Xavier Intes

In vivo continuous‐wave optical breast imaging enhanced with Indocyanine Green

We investigate the uptake of a nontargeted contrast agent by breast tumors using a continuous wave diffuse optical tomography apparatus. The instrument operates in the near-infrared spectral window and employs 16 sources and 16 detectors to collect light in parallel on the surface of the tumor-bearing breast (coronal geometry). In our protocol an extrinsic contrast agent, Indocyanine Green (ICG), was injected by bolus. Three clinical scenarios with three different pathologies were investigated. A two-compartment model was used to analyze the pharmacokinetics of ICG and preprocess the data, and diffuse optical tomography was used for imaging. Localization and delineation of the tumor was achieved in good agreement with a priori information. Moreover, different dynamical features were observed for differing pathologies. The malignant cases exhibited slower rate constants (uptake and outflow) compared to healthy tissue. These results provide further evidence that in vivo pharmacokinetics of ICG in breast tumors may be a useful diagnostic tool for differentiation of benign and malignant pathologies.

Diffuse optical tomography with a priori anatomical information.

Diffuse optical tomography (DOT) poses a typical ill-posed inverse problem with a limited number of measurements and inherently low spatial resolution. In this paper, we propose a hierarchical Bayesian approach to improve spatial resolution and quantitative accuracy by using a priori information provided by a secondary high resolution anatomical imaging modality, such as magnetic resonance (MR) or x-ray. In such a dual imaging approach, while the correlation between optical and anatomical images may be high, it is not perfect. For example, a tumour may be present in the optical image, but may not be discernable in the anatomical image. The proposed hierarchical Bayesian approach allows incorporation of partial a priori knowledge about the noise and unknown optical image models, thereby capturing the function-anatomy correlation effectively. We present a computationally efficient iterative algorithm to simultaneously estimate the optical image and the unknown a priori model parameters. Extensive numerical simulations demonstrate that the proposed method avoids undesirable bias towards anatomical prior information and leads to significantly improved spatial resolution and quantitative accuracy.

Diffuse optical tomography with physiological and spatial a priori constraints.

Diffuse optical tomography is a typical inverse problem plagued by ill-condition. To overcome this drawback, regularization or constraining techniques are incorporated in the inverse formulation. In this work, we investigate the enhancement in recovering functional parameters by using physiological and spatial a priori constraints. More accurate recovery of the two main functional parameters that are the blood volume and the relative saturation is demonstrated through simulations by using our method compared to actual techniques.

The integration of 3-D cell printing and mesoscopic fluorescence molecular tomography of vascular constructs within thick hydrogel scaffolds

Developing methods that provide adequate vascular perfusion is an important step toward engineering large functional tissues. Meanwhile, an imaging modality to assess the three-dimensional (3-D) structures and functions of the vascular channels is lacking for thick matrices (>2 ≈ 3 mm). Herein, we report on an original approach to construct and image 3-D dynamically perfused vascular structures in thick hydrogel scaffolds. In this work, we integrated a robotic 3-D cell printing technology with a mesoscopic fluorescence molecular tomography imaging system, and demonstrated the capability of the platform to construct perfused collagen scaffolds with endothelial lining and to image both the fluid flow and fluorescent-labeled living endothelial cells at high-frame rates, with high sensitivity and accuracy. These results establish the potential of integrating both 3-D cell printing and fluorescence mesoscopic imaging for functional and molecular studies in complex tissue-engineered tissues.

Time Domain Fluorescent Diffuse Optical Tomography: analytical expressions

Light propagation in tissue is known to be favored in the Near Infrared spectral range. Capitalizing on this fact, new classes of molecular contrast agents are engineered to fluoresce in the Near Infrared. The potential of these new agents is vast as it allows tracking non-invasively and quantitatively specific molecular events in-vivo. However, to monitor the bio-distribution of such compounds in thick tissue proper physical models of light propagation are necessary. To recover 3D concentrations of the compound distribution, it is necessary to perform a model based inverse problem: Diffuse Optical Tomography. In this work, we focus on Fluorescent Diffuse Optical Tomography expressed within the normalized Born approach. More precisely, we investigate the performance of Fluorescent Diffuse Optical Tomography in the case of time resolved measurements. The different moments of the time point spread function were analytically derived to construct the forward model. The derivation was performed from the zero order moment to the second order moment. This new forward model approach was validated with simulations based on relevant configurations. Enhanced performance of Fluorescent Diffuse Optical Tomography was achieved using these new analytical solutions when compared to the current formulations.

Projection access order in algebraic reconstruction technique for diffuse optical tomography.

Algebraic reconstruction technique (ART) is one of the popular image reconstruction techniques used in diffuse optical tomography (DOT). We investigate in this note the influence of the order in which data are accessed in ART. Simulations mimicking breast tissues in transmission geometry with contrast agent tumour enhancement were used to evaluate the image quality of the diverse projection access investigated. We show that by selecting proper projection access order, the convergence speed can be significantly improved when ART is used to perform DOT. Moreover, low-contrast detection is improved.

Full-field time-resolved fluorescence tomography of small animals

In this experimental investigation, we explore the feasibility of using wide-field illumination for time-resolved fluorescence molecular tomography. The performance of wide-field patterns with a time-resolved imaging platform is investigated in vitro and in a small animal model. A Monte Carlo-based forward model is employed to reconstruct fluorescence yield based on time-gated datasets. An improvement in resolution and quantification when using the time-gate data type compared to the commonly used cw data type is demonstrated in vitro. Furthermore, the feasibility of wide-field strategies for fluorescence preclinical applications is established by an accurate localization of a fluorescent inclusion implanted in the chest cavity of a murine model.

Monte Carlo based method for fluorescence tomographic imaging with lifetime multiplexing using time gates

Time-resolved fluorescence optical tomography allows 3-dimensional localization of multiple fluorophores based on lifetime contrast while providing a unique data set for improved resolution. However, to employ the full fluorescence time measurements, a light propagation model that accurately simulates weakly diffused and multiple scattered photons is required. In this article, we derive a computationally efficient Monte Carlo based method to compute time-gated fluorescence Jacobians for the simultaneous imaging of two fluorophores with lifetime contrast. The Monte Carlo based formulation is validated on a synthetic murine model simulating the uptake in the kidneys of two distinct fluorophores with lifetime contrast. Experimentally, the method is validated using capillaries filled with 2.5nmol of ICG and IRDye™800CW respectively embedded in a diffuse media mimicking the average optical properties of mice. Combining multiple time gates in one inverse problem allows the simultaneous reconstruction of multiple fluorophores with increased resolution and minimal crosstalk using the proposed formulation.

Real-time diffuse optical tomography based on structured illumination

A new optical acquisition scheme based on a pair of digital micromirror devices is developed and applied to three-dimensional tomographic imaging of turbid media. By using pairs of illumination-detection patterns with a single detector, we were able to perform high-resolution quantitative volumetric imaging of absorption heterogeneities embedded in optically thick samples. Additionally, a tomographic reconstruction algorithm was implemented on a graphical processor unit to provide optical reconstructions at a frame rate of 2 Hz. The structured illumination method proposed in this work has significant cost advantages over camera systems, as only a single detector is required. This configuration also has the potential to increase frame rate.

Comparison of Monte Carlo methods for fluorescence molecular tomography—computational efficiency

PURPOSE The Monte Carlo method is an accurate model for time-resolved quantitative fluorescence tomography. However, this method suffers from low computational efficiency due to the large number of photons required for reliable statistics. This paper presents a comparison study on the computational efficiency of three Monte Carlo-based methods for time-domain fluorescence molecular tomography. METHODS The methods investigated to generate time-gated Jacobians were the perturbation Monte Carlo (pMC) method, the adjoint Monte Carlo (aMC) method and the mid-way Monte Carlo (mMC) method. The effects of the different parameters that affect the computation time and statistics reliability were evaluated. Also, the methods were applied to a set of experimental data for tomographic application. RESULTS In silico results establish that, the investigated parameters affect the computational time for the three methods differently (linearly, quadratically, or not significantly). Moreover, the noise level of the Jacobian varies when these parameters change. The experimental results in preclinical settings demonstrates the feasibility of using both aMC and pMC methods for time-resolved whole body studies in small animals within a few hours. CONCLUSIONS Among the three Monte Carlo methods, the mMC method is a computationally prohibitive technique that is not well suited for time-domain fluorescence tomography applications. The pMC method is advantageous over the aMC method when the early gates are employed and large number of detectors is present. Alternatively, the aMC method is the method of choice when a small number of source-detector pairs are used.