Fast 3D Near-infrared breast imaging using indocyanine green for detection and characterization of breast lesions.

PURPOSE: To evaluate fast 3D near-infrared breast imaging using the optical contrast agent indocyanine green (ICG) for the detection and characterization of breast lesions. MATERIALS AND METHODS: 30 patients with suspicious breast lesions on mammography and/or ultrasound underwent fast 2 Hz 3D optical mammography before, during, and after administration of a 25 mg ICG bolus prior to needle biopsy. The bolus kinetics is analyzed using two perfusion parameters and a derived parameter: "peak amplitude" (PA), "time-to-peak" (TTP) and "peak-time grouped amplitude" (PTA). A receiver operating characteristic curve (ROC) analysis was performed to define a PTA cut-off for reader-independent differentiation of benign and malignant lesions. 8 patients had to be excluded from data analysis. Overall 14 breasts bearing a malignant lesion, 8 breasts bearing a benign lesion and 3 healthy breasts were analyzed. RESULTS: The cut-off-based PTA analysis allowed correct detection for 12 of 14 malignant lesions (tumor size: 8 - 80 mm; sensitivity = 85.7 %). Two malignant lesions were missed. In the benign study group only one fibroadenoma was detected (specificity = 87.5 %). The PTA values differed significantly between the benign group and the malignant group (Mann-Whitney U-test, p < 0.05). Breasts with malignant lesions showed higher peaks at early time-points in ICG perfusion. CONCLUSION: Early perfusion analysis of ICG-enhanced 3D fast optical mammography revealed different enhancement patterns for benign and malignant lesions. This approach might help with the detection of malignant breast lesions and the differentiation from benign lesions.

Biocompatible surfactants for water-in-fluorocarbon emulsions.

Drops of water-in-fluorocarbon emulsions have great potential for compartmentalizing both in vitro and in vivo biological systems; however, surfactants to stabilize such emulsions are scarce. Here we present a novel class of fluorosurfactants that we synthesize by coupling oligomeric perfluorinated polyethers (PFPE) with polyethyleneglycol (PEG). We demonstrate that these block copolymer surfactants stabilize water-in-fluorocarbon oil emulsions during all necessary steps of a drop-based experiment including drop formation, incubation, and reinjection into a second microfluidic device. Furthermore, we show that aqueous drops stabilized with these surfactants can be used for in vitro translation (IVT), as well as encapsulation and incubation of single cells. The compatability of this emulsion system with both biological systems and polydimethylsiloxane (PDMS) microfluidic devices makes these surfactants ideal for a broad range of high-throughput, drop-based applications.

Pulsed photothermal radiometry as a method for investigating blood vessel-like structures.

Pulsed photothermal radiometry (PPTR) is known to be suitable for in vivo investigations of tissue optical properties. As a noncontact, nondestructive method it is a very attractive candidate for on-line dosimetry of laser treatments that rely on thermal laser-tissue interaction. In this article, we extend the one-dimensional (1D) analytical formalism that has widely been used to describe PPTR signals to a two-dimensional treatment of a simplified model of a blood vessel. This approach leads to quantitative description of a PPTR signal that, unlike in an 1D treatment, not only shows changes in time, but also varies in space. Using this approach, we are able to gain instructive understanding on how target characteristics of a blood vessel-like structure influence such a spatiotemporal PPTR signal. Likewise, the ability of extracting target features from those measurements is evaluated. Subsequently, we present experimental realization of the idealized model of a blood vessel as used in our theory. Comparison of actual PPTR measurements with theoretical predictions allow vessel localization laterally and in depth. Using our setup, we furthermore demonstrate the influence of flow inside the vessel on the measured signal.

Optical tomographic imaging of dynamic features of dense-scattering media.

Methods used in optical tomography have thus far proven to produce images of complex target media (e.g., tissue) having, at best, relatively modest spatial resolution. This presents a challenge in differentiating artifact from true features. Further complicating such efforts is the expectation that the optical properties of tissue for any individual are largely unknown and are likely to be quite variable due to the occurrence of natural vascular rhythms whose amplitudes are sensitive to a host of autonomic stimuli that are easily induced. We recognize, however, that rather than frustrating efforts to validate the accuracy of image features, the time-varying properties of the vasculature can be exploited to aid in such efforts, owing to the known structure-dependent frequency response of the vasculature and to the fact that hemoglobin is a principal contrast feature of the vasculature at near-infrared wavelengths. To accomplish this, it is necessary to generate a time series of image data. In this report we have tested the hypothesis that through analysis of time-series data, independent contrast features can be derived that serve to validate, at least qualitatively, the accuracy of imaging data, in effect establishing a self-referencing scheme. A significant finding is the observation that analysis of such data can produce high-contrast images that reveal features that are mainly obscured in individual image frames or in time-averaged image data. Given the central role of hemoglobin in tissue function, this finding suggests that a wealth of new features associated with vascular dynamics can be identified from the analysis of time-series image data.

Instrumentation and calibration protocol for imaging dynamic features in dense-scattering media by optical tomography.

Instrumentation is described that is suitable for acquiring multisource, multidetector, time-series optical data at high sampling rates (up to 150 Hz) from tissues having arbitrary geometries. The design rationale, calibration protocol, and measured performance features are given for both a currently used, CCD-camera-based instrument and a new silicon-photodiode-based system under construction. Also shown are representative images that we reconstructed from data acquired in laboratory studies using the described CCD-based instrument.