disorders

Impact of opiate addiction on neuroinflammation in HIV

Restoration of distorted colour microscopic images from transverse chromatic aberration of imperfect lenses

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