Challenges in developing a quantitative method of measuring breast development using 3D imaging: An example of a novel method for use in induced breast development with exogenous oestrogen.

OBJECTIVE: Optimal breast development is an essential part of exogenous oestrogen treatment in females undergoing pubertal induction. We set out to develop a novel technique using three-dimensional (3D) imaging to determine change in breast volume that is applicable when no pre-existing breast contours are present. DESIGN: A prospective observational study. PATIENTS: The imaging methodology was developed using a single male subject to assess reproducibility and validity. The technique was then applied to 29 participants undergoing pubertal induction with exogenous oestradiol who were recruited from Paediatric Gynaecology and Reproductive Endocrinology clinics at University College London Hospital. MEASUREMENTS: Breast images were taken using a 3D photographic system. Two images, taken at different times, were manually superimposed to produce a differential breast volume. The initial step of method development set out to show that volume change was not secondary to positioning artefact or image manipulation. This was established by using images of a male participant taken on different occasions. The technique was then used to assess reproducibility in participants undergoing pubertal induction treatment. RESULTS: Good intraobserver reproducibility (intraclass correlation (ICC) 0.77) was demonstrated with static image manipulation. Validity of the imaging technique was established as there was no significant difference between the known reference volume produced by computer generated warping and that calculated by manual image manipulation. There was excellent intraobserver reproducibility for breast volume calculation in participants undergoing induced breast development (ICC 0.99). CONCLUSIONS: 3D imaging is a promising novel tool to provide quantitative breast volume assessment in individuals undergoing breast induction with exogenous oestradiol treatment.

Variability of response to early puberty induction demonstrated by transverse uterine diameter measurement and a novel method of 3D breast imaging.

OBJECTIVE: Induction of puberty with exogenous oestrogen results in considerable variability in final uterine and breast volumes. We set out to quantify the variability of these two outcome measures with a view to establishing monitoring methods that could be used to individualise treatment protocols. DESIGN: A prospective observational study. PARTICIPANTS: Sixteen participants with pubertal delay and primary amenorrhoea, due to hypogonadism were recruited from paediatric gynaecology and endocrinology clinics at University College London Hospital. A standardised protocol of transdermal 17ß oestradiol (17ßE) was used (Evorel™), with a starting dose of 12.5 mcg increasing to 25 mcg (patch changed twice weekly) after 4 months. Follow up was every 2 months for a total of 8 months. MEASUREMENTS: Uterine dimensions using ultrasound, oestradiol concentrations and breast development assessed by both Tanner staging and 3D photographic imaging. RESULTS: After 8 months of treatment, the changes in oestradiol concentrations (0-174 pmol), uterine volume growth (4.4-16.4 ml) and breast volume (1.76-140.1 ml) varied greatly between individuals. Of uterine parameters, transverse uterine diameter was most closely associated with serum oestradiol levels at 8 months (beta standardised coefficient = 0.80, p = .001). Change in breast volume was associated with age of treatment initiation (beta standardised coefficient 0.55 p = .04). CONCLUSIONS: We demonstrate variation in response to exogenous oestrogen, emphasising the necessity for individualised dose titration. In the absence of sensitive oestradiol assays, uterine transverse measurements may be used as a surrogate marker of oestrogen sensitivity to guide early dose adjustment. 3D breast imaging may provide a quantitative assessment of breast development to complement Tanner breast staging.

Using principal component analysis to describe the midfacial deformities in patients with craniofacial microsomia.

PURPOSE: Craniofacial microsomia (CFM) is the result of a disturbance in embryologic development and is characterised by an asymmetric, mostly unilateral facial underdevelopment. The aim of this study is to understand the midfacial involvement in CFM using principal component analysis (PCA). MATERIALS AND METHODS: Pre-operative data from 19 CFM and 23 control patients were collected. A set of 71 landmarks was placed on three-dimensional (3D) reconstructions of all skulls to compare both populations. PCA visualised variation within both groups and calculated the vector of change. Linear measurements were taken to compare ratios between the populations and between the affected and unaffected sides in CFM patients. RESULTS: PCA defined a vector that described shape changes between both populations. Videos showed the variation within the control and CFM group and the transformation from a mean CFM skull into a normal phenotype. Linear measurements showed a significant difference between the affected and unaffected sides in CFM patients. CONCLUSION: PCA has not been applied on asymmetrical data before, but it has proved to be a useful method to describe CFM. The virtual normalisation of a mean CFM skull enables visualisation of the bony shape changes, which is promising to delineate and to plan surgical correction and could be used as an outcome measure.

A comparative study to investigate the effect of orthodontic treatment on the uniqueness of the human anterior dentition.

AIM: The human dentition contains many features which can be used to identify an individual from the dentition or from bite marks created and bite mark evidence may be used to link a suspect to a crime. The aim of this research was to investigate the effect of orthodontic treatment on the uniqueness of the human anterior dentition by comparison of the number of dental shape matches between pre- and post-treatment dental casts for a group of patients who have undergone orthodontic treatment (dental braces) to improve the alignment of their teeth. METHOD: This comparative study utilised pre- and post-orthodontic treatment dental casts from 36 patients. The dental casts were scanned and the anterior 6 teeth landmarked with 24 landmarks in total. The dental casts were divided into 4 groups: pre-orthodontic upper jaw (maxillary) and lower jaw (mandibular) and post-orthodontic maxillary and mandibular. Partial and full Procrustes analyses were undertaken to investigate the similarity between dental casts within each group and whether any of the comparisons were similar enough to be classified as a match. A landmarking repeatability study performed on a set of digitised dental casts determined the error of the landmarking procedure and allowed a proposed match threshold to be established. RESULTS: Orthodontic treatment reduced the uniqueness, and increased the similarity, between dentitions, as evidenced by a reduction in the maximum partial Procrustes distances in the post-orthodontic dental cast groups. None of the dental cast comparisons in the pre- or post-orthodontic maxillary or mandibular groups were classified as a match with the partial Procrustes analysis. However, many false positive matches (between 35 and 61) were identified within the post-orthodontic maxillary and mandibular groups using the full Procrustes analysis. CONCLUSIONS: Orthodontic treatment reduced the uniqueness of the human anterior dentition between different patients. There were no matches identified with the partial Procrustes analysis, but a large number of false positive matches were identified using the full Procrustes analysis. It is therefore proposed that full Procrustes analysis is unsuitable for this type of work and that only partial Procrustes analysis should be utilised.

The Role of Bipartition Distraction in the Treatment of Apert Syndrome.

Apert syndrome is characterized by hypertelorism, a negative canthal axis, and central midfacial hypoplasia, resulting in a biconcave face. Bipartition distraction partially corrects these facial anomalies. This study investigates limitations of bipartition distraction using linear, angular, and geometric morphometric analysis. Preoperative and postoperative three-dimensional computed tomographic craniofacial constructs of 10 patients with Apert syndrome (aged 12 to 21 years) were annotated with 98 landmarks. Twelve age-, sex, and ethnicity-matched normal skulls provided control data. Principal component analysis was used to analyze shape characteristics within and between the groups and describe the changes occurring with surgery. Results were displayed graphically using difference color maps. Conventional point-based measurements documented midfacial width, height, and asymmetry. Apert three-dimensional constructs exhibited reduced upper midfacial height and greater extrinsic symmetric variation relative to controls. Facial bipartition partially corrected excessive midfacial width and interorbital distance but did not adequately correct deficient upper midfacial height. Excessive orbital diameter was unaltered by surgery. There was no demonstrable effect on intrinsic or extrinsic midfacial asymmetry. Principal component analysis demonstrated improved midfacial projection and correction of central biconcavity. Bipartition distraction corrects midfacial retrusion, exorbitism, and hypertelorism. It does not treat midfacial height disproportion or correct orbital shape. It leaves the face too wide at the zygomatic level and does not correct facial asymmetry. Although bipartition distraction is an improvement on the unmodified monobloc advancement, further refinements are needed to fully correct Apert dysmorphology.

Evaluating the Efficacy of Monobloc Distraction in the Crouzon-Pfeiffer Craniofacial Deformity Using Geometric Morphometrics.

BACKGROUND: Crouzon-Pfeiffer syndrome is caused by mutations predominantly in the FGFR2 gene leading to syndromic craniosynostosis and midfacial hypoplasia. Monobloc distraction aims to correct both functional and aesthetic disharmony as a result of midfacial hypoplasia. This study evaluates the corrective effects and effectiveness of monobloc distraction in Crouzon-Pfeiffer patients. METHODS: Preoperative and postoperative scans were collected from 20 Crouzon and two Pfeiffer patients aged 7 to 20 years. Fifty-six normal skulls were used as a control group. Geometric morphometrics using 52 frontofacial landmarks were used to analyze the normal skull and preoperative and postoperative patient skulls. Color maps were created to visualize differences among the average normal, preoperative, and postoperative Crouzon-Pfeiffer patients. RESULTS: In the studied patient population, monobloc distraction with the use of an external distractor advanced the upper half of the midface more than the lower half of the midface. There was an anteroinferior rotation in the monobloc segment. The zygomatic arch length improved on average to 88 and 90 percent of normal (right and left, respectively), whereas globe protrusion was corrected from 134 percent to 84 percent and from 131 percent to 87 percent of normal (right and left, respectively) in the studied patient population. Compared with a normal skull, the maxillary region remained retruded. CONCLUSIONS: The advancement achieved by monobloc distraction is effective in the upper half of the midface; the lower half of the midface is advanced but remains retruded in comparison with the normal population. The midface is rotated anteroinferiorly. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

An Automatic 3D Facial Landmarking Algorithm Using 2D Gabor Wavelets.

In this paper, we present a novel approach to automatic 3D facial landmarking using 2D Gabor wavelets. Our algorithm considers the face to be a surface and uses map projections to derive 2D features from raw data. Extracted features include texture, relief map, and transformations thereof. We extend an established 2D landmarking method for simultaneous evaluation of these data. The method is validated by performing landmarking experiments on two data sets using 21 landmarks and compared with an active shape model implementation. On average, landmarking error for our method was 1.9 mm, whereas the active shape model resulted in an average landmarking error of 2.3 mm. A second study investigating facial shape heritability in related individuals concludes that automatic landmarking is on par with manual landmarking for some landmarks. Our algorithm can be trained in 30 min to automatically landmark 3D facial data sets of any size, and allows for fast and robust landmarking of 3D faces.

Describing Crouzon and Pfeiffer syndrome based on principal component analysis.

UNLABELLED: Crouzon and Pfeiffer syndrome are syndromic craniosynostosis caused by specific mutations in the FGFR genes. Patients share the characteristics of a tall, flattened forehead, exorbitism, hypertelorism, maxillary hypoplasia and mandibular prognathism. Geometric morphometrics allows the identification of the global shape changes within and between the normal and syndromic population. METHODS: Data from 27 Crouzon-Pfeiffer and 33 normal subjects were landmarked in order to compare both populations. With principal component analysis the variation within both groups was visualized and the vector of change was calculated. This model normalized a Crouzon-Pfeiffer skull and was compared to age-matched normative control data. RESULTS: PCA defined a vector that described the shape changes between both populations. Movies showed how the normal skull transformed into a Crouzon-Pfeiffer phenotype and vice versa. Comparing these results to established age-matched normal control data confirmed that our model could normalize a Crouzon-Pfeiffer skull. CONCLUSIONS: PCA was able to describe deformities associated with Crouzon-Pfeiffer syndrome and is a promising method to analyse variability in syndromic craniosynostosis. The virtual normalization of a Crouzon-Pfeiffer skull is useful to delineate the phenotypic changes required for correction, can help surgeons plan reconstructive surgery and is a potentially promising surgical outcome measure.

Assessing the corrective effects of facial bipartition distraction in Apert syndrome using geometric morphometrics.

UNLABELLED: Apert syndrome is a congenital disorder characterized by craniosynostosis and midface hypoplasia. This study looks to identify to what extent bipartition distraction corrects the morphological abnormalities of this condition. Preoperative and postoperative three-dimensional computed tomography (3DCT) scans of 10 patients with Apert syndrome (12-21 years) were identified from the Great Ormond Street Hospital database. To analyse preoperative and postoperative scans, 98 landmarks and 13 normal skulls were used. Principal component analysis (PCA) was used to analyse patterns in the datasets. Within each group, eigenvectors were identified that demonstrated the aspects of the skull where most variations were found. The analysis allowed both global shape measurement and local proportions. Postoperative and normal scans both showed the same first three principal components. Warping from preoperative to postoperative illustrates midface advancement and inward rotation of the orbits. Postoperative to normal warps demonstrate some remaining differences. The reliability of the used land marks varied between 77% and 95% for the highly reproducible landmarks between the two observers. 95% versus 100% were at least acceptable reproducible landmarks. This study allows us to understand the way bipartition distraction corrects the abnormalities of the Apert skull. Analysing the surgical outcome of facial bipartition with geometric morphometrics shows that some major Apert characteristics are corrected. Using the data and the output of further studies, surgical procedures can be adapted in order to achieve a postoperative result closer to the normal population. LEVEL OF EVIDENCE: Therapeutic clinical question Level IV.