X-ray excited luminescent chemical imaging (XELCI) for non-invasive imaging of implant infections

Benza, Donald; Uzair, Unaiza; Raval, Yash S.; Tzeng, Tzuen‐Rong; Behrend, Caleb; Anker, Jeffrey N.

doi:10.1117/12.2256049

Cited by 5 publications

(7 citation statements)

References 19 publications

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“…This was then imaged by XELCI through 6 and 11 mm of porcine tissue, and the 620 and 700 nm intensity images were obtained. This tissue thickness tested for XELCI provides a reasonable range for human tibial implantation and small animal studies . The raw data (620 nm PMT counts, 700 nm PMT counts, and stage position vs time) was processed using a MATLAB script to form the 620 nm, 700 nm, and ratio images vs stage position.…”

Section: Methodsmentioning

confidence: 99%

“…This tissue thickness tested for XELCI provides a reasonable range for human tibial implantation 25 and small animal studies. 29 The raw data (620 nm PMT counts, 700 nm PMT counts, and stage position vs time) was processed using a MATLAB script to form the 620 nm, 700 nm, and ratio images vs stage position. The signal was averaged over each disk and normalized to the reference signal.…”

Section: ■ Experimental Detailsmentioning

confidence: 99%

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

Uzair

Johnson

Beladi-Behbahani

et al. 2020

ACS Appl. Mater. Interfaces

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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.

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Section: Methodsmentioning

confidence: 99%

Section: ■ Experimental Detailsmentioning

confidence: 99%

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

Uzair

Johnson

Beladi-Behbahani

et al. 2020

ACS Appl. Mater. Interfaces

Self Cite

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“…The stage position is controlled with a program written in LabVIEW (National Instruments, Austin, TX), which also records PMT counts and stage position versus time, and displayed an image on the computer screen during acquisition. The scanning process and signal processing is explained in our previous work …”

Section: Methodsmentioning

confidence: 99%

“…The scanning process and signal processing is explained in our previous work. 31 Imaging through Tissue. The chicken breast tissue was cut into slices of desired thickness using an electric food slicer (model 630, Chef's Choice, Avondale, PA, USA).…”

Section: ■ Experimental Detailsmentioning

confidence: 99%

Noninvasively Imaging pH at the Surface of Implanted Orthopedic Devices with X-ray Excited Luminescence Chemical Imaging

Uzair¹,

Benza²,

Behrend

et al. 2019

ACS Sens.

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Implanted medical device-associated infections are a leading cause of fixation failure, and early diagnosis is the key to successful treatment. During infection, acidosis near the implant plays a role in antibiotic resistance and low pH is a potential infection indicator. Herein, we describe a pH sensor which attaches to the implants to noninvasively image local pH with high spatial resolution. The sensor has two layers: a scintillator layer which emits 620 and 700 nm light upon X-ray irradiation and a pH indicator layer containing bromocresol green dye that absorbs 620 nm luminescence in neutral/basic pH and passes 700 nm light at all pHs. We also developed a dedicated imaging system capable of scanning relatively large specimens through thick tissues. A focused X-ray beam irradiates one spot on the sensor, and the 620 to 700 nm peak ratio is measured to determine the local pH; images are acquired by scanning the X-ray beam across the surface and measuring the pH point-by-point. The sensor was covered with varying thickness slices of chicken breast tissue (0−19 mm) to evaluate how the tissue affects the peak intensity and ratio. Thick tissues attenuated both 620 and 700 nm light, with more attenuation at 620 nm than 700 nm. Although this spectral distortion shifted the pH calibration curve, the effect could be corrected for using a scintillator film region with no pH indicator layer as a spectral reference. The sensor was attached to an orthopedic plate affixed to a human cadaveric tibia and imaged through tissue. This approach provides both high spatial resolution from focused X-ray excitation and surface chemical specificity from the indicator dye, providing a tool for imaging local pH through tissue.

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“…[21] Herein we introduce Ultrasound Luminescent Chemical Imaging (ULCI), a technique to monitor local pH at the sur-face of a modified implant during infection (Figure 1). [22] Specifically, to image or map a target area via a point-by-point raster scanning with the ULCI system, we modified the X-ray Excited Luminescent Chemical Imaging (XELCI) [12,19,23,24] system that has been successfully used to image pH in human cadaveric tibia [19] and live rabbits. [25] The XELCI system produces high resolution images, but uses a relatively expensive focused X-ray source, and the associated radiation dose that limits repeated measurements.…”

Section: Introductionmentioning

confidence: 99%

Development of pH‐Sensitive Film for Detection of Implant Infection via Ultrasound Luminescent Chemical Imaging

Schober,

Uzair,

Reel

et al. 2024

Advanced Sensor Research

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A new hybrid ultrasound luminescent chemical imaging technique is described along with a pH sensor to image chemical concentrations at the surface of implanted medical devices. The purpose is to detect and study local biochemistry during infection. The sensor comprises a mechanoluminescent film (SrAl2O4:Eu, Dy microphosphors embedded in a biocompatible polymer film) and a pH indicator dye. A focused ultrasound beam generates green luminescence at the ultrasound focal point. By pulsing the ultrasound ON and OFF, the modulated luminescence can be distinguished from persistent luminescence, for high spatial resolution imaging. A red fluorescent dye and the pH indicator dye bromothymol blue are added to the coating to modulate the red‐light transmittance via pH dependent absorbance. Acidosis is observed as an increase in red luminescence intensity in spectroscopy and imaging. The films are sensitive to biologically relevant changes in pH (6.0–8.0) and can be imaged through optically scattering media to mimic tissue. The images have a knife edge spatial resolution of ≈3 mm through optically scattering phantoms, limited by the focused ultrasound spot size. This novel technique may permit the elucidation of implant infection at the implant surface and can be further developed for the measurement of other relevant chemical species in the future.

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X-ray excited luminescent chemical imaging (XELCI) for non-invasive imaging of implant infections

Cited by 5 publications

References 19 publications

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

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

Noninvasively Imaging pH at the Surface of Implanted Orthopedic Devices with X-ray Excited Luminescence Chemical Imaging

Development of pH‐Sensitive Film for Detection of Implant Infection via Ultrasound Luminescent Chemical Imaging

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