Thesis (D.Tech.: Radiography)-Dept. of Radiography, Durban Institute of Technology, 2006 xxiii, 166 leaves / The purpose of this study was to evaluate 99mTc- methoxyisobutylisonitrile (MIBI) imaging, in terms of sensitivity and specificity, for non invasively detecting extracutaneous involvement of Kaposi’s sarcoma (KS) and for differentiating pulmonary infection from malignancy in acquired immunodeficiency syndrome (AIDS) patients before and after treatment. Current investigations are invasive.

Submitted by Claudinei Pracidelli (cpracide@ipen.br) on 2015-01-21T10:32:45Z No. of bitstreams: 0 / Made available in DSpace on 2015-01-21T10:32:45Z (GMT). No. of bitstreams: 0 / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / Tese (Doutorado em Tecnologia Nuclear) / IPEN/T / Instituto de Pesquisas Energeticas e Nucleares - IPEN-CNEN/SP / FAPESP:10/04206-4

Submitted by Claudinei Pracidelli (cpracide@ipen.br) on 2015-01-21T10:32:45Z No. of bitstreams: 0 / Made available in DSpace on 2015-01-21T10:32:45Z (GMT). No. of bitstreams: 0 / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / A NSECT figura como uma nova técnica espectrográfica capaz de avaliar in vivo a concentração de elementos utilizando a reação de espalhamento inelástico (n,n). Desde sua introdução, várias melhorias vem sendo propostas com o objetivo de investigar aplicações para o diagnóstico clínico e redução da dose absorvida associada à aquisição tomográfica. Neste contexto, são apresentadas duas novas aplicações de diagnóstico utilizando as abordagens espectroscópica e tomográfica da NSECT. Uma nova metodologia também foi proposta para otimizar a amostragem do sinograma que está diretamente relacionado com a qualidade de reconstrução através do protocolo de irradiação. Os estudos realizados foram desenvolvidos com base em simulações com o código MCNP5. O diagnóstico de Carcinoma de Célula Renal (CCR) e a detecção de microcalcificações mamárias foram avaliadas nos estudos conduzidos utilizando um objeto simulador humano. Os resultados obtidos demonstram a habilidade da técnica NSECT em detectar a alteração da composição dos tecidos modelados em função do desenvolvimento das patologias avaliadas. O método proposto para a otimização dos sinogramas foi capaz de simular analiticamente a composição do meio irradiado permitindo que a qualidade de reconstrução e a dose efetiva fossem avaliados em função da taxa de amostragem. Entretanto, futuras pesquisas devem ser conduzidas para quantificar o limiar de detecção de acordo com os elementos selecionados. / Tese (Doutorado em Tecnologia Nuclear) / IPEN/T / Instituto de Pesquisas Energeticas e Nucleares - IPEN-CNEN/SP / FAPESP:10/04206-4

INTRODUÇÃO: O diagnóstico da doença de Parkinson (DP) pode ser um desafio, principalmente nas fases precoces da doença. O diagnóstico acurado desta condição requer mais que a avaliação clínica isolada. A Tomografia computadorizada do crânio de fóton único (SPECT) e a ultrassonografia transcraniana (USTC) podem ser úteis na diferenciação entre a DP e as síndromes parkinsonianas atípicas ou entre a DP e o tremor essencial. O presente estudo objetivou investigar a acurácia da USTC combinada com o teste de olfação Sniffin\' Sticks (SST-16) para diferenciar pacientes com DP de controles saudáveis e comparar com a acurácia do SPECT com 99mTc- TRODAT-1 (TRODAT). MÉTODOS: Trata-se de um estudo transversal que incluiu pacientes com DP segundo critérios do United Kingdom Parkinson\'s disease Society e um grupo controle de indivíduos saudáveis pareados para idade e gênero. Os pacientes foram examinados por um especialista em distúrbios do movimento e submetidos a SPECT encefálico com TRODAT, USTC e SST-16. Curvas Receiver Operating Characteristic (ROC) foram obtidas para definir os pontos de corte dos métodos avaliados para detecção de DP. RESULTADOS: Vinte indivíduos com DP (13 homens e 7 mulheres) e 9 participantes saudáveis foram admitidos no estudo. A idade mediana de início dos sintomas foi de 56,5 anos e a mediana do tempo de duração da doença foi de 5 anos. Maior área de ecogênica da substância negra (SN) foi observada no grupo com DP (p=0,013). Área ecogênica da SN de 0,22 cm2 foi definida pela curva ROC para detecção de DP, com acurácia de 79%. O ponto de corte do potencial de ligação do TRODAT no striatum foi 0,90, com acurácia de 99% para o diagnóstico de DP. Escore do SST-16 maior ou igual a 10 pontos foi o ponto de corte para detecção de DP, com acurácia de 85,8%. A combinação da USTC com teste da olfação levou à acurácia de 95% para detecção de DP. CONCLUSÃO: A combinação da USTC com SST-16 eleva a capacidade de ! detecção da DP. A acurácia da USTC combinada ao SST-16 para identificar pacientes com DP idiopática aproximou-se da acurácia do SPECT com TRODAT / INTRODUCTION: Diagnosing Parkinson\'s disease (PD) can be challenging, especially in the early stages of the disease. An accurate diagnosis requires more than clinical findings alone. Brain single-photon emission computed tomography (SPECT) and transcranial sonography (TCS) are helpful for diagnosing PD and differentiating it from atypical parkinsonian syndromes as well as essential tremor. This study aimed to investigate the accuracy of TCS combined with the Sniffin\' sticks olfactory test (SST-16) for differentiation between idiopathic PD patients and healthy controls compared to that of 99mTc-TRODAT-1 SPECT (TRODAT). METHODS: A cross-sectional study included PD patients diagnosed in accordance with United Kingdom PD Society Brain Bank criteria and a control group of age and sex-matched healthy subjects. All patients were examined by a movement disorder specialist and underwent brain SPECT using TRODAT, TCS examination and SST-16 test. Receiver Operating Characteristic (ROC) curves were used to calculate cut-off points for TCS, Striatal TRODAT binding potentials and SST-16. The area under the ROC curve determined the accuracy of the method. RESULTS: Twenty patients with PD (13 males and 7 females) and nine healthy subjects were included. Median age of PD onset was 56.5 years with median disease duration of 5 years. A larger substantia nigra (SN) echogenic area was observed in the PD group (p=0.013). SN echogenic area cut-off point of 0.22 cm2 was obtained from a ROC curve for PD diagnosis. Considering this cut-off point, TCS accuracy was estimated at 79.2% for PD diagnosis. The cut-off value of 0.90 for striatal TRODAT binding was associated with 99% accuracy for the diagnosis of PD. SST-16 values equal or greater than 10 points showed a 85.8% accuracy for PD diagnosis. Combination of both SST-16 and TCS improved the accuracy to 95% for PD diagnosis. CONCLUSION: Combined assessment of SST-16 and TCS are reliable and highly accurate for distinguishing PD patients from healthy controls. The accuracy of TCS combined with SST-16 for differentiation between idiopathic PD patients and healthy controls is similar to that of SPECT TRODAT

Bone is a remarkable multifunctional tissue with the ability to regenerate and remodel without generating any scar tissue. However, bone loss due to injury or diseases can be a great challenge and affect the patient significantly. Autologous bone grafting is commonly used throughout the world. Autograft both fills the void and is bone inductive, housing the particular cells that are needed for bone regeneration. However, a regenerative complement to autograft is of great interest as the use of biomaterials loaded with bioactive molecules can avoid donor site morbidity and the problem of a limited volume of material. Two such regenerative products that utilise bone morphogenetic protein (BMP)-7 and -2 have been used for more than a decade clinically. Unfortunately, several side effects have been reported, such as severe swelling due to inflammation and ectopic bone formation. Additionally, the products require open surgery and use of supra physiological doses of the BMPs due to poor localisation and retention of the growth factor. The purpose of this thesis was to harness the strong inductive capacity of the BMP-2 by optimising the carrier of this bioactive protein, thereby minimising the side effects that are associated with the clinical products and facilitating safe and localised bone regeneration. We focused on an injectable hyaluronan-based carrier developed through polymer chemistry at the University of Uppsala. The strategy was to use the body’s own regenerative pathway to stimulate and enhance bone healing in a manner similar to the natural bone-healing process. The hyaluronan-based carrier has a similar composition to the natural extracellular matrix and is degraded by resident enzymes. Earlier studies have shown improved properties when adding hydroxyapatite, a calcium phosphate that constitutes the inorganic part of the bone matrix. In Paper I, the aim was to improve the carrier by adding other forms of calcium phosphate. The results indicated that bone formation was enhanced when using nano-sized hydroxyapatite. In Paper II, we discovered the importance of crushing the material, thus enhancing permeability and enlarging the surface area. We wished to further develop the carrier system, but were lacking an animal model with relatively high throughput, facilitated access, paired data, and we were also committed to the 3Rs of refinement, reduction, and replacement. To meet these challenges, we developed and refined an animal model, and this is described in Paper III. In Paper IV, we sought to further optimise the biomaterial properties of the hydrogel through covalent bonding of bisphosphonates to the hyaluronan hydrogel. This resulted in exceptional retention of the growth factor BMP-2. In Paper V, SPECT/PET/µCT was combined as a tri-modal imaging method to allow visualisation of the biomaterial’s in situ action, in terms of drug retention, osteoblast activity and mineralisation. Finally, in Paper VI the correlation between existing in vitro results with in vivo outcomes was observed for an array of biomaterials. The study identified a surprisingly poor correlation between in vitro and in vivo assessment of biomaterials for osteogenesis.

Jogo patológico (JP) pode ser definido pela persistência e recorrência do comportamento de apostar em jogos de azar, apesar de prejuízos em diversas áreas da vida decorrentes dessa atividade. O JP é considerado um transtorno do controle de impulso e um modelo de dependência comportamental. Diferentes estudos têm comprovado o envolvimento de vias dopaminérgicas em dependências de substâncias e em jogadores patológicos. O transportador de doamina (DAT) é uma proteína présináptica de neurônios dopaminérgicos nigroestriatais, responsável pela recaptação da dopamina (DA) da fenda sináptica, e tem sido relatada alterações em sua densidade em dependentes de substâncias. O objetivo deste trabalho foi investigar em pacientes com jogo patológico, a densidade de DAT no estriado, através de imagens do exame de SPECT com TRODAT-1- 99mTc verificar por meio de estudo de correlação a associação entre comportamento de jogo (freqüência, tempo, dinheiro, gastos com jogo e fissura/craving) e a densidade DAT em jogadores patológicos. Foram selecionados 15 jogadores e 15 controles normais pareados para gênero, idade e escolaridade. Para inclusão ou exclusão de sujeitos foram utilizados instrumentos de verificação e principais Transtornos Psiquiátricos do Eixo 1 do DSM IV e escalas para depressão e ansiedade; para jogadores patológicos os instrumentos utilizados foram escalas para avaliação do padrão de jogo recente, para avaliação da fissura pelo jogo; para rastreamento de outras dependências comportamentais (sexo e comida). Observou-se que: 1) jogadores patológicos não apresentaram aumento de densidade DAT quando comparados a controles normais; 2) nos jogadores a densidade de DAT foi diretamente proporcional a intensidade de jogo no último mês e inversamente proporcional a auto-eficácia na abstinência do jogo. Não houve correlação significativa entre densidade de DAT e comportamentos de abuso relacionados com sexo ou comida. Desta forma, faz-se necessário estudos futuros para a avaliação da densidade de DAT no início e no fim do tratamento, a fim de verificar se a diminuição da densidade de DAT ao longo do tratamento pode ser utilizada como preditor de boa resposta e bom prognóstico em jogadores patológicos. / Pathological gambling (PG) can be defined by the persistence and recurrence of the behavior of gambling on games of chance, despite losses in many areas of life from this activity. The JP is considered a disorder of impulse control and a model of behavioral dependence. Different studies have demonstrated the involvement of dopaminergic pathways in substance dependency and pathological gamblers. The dopamine transporter (DAT) is a protein pre-synaptic dopaminergic neurons nigroestriatais responsible for the reuptake of dopamine (DA) from the synaptic cleft, and has been reported changes in the density-dependent substances. The objective of this study was to investigate in patients with pathological gambling, the density of DAT in the striatum, through examination of SPECT images with TRODAT-1 - 99mTc to verify through correlation study the association between gambling behavior (frequency, time, money spent on gambling and urge / craving) and DAT density in pathological gamblers. We selected 15 plathological gamblers and 15 controls matched for gender, age and education. For inclusion or exclusion of subjects were used verification tools and major psychiatric disorders in the DSM IV Axis 1 and scales for depression and anxiety; for pathological gamblers were the instruments used scales for assessing the standard of play recently, to evaluate the crack for the game; for tracking other behavioral addictions (sex and food). It was observed that: 1) pathological gamblers did not have increased DAT density compared with normal controls, 2) players in the density of DAT was directly proportional to the intensity of gambling in the last month and inversely proportional to self-efficacy on abstinence of gambling. There was no significant correlation between DAT density and behavior of abuse related to sex or food. Thus, it is necessary to future studies for evaluating the density of DAT at the beginning and end of treatment in order to determine whether the decrease in density during the treatment DAT can be used as predictor of good response and a good prognosis in pathological gamblers.

A análise de imagens médicas auxiliada por computador permite a análise quantitativa das anormalidades e garante maior precisão diagnóstica. Esse tipo de análise é importante para medicina nuclear com Single Photon Emission Computed Tomography (SPECT), pois no grupo de dados tridimensionais de imagens, padrões sutis de anormalidades muitas vezes são importantes achados clínicos. Porém, as imagens podem sofrer interferência de artefatos de atenuação da emissão de fótons por partes moles corporais, o que reduz sua acurácia diagnóstica. Desde que se possuam parâmetros de atenuação computados em um modelo que permita a comparação com imagens de um dado paciente, a interferência dos artefatos pode ser corrigida com ganho na acurácia diagnóstica, sem a necessidade de utilização de técnicas de correção que aumentem a dose de exposição à radiação pelo paciente. A proposta desse estudo foi a criação de um atlas de cintilografia de perfusão miocárdica, que foi obtido a partir de imagens de indíviduos normais, e o desenvolvimento de um algoritmo computacional para a detecção de anormalidades perfusionais miocárdicas, através da comparação estatística dos modelos do atlas com imagens de pacientes. Métodos de corregistro de imagens de mesma modalidade e outras técnicas de processamento de imagens foram estudados e utilizados para a comparação das imagens dos pacientes com o modelo apropriado. Pela análise visual dos modelos, verificou-se a sua validade como imagem representativa de normalidade perfusional. Para avaliação da detecção, a situação dos segmentos miocárdicos (normal ou anormal) indicada pelo algoritmo de detecção foi comparada com a situação apontada no laudo obtido pela concordância de dois especialistas, de modo a se verificar as concordâncias e discordâncias da técnica em relação ao laudo e se obter a significância estatística. Com isso, verificou-se um índice de concordância positiva da técnica em relação ao laudo de aproximadamente 50%, de concordância negativa próxima a 82% e de concordância geral próxima a 68%. O teste exato de Fisher foi aplicado às tabelas de contingência, obtendo-se um valor de p bicaudal inferior a 0,0001, indicando uma probabilidade muito baixa de as concordâncias terem sido obtidas pelo acaso. Melhorias no algoritmo deverão ser implementadas e testes futuros com um padrão-ouro efetivo serão realizados para validação da técnica. / The computer-aided medical imaging analysis allows the quantitative analysis of abnormalities and enhances diagnostic accuracy. This type of analysis is important for nuclear medicine that uses Single Photon Emission Computed Tomography (SPECT), because in the group of three-dimensional data images, subtle patterns of abnormalities often are important clinical findings. However, images can suffer interference from attenuation artifacts of the emission of photons by soft parts of the body, which reduces their diagnostic accuracy. Since there are attenuation parameters computed in a template that allows for comparison with images of a given patient, the artifacts interference can be corrected with a gain in diagnostic accuracy, without the need of using correction techniques that increase the radiation exposure dose of the patient. The purpose of this study was to create an atlas of myocardial perfusion scintigraphy, which was obtained from images of normal individuals and the development of a computational algorithm for detection of myocardial perfusion abnormalities by statistical comparison of atlas templates with images of patients. Methods of image registration of same modality and other image processing techniques were studied and used for comparison of patient images with the appropriate template. By the visual analysis of the templates it was found its validity as a representative image of normal perfusion. For the detection evaluation, the situation of myocardial segments (normal or abnormal) indicated by the detection algorithm was compared with the situation indicated in the medical appraisal report obtained by agreement of two specialists in order to determine the agreement and disagreement of the technique regarding the medical appraisal report and obtaining the statistical significance. Thus, there was a positive agreement index of the technique regarding the medical appraisal report of approximately 50%, a negative agreement index close to 82% and a general agreement index near 68%. The Fisher exact test was applied to the contingency tables, yielding a two-sided p-value less than 0.0001, that indicates a very low probability of the agreements have been obtained by chance. Algorithm improvements should be implemented and further tests with an effective gold-standard will be conducted to validate the technique.

La tomographie d'émission monophotonique (TEMP) dédiée au petit animal est une technique d'imagerie nucléaire qui joue un rôle important en imagerie moléculaire. Les systèmes TEMP, à l'aide de collimateurs pinholes ou multi-pinholes, peuvent atteindre des résolutions spatiales submillimétriques et une haute sensibilité pour un petit champ de vue, ce qui est particulièrement attractif pour imager des souris. Une géométrie de collimation originale a été proposée, dans le cadre d'un projet, appelé SIGAHRS, piloté par la société Biospace. Ce collimateur présente des longueurs focales qui varient spatialement dans le plan transaxial et qui sont fixes dans le plan axial. Une haute résolution spatiale est recherchée au centre du champ de vue, avec un grand champ de vue et une haute sensibilité. Grâce aux simulations Monte Carlo, dont nous pouvons maîtriser tous les paramètres, nous avons étudié cette collimation originale que nous avons positionnée par rapport à un collimateur parallèle et un collimateur monofocal convergent. Afin de générer des données efficacement, nous avons développé un module multi-CPU/GPU qui utilise une technique de lancer de rayons dans le collimateur et qui nous a permis de gagner un facteur ~ 60 en temps de calcul, tout en conservant ~ 90 % du signal, pour l'isotope ⁹⁹^mTc (émettant à 140,5 keV), comparé à une simulation Monte Carlo classique. Cependant, cette approche néglige la pénétration septale et la diffusion dans le collimateur. Les données simulées ont ensuite été reconstruites avec l'algorithme OSEM. Nous avons développé quatre méthodes de projection (une projection simple (S-RT), une projection avec volume d'intersection (S-RT-IV), une projection avec calcul de l'angle solide (S-RT-SA) et une projection tenant compte de la profondeur d'interaction (S-RT-SA-D)). Nous avons aussi modélisé une PSF dans l'espace image, anisotrope et non-stationnaire, en nous inspirant de la littérature existante. Nous avons étudié le conditionnement de la matrice système pour chaque projecteur et collimateur, et nous avons comparé les images reconstruites pour chacun des collimateurs et pour chacun des projecteurs. Nous avons montré que le collimateur original proposé est le système le moins bien conditionné. Nous avons aussi montré que la modélisation de la PSF dans l'image ainsi que de la profondeur d'intéraction améliorent la qualité des images reconstruites ainsi que le recouvrement de contraste. Cependant, ces méthodes introduisent des artefacts de bord. Comparé aux systèmes existants, nous montrons que ce nouveau collimateur a un grand champ de vue (~ 70 mm dans le plan transaxial), avec une résolution de 1,0 mm dans le meilleur des cas, mais qu'il a une sensibilité relativement faible (1,32x10⁻² %). / Small animal single photon emission computed tomography (SPECT) is a nuclear medicine imaging technique that plays an important role in molecular imaging. SPECT systems using pinhole or multi-pinhole collimator can achieve submillimetric spatial resolution and high sensitivity in a small field of view, which is particularly appropriate for imaging mice. In our work, we studied a new collimator dedicated to small animal SPECT, in the context of a project called SIGAHRS, led by the Biospace company. In this collimator, focal lengths vary spatially in the transaxial plane and are fixed in the axial plane. This design aims at achieving high spatial resolution in the center of the field of view, with a large field of view and high sensitivity. Using Monte Carlo simulations, where all parameters can be controlled, we studied this new collimator geometry and compared it to a parallel collimator and a cone-beam collimator. To speed up the simulations, we developed a multi-CPU/GPU module that uses a technique of ray tracing. Using this approach, the acceleration factor was ~ 60 and we restored ~ 90 % of the signal for ⁹⁹^mTc (140.5 keV emission), compared to a classical Monte Carlo simulation. The 10 % difference is due to the fact that the multi-CPU/GPU module neglects the septal penetration and scatter in the collimator. We demonstrated that the data acquired with the new collimator could be reconstructed without artifact using an OSEM algorithm. We developed four forward projectors (simple projector (S-RT), projector accounting for the surface of the detecting pixel (S-RT-IV), projection modeling the solid angle (S-RT-SA) of the projection tube, and projector modeling the depth of interaction (S-RT-SA-D)). We also modeled the point spread function of the collimator in the image domain, using an anisotropic non-stationary function. To characterize the reconstruction, we studied the conditioning number of the system matrix for each projector and each collimator. We showed that the new collimator was more ill-conditioned than a parallel collimator or a cone-beam collimator. We showed that the image based PSF and the modeling of the depth of interaction improved the quality of the images, but edge artefacts were introduced when modeling the PSF in the image domain. Compared to existing systems, we showed that this new collimator has a large field of view (~ 70 mm in the transaxial plane) with a resolution of 1.0 mm in the best case but suffers from a relatively low sensitivity (1.32x10⁻² %).

Bone is a remarkable multifunctional tissue with the ability to regenerate and remodel without generating any scar tissue. However, bone loss due to injury or diseases can be a great challenge and affect the patient significantly. Transplanting bone graft from one site in the patient to the site of fracture or bone void, i.e. autologous bone grafting is commonly used throughout the world. The transplanted bone not only fills voids, but is also bone inductive, housing the particular cells that are needed for bone regeneration. Nevertheless, a regenerative complement to autograft is of great interest and importance because the benefits from an off-the-shelf product with as good of healing capacity as autograft will circumvent most of the drawbacks with autograft. With a regenerative-medicine approach, the use of biomaterials loaded with bioactive molecules can avoid donor site morbidity and the problem of limited volume of material. Two such regenerative products that utilize bone morphogenetic protein 7 and 2 have been used for more than a decade in the clinic. However, some severe side effects have been reported, such as severe swelling due to inflammation and ectopic bone formation. Additionally, the products require open surgery, use of supra physiological doses of the BMPs due to poor localization and retention of the growth factors. The purpose of this thesis was to harness the strong inductive capability of the BMP-2 by optimizing the carrier of this bioactive protein, thereby minimizing the side effects that are associated with the clinical products and facilitating safe and localized bone regeneration at the desired site. We focused on an injectable hyaluronan-based carrier. The strategy was to use the body’s own regenerative pathway to stimulate and enhance bone healing in a manner similar to the natural bone-healing process. The hyaluronan-based carrier has a similar composition to the natural extracellular matrix and is degraded by resident hyaluronidase enzymes. Earlier studies have shown a more controlled release and improved mechanical properties when adding a weight of 25 percent of hydroxyapatite, a calcium phosphate that constitutes the inorganic part of the bone matrix. In Paper I, the aim was to improve the carrier by adding other forms of calcium phosphate. The results indicated that the bone formation was enhanced when using nano-sized hydroxyapatite. We wished to further develop the carrier system but were lacking an animal model with high output and easy access. We also wanted to provide paired data and were committed to the 3 Rs of refinement, reduction and replacement. To meet these challenges, we developed and refined an animal model, and this is described in Paper II. In Paper III, we characterized and optimized the handling properties of the carrier. In Paper IV, we discovered the importance of crushing the material, thus enhancing permeability and enlarging the surface area. In Paper V, we sought to further optimize biomaterial properties of the hydrogel through covalently bonding of bisphosphonates to the hyaluronan hydrogel. The results demonstrated exceptional retention of the growth factor BMP-2. In Paper VI, the in vivo response related to the release of the growth factor was examined by combining a SPECT/PET/µCT imaging method to visualize both the retention of the drug, and the in-vivo response in terms of mineralization.

Laparoscopic operations are a common and popular way for abdominal procedures. They are usually performed by insufflation of carbon dioxide (CO2) into the abdominal cavity. However, insufflation of CO2 may interfere with cardiac and circulatory as well as respiratory functions. The CO2-pneumoperitoneum (PP) may cause hypercarbia and acidosis. The direct effects of CO2 and acidosis lead to decreased cardiac contractility, sensitization of the myocardium to arrhythmogenic effects of catecholamines and systemic vasodilatation. There may even be long-lasting post-operative effects on breathing control. The pneumoperitoneum may also cause several respiratory changes, e.g. decreased functional residual capacity (FRC) and vital capacity (VC), formation of atelectasis, reduced respiratory compliance and increased airway pressure. Still, arterial oxygenation is mostly maintained or even improved during PP. In view of the apparently contradictory results in respiratory mechanics and gas exchange, the present studies were performed to evaluate respiratory changes on gas exchange and ventilation-perfusion distributions during PP in a porcine model. It was demonstrated that atelectasis during anaesthesia and PP may be estimated by an increased arterial to endtidal PCO2-gradient (study I). Perfusion was redistributed away from dorsal, collapsed lung regions when PP was established. This resulted in a better ventilation-perfusion match (study II). Increasing abdominal pressure shifted blood flow more and more away from collapsed lung tissue, decreased pulmonary shunt and improved oxygenation from 8 to 16 mmHg PP, despite an increase of atelectasis formation (study III). CO2-PP enhanced the shift of blood flow towards better ventilated parts of the lung compared to Air-PP. Moreover, sodium natriumprusside worsened the ventilation-perfusion match even more and blunted the effects previously seen with carbon dioxide. CO2 should therefore be the mediator of enhancing HPV during PP. In conclusion, pneumoperitoneum with CO2 causes atelectasis with elimination of ventilation in the dependent lung regions. However, an efficient shift of blood flow away from collapsed, non-ventilated regions results in a better ventilation-perfusion matching and better oxygenation of blood than without PP. A prerequisite for the beneficial effect is the use of carbon dioxide for the abdominal inflation, since it enhances HPV.