Lucian Gruionu

Does Needle Rotation Improve Lesion Targeting

Image‐guided robots are manipulators that operate based on medical images. Perhaps the most common class of image‐guided robots are robots for needle interventions. Typically, these robots actively position and/or orient a needle guide, but needle insertion is still done by the physician. While this arrangement may have safety advantages and keep the physician in control of needle insertion, actuated needle drivers can incorporate other useful features.

Real-Time Image Fusion Involving Diagnostic Ultrasound

OBJECTIVE The aim of our article is to give an overview of the current and future possibilities of real-time image fusion involving ultrasound. We present a review of the existing English-language peer-reviewed literature assessing this technique, which covers technical solutions (for ultrasound and endoscopic ultrasound), image fusion in several anatomic regions, and electromagnetic needle tracking. CONCLUSION The recent progress of real-time ultrasound in image fusion may provide several new possibilities, including diagnosis, treatment, and follow-up of oncologic patients.

Three-dimensional endovascular navigation with electromagnetic tracking: ex vivo and in vivo accuracy.

Purpose To evaluate the accuracy of a 3-dimensional (3D) navigation system using electromagnetically tracked tools to explore its potential in patients. Methods The 3D navigation accuracy was quantified on a phantom and in a porcine model using the same setup and vascular interventional suite. A box-shaped phantom with 16 markers was scanned in 5 different positions using computed tomography (CT). The 3D navigation system registered each CT volume in the magnetic field. A tracked needle was pointed at the physical markers, and the spatial distances between the tracked needle positions and the markers were calculated. Contrast-enhanced CT images were acquired from 6 swine. The 3D navigation system registered each CT volume in the magnetic field. An electromagnetically tracked guidewire and catheter were visualized in the 3D image and navigated to 4 specified targets. At each target, the spatial distance between the tracked guidewire tip position and the actual position, verified by a CT control, was calculated. Results The mean accuracy on the phantom was 1.28±0.53 mm, and 90% of the measured distances were ≤1.90 mm. The mean accuracy in swine was 4.18±1.76 mm, and 90% of the measured distances were ≤5.73 mm. Conclusion This 3D navigation system demonstrates good ex vivo accuracy and is sufficiently accurate in vivo to explore its potential for improved endovascular navigation.

Confocal Laser Endomicroscopy for the Morphometric Evaluation of Microvessels in Human Colorectal Cancer Using Targeted Anti-CD31 Antibodies

Introduction Numerous anti-angiogenic agents are currently developed to limit tumor growth and metastasis. While these drugs offer hope for cancer patients, their transient effect on tumor vasculature is difficult to assess in clinical settings. Confocal laser endomicroscopy (CLE) is a novel endoscopic imaging technology that enables histological examination of the gastrointestinal mucosa. The aim of the present study was to evaluate the feasibility of using CLE to image the vascular network in fresh biopsies of human colorectal tissue. For this purpose we have imaged normal and malignant biopsy tissue samples and compared the vascular network parameters obtained with CLE with established histopathology techniques. Materials and Methods Fresh non-fixed biopsy samples of both normal and malignant colorectal mucosa were stained with fluorescently labeled anti-CD31 antibodies and imaged by CLE using a dedicated endomicroscopy system. Corresponding biopsy samples underwent immunohistochemical staining for CD31, assessing the microvessel density (MVD) and vascular areas for comparison with CLE data, which were measured offline using specific software. Results The vessels were imaged by CLE in both normal and tumor samples. The average diameter of normal vessels was 8.5±0.9 µm whereas in tumor samples it was 13.5±0.7 µm (p = 0.0049). Vascular density was 188.7±24.9 vessels/mm2 in the normal tissue vs. 242.4±16.1 vessels/mm2 in the colorectal cancer samples (p = 0.1201). In the immunohistochemistry samples, the MVD was 211.2±42.9/mm2 and 351.3±39.6/mm2 for normal and malignant mucosa, respectively. The vascular area was 2.9±0.5% of total tissue area for the normal mucosa and 8.5±2.1% for primary colorectal cancer tissue. Conclusion Selective imaging of blood vessels with CLE is feasible in normal and tumor colorectal tissue by using fluorescently labeled antibodies targeted against an endothelial marker. The method could be translated into the clinical setting for monitoring of anti-angiogenic therapy.

Evaluation of new morphometric parameters of neoangiogenesis in human colorectal cancer using confocal laser endomicroscopy (CLE) and targeted panendothelial markers.

The tumor microcirculation is characterized by an abnormal vascular network with dilated, tortuous and saccular vessels. Therefore, imaging the tumor vasculature and determining its morphometric characteristics represent a critical goal for optimizing the cancer treatment that targets the blood vessels (i.e. antiangiogenesis therapy). The aim of this study was to evaluate new vascular morphometric parameters in colorectal cancer, difficult to achieve through conventional immunohistochemistry, by using the confocal laser endomicroscopy method. Fresh biopsies from tumor and normal tissue were collected during colonoscopy from five patients with T3 colorectal carcinoma without metastasis and were marked with fluorescently labeled anti-CD31 antibodies. A series of optical slices spanning 250 µm inside the tissue were immediately collected for each sample using a confocal laser endomicroscope. All measurements were expressed as the mean ± standard error. The mean diameter of tumor vessels was significantly larger than the normal vessels (9.46±0.4 µm vs. 7.60±0.3 µm, p = 0.0166). The vessel density was also significantly higher in the cancer vs. normal tissue samples (5541.05±262.81 vs. 3755.79±194.96 vessels/mm3, p = 0.0006). These results were confirmed by immunohistochemistry. In addition, the tortuosity index and vessel lengths were not significantly different (1.05±0.016 and 28.30±3.27 µm in normal tissue, vs. 1.07±0.008 and 26.49±3.18 µm in tumor tissue respectively, p = 0.5357 and p = 0.7033). The daughter/mother ratio (ratio of the sum of the squares of daughter vessel radii over the square of the mother vessel radius) was 1.15±0.09 in normal tissue, and 1.21±0.08 in tumor tissue (p = 0.6531). The confocal laser endomicroscopy is feasible for measuring more vascular parameters from fresh tumor biopsies than conventional immunohistochemistry alone. Provided new contrast agents will be clinically available, future in vivo use of CLE could lead to identification of novel biomarkers based on the morphometric characteristics of tumor vasculature.

Lead-Free Piezoelectric (Ba,Ca)(Zr,Ti)O3 Thin Films for Biocompatible and Flexible Devices

In this work, we report the synthesis of functional biocompatible piezoelectric (1 - x)Ba(Ti0.8Zr0.2)TiO3-x(Ba0.7Ca0.3)TiO3, x = 0.45 (BCZT45), thin films with high piezoelectric properties. Pulsed-laser-based techniques, classical pulsed-laser deposition and matrix-assisted pulsed-laser evaporation, were used to synthesize the BCZT45 thin films. The second technique was employed in order to ensure growth on polymer flexible Kapton substrates. The BCZT45 thin films grown by both techniques show similar structural properties and high piezoelectric coefficient coupling between the mechanical loading and electrical potential. While it has long been shown that the electrical potential favors biological processes like osteogenesis, the assessment of cell adhesion and osteogenic differentiation onto BCZT materials has not yet been demonstrated. We prove here for the first time that BCZT 45 coatings on Kapton polymer substrates provide optimal support for osteogenic differentiation of mesenchymal stem cells in the bone marrow.

Transbronchial needle aspiration with a new electromagnetically-tracked TBNA needle

Transbronchial needle aspiration (TBNA) is a common method used to collect tissue for diagnosis of different chest diseases and for staging lung cancer, but the procedure has technical limitations. These limitations are mostly related to the difficulty of accurately placing the biopsy needles into the target mass. Currently, pulmonologists plan TBNA by examining a number of Computed Tomography (CT) scan slices before the operation. Then, they manipulate the bronchoscope down the respiratory track and blindly direct the biopsy. Thus, the biopsy success rate is low. The diagnostic yield of TBNA is approximately 70 percent. To enhance the accuracy of TBNA, we developed a TBNA needle with a tip position that can be electromagnetically tracked. The needle was used to estimate the bronchoscopes tip position and enable the creation of corresponding virtual bronchoscopic images from a preoperative CT scan. The TBNA needle was made with a flexible catheter embedding Wang Transbronchial Histology Needle and a sensor tracked by electromagnetic field generator. We used Aurora system for electromagnetic tracking. We also constructed an image-guided research prototype system incorporating the needle and providing a user-friendly interface to assist the pulmonologist in targeting lesions. To test the feasibility of the accuracy of the newly developed electromagnetically-tracked needle, a phantom study was conducted in the interventional suite at Georgetown University Hospital. Five TBNA simulations with a custom-made phantom with a bronchial tree were performed. The experimental results show that our device has potential to enhance the accuracy of TBNA.

A 3D Finite Element Model of a Knee for Joint Contact Stress Analysis during Sport Activities

A 3D finite element model of a human knee was constructed to study the response of articular tissues to loads applied to the surface of the femur similar to normal and extreme movements of the joint as in sports activities. A solid model of the femoral and tibial cartilages and menisci were built from post mortem MR images of human knee at full extension using the Pro/Engineer software package. The knee kinematics data was registered for this model and successive articular surface positions were obtained as a function of flexion angle. The cartilage and menisci were modeled as nonlinear orthotropic materials and contact elements were used to compose the contact layer between articular surfaces. The model determined average contact areas and stress values, which were then compared with published experimental results for equivalent boundary conditions. The presence of menisci increased the contact area in the knee joint, thus creating lower contact stresses on the cartilage than those measured experimentally. Validation of results allows the utilization of 3D knee model for determining the contact areas and the contact stress field for diverse bones positions simulating sports activities.

Intraoperative localized constrained registration in navigated bronchoscopy

Purpose: One of the major challenges in electromagnetic navigated bronchoscopy is the navigation accuracy. An initial rigid image‐to‐patient registration may not be optimal for the entire lung volume, as the lung tissue anatomy is likely to have shifted since the time of computer tomography (CT) acquisition. The accuracy of the initial rigid registration will also be affected throughout the procedure by breathing, coughing, patient movement and tissue displacements due to pressure from bronchoscopy tools. A method to minimize the negative impact from these factors by updating the registration locally during the procedure is needed and suggested in this paper. Methods: The intraoperative local registration method updates the initial registration by optimization in an area of special interest, for example, close to a biopsy position. The local registration was developed through an adaptation of a previously published registration method used for the initial registration of CT to the patient anatomy. The method was tested in an experimental breathing phantom setup, where respiratory movements were induced by a robotic arm. Deformations were also applied to the phantom to see if the local registration could compensate for these. Results: The local registration was successfully applied in all 15 repetitions, five in each of the three parts of the airway phantom. The mean registration accuracy was improved from 11.8–19.4 mm to 4.0–6.7 mm, varying to some degree in the different segments of the airway model. Conclusions: A local registration method, to update and improve the initial image‐to patient registration during navigated bronchoscopy, was developed. The method was successfully tested in a breathing phantom setup. Further development is needed to make the method more automatic. It must also be verified in human studies.

Computer Aided Diagnosis for Confocal Laser Endomicroscopy in Advanced Colorectal Adenocarcinoma.

Introduction Confocal laser endomicroscopy (CLE) is becoming a popular method for optical biopsy of digestive mucosa for both diagnostic and therapeutic procedures. Computer aided diagnosis of CLE images, using image processing and fractal analysis can be used to quantify the histological structures in the CLE generated images. The aim of this study is to develop an automatic diagnosis algorithm of colorectal cancer (CRC), based on fractal analysis and neural network modeling of the CLE-generated colon mucosa images. Materials and Methods We retrospectively analyzed a series of 1035 artifact-free endomicroscopy images, obtained during CLE examinations from normal mucosa (356 images) and tumor regions (679 images). The images were processed using a computer aided diagnosis (CAD) medical imaging system in order to obtain an automatic diagnosis. The CAD application includes image reading and processing functions, a module for fractal analysis, grey-level co-occurrence matrix (GLCM) computation module, and a feature identification module based on the Marching Squares and linear interpolation methods. A two-layer neural network was trained to automatically interpret the imaging data and diagnose the pathological samples based on the fractal dimension and the characteristic features of the biological tissues. Results Normal colon mucosa is characterized by regular polyhedral crypt structures whereas malignant colon mucosa is characterized by irregular and interrupted crypts, which can be diagnosed by CAD. For this purpose, seven geometric parameters were defined for each image: fractal dimension, lacunarity, contrast correlation, energy, homogeneity, and feature number. Of the seven parameters only contrast, homogeneity and feature number were significantly different between normal and cancer samples. Next, a two-layer feed forward neural network was used to train and automatically diagnose the malignant samples, based on the seven parameters tested. The neural network operations were cross-entropy with the results: training: 0.53, validation: 1.17, testing: 1.17, and percent error, resulting: training: 16.14, validation: 17.42, testing: 15.48. The diagnosis accuracy error was 15.5%. Conclusions Computed aided diagnosis via fractal analysis of glandular structures can complement the traditional histological and minimally invasive imaging methods. A larger dataset from colorectal and other pathologies should be used to further validate the diagnostic power of the method.