Enhanced ultrasound for advanced diagnostics, ultrasound tomography for volume limb imaging and prosthetic fitting

Ultrasound imaging methods hold the potential to deliver low-cost, high-resolution, operator-independent and nonionizing imaging systems-such systems couple appropriate algorithms with imaging devices and techniques. The increasing demands on general practitioners motivate us to develop more usable and productive diagnostic imaging equipment. Ultrasound, specifically freehand ultrasound, is a low cost and safe medical imaging technique. It doesn't expose a patient to ionizing radiation. Its safety and versatility make it very well suited for the increasing demands on general practitioners, or for providing improved medical care in rural regions or the developing world. However it typically suffers from sonographer variability; we will discuss techniques to address user variability. We also discuss our work to combine cylindrical scanning systems with state of the art inversion algorithms to deliver ultrasound systems for imaging and quantifying limbs in 3-D in vivo. Such systems have the potential to track the progression of limb health at a low cost and without radiation exposure, as well as, improve prosthetic socket fitting. Current methods of prosthetic socket fabrication remain subjective and ineffective at creating an interface to the human body that is both comfortable and functional. Though there has been recent success using methods like magnetic resonance imaging and biomechanical modeling, a low-cost, streamlined, and quantitative process for prosthetic cup design and fabrication has not been fully demonstrated. Medical ultrasonography may inform the design process of prosthetic sockets in a more objective manner. This keynote talk presents the results of progress in this area. Keywords: Clinical ultrasound, Force control, 3-D ultrasound, Tomograph

Ultrasound and photoacoustic methods for anatomic and functional imaging in image guided radiation therapy

(MATERIAL and METHODS) First, we define the physical principals and optimal protocols that provide contrast when imaging with US and the transducer properties contributing to resolution limits. The US field of view (FOV) was characterized to determine the optimal settings with regard to imaging depth, focal region, with and without harmonic imaging, and artifact identification. This will allow us to determine the minimum errors expected when registering multimodal volumes (CT, US, CBCT). Next, we designed an in-house integrated US manipulator and platform to relate CT, 3D-US and linear accelerator coordinate systems. To validate our platform, an agar-based phantom with measured densities and speed-of-sound consistent with tissues surrounding the bladder was fabricated. This phantom was rotated relative to the CT and US coordinate systems and imaged with both modalities. These CT and 3D-US images were imported into the treatment planning system, where US-to-US and US-to-CT images were co-registered and the registration matrix used to re-align the phantom relative to the linear accelerator. The measured precision in the phantom setup, which is defined by the standard deviation of the transformation matrix components, was consistent with and exceeding acceptable clinical patient re-alignments (2 mm). Statistical errors from US-US registrations for different patient orientations ranged from 0.06-1.66 mm for x, y, and z translational components, and 0.00-1.05 degrees for rotational components. Statistical errors from US-CT registrations were 0.23-1.18 mm for the x, y and z translational components, and 0.08-2.52 degrees for the rotational components. The high precision in the multimodal registrations suggest the ability to use US for patient positioning when targeting abdominal structures. We are now testing this on a dog patient to obtain both inter and intra-fractional positional errors. The objective of this experiment is to confirm Hill’s equation describing the relationship between hemoglobin saturation (SaO2) and the partial pressure of dissolved oxygen (pO2). The relationship is modeled as a sigmoidal curve that is a function of two parameters – the Hill coefficient, n, and the net association constant of HbO2, K (or pO2 at 50% SaO2). The goal is to noninvasively measure SaO2 in breast tumors in mice using photoacoustic computed tomographic (PCT) imaging and compare those measurements to a gold standard for pO2 using the OxyLite probe. First, a calibration study was performed to measure the SaO2 (co-oximeter) and pO2 (Oxylite probe) in blood using Hill’s equation (P50=23.2 mmHg and n=2.26). Next, non-invasive localized measurements of SaO2 in MDA-MD-231 and MCF7 breast tumors using PCT spectroscopic methods were compared to pO 2 levels using Oxylite probe. The fitted results for MCF7 and MDA-MD-231 data resulted in a P50 of 17.2 mmHg and 20.7 mmHg and a n of 1.76 and 1.63, respectively. The lower value of the P50 is consistent with tumors being more acidic than healthy tissue. Current work applying photon fluence corrections and image artifact reduction is expected to improve the quality of the results. In summary, this study demonstrates that photoacoustic imaging can be used to monitor tumor oxygenation, and its potential use to investigate the effectiveness of radiation therapy and the ability to adapt therapeutic protocols

A Low-Cost Camera-based Transducer Tracking System for Freehand Three-Dimensional Ultrasound Imaging

Freehand three-dimensional ultrasound (3D US) imaging is commonly used for clinical diagnosis and therapy monitoring. In this technique, accurate tracking of the US transducer is a crucial requirement to develop high-quality 3D US volumes. However, current methods for transducer tracking are generally expensive and inconvenient. This thesis presents a low-cost camera-based system for tracking the US transducer with six degrees of freedom (DoF). In this system, two orthogonal cameras with non-overlapped views are mounted on the US transducer. During US scanning, the two cameras are employed to track artificial features attached to the skin of the patient. A 3D surface map is constructed based on the tracked features and the 3D poses of each camera with respect to the skin are extracted separately. The estimated poses of the two cameras are spatially combined to provide accurate and robust pose estimation of the US transducer. In particular, the fusion of the estimated poses by the two cameras is performed using Kalman filtering based technique, which is a popular optimization technique in motion guidance and tracking. The camera-based tracking of the US transducer has been applied to synthesize freehand 3D US volumes. The performance of the proposed system is evaluated by performing in-vitro 3D US imaging experiments and quantifying the synthesized US volumes. The results demonstrate that two points in the 3D US volume separated by a distance of 10 mm can be reconstructed with an average error of 0.35 mm and a 3D volume of a cylinder can be estimated within an error of 3.8%

Augmented navigation

Spinal fixation procedures have the inherent risk of causing damage to vulnerable anatomical structures such as the spinal cord, nerve roots, and blood vessels. To prevent complications, several technological aids have been introduced. Surgical navigation is the most widely used, and guides the surgeon by providing the position of the surgical instruments and implants in relation to the patient anatomy based on radiographic images. Navigation can be extended by the addition of a robotic arm to replace the surgeon’s hand to increase accuracy. Another line of surgical aids is tissue sensing equipment, that recognizes different tissue types and provides a warning system built into surgical instruments. All these technologies are under continuous development and the optimal solution is yet to be found. The aim of this thesis was to study the use of Augmented Reality (AR), Virtual Reality (VR), Artificial Intelligence (AI), and tissue sensing technology in spinal navigation to improve precision and prevent surgical errors. The aim of Paper I was to develop and validate an algorithm for automatizing the intraoperative planning of pedicle screws. An AI algorithm for automatic segmentation of the spine, and screw path suggestion was developed and evaluated. In a clinical study of advanced deformity cases, the algorithm could provide correct suggestions for 86% of all pedicles—or 95%, when cases with extremely altered anatomy were excluded. Paper II evaluated the accuracy of pedicle screw placement using a novel augmented reality surgical navigation (ARSN) system, harboring the above-developed algorithm. Twenty consecutively enrolled patients, eligible for deformity correction surgery in the thoracolumbar region, were operated on using the ARSN system. In this cohort, we found a pedicle screw placement accuracy of 94%, as measured according to the Gertzbein grading scale. The primary goal of Paper III was to validate an extension of the ARSN system for placing pedicle screws using instrument tracking and VR. In a porcine cadaver model, it was demonstrated that VR instrument tracking could successfully be integrated with the ARSN system, resulting in pedicle devices placed within 1.7 ± 1.0 mm of the planed path. Paper IV examined the feasibility of a robot-guided system for semi-automated, minimally invasive, pedicle screw placement in a cadaveric model. Using the robotic arm, pedicle devices were placed within 0.94 ± 0.59 mm of the planned path. The use of a semi-automated surgical robot was feasible, providing a higher technical accuracy compared to non-robotic solutions. Paper V investigated the use of a tissue sensing technology, diffuse reflectance spectroscopy (DRS), for detecting the cortical bone boundary in vertebrae during pedicle screw insertions. The technology could accurately differentiate between cancellous and cortical bone and warn the surgeon before a cortical breach. Using machine learning models, the technology demonstrated a sensitivity of 98% [range: 94-100%] and a specificity of 98% [range: 91-100%]. In conclusion, several technological aids can be used to improve accuracy during spinal fixation procedures. In this thesis, the advantages of adding AR, VR, AI and tissue sensing technology to conventional navigation solutions were studied

The beginning of a new era in bone surgery Effectiveness and clinical application of a cold-ablation and robot-guided laser osteotome

Most industrial laser applications utilize computer and robot assistance, for guidance, safety, repeatability, and precision. For industrial applications, the increase in throughput and the processing speed are in the foreground. Nevertheless, these tools cannot just be transferred into clinical and surgical use because the focus in surgical interventions is on the exact implementation of a unique plan. The patient, as an inaccurately defined workpiece, with its individual anatomy and pathology, ultimately needs a single lot planning. Nowadays, medical laser systems are hand driven. The possibility of working precision, as used in industry lasers, is not exhausted. Therefore, medical laser beams have to be coupled to robot guidance. But due to the over-size of commercially available tools, efficient and ergonomic work in an operating room is impossible. Integration of the systems such as the laser source, and the robot arm are needed. Another key issue for the accuracy of the robotic arm is the inclusion of a tracking system. All these issues were encountered developing CARLO®: a Cold-Ablation and Robot-guided Laser Osteotome. This PhD thesis is divided in three parts: - an in-vivo study in sheep, - an in-vitro / wetlab study on human cadavers, and - a theoretical-experimental study to evaluate biomechanical changes in different osteotomy pattern. To test the applicability of the system in an operation theatre similar environment, an in-vivo animal trial was performed. Additionally, we wanted to demonstrate that bone healing after laser osteotomy is not impaired compared to the standard tool the piezo-osteotome. In terms of new mineralized bone formation, histological and micro-CT analysis showed clearly a higher tendency towards the acceleration of the healing process in the laser group. Additionally, no signs of bone necrosis were seen. In addition to the pure functioning of the device, the applicability in the clinic is important for technology to prevail. Therefore, dummy tests for the ergonomics and cadaver tests for the simulation of "real" operations in the cranio-maxillofacial field were performed. Wetlab tests were conducted on human cadavers where different macro-retentive osteotomy patterns were performed. It could be demonstrated that our prototype shows advantages over the current state of the art cutting tools, e.g. reduced bone loss, precise and real-time navigated execution of predefined geometries of freely selected osteotomy patterns. This advantage can be implemented in another indication of our prototype in the cranio-maxillofacial field: in craniosynostosis surgery. We performed a study using finite element analysis to simulate incomplete osteotomies on the inner side of the bone flap to facilitate the re-shaping (skull molding). This biomechanical analysis intended to create basic knowledge in terms of the best stress vs. force relation to obtain the largest projected bone surface. Moreover, a human multicenter study is ready to start for the clinical introduction of the cold-ablation and robot-guided laser osteotome and to gain more experience and information for future work

Development And Utilization Of Ultrasound Imaging Techniques To Evaluate The Role Of Vascularity In Adult And Aged Rat Achilles Tendon Healing

Tendons are hypovascular tissues, undergoing angiogenesis only during development, wound healing, and pathogenesis. Injured tendons exhibit a healing response with vascular ingrowth during the proliferative phase and vascular regression during remodeling. Despite this normal healing response, tendons never fully regain their original structure or composition. Additionally, aging further increases tendon risk of rupture and impairs healing response. Since the optimal vascularization level and timing during tendon healing is currently unknown, modulating the vascular response during healing could elucidate the role of angiogenesis in tendon injury and ultimately improve the tendon healing outcome. Furthermore, new ultrasound technologies allow for the evaluation of vascular response after injury, which could provide a measure for evaluating tendon healing in vivo. Therefore, the objective of this study is to develop methods for, and evaluate the effect of, vascular modulation in adult and aged rat Achilles tendons during healing using both in vivo ultrasound imaging measures of vascularity and structure and ex vivo measures of tendon compositional and mechanical properties. In Specific Aim 1, we will validate the use of in vivo high-frequency ultrasound technologies to measure vascular changes in rat Achilles tendons. In Specific Aim 2, we will develop methodologies for vascular modulation in an Achilles tendon injury model using the delivery of pro- and anti-angiogenic factors. Finally, in Specific Aim 3, we will apply methods of vascular modulation and ultrasound imaging to determine the role of angiogenesis in adult and aged Achilles tendon healing models. To achieve these goals, we will perform bilateral partial-rupture injuries in the Achilles tendons of adult and aged rats, followed by injections to modulate their vascular response after injury. The animals will receive vascular endothelial growth factor (VEGF), anti-VEGF antibody (B20.4-1-1, Genentech), or saline injections following injury. They will be evaluated using B-mode, color Doppler, photoacoustic, and contrast-enhanced ultrasound imaging weekly post-injury. Additionally, they will undergo in vivo functional assays to assess gait and passive ankle motion. Animals will be sacrificed for histological and mechanical analyses. This study will validate new in vivo methods for evaluating vascularity in tendon injury models, develop potential angiogenic therapies for improved healing outcome, and elucidate the differences in vascular response with age after tendon injury and vascular modulation

IMPROVING DAILY CLINICAL PRACTICE WITH ABDOMINAL PATIENT SPECIFIC 3D MODELS

This thesis proposes methods and procedures to proficiently introduce patient 3D models in the daily clinical practice for diagnosis and treatment of abdominal diseases. The objective of the work consists in providing and visualizing quantitative geometrical and topological information on the anatomy of interest, and to develop systems that allow to improve radiology and surgery. The 3D visualization drastically simplifies the interpretation process of medical images and provides benefits both in diagnosing and in surgical planning phases. Further advantages can be introduced registering virtual pre-operative information (3D models) with real intra-operative information (patient and surgical instruments). The surgeon can use mixed-reality systems that allow him/her to see covered structures before reaching them, surgical navigators for see the scene (anatomy and instruments) from different point of view and smart mechatronics devices, which, knowing the anatomy, assist him/her in an active way. All these aspects are useful in terms of safety, efficiency and financial resources for the physicians, for the patient and for the sanitary system too. The entire process, from volumetric radiological images acquisition up to the use of 3D anatomical models inside the surgical room, has been studied and specific applications have been developed. A segmentation procedure has been designed taking into account acquisition protocols commonly used in radiological departments, and a software tool, that allows to obtain efficient 3D models, have been implemented and tested. The alignment problem has been investigated examining the various sources of errors during the image acquisition, in the radiological department, and during to the execution of the intervention. A rigid body registration procedure compatible with the surgical environment has been defined and implemented. The procedure has been integrated in a surgical navigation system and is useful as starting initial registration for more accurate alignment methods based on deformable approaches. Monoscopic and stereoscopic 3D localization machine vision routines, using the laparoscopic and/or generic cameras images, have been implemented to obtain intra-operative information that can be used to model abdominal deformations. Further, the use of this information for fusion and registration purposes allows to enhance the potentialities of computer assisted surgery. In particular a precise alignment between virtual and real anatomies for mixed-reality purposes, and the development of tracker-free navigation systems, has been obtained elaborating video images and providing an analytical adaptation of the virtual camera to the real camera. Clinical tests, demonstrating the usability of the proposed solutions, are reported. Test results and appreciation of radiologists and surgeons, to the proposed prototypes, encourage their integration in the daily clinical practice and future developments

The Need for Standardized Assessment of Muscle Quality in Skeletal Muscle Function Deficit and Other Aging-Related Muscle Dysfunctions: A Symposium Report

A growing body of scientific literature suggests that not only changes in skeletal muscle mass, but also other factors underpinning muscle quality, play a role in the decline in skeletal muscle function and impaired mobility associated with aging. A symposium on muscle quality and the need for standardized assessment was held on April 28, 2016 at the International Conference on Frailty and Sarcopenia Research in Philadelphia, Pennsylvania. The purpose of this symposium was to provide a venue for basic science and clinical researchers and expert clinicians to discuss muscle quality in the context of skeletal muscle function deficit and other aging-related muscle dysfunctions. The present article provides an expanded introduction concerning the emerging definitions of muscle quality and a potential framework for scientific inquiry within the field. Changes in muscle tissue composition, based on excessive levels of inter- and intra-muscular adipose tissue and intramyocellular lipids, have been found to adversely impact metabolism and peak force generation. However, methods to easily and rapidly assess muscle tissue composition in multiple clinical settings and with minimal patient burden are needed. Diagnostic ultrasound and other assessment methods continue to be developed for characterizing muscle pathology, and enhanced sonography using sensors to provide user feedback and improve reliability is currently the subject of ongoing investigation and development. In addition, measures of relative muscle force such as specific force or grip strength adjusted for body size have been proposed as methods to assess changes in muscle quality. Furthermore, performance-based assessments of muscle power via timed tests of function and body size estimates, are associated with lower extremity muscle strength may be responsive to age-related changes in muscle quality. Future aims include reaching consensus on the definition and standardized assessments of muscle quality, and providing recommendations to address critical clinical and technology research gaps within the field

SUBJECT-SPECIFIC 4D ULTRASOUND LIVER MODEL AND DYNAMIC PHANTOM FOR ROBOTIC-ASSISTED LIVER BIOPSY STUDY

Ph.DDOCTOR OF PHILOSOPH