La quantification de la perfusion tissulaire à partir de données dynamiques d’échographie de contraste repose sur une modélisation appropriée de la cinétique de la concentration en agent de contraste dans le tissu étudié. De nombreux facteurs, expérimentaux ou physiologiques, rendent la comparaison inter ou intra-individu de ces paramètres de perfusion difficile. Dans cette thèse, la reproductibilité et la comparaison de différentes méthodes de quantification ont été étudiées dans le cadre d’une étude préclinique de test-retest et sur des simulations numériques. Les méthodes étudiées ont été : le modèle log-normal, le modèle compartimental avec fonction d’entrée et le modèle compartimental avec tissu de référence. Les études précliniques ont montré la difficulté d’estimation d’une fonction d’entrée artérielle et la nécessité de corriger localement le temps d’arrivée de l’agent de contraste dans le tissu pour que l’approximation des cinétiques expérimentales par le modèle soit de qualité suffisante. Une estimation linéaire sous contrainte des paramètres du modèle compartimental avec tissu de référence tirant profit de différentes zones d’intérêt dans l’image a été ensuite proposée pour obtenir à l’échelle régionale et/ou locale des valeurs relatives cohérentes de débit sanguin tissulaire et de volume sanguin tissulaire, exprimées par rapport aux valeurs dans le tissu de référence. Il a été montré que cette approche est la plus robuste et la plus reproductible. L’influence des facteurs tels que la durée d’acquisition, la fréquence d’échantillonnage, le nombre de régions utilisées et l’amplitude du bruit a été étudiée sur des simulations et a permis de formuler des recommandations pour l’acquisition et le traitement des études en échographie de contraste. / Quantification of tissue perfusion from dynamic contrast-enhanced ultrasound data relies on appropriate modeling of the curve representing the evolution of the contrast-agent concentration inside the studied tissue. Many factors, experimental or physiological, make inter-subject or intra-subject comparison of these perfusion parameters difficult. In this thesis, the reproducibility and the comparison of various quantification methods was investigated through preclinical test-retest experiments and through simulations. The investigated methods were: the log-normal model, the one-compartment model using an arterial input function, and the one-compartment model using a reference tissue. The preclinical experiments revealed the difficulty to estimate an arterial input function directly from the image, as well as the necessity to locally correct for the time of arrival of the contrast agent in the tissue in order to ensure the model accurately fits the experimental enhancement curves. A regularized linear estimation of the parameters of the one-compartment model using a reference tissue taking advantage of multiple tissue regions was then proposed to obtain homogeneous relative values of the tissue blood flow and tissue blood volume, expressed relatively to the parameter value inside the reference tissue. The improved robustness and reproducibility of the method was demonstrated. The influence of factors such as the exam duration, the sampling frequency, the number of tissue regions in the analysis, and the noise amplitude were investigated through simulations, and allowed us to formulate recommendations regarding the acquisition and the analysis of contrast-enhanced ultrasound studies.

京都大学 / 新制・論文博士 / 博士(医学) / 乙第13397号 / 論医博第2221号 / 新制||医||1051(附属図書館) / (主査)教授 伊佐 正, 教授 中本 裕士, 教授 渡邉 大 / 学位規則第4条第2項該当 / Doctor of Medical Science / Kyoto University / DFAM

This work consists of three original articles and is focused on the overall question: How can hyperspectral imaging contribute to patient safety and improve outcomes during abdominal surgery? The hypothesis was that HSI is suitable for the intraoperative assessment of tissue structures and decision support in routine clinical use. Spectral imaging was performed with the TIVITA Tissue for open surgery or TIVITA Mini system for laparoscopic HSI from Diaspective Vision GmbH (Am Salzhaff-Pepelow, Germany). Both HSI systems use pushbroom mode and provide 100 spectral channels in the visible and near-infrared spectral range from 500 - 1000 nm. The Number of Effective Pixels is at least 640 × 480 (x-, y-axis), while the field of view and spatial resolution depend on the measurement distance and the used focal length of the objective. Illumination is done by halogen spots for open surgery and broadband LED in the laparoscopic system. The first part of this work aimed to evaluate HSI for the measurement of ischemic conditioning effects of the gastric conduit during esophagectomy. Ischemic preconditioning by dividing major blood vessels of the stomach prior to gastric pull-up is performed to improve the perfusion at the later esophagogastric anastomosis to reduce the risk of leaks. Intraoperative hyperspectral records of the gastric tube were acquired from 22 patients through the mini-thoracotomy. Fourteen of them underwent ischemic conditioning of the stomach several days before the two-step transthoracic esophagectomy and gastric pull-up with intrathoracic anastomosis was performed. The tip of the gastric tube (later esophago-gastric anastomosis) was measured with HSI. These in vivo records showed that the tissue oxygenation of the gastric conduit was significantly higher in patients who underwent ischemic conditioning (78% vs. 66%; p = 0.03). In the second part of this work, a novel hyperspectral imaging system for MIS is described and evaluated to address the requirements for clinical use and high-resolution spectral imaging. Reference objects and resected human tissue were used to show spectral conformity with the approved HSI device for open surgery. Furthermore, varying object distances were investigated and the signal-to-noise ratio (SNR) for different light sources were measured. Measurements with both systems were performed on a human tissue resectate and compared quantitatively. It was shown that the handheld design of the laparoscopic HSI system enables the processing and visualization of spectral data in parallel during acquisition within a few seconds. The obtained measurements from both spectral imaging devices were consistent and a mean SNR of 30 to 43 dB (500 to 950 nm) was found using a standard rigid laparoscope in combination with a broadband LED light source. Finally, in the third part of this work, different image registration methods were investigated to compensate for small movements of the laparoscope and tissue deformations. The obtained image transformation is used to augment the laparoscopic color video with the static HSI data to support intraoperative localization. Multiple feature-based algorithms and a pre-trained deep homography neural network (DH-NN) were evaluated for the estimation of appropriate image transformations (single and multi-homography). The methods were validated with a ground truth dataset of 750 annotated laparoscopic images, that was created during this work, and in vivo data from the TIVITA Mini system. All feature-based single homography methods outperformed the fine-tuned DH-NN in terms of reprojection error, Structural Similarity Index Measure (SSIM), and processing time. The feature detector and descriptor ORB1000 enabled video-rate registration of laparoscopic images on standard hardware with submillimeter accuracy. Therefore, all initially stated research questions could be confirmed with the applied methods. Although technical limitations have been identified, the non-invasive and contact-free measurement principle makes HSI attractive for a variety of surgical disciplines.:1 Introduction 1.1 Interaction of light and biological tissue 1.2 Spectral imaging systems 1.3 Medical applications of spectral imaging 1.4 Intraoperative visualization of spectral data 2 Original Articles 2.1 Evaluation of hyperspectral imaging (HSI) for the measurement of ischemic conditioning effects of the gastric conduit during esophagectomy 2.2 Laparoscopic system for simultaneous high-resolution video and rapid hyperspectral imaging in the visible and near-infrared spectral range 2.3 Comparison of image registration methods for combining laparoscopic video and spectral image data 3 Summary 3.1 Conclusions and Outlook 4 References

No

The historical development, current practice, and the future of interventional neuroradiology are intricately linked to the advancements in the imaging and devices used for neuroendovascular treatments. This thesis explores the advanced imaging potential of the C-arm imaging systems used in the neurointerventional suite and investigates the initial clinical experience with a new flow diverter device to treat the intracranial aneurysms. A cohort of aneurysmal SAH patients who developed delayed cerebral ischaemia (DCI) were prospectively studied with a new parenchymal blood volume (PBV) research protocol C-arm CT examination concurrent with a magnetic resonance (MR) imaging examination that included perfusion and diffusion weighted sequences. Using a robust quantitative volume-of-interest analysis, it was demonstrated that C-arm CT PBV measurements are in agreement with MR-PWI CBV and CBF, and the PBV represents a composite perfusion parameter with both blood-flow (≈60%) and blood-volume (≈40%) weightings. Subsequently, using a voxel-wise ROC curve analysis and MR-DWI, it was shown that using optimal thresholds, C-arm CT PBV measurements allow reliable demarcation of the irreversibly infarcted parenchyma. For evaluation of ischaemic parenchyma, the PBV measurements were reliable for moderate-to-severe ischaemia but were prone to underestimate the mild-to-moderate ischaemia. A catalogue of reference mean PBV measurements was then created for various anatomical regions encompassing the whole brain after excluding any locations with ongoing ischaemia or infarction. Next, using an ROI-based analysis of the C-arm CT projection data, steady-state contrast concentration assumption underlying the PBV calculations was investigated. It was demonstrated that for clinical scans, the ideal steady-state assumption is not fully met, however, for a large majority of C-arm CT examinations the temporal characteristics of TDCs closely approximate the expected ideal steady-state. The degree to which the TDC of a C-arm CT scan approximates the ideal steady-state was found to influence the resulting PBV measurements and their agreement to MR-CBV. Moreover, the temporal characteristics of TDCs showed inter-subject variation. Finally, the C-arm CT cross-sectional soft tissue images were demonstrated to be of adequate quality for the assessment of ventricles and for the detection of procedural vessel rupture. These findings advance the understanding of the nature of PBV parameter, establish the optimal PBV thresholds for infarction, provide reference PBV measurements, and highlight the limitations of C-arm CT PBV imaging. The work is of considerable clinical significance and has implications for implementation of C-arm CT PBV imaging in the interventional suite for management of patients with acute brain ischaemia. In regards to the initial clinical experience with the flow diversion treatment of intracranial aneurysms, the procedural, angiographic, and clinical outcomes were studied. Several pertinent technical and clinical issues were highlighted for this new treatment approach. Based on the observations made during this work, a new grading schema was then developed to monitor the angiographic outcomes after flow diversion treatment. Using the angiographic data for patients treated with FD, the new grading schema was demonstrated to be sufficiently sensitive to register gradual aneurysm occlusion and evaluate parent artery patency, with an excellent inter-rater reliability and applicability to various aneurysm morphologies. This work (largest multi-centre series at the time of its publication) informed the interventional neuroradiology community about the safety, efficacy, and outcomes of flow diversion treatment. Additionally, it provided a sensitive and reliable scale to evaluate the angiographic outcomes after flow diversion treatment, in both research and clinical practice.

Introdução e Objetivos: A craniectomia descompressiva com duroplastia (CDD) reduz a mortalidade e melhora o prognóstico funcional em doentes com acidente vascular encefálico isquêmico (AVEi) hemisférico e proporciona a redução da pressão intracraniana. Entretanto, pouco se sabe sobre sua repercussão na hemodinâmica cerebral. O objetivo do presente trabalho é o de avaliar com a tomografia computadorizada com estudo de perfusão (TCP) as alterações hemodinâmicas nos doentes com AVEi após a CDD e identificar possíveis marcadores prognósticos substitutos. Métodos: Foram avaliados 27 doentes com AVEi com indicação de CDD. Os parâmetros hemodinâmicos da TCP estudados no período pré-operatório e em até 24h após a cirurgia foram: duração média de trânsito (DMT), volume sanguíneo encefálico (VSE) e fluxo sanguíneo encefálico (FSE). O desfecho primário utilizado foi a melhora ou a ausência de melhora hemodinâmica. Os desfechos secundários foram a escala de Rankin modificada em seis meses, dicotomizada como favorável (0-3) ou desfavorável (4-6); casos fatais em um mês e em seis meses. Resultados: 18 (70,3%) doentes eram do sexo feminino e 12 (44,4%) tinham idade superior a 55 anos. Houve melhora da DMT (queda de 8,74 para 8,24, p=0,01) e tendência a melhora do FSE (aumento de 22,37 para 25,26, p=0,06) após a CDD. Não houve diferença estatística em relação ao VSC (aumento de 2,14 para 2,26, p=0,33). A idade superior a 55 anos foi o preditor independente de prognóstico desfavorável (p=0,03) e a DMT pré-operatória, foi preditora hemodinâmica para mortalidade em seis meses (8,20 vs 9,23, p=0,04). Conclusões: A craniectomia descompressiva com expansão dural determinou melhora hemodinâmica na maioria dos doentes com AVEi hemisférico. A DTM préoperatória é um bom marcador substituto para a possibilidade de óbito em seis meses / Background and Objectives: Decompressive craniectomy (DC) reduces the mortality and improves the functional outcome in patients with malignant cerebral infarction (MCI). This procedure causes a decrease of the intracranial pressure, however, little is known about its impact in brain hemodynamics. Therefore, our goal is to study through CT perfusion the hemodynamics changes that may occur in patients with MCI after the DC. Methods: 27 patients with MCI treated with DC were studied. The CT perfusion hemodynamic parameters - the mean transit time (MTT), the cerebral blood volume (CBV) and cerebral blood flow (CBF) - were evaluated preoperatively and within the first 24 hours after the DC. The primary outcome measure was improvement or lack of improvement in cerebral hemodynamics. Secondary outcomes were the modified Rankin scale in 6 months, classified as favorable (0-3) and unfavorable (4-6); and, fatal cases at 1 month and 6 months. Results: 18 (70.3%) patients were female and 12 (44.4%) were older than 55 years. There was improvement of MTT (decrease from 8.74 to 8.24, p = 0.01) and a trend towards improvement of the CBF (increase from 22.37 to 25.26, p = 0.06) after DC. There was no statistical difference in the CBV before and after DC (increase from 2.14 to 2.26, p = 0.33). Patients over 55 years had poorer prognosis (p=0.03) and preoperative MTT was an independent hemodynamic predictor of mortality at 6 months (8.20 vs 9.23, p=0.04). Conclusions: DC improved cerebral hemodynamics in most patients with malignant ischemic stroke. Preoperative MTT seems to be a good marker for case fatality in 6 months

Introdução: A presença de cálcio nas artérias coronárias identifica a existência de aterosclerose coronariana, mesmo em fases precoces. Por outro lado, a decisão quanto à melhor forma de tratamento dessa entidade baseia-se no uso de exames funcionais, em especial, a cintilografia de perfusão do miocárdio (CPM). Existem dúvidas quanto à correlação desses dois exames, o que poderia ser, ao menos em parte, explicada pelo fato dos testes avaliarem fases distintas dessa entidade. Este estudo pretende avaliar o uso de uma abordagem anatômica e funcional combinada por meio da (CPM) e tomografia computadorizada coronária com multidetectores (TCMD) na determinação do escore de cálcio (CACS) e da presença de estenoses e isquemia e examinar a associação de seus resultados entre si e com outras variáveis demográficas, clínicas e funcionais em uma população brasileira com doença arterial coronária (DAC) suspeita ou conhecida. Métodos: foram analisados, retrospectivamente, 413 pacientes que se submeteram à CPM e TCMD por indicação clínica do médico assistente, durante o ano de 2009, com intervalo menor de 90 dias, entre os dois estudos. CACS foi definido automaticamente pelo software dedicado e o escore de Agatston foi calculado de forma semiquatitativa. Na CPM e na TCMD, os resultados foram obtidos por quantificação visual semiobjetiva. A correlação dos resultados dos exames foi analisada e foram obtidos dados da evolução tardia, baseados no contato com o médico assistente ou pela análise dos registros hospitalares. Procurou-se definir os preditores da ocorrência de eventos cardiovasculares adversos na evolução. Resultados: Foram selecionados 303 pacientes (73,3% homens, média de idade de 55,8 ± 10,6 anos, intervalo: 32-86 anos). Destes, 73,3% apresentaram estudos de perfusão normal, 71,6% tinham cálcio coronário e 45,2% tinha perfusão normal e TCDM com cálcio. No grupo sem suspeita de DAC (177), houve associação entre os resultados de TCMD e SPECT com: diabetes (DM) (p=0,045), hipertensão (HAS) (p=0,032), dislipidemia (p=0,030) testes funcionais, resultado do teste (p=0,022), percentil escore de cálcio (p<0,001) e CACS (p<0,001). Nos pacientes sem DAC, houve associação com defeitos de perfusão e TCMD com cálcio que mostraram em casos de DM (30,0%) e CACS igual ou acima do percentil 75 (60,0%) e com valores acima de 400 (40,0%). O grupo com TCMD e perfusão normal apresentou maior percentual de ausência de HAS (78,6%). De outra forma, o grupo com perfusão normal e TCMD com cálcio mostrou mais pacientes com dislipidemia (42,5%) e distribuição dos percentis de CACS e CACS, semelhantes ao grupo com defeitos de perfusão e TCMD com cálcio. No grupo dos pacientes com DAC conhecida, também houve associação entre CACS e a extensão da aterosclerose coronária. Não houve associações entre os resultados da cintilografia e TCMD e outras variáveis. No subgrupo de 128 pacientes, em que se conseguiu seguimento tardio (média de 824,5 dias; DP de 385,9), aconteceram dois óbitos (1,6%), nenhum de causa cardiovascular. O evento mais frequente foi cinecoronariografia (CAT) (21,1%), seguida da angioplastia (ATC) (9,4%) e revascularizações cirúrgicas (3,1%). Não houve infarto do miocárdio (IM). De forma similar, não foram observados determinantes significativos da evolução tardia desses pacientes. Conclusões: Embora o CAC tenha sido tão frequente, como perfusão normal no SPECT, menos da metade daqueles com SPECT normal podem apresentar cálcio coronário à TCMD. Esta combinação de resultados (SPECT normal e cálcio) tinha associação com dislipidemia. Além disso, DM, CACS > 400 e percentil igual ou superior a 75% foram associados com SPECT anormal e cálcio na MDCT. A MDTC combinada ao SPECT foi capaz de detectar isquemia em pacientes com estenose coronariana conhecida, mas não havia associações entre o grau de estenose ou a presença, ou ausência de isquemia e sua extensão, com os resultados combinados. Houve uma baixa taxa de eventos no subgrupo de acompanhamento. / Background: The calcium in coronary arteries identifies the presence of coronary atherosclerosis, even in early stages. On the other hand, the decision about the best form of treatment this entity is based on the use of functional tests, in particular the myocardial perfusion scintigraphy (SPECT). There are doubts about the correlation between the results of these two exams, what could be, at least in part explained by the fact of these tests assess distinct phases of this entity. This study aims to evaluate the use of a combined functional and anatomical approach through SPECT and coronary computed tomography with multi-detectors (MDCT) in determining the calcium score (CACS),presence of stenosis or ischemia and examine the combined results with other demographic, clinical and functional variables, in a Brazilian population with suspected or known coronary artery disease (CAD). Methods: we retrospectively analyzed 413 patients who underwent to SPECT and MDCT by their physician indications during the year 2009, with less than 90 days interval between the two studies. CACS was automatically defined by dedicated software and the Agatston score was semi-automatically calculated. SPECT and MDCT results were evaluated by semi-objective visual quantification. The correlations of both tests results were analyzed and follow-up data were obtained through contact with assistant physician or analysis of hospital records. Results: We included 303 patients with suspect or known DAC who underwent to both, SPECT and MDCT (75.9 % men, mean age 55.8 ± 10.6 years; range:32-86 years); it was observed that 73,3% had normal perfusion studies, CAC was present 71,6% patients and 48.2% had normal perfusion and MDCT with calcium. In 177 patients without DAC there were association between MDCT and SPECT results and following variables: diabetes (DM) (p=0.045), hypertension (HAS) (p=0.032), dyslipidemia (p=0.030), functional test results (p=0.022), percentile of calcium score (p<0.001) and CACS (p<0.001). Patients without DAC, with perfusion defects and calcium showed more occurrences of DM (30.0%) and CACS equal to or above the 75 percentile (60.0%) and with values above 400 (40.0%). The group with normal MDCT and perfusion had higher percentage of absence of HAS (78.6%). The group with normal perfusion and MDCT with calcium had the highest percentage of patients with dyslipidemia (42.5%) and distribution of the calcium score percentiles and CACS were similar to the group with perfusion defects and MDCT with calcium. In the group with known CAD there was association between DM, extent of coronary disease and CACS. There were no associations between the results of SPECT and MDCT and other variables. In the subgroup of 128 patients with follow-up, the average time was 824.5 days (SD 385.9), there were 2 deaths (1.6%) confirmed, however none of cardiovascular cause. Coronary angiography (CATH) (21.1%) was the most frequent event, followed by percutaneous angioplasty (PTCA) (9.4%). Surgical revascularizations were much less frequent (3.1%). There was no myocardial infarction (MI). Similarly, there were no markers of long term prognosis in this sample. Conclusions: Although CAC was as frequent as normal perfusion in SPECT, less than half with normal SPECT may have calcium on MDCT. This results combination (normal SPECT and calcium) had association with dyslipidemia. Also, DM, CACS >400 and percentile equal or above 75% were associate with abnormal SPECT and calcium on MDCT. MDCT combined to SPECT was able to detect ischemia in patients with known coronary stenosis, but there were no associations between the degree of stenosis, or the presence or absence of ischemia and its extent with the combined results. There was a low event rate in the follow-up subgroup.

Introdução: A hipertensão arterial pulmonar (HAP) é uma doença grave da circulação pulmonar, cujo diagnóstico e cuja avaliação funcional dependem do cateterismo cardíaco direito. A tomografia de dupla energia (TCDE), por meio da técnica de decomposição de materiais, permite obter um mapa de Iodo do parênquima pulmonar, que pode ser avaliado de forma qualitativa e quantitativa, e pode ser útil na avaliação da HAP. Objetivos: Avaliar a distribuição de Iodo no parênquima pulmonar, comparando com marcadores hemodinâmicos, marcadores de gravidade e com grupo-controle normopressórico. Métodos: Pacientes com HAP, acompanhados na Unidade de Circulação Pulmonar (InCor-HCFMUSP), foram avaliados por angiotomografia das artérias pulmonares (angioTC) como parte de sua rotina diagnóstica, em modo de dupla energia. O grupo-controle foi composto por pacientes com suspeita clínica de tromboembolismo pulmonar (TEP), com angioTC negativa para TEP e com ecocardiograma normal. Foram avaliadas as concentrações de Iodo no pulmão (mg/mL) por meio de 8 regiões de interesse redondas com 1 cm2 de área, distribuídas ao longo do eixo ântero-posterior do pulmão direito, em 3 níveis predeterminados. Foram obtidas, também, as medidas do ventrículo direito (VD), ventrículo esquerdo (VE), razão VD/VE, diâmetros da aorta (AO) e artéria pulmonar (AP). O realce da artéria pulmonar por meio da TCDE (PAenh) também foi obtido. Os resultados foram comparados entre os grupos, e correlacionados no grupo HAP com parâmetros hemodinâmicos invasivos e marcadores de gravidade. Resultados: O grupo HAP foi composto por 21 pacientes, com idade média de 42 anos, 47,6% em classe funcional I/II. Houve diferença significativa nos diâmetros da AP (p<0,01), VD (p<0,01), e VE (p=0,01), entre os grupos HAP e controle. Também demonstraram diferenças significativas às relações entre os diâmetros AP/AO (p < 0,01) e VD/VE (p < 0,01), entre os grupos. Calibre da artéria pulmonar maior do que 2,9 cm e relação AP/AO maior do que 1,1 cm demonstraram sensibilidade de 90,5% e 87,5%, e especificidade de 100% para o diagnóstico de HP. A PAenh não demonstrou diferenças significativas entre os grupos HAP e controle, contudo se correlacionou significativamente com a medida do débito cardíaco no grupo HAP (r=-0,661, p=0,01). A PAPm demonstrou correlação com a relação AP/AO (r=0,676) e, também, com a relação VD/VE (r=0,679), ambas com p < 0,01. A concentração de Iodo no parênquima foi significativamente menor no grupo HAP em todos os segmentos analisados. O mapa de Iodo demonstrou gradiente progressivo da concentração de Iodo no parênquima pulmonar, de caráter ântero-posterior, em ambos os grupos, de magnitude significativamente menor no grupo HAP. Usando-se o valor de PAenh para correção das medidas de concentração de Iodo, deixa de haver diferença entre os grupos HAP e controle. Conclusões: A TCDE, além das medidas anatômicas obtidas pela técnica convencional, permitiu demonstrar a manutenção do gradiente ântero-posterior da concentração de Iodo em pacientes com HAP, sugerindo que sua menor magnitude seja determinada pelo baixo débito cardíaco / Background: Pulmonary arterial hypertension (PAH) is a severe disease of the pulmonary circulation. Right heart catheterization (RHC) is crucial for diagnosis and management of these patients. High-resolution computed tomography (CT) and CT angiography play a crucial role in the diagnostic work-up of pulmonary hypertension. Dual energy computed tomography (DECT) is a technique of acquisition of modern CT scanners that allows obtaining a computed tomography of the pulmonary arteries with low iodine dose, and providing an estimation of iodine distribution in the lungs. Although the search for non-invasive methods for evaluation of PAH is developing, data concerning application of DECT on PAH patients remain scarce. Objectives: To evaluate the iodine distribution in the lungs obtained by DECT in PAH patients and a control group and compare to the hemodynamic profile, and prognostic markers of PAH patients. Methods: 21 patients followed at the Pulmonary Circulation Unit (InCor-HCFMUSP) and submitted to CT angiography were evaluated by DECT. A matched control group was composed by patients routinely referred to CT angiography to rule out pulmonary embolism with negative results and also a normal echocardiogram obtained at the same day. Eight circular 1cm2 ROIs were placed along the anteroposterior axis, at the middle of the right lung and at predetermined levels to measure the Iodine concentration in the lungs. Measurements of the pulmonary artery (PA), ascending aorta (AO), right ventricle (RV) and left ventricles (LV) were obtained, as well as enhancement of the PA (PAenh). Results were compared to the control group, and correlated with hemodynamic parameters in the PAH group. Results: PAH patients averaged 42 y/o, female/male ratio of 7/1, NYA functional classes I/II. Statistically significant differences between PAH patients and controls were found regarding measurements of PA (p < 0,01), RV (p < 0,01), LV (p=0,01), PA/AO (p < 0,01) and RV/LV (p < 0,01). PA diameter greater than 2,9 cm and PA/AO ratio greater 1,1 were diagnostic for pulmonary hypertension with sensitivity/specifity of 90,5%/100% and 87,5%/100%. PAenh showed no statistical difference between PAH patients and controls . A characteristic anteroposterior Iodine concentration gradient was found in all subjects, both PAH patients showed lower Iodine concentration diffusely (p < 0,01). When corrected by PAenh, Iodine gradients showed no statistical difference between PAH patients and controls. PAenh correlates with cardiac output (r=-0,661), and mPaP correlates with PA/AO ratio (r=0,676), RV/LV ratio VD/VE ratio (r=0,679), and p<0,01. Conclusion: Anteroposterior Iodine concentration gradient is preserved in PAH in comparison with controls, but with lower magnitude. This difference was corrected through the multiplication of individual Iodine measurements by PAenh, suggesting that this could be explained by lower blood flow to the lungs of PAH patients. PAenh correlates with cardiac output, mean pulmonary arterial pressure correlates with PA/AO and RV/LV in PAH patients. DECT provided conventional anatomic measurements and allowed the characterization of preserved anteroposterior Iodine gradients in PAH patients, with decreased magnitude in comparison with controls, that could be atributed to a lower CO of these patients

Introdução: A hipertensão arterial pulmonar (HAP) é uma doença grave da circulação pulmonar, cujo diagnóstico e cuja avaliação funcional dependem do cateterismo cardíaco direito. A tomografia de dupla energia (TCDE), por meio da técnica de decomposição de materiais, permite obter um mapa de Iodo do parênquima pulmonar, que pode ser avaliado de forma qualitativa e quantitativa, e pode ser útil na avaliação da HAP. Objetivos: Avaliar a distribuição de Iodo no parênquima pulmonar, comparando com marcadores hemodinâmicos, marcadores de gravidade e com grupo-controle normopressórico. Métodos: Pacientes com HAP, acompanhados na Unidade de Circulação Pulmonar (InCor-HCFMUSP), foram avaliados por angiotomografia das artérias pulmonares (angioTC) como parte de sua rotina diagnóstica, em modo de dupla energia. O grupo-controle foi composto por pacientes com suspeita clínica de tromboembolismo pulmonar (TEP), com angioTC negativa para TEP e com ecocardiograma normal. Foram avaliadas as concentrações de Iodo no pulmão (mg/mL) por meio de 8 regiões de interesse redondas com 1 cm2 de área, distribuídas ao longo do eixo ântero-posterior do pulmão direito, em 3 níveis predeterminados. Foram obtidas, também, as medidas do ventrículo direito (VD), ventrículo esquerdo (VE), razão VD/VE, diâmetros da aorta (AO) e artéria pulmonar (AP). O realce da artéria pulmonar por meio da TCDE (PAenh) também foi obtido. Os resultados foram comparados entre os grupos, e correlacionados no grupo HAP com parâmetros hemodinâmicos invasivos e marcadores de gravidade. Resultados: O grupo HAP foi composto por 21 pacientes, com idade média de 42 anos, 47,6% em classe funcional I/II. Houve diferença significativa nos diâmetros da AP (p<0,01), VD (p<0,01), e VE (p=0,01), entre os grupos HAP e controle. Também demonstraram diferenças significativas às relações entre os diâmetros AP/AO (p < 0,01) e VD/VE (p < 0,01), entre os grupos. Calibre da artéria pulmonar maior do que 2,9 cm e relação AP/AO maior do que 1,1 cm demonstraram sensibilidade de 90,5% e 87,5%, e especificidade de 100% para o diagnóstico de HP. A PAenh não demonstrou diferenças significativas entre os grupos HAP e controle, contudo se correlacionou significativamente com a medida do débito cardíaco no grupo HAP (r=-0,661, p=0,01). A PAPm demonstrou correlação com a relação AP/AO (r=0,676) e, também, com a relação VD/VE (r=0,679), ambas com p < 0,01. A concentração de Iodo no parênquima foi significativamente menor no grupo HAP em todos os segmentos analisados. O mapa de Iodo demonstrou gradiente progressivo da concentração de Iodo no parênquima pulmonar, de caráter ântero-posterior, em ambos os grupos, de magnitude significativamente menor no grupo HAP. Usando-se o valor de PAenh para correção das medidas de concentração de Iodo, deixa de haver diferença entre os grupos HAP e controle. Conclusões: A TCDE, além das medidas anatômicas obtidas pela técnica convencional, permitiu demonstrar a manutenção do gradiente ântero-posterior da concentração de Iodo em pacientes com HAP, sugerindo que sua menor magnitude seja determinada pelo baixo débito cardíaco / Background: Pulmonary arterial hypertension (PAH) is a severe disease of the pulmonary circulation. Right heart catheterization (RHC) is crucial for diagnosis and management of these patients. High-resolution computed tomography (CT) and CT angiography play a crucial role in the diagnostic work-up of pulmonary hypertension. Dual energy computed tomography (DECT) is a technique of acquisition of modern CT scanners that allows obtaining a computed tomography of the pulmonary arteries with low iodine dose, and providing an estimation of iodine distribution in the lungs. Although the search for non-invasive methods for evaluation of PAH is developing, data concerning application of DECT on PAH patients remain scarce. Objectives: To evaluate the iodine distribution in the lungs obtained by DECT in PAH patients and a control group and compare to the hemodynamic profile, and prognostic markers of PAH patients. Methods: 21 patients followed at the Pulmonary Circulation Unit (InCor-HCFMUSP) and submitted to CT angiography were evaluated by DECT. A matched control group was composed by patients routinely referred to CT angiography to rule out pulmonary embolism with negative results and also a normal echocardiogram obtained at the same day. Eight circular 1cm2 ROIs were placed along the anteroposterior axis, at the middle of the right lung and at predetermined levels to measure the Iodine concentration in the lungs. Measurements of the pulmonary artery (PA), ascending aorta (AO), right ventricle (RV) and left ventricles (LV) were obtained, as well as enhancement of the PA (PAenh). Results were compared to the control group, and correlated with hemodynamic parameters in the PAH group. Results: PAH patients averaged 42 y/o, female/male ratio of 7/1, NYA functional classes I/II. Statistically significant differences between PAH patients and controls were found regarding measurements of PA (p < 0,01), RV (p < 0,01), LV (p=0,01), PA/AO (p < 0,01) and RV/LV (p < 0,01). PA diameter greater than 2,9 cm and PA/AO ratio greater 1,1 were diagnostic for pulmonary hypertension with sensitivity/specifity of 90,5%/100% and 87,5%/100%. PAenh showed no statistical difference between PAH patients and controls . A characteristic anteroposterior Iodine concentration gradient was found in all subjects, both PAH patients showed lower Iodine concentration diffusely (p < 0,01). When corrected by PAenh, Iodine gradients showed no statistical difference between PAH patients and controls. PAenh correlates with cardiac output (r=-0,661), and mPaP correlates with PA/AO ratio (r=0,676), RV/LV ratio VD/VE ratio (r=0,679), and p<0,01. Conclusion: Anteroposterior Iodine concentration gradient is preserved in PAH in comparison with controls, but with lower magnitude. This difference was corrected through the multiplication of individual Iodine measurements by PAenh, suggesting that this could be explained by lower blood flow to the lungs of PAH patients. PAenh correlates with cardiac output, mean pulmonary arterial pressure correlates with PA/AO and RV/LV in PAH patients. DECT provided conventional anatomic measurements and allowed the characterization of preserved anteroposterior Iodine gradients in PAH patients, with decreased magnitude in comparison with controls, that could be atributed to a lower CO of these patients

<p>Knowledge of the relationship between <i>in vivo</i> contrast agent concentration and magnetic resonance (MR) signal response is an important requirement in contrast enhanced MR imaging in general and in MR based perfusion imaging in particular. This relationship is a complex function of the properties of the contrast agent as well as the structure of the target tissue. The aim of the present work was to quantify the effects of the iron oxide nanoparticle based intravascular contrast agent, NC100150 Injection, on proton relaxation rates in different tissue systems <i>in vivo</i> in a pig model and <i>ex vivo</i> in phantoms containing whole blood. Methods that enabled accurate relaxation rate measurements in these organs were developed, and validated. From these measurements, trans-compartmental water exchange rates and blood volume could be estimated and the MR signal response could be predicted as a function of contrast agent concentration under relevant imaging conditions. </p><p>Using a 1.5 Tesla clinical MR system, the longitudinal (R₁=1/T₁) proton relaxation rates in blood, renal cortex, paraspinal muscle and myocardium were measured <i>in vivo</i> as a function of plasma concentration (C_p) of NC100150 Injection. The transverse (R₂^* = 1/T₂^*) relaxation rates were measured <i>in vivo</i> in blood, renal cortex and muscle as a function of C_p and <i>ex vivo</i> in blood as a function of C_p and blood oxygenation tension. The proton nuclear MR (NMR) linewidth and lineshape were analysed as a function of C_p and blood oxygen tension <i>ex vivo</i> at 7.05 T. </p><p>In muscle and renal cortex, there was a linear correlation between R₂^* and C_p whereas R₂^* increased as a quadratic function of C_pin blood. The NMR linewidth increased linearly with C_p in fully oxygenated blood whereas in deoxygenated blood the linewidth initially decreased with increasing Cp, reaching a minimum and then increasing again with further increase in C_p. R₁ increased linearly with C_p in blood and from the slope of R₁ vs. C_p the T₁-relaxivity (r₁) of NC100150 Injection in blood at 1.5 T was estimated to be (mean ± SD) 13.9 ± 0.9 s^-1mM^-1. In tissue, the maximum increase in R₁ was limited by the rate of water exchange between the intravascular and interstitial tissue compartments. Using a two-compartment exchange-limited relaxation model, the permeability surface area (PS) product was estimated to be 61.9 ± 2.9 mL/min/g in renal cortex and 10.1 ± 1.5 mL/min/g in muscle and the total myocardial water exchange rate, <i>k</i><i>t</i>, was 13.5 ± 6.4 s^-1. The estimated blood volumes obtained from the same model were 19.1 ± 1.4 mL/100 g, 2.4 ± 1.4 mL/100 g and 11.2 ± 2.1 mL/100 g, respectively in renal cortex, muscle and myocardium.</p><p>Current T₂^* based first-pass MR perfusion methods assume a linear correlation between R₂^* and C_p both in blood and tissue and our results therefore suggest that quantitative perfusion values can not easily be obtained with existing tracer kinetic models. The correlation between MR signal response and C_p is further complicated in the kidney by a significant first-pass increase in R₁ which may lead to an underestimation of C_p. In T₁-based perfusion methods, low concentrations of NC100150 Injection must be used in order to maintain a linear dose-response relationship between R₁ and C_p. The effect of blood oxygenation on the NMR linewidth in the presence of NC100150 Injection enabled accurate estimation of magnetic susceptibility of deoxyhemoglobin and the effect can potentially be used to determine blood oxygenation status.</p><p>In conclusion, NC100150 Injection is well suited as a T₂^* perfusion agent due to the large magnetisation and intravascular biodistribution of this agent. T₁-based perfusion imaging with this agent is limited by water exchange effects and large T₂^* effects at higher contrast agent concentrations. Quantitative perfusion assessment is unlikely to be feasible with any of these approaches due to the non-linear dose response.</p>