Biennial Scientific Report 2007-2008 : Volume 2: Cancer Research

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The accuracy of cone beam computed tomography (CBCT) to determine newly formed bone within grafted maxillary sinus in sheep

Grafting of the maxillary sinus floor has become a common surgical intervention to increase bone volume for implant placement (Wallace and Froum, 2003); the procedure can be performed either as an 1-stage procedure with simultaneous implant placement or as a 2-stage procedure before implant placement (Bruggenkate and Bergh, 1998). In a 2-stage procedure, the chosen graft material is placed into the sinus floor and the graft material is left to consolidate with newly formed bone. This consolidation should preferably occur before implant placement. However, currently there is no clinical tool to assess healing within the grafted sinus. A trephine bone biopsy can be harvested for histological assessment but this is invasive and not clinically useful. The current clinical guideline is to wait between six to twelve months after maxillary sinus grafting before implant placement (Rodriguez et al., 2003) CBCT (Cone beam computed tomography) is a clinical 3-D (three-dimensional) radiographic tool for assessment of mineralised tissue (Ehrhart et al., 2008; Estrela et al., 2008) and may be used for assessment of graft healing within maxillary sinus. However, there are a limited number of studies looking at the use of CBCT in bone-density measurements (Benavides et al., 2012). Micro-computed tomography (µCT) is a 3-D radiographic tool mainly used for in vitro studies. Specimens with a volume of approximately 5cm3 can be scanned with up to a 1µm voxel resolution producing high-resolution radiographic images for mineralised tissues. There is growing evidence to suggest that µCT can be used as a substitute method for histology to measure mineralised tissue, particularly trabecular bone (Thomsen et al., 2000; Thomsen et al., 2005). With no clinical tool available for assessment of graft healing within the sinus, the purpose of this study was to assess whether CBCT can be used to measure the amount of newly formed bone in grafted maxillary sinus in sheep. To validate this, CBCT was compared with two reference standards; micro-computed tomography (µCT) and histology. Aim: To assess the effectiveness of CBCT for quantifying newly formed bone within grafted sinus sites, using an animal model. Method: Maxillary sinus grafting in six sheep with bovine xenograft (Endobon®) was evaluated after a sixteen-week healing period. Specimens from each animal were analysed using three imaging techniques: CBCT, µCT and resin-embedded histological sections. Two-dimensional "virtual" CBCT sections were matched with corresponding 2-D µCT sections and digitised histological sections. µCT and CBCT images were calibrated using known-density radiographic calibration standards. Using image analysis software (Image J, NIH, USA), % new bone (%NB), % residual graft (%RG), % mineralised tissue (%MT) were measured for matched regions of interest across each imaging technique and compared statistically (p<0.05). Results: CBCT measured %NB and %RG significantly higher than µCT and histology. µCT measured %NB significantly higher than histology. %RG measurements of µCT and histology were not significantly different. CBCT measured %MT significantly higher than both µCT and histology. %MT measurements of µCT and histology were statistically different but were very similar. Conclusion: Micro-computed tomography (µCT) measurements of residual graft and new bone were affected as the radiodensities of residual graft (Endobon®) and new bone were similar. µCT however appeared to be capable of measuring the combined area of graft and new bone (i.e., mineralised tissue) similar to histomorphometry. Cone-beam computerised tomography (CBCT) markedly overestimated new bone, residual graft and the total mineralised tissue. CBCT lacks the resolution to accurately determine newly formed bone after maxillary sinus grafting, an important step before definitive implant placement

Diagnostic imaging of the tympanic bulla and temporomandibular joint in the dog, cat and rabbit.

The area of the skull incorporating the tympanic bulla (TB) and temporomandibular joint (TMJ) is significant clinically in the dog, cat, and more recently the rabbit. Diagnostic imaging is important in the assessment of disease of these structures but there is a relative lack of comparative anatomical information relating to the normal that may be used to understand the abnormal features encountered when using currently available diagnostic imaging modalities. A review of conventional radiography demonstrated that views for imaging the canine and feline TB could be extrapolated for use in the rabbit but the same did not apply to the TMJ. Plastinated multiplanar anatomical sections proved useful for the identification of anatomical features on corresponding tomographic images. Ultrasound imaging of this region has not been widely reported but allowed evaluation of the TB in all three species, although the information obtained regarding the TMJ was limited. Directly acquired computed tomography (CT) and Magnetic Resonance (MR) images were of better quality than previous publications due to technological advances in the equipment available. Directly acquired images were still better than reconstructed ones and reduced image acquisition times are likely to make this viable in clincal cases. CT produced optimal imaging of the TB but only allowed assessment of the bony elements of the TMJ. Little information was obtained regarding the normal TB using MR imaging due to the indistinguishable signal voids produced by the bone wall and gas lumen. However, T1 weighted sequences allowed identification of intra-articular TMJ soft tissue structures in the dog and rabbit. While opening the mouth altered the areas of the TMJ examined using each modality, it did not improve visualisation of the intra-articular structures. The introduction of fluid into the middle ear cavity of dog, cat and rabbit cadavers aided identification of the TB and acted as a model of one of the major features of acute otitis media, or inflammation of the middle ear cavity. CT was most accurate at identifying middle ear material in cadavers and clinical cases, while ultrasound produced better results than radiography in cadavers but not clinical cases. These imaging modalities also proved useful in the characterisation of the unexpected anatomical anomalies that were encountered during the study. The results of this study indicate that the optimal imaging technique will vary with the species and area being examined, and that extrapolation between species is not always appropriate. Continual improvements in technology and image quality make studies such as this necessary to allow selection of the most appropriate single or combination of imaging techniques and to obtain the maximum amount of information from the resulting images

Digitaler kieferorthopädischer Workflow unter Berücksichtigung funktionstherapeutischer Aspekte

Zielstellung Ziel der vorliegenden Studie ist, einen digitalen Workflow für die Erwachsenenkieferorthopädie unter Einbeziehung funktioneller Aspekte des Kiefergelenks zu erarbeiten und die aktuelle Evidenzlage von dafür notwendigen Teilschritten zusammenzutragen sowie zukünftige Entwicklungsbereiche aufzuzeigen. Als klinischer Anteil soll eine Methode entwickelt werden, um die individuelle Scharnierachse ohne extraoralen Registrierbehelf digital zu bestimmen. Material und Methoden Die Literaturübersicht wird als ausführliche Handsuche in PubMed/MEDLINE und aus referenzierten Quellen erstellt. Das neu erdachte, dreidimensionale Verfahren wird als Proof-of-concept an einem Probanden modifiziert und getestet. Mit dem CentricGuide wird die zentrische Kondylenpostion registriert und anschließend per DVT und MRT validiert und beurteilt. Die Berechnung der Scharnierachsen erfolgt in Matlab anhand von im zahntechnischen Laborscanner digitalisierten Endpositionen mehrerer rotatorischer Öffnungsbewegungen aus der registrierten Zentrikposition. Ergebnisse Ein vollständig digitaler, kieferorthopädischer Workflow unter Einbeziehung funktioneller Aspekte des Kiefergelenkes ist technisch möglich. Mit dem CentricGuide gelingt es bei diesem Probanden, reproduzierbar eine zentrale Position der Kondylen in den Fossae einzustellen. Der erdachte Ansatz ist bei diesem Probanden geeignet, die individuelle Scharnierachse auf 2 mm genau zu lokalisieren. Schlussfolgerungen Der digitale Workflow sollte zugunsten einer patientenindividuelleren Planung und Therapie stärkere Verbreitung finden. Dazu sind weitere klinische Studien zur Validierung der Teilschritte und das Zusammenführen all dieser in einer anwenderfreundlichen Software notwendig. Zur schnellen und einfachen, digitalen Bestimmung der individuellen Scharnierachse sollten entsprechende Algorithmen in die Software von Intraoralscannern aufgenommen und klinisch an größeren Kohorten überprüft werden.Objective A fully digital workflow for orthodontics in adults incorporating functional aspects of the temporomandibular joint (TMJ) is proposed. The current scientific evidence of necessary substeps ranging from planning and simulation to execution is presented. Regarding the substep of patient specific hinge axis determination a novel method independent of any facebow is developed and tested. Materials and Methods To gather scientific evidence PubMed/MEDLINE is searched and the bibliography of relevant articles is considered. As a proof-of-concept the novel 3D-method is tested and refined based on one subject. The centric relation is determined using CentricGuide and evaluated through the means of cone-beam computed tomography (CBCT) and magnetic resonance imaging (MRI). To investigate rotatory jaw opening multiple bite registrations of intermediate positions starting from the same centric relation bite are taken and later digitized in a dental laboratory scanner. Calculation of hinge axes is carried out in Matlab. Results A fully digital workflow for orthodontics in adults incorporating functional aspects of the TMJ is technically feasible. Using CentricGuide a centric condyle-fossa-relation was achieved reproducibly in this subject. Furthermore, hinge axis location could be determined with an accuracy of 2 mm using the novel method. Conclusion To improve patient specific planning, simulation and treatment the digital workflow should be increasingly adopted. This can be accelerated by validating all substeps in clinical studies and finally uniting the whole workflow in a user-friendly software. Algorithms for hinge axis determination (possibly similar to the approach presented) should be implemented in the software of intraoral scanners and tested on validation cohorts. This may lead to an easy, digital and more patient specific, clinical procedure

Segmentation automatique des images de tomographie conique pour la radiothérapie de la prostate

The use of CBCT imaging for image-guided radiation therapy (IGRT), and beyond that, image-guided adaptive radiation therapy (IGART), in the context of prostate cancer is challenging due to the poor contrast and high noise in pelvic CBCT images. The principal aim of the thesis is to provide methodological contributions for automatic intra-patient image registration between the planning CT scan and the treatment CBCT scan. The first part of our contributions concerns the development of a CBCT-based prostate setup correction strategy using CT-to-CBCT rigid registration (RR). We established a comparison between different RR algorithms: (a) global RR, (b) bony RR, and (c) bony RR refined by a local RR using the prostate CTV in the CT scan expanded with 1- to-20-mm varying margins. A comprehensive statistical analysis of the quantitative and qualitative results was carried out using the whole dataset composed of 115 daily CBCT scans and 10 planning CT scans from 10 prostate cancer patients. We also defined a novel practical method to automatically estimate rectal distension occurred in the vicinity of the prostate between the CT and the CBCT scans. Using our measure of rectal distension, we evaluated the impact of rectal distension on the quality of local RR and we provided a way to predict registration failure. On this basis, we derived recommendations for clinical practice for the use of automatic RR for prostate localization on CBCT scans. The second part of the thesis provides a methodological development of a new joint segmentation and deformable registration framework. To deal with the poor contrast-to-noise ratio in CBCT images likely to misguide registration, we conceived a new metric (or enery) which included two terms: a global similarity term (the normalized cross correlation (NCC) was used, but any other one could be used instead) and a segmentation term based on a localized adaptation of the piecewise-constant region-based model of Chan-Vese using an evolving contour in the CBCT image. Our principal aim was to improve the accuracy of the registration compared with an ordinary NCC metric. Our registration algorithm is fully automatic and takes as inputs (1) the planning CT image, (2) the daily CBCT image and (3) the binary image associated with the CT image and corresponding to the organ of interest we want to segment in the CBCT image in the course of the registration process.Dans le contexte du traitement du cancer de la prostate, l’utilisation de la tomodensitométrie à faisceau conique (CBCT) pour la radiothérapie guidée par l’image, éventuellement adaptative, présente certaines difficultés en raison du faible contraste et du bruit important dans les images pelviennes. L’objectif principal de cette thèse est d’apporter des contributions méthodologiques pour le recalage automatique entre l’image scanner CT de référence et l’image CBCT acquise le jour du traitement. La première partie de nos contributions concerne le développement d’une stratégie de correction du positionnement du patient à l’aide du recalage rigide (RR) CT/CBCT. Nous avons comparé plusieurs algorithmes entre eux : (a) RR osseux, (b) RR osseux suivi d’un RR local dans une région qui correspond au clinical target volume (CTV) de la prostate dans l’image CT élargie d’une marge allant de 1 à 20 mm. Une analyse statistique complète des résultats quantitatifs et qualitatifs utilisant toute la base de données, composée de 115 images cone beam computed tomography (CBCT) et de 10 images computed tomography (CT) de 10 patients atteints du cancer de la prostate, a été réalisée. Nous avons également défini une nouvelle méthode pratique et automatique pour estimer la distension rectale produite dans le voisinage de la prostate entre l’image CT et l’image CBCT. A l’aide de notre mesure de distension rectale, nous avons évalué l’impact de la distension rectale sur la qualité du RR local et nous avons fourni un moyen de prédire les échecs de recalage. Sur cette base, nous avons élaboré des recommandations concernant l’utilisation du RR automatique pour la localisation de la prostate sur les images CBCT en pratique clinique. La seconde partie de la thèse concerne le développement méthodologique d’une nouvelle méthode combinant le recalage déformable et la segmentation. Pour contourner le problème du faible rapport qualité/bruit dans les images CBCT qui peut induire le processus de recalage en erreur, nous avons imaginé une nouvelle énergie composée de deux termes : un terme de similarité globale (la corrélation croisée normalisée (NCC) a été utilisée, mais tout autre mesure de similarité pourrait être utilisée à la place) et un terme de segmentation qui repose sur une adaptation locale du modèle de l’image homogène par morceaux de Chan-Vese utilisant un contour actif dans l’image CBCT. Notre but principal était d’améliorer la précision du recalage comparé à une énergie constituée de la NCC seule. Notre algorithme de recalage est complètement automatique et accepte comme entrées (1) l’image CT de planification, (2) l’image CBCT du jour et (3) l’image binaire associée à l’image CT et correspondant à l’organe d’intérêt que l’on cherche à segmenter dans l’image CBCT au cours du recalage

Synchrotron imaging of bovine and human ovaries ex vivo

Background and Rationale: Reproductive dysfunction affects more than 15% of Canadian women; however, the underlying causes remain largely unknown. Ultrasonography is the most commonly used research and diagnostic tool for imaging the ovaries and uterus. However, current ultrasonographic techniques allow the detection of ovarian structures (eg. follicles, corpora lutea) at diameters of only ≥2 mm. The increased effectiveness of synchrotron technology for imaging ovaries in comparison to conventional imaging methods is currently unknown. Overall Objective: The overall objective of this research was to determine the effectiveness of synchrotron techniques for imaging ovaries. We hypothesized that synchrotron techniques would provide greater contrast for visualizing structural details of follicles, corpora lutea (CL), and cumulus oocyte complexes (COC), compared to conventional ultrasonography. Materials and Methods: Three studies were conducted to evaluate phase-contrast based synchrotron imaging methods. The first study involved Diffraction Enhanced Imaging (DEI) of bovine ovaries (n=6). The second study involved Propagation-Based Computed Tomography (PB-CT) imaging of bovine (n=4) and human ovaries (n=4). A third, preliminary study was conducted to explore the use of Talbot Grating Interferometry (TGI-CT) imaging of bovine (n=1) and human ovaries (n=1). Fresh and formalin-fixed bovine and human ovaries were imaged without or with contrast injection into the ovarian artery. Following synchrotron imaging, all ovarian samples were evaluated using diagnostic ultrasonography and histology. Images obtained using synchrotron techniques, ultrasonography and histology were qualitative and quantitatively compared. Results: DEI allowed the identification of 71% of follicles ≥2 mm and 67% of CL detected using ultrasonography. Mean follicle diameter was similar between DEI (9.6 ± 2.4 mm), ultrasonography (9.0 ± 2.6 mm), and histology (6.9 ± 1.9 mm) for fresh ovaries without contrast (P = 0.70). Likewise, no difference in CL diameter was detected between DEI (11.64 ± 1.67 mm), ultrasonography (9.34 ± 0.35 mm), and histology (9.6 ± 0.4 mm), (P = 0.34). Antral Follicle Count (AFC; ≥2mm) was similar between ultrasonography (6.5 ± 0.7 mm, fresh with no contrast; 6.5 ± 2.5 mm, preserved with no contrast) and DEI ( 4.5 ± 0.5 mm, fresh with no contrast; 6.5 ± 0.50 mm, preserved with no contrast) (P > 0.05). However, the contrast resolution for differentiating follicles and CL was inferior with DEI compared to ultrasonography. Small antral follicles <2mm, cell layers comprising the follicle wall and COC were not detected using either DEI or ultrasonography. PB-CT imaging enabled the visualization of 100% of follicles ≥2 mm and 100% of CL that were detected with ultrasonography. CL containing a central cystic cavity were identified using PB-CT; however, CL without a central cystic cavity were not well-visualized. Mean follicle and luteal diameters did not differ among PB-CT, ultrasonography and histology (P>0.05). PB-CT was superior to ultrasonography for detecting small antral follicles <2 mm in bovine ovaries (P = 0.04), and the granulosa and theca cell layers of the follicle wall in bovine and human ovaries (P < 0.0001). However, TGI-CT images exhibited greater contrast resolution for visualizing small and large antral follicles, CL, and the cell layers of the follicle wall compared to both PB-CT and ultrasonography. High contrast structures resembling COC were detected with both PB-CT and TGI-CT, but not with ultrasonography. Only TGI-CT permitted the visualization of the oocyte within the COC in fresh and preserved ovaries. Conclusions: DEI was inferior to ultrasonography for detecting ovarian follicles and CL. PB-CT was superior to ultrasonography for visualizing follicles <2 mm, COC, and the cell layers of the follicle wall. However, PB-CT was as effective as ultrasonography for detecting and measuring follicles ≥2 mm and cystic CL. Preliminary findings suggest that TGI-CT provides the greatest contrast for imaging both ovarian macro- and microanatomy compared to PB-CT, DEI, and ultrasonography

Alveolar Ridge Preservation in the Sheep Model

Abstract Post extraction remodelling of the alveolar ridge results in significant reduction in the width of the ridge, which may preclude the placement of dental implants. Alveolar ridge preservation (ARP) procedures have been shown to reduce these changes, and thus are desirable, especially when the buccal plate is partially missing. Bovine-derived xenografts with porcine collagen membrane (BX) are considered the “gold standard” against which novel ARP materials should be compared. Four equine collagen products developed for ARP were tested: membrane (CM), cone with/without biphasic phosphate particles (CC, CO), and cone with integrated membrane (CS). Objectives To compare four novel products against BX in a novel sheep mandibular extraction socket model with standardised buccal defect. Methodology In 11 animals, mandibular premolars were extracted and standardised 5x2 mm buccal dehiscence defects were created. The sockets were grafted (Latin-square allocation) with BX, CC, CS, CO, CO+CM or ungrafted control (CON). The animals were euthanised after 16 weeks. Socket healing, new bone formation and reduction in the alveolar ridge width were analysed in undemineralised sections. Results No distinctive pattern of healing was noted for any of the materials. BX particles were partially resorbed by osteoclast-like multinuclear cells. Remnants of equine collagen-based products were not observed. BX grafted sites, compared to CON, showed a threefold decrease in reduction of the alveolar ridge width (p=0.002). Width preservation achieved by equine collagen products compared to non-grafted controls was not statistically significant, however better results were observed in groups CS and CO+CM. Conclusion A challenging extraction socket model with buccal defects representative of a “real-life” clinical situation was created. The test materials did not preclude new bone formation and were completely resorbed during the healing period, whereas BX-grafted sites have shown only partial resorption of the graft. The test materials, unlike the “gold standard” BX, were unable to demonstrate significant width preservation, although the results suggested that barrier membranes play an important role in ARP procedures

Applications of micro-CT in the Criminal Justice System of England and Wales: an impact assessment

The Criminal Justice System of England and Wales is currently facing major challenges. One is the financial pressure of government funding cuts, the other the increasing need for professionalisation and rigour within the system. This thesis presents the use of micro Computed Tomography, Additive Manufacturing, and 3D visualisation to address both challenges. By drawing on data from live murder investigations the project examines how these digital technologies can be used to improve the investigation of strangulation deaths, sharp force injuries, and fractures. Each of these categories was treated as a separate case in the overall multiple-case study research design. The increased detail enabled by micro-CT assisted pathologists in the diagnosis of strangulation as previously undetected injuries of the larynx could be identified. A validation study comparing injured to uninjured samples was conducted to increase the strength of the interpretations. For sharp force injuries analysis, micro-CT proved useful for providing the necessary injury characteristics and highly accurate measurements to allow weapon identification. The high resolution of micro-CT scanning also enabled the visualisation of trauma on the smallest of skeletal elements, often encountered in non-accidental injuries in children. The cross-case synthesis revealed the main themes of clarity, objectivity, and visualisation which were improved by using micro-CT irrespective of type of homicide. The significance of these themes further crystallised in semi-structured interviews conducted with various stakeholders of the Criminal Justice System. Management concepts proved suitable to assess the project’s success as the themes used in operations management such as quality, delivery, and cost apply to the delivery of justice as well. A good working relationship with West Midlands Police’s homicide investigators and researchers at WMG was crucial to providing the technology and expertise to address real-life problems whilst ultimately saving taxpayers’ money