scholarly journals Coupling Diffusion Imaging with Histological and Gene Expression Analysis to Examine the Dynamics of Cortical Areas across the Fetal Period of Human Brain Development

2012 ◽  
Vol 23 (11) ◽  
pp. 2620-2631 ◽  
Author(s):  
H. Huang ◽  
T. Jeon ◽  
G. Sedmak ◽  
M. Pletikos ◽  
L. Vasung ◽  
...  
PLoS ONE ◽  
2014 ◽  
Vol 9 (6) ◽  
pp. e100858 ◽  
Author(s):  
Veronica H. Ryan ◽  
Christopher T. Primiani ◽  
Jagadeesh S. Rao ◽  
Kwangmi Ahn ◽  
Stanley I. Rapoport ◽  
...  

Neurosurgery ◽  
2019 ◽  
Vol 66 (Supplement_1) ◽  
Author(s):  
Kunal S Patel ◽  
Catalina Raymond ◽  
Jingwen Yao ◽  
Joseph Tsung ◽  
Linda M Liau ◽  
...  

Abstract INTRODUCTION Significant evidence from multiple phase II trials have suggested diffusion-weighted imaging estimates of apparent diffusion coefficient (ADC) are a predictive imaging biomarker for survival benefit for recurrent glioblastoma when treated with anti-VEGF therapies, including bevacizumab, cediranib, and cabozantinib. Despite this observation, the underlying mechanism linking anti-VEGF therapeutic efficacy with diffusion MR characteristics remains unknown. We hypothesized that a high expression of decorin, a small proteoglycan that has been associated with sequestration of pro-angiogenic signaling as well as reduction in the viscosity of the extracellular environment, may be associated with elevated ADC. METHODS A differential gene expression analysis was carried out in human glioblastoma samples in whom preoperative diffusion imaging was obtained. ADC histogram analysis was carried out to calculate preoperative ADCL values, the average ADC in the lower distribution using a double Gaussian mixed model. The Cancer Imaging Archive (TCIA) and The Cancer Genome Atlas (TCGA) databases were queried to identify diffusion imaging and levels of decorin protein expression. Patients with recurrent glioblastoma who undergo resection prospectively had targeted biopsies based on the ADC analysis collected. These samples were stained for decorin and quantified using whole-slide image analysis software. RESULTS Differential gene expression analysis between tumors associated with high and low preoperative ADCL showed that patients with high ADCL had increased decorin gene expression. Patients from the TCGA database with elevated ADCL had a significantly higher level of decorin gene expression (P = .01). These patients had a survival advantage with a log-rank analysis (P = .002). Patients with preoperative diffusion imaging had multiple targeted intraoperative biopsies stained for decorin. Patients with high ADCL had increased decorin expression on immunohistochemistry (P = .002). CONCLUSION Increased ADCL on diffusion MR imaging is associated with high decorin expression as well as increased survival in glioblastoma. Decorin may play an important role the imaging features on diffusion MR and anti-VEGF treatment efficacy. Decorin expression may serve as a future therapeutic target in patients with favorable diffusion MR characteristics.


2018 ◽  
Author(s):  
Heath E. O’Brien ◽  
Eilis Hannon ◽  
Aaron R. Jeffries ◽  
William Davies ◽  
Matthew J. Hill ◽  
...  

ABSTRACTWidespread structural, chemical and molecular differences have been reported between the male and female human brain. Although several neurodevelopmental disorders are more commonly diagnosed in males, little is known regarding sex differences in early human brain development. Here, we used RNA sequencing data from a large collection of human brain samples from the second trimester of gestation (N = 120) to assess sex biases in gene expression within the human fetal brain. In addition to 43 genes (102 Ensembl transcripts) transcribed from the Y-chromosome in males, we detected sex differences in the expression of 2558 autosomal genes (2723 Ensembl transcripts) and 155 genes on the X-chromosome (207 Ensembl transcripts) at a false discovery rate (FDR) < 0.1. Genes exhibiting sex-biased expression in human fetal brain are enriched for high-confidence risk genes for autism and other developmental disorders. Male-biased genes are enriched for expression in neural progenitor cells, whereas female-biased genes are enriched for expression in Cajal-Retzius cells and glia. All gene- and transcript-level data are provided as an online resource (available at http://fgen.psycm.cf.ac.uk/FBSeq1) through which researchers can search, download and visualize data pertaining to sex biases in gene expression during early human brain development.


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