X-Ray Excited Luminescent Chemical Sensors

Figure: Spatial resolution of XELCI. a) Working principle of XELCI versus fluorescence tomography. A narrowly collimated X-ray source only generates light in the excited spot as compared to a scanning fluorescence excitation mode where the tissue scatters the excitation beam. b) Photograph of “CU” (target) on transparency. c) Target mapping without tissue, irradiated with a 1.5-mm X-ray beam. d) Target mapped through tissue with white light as the illumination source. e) Target mapped through tissue, irradiated with a 3-mm X-ray beam. f) Target mapped through tissue, irradiated with a 1.5-mm X-ray beam; g) Target mapped through tissue, irradiated with a 1-mm X-ray beam. The color bars on the right are the ratios of the peak intensity at 620 nm over that at 700 nm. The x - and y -axis in (c–g) represent position. Step size = 300 μm, scale bar = 1 mm. [Wang et al.]

In order to measure infection-induced chemical changes at the surface of implanted orthopedic plates, we develop and characterize a pH sensor based on the use of X-ray Excited Luminescence Chemical Imaging (XELCI) to non-invasively detect and image changes in pH at the implant surface with high spatial and pH resolution while minimizing tissue scattering effects.

Diagnosis and treatment of infections associated with implanted medical devices is a challenge, as clinical symptoms of implant associated infection are often delayed and can sometimes be completely absent till infection reaches a later stage. Early diagnosis of implant associated infection and non-invasive continuous monitoring of infection to evaluate eradication and success of treatment has not been established yet. Treatment of implant infection without implant removal is possible if infection can be diagnosed at its onset. Bacteria and inflammatory responses cause a pH drop in the affected area and pH shifts to acidic from physiological pH (~ 7.4). Our sensor detects this change in pH using a combination of X-ray excited optical luminescence and pH-dependent optical absorption. It consists of a layered structure of a pH sensitive polymer film over radioluminescent particles. Our sensor provides a novel approach to non-invasively diagnose implant associated infection and assess treatment.

X-ray excited luminescent chemical imaging (XELCI) is a form of functional x-ray imaging used to detect changes in chemical concentration on surface of embedded objects by imaging scintillators embedded in tissue with high resolution using x-ray excitation and optical detection. It uses a combination of x-ray excited scintillator particles whose emission overlaps the optical absorbance of an indicator dye and thus alter the luminescent spectrum of the scintillators which can be detected optically. XELCI provides high spatial resolution images mainly limited by X-ray beam width with minimum increase from X-ray scattering in tissue. It allows point by point mapping of the surface with minimum background. XELCI is similar to x-ray luminescent computed tomography (XLCT) which constructs tomographic images of scintillator particles by point-by-point irradiation of the tissue and measurement of resultant luminescence. But XLT uses relatively high doses of x-rays to detect signal from a small quantity (0.1 – 1 µg/ml) of scintillators whereas XELCI uses much higher concentration (5g/cm3) of scintillators which enables use of significantly lower doses of x-rays. XELCI is also similar to x-ray fluorescence computed tomography (XFCT) but detects the visible photons (produced by conversion of x-ray photons by the scintillators) in place of secondary fluorescent x-rays. The advantage of using x-rays is that x-rays does not scatter much in tissue so the x-ray luminescence is only generated in the path of the x-ray beam which obviates the need to spatially resolve the illumination source thereby limiting the resolution to the size of x-ray beam. Techniques such as x-ray transmission, CT, MRI and ultrasound provide high resolution bone and tissue imaging but they have limited chemical sensitivity. Positron emission tomography (PET), single photon emission computed tomography (SPECT) and optical techniques such as confocal microscopy are generally not good for deep tissue imaging. XELCI can be used to study local chemical concentrations such as pH at the implant surface for early detection of biofilms. Figure shows the spatial resolution of XELCI and its dependence on the size of x-ray beam.