Cup Implant Planning Based on 2-D/3-D Radiographic Pelvis Reconstruction-First Clinical Results.

GOAL: In the following, we will present a newly developed X-ray calibration phantom and its integration for 2-D/3-D pelvis reconstruction and subsequent automatic cup planning. Two different planning strategies were applied and evaluated with clinical data. METHODS: Two different cup planning methods were investigated: The first planning strategy is based on a combined pelvis and cup statistical atlas. Thereby, the pelvis part of the combined atlas is matched to the reconstructed pelvis model, resulting in an optimized cup planning. The second planning strategy analyzes the morphology of the reconstructed pelvis model to determine the best fitting cup implant. RESULTS: The first planning strategy was compared to 3-D CT-based planning. Digitally reconstructed radiographs of THA patients with differently severe pathologies were used to evaluate the accuracy of predicting the cup size and position. Within a discrepancy of one cup size, the size was correctly identified in 100% of the cases for Crowe type I datasets and in 77.8% of the cases for Crowe type II, III, and IV datasets. The second planning strategy was analyzed with respect to the eventually implanted cup size. In seven patients, the estimated cup diameter was correct within one cup size, while the estimation for the remaining five patients differed by two cup sizes. CONCLUSION: While both planning strategies showed the same prediction rate with a discrepancy of one cup size (87.5%), the prediction of the exact cup size was increased for the statistical atlas-based strategy (56%) in contrast to the anatomically driven approach (37.5%). SIGNIFICANCE: The proposed approach demonstrated the clinical validity of using 2-D/3-D reconstruction technique for cup planning.

Submaximal cardiopulmonary thresholds on a robotics-assisted tilt table, a cycle and a treadmill: a comparative analysis

BACKGROUND: The robotics-assisted tilt table (RATT), including actuators for tilting and cyclical leg movement, is used for rehabilitation of severely disabled neurological patients. Following further engineering development of the system, i.e. the addition of force sensors and visual bio-feedback, patients can actively participate in exercise testing and training on the device. Peak cardiopulmonary performance parameters were previously investigated, but it also important to compare submaximal parameters with standard devices. The aim of this study was to evaluate the feasibility of the RATT for estimation of submaximal exercise thresholds by comparison with a cycle ergometer and a treadmill. METHODS: 17 healthy subjects randomly performed six maximal individualized incremental exercise tests, with two tests on each of the three exercise modalities. The ventilatory anaerobic threshold (VAT) and respiratory compensation point (RCP) were determined from breath-by-breath data. RESULTS: VAT and RCP on the RATT were lower than the cycle ergometer and the treadmill: oxygen uptake (V'O2) at VAT was [mean (SD)] 1.2 (0.3), 1.5 (0.4) and 1.6 (0.5) L/min, respectively (p < 0.001); V'O2 at RCP was 1.7 (0.4), 2.3 (0.8) and 2.6 (0.9) L/min, respectively (p = 0.001). High correlations for VAT and RCP were found between the RATT vs the cycle ergometer and RATT vs the treadmill (R on the range 0.69-0.80). VAT and RCP demonstrated excellent test-retest reliability for all three devices (ICC from 0.81 to 0.98). Mean differences between the test and retest values on each device were close to zero. The ventilatory equivalent for O2 at VAT for the RATT and cycle ergometer were similar and both were higher than the treadmill. The ventilatory equivalent for CO2 at RCP was similar for all devices. Ventilatory equivalent parameters demonstrated fair-to-excellent reliability and repeatability. CONCLUSIONS: It is feasible to use the RATT for estimation of submaximal exercise thresholds: VAT and RCP on the RATT were lower than the cycle ergometer and the treadmill, but there were high correlations between the RATT vs the cycle ergometer and vs the treadmill. Repeatability and test-retest reliability of all submaximal threshold parameters from the RATT were comparable to those of standard devices.

Nitinol Stent Oversizing in Patients Undergoing Popliteal Artery Revascularization: A Finite Element Study

Nitinol stent oversizing is frequently performed in peripheral arteries to ensure a desirable lumen gain. However, the clinical effect of mis-sizing remains controversial. The goal of this study was to provide a better understanding of the structural and hemodynamic effects of Nitinol stent oversizing. Five patient-specific numerical models of non-calcified popliteal arteries were developed to simulate the deployment of Nitinol stents with oversizing ratios ranging from 1.1 to 1.8. In addition to arterial biomechanics, computational fluid dynamics methods were adopted to simulate the physiological blood flow inside the stented arteries. Results showed that stent oversizing led to a limited increase in the acute lumen gain, albeit at the cost of a significant increase in arterial wall stresses. Furthermore, localized areas affected by low Wall Shear Stress increased with higher oversizing ratios. Stents were also negatively impacted by the procedure as their fatigue safety factors gradually decreased with oversizing. These adverse effects to both the artery walls and stents may create circumstances for restenosis. Although the ideal oversizing ratio is stent-specific, this study showed that Nitinol stent oversizing has a very small impact on the immediate lumen gain, which contradicts the clinical motivations of the procedure.

Biomechanical Role of Bone Anisotropy Estimated on Clinical CT Scans by Image Registration

Image-based modeling is a popular approach to perform patient-specific biomechanical simulations. Accurate modeling is critical for orthopedic application to evaluate implant design and surgical planning. It has been shown that bone strength can be estimated from the bone mineral density (BMD) and trabecular bone architecture. However, these findings cannot be directly and fully transferred to patient-specific modeling since only BMD can be derived from clinical CT. Therefore, the objective of this study was to propose a method to predict the trabecular bone structure using a µCT atlas and an image registration technique. The approach has been evaluated on femurs and patellae under physiological loading. The displacement and ultimate force for femurs loaded in stance position were predicted with an error of 2.5% and 3.7%, respectively, while predictions obtained with an isotropic material resulted in errors of 7.3% and 6.9%. Similar results were obtained for the patella, where the strain predicted using the registration approach resulted in an improved mean squared error compared to the isotropic model. We conclude that the registration of anisotropic information from of a single template bone enables more accurate patient-specific simulations from clinical image datasets than isotropic model.

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.

Lung Pattern Classification for Interstitial Lung Diseases Using a Deep Convolutional Neural Network

Automated tissue characterization is one of the most crucial components of a computer aided diagnosis (CAD) system for interstitial lung diseases (ILDs). Although much research has been conducted in this field, the problem remains challenging. Deep learning techniques have recently achieved impressive results in a variety of computer vision problems, raising expectations that they might be applied in other domains, such as medical image analysis. In this paper, we propose and evaluate a convolutional neural network (CNN), designed for the classification of ILD patterns. The proposed network consists of 5 convolutional layers with 2×2 kernels and LeakyReLU activations, followed by average pooling with size equal to the size of the final feature maps and three dense layers. The last dense layer has 7 outputs, equivalent to the classes considered: healthy, ground glass opacity (GGO), micronodules, consolidation, reticulation, honeycombing and a combination of GGO/reticulation. To train and evaluate the CNN, we used a dataset of 14696 image patches, derived by 120 CT scans from different scanners and hospitals. To the best of our knowledge, this is the first deep CNN designed for the specific problem. A comparative analysis proved the effectiveness of the proposed CNN against previous methods in a challenging dataset. The classification performance (~85.5%) demonstrated the potential of CNNs in analyzing lung patterns. Future work includes, extending the CNN to three-dimensional data provided by CT volume scans and integrating the proposed method into a CAD system that aims to provide differential diagnosis for ILDs as a supportive tool for radiologists.

Correlation between alveolar ventilation and electrical properties of lung parenchyma.

One key problem in modern medical imaging is linking measured data and actual physiological quantities. In this article we derive such a link between the electrical bioimpedance of lung parenchyma, which can be measured by electrical impedance tomography (EIT), and the magnitude of regional ventilation, a key to understanding lung mechanics and developing novel protective ventilation strategies. Two rat-derived three-dimensional alveolar microstructures obtained from synchrotron-based x-ray tomography are each exposed to a constant potential difference for different states of ventilation in a finite element simulation. While the alveolar wall volume remains constant during stretch, the enclosed air volume varies, similar to the lung volume during ventilation. The enclosed air, serving as insulator in the alveolar ensemble, determines the resulting current and accordingly local tissue bioimpedance. From this we can derive a relationship between lung tissue bioimpedance and regional alveolar ventilation. The derived relationship shows a linear dependence between air content and tissue impedance and matches clinical data determined from a ventilated patient at the bedside.

E-Racer

The E-Racer was made for a young boy with cerebral palsy. The client cannot use his legs and control in his left arm is very limited. The client's family expressed a desire for an electric go-kart, and also for the go-kart to resemble a "normal" go-kart. To that end, the E-Racer has been outfitted with both steering wheel and joystick modes so the client can choose which control system he would like to use depending on what he is comfortable with. The E-Racer is a stock go-kart which was modified in several key ways. The electronics were drastically modified to accommodate the two controls systems. In addition, both the steering and braking systems were modified so they could be controlled electrically rather than mechanically. Finally, several modifications were made to the go-kart to improve the rider's comfort and safety.

Adjustable Art Table Project

An adjustable art table was designed for the artists at Passion Works Studio to fulfill a need for a wheelchair-friendly art table. The client desired that the table be sturdy, not electronic and can be used by multiple users. In response, a mechanical approach was taken and various raising devices were explored. A mechanical height adjustment would make for a more stable table and would not require any electricity or motor to adjust. The table also was built with a large, smooth tabletop designed specifically for multiple users making art. The highlight feature is the height adjustment which allows the table to adjust between 29 and 42.5 inches. The table requires just one person to raise, and two people to lower. To raise the table, an individual only needs to unlock the legs and then press in a button to activate the gas springs, which raise the table. Once the table is set to the desired height, the table can lock into place securely. To lower the table, one person must activate the gas springs and push down simultaneously with another person pushing down on the other side of the table. There is enough room for three people, depending on the size of the wheelchairs. With no wheelchairs, as many as six people can use the table. Therefore, the specifications were met, since it raises and lowers within the desired range, and it provides a solid surface for multiple users to do art work.

Design and Optimization of Four-dimensional Cone-beam Computed Tomography in Image-guided Radiation Therapy

The influence of respiratory motion on patient anatomy poses a challenge to accurate radiation therapy, especially in lung cancer treatment. Modern radiation therapy planning uses models of tumor respiratory motion to account for target motion in targeting. The tumor motion model can be verified on a per-treatment session basis with four-dimensional cone-beam computed tomography (4D-CBCT), which acquires an image set of the dynamic target throughout the respiratory cycle during the therapy session. 4D-CBCT is undersampled if the scan time is too short. However, short scan time is desirable in clinical practice to reduce patient setup time. This dissertation presents the design and optimization of 4D-CBCT to reduce the impact of undersampling artifacts with short scan times. This work measures the impact of undersampling artifacts on the accuracy of target motion measurement under different sampling conditions and for various object sizes and motions. The results provide a minimum scan time such that the target tracking error is less than a specified tolerance. This work also presents new image reconstruction algorithms for reducing undersampling artifacts in undersampled datasets by taking advantage of the assumption that the relevant motion of interest is contained within a volume-of-interest (VOI). It is shown that the VOI-based reconstruction provides more accurate image intensity than standard reconstruction. The VOI-based reconstruction produced 43% fewer least-squares error inside the VOI and 84% fewer error throughout the image in a study designed to simulate target motion. The VOI-based reconstruction approach can reduce acquisition time and improve image quality in 4D-CBCT.

Modeling Techniques for the High-Resolution Interpretation of Cryo-Electron Microscopy Reconstructions

Essential biological processes are governed by organized, dynamic interactions between multiple biomolecular systems. Complexes are thus formed to enable the biological function and get dissembled as the process is completed. Examples of such processes include the translation of the messenger RNA into protein by the ribosome, the folding of proteins by chaperonins or the entry of viruses in host cells. Understanding these fundamental processes by characterizing the molecular mechanisms that enable then, would allow the (better) design of therapies and drugs. Such molecular mechanisms may be revealed trough the structural elucidation of the biomolecular assemblies at the core of these processes. Various experimental techniques may be applied to investigate the molecular architecture of biomolecular assemblies. High-resolution techniques, such as X-ray crystallography, may solve the atomic structure of the system, but are typically constrained to biomolecules of reduced flexibility and dimensions. In particular, X-ray crystallography requires the sample to form a three dimensional (3D) crystal lattice which is technically di‑cult, if not impossible, to obtain, especially for large, dynamic systems. Often these techniques solve the structure of the different constituent components within the assembly, but encounter difficulties when investigating the entire system. On the other hand, imaging techniques, such as cryo-electron microscopy (cryo-EM), are able to depict large systems in near-native environment, without requiring the formation of crystals. The structures solved by cryo-EM cover a wide range of resolutions, from very low level of detail where only the overall shape of the system is visible, to high-resolution that approach, but not yet reach, atomic level of detail. In this dissertation, several modeling methods are introduced to either integrate cryo-EM datasets with structural data from X-ray crystallography, or to directly interpret the cryo-EM reconstruction. Such computational techniques were developed with the goal of creating an atomic model for the cryo-EM data. The low-resolution reconstructions lack the level of detail to permit a direct atomic interpretation, i.e. one cannot reliably locate the atoms or amino-acid residues within the structure obtained by cryo-EM. Thereby one needs to consider additional information, for example, structural data from other sources such as X-ray crystallography, in order to enable such a high-resolution interpretation. Modeling techniques are thus developed to integrate the structural data from the different biophysical sources, examples including the work described in the manuscript I and II of this dissertation. At intermediate and high-resolution, cryo-EM reconstructions depict consistent 3D folds such as tubular features which in general correspond to alpha-helices. Such features can be annotated and later on used to build the atomic model of the system, see manuscript III as alternative. Three manuscripts are presented as part of the PhD dissertation, each introducing a computational technique that facilitates the interpretation of cryo-EM reconstructions. The first manuscript is an application paper that describes a heuristics to generate the atomic model for the protein envelope of the Rift Valley fever virus. The second manuscript introduces the evolutionary tabu search strategies to enable the integration of multiple component atomic structures with the cryo-EM map of their assembly. Finally, the third manuscript develops further the latter technique and apply it to annotate consistent 3D patterns in intermediate-resolution cryo-EM reconstructions. The first manuscript, titled An assembly model for Rift Valley fever virus, was submitted for publication in the Journal of Molecular Biology. The cryo-EM structure of the Rift Valley fever virus was previously solved at 27Å-resolution by Dr. Freiberg and collaborators. Such reconstruction shows the overall shape of the virus envelope, yet the reduced level of detail prevents the direct atomic interpretation. High-resolution structures are not yet available for the entire virus nor for the two different component glycoproteins that form its envelope. However, homology models may be generated for these glycoproteins based on similar structures that are available at atomic resolutions. The manuscript presents the steps required to identify an atomic model of the entire virus envelope, based on the low-resolution cryo-EM map of the envelope and the homology models of the two glycoproteins. Starting with the results of the exhaustive search to place the two glycoproteins, the model is built iterative by running multiple multi-body refinements to hierarchically generate models for the different regions of the envelope. The generated atomic model is supported by prior knowledge regarding virus biology and contains valuable information about the molecular architecture of the system. It provides the basis for further investigations seeking to reveal different processes in which the virus is involved such as assembly or fusion. The second manuscript was recently published in the of Journal of Structural Biology (doi:10.1016/j.jsb.2009.12.028) under the title Evolutionary tabu search strategies for the simultaneous registration of multiple atomic structures in cryo-EM reconstructions. This manuscript introduces the evolutionary tabu search strategies applied to enable a multi-body registration. This technique is a hybrid approach that combines a genetic algorithm with a tabu search strategy to promote the proper exploration of the high-dimensional search space. Similar to the Rift Valley fever virus, it is common that the structure of a large multi-component assembly is available at low-resolution from cryo-EM, while high-resolution structures are solved for the different components but lack for the entire system. Evolutionary tabu search strategies enable the building of an atomic model for the entire system by considering simultaneously the different components. Such registration indirectly introduces spatial constrains as all components need to be placed within the assembly, enabling the proper docked in the low-resolution map of the entire assembly. Along with the method description, the manuscript covers the validation, presenting the benefit of the technique in both synthetic and experimental test cases. Such approach successfully docked multiple components up to resolutions of 40Å. The third manuscript is entitled Evolutionary Bidirectional Expansion for the Annotation of Alpha Helices in Electron Cryo-Microscopy Reconstructions and was submitted for publication in the Journal of Structural Biology. The modeling approach described in this manuscript applies the evolutionary tabu search strategies in combination with the bidirectional expansion to annotate secondary structure elements in intermediate resolution cryo-EM reconstructions. In particular, secondary structure elements such as alpha helices show consistent patterns in cryo-EM data, and are visible as rod-like patterns of high density. The evolutionary tabu search strategy is applied to identify the placement of the different alpha helices, while the bidirectional expansion characterizes their length and curvature. The manuscript presents the validation of the approach at resolutions ranging between 6 and 14Å, a level of detail where alpha helices are visible. Up to resolution of 12 Å, the method measures sensitivities between 70-100% as estimated in experimental test cases, i.e. 70-100% of the alpha-helices were correctly predicted in an automatic manner in the experimental data. The three manuscripts presented in this PhD dissertation cover different computation methods for the integration and interpretation of cryo-EM reconstructions. The methods were developed in the molecular modeling software Sculptor (http://sculptor.biomachina.org) and are available for the scientific community interested in the multi-resolution modeling of cryo-EM data. The work spans a wide range of resolution covering multi-body refinement and registration at low-resolution along with annotation of consistent patterns at high-resolution. Such methods are essential for the modeling of cryo-EM data, and may be applied in other fields where similar spatial problems are encountered, such as medical imaging.

Investigación en Biomedicina : encendiendo luces en las penumbras de la vida humana

El dolor y las enfermedades del hombre nos han acompañado en el pasado y nos seguirán acompañando en el futuro. La Medicina intenta encender luces para aliviar ¿con su arte y su ciencia? los males que aquejan la salud de la humanidad. La Ciencia robustece con su calidad y rigurosidad la respuesta a esos interrogantes. Quienes formamos parte de la población de investigadores de la Medicina recorremos un difícil camino de oscuridades y dudas. Nuestros escudos son el cultivo de actitudes, aptitudes y destrezas para saber preguntarnos sobre los fenómenos de la naturaleza humana y encontrar respuestas acertadas. Sabemos que estas respuestas necesitan el permanente contraste con la realidad. Sabemos también que el resultado de nuestro esfuerzo investigativo no nos pertenece, sino que forma parte del conocimiento universal. Recordemos que las múltiples tecnologías utilizadas en el descubrimiento de los fenómenos biomédicos tienen un faro, un único destino final: la PERSONA HUMANA

Evaluation of APD and SiPM Matrices as Sensors for Monolithic PET Detector Block

Gamma detectors based on monolithic scintillator blocks coupled to APDs matrices have proved to be a good alternative to pixelated ones for PET scanners. They provide comparable spatial resolution, improve the sensitivity and make easier the mechanical design of the system. In this study we evaluate by means of Geant4-based simulations the possibility of replacing the APDs by SiPMs. Several commercial matrices of light sensors coupled to LYSO:Ce monolithic blocks have been simulated and compared. Regarding the spatial resolution and linearity of the detector, SiPMs with high photo detection efficiency could become an advantageous replacement for the APDs

Evaluation of a PET Prototype Using LYSO:Ce Monolithic Detector Block

We have analyzed the performance of a PET demonstrator formed by two sectors of four monolithic detector blocks placed face-to-face. Both front-end and read-out electronics have been evaluated by means of coincidence measurements using a rotating 22Na source placed at the center of the sectors in order to emulate the behavior of a complete full ring. A continuous training method based on neural network (NN) algorithms has been carried out to determine the entrance points over the surface of the detectors. Reconstructed images from 1 MBq 22Na point source and 22Na Derenzo phantom have been obtained using both filtered back projection (FBP) analytic methods and the OSEM 3D iterative algorithm available in the STIR software package [1]. Preliminary data on image reconstruction from a 22Na point source with Ø = 0.25 mm show spatial resolutions from 1.7 to 2.1 mm FWHM in the transverse plane. The results confirm the viability of this design for the development of a full-ring brain PET scanner compatible with magnetic resonance imaging for human studies.

Characterization and Test of a Data Acquisition System for PET

A small Positron Emission Tomography demonstrator based on LYSO slabs and Silicon Photomultiplier matrices is under construction at the University and INFN of Pisa. In this paper we present the characterization results of the read-out electronics and of the detection system. Two SiPM matrices, composed by 8 × 8 SiPM pixels, 1.5 mm pitch, have been coupled one to one to a LYSO crystals array. Custom Front-End ASICs were used to read the 64 channels of each matrix. Data from each Front-End were multiplexed and sent to a DAQ board for the digital conversion; a motherboard collects the data and communicates with a host computer through a USB port. Specific tests were carried out on the system in order to assess its performance. Futhermore we have measured some of the most important parameters of the system for PET application.