Abstract-Label-Free Observation of Micrometric Inhomogeneity of Human Breast Cancer Cell Density Using Terahertz Near-Field Microscopy

 

Kosuke Okada, Quentin Cassar, Hironaru Murakami, Gaëtan MacGrogan , Jean-Paul Guillet, Patrick Mounaix, Masayoshi Tonouchi, Kazunori Serita

https://www.mdpi.com/2304-6732/8/5/151

Terahertz-light imaging is attracting great attention as a new approach in non-invasive/non-staining biopsy of cancerous tissues. Positively, terahertz light has been shown to be sensitive to the cell density, the hydration content, and the chemical composition of biological samples. However, the spatial resolution of terahertz imaging is typically limited to several millimeters, making it difficult to apply the technology to image biological tissues which have sub-terahertz-wavelength-scale inhomogeneity. For overcoming the resolution, we have recently developed a terahertz near-field microscope with a spatial resolution of 10 µm, named scanning point terahertz source (SPoTS) microscope. In contrast to conventional far-field terahertz techniques, this microscope features the near-field interactions between samples and point terahertz sources on a sub-terahertz-wavelength scale. Herein, to evaluate the usefulness of terahertz imaging in cancer tissue biopsy in greater detail, we performed terahertz near-field imaging of a paraffin-embedded human-breast-cancer section having sub-terahertz-wavelength-scale inhomogeneity of the cancer cell density using the SPoTS microscope. The observed terahertz images successfully visualized local (~250 µm) inhomogeneities of the cell density in breast invasive ductal carcinoma. These results may bypass the terahertz limitation in terms of spatial resolution and may further motivate the application of terahertz light to cancer tissue biopsy.

Abstract-Terahertz refractive index-based morphological dilation for breast carcinoma delineation

 

Quentin Cassar, Samuel Caravera, Gaëtan MacGrogan, Thomas Bücher, Philipp Hillger, Ullrich Pfeiffer, Thomas Zimmer, Jean-Paul Guillet,  Patrick Mounaix

https://www.nature.com/articles/s41598-021-85853-8

This paper reports investigations led on the combination of the refractive index and morphological dilation to enhance performances towards breast tumour margin delineation during conserving surgeries. The refractive index map of invasive ductal and lobular carcinomas were constructed from an inverse electromagnetic problem. Morphological dilation combined with refractive index thresholding was conducted to classify the tissue regions as malignant or benign. A histology routine was conducted to evaluate the performances of various dilation geometries associated with different thresholds. It was found that the combination of a wide structuring element and high refractive index was improving the correctness of tissue classification in comparison to other configurations or without dilation. The method reports a sensitivity of around 80% and a specificity of 82% for the best case. These results indicate that combining the fundamental optical properties of tissues denoted by their refractive index with morphological dilation may open routes to define supporting procedures during breast-conserving surgeries.

Abstract-Guided terahertz pulse reflectometry with double photoconductive antenna

Mingming Pan, Quentin Cassar, Frédéric Fauquet, Georges Humbert, Patrick Mounaix, and Jean-Paul Guillet

https://www.osapublishing.org/ao/abstract.cfm?uri=ao-59-6-1641

Developments toward the implementation of a terahertz pulse imaging system within a guided reflectometry configuration are reported. Two photoconductive antennas patterned on the same LT-GaAs active layer in association with a silica pipe hollow-core waveguide allowed us to obtain a guided optics-free imager. Besides working in a pulsed regime, the setup does not require additional optics to focus and couple the terahertz pulses into the waveguide core, simplifying the global implementation in comparison with other reported guided terahertz reflectometry systems. The system is qualified for imaging purposes by means of a 1951 USAF resolution test chart. An image resolution, after a 53 mm propagation length, by about 0.707 LP/mm over the 400–550 GHz integrated frequency band, was obtained, thus providing a promising basis to pursue efforts toward compact guided pulse imagers for sample inspection within the terahertz range.

© 2020 Optical Society of America

Abstract-Terahertz pulse time-domain holography method for phase imaging of breast tissue

Nikolay S. Balbekin, Quentin Cassar,  Olga A. Smolyanskaya, Maksim S. Kulya,  Nikolay V. Petrov,  Gaetan MacGrogan,  Jean-Paul Guillet,  Patrick Mounaix,  Valery V. Tuchin, 

https://www.spiedigitallibrary.org/conference-proceedings-of-spie/10887/108870G/Terahertz-pulse-time-domain-holography-method-for-phase-imaging-of/10.1117/12.2508711.short?SSO=1

Pulse holographic imaging along with time-domain spectroscopy scan and tomographic techniques are of great interest. Since the advantages of holography are the lack of focusing optics and high spatial resolution, and, comparing with tomography, less computation cost for numerical reconstruction, this technique is preferable for the analysis of thin histological samples. In this work we have created the experimental scheme that involves measurement of diffraction pattern of the collimated THz pulse field spatial distribution at some distance behind the object in the time-domain mode, thus allowing reconstruction of amplitude and phase distribution at the object plane by numerical backpropagation of the wavefront in the spectral domain. In our experiment, we used a breast biopsy sample containing cancer tissues, we also performed numerical simulations accounting for experimental conditions to confirm the conceptual applicability of the reconstruction method.

Abstract-Terahertz Spectroscopy and Quantum Mechanical Simulations of Crystalline Copper-Containing Historical Pigments

Elyse M. Kleist, Corinna L. Koch Dandolo, Jean-Paul Guillet, Patrick Mounaix,Timothy M. Korter,

https://pubs.acs.org/doi/10.1021/acs.jpca.8b11676

Terahertz spectroscopy, a non-invasive and non-destructive analytical technique used in art conservation and restoration, can provide compelling data concerning the composition and condition of culturally valuable and historical objects. Terahertz spectral databases of modern and ancient artists’ pigments exist, but lack explanations for the origins of the unique spectral features. Solid-state density functional theory simulations can provide insight into the molecular and intermolecular forces that dominate the observed absorption features, as well as reveal deviations from simple harmonic vibrational behavior that can complicate these spectra. The characteristic terahertz spectra of solid azurite, malachite, and verdigris are presented here, along with simulations of their crystalline structures and sub-3.0 THz lattice vibrations. The powerful combination of theory and experiment enables unambiguous spectral assignment of these complex materials and highlights the challenges that anharmonic peak broadening in organic-containing materials may present in the construction of reference pigment databases.

Abstract-Terahertz frequency modulated continuous wave imaging advanced data processing for art painting analysis

Corinna L. Koch Dandolo, Jean-Paul Guillet, Xue Ma, Frédéric Fauquet, Marie Roux, and Patrick Mounaix

https://www.osapublishing.org/oe/abstract.cfm?uri=oe-26-5-5358

Reflection terahertz frequency modulated continuous waves scanner (300 GHz) has been proficiently optimized for imaging two easel paintings of different age. The information content of the obtained THz images has been fully inspected by selecting the appropriate THz image parameter. At the same time, a new data processing has been developed for improving the level of detail held by the axial parametric THz images by means of Gaussian fit of the reflected signals. By carefully weighting the reflected signals as a function of the optical path, the reflected amplitude has been corrected for the positioning of the object surface with respect to the beam focal point. The artifact affecting the THz images recorded from an uneven painting surface have been resolved and the obtained images fairly represent to the original painting.

© 2018 Optical Society of America under the terms of the OSA Open Access Publishing Agreement

Abstract-Art Painting Diagnostic Before Restoration with Terahertz and Millimeter Waves

Jean-Paul Guillet, M. Roux, K. Wang, X. Ma, F. Fauquet, H. Balacey, B. Recur, F. Darracq, P. Mounaix
http://link.springer.com/article/10.1007/s10762-017-0358-1

Art painting diagnostic is commonly performed using electromagnetic waves at wavelengths from terahertz to X-ray. These former techniques are essential in conservation and art history research, but they could be also very useful for restoring artwork. While most studies use time domain imaging technique, in this study, a painting has been investigated using both time domain imaging (TDI) and frequency-modulated continuous wave (FMCW) system in the millimeter frequency range. By applying these systems to a painting of the eighteenth century, we detect and analyze the structure of some defects. This study underlines the differences between FMCW and TDI. We present the advantages and disadvantages of each technique on a real artwork.

Abstract-Room temperature Si–Ti thermopile THz sensor

• Sofiane Ben Mbarek, 
• Sébastien Euphrasie, 
• Thomas Baron, 
• Laurent Thiery, 
• Pascal Vairac, 
• Danick Briand,
• Jean-Paul Guillet, 
• Laurent Chusseau

http://link.springer.com/article/10.1007/s00542-014-2252-2

In this paper, we present the conception, fabrication and characterization of a thermopile designed to detect terahertz electromagnetic fields at room temperature. The thermopile is made of four doped silicon/titanium thermocouples. The absorber consists of a metallic grid made of titanium, deposited at the same time as the metal part of the thermocouples. The design of the grid is based on a theoretical multilayer model using equivalent resistivity and taking into account small diffraction effects. The grid is deposited on a 2.4 mm × 2.4 mm silicon nitride square membrane. The time constant of the sensor is measured at 0.3 THz to be 10 ms, which is consistent with finite elements simulations. The responsivity is evaluated at 4.8 μV/(W m−2). Due to a large impedance, which leads to a large Johnson noise, the noise equivalent power is 1.5 × 10−6 W Hz−1/2.