3D reconstruction of cerebral blood flow and vessel morphology from x-ray rotational angiography

Three-dimensional (3D) information on blood flow and vessel morphology is important when assessing cerebrovascular disease and when monitoring interventions. Rotational angiography is nowadays routinely used to determine the geometry of the cerebral vasculature. To this end, contrast agent is injected into one of the supplying arteries and the x-ray system rotates around the head of the patient while it acquires a sequence of x-ray images. Besides information on the 3D geometry, this sequence also contains information on blood flow, as it is possible to observe how the contrast agent is transported by the blood. The main goal of this thesis is to exploit this information for the quantitative analysis of blood flow. I propose a model-based method, called flow map fitting, which determines the blood flow waveform and the mean volumetric flow rate in the large cerebral arteries. The method uses a model of contrast agent transport to determine the flow parameters from the spatio-temporal progression of the contrast agent concentration, represented by a flow map. Furthermore, it overcomes artefacts due to the rotation (overlapping vessels and foreshortened vessels at some projection angles) of the c-arm using a reliability map. For the flow quantification, small changes to the clinical protocol of rotational angiography are desirable. These, however, hamper the standard 3D reconstruction. Therefore, a new method for the 3D reconstruction of the vessel morphology which is tailored to this application is also presented. To the best of my knowledge, I have presented the first quantitative results for blood flow quantification from rotational angiography. Additionally, the model-based approach overcomes several problems which are known from flow quantification methods for planar angiography. The method was mainly validated on images from different phantom experiments. In most cases, the relative error was between 5% and 10% for the volumetric mean flow rate and between 10% and 15% for the blood flow waveform. Additionally, the applicability of the flow model was shown on clinical images from planar angiographic acquisitions. From this, I conclude that the method has the potential to give quantitative estimates of blood flow parameters during cerebrovascular interventions

Development of a Physiologic In-Vitro Testing Methodology for Assessment of Cervical Spine Kinematics

In-vitro biomechanical testing has been critical in the design and evaluation of spinal surgical instrumentation, however determination of realistic physiologic loading levels has proven difficult outside of the in-vivo setting. Unconstrained pure moment testing combined with the hybrid testing method is currently the gold standard test protocol for evaluation of motion preservation technology and adjacent level effects. Pure moment testing is well suited for making relative comparisons between treatments, but is currently not based on or representative of in-vivo spine motion, bringing the clinical relevance into question. The human cervical spine supports substantial compressive load in-vivo arising from muscle forces and the weight of the head. However, traditional in-vitro testing methods rarely include compressive loads, especially in investigations of multi-segment cervical spine constructs. Therefore, a systematic comparison of standard pure moment testing without compressive loading versus published and novel compressive loading techniques (follower load, axial load, and combined load) was performed. To achieve a pure moment test, a robot/UFS testing system was programmed with hybrid control, which combined load and displacement control to overcome the limitations of either control methodology alone. A follower load system was developed with actively controlled linear actuators and integrated into the robot/UFS testing system’s control algorithm. Thorough investigation of the integrated system ensured that the pure moment assumption was upheld and enabled characterization of the kinetics resulting from the application of follower load. In contrast, axial load was applied perpendicular to superior most vertebral body using the robot end-effector; it did not maintain the pure moment assumption resulting in alterations of the segmental motion patterns. The pure moment testing protocol without compression or follower load was not able to replicate the typical in-vivo segmental motion patterns throughout the entire motion path. Axial load or a combination of axial and follower load was necessary to mimic the in-vivo segmental contributions at the extremes of the extension-flexion motion path. It is hypothesized that dynamically altering the compressive loading throughout the motion path is necessary to mimic the segmental contribution patterns exhibited in-vivo—a novel concept that will be explored in future investigations

3D Submillisecond tracking microscopy of single fluorescent particles with adaptive optics

Single particle tracking microscopy in combination with fluorescent labeling has opened the door to investigations of nanoscale dynamics in living cells. While conventional instruments feature temporal resolutions of typically 5–30 ms, nanoscale processes happen on a millisecond or submillisecond time scale. To overcome this limitation, I have developed a single particle tracking microscope with 130 μs temporal resolution and single-fluorophore sensitivity. The instrument acquires 3D trajectories by active tracking of a fluorescent particle with a focused laser beam. This is accomplished by fast beam steering, which is feedback-driven by the detected particle position in the focal volume. For translation of the laser focus along the optical axis, I have implemented a novel vibration-free remote focusing mechanism based on a deformable mirror, an adaptive optics wavefront correction device. In characterization experiments with fluorescent beads, I have found that the instrument is capable of tracking directed motion up to 150 μm/s and free 3D Brownian motion with diffusion coefficients of more than 2 μm²/s. The potential for biological applications is demonstrated by tracking fluorescently labeled viruses on cell membranes and transport vesicles in the cytoplasm of living cells

Compact realizations of optical super-resolution microscopy for the life sciences

Sandmeyer A. Compact realizations of optical super-resolution microscopy for the life sciences. Bielefeld: Universität Bielefeld; 2019

Multiscale Musculoskeletal Modeling of the Lower Limb to Perform Personalized Simulations of Movement

Computational modeling has been used for many decades to inform design and decision-making in several fields of engineering, such as aerospace, automotive, petroleum, and others. However, it still struggles to have a similar impact in fields of medicine, such as orthopaedics. Three of the challenges that have limited the use of computational modeling in the clinical practice and in product development are model validation, personalization, and realism. Validation is a challenge because several internal parameters of the human body, such as muscle forces, are not safely measurable in vivo and, consequently, a thorough comparison between model outputs and experimental measurements is not always possible. Personalization is an additional issue because the inherent variability across a population needs to be accounted for in a model. Finally, the computational burden of simulations performed with a musculoskeletal model limits its level of realism. The purpose of the work presented in this dissertation is to investigate the applicability of state-of-the-art tools, and propose novel approaches to foster an evolution of computational modeling in orthopaedics. Specifically, (1) the reliability of the knee contact force predictions of a musculoskeletal model commonly used in the literature was analyzed using a global probabilistic analysis for three subjects with instrumented implants; (2) subject-specific and activity-specific moment arms of the muscles spanning the knee were estimated replacing the generic passive cadaveric motion implemented in the knee joint of a musculoskeletal model with in vivo kinematics measured from stereo-radiography images; (3) subject-specific joint mechanics for 6 total knee arthroplasty patients performing daily activities was estimated with a sequential multiscale modeling approach that combined joint loads estimated with a whole body musculoskeletal model, personalized joint geometries, and subject-specific fluoroscopy-measured kinematics; finally, (4) a closed-loop muscle control strategy was designed to track experimental joint kinematics and concurrently estimate muscle forces and knee mechanics with a finite element musculoskeletal model of the lower limb including a deformable representation of the joint. The utility of the modeling techniques proposed in this dissertation is presented within a clinical perspective in order to encourage the utilization of musculoskeletal modeling for clinical applications and product development

Application of engineering methodologies to address patient-specific clinical questions in congenital heart disease

The recent advances in medical imaging and in computer technologies have improved the prediction capabilities of biomechanical models. In order to replicate physiological, pathological or surgically corrected portions of the cardiovascular system, several engineering methodologies and their combinations can be adopted. Specifically, in this thesis, 3D reconstructions of patient-specific implanted devices and cardiovascular anatomies have been realised using both volumetric and biplanar visualisation methods, such as CT, MR, 4D-MR Flow and fluoroscopy. Finite Element techniques have been used to computationally deploy cardiovascular endoprosthesis, such as stents and percutaneous pulmonary valve devices, under patient-specific boundary conditions. To analyse pressure and velocity fields occurring in patient-specific vessel anatomies under patient-specific conditions, Lumped Parameter Networks and Computational Fluid Dynamics simulations have been employed. The above mentioned engineering tools have been here applied to address three clinical topics: 1 - Percutaneous pulmonary valve implantation (PPVI) Nowadays, more than 5,000 patients with pulmonary valve dysfunctions have been treated successfully with a percutaneous device, consisting in a bovine jugular venous valve sewn inside a balloon expandable stent. However, 25% of the treated patients experienced stent fracture. Using a novel methodological patient-specific approach that combines 3D reconstructions of the implanted stent from patients’ biplane fluoroscopy images and FE analyses, I carried out a risk stratification for stent fracture prediction. 2 - Transposition of the Great Arteries (TGA) Patients born with the congenital heart defect TGA need a surgical correction, which however, is associated with long term complications: the enlargement of the aortic root, and the development of a unilateral pulmonary stenosis. These may originate a complex hemodynamics that I tried to investigate by using patient-specific LPN and CFD models. 3 - Aortic Coarctation (CoA) Finally, combinations of FE and CFD-LPN models have been used to plan treatment in a patient with CoA and aberrant right subclavian

Annual report of the National Advisory Committee for Aeronautics (22nd).administrative report including Technical Report nos. 542 to 576

Report includes the National Advisory Committee for Aeronautics letter of submittal to the President, Congressional report, summaries of the committee's activities and research accomplished, bibliographies, and financial report