We report on the development of an automated scanning system for nuclear emulsions aiming at very precise spatial and angular measurements. An accuracy of
0.06
μ
m
in position was achieved with the ...emulsion films used for the measurement. An accuracy of 0.4
mrad was achieved for tracks penetrating orthogonally the emulsion films while an accuracy of 1
mrad was obtained for tracks inclined by about 300
mrad with respect to the perpendicular direction. This result shows unprecedented position and angular resolutions achieved by automated measurements.
Two photon fluorescent lifetime imaging is a modality that enables depth-sectioned, molecularly-specific imaging of cells and tissue using intrinsic contrast. However, clinical applications have not ...been well explored due to low imaging speed and limited field of view, which make evaluating large pathology samples extremely challenging. To address these limitations, we have developed direct temporal sampling two photon fluorescent lifetime imaging (DTS-FLIM), a method which enables a several order of magnitude increase in imaging speed by capturing an entire lifetime decay in a single fluorescent excitation. We use this greatly increased speed to perform a preliminary study using gigapixel-scale imaging of human breast pathology surgical specimens.
Mohs surgery uses
frozen section analysis (FSA) with complete margin examination for the excision of select basal cell carcinomas (BCC), obtaining excellent cosmetic outcomes and extremely low ...recurrence rates. However, Mohs with FSA is time-consuming because of the need to iteratively perform cryosectioning on sequential excisions. Fluorescent microscopies can image tissue specimens without requiring physical sectioning, potentially reducing the time to perform Mohs surgery. We demonstrate a protocol for nonlinear microscopy (NLM) imaging of surgical specimens that combines dual agent staining, virtual H&E rendering, and video rate imaging. We also introduce a novel protocol that enables micron-level co-registration of NLM images with FSA histology, and demonstrate that NLM can reproduce similar features similar to FSA in BCC specimens with both negative and positive surgical margins. We show that the fluorescent labels can be extracted with conventional vacuum infiltration processing, enabling subsequent immunohistochemistry on fluorescently labeled tissue. This protocol can also be applied to evaluate the performance of NLM compared with FSA in a wide range of pathologies for intraoperative consultation.
► Search for neutrino radiative decays during 2006 total solar eclipse. ► Analysis of the ashen light image of the Moon. ► Lower lifetime limits improved of about 3 orders of magnitude.
The data ...collected during the 2006 total solar eclipse are analyzed in the search for signals produced by a hypothetical radiative decay of heavy neutrinos. In the absence of the expected light pattern, we extract lower limits for the heavy neutrino components proper lifetime. The present analysis restricts to the direct hierarchy hypothesis (
m
3
≫
m
2
>
m
1). The quality of the data in terms of reached sensitivity suggests that those are the best limits obtainable using this technique.
We present an imaging system based on low coherence interferometric detection of multiply scattered light for extended depth imaging into highly scattering media. By incorporating angle-resolved ...detection, coherence imaging with multiply scattered photons is shown to be both feasible and potentially superior to existing techniques for performing time-resolved measurements of scattered light. Imaging is demonstrated through nearly 100 mean free paths of scattering phantom in a single-ended geometry. The resolution and imaging contrast are compared to those obtained with conventional OCT systems which chiefly detect singly scattered light.
Cells sense cues in their surrounding microenvironment. These cues are converted into intracellular signals and transduced to the nucleus in order for the cell to respond and adapt its function. ...Within the nucleus, structural changes occur that ultimately lead to changes in the gene expression. In this study, we explore the structural changes of the nucleus of human mesenchymal stem cells as an effect of topographical cues. We use a controlled nanotopography to drive shape changes to the cell nucleus, and measure the changes with both fluorescence microscopy and a novel light scattering technique. The nucleus changes shape dramatically in response to the nanotopography, and in a manner dependent on the mechanical properties of the substrate. The kinetics of the nuclear deformation follows an unexpected trajectory. As opposed to a gradual shape change in response to the topography, once the cytoskeleton attains an aligned and elongation morphology on the time scale of several hours, the nucleus changes shape rapidly and intensely.
The ability to histologically assess surgical specimens in real-time is a long-standing challenge in cancer surgery, including applications such as breast conserving therapy (BCT). Up to 40% of women ...treated with BCT for breast cancer require a repeat surgery due to postoperative histological findings of close or positive surgical margins using conventional formalin fixed paraffin embedded histology. Imaging technologies such as nonlinear microscopy (NLM), combined with exogenous fluorophores can rapidly provide virtual H&E imaging of surgical specimens without requiring microtome sectioning, facilitating intraoperative assessment of margin status. However, the large volume of typical surgical excisions combined with the need for rapid assessment, make comprehensive cellular resolution margin assessment during surgery challenging. To address this limitation, we developed a multiscale, real-time microscope with variable magnification NLM and real-time, co-registered position display using a widefield white light imaging system. Margin assessment can be performed rapidly under operator guidance to image specific regions of interest located using widefield imaging. Using simulated surgical margins dissected from human breast excisions, we demonstrate that multi-centimeter margins can be comprehensively imaged at cellular resolution, enabling intraoperative margin assessment. These methods are consistent with pathology assessment performed using frozen section analysis (FSA), however NLM enables faster and more comprehensive assessment of surgical specimens because imaging can be performed without freezing and cryo-sectioning. Therefore, NLM methods have the potential to be applied to a wide range of intra-operative applications.
We have implemented multispectral multiple scattering low coherence interferometry (ms2/LCI) with Fourier domain data collection. The ms2/LCI system is designed to localize features with ...spectroscopic contrast with millimeter resolution up to 1 cm deep in scattering samples by using photons that have undergone multiple low-angle (forward) scattering events. Fourier domain detection both increases the data acquisition speed of the system and gives access to rich spectroscopic information, compared to the previous single channel, time-domain implementation. Separate delivery and detection angular apertures reduce collection of the diffuse background signal in order to isolate localized spectral features from deeper in scattering samples than would be possible with traditional spectroscopic optical coherence tomography. Light from a supercontinuum source is used to acquire absorption spectra of chromophores in the visible range within a tissue-like scattering phantom. An intensity modulation and digital lock-in detection scheme is implemented to mitigate relative intensity and spectral noise inherent in supercontinuum sources. The technical parameters of the system and comparative analysis are presented.
The energy spectrum of neutrino-induced upward-going muons in MACRO has been analysed in terms of relativity principles violating effects, keeping standard mass-induced atmospheric neutrino ...oscillations as the dominant source of νμ→ντ transitions. The data disfavor these exotic possibilities even at a subdominant level, and stringent 90% C.L. limits are placed on the Lorentz invariance violation parameter |Δv|<6×10−24 at sin2θv=0 and |Δv|<2.5–5×10−26 at sin2θv=±1. These limits can also be re-interpreted as upper bounds on the parameters describing violation of the equivalence principle.
CAKE (Cosmic Abundances below Knee Energies) was a prototype balloon experiment for the determination of the charge spectra and abundances of the primary cosmic rays (CR) with
Z
>
10. It was a ...passive instrument made of layers of CR39® and Lexan®/Makrofol® nuclear track detectors; it had a geometric acceptance of ∼0.7
m
2
sr for Fe nuclei. Here, the scanning and analysis strategies, the algorithms used for the off-line filtering and for the tracking in automated mode of the primary cosmic rays are presented, together with the resulting CR charge distribution and their abundances.
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