The dynamics of brain and cerebrospinal fluid growth in normal versus hydrocephalic mice

Laboratory investigation

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  • 1 Center for Neural Engineering, Department of Engineering Science and Mechanics,
  • 2 Department of Bioengineering,
  • 3 Huck Institutes of the Life Sciences, and
  • 5 Departments of Neurosurgery and Physics, Pennsylvania State University, University Park, Pennsylvania; and
  • 4 C. J. Gorter Center for High Field MR Imaging, Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands
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Object

Hydrocephalus has traditionally been quantified by linear measures of ventricular size, with adjunct use of cortical mantle thickness. However, clinical outcome depends on cognitive function, which is more directly related to brain volume than these previous measures. The authors sought to quantify the dynamics of brain and ventricular volume growth in normal compared with hydrocephalic mice.

Methods

Hydrocephalus was induced in 14-day-old C57BL/6 mice by percutaneous injection of kaolin into the cisterna magna. Nine hydrocephalic and 6 normal mice were serially imaged from age 2–12 weeks with a 14.1-T MR imaging unit. Total brain and ventricle volumes were calculated, and linear discriminant analysis was applied.

Results

Two very different patterns of response were seen in hydrocephalic mice compared with mice with normative growth. In one pattern (3 mice) brain growth was normal despite accumulation of CSF, and in the second pattern (6 mice) abnormal brain enlargement was accompanied by increased CSF volume along with parenchymal edema. In this latter pattern, spontaneous ventricular rupture led to normalization of brain volume, implying edema from transmantle pressure gradients. These 2 patterns of hydrocephalus were significantly discriminable using linear discriminant analysis (p < 0.01). In contrast, clinically relevant measurements of head circumference or frontal and occipital horn ratios were unable to discriminate between these patterns.

Conclusions

This study is, to the authors' knowledge, the first serial quantification of the growth of brain and ventricle volumes in normal versus hydrocephalic development. The authors' findings demonstrate the feasibility of constructing normative curves of brain and fluid growth as complements to normative head circumference curves. By measuring brain volumes, distinct patterns of brain growth and enlargement can be observed, which are more likely linked to cognitive development and clinical outcome than fluid volumes alone.

Abbreviation used in this paper: LDA = linear discrimination analysis.

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Contributor Notes

Address correspondence to: Steven J. Schiff, M.D., Ph.D., 212 Earth–Engineering Sciences Building, University Park, Pennsylvania 16802. email: sschiff@psu.edu.
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