A Computational Framework to Predict Calvarial Growth: Optimising Management of Sagittal Craniosynostosis.
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ABSTRACT:
SUBMITTER: Cross C
PROVIDER: S-EPMC9170984 | biostudies-literature | 2022
REPOSITORIES: biostudies-literature
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A Computational Framework to Predict Calvarial Growth: Optimising Management of Sagittal Craniosynostosis.
Cross Connor C Khonsari Roman H RH Patermoster Giovanna G Arnaud Eric E Larysz Dawid D Kölby Lars L Johnson David D Ventikos Yiannis Y Moazen Mehran M
Frontiers in bioengineering and biotechnology 20220524
The neonate skull consists of several bony plates, connected by fibrous soft tissue called sutures. Premature fusion of sutures is a medical condition known as craniosynostosis. Sagittal synostosis, caused by premature fusion of the sagittal suture, is the most common form of this condition. The optimum management of this condition is an ongoing debate in the craniofacial community while aspects of the biomechanics and mechanobiology are not well understood. Here, we describe a computational fra ...[more]
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Project description:Early fusion of the sagittal suture is a clinical condition called, sagittal craniosynostosis. Calvarial reconstruction is the most common treatment option for this condition with a range of techniques being developed by different groups. Computer simulations have a huge potential to predict the calvarial growth and optimise the management of this condition. However, these models need to be validated. The aim of this study was to develop a validated patient-specific finite element model of a sagittal craniosynostosis. Here, the finite element method was used to predict the calvarial morphology of a patient based on its preoperative morphology and the planned surgical techniques. A series of sensitivity tests and hypothetical models were carried out and developed to understand the effect of various input parameters on the result. Sensitivity tests highlighted that the models are sensitive to the choice of input parameter. The hypothetical models highlighted the potential of the approach in testing different reconstruction techniques. The patient-specific model highlighted that a comparable pattern of calvarial morphology to the follow up CT data could be obtained. This study forms the foundation for further studies to use the approach described here to optimise the management of sagittal craniosynostosis.
| S-EPMC6949270 | biostudies-literature
Project description:Craniosynostosis is the premature fusion of one or more sutures across the calvaria, resulting in morphological and health complications that require invasive corrective surgery. Finite element (FE) method is a powerful tool that can aid with preoperative planning and post-operative predictions of craniosynostosis outcomes. However, input factors can influence the prediction of skull growth and the pressure on the growing brain using this approach. Therefore, the aim of this study was to carry out a series of sensitivity studies to understand the effect of various input parameters on predicting the skull morphology of a sagittal synostosis patient post-operatively. Preoperative CT images of a 4-month old patient were used to develop a 3D model of the skull, in which calvarial bones, sutures, cerebrospinal fluid (CSF), and brain were segmented. Calvarial reconstructive surgery was virtually modeled and two intracranial content scenarios labeled "CSF present" and "CSF absent," were then developed. FE method was used to predict the calvarial morphology up to 76 months of age with intracranial volume-bone contact parameters being established across the models. Sensitivity tests with regards to the choice of material properties, methods of simulating bone formation and the rate of bone formation across the sutures were undertaken. Results were compared to the in vivo data from the same patient. Sensitivity tests to the choice of various material properties highlighted that the defined elastic modulus for the craniotomies appears to have the greatest influence on the predicted overall skull morphology. The bone formation modeling approach across the sutures/craniotomies had a considerable impact on the level of contact pressure across the brain with minimum impact on the overall predicated morphology of the skull. Including the effect of CSF (based on the approach adopted here) displayed only a slight reduction in brain pressure outcomes. The sensitivity tests performed in this study set the foundation for future comparative studies using FE method to compare outcomes of different reconstruction techniques for the management of craniosynostosis.
| S-EPMC8187911 | biostudies-literature
Project description:PurposeNumerous classification systems of nonsyndromic sagittal craniosynostosis (NSC) are applied but none has gained a wide acceptance, since each classification is focused on distinct aspects of cranial dysmorphology. The goal of this study was to depict the most common combinations of radiomorphologic characteristics of NSC and to separate groups where the patients were morphologically similar to one another and at the same time significantly different from others.MethodsThe study was conducted on anonymized thin-cut CT scans of 131 children with NSC aged 1-12 months (mean age 5.42 months). The type of cranial dysmorphology was assessed using four criteria: skull shape, pattern of sagittal suture fusion, morphologic features and cerebrospinal fluid (CSF) spaces alterations. After assigning the categories, an unsupervised k-modes clustering algorithm was applied to identify distinct patients clusters representing radiomorphologic profiles determined by investigated characteristics.ResultsCluster analysis revealed three distinct radiomorphologic profiles including the most common combinations of features. The profiles were not influenced by sex nor age but were significantly determined by skull shape (V = 0.58, P < 0.0001), morphologic features (V = 0.50, P < 0.0001) and pattern of sagittal suture fusion (V = 0.47, P < 0.0001). CSF alterations did not significantly correlate with the profiles (P = 0.3585).ConclusionNSC is a mosaic of radiologic and morphologic features. The internal diversity of NSC results in dissimilar groups of patients defined by unique combinations of radiomorphologic characteristics, from which the skull shape is the most differentiating factor. Radiomorphologic profiles support the idea of clinical trials targeted at more selective outcomes assessment.
| S-EPMC10643241 | biostudies-literature
Project description:Ellis-van Creveld syndrome (EVC) is a rare disorder (the incidence is estimated at around 7/1,000,000) characterized by the clinical tetrad of chondrodystrophy, polydactyly, ectodermal dysplasia, and cardiac anomalies. Sagittal synostosis is characterized by a dolichocephalic head shape resulting from premature fusion of the sagittal suture. Both are rare disorders, which have never been reported together. We present a case of EVC and sagittal synostosis. We report the clinical features of a Hispanic boy with EVC and sagittal craniosynostosis who underwent cranial vault remodeling. The presentation of this patient is gone over in detail. A never before reported case of EVC and sagittal synostosis is presented in detail.
| S-EPMC4428735 | biostudies-other
Project description:IntroductionLatent cranial suture fusions may present with mild or absent phenotypic changes that make the clinical diagnosis challenging. Recent reports describe patients with sagittal synostosis and a normal cranial index (CI), a condition termed normocephalic sagittal craniosynostosis (NSC). The goal of this study is to evaluate the shape and intracranial volume (ICV) in a cohort of NSC patients using quantitative cranial shape analysis (CSA).MethodsWe identified 19 patients (7.5 ± 2.28 years) between 2011 and 2016, who presented to our hospital with NSC. Cranial index and CSA were measured from the computed tomography image. Cranial shape analysis calculates the distances between the patient's cranial shape and its closest normal shape. Intracranial volume was measured and compared to an established age-matched normative database.ResultsCranial index revealed 15 (78.9%) patients within the mesocephalic range and 4 patients (21.1%) in the brachycephalic range. Detailed CSA identified 15 (78.9%) patients with subtle phenotypic changes along the scaphocephalic spectrum (ie, subtle anterior and posterior elongation with inter-parietal narrowing) and 1 patient (5.3%) with isolated overdevelopment on the posterior part of the right parietal bone. Three patients (15.8%) had a CSA close to normal. Mean ICV was 1410.5 ± 192.77cc; most patients (78.9%) fell within ±2 standard deviations.ConclusionQuantitative CSA revealed that most of the patients with NSC had cranial shape abnormalities, consistent with a forme fruste scaphocephaly that could not be otherwise recognized by clinical observation or CI. Given these findings, we propose the term occult scaphocephaly to describe this condition. The associated incidence of intracranial hypertension is unknown.
| S-EPMC7343588 | biostudies-literature
Project description:Numerous classification systems of nonsyndromic sagittal craniosynostosis (NSC) are applied but none has gained a wide acceptance, since each classification is focused on distinct aspects. The aim of the study was to assess the accuracy of 4 classifications of NSC discussed in the literature by defining the associations among the classifications, individual features (sex, age, cranial index), and objective morphologic criteria (frontal bossing, retrocoronal constriction, sagittal ridge, and occipital bulleting). The study was conducted on anonymized thin-cut CT scans of 133 children with NSC 1 to 12 months old (mean age 5.42 mo). The type of cranial dysmorphology was assessed using 4 classification systems, focusing on skull shape, pattern of sagittal suture closure (Heuzé classification), deformation of skull vault (Sakamoto classification), and a single-dominant feature (David classification). Each patient was also independently investigated for the presence of morphologic criteria. A multivariate analysis was performed to explore the relations among the classifications and assess their accuracy. In the analyzed cohort sphenocephaly (38.3%), CFF type by Heuzé (30.8%), type I by Sakamoto (72.9%), and a central type by David (42.9%) were dominant findings. Regarding the morphologic criteria, frontal bossing was observed the most frequently (91.7%). The age of patients and cranial index differed significantly among the shapes of skull and David classifications (P<0.001). The shape-based system showed the strongest correlation with other classifications and with measurable variables. Other classifications have much in common and some overlap, but none of them constitutes a standalone system to define all aspects of cranial dysmorphology in NSC.
| S-EPMC10749678 | biostudies-literature
Project description:Sagittal synostosis is the most occurring form of craniosynostosis, resulting in calvarial deformation and possible long-term neurocognitive deficits. Several surgical techniques have been developed to correct these issues. Debates as to the most optimal approach are still ongoing. Finite element method is a computational tool that's shown to assist with the management of craniosynostosis. The aim of this study was to compare and predict the outcomes of three reconstruction methods for sagittal craniosynostosis. Here, a generic finite element model was developed based on a patient at 4 months of age and was virtually reconstructed under all three different techniques. Calvarial growth was simulated to predict the skull morphology and the impact of different reconstruction techniques on the brain growth up to 60 months of age. Predicted morphology was then compared with in vivo and literature data. Our results show a promising resemblance to morphological outcomes at follow up. Morphological characteristics between considered techniques were also captured in our predictions. Pressure outcomes across the brain highlight the potential impact that different techniques have on growth. This study lays the foundation for further investigation into additional reconstructive techniques for sagittal synostosis with the long-term vision of optimizing the management of craniosynostosis.
| S-EPMC8551239 | biostudies-literature
Project description:Craniosynostosis is a group of disorders of premature calvarial suture fusion. The identity of the calvarial stem cells (CSCs) that produce fusion-driving osteoblasts in craniosynostosis remains poorly understood. Here we show that both physiologic calvarial mineralization and pathologic calvarial fusion in craniosynostosis reflect the interaction of two separate stem cell lineages; a previously identified cathepsin K (CTSK) lineage CSC1 (CTSK+ CSC) and a separate discoidin domain-containing receptor 2 (DDR2) lineage stem cell (DDR2+ CSC) that we identified in this study. Deletion of Twist1, a gene associated with craniosynostosis in humans2,3, solely in CTSK+ CSCs is sufficient to drive craniosynostosis in mice, but the sites that are destined to fuse exhibit an unexpected depletion of CTSK+ CSCs and a corresponding expansion of DDR2+ CSCs, with DDR2+ CSC expansion being a direct maladaptive response to CTSK+ CSC depletion. DDR2+ CSCs display full stemness features, and our results establish the presence of two distinct stem cell lineages in the sutures, with both populations contributing to physiologic calvarial mineralization. DDR2+ CSCs mediate a distinct form of endochondral ossification without the typical haematopoietic marrow formation. Implantation of DDR2+ CSCs into suture sites is sufficient to induce fusion, and this phenotype was prevented by co-transplantation of CTSK+ CSCs. Finally, the human counterparts of DDR2+ CSCs and CTSK+ CSCs display conserved functional properties in xenograft assays. The interaction between these two stem cell populations provides a new biologic interface for the modulation of calvarial mineralization and suture patency.
| S-EPMC10799660 | biostudies-literature
Project description:The mammalian cranial vault largely consists of five flat bones that are joined together along their edges by soft fibrous tissues called sutures. Premature closure of the cranial sutures, craniosynostosis, can lead to serious clinical pathology unless there is surgical intervention. Research into the genetic basis of the disease has led to the development of various animal models that display this condition, e.g. mutant type Fgfr2C342Y/+ mice which display early fusion of the coronal suture (joining the parietal and frontal bones). However, whether the biomechanical properties of the mutant and wild type bones are affected has not been investigated before. Therefore, nanoindentation was used to compare the elastic modulus of cranial bone and sutures in wild type (WT) and Fgfr2C342Y/+mutant type (MT) mice during their postnatal development. Further, the variations in properties with indentation position and plane were assessed. No difference was observed in the elastic modulus of parietal bone between the WT and MT mice at postnatal (P) day 10 and 20. However, the modulus of frontal bone in the MT group was lower than the WT group at both P10 (1.39±0.30 vs. 5.32±0.68 GPa; p<0.05) and P20 (5.57±0.33 vs. 7.14±0.79 GPa; p<0.05). A wide range of values was measured along the coronal sutures for both the WT and MT samples, with no significant difference between the two groups. Findings of this study suggest that the inherent mechanical properties of the frontal bone in the mutant mice were different to the wild type mice from the same genetic background. These differences may reflect variations in the degree of biomechanical adaptation during skull growth, which could have implications for the surgical management of craniosynostosis patients.
| S-EPMC4429024 | biostudies-literature
Project description:BackgroundCraniosynostosis is a condition that includes the premature fusion of one or multiple cranial sutures. Among various craniosynostosis forms, sagittal nonsyndromic craniosynostosis is the most prevalent. Although different gene mutations have been identified in some craniosynostosis syndromes, the cause of sagittal nonsyndromic craniosynostosis remains largely unknown.MethodsTo screen for candidate genes for sagittal nonsyndromic craniosynostosis, the authors sequenced DNA of 93 sagittal nonsyndromic craniosynostosis patients from a population-based study conducted in Iowa and New York states. FGFR1-3 mutational hotspots and the entire TWIST1, RAB23, and BMP2 coding regions were screened because of their known roles in human nonsyndromic or syndromic sagittal craniosynostosis, expression patterns, and/or animal model studies.ResultsThe authors identified two rare variants in their cohort. A FGFR1 insertion c.730_731insG, which led to a premature stop codon, was predicted to abolish the entire immunoglobulin-like III domain, including the ligand-binding region. A c.439C>G variant was observed in TWIST1 at its highly conserved loop domain in another patient. The patient's mother harbored the same variant and was reported with jaw abnormalities. These two variants were not detected in 116 alleles from unaffected controls or seen in the several databases; however, TWIST1 variant was found in a low frequency of 0.000831 percent in Exome Aggregation Consortium database.ConclusionsThe low mutation detection rate indicates that these genes account for only a small proportion of sagittal nonsyndromic craniosynostosis patients. The authors' results add to the perception that sagittal nonsyndromic craniosynostosis is a complex developmental defect with considerable genetic heterogeneity.Clinical question/level of evidenceRisk, II.
| S-EPMC4770826 | biostudies-literature