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Anuradha Godavarty

Publications and source records attributed to Anuradha Godavarty.

6 recordsLinked to original sources

Three-dimensional fluorescence lifetime tomography.

Near-infrared fluorescence tomography using molecularly targeted lifetime-sensitive, fluorescent contrast agents have applications for early-stage cancer diagnostics. Yet, although the measurement of fluorescent lifetime imaging microscopy (FLIM) is extensively used in microscopy and spectroscopy applications, demonstration of fluorescence lifetime tomography for medical imaging is limited to two-dimensional studies. Herein, the feasibility of three-dimensional fluorescence-lifetime tomography on clinically relevant phantom volumes is established, using (i) a gainmodulated intensified charge coupled device (CCD) and modulated laser diode imaging system, (ii) two fluorescent contrast agents, e.g., Indocyanine green and 3-3'-Diethylthiatricarbocyanine iodide differing in their fluorescence lifetime by 0.62 ns, and (iii) a two stage approximate extended Kalman filter reconstruction algorithm. Fluorescence measurements of phase and amplitude were acquired on the phantom surface under different target to background fluorescence absorption (70:1, 100:1) and fluorescence lifetime (1:1, 2.1:1) contrasts at target depths of 1.4-2 cm. The Bayesian tomography algorithm was employed to obtain three-dimensional images of lifetime and absorption owing to the fluorophores.

Algorithms↗

Detection of single and multiple targets in tissue phantoms with fluorescence-enhanced optical imaging: feasibility study.

PURPOSE: To evaluate the feasibility of reconstructing single and multiple targets by using fluorescence-enhanced tomography of a breast tissue phantom. MATERIALS AND METHODS: Frequency-domain fluorescence measurements were performed in cup-shaped tissue phantoms of clinically relevant size (diameter, 10 cm) in which single or multiple 0.5-1.0-cm(3) targets that contained micromolar concentrations of indocyanine green with 1:0 and 100:1 target-to-background (T:B) contrast ratios had been embedded. Rapid acquisition of time-dependent fluorescent light measurements was performed at the phantom surface in response to point illumination of excitation light by using a gain-modulated intensified charge-coupled device detection system. Boundary surface measurements were used to tomographically reconstruct the interior targets located with various experimental conditions. RESULTS: Single 1.0-cm(3) targets located between 1.43 and 2.82 cm deep from the phantom surface at a T:B contrast ratio of 100:1 and three approximately 0.55-cm(3) targets located about 1.30 cm deep at a T:B contrast ratio of 1:0 were reconstructed with minimal or no artifacts by using boundary surface fluorescence measurements and an approximate extended Kalman filter algorithm. CONCLUSION: It is feasible to detect single or multiple fluorescent targets in tissue phantoms of clinically relevant size by using fluorescence-enhanced optical tomography.

Algorithms↗

Fluorescence-enhanced optical imaging in large tissue volumes using a gain-modulated ICCD camera.

A novel image-intensified charge-coupled device (ICCD) imaging system has been developed to perform 3D fluorescence tomographic imaging in the frequency-domain using near-infrared contrast agents. The imager is unique since it (i) employs a large tissue-mimicking phantom, which is shaped and sized to resemble a female breast and part of the extended chest-wall region, and (ii) enables rapid data acquisition in the frequency-domain by using a gain-modulated ICCD camera. Diffusion model predictions are compared to experimental measurements using two different referencing schemes under two different experimental conditions of perfect and imperfect uptake of fluorescent agent into a target. From these experimental measurements, three-dimensional images of fluorescent absorption were reconstructed using a computationally efficient variant of the approximate extended Kalman filter algorithm. The current work represents the first time that 3D fluorescence-enhanced optical tomographic reconstructions have been achieved from experimental measurements of the time-dependent light propagation on a clinically relevant breast-shaped tissue phantom using a gain-modulated ICCD camera.

Biophysical Phenomena↗

Fluorescence-enhanced optical tomography using referenced measurements of heterogeneous media.

A three-dimensional image reconstruction for fluorescence-enhanced frequency-domain photon migration (FDPM) measurements in turbid media is developed and investigated for three different simulated measurement types: 1) absolute emission measurement, or emission measurements of phase and amplitude attenuation made for a given incident point source of excitation light; 2) referenced emission measurements made relative to an excitation measurement conducted at a single reference point away from the incident source; and 3) referenced emission measurements made relative to the excitation measurement conducted at identical points of detection. The image reconstruction algorithm employs a gradient-based constrained truncated Newton (CONTN) method which implements a bounding parameter, which can be used to govern the level of contrast used to discriminate tissue volumes from heterogeneous background tissues. Reverse differentiation technique is used to calculate the gradients. Using simulated data with superimposed noise to achieve a signal-to-noise ratio of 55 and 35 dB to mimic experimental excitation and emission FDPM measurements, respectively, we show the robustness of emission measurements referenced to excitation light. We investigate the performance of algorithm CONTN using these measurement techniques and show that the absorption coefficients due to fluorophore are reconstructed by CONTN accurately and efficiently. Furthermore, we demonstrate the performance of the bounding parameter for rejection of background artifacts owing to background tissue heterogeneity.

Algorithms↗

Three-dimensional, Bayesian image reconstruction from sparse and noisy data sets: near-infrared fluorescence tomography.

A method for inverting measurements made on the surfaces of tissues for recovery of interior optical property maps is demonstrated for sparse near-infrared (NIR) fluorescence measurement sets on large tissue-simulating volumes with highly variable signal-to-noise ratio. A Bayesian minimum-variance reconstruction algorithm compensates for the spatial variability in signal-to-noise ratio that must be expected to occur in actual NIR contrast-enhanced diagnostic medical imaging. Image reconstruction is demonstrated by using frequency-domain photon migration measurements on 256-cm(3) tissue-mimicking phantoms containing none, one, or two 1-cm(3) heterogeneities with 50- to 100-fold greater concentration of Indocyanine Green dye over background levels. The spatial parameter estimate of absorption owing to the dye was reconstructed from only 160 to 296 surface measurements of emission light at 830 nm in response to incident 785-nm excitation light modulated at 100 MHz. Measurement error of acquired fluence at fluorescent emission wavelengths is shown to be highly variable. Convergence and quality of image reconstructions are improved by Bayesian conditioning incorporating (i) experimentally determined measurement error variance, (ii) recursively updated estimates of parameter uncertainty, and (iii) dynamic zonation. The results demonstrate that, to employ NIR fluorescence-enhanced optical imaging for large volumes, reconstruction approaches must account for the large range of signal-to-noise ratio associated with the measurements.

Analysis of Variance↗

Fluorescence-enhanced optical tomography of a large tissue phantom using point illumination geometries.

We demonstrate fluorescence-enhanced optical imaging of single and multiple fluorescent targets within a large (approximately 1081 cm3) phantom using frequency-domain photon migration measurements of fluorescence collected at individual points in response to illumination of excitation light at individual points on the boundary. The tissue phantom was filled with a 1% lipid solution with and without 0.01 microM Indocyanine Green (ICG) and targets consisted of vials filled with the 1% lipid containing 1-2.5 microM ICG. Measurements were acquired using a modulated intensified CCD imaging system under different experimental conditions. For 3-D image reconstruction, the gradient-based penalty modified barrier function (PMBF) method with simple bounds constrained truncated Newton with trust region method (CONTN) was used. Targets of 0.5, 0.6, and 1.0 cm3 at depths of 1.4-2.8 cm from the phantom surface were tomographically reconstructed. This work demonstrates the practicality of fluorescence-enhanced tomography in clinically relevant volumes.

Breast Neoplasms↗