A system for 3-D reconstruction of a patient-specific surface model from calibrated X-ray images

This paper presents a system for 3-D reconstruction of a patient-specific surface model from calibrated X-ray images. Our system requires two X-ray images of a patient with one acquired from the anterior-posterior direction and the other from the axial direction. A custom-designed cage is utilized in our system to calibrate both images. Starting from bone contours that are interactively identified from the X-ray images, our system constructs a patient-specific surface model of the proximal femur based on a statistical model based 2D/3D reconstruction algorithm. In this paper, we present the design and validation of the system with 25 bones. An average reconstruction error of 0.95 mm was observed.

Automatic Segmentation of the Eye in 3D Magnetic Resonance Imaging: A novel Statistical Shape Model for treatment planning of Retinoblastoma

Purpose: Proper delineation of ocular anatomy in 3D imaging is a big challenge, particularly when developing treatment plans for ocular diseases. Magnetic Resonance Imaging (MRI) is nowadays utilized in clinical practice for the diagnosis confirmation and treatment planning of retinoblastoma in infants, where it serves as a source of information, complementary to the Fundus or Ultrasound imaging. Here we present a framework to fully automatically segment the eye anatomy in the MRI based on 3D Active Shape Models (ASM), we validate the results and present a proof of concept to automatically segment pathological eyes. Material and Methods: Manual and automatic segmentation were performed on 24 images of healthy children eyes (3.29±2.15 years). Imaging was performed using a 3T MRI scanner. The ASM comprises the lens, the vitreous humor, the sclera and the cornea. The model was fitted by first automatically detecting the position of the eye center, the lens and the optic nerve, then aligning the model and fitting it to the patient. We validated our segmentation method using a leave-one-out cross validation. The segmentation results were evaluated by measuring the overlap using the Dice Similarity Coefficient (DSC) and the mean distance error. Results: We obtained a DSC of 94.90±2.12% for the sclera and the cornea, 94.72±1.89% for the vitreous humor and 85.16±4.91% for the lens. The mean distance error was 0.26±0.09mm. The entire process took 14s on average per eye. Conclusion: We provide a reliable and accurate tool that enables clinicians to automatically segment the sclera, the cornea, the vitreous humor and the lens using MRI. We additionally present a proof of concept for fully automatically segmenting pathological eyes. This tool reduces the time needed for eye shape delineation and thus can help clinicians when planning eye treatment and confirming the extent of the tumor.

Articulated Statistical Shape Model-Based 2D-3D Reconstruction of a Hip Joint

In this paper, reconstruction of three-dimensional (3D) patient-specific models of a hip joint from two-dimensional (2D) calibrated X-ray images is addressed. Existing 2D-3D reconstruction techniques usually reconstruct a patient-specific model of a single anatomical structure without considering the relationship to its neighboring structures. Thus, when those techniques would be applied to reconstruction of patient-specific models of a hip joint, the reconstructed models may penetrate each other due to narrowness of the hip joint space and hence do not represent a true hip joint of the patient. To address this problem we propose a novel 2D-3D reconstruction framework using an articulated statistical shape model (aSSM). Different from previous work on constructing an aSSM, where the joint posture is modeled as articulation in a training set via statistical analysis, here it is modeled as a parametrized rotation of the femur around the joint center. The exact rotation of the hip joint as well as the patient-specific models of the joint structures, i.e., the proximal femur and the pelvis, are then estimated by optimally fitting the aSSM to a limited number of calibrated X-ray images. Taking models segmented from CT data as the ground truth, we conducted validation experiments on both plastic and cadaveric bones. Qualitatively, the experimental results demonstrated that the proposed 2D-3D reconstruction framework preserved the hip joint structure and no model penetration was found. Quantitatively, average reconstruction errors of 1.9 mm and 1.1 mm were found for the pelvis and the proximal femur, respectively.

Development and characterization of a scaffold-free 3D spheroid model of iPSC-derived human cardiomyocytes

Purpose: Cardiomyocytes are terminally differentiated cells in the adult heart and ischemia and cardiotoxic compounds can lead to cell death and irreversible decline of cardiac function. As testing platforms, isolated organs and primary cells from rodents have been the standard in research and toxicology, but there is a need for better models that more faithfully recapitulate native human biology. Hence, a new in vitro model comprising the advantages of 3D cell culture and the availability of induced pluripotent stem cells (iPSC) from human origin was developed and characterized. Methods: Human cardiomyocytes (CMs) derived from induced pluripotent stem cells (iPSCs) were studied in standard 2D culture and as cardiac microtissues (MTs) formed in hanging drops. 2D cultures were examined using immunofluorescence microscopy and Western blotting while the cardiac MTs were subjected to immunofluorescence, contractility, and pharmacological investigations. Results: iPSC-derived CMs in 2D culture showed well-formed myofibrils, cell-cell contacts positive for connexin-43, and other typical cardiac proteins. The cells reacted to pro-hypertrophic growth factors with a substantial increase in myofibrils and sarcomeric proteins. In hanging drop cultures, iPSC-derived cardiomyocytes formed spheroidal MTs within 4 days showing a homogeneous tissue structure with well-developed myofibrils extending throughout the whole spheroid without a necrotic core. MTs showed spontaneous contractions for more than 4 weeks that were recorded by optical motion tracking, sensitive to temperature, and responsive to electrical pacing. Contractile pharmacology was tested with several agents known to modulate cardiac rate and viability. Calcium-transients underlay the contractile activity and were also responsive to electrical stimulation, caffeine-induced Ca2+-release, extracellular calcium levels. Conclusions: 3D culture using iPSC-derived human cardiomyocytes provides an organoid human-based cellular platform that is free of necrosis and recapitulates vital cardiac functionality, thereby providing new and promising relevant model for the evaluation and development of new therapies and detection of cardiotoxicity.

Optimization of TRPV6 Calcium Channel Inhibitors Using a 3D Ligand-Based Virtual Screening Method

Herein, we report the discovery of the first potent and selective inhibitor of TRPV6, a calcium channel overexpressed in breast and prostate cancer, and its use to test the effect of blocking TRPV6-mediated Ca2+-influx on cell growth. The inhibitor was discovered through a computational method, xLOS, a 3D-shape and pharmacophore similarity algorithm, a type of ligand-based virtual screening (LBVS) method described briefly here. Starting with a single weakly active seed molecule, two successive rounds of LBVS followed by optimization by chemical synthesis led to a selective molecule with 0.3 μM inhibition of TRPV6. The ability of xLOS to identify different scaffolds early in LBVS was essential to success. The xLOS method may be generally useful to develop tool compounds for poorly characterized targets.

Stereoselective virtual screening of the ZINC database using atom pair 3D-fingerprints

Background Tools to explore large compound databases in search for analogs of query molecules provide a strategically important support in drug discovery to help identify available analogs of any given reference or hit compound by ligand based virtual screening (LBVS). We recently showed that large databases can be formatted for very fast searching with various 2D-fingerprints using the city-block distance as similarity measure, in particular a 2D-atom pair fingerprint (APfp) and the related category extended atom pair fingerprint (Xfp) which efficiently encode molecular shape and pharmacophores, but do not perceive stereochemistry. Here we investigated related 3D-atom pair fingerprints to enable rapid stereoselective searches in the ZINC database (23.2 million 3D structures). Results Molecular fingerprints counting atom pairs at increasing through-space distance intervals were designed using either all atoms (16-bit 3DAPfp) or different atom categories (80-bit 3DXfp). These 3D-fingerprints retrieved molecular shape and pharmacophore analogs (defined by OpenEye ROCS scoring functions) of 110,000 compounds from the Cambridge Structural Database with equal or better accuracy than the 2D-fingerprints APfp and Xfp, and showed comparable performance in recovering actives from decoys in the DUD database. LBVS by 3DXfp or 3DAPfp similarity was stereoselective and gave very different analogs when starting from different diastereomers of the same chiral drug. Results were also different from LBVS with the parent 2D-fingerprints Xfp or APfp. 3D- and 2D-fingerprints also gave very different results in LBVS of folded molecules where through-space distances between atom pairs are much shorter than topological distances. Conclusions 3DAPfp and 3DXfp are suitable for stereoselective searches for shape and pharmacophore analogs of query molecules in large databases. Web-browsers for searching ZINC by 3DAPfp and 3DXfp similarity are accessible at www.gdb.unibe.ch webcite and should provide useful assistance to drug discovery projects.

Non-rigid Free-Form 2D-3D Registration Using Statistical Deformation Model

This paper presents a non-rigid free-from 2D-3D registration approach using statistical deformation model (SDM). In our approach the SDM is first constructed from a set of training data using a non-rigid registration algorithm based on b-spline free-form deformation to encode a priori information about the underlying anatomy. A novel intensity-based non-rigid 2D-3D registration algorithm is then presented to iteratively fit the 3D b-spline-based SDM to the 2D X-ray images of an unseen subject, which requires a computationally expensive inversion of the instantiated deformation in each iteration. In this paper, we propose to solve this challenge with a fast B-spline pseudo-inversion algorithm that is implemented on graphics processing unit (GPU). Experiments conducted on C-arm and X-ray images of cadaveric femurs demonstrate the efficacy of the present approach.

The virtual patient in dental medicine

OBJECTIVES The aim of this Short Communication was to present a workflow for the superimposition of intraoral scan (IOS), cone-beam computed tomography (CBCT), and extraoral face scan (EOS) creating a 3D virtual dental patient. MATERIAL AND METHODS As a proof-of-principle, full arch IOS, preoperative CBCT, and mimic EOS were taken and superimposed to a unique 3D data pool. The connecting link between the different files was to detect existing teeth as constant landmarks in all three data sets. RESULTS This novel application technique successfully demonstrated the feasibility of building a craniofacial virtual model by image fusion of IOS, CBCT, and EOS under 3D static conditions. CONCLUSIONS The presented application is the first approach that realized the fusion of intraoral and facial surfaces combined with skeletal anatomy imaging. This novel 3D superimposition technique allowed the simulation of treatment planning, the exploration of the patients' expectations, and the implementation as an effective communication tool. The next step will be the development of a real-time 4D virtual patient in motion.

Virtobot--a multi-functional robotic system for 3D surface scanning and automatic post mortem biopsy

The Virtopsy project, a multi-disciplinary project that involves forensic science, diagnostic imaging, computer science, automation technology, telematics and biomechanics, aims to develop new techniques to improve the outcome of forensic investigations. This paper presents a new approach in the field of minimally invasive virtual autopsy for a versatile robotic system that is able to perform three-dimensional (3D) surface scans as well as post mortem image-guided soft tissue biopsies.

An interactive surgical planning tool for acetabular fractures: initial results

Background Acetabular fractures still are among the most challenging fractures to treat because of complex anatomy, involved surgical access to fracture sites and the relatively low incidence of these lesions. Proper evaluation and surgical planning is necessary to achieve anatomic reduction of the articular surface and stable fixation of the pelvic ring. The goal of this study was to test the feasibility of preoperative surgical planning in acetabular fractures using a new prototype planning tool based on an interactive virtual reality-style environment. Methods 7 patients (5 male and 2 female; median age 53 y (25 to 92 y)) with an acetabular fracture were prospectively included. Exclusion criterions were simple wall fractures, cases with anticipated surgical dislocation of the femoral head for joint debridement and accurate fracture reduction. According to the Letournel classification 4 cases had two column fractures, 2 cases had anterior column fractures and 1 case had a T-shaped fracture including a posterior wall fracture. The workflow included following steps: (1) Formation of a patient-specific bone model from preoperative computed tomography scans, (2) interactive virtual fracture reduction with visuo-haptic feedback, (3) virtual fracture fixation using common osteosynthesis implants and (4) measurement of implant position relative to landmarks. The surgeon manually contoured osteosynthesis plates preoperatively according to the virtually defined deformation. Screenshots including all measurements for the OR were available. The tool was validated comparing the preoperative planning and postoperative results by 3D-superimposition. Results Preoperative planning was feasible in all cases. In 6 of 7 cases superimposition of preoperative planning and postoperative follow-up CT showed a good to excellent correlation. In one case part of the procedure had to be changed due to impossibility of fracture reduction from an ilioinguinal approach. In 3 cases with osteopenic bone patient-specific prebent fixation plates were helpful in guiding fracture reduction. Additionally, anatomical landmark based measurements were helpful for intraoperative navigation. Conclusion The presented prototype planning tool for pelvic surgery was successfully integrated in a clinical workflow to improve patient-specific preoperative planning, giving visual and haptic information about the injury and allowing a patient-specific adaptation of osteosynthesis implants to the virtually reduced pelvis.

Personalized X-Ray Reconstruction of the Proximal Femur via Intensity-Based Non-rigid 2D-3D Registration

This paper presents a new approach for reconstructing a patient-specific shape model and internal relative intensity distribution of the proximal femur from a limited number (e.g., 2) of calibrated C-arm images or X-ray radiographs. Our approach uses independent shape and appearance models that are learned from a set of training data to encode the a priori information about the proximal femur. An intensity-based non-rigid 2D-3D registration algorithm is then proposed to deformably fit the learned models to the input images. The fitting is conducted iteratively by minimizing the dissimilarity between the input images and the associated digitally reconstructed radiographs of the learned models together with regularization terms encoding the strain energy of the forward deformation and the smoothness of the inverse deformation. Comprehensive experiments conducted on images of cadaveric femurs and on clinical datasets demonstrate the efficacy of the present approach.

Investigating the interaction of cellulose nanofibers derived from cotton with a sophisticated 3D human lung cell coculture

Cellulose nanofibers are an attractive component of a broad range of nanomaterials. Their intriguing mechanical properties and low cost, as well as the renewable nature of cellulose make them an appealing alternative to carbon nanotubes (CNTs), which may pose a considerable health risk when inhaled. Little is known, however, concerning the potential toxicity of aerosolized cellulose nanofibers. Using a 3D in vitro triple cell coculture model of the human epithelial airway barrier, it was observed that cellulose nanofibers isolated from cotton (CCN) elicited a significantly (p < 0.05) lower cytotoxicity and (pro-)inflammatory response than multiwalled CNTs (MWCNTs) and crocidolite asbestos fibers (CAFs). Electron tomography analysis also revealed that the intracellular localization of CCNs is different from that of both MWCNTs and CAFs, indicating fundamental differences between each different nanofibre type in their interaction with the human lung cell coculture. Thus, the data shown in the present study highlights that not only the length and stiffness determine the potential detrimental (biological) effects of any nanofiber, but that the material used can significantly affect nanofiber-cell interactions.

Percutaneous radiofrequency ablation of virtual tumours in canine kidney using Global Positioning System-like technology

What's known on the subject? And what does the study add? We have previously shown that percutaneous radiofrequency ablation guided by image-fusion technology allows for precise needle placement with real time ultrasound superimposed with pre-loaded imaging, removing the need for real-time CT or MR guidance. Emerging technology also allows real-time tracking of a treatment needle within an organ in a virtually created 3D format. To our knowledge, this is the first study utilising a sophisticated ultrasound-based navigation system that uses both image-fusion and real-time probe-tracking technologies for in-vivo renal ablative intervention.