A cost-effective surgical navigation solution for periacetabular osteotomy (PAO) surgery

In this chapter a low-cost surgical navigation solution for periacetabular osteotomy (PAO) surgery is described. Two commercial inertial measurement units (IMU, Xsens Technologies, The Netherlands), are attached to a patient’s pelvis and to the acetabular fragment, respectively. Registration of the patient with a pre-operatively acquired computer model is done by recording the orientation of the patient’s anterior pelvic plane (APP) using one IMU. A custom-designed device is used to record the orientation of the APP in the reference coordinate system of the IMU. After registration, the two sensors are mounted to the patient’s pelvis and acetabular fragment, respectively. Once the initial position is recorded, the orientation is measured and displayed on a computer screen. A patient-specific computer model generated from a pre-operatively acquired computed tomography (CT) scan is used to visualize the updated orientation of the acetabular fragment. Experiments with plastic bones (7 hip joints) performed in an operating room comparing a previously developed optical navigation system with our inertial-based navigation system showed no statistical difference on the measurement of acetabular component reorientation (anteversion and inclination). In six out of seven hip joints the mean absolute difference was below five degrees for both anteversion and inclination.

Periacetabular osteotomy restores the typically excessive range of motion in dysplastic hips with a spherical head

BACKGROUND Residual acetabular dysplasia is seen in combination with femoral pathomorphologies including an aspherical femoral head and valgus neck-shaft angle with high antetorsion. It is unclear how these femoral pathomorphologies affect range of motion (ROM) and impingement zones after periacetabular osteotomy. QUESTIONS/PURPOSES (1) Does periacetabular osteotomy (PAO) restore the typically excessive ROM in dysplastic hips compared with normal hips; (2) how do impingement locations differ in dysplastic hips before and after PAO compared with normal hips; (3) does a concomitant cam-type morphology adversely affect internal rotation; and (4) does a concomitant varus-derotation intertrochanteric osteotomy (IO) affect external rotation? METHODS Between January 1999 and March 2002, we performed 200 PAOs for dysplasia; of those, 27 hips (14%) met prespecified study inclusion criteria, including availability of a pre- and postoperative CT scan that included the hip and the distal femur. In general, we obtained those scans to evaluate the pre- and postoperative acetabular and femoral morphology, the degree of acetabular reorientation, and healing of the osteotomies. Three-dimensional surface models based on CT scans of 27 hips before and after PAO and 19 normal hips were created. Normal hips were obtained from a population of CT-based computer-assisted THAs using the contralateral hip after exclusion of symptomatic hips or hips with abnormal radiographic anatomy. Using validated and computerized methods, we then determined ROM (flexion/extension, internal- [IR]/external rotation [ER], adduction/abduction) and two motion patterns including the anterior (IR in flexion) and posterior (ER in extension) impingement tests. The computed impingement locations were assigned to anatomical locations of the pelvis and the femur. ROM was calculated separately for hips with (n = 13) and without (n = 14) a cam-type morphology and PAOs with (n = 9) and without (n = 18) a concomitant IO. A post hoc power analysis based on the primary research question with an alpha of 0.05 and a beta error of 0.20 revealed a minimal detectable difference of 4.6° of flexion. RESULTS After PAO, flexion, IR, and adduction/abduction did not differ from the nondysplastic control hips with the numbers available (p ranging from 0.061 to 0.867). Extension was decreased (19° ± 15°; range, -18° to 30° versus 28° ± 3°; range, 19°-30°; p = 0.017) and ER in 0° flexion was increased (25° ± 18°; range, -10° to 41° versus 38° ± 7°; range, 17°-41°; p = 0.002). Dysplastic hips had a higher prevalence of extraarticular impingement at the anteroinferior iliac spine compared with normal hips (48% [13 of 27 hips] versus 5% [one of 19 hips], p = 0.002). A PAO increased the prevalence of impingement for the femoral head from 30% (eight of 27 hips) preoperatively to 59% (16 of 27 hips) postoperatively (p = 0.027). IR in flexion was decreased in hips with a cam-type deformity compared with those with a spherical femoral head (p values from 0.002 to 0.047 for 95°-120° of flexion). A concomitant IO led to a normalization of ER in extension (eg, 37° ± 7° [range, 21°-41°] of ER in 0° of flexion in hips with concomitant IO compared with 38° ± 7° [range, 17°-41°] in nondysplastic control hips; p = 0.777). CONCLUSIONS Using computer simulation of hip ROM, we could show that the PAO has the potential to restore the typically excessive ROM in dysplastic hips. However, a PAO can increase the prevalence of secondary intraarticular impingement of the aspherical femoral head and extraarticular impingement of the anteroinferior iliac spines in flexion and internal rotation. A cam-type morphology can result in anterior impingement with restriction of IR. Additionally, a valgus hip with high antetorsion can result in posterior impingement with decreased ER in extension, which can be normalized with a varus derotation IO of the femur. However, indication of an additional IO needs to be weighed against its inherent morbidity and possible complications. The results are based on a limited number of hips with a pre- and postoperative CT scan after PAO. Future prospective studies are needed to verify the current results based on computer simulation and to test their clinical importance.

Detection of haemorrhagic shock: Are vital signs obsolete? A commentary by Dr M. Luginbühl

The ATLS program by the American college of surgeons is probably the most important globally active training organization dedicated to improve trauma management. Detection of acute haemorrhagic shock belongs to the key issues in clinical practice and thus also in medical teaching. (In this issue of the journal William Schulz and Ian McConachrie critically review the ATLS shock classification Table 1), which has been criticized after several attempts of validation have failed [1]. The main problem is that distinct ranges of heart rate are related to ranges of uncompensated blood loss and that the heart rate decrease observed in severe haemorrhagic shock is ignored [2]. Table 1. Estimated blood loos based on patient's initial presentation (ATLS Students Course Manual, 9th Edition, American College of Surgeons 2012). Class I Class II Class III Class IV Blood loss ml Up to 750 750–1500 1500–2000 >2000 Blood loss (% blood volume) Up to 15% 15–30% 30–40% >40% Pulse rate (BPM) <100 100–120 120–140 >140 Systolic blood pressure Normal Normal Decreased Decreased Pulse pressure Normal or ↑ Decreased Decreased Decreased Respiratory rate 14–20 20–30 30–40 >35 Urine output (ml/h) >30 20–30 5–15 negligible CNS/mental status Slightly anxious Mildly anxious Anxious, confused Confused, lethargic Initial fluid replacement Crystalloid Crystalloid Crystalloid and blood Crystalloid and blood Table options In a retrospective evaluation of the Trauma Audit and Research Network (TARN) database blood loss was estimated according to the injuries in nearly 165,000 adult trauma patients and each patient was allocated to one of the four ATLS shock classes [3]. Although heart rate increased and systolic blood pressure decreased from class I to class IV, respiratory rate and GCS were similar. The median heart rate in class IV patients was substantially lower than the value of 140 min−1 postulated by ATLS. Moreover deterioration of the different parameters does not necessarily go parallel as suggested in the ATLS shock classification [4] and [5]. In all these studies injury severity score (ISS) and mortality increased with in increasing shock class [3] and with increasing heart rate and decreasing blood pressure [4] and [5]. This supports the general concept that the higher heart rate and the lower blood pressure, the sicker is the patient. A prospective study attempted to validate a shock classification derived from the ATLS shock classes [6]. The authors used a combination of heart rate, blood pressure, clinically estimated blood loss and response to fluid resuscitation to classify trauma patients (Table 2) [6]. In their initial assessment of 715 predominantly blunt trauma patients 78% were classified as normal (Class 0), 14% as Class I, 6% as Class II and only 1% as Class III and Class IV respectively. This corresponds to the results from the previous retrospective studies [4] and [5]. The main endpoint used in the prospective study was therefore presence or absence of significant haemorrhage, defined as chest tube drainage >500 ml, evidence of >500 ml of blood loss in peritoneum, retroperitoneum or pelvic cavity on CT scan or requirement of any blood transfusion >2000 ml of crystalloid. Because of the low prevalence of class II or higher grades statistical evaluation was limited to a comparison between Class 0 and Class I–IV combined. As in the retrospective studies, Lawton did not find a statistical difference of heart rate and blood pressure among the five groups either, although there was a tendency to a higher heart rate in Class II patients. Apparently classification during primary survey did not rely on vital signs but considered the rather soft criterion of “clinical estimation of blood loss” and requirement of fluid substitution. This suggests that allocation of an individual patient to a shock classification was probably more an intuitive decision than an objective calculation the shock classification. Nevertheless it was a significant predictor of ISS [6]. Table 2. Shock grade categories in prospective validation study (Lawton, 2014) [6]. Normal No haemorrhage Class I Mild Class II Moderate Class III Severe Class IV Moribund Vitals Normal Normal HR > 100 with SBP >90 mmHg SBP < 90 mmHg SBP < 90 mmHg or imminent arrest Response to fluid bolus (1000 ml) NA Yes, no further fluid required Yes, no further fluid required Requires repeated fluid boluses Declining SBP despite fluid boluses Estimated blood loss (ml) None Up to 750 750–1500 1500–2000 >2000 Table options What does this mean for clinical practice and medical teaching? All these studies illustrate the difficulty to validate a useful and accepted physiologic general concept of the response of the organism to fluid loss: Decrease of cardiac output, increase of heart rate, decrease of pulse pressure occurring first and hypotension and bradycardia occurring only later. Increasing heart rate, increasing diastolic blood pressure or decreasing systolic blood pressure should make any clinician consider hypovolaemia first, because it is treatable and deterioration of the patient is preventable. This is true for the patient on the ward, the sedated patient in the intensive care unit or the anesthetized patients in the OR. We will therefore continue to teach this typical pattern but will continue to mention the exceptions and pitfalls on a second stage. The shock classification of ATLS is primarily used to illustrate the typical pattern of acute haemorrhagic shock (tachycardia and hypotension) as opposed to the Cushing reflex (bradycardia and hypertension) in severe head injury and intracranial hypertension or to the neurogenic shock in acute tetraplegia or high paraplegia (relative bradycardia and hypotension). Schulz and McConachrie nicely summarize the various confounders and exceptions from the general pattern and explain why in clinical reality patients often do not present with the “typical” pictures of our textbooks [1]. ATLS refers to the pitfalls in the signs of acute haemorrhage as well: Advanced age, athletes, pregnancy, medications and pace makers and explicitly state that individual subjects may not follow the general pattern. Obviously the ATLS shock classification which is the basis for a number of questions in the written test of the ATLS students course and which has been used for decades probably needs modification and cannot be literally applied in clinical practice. The European Trauma Course, another important Trauma training program uses the same parameters to estimate blood loss together with clinical exam and laboratory findings (e.g. base deficit and lactate) but does not use a shock classification related to absolute values. In conclusion the typical physiologic response to haemorrhage as illustrated by the ATLS shock classes remains an important issue in clinical practice and in teaching. The estimation of the severity haemorrhage in the initial assessment trauma patients is (and was never) solely based on vital signs only but includes the pattern of injuries, the requirement of fluid substitution and potential confounders. Vital signs are not obsolete especially in the course of treatment but must be interpreted in view of the clinical context. Conflict of interest None declared. Member of Swiss national ATLS core faculty.

Comparison of 2.5D and 3D Quantification of Femoral Head Coverage in Normal Control Subjects and Patients with Hip Dysplasia.

Hip dysplasia is characterized by insufficient femoral head coverage (FHC). Quantification of FHC is of importance as the underlying goal of the surgery to treat hip dysplasia is to restore a normal acetabular morphology and thereby to improve FHC. Unlike a pure 2D X-ray radiograph-based measurement method or a pure 3D CT-based measurement method, previously we presented a 2.5D method to quantify FHC from a single anteriorposterior (AP) pelvic radiograph. In this study, we first quantified and compared 3D FHC between a normal control group and a patient group using a CT-based measurement method. Taking the CT-based 3D measurements of FHC as the gold standard, we further quantified the bias, precision and correlation between the 2.5D measurements and the 3D measurements on both the control group and the patient group. Based on digitally reconstructed radiographs (DRRs), we investigated the influence of the pelvic tilt on the 2.5D measurements of FHC. The intraclass correlation coefficients (ICCs) for absolute agreement was used to quantify interobserver reliability and intraobserver reproducibility of the 2.5D measurement technique. The Pearson correlation coefficient, r, was used to determine the strength of the linear association between the 2.5D and the 3D measurements. Student's t-test was used to determine whether the differences between different measurements were statistically significant. Our experimental results demonstrated that both the interobserver reliability and the intraobserver reproducibility of the 2.5D measurement technique were very good (ICCs > 0.8). Regression analysis indicated that the correlation was very strong between the 2.5D and the 3D measurements (r = 0.89, p < 0.001). Student's t-test showed that there were no statistically significant differences between the 2.5D and the 3D measurements of FHC on the patient group (p > 0.05). The results of this study provided convincing evidence demonstrating the validity of the 2.5D measurements of FHC from a single AP pelvic radiograph and proved that it could serve as a surrogate for 3D CT-based measurements. Thus it may be possible to use this method to avoid a CT scan for the purpose of estimating 3D FHC in diagnosis and post-operative treatment evaluation of patients with hip dysplasia.

Final Results of a Prospective Evaluation of the Predictive Value of Interim Positron Emission Tomography in Patients With Diffuse Large B-Cell Lymphoma Treated With R-CHOP-14 (SAKK 38/07)

PURPOSE Our main objective was to prospectively determine the prognostic value of [(18)F]fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) after two cycles of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone given every 14 days (R-CHOP-14) under standardized treatment and PET evaluation criteria. PATIENTS AND METHODS Patients with any stage of diffuse large B-cell lymphoma were treated with six cycles of R-CHOP-14 followed by two cycles of rituximab. PET/CT examinations were performed at baseline, after two cycles (and after four cycles if the patient was PET-positive after two cycles), and at the end of treatment. PET/CT examinations were evaluated locally and by central review. The primary end point was event-free survival at 2 years (2-year EFS). RESULTS Median age of the 138 evaluable patients was 58.5 years with a WHO performance status of 0, 1, or 2 in 56%, 36%, or 8% of the patients, respectively. By local assessment, 83 PET/CT scans (60%) were reported as positive and 55 (40%) as negative after two cycles of R-CHOP-14. Two-year EFS was significantly shorter for PET-positive compared with PET-negative patients (48% v 74%; P = .004). Overall survival at 2 years was not significantly different, with 88% for PET-positive versus 91% for PET-negative patients (P = .46). By using central review and the Deauville criteria, 2-year EFS was 41% versus 76% (P < .001) for patients who had interim PET/CT scans after two cycles of R-CHOP-14 and 24% versus 72% (P < .001) for patients who had PET/CT scans at the end of treatment. CONCLUSION Our results confirmed that an interim PET/CT scan has limited prognostic value in patients with diffuse large B-cell lymphoma homogeneously treated with six cycles of R-CHOP-14 in a large prospective trial. At this point, interim PET/CT scanning is not ready for clinical use to guide treatment decisions in individual patients.

Robustness of the Voluntary Breath-Hold Approach for the Treatment of Peripheral Lung Tumors Using Hypofractionated Pencil Beam Scanning Proton Therapy.

PURPOSE The safe clinical implementation of pencil beam scanning (PBS) proton therapy for lung tumors is complicated by the delivery uncertainties caused by breathing motion. The purpose of this feasibility study was to investigate whether a voluntary breath-hold technique could limit the delivery uncertainties resulting from interfractional motion. METHODS AND MATERIALS Data from 15 patients with peripheral lung tumors previously treated with stereotactic radiation therapy were included in this study. The patients had 1 computed tomographic (CT) scan in voluntary breath-hold acquired before treatment and 3 scans during the treatment course. PBS proton treatment plans with 2 fields (2F) and 3 fields (3F), respectively, were calculated based on the planning CT scan and subsequently recalculated on the 3 repeated CT scans. Recalculated plans were considered robust if the V95% (volume receiving ≥95% of the prescribed dose) of the gross target volume (GTV) was within 5% of what was expected from the planning CT data throughout the simulated treatment. RESULTS A total of 14/15 simulated treatments for both 2F and 3F met the robustness criteria. Reduced V95% was associated with baseline shifts (2F, P=.056; 3F, P=.008) and tumor size (2F, P=.025; 3F, P=.025). Smaller tumors with large baseline shifts were also at risk for reduced V95% (interaction term baseline/size: 2F, P=.005; 3F, P=.002). CONCLUSIONS The breath-hold approach is a realistic clinical option for treating lung tumors with PBS proton therapy. Potential risk factors for reduced V95% are small targets in combination with large baseline shifts. On the basis of these results, the baseline shift of the tumor should be monitored (eg, through image guided therapy), and appropriate measures should be taken accordingly. The intrafractional motion needs to be investigated to confirm that the breath-hold approach is robust.

Capgras syndrome: a clinical manifestation of watershed cerebral infarct complicating the use of extracorporeal membrane oxygenation

Ischaemic cerebral accidents are frequent following extracorporeal membrane oxygenation (ECMO), especially after fixing the reinjection cannula in the right primitive carotid artery, which leads to an interruption in downstream flow. We describe a rare and unusual symptom of cerebral ischaemic accident that is known as Capgras syndrome. This feature is interesting because it may be documented by computed tomography (CT) scan and particular electroencephalography signals. It appears that our observation represents the first documented case of Capgras syndrome complicating ECMO. This incident emphasizes the potential hazards associated with right common artery ligature for venoarterial extracorporeal membrane oxygenation (VAECMO). In addition, it shows that this psychiatric symptom (that has been interpreted psychodynamically for many years) can have an organic basis, which should be studied.

Descrição morfológica e posicionamento filogenético de um lagarto (Reptilia, Squamata) do Mioceno Inferior da Formação Chichínales, General Roca, Província de Río Negro, Argentina

Embora os escamados sejam comumente encontrados em sítios fossilíferos cenozóicos sul−americanos, materiais esqueléticos completos são raros. Apenas alguns poucos exemplares assim foram registrados, com a maioria dos achados representando materiais fragmentários de crânio e mandíbulas ou vértebras isoladas. Dentre as localidades provedoras de vertebrados fósseis na América do Sul, a Formação Chichínales se destaca pela recente descoberta, em seus sedimentos, de um crânio quase completo de um lagarto teiídeo previamente desconhecido. Dada a fauna associada, a idade da formação é definida como Mioceno Temprano (Colhuehuapense). No presente estudo, conclui−se, através de uma análise filogenética contendo 39 espécies viventes e fósseis de escamados e 149 caracteres osteológicos, que este material pertence a uma nova espécie do gênero contemporâneo Callopistes. Uma descrição morfológica detalhada do fóssil, obtida através de análises estereoscópicas e de microtomografia computadorizada de alta resolução (CT Scan), também é apresentada. A matriz morfológica foi analisada com o auxílio do software TNT Versão 1.1, seguindo o princípio de máxima parcimônia, com todos os caracteres tratados com a mesma pesagem, resultando em quatro árvores igualmente parcimoniosas, que foram então utilizadas para a construção de uma árvore de consenso estrito. Em todas as quatro árvores, o novo táxon posicionou−se dentro da família Teiidae como um membro do clado formado pelas demais espécies viventes de Callopistes. Entretanto, não foi possível estabelecer uma relação de grupo−irmão inequívoca entre as duas espécies de Callopistes presentes na análise e o fóssil. A atual distribuição das duas espécies viventes de Callopistes e a localidade de onde foi recuperado o fóssil em estudo indicam que esse gênero possuía uma distribuição muito mais ampla no passado, chegando a áreas patagônicas cis−Andinas, diferentemente das áreas trans−Andinas de altitude onde as duas espécies atuais estão restritas

Papiloma invertido das fossas nasais e seios perinasais : revisão sistemática

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014

Portal cavernoma cholangiopathy : case report and systematic review

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014

Avaliação da composição corporal e do estado nutricional em doentes com neoplasias gastrointestinais : bioimpedância elétrica e tomografia axial computorizada, que correlação?

Tese de mestrado, Nutrição Clínica, Faculdade de Medicina, Universidade de Lisboa, 2015

Biomechanics of the rostrum in crocodilians: A comparative analysis using finite-element modeling

This article reports the use of simple beam and finite-element models to investigate the relationship between rostral shape and biomechanical performance in living crocodilians under a range of loading conditions. Load cases corresponded to simple biting, lateral head shaking, and twist feeding behaviors. The six specimens were chosen to reflect, as far as possible, the full range of rostral shape in living crocodilians: a juvenile Caiman crocodilus, subadult Alligator mississippiensis and Crocodylus johnstoni, and adult Caiman crocodilus, Melanosuchus niger, and Paleosuchus palpebrosus. The simple beam models were generated using morphometric landmarks from each specimen. Three of the finite-element models, the A. mississippiensis, juvenile Caiman crocodilus, and the Crocodylus johnstoni, were based on CT scan data from respective specimens, but these data were not available for the other models and so these-the adult Caiman crocodilus, M. niger, and P. palpebrosus-were generated by morphing the juvenile Caiman crocodilus mesh with reference to three-dimensional linear distance measured from specimens. Comparison of the mechanical performance of the six finite-element models essentially matched results of the simple beam models: relatively tall skulls performed best under vertical loading and tall and wide skulls performed best under torsional loading. The widely held assumption that the platyrostral (dorsoventrally flattened) crocodilian skull is optimized for torsional loading was not supported by either simple beam theory models or finite-element modeling. Rather than being purely optimized against loads encountered while subduing and processing food, the shape of the crocodilian rostrum may be significantly affected by the hydrodynamic constraints of catching agile aquatic prey. This observation has important implications for our understanding of biomechanics in crocodilians and other aquatic reptiles.

Multi-frequency segmental bio-impedance device:design, development and applications

Bio-impedance analysis (BIA) provides a rapid, non-invasive technique for body composition estimation. BIA offers a convenient alternative to standard techniques such as MRI, CT scan or DEXA scan for selected types of body composition analysis. The accuracy of BIA is limited because it is an indirect method of composition analysis. It relies on linear relationships between measured impedance and morphological parameters such as height and weight to derive estimates. To overcome these underlying limitations of BIA, a multi-frequency segmental bio-impedance device was constructed through a series of iterative enhancements and improvements of existing BIA instrumentation. Key features of the design included an easy to construct current-source and compact PCB design. The final device was trialled with 22 human volunteers and measured impedance was compared against body composition estimates obtained by DEXA scan. This enabled the development of newer techniques to make BIA predictions. To add a ‘visual aspect’ to BIA, volunteers were scanned in 3D using an inexpensive scattered light gadget (Xbox Kinect controller) and 3D volumes of their limbs were compared with BIA measurements to further improve BIA predictions. A three-stage digital filtering scheme was also implemented to enable extraction of heart-rate data from recorded bio-electrical signals. Additionally modifications have been introduced to measure change in bio-impedance with motion, this could be adapted to further improve accuracy and veracity for limb composition analysis. The findings in this thesis aim to give new direction to the prediction of body composition using BIA. The design development and refinement applied to BIA in this research programme suggest new opportunities to enhance the accuracy and clinical utility of BIA for the prediction of body composition analysis. In particular, the use of bio-impedance to predict limb volumes which would provide an additional metric for body composition measurement and help distinguish between fat and muscle content.

Prospective Estimation of Organ Dose Prior to Examination: Matching Patient to Digital Phantoms

Prospective estimation of patient CT organ dose prior to examination can help technologist adjust CT scan settings to reduce radiation dose to patient while maintaining certain image quality. One possible way to achieve this is matching patient to digital models precisely. In previous work, patient matching was performed manually by matching the trunk height which was defined as the distance from top of clavicle to bottom of pelvis. However, this matching method is time consuming and impractical in scout images where entire trunk is not included. Purpose of this work was to develop an automatic patient matching strategy and verify its accuracy.

Open-source virtual bronchoscopy for image guided navigation

This thesis describes the development of an open-source system for virtual bronchoscopy used in combination with electromagnetic instrument tracking. The end application is virtual navigation of the lung for biopsy of early stage cancer nodules. The open-source platform 3D Slicer was used for creating freely available algorithms for virtual bronchscopy. Firstly, the development of an open-source semi-automatic algorithm for prediction of solitary pulmonary nodule malignancy is presented. This approach may help the physician decide whether to proceed with biopsy of the nodule. The user-selected nodule is segmented in order to extract radiological characteristics (i.e., size, location, edge smoothness, calcification presence, cavity wall thickness) which are combined with patient information to calculate likelihood of malignancy. The overall accuracy of the algorithm is shown to be high compared to independent experts' assessment of malignancy. The algorithm is also compared with two different predictors, and our approach is shown to provide the best overall prediction accuracy. The development of an airway segmentation algorithm which extracts the airway tree from surrounding structures on chest Computed Tomography (CT) images is then described. This represents the first fundamental step toward the creation of a virtual bronchoscopy system. Clinical and ex-vivo images are used to evaluate performance of the algorithm. Different CT scan parameters are investigated and parameters for successful airway segmentation are optimized. Slice thickness is the most affecting parameter, while variation of reconstruction kernel and radiation dose is shown to be less critical. Airway segmentation is used to create a 3D rendered model of the airway tree for virtual navigation. Finally, the first open-source virtual bronchoscopy system was combined with electromagnetic tracking of the bronchoscope for the development of a GPS-like system for navigating within the lungs. Tools for pre-procedural planning and for helping with navigation are provided. Registration between the lungs of the patient and the virtually reconstructed airway tree is achieved using a landmark-based approach. In an attempt to reduce difficulties with registration errors, we also implemented a landmark-free registration method based on a balanced airway survey. In-vitro and in-vivo testing showed good accuracy for this registration approach. The centreline of the 3D airway model is extracted and used to compensate for possible registration errors. Tools are provided to select a target for biopsy on the patient CT image, and pathways from the trachea towards the selected targets are automatically created. The pathways guide the physician during navigation, while distance to target information is updated in real-time and presented to the user. During navigation, video from the bronchoscope is streamed and presented to the physician next to the 3D rendered image. The electromagnetic tracking is implemented with 5 DOF sensing that does not provide roll rotation information. An intensity-based image registration approach is implemented to rotate the virtual image according to the bronchoscope's rotations. The virtual bronchoscopy system is shown to be easy to use and accurate in replicating the clinical setting, as demonstrated in the pre-clinical environment of a breathing lung method. Animal studies were performed to evaluate the overall system performance.