Facing the Future of Craniofacial Genetics

“It is the common wonder of all men, how among so many millions of faces, there should be none alike,” wrote Sir Thomas Browne in Religio Medici published in 1643. Ever since, people have been intrigued by the development of the human head and face and its biodiversity. Nowadays, we know that both nurture and nature, like cellular and molecular pathways, play a key role in this craniofacial development. If the cellular and/or molecular pathways are disturbed by gene mutations a malformation can occur. The aim of this thesis is to explore the genetic alterations that cause craniofacial malformations using next generation sequencing

Physical and statistical shape modelling in craniomaxillofacial surgery: a personalised approach for outcome prediction

Orthognathic surgery involves repositioning of the jaw bones to restore face function and shape for patients who require an operation as a result of a syndrome, due to growth disturbances in childhood or after trauma. As part of the preoperative assessment, three-dimensional medical imaging and computer-assisted surgical planning help to improve outcomes, and save time and cost. Computer-assisted surgical planning involves visualisation and manipulation of the patient anatomy and can be used to aid objective diagnosis, patient communication, outcome evaluation, and surgical simulation. Despite the benefits, the adoption of three-dimensional tools has remained limited beyond specialised hospitals and traditional two-dimensional cephalometric analysis is still the gold standard. This thesis presents a multidisciplinary approach to innovative surgical simulation involving clinical patient data, medical image analysis, engineering principles, and state-of-the-art machine learning and computer vision algorithms. Two novel three-dimensional computational models were developed to overcome the limitations of current computer-assisted surgical planning tools. First, a physical modelling approach – based on a probabilistic finite element model – provided patient-specific simulations and, through training and validation, population-specific parameters. The probabilistic model was equally accurate compared to two commercial programs whilst giving additional information regarding uncertainties relating to the material properties and the mismatch in bone position between planning and surgery. Second, a statistical modelling approach was developed that presents a paradigm shift in its modelling formulation and use. Specifically, a 3D morphable model was constructed from 5,000 non-patient and orthognathic patient faces for fully-automated diagnosis and surgical planning. Contrary to traditional physical models that are limited to a finite number of tests, the statistical model employs machine learning algorithms to provide the surgeon with a goal-driven patient-specific surgical plan. The findings in this thesis provide markers for future translational research and may accelerate the adoption of the next generation surgical planning tools to further supplement the clinical decision-making process and ultimately to improve patients’ quality of life

PRELIMINARY FINDINGS OF A POTENZIATED PIEZOSURGERGICAL DEVICE AT THE RABBIT SKULL

The number of available ultrasonic osteotomes has remarkably increased. In vitro and in vivo studies have revealed differences between conventional osteotomes, such as rotating or sawing devices, and ultrasound-supported osteotomes (Piezosurgery®) regarding the micromorphology and roughness values of osteotomized bone surfaces. Objective: the present study compares the micro-morphologies and roughness values of osteotomized bone surfaces after the application of rotating and sawing devices, Piezosurgery Medical® and Piezosurgery Medical New Generation Powerful Handpiece. Methods: Fresh, standard-sized bony samples were taken from a rabbit skull using the following osteotomes: rotating and sawing devices, Piezosurgery Medical® and a Piezosurgery Medical New Generation Powerful Handpiece. The required duration of time for each osteotomy was recorded. Micromorphologies and roughness values to characterize the bone surfaces following the different osteotomy methods were described. The prepared surfaces were examined via light microscopy, environmental surface electron microscopy (ESEM), transmission electron microscopy (TEM), confocal laser scanning microscopy (CLSM) and atomic force microscopy. The selective cutting of mineralized tissues while preserving adjacent soft tissue (dura mater and nervous tissue) was studied. Bone necrosis of the osteotomy sites and the vitality of the osteocytes near the sectional plane were investigated, as well as the proportion of apoptosis or cell degeneration. Results and Conclusions: The potential positive effects on bone healing and reossification associated with different devices were evaluated and the comparative analysis among the different devices used was performed, in order to determine the best osteotomes to be employed during cranio-facial surgery