Publicação
Quantifying age-related differences in diffusion tensor imaging biomarkers for the male urethral sphincter of prostate cancer patients
| Resumo: | For the past years, radical prostatectomy (RP) has been the treatment of choice for locally advanced prostate cancer (PC) because of its high accuracy in tumor removal. However, the surgical techniques performed tend to be invasive, with a complete removal of the proximal lisso-sphincter and partial removal of the distal rhabdosphincter. Whereas the former has been related with maintenance of continence at rest, the latter is related with active continence. Between 4 to 69 % [1] of patients undergoing RP develop urinary incontinence, with a reported decrease in quality of life. This can be a consequence, not only from the surgical technique used, but from other factors including the competence of the sphincter function, that it is expected to decrease with age [2]. It is important to find preoperative imaging biomarkers that can help predict the risk of the patient developing postoperative urinary incontinence. The TransDouglas project, approved by the Ethics Committee of Champalimaud Foundation since July 2018, aims at validating the implementation of a new surgical procedure for RP, which is an improved version of the robotic-assisted laparoscopic radical prostatectomy (RALRP) procedure. Preoperative anatomical parameters are extracted from the T2-weighted magnetic resonance imaging (MRI) that can be related with urinary incontinence after the new surgical technique, and to construct a model that can help predict the likely time until urinary continence recovery. Diffusion tensor imaging (DTI) is a MRI-based technique that allows the quantification of anisotropic movement of water molecules. It has been proven [3] that this technique can be used to visualize the microarchitecture of the urethral sphincters, and to extract relevant diffusion metrics. DTI metrics can be incorporated in the model to predict urinary incontinence recovery after RP. Considering this, an addendum to the TransDouglas project that requests the acquisition of an additional DTI sequence to the standard multiparametric (mpMRI) of the prostate has been approved this January, enabling the use of DTI to study the microarchitecture of the urethral sphincters in vivo and non-invasively. However, since parameters of sphincter function significantly change with age [2], it is important to study the influence of patient age at scan on these parameters prior to predicting the likely chance of continence recovery after RP. Therefore, the main goal of this thesis was to investigate age-related differences in DTI metrics of the male urethral sphincter complex. Furthermore, the influence of a prostate condition, including PC and benign prostatic hyperplasia (BPH), was studied. The proximal and distal sphincters, as well as the membranous urethra, were reconstructed for 95 subjects by using the deterministic tractography algorithm in DSIStudio software [4]. DTI metrics were extracted including tract length and density, fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) and additional histogram parameters for each DTI metric, namely standard deviation, median, trimmed mean, median absolute deviation, minimum, maximum, range, skewness, kurtosis, standard error and the 5th, 25th, 75th and 95th percentiles. The influence of subject motion and eddy currents corrections on the extracted DTI metrics was investigated. Linear regressions and Pearson or Spearman correlations were performed between age and each of the DTI metrics. Additionally, analysis of variance (ANOVA), or the non-parametric Kruskal-Wallis test, were used to compare DTI metrics between four age groups (from 50 to 59, 60 to 69, 70 to 79 and 80 to 89 years old). For a subset of the 69 subjects with a confirmed diagnosis for PC, BPH and the absence of any of both, ANOVA testing was used to compare between disease groups, and t-tests, or the nonparametric Wilcoxon test, to compare between cancer status. For statistically significant ANOVA test results, post-hoc t-tests were used to investigate the groups between which the difference lied. No statistically significant differences were found on DTI metrics with and without motion and eddy currents corrections, so the non-corrected DTI data was used for the subsequent analysis. In this study, it was found that MD and RD distributions statistical significantly changed with age. In particular, older subjects evidenced lower RD kurtosis in the proximal sphincter, lower MD maximum in the distal sphincter and higher MD median absolute deviation in the membranous urethra. On the other hand, further investigations are needed to understand if the presence of a prostate condition affects the DTI metrics of the sphincters and membranous urethra. This project was the first to examine age related differences in the urethral sphincter complex using DTI, as well as, the first time a DTI sequence for the prostate was implemented at Champalimaud Centre for the Unknown (CCU). It was concluded that age should be used as a covariate in a model that makes use of DTI biomarkers representative of the male urethral complex microstructure to predict the likely time of post-surgical continence recovery. Ultimately, this investigation should be a starting point for helping clinicians in the prediction of the risk of complications for each patient before undergoing RP, and balance the advantages and disadvantages comparing with other available treatment options for PC. |
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| Autores principais: | Verde, Ana Sofia de Castro |
| Assunto: | Imagem por tensor de difusao Tractografia Esfincter uretral Idade Cancro da prostata Teses de mestrado - 2019 |
| Ano: | 2019 |
| País: | Portugal |
| Tipo de documento: | dissertação de mestrado |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade de Lisboa |
| Idioma: | inglês |
| Origem: | Repositório da Universidade de Lisboa |
| Resumo: | For the past years, radical prostatectomy (RP) has been the treatment of choice for locally advanced prostate cancer (PC) because of its high accuracy in tumor removal. However, the surgical techniques performed tend to be invasive, with a complete removal of the proximal lisso-sphincter and partial removal of the distal rhabdosphincter. Whereas the former has been related with maintenance of continence at rest, the latter is related with active continence. Between 4 to 69 % [1] of patients undergoing RP develop urinary incontinence, with a reported decrease in quality of life. This can be a consequence, not only from the surgical technique used, but from other factors including the competence of the sphincter function, that it is expected to decrease with age [2]. It is important to find preoperative imaging biomarkers that can help predict the risk of the patient developing postoperative urinary incontinence. The TransDouglas project, approved by the Ethics Committee of Champalimaud Foundation since July 2018, aims at validating the implementation of a new surgical procedure for RP, which is an improved version of the robotic-assisted laparoscopic radical prostatectomy (RALRP) procedure. Preoperative anatomical parameters are extracted from the T2-weighted magnetic resonance imaging (MRI) that can be related with urinary incontinence after the new surgical technique, and to construct a model that can help predict the likely time until urinary continence recovery. Diffusion tensor imaging (DTI) is a MRI-based technique that allows the quantification of anisotropic movement of water molecules. It has been proven [3] that this technique can be used to visualize the microarchitecture of the urethral sphincters, and to extract relevant diffusion metrics. DTI metrics can be incorporated in the model to predict urinary incontinence recovery after RP. Considering this, an addendum to the TransDouglas project that requests the acquisition of an additional DTI sequence to the standard multiparametric (mpMRI) of the prostate has been approved this January, enabling the use of DTI to study the microarchitecture of the urethral sphincters in vivo and non-invasively. However, since parameters of sphincter function significantly change with age [2], it is important to study the influence of patient age at scan on these parameters prior to predicting the likely chance of continence recovery after RP. Therefore, the main goal of this thesis was to investigate age-related differences in DTI metrics of the male urethral sphincter complex. Furthermore, the influence of a prostate condition, including PC and benign prostatic hyperplasia (BPH), was studied. The proximal and distal sphincters, as well as the membranous urethra, were reconstructed for 95 subjects by using the deterministic tractography algorithm in DSIStudio software [4]. DTI metrics were extracted including tract length and density, fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) and additional histogram parameters for each DTI metric, namely standard deviation, median, trimmed mean, median absolute deviation, minimum, maximum, range, skewness, kurtosis, standard error and the 5th, 25th, 75th and 95th percentiles. The influence of subject motion and eddy currents corrections on the extracted DTI metrics was investigated. Linear regressions and Pearson or Spearman correlations were performed between age and each of the DTI metrics. Additionally, analysis of variance (ANOVA), or the non-parametric Kruskal-Wallis test, were used to compare DTI metrics between four age groups (from 50 to 59, 60 to 69, 70 to 79 and 80 to 89 years old). For a subset of the 69 subjects with a confirmed diagnosis for PC, BPH and the absence of any of both, ANOVA testing was used to compare between disease groups, and t-tests, or the nonparametric Wilcoxon test, to compare between cancer status. For statistically significant ANOVA test results, post-hoc t-tests were used to investigate the groups between which the difference lied. No statistically significant differences were found on DTI metrics with and without motion and eddy currents corrections, so the non-corrected DTI data was used for the subsequent analysis. In this study, it was found that MD and RD distributions statistical significantly changed with age. In particular, older subjects evidenced lower RD kurtosis in the proximal sphincter, lower MD maximum in the distal sphincter and higher MD median absolute deviation in the membranous urethra. On the other hand, further investigations are needed to understand if the presence of a prostate condition affects the DTI metrics of the sphincters and membranous urethra. This project was the first to examine age related differences in the urethral sphincter complex using DTI, as well as, the first time a DTI sequence for the prostate was implemented at Champalimaud Centre for the Unknown (CCU). It was concluded that age should be used as a covariate in a model that makes use of DTI biomarkers representative of the male urethral complex microstructure to predict the likely time of post-surgical continence recovery. Ultimately, this investigation should be a starting point for helping clinicians in the prediction of the risk of complications for each patient before undergoing RP, and balance the advantages and disadvantages comparing with other available treatment options for PC. |
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