Quantitative Magnetic Resonance Imaging Methodology Development

Magnetic Resonance Imaging (MRI) is a non-invasive medical imaging modality that provides excellent soft tissue contrast and resolution. Objects with high magnetic susceptibility distort the magnetic field, leading to severe artifacts in conventional MRI. It is very challenging to image around metal implants. Novel strategies may exploit the field distortion for spatial encoding. The magnetic field map is required in the development of these methods. A robust field map can also be employed to quantify high susceptibility particles that play a major role in cell tracking studies and hyperthermic treatment of cancers. Pure phase encoding (PPE) techniques with short encoding times are largely immune to magnetic field inhomogeneity artifacts. Artifact-free MR images around titanium were acquired with PPE techniques, from which the magnetic field distribution was derived. The approach was extended to quantify iron microparticles and was compared with conventional MRI to demonstrate its superiority

Quantitative MRI and 3D-Printing for Monitoring Periprosthetic Joint Infection

Joint replacements are becoming increasingly commonplace with over 130,000 joint arthroplasties being performed annually in Canada. Although joint replacement surgery is highly successful, implants do occasionally fail and need to be replaced via costly and difficult revision surgery. Periprosthetic joint infection (PJI) has recently become the leading reason for revision of both hip and knee replacements, which is unfortunate because PJI is difficult to diagnose and treat effectively; diagnosis is made particularly difficult by the lack of established non-invasive (imaging) means of evaluating PJI. This thesis aims to demonstrate that magnetic resonance imaging (MRI) has potential for diagnosing and monitoring PJI through advances in implant design and novel application of quantitative imaging. The recent proliferation of metal 3D-printing has already inspired the clinical use of 3D-printed porous metal devices due to their favorable osseointegration and mechanical properties. This thesis explores an important MRI benefit to porous implants: their decreased effective magnetic susceptibility and proportional decrease in imaging artifacts. This is relevant to PJI because MRI is already well-established in diagnosing musculoskeletal infections, but metals cause image obscuring signal loss. This work shows that 3D-printed porous metal structures are likely to avoid this limitation, as their effective magnetic susceptibility is linearly proportional to porosity; if true, MRI will be able to diagnose PJI as easily as non-prosthetic joint infections. This thesis describes a novel use for two important parameters measured by quantitative MRI: effective relaxation rate (R2*) and magnetic susceptibility (QSM; quantitative susceptibility mapping). This work seeks to address an important unmet need in PJI treatment – the ability to monitor drug release during localized antibiotic delivery – by exploiting these parameters’ proportionality to gadolinium concentration. This idea is centered around using gadolinium-based MRI contrast agents as a surrogate small-molecule that acts as a proxy for drugs to study diffusion-controlled release. An initial implementation of this concept showed promising results, including the ability to fit the data to a mathematical model of drug release. This shows the potential of MRI as a non-invasive means of monitoring localized antibiotic treatment of PJI post-revision

3 versus 7 Tesla magnetic resonance imaging for parcellations of subcortical brain structures in clinical settings

7 Tesla (7T) magnetic resonance imaging holds great promise for improved visualization of the human brain for clinical purposes. To assess whether 7T is superior regarding localization procedures of small brain structures, we compared manual parcellations of the red nucleus, subthalamic nucleus, substantia nigra, globus pallidus interna and externa. These parcellations were created on a commonly used clinical anisotropic clinical 3T with an optimized isotropic (o)3T and standard 7T scan. The clinical 3T MRI scans did not allow delineation of an anatomically plausible structure due to its limited spatial resolution. o3T and 7T parcellations were directly compared. We found that 7T outperformed the o3T MRI as reflected by higher Dice scores, which were used as a measurement of interrater agreement for manual parcellations on quantitative susceptibility maps. This increase in agreement was associated with higher contrast to noise ratios for smaller structures, but not for the larger globus pallidus segments. Additionally, control-analyses were performed to account for potential biases in manual parcellations by assessing semi-automatic parcellations. These results showed a higher consistency for structure volumes for 7T compared to optimized 3T which illustrates the importance of the use of isotropic voxels for 3D visualization of the surgical target area. Together these results indicate that 7T outperforms c3T as well as o3T given the constraints of a clinical setting

Microelectromechanical Systems and Devices

The advances of microelectromechanical systems (MEMS) and devices have been instrumental in the demonstration of new devices and applications, and even in the creation of new fields of research and development: bioMEMS, actuators, microfluidic devices, RF and optical MEMS. Experience indicates a need for MEMS book covering these materials as well as the most important process steps in bulk micro-machining and modeling. We are very pleased to present this book that contains 18 chapters, written by the experts in the field of MEMS. These chapters are groups into four broad sections of BioMEMS Devices, MEMS characterization and micromachining, RF and Optical MEMS, and MEMS based Actuators. The book starts with the emerging field of bioMEMS, including MEMS coil for retinal prostheses, DNA extraction by micro/bio-fluidics devices and acoustic biosensors. MEMS characterization, micromachining, macromodels, RF and Optical MEMS switches are discussed in next sections. The book concludes with the emphasis on MEMS based actuators

Imaging the subthalamic nucleus in Parkinson’s disease

This thesis is comprised of a set of work that aims to visualize and quantify the anatomy, structural variability, and connectivity of the subthalamic nucleus (STN) with optimized neuroimaging methods. The study populations include both healthy cohorts and individuals living with Parkinson's disease (PD). PD was chosen specifically due to the involvement of the STN in the pathophysiology of the disease. Optimized neuroimaging methods were primarily obtained using ultra-high field (UHF) magnetic resonance imaging (MRI). An additional component of this thesis was to determine to what extent UHF-MRI can be used in a clinical setting, specifically for pre-operative planning of deep brain stimulation (DBS) of the STN for patients with advanced PD. The thesis collectively demonstrates that i, MRI research, and clinical applications must account for the different anatomical and structural changes that occur in the STN with both age and PD. ii, Anatomical connections involved in preparatory motor control, response inhibition, and decision-making may be compromised in PD. iii. The accuracy of visualizing and quantifying the STN strongly depends on the type of MR contrast and voxel size. iv, MRI at a field strength of 3 Tesla (T) can under certain circumstances be optimized to produce results similar to that of 7 T at the expense of increased acquisition time

Towards tactile sensing active capsule endoscopy

Examination of the gastrointestinal(GI) tract has traditionally been performed using tethered endoscopy tools with limited reach and more recently with passive untethered capsule endoscopy with limited capability. Inspection of small intestines is only possible using the latter capsule endoscopy with on board camera system. Limited to visual means it cannot detect features beneath the lumen wall if they have not affected the lumen structure or colour. This work presents an improved capsule endoscopy system with locomotion for active exploration of the small intestines and tactile sensing to detect deformation of the capsule outer surface when it follows the intestinal wall. In laboratory conditions this system is capable of identifying sub-lumen features such as submucosal tumours.Through an extensive literary review the current state of GI tract inspection in particular using remote operated miniature robotics, was investigated, concluding no solution currently exists that utilises tactile sensing with a capsule endoscopy. In order to achieve such a platform, further investigation was made in to tactile sensing technologies, methods of locomotion through the gut, and methods to support an increased power requirement for additional electronics and actuation. A set of detailed criteria were compiled for a soft formed sensor and flexible bodied locomotion system. The sensing system is built on the biomimetic tactile sensing device, Tactip, \cite{Chorley2008, Chorley2010, Winstone2012, Winstone2013} which has been redesigned to fit the form of a capsule endoscopy. These modifications have required a $360^{o}$ cylindrical sensing surface with $360^{o}$ panoramic optical system. Multi-material 3D printing has been used to build an almost complete sensor assembly with a combination of hard and soft materials, presenting a soft compliant tactile sensing system that mimics the tactile sensing methods of the human finger. The cylindrical Tactip has been validated using artificial submucosal tumours in laboratory conditions. The first experiment has explored the new form factor and measured the device's ability to detect surface deformation when travelling through a pipe like structure with varying lump obstructions. Sensor data was analysed and used to reconstruct the test environment as a 3D rendered structure. A second tactile sensing experiment has explored the use of classifier algorithms to successfully discriminate between three tumour characteristics; shape, size and material hardness. Locomotion of the capsule endoscopy has explored further bio-inspiration from earthworm's peristaltic locomotion, which share operating environment similarities. A soft bodied peristaltic worm robot has been developed that uses a tuned planetary gearbox mechanism to displace tendons that contract each worm segment. Methods have been identified to optimise the gearbox parameter to a pipe like structure of a given diameter. The locomotion system has been tested within a laboratory constructed pipe environment, showing that using only one actuator, three independent worm segments can be controlled. This configuration achieves comparable locomotion capabilities to that of an identical robot with an actuator dedicated to each individual worm segment. This system can be miniaturised more easily due to reduced parts and number of actuators, and so is more suitable for capsule endoscopy. Finally, these two developments have been integrated to demonstrate successful simultaneous locomotion and sensing to detect an artificial submucosal tumour embedded within the test environment. The addition of both tactile sensing and locomotion have created a need for additional power beyond what is available from current battery technology. Early stage work has reviewed wireless power transfer (WPT) as a potential solution to this problem. Methods for optimisation and miniaturisation to implement WPT on a capsule endoscopy have been identified with a laboratory built system that validates the methods found. Future work would see this combined with a miniaturised development of the robot presented. This thesis has developed a novel method for sub-lumen examination. With further efforts to miniaturise the robot it could provide a comfortable and non-invasive procedure to GI tract inspection reducing the need for surgical procedures and accessibility for earlier stage of examination. Furthermore, these developments have applicability in other domains such as veterinary medicine, industrial pipe inspection and exploration of hazardous environments

Unveiling the prospects of point-of-care 3D printing of Polyetheretherketone (PEEK) patient-specific implants

Additive manufacturing (AM) or three-dimensional (3D) printing is rapidly gaining acceptance in the healthcare sector. With the availability of low-cost desktop 3D printers and inexpensive materials, in-hospital or point-of-care (POC) manufacturing has gained considerable attention in personalized medicine. Material extrusion-based [Fused Filament Fabrication (FFF)] 3D printing of low-temperature thermoplastic polymer is the most commonly used 3D printing technology in hospitals due to its ease of operability and availability of low-cost machines. However, this technology has been limited to the production of anatomical biomodels, surgical guides, and prosthetic aids and has not yet been adopted into the mainstream production of patient-specific or customized implants. Polyetheretherketone (PEEK), a high-performance thermoplastic polymer, has been used mainly in reconstructive surgeries as a reliable alternative to other alloplastic materials to fabricate customized implants. With advancements in AM systems, prospects for customized 3D printed surgical implants have emerged, increasing attention for POC manufacturing. A customized implant may be manufactured within few hours using 3D printing, allowing hospitals to become manufacturers. However, manufacturing customized implants in a hospital environment is challenging due to the number of actions necessary to design and fabricate the implants. The focus of this thesis relies on material extrusion-based 3D printing of PEEK patient-specific implants (PSIs). The ambitious challenge was to bridge the performance gap between 3D printing of PEEK PSIs for reconstructive surgery and the clinical applicability at the POC by taking advantage of recent developments in AM systems. The main reached milestones of this project include: (i) assessment of the fabrication feasibility of PEEK surgical implants using material extrusion-based 3D printing technology, (ii) incorporation of a digital clinical workflow for POC manufacturing, (iii) assessment of the clinical applicability of the POC manufactured patient-specific PEEK scaphoid prosthesis, (iv) visualization and quantification of the clinical reliability of the POC manufactured patient-specific PEEK cranial implants, and (v) assessment of the clinical performance of the POC manufactured porous patient-specific PEEK orbital implants. During this research work, under the first study, we could demonstrate the prospects of FFF 3D printing technology for POC PEEK implant manufacturing. It was established that FFF 3D printing of PEEK allows the construction of complex anatomical geometries which cannot be manufactured using other technologies. With a clinical digital workflow implementation at the POC, we could further illustrate a smoother integration and faster implant production (within two hours) potential for a complex-shaped, patented PEEK patient-specific scaphoid prosthesis. Our results revealed some key challenges during the FFF printing process, exploring the applicability of POC manufactured FFF 3D printed PEEK customized implants in craniofacial reconstructions. It was demonstrated that optimal heat distribution around the cranial implants and heat management during the printing process are essential parameters that affect crystallinity, and thus the quality of the FFF 3D printed PEEK cranial implants. At this stage of the investigation, it was observed that the root mean square (RMS) values for dimensional accuracy revealed higher deviations in large-sized cranial prostheses with “horizontal lines” characteristics. Further optimization of the 3D printer, a layer-by-layer increment in the airflow temperature was done, which improved the performance of the FFF PEEK printing process for large-sized cranial implants. We then evaluated the potential clinical reliability of the POC manufactured 3D printed PEEK PSIs for cranial reconstruction by quantitative assessment of geometric, morphological, and biomechanical characteristics. It was noticed that the 3D printed customized cranial implants had high dimensional accuracy and repeatability, displaying clinically acceptable morphologic similarity concerning fit and contours continuity. However, the tested cranial implants had variable peak load values with discrete fracture patterns from a biomechanical standpoint. The implants with the highest peak load had a strong bonding with uniform PEEK fusion and interlayer connectivity, while air gaps and infill fusion lines were observed in implants with the lowest strength. The results of this preclinical study were in line with the clinical applicability of cranial implants; however, the biomechanical attribute can be further improved. It was noticed that each patient-specific reconstructive implant required a different set of manufacturing parameters. This was ascertained by manufacturing a porous PEEK patient-specific orbital implant. We evaluated the FFF 3D printed PEEK orbital mesh customized implants with a metric considering the design variants, biomechanical, and morphological parameters. We then studied the performance of the implants as a function of varying thicknesses and porous design constructs through a finite element (FE) based computational model and a decision matrix based statistical approach. The maximum stress values achieved in our results predicted the high durability of the implants. In all the implant profile configurations, the maximum deformation values were under one-tenth of a millimeter (mm) domain. The circular patterned design variant implant revealed the best performance score. The study further demonstrated that compounding multi-design computational analysis with 3D printing can be beneficial for the optimal restoration of the orbital floor. In the framework of the current thesis, the potential clinical application of material extrusion-based 3D printing for PEEK customized implants at the POC was demonstrated. We implemented clinical experience and engineering principles to generate a technical roadmap from preoperative medical imaging datasets to virtual surgical planning, computer-aided design models of various reconstructive implant variants, to the fabrication of PEEK PSIs using FFF 3D printing technology. The integration of 3D printing PEEK implants at the POC entails numerous benefits, including a collaborative team approach, quicker turnaround time of customized implants, support in pre-surgical and intraoperative planning, improved patient outcomes, and decreased overall healthcare cost. We believe that FFF 3D printing of customized PEEK implants could become an integral part of the hospitals and holds potential for various reconstructive surgery applications