Tron A. Darvann

Helmet Versus Active Repositioning for Plagiocephaly: A Three-Dimensional Analysis

BACKGROUND AND PURPOSE: Orthotic helmets and active repositioning are the most common treatments for deformational plagiocephaly (DP). Existing evidence is not sufficient to objectively inform decisions between these options. A three-dimensional (3D), whole-head asymmetry analysis was used to rigorously compare outcomes of these 2 treatment methods. PATIENTS AND METHODS: Whole-head 3D surface scans of 70 infants with DP were captured before and after treatment by using stereophotogrammetric imaging technology. Helmeted (n = 35) and nonhelmeted/actively repositioned (n = 35) infants were matched for severity of initial deformity. Surfaces were spatially registered to a symmetric template, which was deformed to achieve detailed right-to-left point correspondence for every point on the head surface. A ratiometric asymmetry value was calculated for each point relative to its contralateral counterpart. Maximum and mean asymmetry values were determined. Change in mean and maximum asymmetry with treatment was the basis for group comparison. RESULTS: The helmeted group had a larger reduction than the repositioned group in both maximum (4.0% vs 2.5%; P = .02) and mean asymmetry (0.9% vs 0.5%; P = .02). The greatest difference was localized to the occipital region. CONCLUSIONS: Whole-head 3D asymmetry analysis is capable of rigorously quantifying the relative efficacy of the 2 common treatments of DP. Orthotic helmets provide statistically superior improvement in head symmetry compared with active repositioning immediately after therapy. Additional studies are needed to (1) establish the clinical significance of these quantitative differences in outcome, (2) define what constitutes pathologic head asymmetry, and (3) determine whether superiority of orthotic treatment lasts as the child matures.

The Craniofacial Phenotype of the Crouzon Mouse: Analysis of a Model for Syndromic Craniosynostosis Using Three-Dimensional MicroCT

Objective: To characterize the craniofacial phenotype of a mouse model for Crouzon syndrome by a quantitative analysis of skull morphology in mutant and wild-type mice and to compare the findings with skull features observed in humans with Crouzon syndrome. Methods: MicroCT scans and skeletal preparations were obtained on previously described Fgfr2C342Y/+ Crouzon mutant mice and wild-type mice at 6 weeks of age. Three-dimensional coordinate data from biologically relevant landmarks on the skulls were collected. Euclidean Distance Matrix Analysis was used to quantify and compare skull shapes using these landmark data. Results: Obliteration of bilateral coronal sutures was observed in 80% of skulls, and complete synostosis of the sagittal suture was observed in 70%. In contrast, fewer than 40% of lambdoid sutures were found to be fully fused. In each of the 10 Fgfr2C342Y/+ mutant mice analyzed, the presphenoid-basisphenoid synchondrosis was fused. Skull height and width were increased in mutant mice, whereas skull length was decreased. Interorbital distance was also increased in Fgfr2C342Y/+ mice as compared with wild-type littermates. Upper-jaw length was shorter in the Fgfr2C342Y/+ mutant skulls, as was mandibular length. Conclusion: Skulls of Fgfr2C342Y/+ mice differ from normal littermates in a comparable manner with differences between the skulls of humans with Crouzon syndrome and those of unaffected individuals. These findings were consistent across several regions of anatomic interest. Further investigation into the molecular mechanisms underlying the anomalies seen in the Crouzon mouse model is currently under way.

Three-dimensional analysis of mandibular growth and tooth eruption

Normal and abnormal jaw growth and tooth eruption are topics of great importance for several dental and medical disciplines. Thus far, clinical studies on these topics have used two‐dimensional (2D) radiographic techniques. The purpose of the present study was to analyse normal mandibular growth and tooth eruption in three dimensions based on computer tomography (CT) scans, extending the principles of mandibular growth analysis proposed by Björk in 1969 from two to three dimensions. As longitudinal CT data from normal children are not available (for ethical reasons), CT data from children with Apert syndrome were employed, because it has been shown that the mandible in Apert syndrome is unaffected by the malformation, and these children often have several craniofacial CT scans performed during childhood for planning of cranial and midface surgery and for follow‐up after surgery. A total of 49 datasets from ten children with Apert syndrome were available for study. The number of datasets from each individual ranged from three to seven. The first CT scan in each of the ten series was carried out before 1 year of age, and the ages for the 49 scans ranged from 1 week to 14.5 years. The mandible and the teeth were segmented and iso‐surfaces generated. Landmarks were placed on the surface of the mandible, along the mandibular canals, the inner contour of the cortical plate at the lower border of the symphysis menti, and on the teeth. Superimposition of the mandibles in the longitudinal series was performed using the symphysis menti and the mandibular canals as suggested by Björk. The study supported the findings of stability of the symphysis menti and the mandibular canals as seen in profile view previously reported by Björk & Skieller in 1983. However, the mandibular canals were, actually, relocated laterally during growth. Furthermore, the position of tooth buds remained relatively stable inside the jaw until root formation started. Eruption paths of canines and premolars were vertical, whereas molars erupted in a lingual direction. The 3D method would seem to offer new insight into jaw growth and tooth eruption, but further studies are needed.

Early Craniofacial Morphology and Growth in Children With Unoperated Isolated Cleft Palate

OBJECTIVE Analysis of craniofacial morphology and growth in children with untreated isolated cleft palate (ICP) (cleft of the secondary palate only) at 2 and 22 months of age and comparison of the morphology and growth to that of a control group with unilateral incomplete cleft lip (UICL). MATERIAL AND METHODS A total of 98 cleft children (53 with ICP and 45 with UICL) drawn from a larger group representing all Danish children with cleft born in the period 1976 to 1981 were included in the study. Craniofacial morphology and growth were analyzed using three-projection infant cephalometry. RESULTS The ICP group differed significantly from the UICL group. The most striking findings in the ICP group were: short maxilla; reduced posterior maxillary height; increased posterior maxillary width (in the 2-month-old); short mandible; reduced posterior height of the mandible; bimaxillary retrognathia; and reduced pharyngeal depth, height, and area. The facial growth pattern was fairly similar in the two groups except for a somewhat more vertical growth direction in the ICP group. CONCLUSION The facial morphology in ICP children differs significantly from that of children with UICL of the same age. The differences in facial morphology can be ascribed to the difference in the primary anomaly in the ICP group. The facial growth pattern was fairly similar in the ICP and UICL group; however, a somewhat more vertical growth direction was observed in the ICP group.

Early postnatal development of the mandible in children with isolated cleft palate and children with nonsyndromic Robin sequence.

Objective Analysis of early postnatal mandibular size and growth velocity in children with untreated isolated cleft palate (ICP), nonsyndromic Robin sequence (RS), and a control group of children with unilateral incomplete cleft lip (UICL). Material 114 children (66 isolated cleft palate, 7 Robin sequence, 41 unilateral incomplete cleft lip) drawn from a group representing all Danish cleft children born from 1976 through 1981. All children were examined at both 2 and 22 months of age. Methods Cephalometric x-rays and maxillary plaster casts. Mandibular length and height were measured and mandibular growth velocity (mm/year) was calculated. Cleft width was measured on the casts at 2 months of age. Results Mean mandibular length and posterior height were significantly smaller in isolated cleft palate and Robin sequence, compared with unilateral incomplete cleft lip. Mandibular length in Robin sequence was also significantly shorter, compared with isolated cleft palate. No significant difference was found between mean mandibular growth velocities in the three groups. No significant correlation was found between mandibular length and cleft width in either isolated cleft palate or Robin sequence at 2 months of age. Conclusion The children with isolated cleft palate and Robin sequence had small mandibles shortly after birth, but with a relatively normal growth potential. No true mandibular catch-up growth was found up to 22 months of age in either group. No significant correlation was found between mandibular size and cleft width in either group at 2 months of age. However, there was a significant trend toward the shorter the mandible, the more severe the sagittal extension of the cleft.

Early Craniofacial Morphology and Growth in Children With Nonsyndromic Robin Sequence

PURPOSE Craniofacial morphology and growth comparisons in children with untreated nonsyndromic Robin Sequence (RS) and a control group with unilateral incomplete cleft lip (UICL) in which the lip was surgically closed at 2 months of age. MATERIAL The 52 children (7 RS and 45 UICL) included in the study were drawn from a group representing all Danish cleft children born 1976 through 1981. The ages of the children were 2 and 22 months at the time of examination 1 and 2, respectively. METHOD The method of investigation was three-projection cephalometry. Craniofacial morphology was analyzed by means of linear, angular, and area variables. Growth at a specific anatomical location in a patient was defined as the displacement vector from the coordinate of the corresponding landmark at examination 1 to its coordinate at examination 2. RESULTS The most striking findings in the RS group were markedly increased posterior maxillary width, increased width of the nasal cavity, short maxilla with reduced posterior height, short mandible, bimaxillary retrognathia, and severe reduction in size of the pharyngeal airway. The amount of facial growth was similar in the two groups; however, a tendency toward a more vertical growth direction was observed in the RS group. CONCLUSION Facial morphology in children with RS differed significantly from that of children with UICL at both 2 and 22 months of age. The magnitude of facial growth was similar in the two groups, whereas a tendency toward a more vertical facial growth direction was observed in the RS group.

The visible ear: A digital image library of the temporal bone

High-fidelity computer-based modeling, simulation and visualization systems for the study of temporal bone anatomy and training for middle ear surgery are based on a sequence of digital anatomical images, which must cover a large tissue volume and yet display details in high resolution and with high fidelity. However, the use of existing image libraries by independent developers of virtual models of the ear is limited by copyright protection and low image resolution. A fresh frozen human temporal bone was CT-scanned and serially sectioned at 25 µm and digital images of the block surface were recorded at 50- to 100-µm increments with a Light PhaseTM single-shot camera back attachment. A total of 605 images were recorded in 24-bit RGB resolution. After color correction and elimination of image size variation by differential cropping to 15.4 cm × 9.7 cm, all images were resampled to 3,078 × 1,942 pixels at a final resolution of 50 µm/pixel and stored as 605 one-Mb JPEG files together with a three-dimensional viewer. The resulting complete set of image data provides: (1) a source material suitable for generating computer models of the human ear; (2) a resource of high-quality digital images of anatomical cross sections from the human ear, and (3) a PC-based viewer of the temporal bone in three perpendicular planes of section.

A MODEL FOR THE PHARMACOLOGICAL TREATMENT OF CROUZON SYNDROME

OBJECTIVE Crouzon syndrome is caused by mutations in fibroblast growth factor receptor 2 (FGFR2) leading to constitutive activation of receptors in the absence of ligand binding. The syndrome is characterized by premature fusion of the cranial sutures that leads to abnormal cranium shape, restricted brain growth, and increased intracranial pressure. Surgical remodeling of the cranial vault is currently used to treat affected infants. The purpose of this study was to develop a pharmacological strategy using tyrosine kinase inhibition as a novel treatment for craniosynostotic syndromes caused by constitutive FGFR activation. METHODS Characterization of cranial suture fusion in Fgfr2 mutant mice, which carry the most common Crouzon mutation, was performed using micro-computed tomographic analysis from embryogenesis through maturation. Whole calvarial cultures from wild-type and Fgfr2 mice were established and cultured for 2 weeks in the presence of dimethyl sulfoxide control or PD173074, an FGFR tyrosine kinase inhibitor. Paraffin sections were prepared to show suture morphology and calcium deposition. RESULTS In untreated Fgfr2 cultures, the coronal suture fused bilaterally with loss of overlap between the frontal bone and parietal bone. Calvaria treated with PD173074 (2 micromol/L) showed patency of the coronal suture and were without evidence of any synostosis. CONCLUSION We report the successful use of PD173074 to prevent in vitro suture fusion in a model for Crouzon syndrome. Further studies are underway to develop an in vivo treatment protocol as a novel therapeutic modality for FGFR associated craniosynostotic syndromes.

Craniofacial morphology and growth comparisons in children with Robin Sequence, isolated cleft palate, and unilateral complete cleft lip and palate.

OBJECTIVE Comparison of early craniofacial morphology and growth in children with nonsyndromic Robin Sequence (RS), isolated cleft palate (ICP), and unilateral complete cleft lip and palate (UCCLP). SUBJECTS One hundred eight children with cleft: 7 with RS, 53 with ICP, and 48 with UCCLP were included in the study. The children were drawn from the group of all Danish children with cleft born 1976 through 1981. METHOD Three-projection infant cephalometry. RESULTS The craniofacial morphology in the RS, ICP, and UCCLP groups had some common characteristics: a wide maxilla with decreased length and posterior height, wide nasal cavity, short mandible, bimaxillary retrognathia, and reduced pharyngeal airway. The shortest mandible was found in RS followed by ICP and UCCLP; the pharyngeal airway was reduced in RS and ICP, compared with UCCLP; and the maxillary complex and nasal cavity were wider in UCCLP than in the other groups. The amount of facial growth in all three groups was similar; however, the direction was more vertical in UCCLP than in RS and ICP. CONCLUSION Except for a shorter RS mandible, the facial morphology of infants with RS and ICP was similar, as was the amount of facial growth and the growth pattern. The differences in facial morphology can be ascribed to the difference in the primary anomaly. The amount of facial growth was similar in the three groups; however, the growth pattern showed a more vertical direction in UCCLP than in RS and ICP. It is hypothesized that the mandibular retrognathia in RS represents the outer end of that of the ICP distribution.

Quantitative ultrasound tissue characterization in shoulder and thigh muscles – a new approach

BackgroundThe echogenicity patterns of ultrasound scans contain information of tissue composition in muscles. The aim was: (1) to develop a quantitative ultrasound image analysis to characterize tissue composition in terms of intensity and structure of the ultrasound images, and (2) to use the method for characterization of ultrasound images of the supraspinatus muscle, and the vastus lateralis muscle.MethodsComputerized texture analyses employing first-order and higher-order grey-scale statistics were developed to objectively characterize ultrasound images of m. supraspinatus and m. vastus lateralis from 9 healthy participants.ResultsThe mean grey-scale intensity was higher in the vastus lateralis muscle (p < 0.05) than in the supraspinatus muscle (average value of middle measuring site 51.4 compared to 35.0). Furthermore, the number of spatially connected and homogeneous regions (blobs) was higher in the vastus lateralis (p < 0.05) than in the supraspinatus (average for m. vastus lateralis: 0.092 mm-2 and for m. supraspinatus: 0.016 mm-2).ConclusionThe higher intensity and the higher number of blobs in the vastus lateralis muscle indicates that the thigh muscle contained more non-contractile components than the supraspinatus muscle, and that the muscle was coarser. The image analyses supplemented each other and gave a more complete description of the tissue composition in the muscle than the mean grey-scale value alone.