Pedro L. Rodrigues

Neuron-specific proteotoxicity of mutant ataxin-3 in C. elegans: rescue by the DAF-16 and HSF-1 pathways

The risk of developing neurodegenerative diseases increases with age. Although many of the molecular pathways regulating proteotoxic stress and longevity are well characterized, their contribution to disease susceptibility remains unclear. In this study, we describe a new Caenorhabditis elegans model of Machado-Joseph disease pathogenesis. Pan-neuronal expression of mutant ATXN3 leads to a polyQ-length dependent, neuron subtype-specific aggregation and neuronal dysfunction. Analysis of different neurons revealed a pattern of dorsal nerve cord and sensory neuron susceptibility to mutant ataxin-3 that was distinct from the aggregation and toxicity profiles of polyQ-alone proteins. This reveals that the sequences flanking the polyQ-stretch in ATXN3 have a dominant influence on cell-intrinsic neuronal factors that modulate polyQ-mediated pathogenesis. Aging influences the ATXN3 phenotypes which can be suppressed by the downregulation of the insulin/insulin growth factor-1-like signaling pathway and activation of heat shock factor-1.

Collecting System Percutaneous Access Using Real-Time Tracking Sensors: First Pig Model In Vivo Experience

PURPOSE Precise needle puncture of the renal collecting system is an essential but challenging step for successful percutaneous nephrolithotomy. We evaluated the efficiency of a new real-time electromagnetic tracking system for in vivo kidney puncture. MATERIALS AND METHODS Six anesthetized female pigs underwent ureterorenoscopy to place a catheter with an electromagnetic tracking sensor into the desired puncture site and ascertain puncture success. A tracked needle with a similar electromagnetic tracking sensor was subsequently navigated into the sensor in the catheter. Four punctures were performed by each of 2 surgeons in each pig, including 1 each in the kidney, middle ureter, and right and left sides. Outcome measurements were the number of attempts and the time needed to evaluate the virtual trajectory and perform percutaneous puncture. RESULTS A total of 24 punctures were easily performed without complication. Surgeons required more time to evaluate the trajectory during ureteral than kidney puncture (median 15 seconds, range 14 to 18 vs 13, range 11 to 16, p=0.1). Median renal and ureteral puncture time was 19 (range 14 to 45) and 51 seconds (range 45 to 67), respectively (p=0.003). Two attempts were needed to achieve a successful ureteral puncture. The technique requires the presence of a renal stone for testing. CONCLUSIONS The proposed electromagnetic tracking solution for renal collecting system puncture proved to be highly accurate, simple and quick. This method might represent a paradigm shift in percutaneous kidney access techniques.

Kidney Targeting and Puncturing During Percutaneous Nephrolithotomy: Recent Advances and Future Perspectives

BACKGROUND AND PURPOSE Precise needle puncture of the kidney is a challenging and essential step for successful percutaneous nephrolithotomy (PCNL). Many devices and surgical techniques have been developed to easily achieve suitable renal access. This article presents a critical review to address the methodologies and techniques for conducting kidney targeting and the puncture step during PCNL. Based on this study, research paths are also provided for PCNL procedure improvement. METHODS Most relevant works concerning PCNL puncture were identified by a search of Medline/PubMed, ISI Web of Science, and Scopus databases from 2007 to December 2012. Two authors independently reviewed the studies. RESULTS A total of 911 abstracts and 346 full-text articles were assessed and discussed; 52 were included in this review as a summary of the main contributions to kidney targeting and puncturing. CONCLUSIONS Multiple paths and technologic advances have been proposed in the field of urology and minimally invasive surgery to improve PCNL puncture. The most relevant contributions, however, have been provided by the application of medical imaging guidance, new surgical tools, motion tracking systems, robotics, and image processing and computer graphics. Despite the multiple research paths for PCNL puncture guidance, no widely acceptable solution has yet been reached, and it remains an active and challenging research field. Future developments should focus on real-time methods, robust and accurate algorithms, and radiation free imaging techniques.

An image processing application for liver tumour segmentation

Liver cancer is one of the leading causes of death worldwide. Consequently, the development of accurate and reliable segmentation techniques is indispensable for tumour volume measurement and staging analysis. An interactive algorithm for liver tumour segmentation was developed, allowing the user to quickly paint the object of interest in the image using an intelligent paintbrush. This technique was based on an image partitioning into homogeneous primitives regions by applying a pseudo-watershed algorithm on an image gradient magnitude. Outcome of this initial segmentation was the input of an efficient region merging process to find the best image partitioning, based on the minimum description length principle. The algorithm was evaluated on Computed Tomography (CT) and Magnetic Resonance (MR) data using the dice similarity coefficient (DSC) as a statistical validation metric. This led to a DCS mean scores of 87% and 84% on the CT and MR studies, respectively.

Ureteroscopy-assisted Percutaneous Kidney Access Made Easy: First Clinical Experience with a Novel Navigation System Using Electromagnetic Guidance (IDEAL Stage 1)

BACKGROUND Puncture of the renal collecting system represents a challenging step in percutaneous nephrolithotomy (PCNL). Limitations related to the use of standard fluoroscopic-based and ultrasound-based maneuvers have been recognized. OBJECTIVES To describe the technique and early clinical outcomes of a novel navigation system for percutaneous kidney access. DESIGN, SETTING, AND PARTICIPANTS This was a proof-of-concept study (IDEAL phase 1) conducted at a single academic center. Ten PCNL procedures were performed for patients with kidney stones. SURGICAL PROCEDURE Flexible ureterorenoscopy was performed to determine the optimal renal calyx for access. An electromagnetic sensor was inserted through the working channel. Then the selected calyx was punctured with a needle with a sensor on the tip guided by real-time three-dimensional images observed on the monitor. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS The primary endpoints were the accuracy and clinical applicability of the system in clinical use. Secondary endpoints were the time to successful puncture, the number of attempts for successful puncture, and complications. RESULTS AND LIMITATIONS Ten patients were enrolled in the study. The median age was 47.1 yr (30-63), median body mass index was 22.85kg/m2 (19-28.3), and median stone size was 2.13cm (1.5-2.5cm). All stones were in the renal pelvis. The Guys stone score was 1 in nine cases and 2 in one case. All 10 punctures of the collecting system were successfully completed at the first attempt without X-ray exposure. The median time to successful puncture starting from insertion of the needle was 20 s (range 15-35). No complications occurred. CONCLUSIONS We describe the first clinical application of a novel navigation system using real-time electromagnetic sensors for percutaneous kidney access. This new technology overcomes the intrinsic limitations of traditional methods of kidney access, allowing safe, precise, fast, and effective puncture of the renal collecting system. PATIENT SUMMARY We describe a new technology allowing safe and easy puncture of the kidney without radiation exposure. This could significantly facilitate one of the most challenging steps in percutaneous removal of kidney stones.

Pectus excavatum postsurgical outcome based on preoperative soft body dynamics simulation

Pectus excavatum is the most common congenital deformity of the anterior chest wall, in which an abnormal formation of the rib cage gives the chest a caved-in or sunken appearance. Today, the surgical correction of this deformity is carried out in children and adults through Nuss technic, which consists in the placement of a prosthetic bar under the sternum and over the ribs. Although this technique has been shown to be safe and reliable, not all patients have achieved adequate cosmetic outcome. This often leads to psychological problems and social stress, before and after the surgical correction. This paper targets this particular problem by presenting a method to predict the patient surgical outcome based on pre-surgical imagiologic information and chest skin dynamic modulation. The proposed approach uses the patient pre-surgical thoracic CT scan and anatomical-surgical references to perform a 3D segmentation of the left ribs, right ribs, sternum and skin. The technique encompasses three steps: a) approximation of the cartilages, between the ribs and the sternum, trough b-spline interpolation; b) a volumetric mass spring model that connects two layers - inner skin layer based on the outer pleura contour and the outer surface skin; and c) displacement of the sternum according to the prosthetic bar position. A dynamic model of the skin around the chest wall region was generated, capable of simulating the effect of the movement of the prosthetic bar along the sternum. The results were compared and validated with patient postsurgical skin surface acquired with Polhemus FastSCAN system.

Automatic Prebent Customized Prosthesis for Pectus Excavatum Minimally Invasive Surgery Correction

Pectus excavatum is the most common deformity of the thorax. A minimally invasive surgical correction is commonly carried out to remodel the anterior chest wall by using an intrathoracic convex prosthesis in the substernal position. The process of prosthesis modeling and bending still remains an area of improvement. The authors developed a new system, i3DExcavatum, which can automatically model and bend the bar preoperatively based on a thoracic CT scan. This article presents a comparison between automatic and manual bending. The i3DExcavatum was used to personalize prostheses for 41 patients who underwent pectus excavatum surgical correction between 2007 and 2012. Regarding the anatomical variations, the soft-tissue thicknesses external to the ribs show that both symmetric and asymmetric patients always have asymmetric variations, by comparing the patients’ sides. It highlighted that the prosthesis bar should be modeled according to each patient’s rib positions and dimensions. The average differences between the skin and costal line curvature lengths were 84 ± 4 mm and 96 ± 11 mm, for male and female patients, respectively. On the other hand, the i3DExcavatum ensured a smooth curvature of the surgical prosthesis and was capable of predicting and simulating a virtual shape and size of the bar for asymmetric and symmetric patients. In conclusion, the i3DExcavatum allows preoperative personalization according to the thoracic morphology of each patient. It reduces surgery time and minimizes the margin error introduced by the manually bent bar, which only uses a template that copies the chest wall curvature.

Automatic modeling of pectus excavatum corrective prosthesis using artificial neural networks

Pectus excavatum is the most common deformity of the thorax. Pre-operative diagnosis usually includes Computed Tomography (CT) to successfully employ a thoracic prosthesis for anterior chest wall remodeling. Aiming at the elimination of radiation exposure, this paper presents a novel methodology for the replacement of CT by a 3D laser scanner (radiation-free) for prosthesis modeling. The complete elimination of CT is based on an accurate determination of ribs position and prosthesis placement region through skin surface points. The developed solution resorts to a normalized and combined outcome of an artificial neural network (ANN) set. Each ANN model was trained with data vectors from 165 male patients and using soft tissue thicknesses (STT) comprising information from the skin and rib cage (automatically determined by image processing algorithms). Tests revealed that ribs position for prosthesis placement and modeling can be estimated with an average error of 5.0 ± 3.6mm. One also showed that the ANN performance can be improved by introducing a manually determined initial STT value in the ANN normalization procedure (average error of 2.82 ± 0.76 mm). Such error range is well below current prosthesis manual modeling (approximately 11 mm), which can provide a valuable and radiation-free procedure for prosthesis personalization.

Variations of the soft tissue thicknesses external to the ribs in pectus excavatum patients.

BACKGROUND Surgical repair of pectus excavatum (PE) has become more popular due to improvements in the minimally invasive Nuss procedure. The pre-surgical assessment of PE patients requires Computerized Tomography (CT), as the malformation characteristics vary from patient to patient. OBJECTIVE This work aims to characterize soft tissue thickness (STT) external to the ribs among PE patients. It also presents a comparative analysis between the anterior chest wall surface before and after surgical correction. METHODS Through surrounding tissue segmentation in CT data, STT values were calculated at different lines along the thoracic wall, with a reference point in the intersection of coronal and median planes. The comparative analysis between the two 3D anterior chest surfaces sets a surgical correction influence area (SCIA) and a volume of interest (VOI) based on image processing algorithms, 3D surface algorithms, and registration methods. RESULTS There are always variations between left and right side STTs (2.54 ± 2.05 mm and 2.95 ± 2.97 mm for female and male patients, respectively). STTs are dependent on age, sex, and body mass index of each patient. On female patients, breast tissue induces additional errors in bar manual conception. The distances starting at the deformitys largest depression point at the SCIA are similar in all directions. Some diverging measures and outliers were found, being difficult to find similar characteristics between them, especially in asymmetric patients. CONCLUSION The Nuss procedure metal bar must be modeled according to each patients special characteristics. The studied relationships between STT and chest surface could represent a step forward to eliminate the CT scan from PE pre-surgical evaluation.

Thoracic wall reconstruction using ultrasound images to model/bend the thoracic prosthesis for correction of pectus excavatum

Pectus excavatum is the most common congenital deformity of the anterior thoracic wall. The surgical correction of such deformity, using Nuss procedure, consists in the placement of a personalized convex prosthesis into sub-sternal position to correct the deformity. The aim of this work is the CT-scan substitution by ultrasound imaging for the pre-operative diagnosis and pre-modeling of the prosthesis, in order to avoid patient radiation exposure. To accomplish this, ultrasound images are acquired along an axial plane, followed by a rigid registration method to obtain the spatial transformation between subsequent images. These images are overlapped to reconstruct an axial plane equivalent to a CT-slice. A phantom was used to conduct preliminary experiments and the achieved results were compared with the corresponding CT-data, showing that the proposed methodology can be capable to create a valid approximation of the anterior thoracic wall, which can be used to model/bend the prosthesis.