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Correlation of histology with diffusion tensor imaging in the developing cerebellum.

The study was performed on 15 human fetuses with gestational age (GA) ranging from 14 to 40 weeks to observe the histogenesis of different cortical layers during the development of cerebellum and correlate the histogenesis of different cortical layers with diffusion tensor imaging.

Whole brain conventional MRI including diffusion tensor imaging (DTI) was performed on a 1.5T MRI scanner using a standard quadrature extremity coil/head coil for both transmission of radiofrequency pulses and signal reception. DTI data were acquired using a single-shot echo-planar dual spin echo sequence with ramp sampling. DTI data were processed and evaluated using JAVA based software to generate various DTI derived metrics i.e. fractional anisotropy (FA) and mean diffusivity (MD). Region of interest (ROI) analysis was performed for the calculation of the various DTI derived metrics.

In the fetuses, ROIs were placed in the cerebellar cortical region and middle cerebellar preduncles (MCP) at the level of fourth ventricle. After imaging, the whole of the excised cerebellum was cut in axial axis and blocked, sectioned and stained. Morphometric analysis was done in the digitalized images using BIOVIS image analysis system.

It was observed that the cerebellar cortical fractional anisotrophy (FA) reached its peak value at 28 weeks, and then decreased gradually until 37 weeks. The time course of glial fibrillary acidic protein (GFAP) expression paralleled that of FA in the cerebellar cortex from 20 weeks of gestation upto the GA at which the FA reached its peak value (28 weeks GA). No significant correlation was observed between cortical FA values and percentage of neuron specific enclose (NSE) positive neurons in the internal granular layer of the cerebellar cortex. In the middle cerebellar penduncle the FA increased continuously upto 37 weeks of GA and showed a significant positive correlation with myelin basic protein (MBP) immunostained fibres.

The immunohistochemical data demonstrated the temporal changes in the expression of different markers i.e. GFAP, NSE in the cerebellar cortical region and MBP in the cerebellar white matter of the human fetal brain ranging from 20 to 37 weeks respectively. It was found that in the cerebellar cortex, the intensity of GFAP expression was maximum at 28 weeks GA while diffuse lower intensity staining was observed in fetuses at 32 and 37 weeks GA. The percentage of NSE positive cells showed an increasing trend from 20 weeks onwards in the internal granular layer of the cerebellar cortex and was found to be maximum at 37 weeks. In the MCP, at 20 and 24 weeks GA, the percentage of MBP positive fibres was minimum while at 28 weeks GA the percentage of MBP fibres increased which continued till the late third trimester of gestation.

It was conclusively demonstrated that DTI can be used to assess the migrational and maturation changes during the development of the human fetal cerebellum and these findings are supported by the immunohistochemical analysis. This confirms that DTI has the ability to monitor the neuronal migratioin and maturation processes noninvasively in vivo, and may improve our understanding of the normal developmental pattern of cerebellar cortical gray matter and cerebellar white matter.

Sona Saksena

Prof. Nuzhat Husain

Department of Pathology

CSM Medical University, Lucknow


1. Saksena, S., Husain, N., Malik, G.K., Trivedi, R., Sarma, M., Rathore, R.K.S., Pandey, C.M. and Gupta, R.K. Comparative evaluation of the cerebral and cerebellar white matter development in pediatric age group using quantitative diffusion tensor imaging. Cerebellum 7: 392, 2008.

2. Saksena, S., Husain, N., Das, V., Pradhan, M., Trivedi, R., Srivastava, S., Malik, G.K., Rathore, R.K.S., Sarma, M., Pandey, C.M. and Gupta, R.K. Diffusion tensor imaging in the developing human cerebellum with histologic correlation. J Develop Neuros 26: 705, 2008.

3. Trivedi, R., Gupta, R.K., Husain, N., Rathore, R.K.S., Saksena, S., Srivastava, S., Malik, G.K., Das, V., Pradhan, M., Sarma, M.K., Pandey, C.M. and Narayana, P.A.. Region-specific maturation of cerebral cortex in human fetal brain: Diffusion tensor imaging and histology. Neuroradiol 51 : 567, 2009.
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Title Annotation:ABSTRACTS: Some Research Projects Completed Recently
Author:Saksena, Sona; Husain, Nuzhat
Publication:ICMR Bulletin
Article Type:Abstract
Date:Mar 1, 2010
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