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 Pade 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 Pade approximants yield tumor absorption coefficients similar to third-order perturbation theory, yet at noticeable lower computational efforts

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.Fil: Carbone, Nicolás Abel. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigaciones en Física e Ingeniería del Centro de la Provincia de Buenos Aires. - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigaciones en Física e Ingeniería del Centro de la Provincia de Buenos Aires. - Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Centro de Investigaciones en Física e Ingeniería del Centro de la Provincia de Buenos Aires; ArgentinaFil: Vera, Demián Augusto. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigaciones en Física e Ingeniería del Centro de la Provincia de Buenos Aires. - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigaciones en Física e Ingeniería del Centro de la Provincia de Buenos Aires. - Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Centro de Investigaciones en Física e Ingeniería del Centro de la Provincia de Buenos Aires; ArgentinaFil: Iriarte, Daniela Ines. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigaciones en Física e Ingeniería del Centro de la Provincia de Buenos Aires. - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigaciones en Física e Ingeniería del Centro de la Provincia de Buenos Aires. - Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Centro de Investigaciones en Física e Ingeniería del Centro de la Provincia de Buenos Aires; ArgentinaFil: Pomarico, Juan Antonio. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigaciones en Física e Ingeniería del Centro de la Provincia de Buenos Aires. - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigaciones en Física e Ingeniería del Centro de la Provincia de Buenos Aires. - Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Centro de Investigaciones en Física e Ingeniería del Centro de la Provincia de Buenos Aires; ArgentinaFil: Macdonald, R.. Physikalisch-Technische Bundesanstalt; AlemaniaFil: Grosenick, D.. Physikalisch-Technische Bundesanstalt; Alemani

Detailing renal hemodynamics and oxygenation in rats by a combined near-infrared spectroscopy and invasive probe approach

We hypothesize that combining quantitative near-infrared spectroscopy (NIRS) with established invasive techniques will enable advanced insights into renal hemodynamics and oxygenation in small animal models. We developed a NIRS technique to monitor absolute values of oxygenated and deoxygenated hemoglobin and of oxygen saturation of hemoglobin within the renal cortex of rats. This NIRS technique was combined with invasive methods to simultaneously record renal tissue oxygen tension and perfusion. The results of test procedures including occlusions of the aorta or the renal vein, hyperoxia, hypoxia, and hypercapnia demonstrated that the combined approach, by providing different but complementary information, enables a more comprehensive characterization of renal hemodynamics and oxygenation

Experimental MRI monitoring of renal blood volume fraction variations en route to renal magnetic resonance oximetry

Diagnosis of early-stage acute kidney injury (AKI) will benefit from a timely identification of local tissue hypoxia. Renal tissue hypoxia is an early feature in AKI pathophysiology, and renal oxygenation is increasingly being assessed through T(2)*-weighted magnetic resonance imaging (MRI). However, changes in renal blood volume fraction (BVf) confound renal T(2)*. The aim of this study was to assess the feasibility of intravascular contrast-enhanced MRI for monitoring renal BVf during physiological interventions that are concomitant with variations in BVf and to explore the possibility of correcting renal T(2)* for BVf variations. A dose-dependent study of the contrast agent ferumoxytol was performed in rats. BVf was monitored throughout short-term occlusion of the renal vein, which is known to markedly change renal blood partial pressure of O(2) and BVf. BVf calculated from MRI measurements was used to estimate oxygen saturation of hemoglobin (SO(2)). BVf and SO(2) were benchmarked against cortical data derived from near-infrared spectroscopy. As estimated from magnetic resonance parametric maps of T(2) and T(2)*, BVf was shown to increase, whereas SO(2) was shown to decline during venous occlusion (VO). This observation could be quantitatively reproduced in test-retest scenarios. Changes in BVf and SO(2) were in good agreement with data obtained from near-infrared spectroscopy. Our findings provide motivation to advance multiparametric MRI for studying AKIs, with the ultimate goal of translating MRI-based renal BVf mapping into clinical practice en route noninvasive renal magnetic resonance oximetry as a method of assessing AKI and progression to chronic damage

3D-printed tissue-simulating phantoms for near-infrared fluorescence imaging of rheumatoid diseases

SIGNIFICANCE: Fluorescence imaging of rheumatoid diseases with indocyanine green (ICG) is an emerging technique with unique potential for diagnosis and therapy. Device characterization, monitoring of the performance, and further developments of the technique require tissue-equivalent fluorescent phantoms of high stability with appropriate anatomical shapes. AIM: Our investigations aim at the development of a three-dimensional (3D) printing technique to fabricate hand and finger models with appropriate optical properties in the near-infrared spectral range. These phantoms should have fluorescence properties similar to ICG, and excellent photostability and durability over years. APPROACH: We modified a 3D printing methacrylate photopolymer by adding the fluorescent dye Lumogen IR 765 to the raw material. Reduced scattering and absorption coefficients were adjusted to values representative of the human hand by incorporating titanium dioxide powder and black ink. The properties of printed phantoms of various compositions were characterized using UV/Vis and fluorescence spectroscopy, and time-resolved measurements. Photostability and bleaching were investigated with a hand imager. For comparison, several phantoms with ICG as fluorescent dye were printed and characterized as well. RESULTS: The spectral properties of Lumogen IR 765 are very similar to those of ICG. By optimizing the concentrations of Lumogen, titanium dioxide, and ink, anatomically shaped hand and vessel models with properties equivalent to in vivo investigations with a fluorescence hand imager could be printed. Phantoms with Lumogen IR 765 had an excellent photostability over up to 4 years. In contrast, phantoms printed with ICG showed significant bleaching and degradation of fluorescence over time. CONCLUSIONS: 3D printing of phantoms with Lumogen IR 765 is a promising method for fabricating anatomically shaped fluorescent tissue models of excellent stability with spectral properties similar to ICG. The phantoms are well-suited to monitor the performance of hand imagers. Concepts can easily be transferred to other fluorescence imaging applications of ICG

Diffusion-weighted renal MRI at 9.4 Tesla using RARE to improve anatomical integrity

Diffusion-weighted magnetic resonance imaging (DWI) is a non-invasive imaging technique sensitive to tissue water movement. By enabling a discrimination between tissue properties without the need of contrast agent administration, DWI is invaluable for probing tissue microstructure in kidney diseases. DWI studies commonly make use of single-shot Echo-Planar Imaging (ss-EPI) techniques that are prone to suffering from geometric distortion. The goal of the present study was to develop a robust DWI technique tailored for preclinical magnetic resonance imaging (MRI) studies that is free of distortion and sensitive to detect microstructural changes. Since fast spin-echo imaging techniques are less susceptible to B(0) inhomogeneity related image distortions, we introduced a diffusion sensitization to a split-echo Rapid Acquisition with Relaxation Enhancement (RARE) technique for high field preclinical DWI at 9.4 T. Validation studies in standard liquids provided diffusion coefficients consistent with reported values from the literature. Split-echo RARE outperformed conventional ss-EPI, with ss-EPI showing a 3.5-times larger border displacement (2.60 vs. 0.75) and a 60% higher intra-subject variability (cortex = 74%, outer medulla = 62% and inner medulla = 44%). The anatomical integrity provided by the split-echo RARE DWI technique is an essential component of parametric imaging on the way towards robust renal tissue characterization, especially during kidney disease

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.Fil: Carbone, Nicolás Abel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tandil. Centro de Investigaciones en Física e Ingeniería del Centro de la Provincia de Buenos Aires; Argentina. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Exactas. Instituto de Fisica Arroyo Seco; ArgentinaFil: Baez, Guido Rodrigo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tandil. Centro de Investigaciones en Física e Ingeniería del Centro de la Provincia de Buenos Aires; Argentina. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Exactas. Instituto de Fisica Arroyo Seco; ArgentinaFil: García, Héctor Alfredo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tandil. Centro de Investigaciones en Física e Ingeniería del Centro de la Provincia de Buenos Aires; Argentina. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Exactas. Instituto de Fisica Arroyo Seco; ArgentinaFil: Waks Serra, María Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tandil. Centro de Investigaciones en Física e Ingeniería del Centro de la Provincia de Buenos Aires; Argentina. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Exactas. Instituto de Fisica Arroyo Seco; ArgentinaFil: Di Rocco, Hector Omar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tandil. Centro de Investigaciones en Física e Ingeniería del Centro de la Provincia de Buenos Aires; Argentina. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Exactas. Instituto de Fisica Arroyo Seco; ArgentinaFil: Iriarte, Daniela Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tandil. Centro de Investigaciones en Física e Ingeniería del Centro de la Provincia de Buenos Aires; Argentina. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Exactas. Instituto de Fisica Arroyo Seco; ArgentinaFil: Pomarico, Juan Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tandil. Centro de Investigaciones en Física e Ingeniería del Centro de la Provincia de Buenos Aires; Argentina. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Exactas. Instituto de Fisica Arroyo Seco; ArgentinaFil: Grosenick, D.. Physikalisch-Technische Bundesanstalt; AlemaniaFil: Macdonald, R.. Physikalisch-Technische Bundesanstalt; Alemani

Time-resolved diffusing wave spectroscopy applied to dynamic heterogeneity imaging

We report in this paper what is to our knowledge the first observation of a time-resolved diffusing wave spectroscopy signal recorded by transillumination through a thick turbid medium: the DWS signal is measured for a fixed photon transit time, which opens the possibility of improving the spatial resolution. This technique could find biomedical applications, especially in mammography.Comment: 9 pages, 4 figure

Image informatics strategies for deciphering neuronal network connectivity

Brain function relies on an intricate network of highly dynamic neuronal connections that rewires dramatically under the impulse of various external cues and pathological conditions. Among the neuronal structures that show morphologi- cal plasticity are neurites, synapses, dendritic spines and even nuclei. This structural remodelling is directly connected with functional changes such as intercellular com- munication and the associated calcium-bursting behaviour. In vitro cultured neu- ronal networks are valuable models for studying these morpho-functional changes. Owing to the automation and standardisation of both image acquisition and image analysis, it has become possible to extract statistically relevant readout from such networks. Here, we focus on the current state-of-the-art in image informatics that enables quantitative microscopic interrogation of neuronal networks. We describe the major correlates of neuronal connectivity and present workflows for analysing them. Finally, we provide an outlook on the challenges that remain to be addressed, and discuss how imaging algorithms can be extended beyond in vitro imaging studies