Theoretical lateral and axial sensitivity limits and choices of molecular reporters for Cherenkov-excited luminescence in tissue during x-ray beam scanning.

Ethan P M Larochelle,Brian W Pogue

doi:10.1117/1.jbo.25.11.116004

Abstract

.Purpose: Unlike fluorescence imaging utilizing an external excitation source, Cherenkov emissions and Cherenkov-excited luminescence occur within a medium when irradiated with high-energy x-rays. Methods to improve the understanding of the lateral spread and axial depth distribution of these emissions are needed as an initial step to improve the overall system resolution.Methods: Monte Carlo simulations were developed to investigate the lateral spread of thin sheets of high-energy sources and compared to experimental measurements of similar sources in water. Additional simulations of a multilayer skin model were used to investigate the limits of detection using both 6- and 18-MV x-ray sources with fluorescence excitation for inclusion depths up to 1 cm.Results: Simulations comparing the lateral spread of high-energy sources show approximately higher optical yield from electrons than photons, although electrons showed a larger penumbra in both the simulations and experimental measurements. Cherenkov excitation has a roughly inverse wavelength squared dependence in intensity but is largely redshifted in excitation through any distance of tissue. The calculated emission spectra in tissue were convolved with a database of luminescent compounds to produce a computational ranking of potential Cherenkov-excited luminescence molecular contrast agents.Conclusions: Models of thin x-ray and electron sources were compared with experimental measurements, showing similar trends in energy and source type. Surface detection of Cherenkov-excited luminescence appears to be limited by the mean free path of the luminescence emission, where for the given simulation only 2% of the inclusion emissions reached the surface from a depth of 7 mm in a multilayer tissue model.

Highlights

Cherenkov-excited luminescence has previously been demonstrated as a method to improve the depth sensitivity of in vivo optical imaging[1,2,3,4] and could be an alternative to optical imaging with fluorescence in deeper penetrance
One method to improve spatial resolution of Cherenkov-excited luminescence images is to utilize known information about the beam geometry, which has previously been accomplished experimentally by delivering thin sheets of x-rays.[1,2]. This method applies a deconvolution kernel to account for the beam shape, assuming an XY Gaussian distribution of the Cherenkov emissions corresponding to the multileaf collimator (MLC) leaf opening,[1] and accounting for the depth dependence of the Cherenkov emissions.[2]
Since Cherenkov emissions are correlated with dose, but not a direct measurement of dose, deconvolution can be applied to improve the spatial resolution of the estimated delivered dose based on images of surface Cherenkov emissions.[1,7,8]

Summary

Introduction

Cherenkov-excited luminescence has previously been demonstrated as a method to improve the depth sensitivity of in vivo optical imaging[1,2,3,4] and could be an alternative to optical imaging with fluorescence in deeper penetrance. While in both cases, laser or Cherenkov excitation, the light still has to escape the tissue and is attenuated exponentially by μeff on the way out at the emission wavelength bands, there is still a major benefit from having the exciting light within the volume of tissue. Since Cherenkov emissions are correlated with dose, but not a direct measurement of dose, deconvolution can be applied to improve the spatial resolution of the estimated delivered dose based on images of surface Cherenkov emissions.[1,7,8]

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