Enhanced diffuse optical tomographic reconstruction using concurrent ultrasound information.

Multimodal imaging is an active branch of research as it has the potential to improve common medical imaging techniques. Diffuse optical tomography (DOT) is an example of a low resolution, functional imaging modality that typically has very low resolution due to the ill-posedness of its underlying inverse problem. Combining the functional information of DOT with a high resolution structural imaging modality has been studied widely. In particular, the combination of DOT with ultrasound (US) could serve as a useful tool for clinicians for the formulation of accurate diagnosis of breast lesions. In this paper, we propose a novel method for US-guided DOT reconstruction using a portable time-domain measurement system. B-mode US imaging is used to retrieve morphological information on the probed tissues by means of a semi-automatical segmentation procedure based on active contour fitting. A two-dimensional to three-dimensional extrapolation procedure, based on the concept of distance transform, is then applied to generate a three-dimensional edge-weighting prior for the regularization of DOT. The reconstruction procedure has been tested on experimental data obtained on specifically designed dual-modality silicon phantoms. Results show a substantial quantification improvement upon the application of the implemented technique. This article is part of the theme issue 'Synergistic tomographic image reconstruction: part 2'.

Order-Disorder Structural Transitions in Mazes Built by Evaporating Drops.

We show that the evaporation of surfactant solutions confined in quasi-two-dimensional porous media creates micron-sized labyrinthine patterns composing the walls of a centimeter-sized maze. These walls are made of solid deposits formed during drying via a sequence of individual Haines jumps occurring at the pore scale. We rationalize this process driven by simple iterative rules with a cellular automaton that acts as a maze generator. This model well describes the formation dynamics and final structure of an experimental maze as functions of the wettability heterogeneities of a porous medium and its geometry. Also, our findings unveil the crucial role of two geometric dimensionless quantities that control the structural order of a maze.

Prediction of Chemoresistance in Women Undergoing Neo-Adjuvant Chemotherapy for Locally Advanced Breast Cancer: Volumetric Analysis of First-Order Textural Features Extracted from Multiparametric MRI.

Purpose: To assess correlations between volumetric first-order texture parameters on baseline MRI and pathological response after neoadjuvant chemotherapy (NAC) for locally advanced breast cancer (BC). Materials and Methods: 69 patients with locally advanced BC candidate to neoadjuvant chemotherapy underwent MRI within 4 weeks from the start of therapeutic regimen. T2, DWI, and DCE sequences were analyzed and maps were generated for Apparent Diffusion Coefficient (ADC), T2 signal intensity, and the following dynamic parameters: k-trans, peak enhancement, area under curve (AUC), time to maximal enhancement (TME), wash-in rate, and washout rate. Volumetric analysis of these parameters was performed, yielding a histogram analysis including first-order texture kinetics (percentiles, maximum value, minimum value, range, standard deviation, mean, median, mode, skewness, and kurtosis). Finally, correlations between these values and response to NAC (evaluated on the surgical specimen according to RECIST 1.1 criteria) were assessed. Results: Out of 69 tumors, 33 (47.8%) achieved complete pathological response, 26 (37.7%) partial response, and 10 (14.5%) no response. Higher levels of AUCmax (p value = 0.0338), AUCrange (p value = 0.0311), and TME75 (p value = 0.0452) and lower levels of washout10 (p value = 0.0417), washout20 (p value = 0.0138), washout25 (p value = 0.0114), and washout30 (p value = 0.05) were predictive of noncomplete response. Conclusion: Histogram-derived texture analysis of MRI images allows finding quantitative parameters predictive of nonresponse to NAC in women affected by locally advanced BC.

Path selection rules for droplet trains in single-lane microfluidic networks.

We investigate the transport of periodic trains of droplets through microfluidic networks having one inlet, one outlet, and nodes consisting of T junctions. Variations of the dilution of the trains, i.e., the distance between drops, reveal the existence of various hydrodynamic regimes characterized by the number of preferential paths taken by the drops. As the dilution increases, this number continuously decreases until only one path remains explored. Building on a continuous approach used to treat droplet traffic through a single asymmetric loop, we determine selection rules for the paths taken by the drops and we predict the variations of the fraction of droplets taking these paths with the parameters at play including the dilution. Our results show that as dilution decreases, the paths are selected according to the ascending order of their hydrodynamic resistance in the absence of droplets. The dynamics of these systems controlled by time-delayed feedback is complex: We observe a succession of periodic regimes separated by a wealth of bifurcations as the dilution is varied. In contrast to droplet traffic in single asymmetric loops, the dynamical behavior in networks of loops is sensitive to initial conditions because of extra degrees of freedom.

Acidic lipase Lip I.3 from a Pseudomonas fluorescens-like strain displays unusual properties and shows activity on secondary alcohols.

AIMS: Identification, cloning, expression and characterization of a novel lipase--Lip I.3--from strain Pseudomonas CR-611. METHODS AND RESULTS: The corresponding gene was identified and isolated by PCR-amplification, cloned and expressed in Escherichia coli, and purified by refolding from inclusion bodies. Analysis of the deduced amino acid sequence revealed high homology with members of the bacterial lipase family I.3, showing 97% identity to a putative lipase from Pseudomonas fluorescens Pf0-1, and 93% identity to a crystallized extracellular lipase from Pseudomonas sp. MIS38. A typical C-terminal type I secretion signal and several putative Ca(2+) binding sites were also identified. Experimental data confirmed that Lip I.3 requires Ca(2+) ions for correct folding and activity. The enzyme differs from the previously reported family I.3 lipases in optimal pH, being the first acidophilic lipase reported in this family. Furthermore, Lip I.3 shows a strong preference for medium chain fatty acid esters and does not display interfacial activation. When tested for activity on secondary alcohol hydrolysis, Lip I.3 displayed higher efficiency on aromatic alcohols rather than on alkyl alcohols. CONCLUSIONS: A new family I.3 lipase with unusual properties has been isolated, cloned and described. This will contribute to a better knowledge of family I.3 lipases, a family that has been scarcely explored, and that might provide a novel source of biocatalysts. SIGNIFICANCE AND IMPACT OF THE STUDY: The unusual properties shown by Lip I.3 and the finding of activity and enantioselectivity on secondary alcohol esters may contribute to the development of new enzymatic tools for applied biocatalysis.

Nonpalpable breast lesions: preoperative radiological guidance in radioguided occult lesion localisation (ROLL).

PURPOSE: This study evaluated the methods, technical aspects and impact of preoperative radiological guidance in radioguided occult lesion localisation (ROLL) for single nonpalpable breast lesions. MATERIALS AND METHODS: A total of 288 patients underwent ROLL before surgery. Human serum albumin macroaggregates labelled with 3.7-7.4 MBq of technetium(99) were injected into the lesion. In the case of ultrasonographic guidance (221/288 patients), inoculum positioning resulted in a change of echogenicity at the lesion site. In the case of mammographic guidance (67/288 patients), iodinated contrast medium was injected following the radiotracer for subsequent mammographic evaluation. Patients underwent surgery within 24 h from ROLL. A gamma-detecting probe was used to locate the lesion during surgery and guide its removal. After excision, the specimen was examined by either ultrasonography or mammography to verify complete lesion removal before histological evaluation. RESULTS: The lesion was correctly localised in 281/288 patients (97.5%). One ROLL procedure failed because surgery could not be performed within 24 h and the radioactivity decayed. Of the six incorrect localisations, 2 were due to the radiological guidance and 4 to technetium(99) dispersion. CONCLUSIONS: Radiological guidance in ROLL ensured the outcome of the procedure of localisation and removal of single, nonpalpable breast lesions in the majority of cases.

Towards high throughput production of artificial egg oocytes using microfluidics.

The production of micron-size droplets using microfluidic tools offers new opportunities to carry out biological assays in a controlled environment. We apply these strategies by using a flow-focusing microfluidic device to encapsulate Xenopus egg extracts, a biological system recapitulating key events of eukaryotic cell functions in vitro. We present a method to generate monodisperse egg extract-in-oil droplets and use high-speed imaging to characterize the droplet pinch-off dynamics leading to the production of trains of droplets. We use fluorescence microscopy to show that our method does not affect the biological activity of the encapsulated egg extract by observing the self-organization of microtubules and actin filaments, two main biopolymers of the cell cytoskeleton, encapsulated in the produced droplets. We anticipate that this assay might be useful for quantitative studies of biological systems in a confined environment as well as high throughput screenings for drug discovery.

"CADEAT": considerations on the use of CAD (computer-aided diagnosis) in mammography.

Computer-aided diagnosis (CAD) has been extensively reported to increase sensitivity by about 10% when added to a single reading while increasing recall rate by 12%, and its current use can be safely recommended in clinical practice. CAD has been suggested as a possible alternative to conventional double reading in screening. Uncontrolled comparison is consistent and suggests that CAD is comparable to double reading in incremental cancer detection rate (CAD +10.6%, double reading +9.1%) and possibly better in recall rate (CAD +12.5%, double reading +28.8%). However, controlled studies comparing single reading + CAD to conventional double reading are not consistent and on average suggest a lower cancer detection rate (-5.1%) and a lower recall rate (-9.8%) for CAD. Scientific evidence is not sufficient for a safe recommendation of single reading + CAD as a current alternative to conventional double reading.

Complex dynamics of droplet traffic in a bifurcating microfluidic channel: periodicity, multistability, and selection rules.

The binary path selection of droplets reaching a T junction is regulated by time-delayed feedback and nonlinear couplings. Such mechanisms result in complex dynamics of droplet partitioning: numerous discrete bifurcations between periodic regimes are observed. We introduce a model based on an approximation that makes this problem tractable. This allows us to derive analytical formulae that predict the occurrence of the bifurcations between consecutive regimes, establish selection rules for the period of a regime, and describe the evolutions of the period and complexity of droplet pattern in a cycle with the key parameters of the system. We discuss the validity and limitations of our model which describes semiquantitatively both numerical simulations and microfluidic experiments.

Droplet motion in microfluidic networks: Hydrodynamic interactions and pressure-drop measurements.

We present experimental, numerical, and theoretical studies of droplet flows in hydrodynamic networks. Using both millifluidic and microfluidic devices, we study the partitioning of monodisperse droplets in an asymmetric loop. In both cases, we show that droplet traffic results from the hydrodynamic feedback due to the presence of droplets in the outlet channels. We develop a recently-introduced phenomenological model [W. Engl, Phys. Rev. Lett. 95, 208304 (2005)] and successfully confront its predictions to our experimental results. This approach offers a simple way to measure the excess hydrodynamic resistance of a channel filled with droplets. We discuss the traffic behavior and the variations in the corresponding hydrodynamic resistance length L_{d} and of the droplet mobility beta , as a function of droplet interdistance and confinement for channels having circular or rectangular cross sections.

Competition between local collisions and collective hydrodynamic feedback controls traffic flows in microfluidic networks.

By studying the repartition of monodisperse droplets at a simple T junction, we show that the traffic of discrete fluid systems in microfluidic networks results from two competing mechanisms, whose significance is driven by confinement. Traffic is dominated by collisions occurring at the junction for small droplets and by collective hydrodynamic feedback for large ones. For each mechanism, we present simple models in terms of the pertinent dimensionless parameters of the problem.

Indications for breast magnetic resonance imaging. Consensus document "Attualità in senologia", Florence 2007.

The clinical use of breast magnetic resonance (MR) imaging is increasing, especially for applications requiring paramagnetic contrast-agent injection. This document presents a synthetic list of acceptable indications with potential advantages for women according to evidence from the literature and the expert opinion of the panel that developed this statement. We generally recommend that breast MR imaging be performed in centres with experience in conventional breast imaging [mammography and ultrasonography (US)] and needle-biopsy procedures (under stereotactic or US guidance) as well as in breast MR imaging and second-look US for findings not revealed by conventional imaging performed before MR imaging. In our opinion, there is no evidence in favour of breast MR imaging as a diagnostic tool to characterise equivocal findings at conventional imaging when needle-biopsy procedures can be performed, nor for the study of asymptomatic, non-high-risk women with negative conventional imaging. After a description of technical and methodological requirements, we define the indications and limitations of breast MR imaging for surveillance of high-risk women, local staging before surgery, evaluation of the effect of neoadjuvant chemotherapy, breast previously treated for carcinoma, carcinoma of unknown primary syndrome, nipple discharge and breast implants.

What is the sensitivity of mammography and dynamic MR imaging for DCIS if the whole-breast histopathology is used as a reference standard?

PURPOSE: Our purpose was to compare mammography and dynamic contrast-enhanced magnetic resonance imaging (MRI) in the detection of ductal carcinoma in situ (DCIS). MATERIALS AND METHODS: Ninety patients (aged 58.6+/-16.1 years) who were candidates for unilateral (n=81) or bilateral (n=9) mastectomy underwent mammography and dynamic contrast-enhanced breast MRI using a coronal three-dimensional gradient-echo sequence with slice thickness < or =3 mm before and after intravenous injection of gadoteridol (0.1 mmol/kg). Mammographic and MR images were evaluated by two offsite readers working in consensus. Pathological examination performed on 5-mm sections covering the whole breast was used as a reference standard. RESULTS: Out of 99 breasts, pathology revealed 26 DCIS in 14 breasts of 14 patients, aged 52.0 +/- 9.6 years. Lesion diameter at pathology was <5 mm (n=4); > or =5 and <10 mm (n=7); > or =10 and <20 mm (n=3); > or =20 mm (n=2); not assessed (n=10). Sensitivity was 35% (9/26) for mammography and 38% (10/26) for MRI (not significant difference, McNemar test). Both mammography and MRI provided a true positive result in seven cases (four of them measured at pathology, with a diameter of 20.0+/-12.9 mm; median 20 mm) and a false negative result in 14 cases (10 of them measured at pathology, with a diameter of 4.2+/-1.9 mm; median 4.6 mm) (p=0.024, Mann-Whitney U test). Only 46% (12/26) of DCIS were detected at mammography and/or MRI; the remaining 54% (14/26) were diagnosed only at pathological examination. CONCLUSIONS: When the whole breast is used as the histopathological reference standard, both mammography and MRI show low sensitivity for DCIS.

Slow relaxation mode in concentrated oil-in-water microemulsions consisting of repulsive droplets.

The present contribution reports on the observation of two diffusive relaxation modes in a concentrated microemulsion made of repulsive droplets. These two modes can be interpreted in the frame of Weissman's and Pusey's theoretical pioneering works. The fast mode is associated to the collective diffusion of droplets whereas the slow one corresponds to the relaxation of droplet concentration fluctuations associated with composition and/or size. We show that (i) repulsive interactions considerably slow down the latter and (ii) a generalized Stokes Einstein relationship between its coefficient of diffusion and the Newtonian viscosity of the solutions, similar to the Walden's rule for electrolytes, holds for concentrated microemulsion systems made of repulsive droplets.

Selection of two-phase flow patterns at a simple junction in microfluidic devices.

We study the behavior of a confined stream made of two immiscible fluids when it reaches a T junction. Two flow patterns are witnessed: the stream is either directed in only one sidearm, yielding a preferential flow pathway for the dispersed phase, or splits between both. We show that the selection of these patterns is not triggered by the shape of the junction nor by capillary effects, but results from confinement. It can be anticipated in terms of the hydrodynamic properties of the flow. A simple model yielding universal behavior in terms of the relevant adimensional parameters of the problem is presented and discussed.

Study and formation of vesicle systems with low polydispersity index by ultrasound method.

The formation of liposomes with low polydispersity index by application of ultrasounds was investigated considering methodology specifications such as sonication time and sonication power. Phosphatidylcholine (PC) liposomes were formed by the evaporation-hydration method. The vesicles were sonicated using several sonication conditions. The liposomes were then characterized by dynamic light scattering (DLS) and freeze-fracture electron microscopy (FFEM). Correlation functions from DLS were treated by cumulants method and GENDIST to obtain the mean radius and polydispersity index. These calculations allowed to fix an optimal sonication time (3000 s) and a useful interval of ultrasound power between 39 and 91 W. DLS and FFEM results confirmed that vesicle size, lamellarity and the polydispersity index decreased with the increase of sonication power. Thus, we propose a systematic method to form liposomes in which the physical characteristics of the vesicles may be controlled as a function of sonication time and power.

Structural steady states and relaxation oscillations in a two-phase fluid under shear flow: experiments and phenomenological model.

By means of several rheophysics techniques, we report on an extensive study of the couplings between flow and microstructures in a two-phase fluid made of lamellar (L(alpha)) and sponge (L(3)) phases. Depending on the nature of the imposed dynamical parameter (stress or shear rate) and on the experimental conditions (brine salinity or temperature), we observe several different structural steady states consisting of either multilamellar droplets (with or without a long range order) or elongated (L(3)) phase domains. Two different astonishing phenomena, shear-induced phase inversion and relaxation oscillations, are observed. We show that (i) phase inversion is related to a shear-induced topological change between monodisperse multilamellar droplets and elongated structures and (ii) droplet size relaxation oscillations result from a shear-induced change of the surface tension between both coexisting (L(alpha)) and (L(3)) phases. To explain these relaxation oscillations, we present a phenomenological model and compare its numerical predictions to our experimental results.

Smart control of monodisperse Stöber silica particles: effect of reactant addition rate on growth process.

Control over the synthesis of monodisperse silica particles up to mesoscopic scale is generally made difficult due to intrinsic limitation to submicrometric dimensions and secondary nucleation in seeded experiments. To investigate this issue and overcome these difficulties, we have implemented single step processing by quantifying the effects of the progressive addition of a diluted tetraethyl orthosilicate solution in ethanol on the size and monodispersity of silica particles. Contrary to particles grown in seeded polymerization, monodisperse particles with size up to 2 microm were synthesized. Moreover, the particles exhibit a final diameter (d(f)), which varies with V(-1/3) over more than 2 orders of magnitude in rate of addition (V). On the basis of a kinetic study in the presence of addition showing that particle growth is limited by the diffusion of monomer species, we developed a diffusion-limited growth model to theoretically explain the observed d(f)(V) behavior and quantitatively retrieve the measured amplitude and exponent. Using a single parameter procedure, we can therefore predict and generate in the room temperature range, monodisperse particles of a targeted size by simply adjusting the rate of addition.

Can a droplet break up under flow without elongating? Fragmentation of smectic monodisperse droplets.

We study the fragmentation under shear flow of smectic monodisperse droplets at high volume fraction. Using small angle light scattering and optical microscopy, we reveal the existence of a break-up mechanism for which the droplets burst into daughter droplets of the same size. Surprisingly, this fragmentation process, which is strain controlled and occurs homogeneously in the cell, does not require any transient elongation of the droplets. Systematic experiments as a function of the initial droplet size and the applied shear rate show that the rupture is triggered by an instability of the inner droplet structure.

Shear-induced formation of vesicles in membrane phases: kinetics and size selection mechanisms, elasticity versus surface tension.

Multilamellar vesicles can be formed upon shearing lamellar phases (L(alpha)) and phase-separated lamellar-sponge (L(alpha)/L(3)) mixtures. In the first case, the vesicle volume fraction is always 100% and the vesicle size is monitored by elasticity ("onion textures"). In the second system the vesicle volume fraction can be tuned from 0 to 100% and the mean size results from a balance between capillary and viscous forces ("Taylor droplets"). However, despite these differences, in both systems we show that the formation of vesicles is a strain-controlled process monitored by a universal primary buckling instability of the lamellae.