The influence of surgical correction on white matter microstructural integrity in rabbits with familial coronal suture craniosynostosis

Abstract

<jats:sec> <jats:title>OBJECT</jats:title> <jats:p>Craniosynostosis is a condition in which one or more of the calvarial sutures fuses prematurely. In addition to the cosmetic ramifications attributable to premature suture fusion, aberrations in neurophysiological parameters are seen, which may result in more significant damage. This work examines the microstructural integrity of white matter, using diffusion tensor imaging (DTI) in a homogeneous strain of rabbits with simple, familial coronal suture synostosis before and after surgical correction.</jats:p></jats:sec> <jats:sec> <jats:title>METHODS</jats:title> <jats:p>After diagnosis, rabbits were assigned to different groups: wild-type (WT), rabbits with early-onset complete fusion of the coronal suture (BC), and rabbits that had undergone surgical correction with suturectomy (BC-SU) at 10 days of age. Fixed rabbit heads were imaged at 12, 25, or 42 days of life using a 4.7-T, 40-cm bore Avance scanner with a 7.2-cm radiofrequency coil. For DTI, a 3D spin echo sequence was used with a diffusion gradient (b = 2000 sec/mm<jats:sup>2</jats:sup>) applied in 6 directions.</jats:p></jats:sec> <jats:sec> <jats:title>RESULTS</jats:title> <jats:p>As age increased from 12 to 42 days, the DTI differences between WT and BC groups became more pronounced (p &lt; 0.05, 1-way ANOVA), especially in the corpus callosum, cingulum, and fimbriae. Suturectomy resulted in rabbits with no significant differences compared with WT animals, as assessed by DTI of white matter tracts. Also, it was possible to predict to which group an animal belonged (WT, BC, and BC-SU) with high accuracy based on imaging data alone using a linear support vector machine classifier. The ability to predict to which group the animal belonged improved as the age of the animal increased (71% accurate at 12 days and 100% accurate at 42 days).</jats:p></jats:sec> <jats:sec> <jats:title>CONCLUSIONS</jats:title> <jats:p>Craniosynostosis results in characteristic changes of major white matter tracts, with differences becoming more apparent as the age of the rabbits increases. Early suturectomy (at 10 days of life) appears to mitigate these differences.</jats:p></jats:sec>

The influence of suturectomy on age-related changes in cerebral blood flow in rabbits with familial bicoronal suture craniosynostosis: A quantitative analysis

“…While direct neurohistopathological analysis was beyond the scope of the present study, previous results from this rabbit model have shown that early suturectomy resulted in the preservation of white matter integrity as assessed by diffusion tensor imaging (DTI) [ 17 ], an increase in intracranial volume and a normalization of brain surface morphology as assessed with CT-imaging, and a normalization of cranial vault and cranial base angulation as assessed radiographically [ 13 , 23 , 24 , 45 , 46 , 47 ]. Furthermore, studies have shown reossification of the suture following suturectomy can halt the initial improvements in intracranial volume and brain morphology after suturectomy, and further research has aimed to prevent reossification of the suture through molecular therapies [ 47 – 50 ].…”

“…Our well-established rabbit model of familial coronal suture synostosis [ 9 – 13 , 17 , 21 , 25 , 51 ] was used due to the similarity in the sutural, cranial vault, and cerebrovascular architecture dysmorphology, compared to infants with craniosynostosis [ 13 , 21 , 23 , 39 , 48 – 50 , 52 – 54 ]; however, we acknowledge the limitation of extrapolating these results to a human clinical setting given the differences in brain morphology and growth patterns between humans and lagomorphs. Approximately 90% of brain growth in rabbits is completed by 35 days of age [ 13 , 55 ], as compared to about 4 to 6 years of age in humans [ 56 ].…”

“…Synostotic rabbits were initially diagnosed at 10 days of age using previously described criteria [ 9 , 10 , 12 , 13 , 17 , 21 – 24 ]. Briefly, all rabbits were anesthetized with an IM injection (0.59 mL/kg) of a solution containing 91% Ketaset (ketamine hydrochloride, 100 mg/mL, Aveco Co., Inc., Fort Dodge, IA) and 9% Rompun (xylazine, 20 mg/mL, Mobay Corp., Shawnee, KS).…”

“…Along with increased intracranial pressure (ICP) [ 9 – 13 ], other aberrations in neurophysiologic parameters have been noted, most notably, abnormal cerebral blood flow (CBF) [ 14 – 16 ]. Observed downstream neuroanatomic consequences of these perturbations include white matter injury [ 17 ] and atypical venous drainage [ 18 – 20 ]. Examining CBF before and after surgical intervention for craniosynostosis could help characterize the effect of surgery on the pathophysiology of craniosynostosis.…”

“…We have developed an inbred rabbit model of early-onset bilateral coronal craniosynostosis (EOCS) and have extensively described growth changes in the cranial vault and intracranial contents on these rabbits. Phenotypically, EOCS rabbits exhibit bony bridging of the coronal suture by 21 days gestation (gestation is 30 days in the rabbit), obliterated coronal sutures at birth, coronal ridging and brachycephalic cranial vaults by 10 days of age, and secondary changes in the cranial vault base, brain, and intracranial volume by 42 days of age [ 9 , 10 , 12 , 13 , 17 , 21 – 24 ]. CBF was studied in EOCS rabbits at 10, 25 and 42 days of age using ASL-MRI.…”