The dynamics of brain and cerebrospinal fluid growth in normal versus hydrocephalic mice.
OBJECTIVE
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.
Mandell
Jason G
JG
Department of Engineering Science and Mechanics, Center for Neural Engineering, Pennsylvania State University, University Park, Pennsylvania, USA.
Neuberger
Thomas
T
Drapaca
Corina S
CS
Webb
Andrew G
AG
Schiff
Steven J
SJ
D000367:Age Factors; D000465:Algorithms; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000473:pathology*; D002508:Cephalometry / Q000706:statistics & numerical data*; D002535:Cerebral Aqueduct / Q000473:pathology; D002552:Cerebral Ventricles / Q000473:pathology*; D004195:Disease Models, Animal; D005583:Fourier Analysis; D005625:Frontal Lobe / Q000473:pathology; D006849:Hydrocephalus / Q000473:pathology*; D007091:Image Processing, Computer-Assisted; D021621:Imaging, Three-Dimensional; D007427:Intracranial Pressure / Q000502:physiology; D020547:Lateral Ventricles / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008432:Mathematical Computing; D051379:Mice; D008810:Mice, Inbred C57BL; D009778:Occipital Lobe / Q000473:pathology; D009929:Organ Size / Q000502:physiology; D012016:Reference Values