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Insight into the vasculature of the tumor in small animals has the potential to impact many areas of cancer research. The heterogeneity of the vasculature of a tumor is directly related to tumor stage and disease progression. In this small scale animal study, we investigated the feasibility of differentiating tumors with different levels of vasculature heterogeneity in vivo using a previously developed hybrid magnetic resonance imaging (MRI) and diffuse optical tomography (DOT) system for small animal imaging. Cross-sectional total hemoglobin concentration maps of 10 Fisher rats bearing R3230 breast tumors are reconstructed using multi-wavelength DOT measurements both with and without magnetic resonance (MR) structural a priori information. Simultaneously acquired MR structural images are used to guide and constrain the DOT reconstruction, while dynamic contrast-enhanced MR functional images are used as the gold standard to classify the vasculature of the tumor into two types: high versus low heterogeneity. These preliminary results show that the stand-alone DOT is unable to differentiate tumors with low and high vascular heterogeneity without structural a priori information provided by a high resolution imaging modality. The mean total hemoglobin concentrations comparing the vasculature of the tumors with low and high heterogeneity are significant (p-value 0.02) only when MR structural a priori information is utilized.

Conventional fluorescence tomography provides images of the distribution of fluorescent agents within highly scattering media, but suffers from poor spatial resolution. Previously, we introduced a new method termed “temperature-modulated fluorescence tomography” (TM-FT) that generates fluorescence images with high spatial resolution. TM-FT first uses focused ultrasound to locate the distribution of temperature-sensitive fluorescence probes. Afterward, this a priori information is utilized to improve the performance of the inverse solver for conventional fluorescence tomography and reveal quantitatively accurate fluorophore concentration maps. However, the disadvantage of this novel method is the long data acquisition time as the ultrasound beam was scanned in a step-and-shoot mode. In this Letter, we present a new, fast scanning method that reduces the imaging time 40 fold. By continuously scanning the ultrasound beam over a 50 mm by 25 mm field-of-view, high-resolution fluorescence images are obtained in less than 29 min, which is critical for in vivo small animal imaging.

In fluorescence imaging, both fluorescence yield and lifetime are of great importance. Traditionally, with the frequency-domain data, two parameters can be directly recovered through a nonlinear formulation. However, the reconstruction accuracy highly depends on initial guesses. To overcome this hurdle, we propose the linear scheme via an inverse complex-source formulation. Using the real and imaginary parts of the frequency-domain data, the proposed method is fully linear; it is not sensitive to initial guesses and is stable with high-level noise. Meanwhile, the algorithm is efficient, and the reconstruction takes one or a few iterations. In addition, the colocalization constraint due to the unique feature of fluorescence imaging is imposed to enhance algorithm performance. The algorithms are tested with simulated data.

In this work, a first-of-its-kind fully integrated tri-modality system that combines fluorescence, diffuse optical and x-ray tomography (FT/DOT/XCT) into the same setting is presented. The purpose of this system is to perform quantitative fluorescence tomography using multi-modality imaging approach. XCT anatomical information is used as structural priori while optical background heterogeneity information obtained by DOT measurements is used as functional priori. The performance of the hybrid system is evaluated using multi-modality phantoms. In particular, we show that a 2.4 mm diameter fluorescence inclusion located in a heterogeneous medium can be localized accurately with the functional a priori information, although the fluorophore concentration is recovered with 70% error. On the other hand, the fluorophore concentration can be accurately recovered within 8% error only when both DOT optical background functional and XCT structural a priori information are utilized to guide and constrain the FT reconstruction algorithm. (C) 2010 Optical Society of America

We demonstrate the necessity of functional and structural a priori information for quantitative fluorescence tomography (FT) with phantom studies. Here the functional a priori information is defined as the optical properties of the heterogeneous background that can be measured by a diffuse optical tomography (DOT) system. A CCD-based noncontact hybrid FT/DOT system that could take measurements at multiple views was built. Multimodality phantoms with multiple compartments were constructed and used in the experiments to mimic a heterogeneous optical background. A 3.6 mm diameter object deeply embedded in a heterogeneous optical background could be localized without any a priori information, but the recovered fluorophore concentration only reached one tenth of the true concentration. On the other hand, the true fluorophore concentration could be recovered when both functional and structural a priori information is utilized to guide and constrain the FT reconstruction algorithm.

We present a study of the dynamics of optical contrast agents indocyanine green (ICG) and methylene blue (MB) in an adenocarcinoma rat tumor model. Measurements are conducted with a combined frequency-domain and steady-state optical technique that facilitates rapid measurement of tissue absorption in the 650–1000-nm spectral region. Tumors were also imaged by use of contrast-enhanced magnetic resonance imaging (MRI) and coregistered with the location of the optical probe. The absolute concentrations of contrast agent, oxyhemoglobin, deoxyhemoglobin, and water are measured simultaneously each second for approximately 10 min. The differing tissue uptake kinetics of ICG and MB in these late-stage tumors arise from differences in their effective molecular weights. ICG, because of its binding to plasma proteins, behaves as a macromolecular contrast agent with a low vascular permeability. A compartmental model describing ICG dynamics is used to quantify physiologic parameters related to capillary permeability. In contrast, MB behaves as a small-molecular-weight contrast agent that leaks rapidly from the vasculature into the extravascular, extracellular space, and is sensitive to blood flow and the arterial input function. © 2003 Optical Society of America.