Conformal Coating of Orthopedic Plates with X-ray Scintillators and pH Indicators for X-ray Excited Luminescence Chemical Imaging through Tissue

Abstract

We describe a material that allows for high spatial resolution pH mapping through tissue using X-ray excited luminescence chemical imaging (XELCI). This is especially useful for detecting implant associated infection and elucidating how the local biochemical environment changes during infection and treatment. To acquire one pixel in the image, a focused X-ray beam irradiates a small region of scintillators coated on the implant and the X-ray excited optical luminescence spectrum is modulated by indicator dyes to provide a chemically sensitive measurement with low background. Scanning the X-ray beam across the implant surface generates high spatial resolution chemical measurements. Two associated challenges are 1) to make robust sensors that can be implanted in tissue to measure local chemical concentrations and specifically for metal orthopedic implants, and 2) to conformally coat the implant surface with scintillators and pH indicator dyes in order to make measurements over a large area. Previously, we have physically pressed or glued a pH-sensitive hydrogel sensor to the surface of an implant, but this is impractical for imaging over large irregular device areas such as an orthopedic plate with holes and edges. Herein we describe a chemically sensitive and biocompatible XELI sensor material containing scintillator particles (Gd 2 O 2 S:Eu) and a pH sensitive hydrogel coating using a roughened epoxy coating. A two-part commercial grade epoxy film was tested and found to make the coating of pH sensitive layer adhere better to the titanium surface. Sugar and salt particles were added to the surface of the epoxy as it cured to create a roughened surface and increase surface area. On this roughened surface, a secondary layer of diacrylated polyethylene glycol (PEG) hydrogel, containing a pH sensitive dye, was polymerized. This layer was found to adhere well to the epoxy-coated implant unlike other previously tested polymer surfaces which delaminated when exposed to water or humidity. The focused X-ray beam enabled 0.5 mm spatial resolution through 1 cm thick tissue. The pH sensor coated orthopedic plate was imaged with XELCI through tissue with different pH to acquire a calibration curve. The plates were also imaged through tissue with low pH region from a Staphylococcus aureus biofilm grown on one section. These studies demonstrate the use of pH sensor coated orthopedic plates for mapping the surface pH through tissue during biofilm formation using XELCI.

Radioluminescence Imaging of Drug Elution from Biomedical Implants

“…Previous studies have shown that the point spread function is about 20 mm for 650–800 nm light through 10 mm of tissue (in slab geometry). [ 46 ] The intensity profile of vertical lines through the center of each image demonstrates the signal decrease and spread for the drug release region (left‐most peak) and constant drug reference region (right‐most peak) (Figure 3E). The full‐width half‐maximum(FWHM) for the signal through 5 and 10 mm of tissue, calculated after four iterations of Gaussian smoothing (Figure S3, Supporting Information) to reduce image noise, is 13.1 and 16.5 mm, respectively.…”

pH variation in medical implant biofilms: Causes, measurements, and its implications for antibiotic resistance

“…X-ray excited luminescent chemical imaging (XELCI) is a novel medical imaging technique used to non-invasively detect and monitor bacterial biofilm on implant surfaces ( Wang et al, 2015 ; Uzair et al, 2020 ). In the XELCI technique, a combination of X-ray excitation to provide high-resolution images and optical detection of infection is used.…”

“…The light that passes through tissue is then collected, and the spectral ratio is measured to determine the pH. A focused X-ray beam irradiates a point in the scintillator film, and a pH image is formed point-by-point by scanning the beam across the sample ( Uzair et al, 2020 ). A pH sensor film was developed by Wang et al and can be coated on implant surfaces to noninvasively map pH ex vivo in porcine tissue using XELCI ( Wang et al, 2015 ).…”

“…A similar pH sensor attached to implants was developed to noninvasively detect local implant pH. Both these sensors enabled noninvasive mapping of local pH, with high spectral resolution ( Wang et al, 2015 ; Uzair et al, 2019 , 2020 ). A hydrogel sensor that can be attached to a prosthetic hip implant is able to measure synovial fluid pH using plain radiography ( Wijayaratna et al, 2021 ).…”

Upconversion Spectral Rulers for Transcutaneous Displacement Measurements

“…In this study, we have shown that we can image through 6 mm of chicken breast. We do not know the maximum but would expect around 2 cm should be feasible because we are able to acquire focused X-ray luminescence images through around 2 cm of tissue and bone in an ex vivo rabbit model [42], and we typically observe much higher signals from upconversion luminescence than for X-ray luminescence [43]. However, deeper tissue imaging may require better optical collection efficiency, larger or brighter sensors, longer acquisition times, and/or higher noise levels because the excitation and emission light are exponentially attenuated by tissue.…”