Accuracy of fluorescent tomography in the presence of heterogeneities:study of the normalized born ratio

Abstract

We studied the performance of three-dimensional fluorescence tomography of diffuse media in the presence of heterogeneities. Experimental measurements were acquired using an imaging system consisting of a parallel plate-imaging chamber and a lens coupled charge coupled device camera, which enables conventional planar imaging as well as fluorescence tomography. To simulate increasing levels of background heterogeneity, we employed phantoms made of a fluorescent tube surrounded by several absorbers in different combinations of absorption distribution. We also investigated the effect of low absorbing thin layers (such as membranes). We show that the normalized Born approach accurately retrieves the position and shape of the fluorochrome even at high background heterogeneity. We also demonstrate that the quantification is relatively insensitive to a varying degree of heterogeneity and background optical properties. Findings are further contrasted to images obtained with the standard Born expansion and with a normalized approach that divides the fluorescent field with excitation measurements through a homogeneous medium.

Early photon tomography allows fluorescence detection of lung carcinomas and disease progression in mice in vivo

“…The intensities of the virtual detector directly opposite from the source positions were used for each projection. The fluorescence data were normalized to the intrinsic data according to the normalized Born ratio (17), an operation that virtually cancels the effects of the variation of optical properties and index of refraction along the path of photon propagation on the fluorescence signal collected. This data-processing step is critical because it compensates for the large optical heterogeneity in the torso of the animal.…”

“…For our application, the ballistic (unscattered) contribution is essentially zero because of the relatively thick tissue volume used so that it is strongly dominated by the ''early-diffuse'' component. Normalization of the forward model with the calculated transmitted intensity between the source-detector pair [i.e., G(r s, rd, t)], follows after the corresponding normalization of the fluorescence measurement with a measurement representative of photon propagation in the medium and is necessary for accurate reconstruction in optically heterogeneous media in analogy to improvements seen in constant wave fluorescence tomography (17).…”

Computed Tomography-guided Time-domain Diffuse Fluorescence Tomography in Small Animals for Localization of Cancer Biomarkers

“…The fourth critical step of the methodology is referencing the collected fluorescence data to the amount of transmitted excitation light. This referencing is often called the Born ratio, and provides many benefits for FT, with the main one being a mitigation of model-data mismatch errors 23,24 . The presented system was designed to detect both fluorescence and transmitted excitation light simultaneously by channeling the light in each detection channel into 2 separate photomultiplier tubes.…”

“…Take the Born Ratio of the data (fluorescence divided by transmittance) for each source-detector position and multiply with a forward model simulation of transmittance based on the finite-element animal mesh for uniform optical properties. This is done to mitigate errors associated with source-or detector-tissue coupling 21 , to calibrate the data to the model 22 , and to adjust data for other aspects of model-data mismatch 23,24 . 7.…”

A microcomputed tomography guided fluorescence tomography system for small animal molecular imaging

“…31,32 Here, to minimize the impact of excitation light leakage through the Fl filter as well as to minimize endogenous background Fl, a point-bypoint difference technique was applied to the Fl intensity measurements as follows:…”