Recent evidence suggests that radiation may have a significant effect on tumour vascu lature in addition to damaging tumour cell DNA. It is well established that endothelial cells are among the first cells to respond after administration of ionizing radiation in both normal and tumour tissues. It has also been suggested that microvascular dysfunction may regulate tumour response to radiotherapy at high doses. However, due to limitations in imaging the microcirculation this response is not well characterized. Advances in high-frequency ultrasound and computation methods now make it possible to acquire and analyze 3-D ultrasound data of tumour blood flow in tumour micro-circulation. This thesis outlines the work done to test the hypothesis that single dose 8 Gy radio- therapy produces changes in tumour blood vessels which can be quantified using high- frequency power Doppler ultrasound. In addition, the issue of reproducibility of power Doppler measurements and the relationship between histopathology and power Doppler measurements have been examined.

Recent evidence suggests that radiation may have a significant effect on tumour vascu lature in addition to damaging tumour cell DNA. It is well established that endothelial cells are among the first cells to respond after administration of ionizing radiation in both normal and tumour tissues. It has also been suggested that microvascular dysfunction may regulate tumour response to radiotherapy at high doses. However, due to limitations in imaging the microcirculation this response is not well characterized. Advances in high-frequency ultrasound and computation methods now make it possible to acquire and analyze 3-D ultrasound data of tumour blood flow in tumour micro-circulation. This thesis outlines the work done to test the hypothesis that single dose 8 Gy radio- therapy produces changes in tumour blood vessels which can be quantified using high- frequency power Doppler ultrasound. In addition, the issue of reproducibility of power Doppler measurements and the relationship between histopathology and power Doppler measurements have been examined.

Made available in DSpace on 2014-06-11T19:26:18Z (GMT). No. of bitstreams: 0 Previous issue date: 2004Bitstream added on 2014-06-13T18:54:34Z : No. of bitstreams: 1 komatsu_my_me_botfm_prot.pdf: 2888253 bytes, checksum: 2a008d09d5316840782f66ef671ef847 (MD5) / Universidade Estadual Paulista (UNESP) / O aumento progressivo nas últimas décadas na incidência do câncer de mama é um fato que assola a humanidade, entretanto, as taxas de mortalidade tendem ao decréscimo em virtude da detecção precoce através de métodos de rastreio não invasivos, e do conhecimento cada vez maior do comportamento biológico do tumor. A maior adesão aos meios de rastreamento existentes hoje, deve-se não apenas ao medo que o câncer provoca nas mulheres, mas também ao fato dos exames utilizados para este rastreio não serem invasivos. Infelizmente, ainda não existem métodos capazes de dar indícios do comportamento biológico do tumor de forma instantânea, sem que haja a necessidade de submeter as pacientes portadoras de tumores malignos da mama a procedimentos cirúrgicos. Desde o início da última década do século XX, tem-se estudado a angiogênese do tumor através da ultra-sonografia, utilizando-se dos recursos de Color Doppler e Power Doppler. Neste trabalho, realizado no Hospital Santa Marcelina de Itaquaquecetuba, em conjunto com a Disciplina de Mastologia da Faculdade de Medicina de Botucatu - UNESP, foram estudadas trinta e cinco pacientes com tumores malignos da mama, onde os parâmetros hemodinâmicos (Índice de Resistência, Índice de Pulsatibilidade e a Velocidade Máxima no Pico Sistólico) através do Color Doppler... / Although a progressive increase in the incidence of breast cancer is a fact that plagues mankind, mortality rates tend to decrease given precocious detection using non-invasive tracking methods and an ever-growing knowledge of tumoral biological behaviour. The current large adhesion to tracking methods is explained not only by the fear cancer raises in women but also to the use of non-invasive exams. Unfortunately, there are no methods capable of giving instantaneous indication of tumoral biological behaviour without submitting patients with malignant tumors to surgical procedure. Since the early nineties and now at the dawn of the 21st Century, the angiogenesis of the tumor is being studied with the help of Color Doppler and Power Doppler ultrasonography. In this research - carried out at Santa Marcelina Hospital in Itaquaquecetuba in cooperation with the Department of Mastology of the Botucatu Medical School, São Paulo State University, thirty five patientes with mammary malignat tumors were... (Complete abstract click electronic access below)

Submitted by Caroline Xavier (caroline.xavier@pucrs.br) on 2017-05-19T17:37:33Z No. of bitstreams: 1 TES_MELISSA_CLAUDIA_BISI_PARCIAL.pdf: 474029 bytes, checksum: cd9002527f3261fb305955c53e4f5cc3 (MD5) / Made available in DSpace on 2017-05-19T17:37:33Z (GMT). No. of bitstreams: 1 TES_MELISSA_CLAUDIA_BISI_PARCIAL.pdf: 474029 bytes, checksum: cd9002527f3261fb305955c53e4f5cc3 (MD5) Previous issue date: 2016-12-09 / Introduction: Ultrasonography (US) is an useful tool for evaluation of synovial vascularization and proliferation in rheumatoid arthritis (RA). Differently from US power Doppler (PD), the resistive index (RI) of spectral Doppler (SD) provides a quantitative analysis of vascular inflammation, but its utility in the ultrasonographic evaluation of RA activity has not been established. Objetives: To associate the RI with US parameters of synovitis and disease activity in patients with established RA. Methods: Consecutive pD-positive RA patients were included in a prospective cross-sectional study. Disease activity and disability were evaluated using the Disease Activity Score in 28-joints (DAS28) and Health Assessment Questionnaire (HAQ), respectively. Gray scale (GS) synovitis, PD and SD analysis were performed by one of two examiners in wrists, second and third metacarpophalangeal, and proximal interphalangeal joints. The 10 joint-GS and -PD scores and the mean RI were then calculated. Weighted kappa values were employed to assess interobserver reliability. Results: out of 112 patients scanned initially, 95 patients with PD signal were included (median duration of disease, 7 years and mean DAS28, 4.32 ? 1.66). Weighted kappa values in real-time US were 0.77 for synovitis, 0.87 for PD and 0.68 for RI. There was a significant association of 10 joint-GS and -PD with swollen joints count (rs = 0.54, p <0.001 and rs = 0.39, P <0.001, respectively). There were no significant correlations of the RI with 10-joint- GS, 10-joint-PD, DAS28, joint counts or HAQ (P>0.10 for all tests). Conclusion: Spectral Doppler RI did not correlate to any US or clinical parameters of disease activity in our sample of established RA patients. The addition of the RI score does not seem to improve US performance in this scenario. / Introdu??o: A ultrassonografia (US) ? uma ferramenta ?til para a avalia??o da vasculariza??o sinovial e prolifera??o na artrite reumatoide (AR). Diferentemente do sinal de power Doppler (PD), o ?ndice de resist?ncia (RI) do Doppler espectral(SD) fornece uma an?lise quantitativa de inflama??o vascular, mas a sua utilidade na avalia??o ultrassonogr?fica da atividade reumatoide n?o foi estabelecida. Objetivos: Associar o RI com par?metros ultrassonogr?ficos e ?ndices de atividade da doen?a em pacientes com AR estabelecida. M?todos: pacientes com AR PDpositivos, consecutivos, foram inclu?dos neste estudo transversal. A atividade da doen?a e a capacidade funcional foram avaliados usando o Disease Activity Score em 28 articula??es (DAS28) e Health Assessment Questionnaire (HAQ), respectivamente. Sinovite em escala de cinza (GS), PD e an?lise do SD foram realizadas por dois examinadores em punhos, segunda e terceira metacarpofalangeanas e articula??es interfalangianas proximais. Os escores 10 GS, escore10 PD e media do RI foram calculados. Os valores de kappa ponderado foram empregados para avaliar a correla??o interobservador. Resultados: dos 112 pacientes recrutados inicialmente, 95 pacientes com sinal PD foram inclu?dos (dura??o m?dia da doen?a: 7 anos; DAS28 m?dio: 4,32 ? 1,66). Os valores de kappa em tempo real US foram 0,77 para sinovite, 0,87 para PD e de 0,68 para RI. Houve associa??o significativa dos escores 10 PD e 10 GS com a contagem de articula??es edemaciadas (rS=0.54, P<0.001 e rS=0.39, P<0.001, respectivamente). N?o foram obtidas correla??es significativas entre RI e escore 10 GS, escore 10 PD, DAS28 ou HAQ (P> 0,10 para todos os testes). Conclus?o: o RI n?o se correlacionou com dados ultrassonogr?ficos ou par?metros cl?nicos de atividade da doen?a em nossos pacientes com AR estabelecida. A adi??o do RI n?o pareceu melhorar o desempenho da US neste cen?rio.

<p>The purpose of this work was to: a) Determine whether the amount of colour in a power Doppler image is dependent on the angle between the examined vessel and the soundbeam and/or on the velocity of the flow within the vessel; b) Investigate if a dependency on flow velocity could be used for the detection of volume flow differences and c) Define clinical applications utilising the improved sensitivity to low flow of PD.</p><p>In the experimental studies (study I and II) a silicon tube in a water bath was insonated, the insonation angle and the volume flow changed and the resulting images stored, transferred to a personal computer and analysed with regard to the amount of colour present in the image.</p><p>In study III and IV the ability of power Doppler to depict low flow was used to produce a map of the perfusion in well perfused organs, lack of colour in all or part of an organ taken as a sign of decreased perfusion. 150 patients with a renal transplant (study III) and 15 patients with abdominal trauma (study IV) were examined; the detected areas of decreased perfusion were correlated to other imaging modalities, laboratory and clinical records in order to determine the underlying pathology.</p><p>In study V the power Doppler sensitivity was used to look for and describe small portosystemic shunts in 141 patients with liver cirrhoses and suspected portal hypertension.</p><p>The colour representation in a power Doppler image was found to be dependent both on the insonation angle and the flow velocity. Computer analysis of the images could detect differences in volume flow down to a change of 10 ml/min.</p><p>Of the 150 renal transplants, areas of decreased perfusion were found in 12, all of which could be given a plausible explanation (2 focal infections, 4 AV fistulae, 1 kinked segmental artery and 5 with problems related to an accessory artery).</p><p>Of the 20 organs (7 livers and 13 spleens) examined in the 15 trauma patients, 5 were found to have areas without colour, corresponding to localised haematomas. Using computed tomography as gold standard, ultrasound showed neither false positive nor false negative findings.</p><p>Of the 141 patients with cirrhosis, 40 had Doppler ultrasound findings of a shunt, consistent with a portal hypertension. 7 of these 40 shunts showed a typical “ball ” or “corkscrew ” pattern.</p><p>Conclusion: The colour in a power Doppler image is dependent not only on reflector concentration (as it should be in theory) but also on the insonation angle and the velocity of the flow. This can be used to detect relative changes in volume flow. Clinical applications of power Doppler include mapping of organ perfusion and the detection of small vessels. These applications are based on the high sensitivity of power Doppler.</p>

The purpose of this work was to: a) Determine whether the amount of colour in a power Doppler image is dependent on the angle between the examined vessel and the soundbeam and/or on the velocity of the flow within the vessel; b) Investigate if a dependency on flow velocity could be used for the detection of volume flow differences and c) Define clinical applications utilising the improved sensitivity to low flow of PD. In the experimental studies (study I and II) a silicon tube in a water bath was insonated, the insonation angle and the volume flow changed and the resulting images stored, transferred to a personal computer and analysed with regard to the amount of colour present in the image. In study III and IV the ability of power Doppler to depict low flow was used to produce a map of the perfusion in well perfused organs, lack of colour in all or part of an organ taken as a sign of decreased perfusion. 150 patients with a renal transplant (study III) and 15 patients with abdominal trauma (study IV) were examined; the detected areas of decreased perfusion were correlated to other imaging modalities, laboratory and clinical records in order to determine the underlying pathology. In study V the power Doppler sensitivity was used to look for and describe small portosystemic shunts in 141 patients with liver cirrhoses and suspected portal hypertension. The colour representation in a power Doppler image was found to be dependent both on the insonation angle and the flow velocity. Computer analysis of the images could detect differences in volume flow down to a change of 10 ml/min. Of the 150 renal transplants, areas of decreased perfusion were found in 12, all of which could be given a plausible explanation (2 focal infections, 4 AV fistulae, 1 kinked segmental artery and 5 with problems related to an accessory artery). Of the 20 organs (7 livers and 13 spleens) examined in the 15 trauma patients, 5 were found to have areas without colour, corresponding to localised haematomas. Using computed tomography as gold standard, ultrasound showed neither false positive nor false negative findings. Of the 141 patients with cirrhosis, 40 had Doppler ultrasound findings of a shunt, consistent with a portal hypertension. 7 of these 40 shunts showed a typical “ball ” or “corkscrew ” pattern. Conclusion: The colour in a power Doppler image is dependent not only on reflector concentration (as it should be in theory) but also on the insonation angle and the velocity of the flow. This can be used to detect relative changes in volume flow. Clinical applications of power Doppler include mapping of organ perfusion and the detection of small vessels. These applications are based on the high sensitivity of power Doppler.

OBJETIVO. El objetivo de este estudio fue explorar la capacidad de la ecografía tridimensional con Power Doppler (3DPD) para discriminar los tumores benignos y malignos dentro del grupo de masas anexiales sólido-quísticas con vascularización central y definir los puntos de corte de los índices 3DPD que se deben utilizar en un entorno clínico. MÉTODOS. Un total de 143 mujeres consecutivas (edad media, 50,4 años, rango, 17-82 años) con diagnóstico de lesión sólido-quística o sólida en modo B y con vascularización central en el 2DPD fueron evaluadas con ecografía 3D PD antes de la cirugía. El 3DPD se utilizó para evaluar la vascularización en las proyecciones papilares y áreas sólidas. Los índices vasculares (índice de vascularización [VI], índice de flujo [FI], y el índice vascularization-flujo [VFI]) se calculan automáticamente. El diagnóstico histológico definitivo se obtuvo en cada caso. RESULTADOS. Un total de 113 masas (74%) eran malignas y 39 (26%) fueron benignoa. La evaluación morfológica reveló 30 uniloculares sólidas (19,7%), 43 multilocular sólidas (28,3%), y 79 masas sólidas (52%). La media VI (9,365% frente al 3,3%, P <.001), FI (34,318 versus 28,794; p <.001), y VFI (3,233 frente a 1,15; P <0,01) fueron significativamente mayores en los tumores malignos. No se encontraron diferencias en el índice de resistencia, índice de pulsatilidad, y la velocidad pico sistólica. El análisis de la curva ROC reveló un área bajo la curva de 0,77 (intervalo de confianza del 95%, 0.69-0.85), 0,71 (0.60-0.81) y 0.75 (0.66-0.83) para la VI, FI y VFI, respectivamente. Para reducir la tasa de falsos positivos en casi una tercera parte, los valores de sensibilidad para el VI (corte, 1,556%), FI (25,212), y VFI (0,323) fueron 92%, 95% y 93%, respectivamente. CONCLUSIONES. Los índices vasculares con 3DPD son útiles para reducir la tasa de falsos positivos en lesiones sólidas y sólido-quísticas con vascularización central. PALABRAS CLAVE: masa anexial; cáncer de ovario; Power Doppler, 3DPD / OBJECTIVE. The purpose of this study was to explore the role of 3-dimensional (3D) power Doppler (PD) sonography to discriminate between benign and malignant cystic-solid and solid vascularized adnexal masses and to define cutoff values for 3D PD indices to be used in a clinical setting. METHODS. A total of 143 consecutive women (mean age, 50.4 years; range, 17-82 years) with diagnoses of cystic-solid or solid vascularized adnexal masses on B-mode and 2-dimensional PD sonography were evaluated by 3D PD sonography before surgery. Three-dimensional PD sonography was used to assess vascularization within papillary projections and solid areas with a virtual organ computer-aided analysis program.Three-dimensional PD vascular indices (vascularization index [VI], flow index [FI], and vascularizationflow index [VFI]) were automatically calculated. A definitive histologic diagnosis was obtained in each case. RESULTS. A total of 113 masses (74%) were malignant, and 39 (26%) were benign. Morphologic evaluation revealed 30 unilocular solid masses (19.7%), 43 multilocular solid masses (28.3%), and 79 mostly solid masses (52%). The mean VI (9.365% versus 3.3%; P < .001), FI (34.318 versus 28.794; P < .001), and VFI (3.233 versus 1.15; P < 0.01) were significantly higher in malignant tumors. No differences were found in the resistive index, pulsatility index, and peak systolic velocity. Receiver operating characteristic analysis revealed an area under the curve of 0.77 (95% confidence interval, 0.69-0.85), 0.71 (0.60-0.81), and 0.75 (0.66-0.83) for the VI, FI and VFI, respectively. For reducing the false-positive rate by almost one-third, sensitivity values for the VI (cutoff, 1.556%), FI (25.212), and VFI (0.323) were 92%, 95%, and 93%, respectively. CONCLUSIONS. Three-dimensional PD vascular indices could be helpful for reducing the false-positive rate in cystic-solid and solid vascularized adnexal masses. KEY WORDS: adnexal mass; ovarian cancer; 3-dimensional power Doppler sonography.

Objetivo - Comparar índices 3D Power Doppler (PD3D) da circulação úteroplacentária (UPC) no primeiro e segundo trimestre em pacientes que desenvolveram pré-eclâmpsia (PE) e aquelas que não fizeram e testar a hipótese de que os parâmetros da vascularização e intensidade de fluxo da placenta, tal como determinado por PD3D, são diferentes em gestações normais em comparação com pré-eclâmpsia. Método - Foi realizado um estudo observacional prospectivo usando PD3D para avaliar a perfusão da placenta em 96 gestantes que fizeram o exame ecográfico de rotina entre 11 e 14 semanas. O índice vascular (VI), o índice de fluxo (FI) e o índice de fluxo vascular (VFI) por histograma Doppler tridimensional foram calculados. Todas pacientes repetiram o exame entre 16 e 20 semanas. Após o nascimento as pacientes foram classificadas como normais ou com pré-eclâmpsia. Resultados - Os índices vasculares placentários incluindo VI, FI e VFI foram significativamente menores em placentas com PE em comparação com os controles no exame realizado no segundo trimestre (p <0,001). Não houve diferença estatística nas pacientes examinadas no primeiro trimestre. Conclusão - Nossos resultados sugerem que a avaliação de índices vasculares placentários com Power Doppler 3D no segundo trimestre tem o potencial para detectar as mulheres em risco para o desenvolvimento posterior de PE. / Objective - To compare 3D power Doppler indices (3DPD) of utero-placental circulation (UPC) in the first and second quarter in patients who developed preeclampsia and those who did not and to test the hypothesis that the parameters of vascularization and placenta flow intensity, as determined by three-dimensional ultrasound (3D) are different in normal pregnancies compared with preeclampsia. Methods - A prospective observational study using 3D power Doppler was performed to evaluate the placental perfusion in 96 pregnant women who came to do the ultrasound routine between 11 and 14 weeks. The placental vascular index (VI), flow index (FI), blood vessels and blood flow index (VFI) by three-dimensional Doppler histogram were calculated. All patients repeated the exam between 16 and 20 weeks. The outcome was scored as normal or preeclamptic. Results - The placental vascular indices including VI, FI and VFI were significantly lower in preeclamptic placentas compared with controls in the study performed in the second trimester (p <0.001). There was no statistical difference in the patients examined in the first trimester. Conclusion - Our findings suggest that 3D-Power Doppler assessment of placental vascular indices in the second trimester has the potential to detect women at risk for subsequent development of PE.

Objetivo - Comparar índices 3D Power Doppler (PD3D) da circulação úteroplacentária (UPC) no primeiro e segundo trimestre em pacientes que desenvolveram pré-eclâmpsia (PE) e aquelas que não fizeram e testar a hipótese de que os parâmetros da vascularização e intensidade de fluxo da placenta, tal como determinado por PD3D, são diferentes em gestações normais em comparação com pré-eclâmpsia. Método - Foi realizado um estudo observacional prospectivo usando PD3D para avaliar a perfusão da placenta em 96 gestantes que fizeram o exame ecográfico de rotina entre 11 e 14 semanas. O índice vascular (VI), o índice de fluxo (FI) e o índice de fluxo vascular (VFI) por histograma Doppler tridimensional foram calculados. Todas pacientes repetiram o exame entre 16 e 20 semanas. Após o nascimento as pacientes foram classificadas como normais ou com pré-eclâmpsia. Resultados - Os índices vasculares placentários incluindo VI, FI e VFI foram significativamente menores em placentas com PE em comparação com os controles no exame realizado no segundo trimestre (p <0,001). Não houve diferença estatística nas pacientes examinadas no primeiro trimestre. Conclusão - Nossos resultados sugerem que a avaliação de índices vasculares placentários com Power Doppler 3D no segundo trimestre tem o potencial para detectar as mulheres em risco para o desenvolvimento posterior de PE. / Objective - To compare 3D power Doppler indices (3DPD) of utero-placental circulation (UPC) in the first and second quarter in patients who developed preeclampsia and those who did not and to test the hypothesis that the parameters of vascularization and placenta flow intensity, as determined by three-dimensional ultrasound (3D) are different in normal pregnancies compared with preeclampsia. Methods - A prospective observational study using 3D power Doppler was performed to evaluate the placental perfusion in 96 pregnant women who came to do the ultrasound routine between 11 and 14 weeks. The placental vascular index (VI), flow index (FI), blood vessels and blood flow index (VFI) by three-dimensional Doppler histogram were calculated. All patients repeated the exam between 16 and 20 weeks. The outcome was scored as normal or preeclamptic. Results - The placental vascular indices including VI, FI and VFI were significantly lower in preeclamptic placentas compared with controls in the study performed in the second trimester (p <0.001). There was no statistical difference in the patients examined in the first trimester. Conclusion - Our findings suggest that 3D-Power Doppler assessment of placental vascular indices in the second trimester has the potential to detect women at risk for subsequent development of PE.

Objetivo - Comparar índices 3D Power Doppler (PD3D) da circulação úteroplacentária (UPC) no primeiro e segundo trimestre em pacientes que desenvolveram pré-eclâmpsia (PE) e aquelas que não fizeram e testar a hipótese de que os parâmetros da vascularização e intensidade de fluxo da placenta, tal como determinado por PD3D, são diferentes em gestações normais em comparação com pré-eclâmpsia. Método - Foi realizado um estudo observacional prospectivo usando PD3D para avaliar a perfusão da placenta em 96 gestantes que fizeram o exame ecográfico de rotina entre 11 e 14 semanas. O índice vascular (VI), o índice de fluxo (FI) e o índice de fluxo vascular (VFI) por histograma Doppler tridimensional foram calculados. Todas pacientes repetiram o exame entre 16 e 20 semanas. Após o nascimento as pacientes foram classificadas como normais ou com pré-eclâmpsia. Resultados - Os índices vasculares placentários incluindo VI, FI e VFI foram significativamente menores em placentas com PE em comparação com os controles no exame realizado no segundo trimestre (p <0,001). Não houve diferença estatística nas pacientes examinadas no primeiro trimestre. Conclusão - Nossos resultados sugerem que a avaliação de índices vasculares placentários com Power Doppler 3D no segundo trimestre tem o potencial para detectar as mulheres em risco para o desenvolvimento posterior de PE. / Objective - To compare 3D power Doppler indices (3DPD) of utero-placental circulation (UPC) in the first and second quarter in patients who developed preeclampsia and those who did not and to test the hypothesis that the parameters of vascularization and placenta flow intensity, as determined by three-dimensional ultrasound (3D) are different in normal pregnancies compared with preeclampsia. Methods - A prospective observational study using 3D power Doppler was performed to evaluate the placental perfusion in 96 pregnant women who came to do the ultrasound routine between 11 and 14 weeks. The placental vascular index (VI), flow index (FI), blood vessels and blood flow index (VFI) by three-dimensional Doppler histogram were calculated. All patients repeated the exam between 16 and 20 weeks. The outcome was scored as normal or preeclamptic. Results - The placental vascular indices including VI, FI and VFI were significantly lower in preeclamptic placentas compared with controls in the study performed in the second trimester (p <0.001). There was no statistical difference in the patients examined in the first trimester. Conclusion - Our findings suggest that 3D-Power Doppler assessment of placental vascular indices in the second trimester has the potential to detect women at risk for subsequent development of PE.