All PhD Theses

M.A.R. Kuijpers

3D imaging in patients with orofacial clefts


A scientific essay in Medical Sciences

DOCTORAL THESIS defended in public on 16th of November 2018


Cleft lip and/or cleft palate is a congenital malformation in humans, which comprises a heterogeneous group due to the large variety in the cleft phenotype. Patients undergo treatment by an interdisciplinary team of specialists from infancy to adulthood to correct anatomy, improve facial esthetics and restore function. There are many different treatment protocols and there is still uncertainty about which are the best. Therefore, evaluation of treatment outcomes following different treatment protocols remains important. For this purpose, in the past mainly information derived from two-dimensional imaging modalities has been used next to information from plaster models, which is inherently three-dimensionally. However, current technology enables digital outcome assessment using three-dimensional imaging methods. This study describes the rise of three-dimensional imaging of the face and investigates some clinical possibilities for its use after birth. In Chapter 1 the background and rationale of this PhD study are explained.

In Chapter 2 a systematic review was presented that aimed at identifying 3D imaging methods for quantitative assessment of soft tissue and skeletal morphology in patients with cleft lip and palate. We included publications using 3D imaging techniques to assess facial soft tissue or skeletal morphology in patients older than 5 years with a cleft lip with/or without cleft palate. We reviewed studies involving the facial region when at least 10 subjects in the sample had at least one cleft type. Independent extraction of data and quality assessments were performed by two observers. Five hundred full text publications were retrieved, 144 met the inclusion criteria, with 63 high quality studies. There were differences in study designs, topics studied, patient characteristics, and success measurements which hampered a meta-analysis of the collected data. Main 3D-techniques that are used in cleft lip and palate patients are CT, CBCT, MRI, stereophotogrammetry, and laser surface scanning. These techniques are mainly used for soft tissue analysis, evaluation of bone grafting, and changes in the craniofacial skeleton. Digital dental casts are used to evaluate treatment and changes over time. We concluded that available evidence implies that 3D imaging methods can be used for documentation of CLP patients. No data are available yet showing that 3D methods are more informative than conventional 2D methods. Further research is warranted to elucidate that.

In Chapter 3 we presented a study on incidental findings on CBCTs in patients with OFC. CBCTs taken of consecutive patients with a non-syndromic orofacial cleft were systematically evaluated. Of these patients, 28 had their first CBCT after bone grafting. The whole CBCT image meaning sinuses, nasopharynx, oropharynx, throat, skull, vertebrae, temporomandibular joint (TMJ), maxilla and mandible were checked for incidental findings. Besides the cleft in 95% of the patients incidental findings were found. Most of these findings concerned sinus and airway findings, followed by dental findings, nasal septum deviation, ear related findings, abnormal temporomandibular joint and vertebral anatomy. Donor site of the alveolar bone graft was still recognizable in half of the patients. A tenth of the patients needed referral for further diagnosis and 9% needed further dental treatment. Some findings in patients who were referred to other clinicians appeared to be related to cleft palate treatment. Together with the other findings in the craniofacial area it shows that the CBCT provides diagnostic information for all specialties involved in cleft palate treatment, and therefore the image should be reviewed by all specialists in de the CLP team.

In Chapter 4 we described a study on the reliability of the application of the EUROCRAN index on 3D digital models or photographs of plaster models instead of using plaster models. The EUROCRAN index has been used in intercenter studies to assess dental arch relationship and palatal morphology in children with unilateral cleft lip and palate (UCLP). The EUROCRAN reference models, which are used as anchor models in studies rating plaster casts, were presented in three formats: plaster models, 2D photographs of plaster models and 3D digital models. Plaster models, 2D photographs of plaster models and 3D digital models of 45 children with UCLP were rated by six calibrated observers in random order. The strength of agreement of the ratings was assessed as well concordance between observers. It appeared that dental arch relationship could be reliably assessed in all formats, Palatal morphology was more difficult to assess and the reliability was moderate to poor between raters and between formats. The overall results show that all formats - plaster models, 3D models and 2D pictures of plaster models - can be used for intercenter treatment evaluation when the dental arch relationship is concerned. Palatal morphology is difficult to assess with the EUROCRAN index.

In Chapter 5 a study was described that investigated differences in facial morphology between non- cleft individuals and patients with a unilateral cleft using stereophotogrammetry. Standardized three-dimensional facial images of 58 patients (9 UCL, 21 UCLA, and 28 UCLP and 121 controls were mirrored and distance maps were created for each subject. After that, absolute mean asymmetry values were calculated from distance maps for the whole face and for different areas (cheek, nose, lips and chin). Differences between clefts and controls for the whole face and separate areas were calculated. It appeared that clefts and controls differ significantly for the whole face as well as in all areas. Each group had its own distinct asymmetry pattern. Asymmetry of the nose was the most distinct feature in the cleft patients whereas the chin was most asymmetric in the control group. In the UCLP group the nose followed by the lips was the most asymmetric area. UCL and UCLA patients were closer to the asymmetry pattern of the control group. This study shows that differences between patients can be objectively measured using stereophotogrammetry.

In Chapter 6 we addressed the question whether the amount of deviation in nasal and labial shape is related to the rating of esthetics of the nasolabial area in patients with cleft lip and palate. Stereophotogrammetric images of 60 patients with a unilateral orofacial cleft (UCL n=10; UCLA n=23 and UCLP n=27), prior to bone grafting and hard palate closure, were used. Four average faces, girls and boys below 10.5 year, girls and boys above 10.5 year, were constructed of stereophotogrammetric images of 141 girls and 60 boys without a cleft. Three- dimensional shape differences were calculated between the superimposed cleft faces and the average non-cleft face for the patient’s same sex and age group. Nasolabial esthetics rating was done on 3D images of the cleft patients using the modified Asher-McDade Aesthetic Index using a visual analogue scale (VAS). The mean overall esthetic scores (mean VAS, nasal deviation, nasal form, nasal profile) ranged from 51.44 (sd 8.70) to 60.21 (sd 8.41) for the three cleft groups, with lower esthetic ratings associated with increasing cleft severity. The same pattern was observed for the three esthetic components of the nose separately. As expected, shape differences were found between cleft faces and the average non-cleft face, independent of the cleft type. However, when relating these shape differences to VAS, no relation was found for the VAS, age, and sex, except that a lower VAS was related to a higher nose and lip distance in the nasal profile (p=0.02). Yet the explained variance was very low (R2 = 0.066). Except for the nasal profile, the nasolabial esthetics were not influenced by the extent of shape differences from the average non-cleft face. Thus, factors other than the amount of deviation from the non-cleft face may influence nasolabial esthetics in patients with clefts.

In Chapter 7 methodological issues and results are discussed for the 5 research questions addressed in this thesis. Currently there is a switch noticeable from 2D to 3D facial imaging and 3D methods used to evaluate treatment outcome, occlusion, maxillary growth and development seem to be valid methods to justify this switch. Large-scale intercentre studies and International organizations like the International Consortium for Health Outcome Measurement (ICHOM) and the American Cleft Palate Craniofacial Association (ACPA) have also made an effort to propose standard record sets to facilitate treatment evaluation and intercentre comparisons but all still rely on 2D-based documentation sets extended with patient related outcome measures, PROMs (ICHOM). We propose a documentation set that on the one hand is strongly inspired by the ICHOM data set but at the same time enables objective treatment outcome measures taking into account the latest developments in 3D- imaging. Research of the relationship between patient-reported outcomes like the ones proposed by ICHOM, and objectively measured outcomes (with 3D imaging) is recommended.