Camera-based CW Diffuse Optical Tomography for obtaining 3D absorption maps by means of digital tomosynthesis.

We present a novel method for obtaining a 3D absorption map of a tissue-like turbid slab in the near-infrared spectral range by tomosynthesis. Transmittance data are obtained for a large number of oblique projection directions by scanning a cw laser source across the surface of the slab and by using a CCD camera for spatially resolved light detection. A perturbation model of light transport is used to convert the intensity maps for the different projections into absorption maps. By applying the tomosynthesis approach to these new maps, 3D absorption information on embedded inclusions has been obtained for the first time. The number and the positions of the lateral offset detectors have been optimized by employing a structural similarity index for comparison of the reconstructed with the true absorption data. We present 3D reconstruction of absorption maps using both Monte Carlo simulations and experiments on phantoms with breast-like optical properties. A comparison with conventional 3D reconstruction by a finite element approach shows the superior location performance of tomosynthesis.

Evaluation of higher-order time-domain perturbation theory of photon diffusion on breast-equivalent phantoms and optical mammograms.

Time-domain perturbation theory of photon diffusion up to third order was evaluated for its accuracy in deducing optical properties of breast tumors using simulated and physical phantoms and by analyzing 141 projection mammograms of 87 patients with histology-validated tumors that had been recorded by scanning time-domain optical mammography. The slightly compressed breast was modeled as (partially) homogeneous diffusely scattering infinite slab containing a scattering and absorbing spherical heterogeneity representing the tumor. Photon flux densities were calculated from densities of transmitted photons, assuming extended boundary conditions. Explicit formulas are provided for second-order changes in transmitted photon density due to the presence of absorbers or scatterers. The results on phantoms obtained by perturbation theory carried up to third order were compared with measured temporal point spread functions, with numerical finite-element method (FEM) simulations of transmitted photon flux density, with results obtained from the diffraction of diffuse photon density waves, and from Padé approximants. The breakdown of first-, second-, and third-order perturbation theory is discussed for absorbers and a general expression was derived for the convergence of the Born series in this case. Taking tumor optical properties derived by the diffraction model as reference we conclude that estimates of tumor absorption coefficients by perturbation theory agree with reference values within +/-25% in only 65% (first order), 66% (second order), and 77% (third order) of all mammograms analyzed. In the remaining cases tumor absorption is generally underestimated due to the breakdown of perturbation theory. On average the empirical Padé approximants yield tumor absorption coefficients similar to third-order perturbation theory, yet at noticeable lower computational efforts.

In-vivo tissue optical properties derived by linear perturbation theory for edge-corrected time-domain mammograms.

A valuable method is described to analyze time-domain optical mammograms measured in the slab-like geometry of the slightly compressed female breast with a method based on linear perturbation theory including edge correction. Perturbations in scattering and absorption coefficients were mapped applying a computationally efficient point model.

How bold is blood oxygenation level-dependent (BOLD) magnetic resonance imaging of the kidney? Opportunities, challenges and future directions.

Renal tissue hypoperfusion and hypoxia are key elements in the pathophysiology of acute kidney injury and its progression to chronic kidney disease. Yet, in vivo assessment of renal haemodynamics and tissue oxygenation remains a challenge. Many of the established approaches are invasive, hence not applicable in humans. Blood oxygenation level-dependent (BOLD) magnetic resonance imaging (MRI) offers an alternative. BOLD-MRI is non-invasive and indicative of renal tissue oxygenation. Nonetheless, recent (pre-) clinical studies revived the question as to how bold renal BOLD-MRI really is. This review aimed to deliver some answers. It is designed to inspire the renal physiology, nephrology and imaging communities to foster explorations into the assessment of renal oxygenation and haemodynamics by exploiting the powers of MRI. For this purpose, the specifics of renal oxygenation and perfusion are outlined. The fundamentals of BOLD-MRI are summarized. The link between tissue oxygenation and the oxygenation-sensitive MR biomarker T2∗ is outlined. The merits and limitations of renal BOLD-MRI in animal and human studies are surveyed together with their clinical implications. Explorations into detailing the relation between renal T2∗ and renal tissue partial pressure of oxygen (pO2 ) are discussed with a focus on factors confounding the T2∗ vs. tissue pO2 relation. Multi-modality in vivo approaches suitable for detailing the role of the confounding factors that govern T2∗ are considered. A schematic approach describing the link between renal perfusion, oxygenation, tissue compartments and renal T2∗ is proposed. Future directions of MRI assessment of renal oxygenation and perfusion are explored.

Near-infrared fluorescent dyes for enhanced contrast in optical mammography: phantom experiments.

Optical mammography with near-infrared (NIR) light using time-domain, frequency-domain, or continuous-wave techniques is a novel imaging modality to locate human breast tumors. By investigating excised specimens of normal and diseased mamma tissue we were able to demonstrate that differences in their scattering properties are a poor predictive parameter for normal and diseased mamma tissue. This paper describes the application of a NIR dye to improve the differentiation between breast tumors and normal tissue in a rat model. The NIR dye furnished a high tumor-to-tissue contrast ratio (6:1) in fluorescence images. Furthermore, this dye was used to develop liquid scattering phantoms with absorbing and fluorescent inhomogeneities. Using frequency-domain and time-domain instrumentation these inhomogeneities were localized at sufficient contrast by their increased absorption and fluorescence. Contrast between inhomogeneities and surrounding medium could be improved by combining fluorescence and transmittance images.

Preparation of solid phantoms with defined scattering and absorption properties for optical tomography.

We have developed diffusely scattering solid phantoms with optical (scattering) properties amenable to theoretical calculations. Monodisperse quartz glass spheres were used as scatterers embedded in polyester resin. An infrared dye was added to simulate absorption by biological tissue. Solid phantoms were tested for their macroscopic homogeneity. Several phantoms were built with well-defined spatial variations in their transport scattering and absorption coefficients to be used for optical tomography. Scattering, transport scattering, and absorption coefficients of solid, homogeneous phantoms and of aqueous suspensions of monodisperse quartz glass spheres were derived from measurements of time-integrated collimated transmittance and time-resolved diffuse transmittance. For aqueous suspensions of monodisperse quartz glass spheres at known number density scattering and transport scattering coefficients calculated by Mie theory are in quantitative agreement with experimentally derived values. In addition, diffuse reflectance and diffuse transmittance of aqueous suspensions at various number densities were measured and found to be in excellent agreement with results of Monte Carlo calculations using theoretical values for the scattering coefficients and anisotropy parameters.

Diffuse reflectance optical topography: location of inclusions in 3D and detectability limits.

In the present contribution we investigate the images of CW diffusely reflected light for a point-like source, registered by a CCD camera imaging a turbid medium containing an absorbing lesion. We show that detection of µa variations (absorption anomalies) is achieved if images are normalized to background intensity. A theoretical analysis based on the diffusion approximation is presented to investigate the sensitivity and the limitations of our proposal and a novel procedure to find the location of the inclusions in 3D is given and tested. An analysis of the noise and its influence on the detection capabilities of our proposal is provided. Experimental results on phantoms are also given, supporting the proposed approach.

Time-resolved imaging of solid phantoms for optical mammography.

We have recorded time-resolved transillumination images of solid phantoms with objects embedded that differ in their scattering and absorption coefficients from those of the bulk material, simulating a compressed human breast with a tumor inside. Employing time-correlated single photon counting at rates of up to 1 MHz, we recorded distributions of times of flight of photons at 1369 scan positions within 2.5 min. Several quantities, such as fractional transmittance, first moments, Fourier amplitudes, phase shifts, and frequency-dependent effective transport scattering and absorption coefficients, have been derived from experimental data to form two-dimensional images. By recording such images at a selected total number of photons detected, we have determined the contrast and effective signal-to-noise ratio in each case.

Development of a time-domain optical mammograph and first in vivo applications.

We have developed a laser-pulse mammograph capable of recording optical mammograms within approximately 3 min by measuring time-resolved transmittance at each of typically 1500 scan positions, 2.5 mm apart. As a first application two patients who have tumors were investigated successfully. From measured distributions of times of flight of photons corrected for edge effects we derived (1) characteristic quantities, such as photon counts in selected time windows, to generate optical mammograms; (2) effective transport scattering and absorption coefficients of breast tissue at each scan position, assuming the breast to be homogeneous; and (3) optical properties of a selected tumor by applying the theory of diffraction of photon density waves by spherical inhomogeneity. Mammograms recorded at different lateral offsets between source and detector fiber were used to estimate the depth of inhomogeneities.