Electronic Thesis and Dissertation Repository

Thesis Format

Integrated Article

Degree

Doctor of Philosophy

Program

Medical Biophysics

Collaborative Specialization

Musculoskeletal Health Research

Supervisor

Drangova, Maria

2nd Supervisor

Holdsworth, David W.

Joint Supervisor

Abstract

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.

Summary for Lay Audience

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. Unfortunately, the top reason for implant failure is now periprosthetic joint infection (PJI), which is a devastating form of infection that is attached to the implanted joint. PJI is difficult to treat systemically and usually requires targeted drug delivery to eradicate. Furthermore, imaging-based diagnosis of PJI remains outside of standard practice as many types of imaging perform poorly around metal. The ability to use magnetic resonance imaging (MRI) is a particularly unfortunate loss, as it is well-established that MRI is highly useful for looking at musculoskeletal infection (without implants) and has many technical advances that remain unused in orthopedics. These capabilities motivate the objective of this thesis: to demonstrate that MRI has potential for diagnosing and monitoring PJI through both advances in implant design and novel application of quantitative imaging.

One of the most exciting recent advances in orthopedics is the adoption of metal 3D-printing, which has led to a variety of porous implants that are proving to be highly compatible with bone. In this thesis, I demonstrate that these porous implants have an unexplored benefit: they drastically improve MRI image quality relative to solid metal, particularly at higher porosities, which should enable MRI-based diagnosis of PJI in a manner similar to other musculoskeletal infections.

Quantitative MRI techniques, which provide measurements of tissue properties instead of just signal, remain largely unused in orthopedic imaging. Here I describe a novel use for the fact that some of these measurements are directly proportional to contrast agent concentration, which are routinely used for signal enhancement: tracking antibiotic release from localized drug delivery systems by using a contrast agent as a proxy. As there is currently no way to measure antibiotic release during PJI treatment, this could be an impactful clinical tool.

Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

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