Review of optical breast imaging and spectroscopy

Diffuse optical imaging and spectroscopy of the female breast is an area of active research. We review the present status of this field and discuss the broad range of methodologies and applications. Starting with a brief overview on breast physiology, the remodeling of vasculature and extracellular matrix caused by solid tumors is highlighted that is relevant for contrast in optical imaging. Then, the various instrumental techniques and the related methods of data analysis and image generation are described and compared including multimodality instrumentation, fluorescence mammography, broadband spectroscopy, and diffuse correlation spectroscopy. We review the clinical results on functional properties of malignant and benign breast lesions compared to host tissue and discuss the various methods to improve contrast between healthy and diseased tissue, such as enhanced spectroscopic information, dynamic variations of functional properties, pharmacokinetics of extrinsic contrast agents, including the enhanced permeability and retention effect. We discuss research on monitoring neoadjuvant chemotherapy and on breast cancer risk assessment as potential clinical applications of optical breast imaging and spectroscopy. Moreover, we consider new experimental approaches, such as photoacoustic imaging and long-wavelength tissue spectroscopy

Implementation of the extended Kalman filter for determining the optical and geometrical properties of turbid layered media by time-resolved single distance measurements

In this article we propose an implementation of the extended Kalman filter (EKF) for the retrieval of optical and geometrical properties in two-layered turbid media assuming a dynamic setting, where absorption of each layer was changed in different steps. Prior works implemented the EKF in frequency-domain with several pairs of light sources and detectors and for static parameters estimation problems. Here we explore the use of the EKF in single distance, time-domain measurements, together with a corresponding forward model. Results show good agreement between retrieved and nominal values, with rather narrow analytical credibility intervals, indicating that the recovery process has low uncertainty, especially for the absorption coefficients.Fil: Baez, Guido Rodrigo. 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: García, Héctor Alfredo. 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: Grosenick, Dirk. Physikalisch-technische Bundesanstalt; AlemaniaFil: Wabnitz, Heidrun. Physikalisch-technische Bundesanstalt; Alemani

Acute effects of ferumoxytol on regulation of renal hemodynamics and oxygenation

The superparamagnetic iron oxide nanoparticle ferumoxytol is increasingly used as intravascular contrast agent in magnetic resonance imaging (MRI). This study details the impact of ferumoxytol on regulation of renal hemodynamics and oxygenation. In 10 anesthetized rats, a single intravenous injection of isotonic saline (used as volume control) was followed by three consecutive injections of ferumoxytol to achieve cumulative doses of 6, 10, and 41 mg Fe/kg body mass. Arterial blood pressure, renal blood flow, renal cortical and medullary perfusion and oxygen tension were continuously measured. Regulation of renal hemodynamics and oxygenation was characterized by dedicated interventions: brief periods of suprarenal aortic occlusion, hypoxia, and hyperoxia. None of the three doses of ferumoxytol resulted in significant changes in any of the measured parameters as compared to saline. Ferumoxytol did not significantly alter regulation of renal hemodynamics and oxygenation as studied by aortic occlusion and hypoxia. The only significant effect of ferumoxytol at the highest dose was a blunting of the hyperoxia-induced increase in arterial pressure. Taken together, ferumoxytol has only marginal effects on the regulation of renal hemodynamics and oxygenation. This makes ferumoxytol a prime candidate as contrast agent for renal MRI including the assessment of renal blood volume fraction

Multi-laboratory performance assessment of diffuse optics instruments: the BitMap exercise

SIGNIFICANCE: Multi-laboratory initiatives are essential in performance assessment and standardization-crucial for bringing biophotonics to mature clinical use-to establish protocols and develop reference tissue phantoms that all will allow universal instrument comparison. AIM: The largest multi-laboratory comparison of performance assessment in near-infrared diffuse optics is presented, involving 28 instruments and 12 institutions on a total of eight experiments based on three consolidated protocols (BIP, MEDPHOT, and NEUROPT) as implemented on three kits of tissue phantoms. A total of 20 synthetic indicators were extracted from the dataset, some of them defined here anew. APPROACH: The exercise stems from the Innovative Training Network BitMap funded by the European Commission and expanded to include other European laboratories. A large variety of diffuse optics instruments were considered, based on different approaches (time domain/frequency domain/continuous wave), at various stages of maturity and designed for different applications (e.g., oximetry, spectroscopy, and imaging). RESULTS: This study highlights a substantial difference in hardware performances (e.g., nine decades in responsivity, four decades in dark count rate, and one decade in temporal resolution). Agreement in the estimates of homogeneous optical properties was within 12% of the median value for half of the systems, with a temporal stability of <5  %   over 1 h, and day-to-day reproducibility of <3  %  . Other tests encompassed linearity, crosstalk, uncertainty, and detection of optical inhomogeneities. CONCLUSIONS: This extensive multi-laboratory exercise provides a detailed assessment of near-infrared Diffuse optical instruments and can be used for reference grading. The dataset-available soon in an open data repository-can be evaluated in multiple ways, for instance, to compare different analysis tools or study the impact of hardware implementations

Visual Information Alone Changes Behavior and Physiology during Social Interactions in a Cichlid Fish (Astatotilapia burtoni)

Social behavior can influence physiological systems dramatically yet the sensory cues responsible are not well understood. Behavior of male African cichlid fish, Astatotilapia burtoni, in their natural habitat suggests that visual cues from conspecifics contribute significantly to regulation of social behavior. Using a novel paradigm, we asked whether visual cues alone from a larger conspecific male could influence behavior, reproductive physiology and the physiological stress response of a smaller male. Here we show that just seeing a larger, threatening male through a clear barrier can suppress dominant behavior of a smaller male for up to 7 days. Smaller dominant males being “attacked” visually by larger dominant males through a clear barrier also showed physiological changes for up to 3 days, including up-regulation of reproductive- and stress-related gene expression levels and lowered plasma 11-ketotestesterone concentrations as compared to control animals. The smaller males modified their appearance to match that of non-dominant males when exposed to a larger male but they maintained a physiological phenotype similar to that of a dominant male. After 7 days, reproductive- and stress- related gene expression, circulating hormone levels, and gonad size in the smaller males showed no difference from the control group suggesting that the smaller male habituated to the visual intruder. However, the smaller male continued to display subordinate behaviors and assumed the appearance of a subordinate male for a full week despite his dominant male physiology. These data suggest that seeing a larger male alone can regulate the behavior of a smaller male but that ongoing reproductive inhibition depends on additional sensory cues. Perhaps, while experiencing visual social stressors, the smaller male uses an opportunistic strategy, acting like a subordinate male while maintaining the physiology of a dominant male

The Function of Anal Fin Egg-Spots in the Cichlid Fish Astatotilapia burtoni

Color and pigmentation patterns of animals are often targets of sexual selection because of their role in communication. Although conspicuous male traits are typically implicated with intersexual selection, there are examples where sex-specific displays play a role in an intrasexual context, e.g. when they serve as signals for aggression level and/or status. Here, we focus on the function of a conspicuous male ornament in the most species-rich tribe of cichlid fishes, the haplochromines. A characteristic feature of these ca. 1500 species are so-called egg-spots in form of ovoid markings on the anal fins of males, which are made up of carotenoid based pigment cells. It has long been assumed that these yellow, orange or reddish egg-spots play an important role in the courtship and spawning behavior of these maternal mouth-brooding fishes by mimicking the eggs of a conspecific female. The exact function of egg-spots remains unknown, however, and there are several hypotheses about their mode of action. To uncover the function of this cichlid-specific male ornament, we used female mate choice experiments and a male aggression test in the haplochromine species Astatotilapia burtoni. We manipulated the number and arrangement of egg-spots on the anal fins of males, or removed them entirely, and tested (1) female preference with visual contact only using egg-traps, (2) female preference with free contact using paternity testing with microsatellites and (3) male aggression. We found that females did not prefer males with many egg-spots over males with fewer egg-spots and that females tended to prefer males without egg-spots over males with egg-spots. Importantly, males without egg-spots sired clutches with the same fertilization rate as males with egg-spots. In male aggression trials, however, males with fewer egg-spots received significantly more attacks, suggesting that egg-spots are an important signal in intrasexual communication

Short and long-term photostability of 3D printed fluorescent phantoms for near-infrared diffuse optical imaging

We have successfully printed an anatomically shaped hand model with properties similar to in vivo investigations with a fluorescence hand imager using indocyanine green (ICG). By adding the fluorescent dye Lumogen IR 765, titanium dioxide powder and black ink to a 3D printing methacrylate photopolymer we realized phantoms with physiologically relevant absorption and reduced scattering coefficients as well as fluorescence properties similar to the widely applied contrast agent ICG. The phantoms show an excellent long-term photostability making them well suited for device performance monitoring and comparison. In contrast, fluorescence of phantoms printed with ICG continuously decreases over time

A systematic study on fluorescence contrast in near infrared diffuse transmittance imaging with indocyanine green

Near infrared fluorescence imaging is a sensitive, noninvasive technique for diagnostic applications in biomedical optics. The main purpose of this work is thus to explore how to improve the contrast of images obtained by near infrared light using a fluorescent extrinsic agent. Among different fluorophores, indocyanine green has been mostly studied because it is approved for use in humans. In this work, simulations and experimental studies on phantoms (systems that optically emulate biological tissues) are used to systematically investigate the influence of the increased intrinsic tissue absorption by adding indocyanine green. The experiments reproduce the situation of fluorescence imaging of carcinomas in the human breast, where the natural absorption due to neovascularization is increased by the injection of this fluorophore. Assuming measurements in transmission geometry, the breast is modeled by a homogeneous background medium containing a tumor-like inclusion (or lesion) with two- or threefold increased absorption. Fluorescence contrast is simulated over a broad range of dye concentrations using diffusion theory. Selected concentrations ratios are applied in experimental studies with laser excitation of indocyanine green fluorescence and with a charge-coupled device camera for fluorescence detection. Both simulations and experiments show that the intrinsic absorption of the inclusion strongly reduces the number of detected fluorescence photons and that the fluorescence contrast can be canceled or become even negative. It was found that for typical optical properties and geometrical conditions, in fluorescence imaging of breast cancer, a dye ratio of about 10:1 (lesion:background) is required to turn from negative to positive fluorescence contrast. Since such a high ratio is difficult to attain, raw fluorescence images need to be normalized by the intrinsic lesion absorption (without indocyanine green (ICG)) to enhance the presence of the dye in the lesion.Fil: Waks Serra, María Victoria. 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: Grosenick, Dirk. Physikalisch Technische Bundesanstalt; AlemaniaFil: Macdonald, Rainer. Physikalisch Technische Bundesanstalt; AlemaniaFil: 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: 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; Argentin