A method for preprocessing and classifying fluorescence measurements to distinguish tumorous from healthy tissue is proposed, as 5-ALA fluorescence-guided surgery, effective for high-grade gliomas, is less useful for low-grade gliomas without visible fluorescence. (c) 2025 The Author(s)

We present a computational approach for hyperspectral computational Selective Plane Illumination Microscopy (SPIM), offering fast 3D imaging with reduced photobleaching. Inspired by Hadamard spectroscopy, our method employs structured light sheets via a digital micromirror device. A data-driven reconstruction strategy, implemented through an end-to-end trained neural network, demonstrates robust performance under varying noise levels. Leveraging non-negative least squares minimization, we obtain component maps, exemplifying applications such as autofluorescence removal in transgenic zebrafish and discrimination of closely matched red proteins. Our findings showcase the potential of computational strategies to advance hyperspectral SPIM in photonic research.

Diffuse low-grade gliomas are infiltrative tumors whose margins are not distinguishable from the adjacent healthy brain parenchyma. The aim was to precisely examine the results provided by the intraoperative use of macroscopic fluorescence in diffuse low-grade gliomas and to describe the new fluorescence-based techniques capable of guiding the resection of low-grade gliomas. Only about 20% and 50% of low-grade gliomas are macroscopically fluorescent after 5-amino-levulinic acid (5-ALA) or fluorescein sodium intake, respectively. However, 5-ALA is helpful for detecting anaplastic foci, and thus choosing the best biopsy targets in diffuse gliomas. Spectroscopic detection of 5-ALA-induced fluorescence can detect very low and non-macroscopically visible concentrations of protoporphyrin IX, a 5-ALA metabolite, and, consequently, has excellent performances for the detection of low-grade gliomas. Moreover, these tumors have a specific spectroscopic signature with two fluorescence emission peaks, which is useful for distinguishing them not only from healthy brain but also from high-grade gliomas. Confocal laser endomicroscopy can generate intraoperative optic biopsies, but its sensitivity remains limited. In the future, the coupled measurement of autofluorescence and induced fluorescence, and the introduction of fluorescence detection technologies providing a wider field of view could result in the development of operator-friendly tools implementable in the operative routine.

We describe a computational hyperspectral microscope based on a structured light sheet that is generated using a digital micromirror device only. To reduce the acquisition time, we consider a small number of structured patterns. We solve the resulting inverse problem using an unrolled deep neural network, which limits the loss of spatial resolution.

Optical imaging has become an invaluable tool in life science. Among the variety of available techniques, selective plane illumination microscopy (SPIM) allows for fast (x,y,z) imaging of fluorescent samples with reduced photobleaching. SPIM directly acquire the (x,y) slice corresponding to a thin light sheet that illuminates the sample, while the third spatial dimension is scanned. Promoted by the open source SPIM project, many designs variants are now available. This enables the study of various samples such as fly embryos, zebrafish embryos and others. The study of multi-labeled specimens implies to unmix the fluorophores, which usually relies on optical filters. As most of the light is rejected, this approach has a major drawback, as a large amount of information is lost (e.g., fluorophores with overlapping spectra cannot be unmixed). Therefore, there is a need for 3D imagers with hyperspectral capabilities, which can exploit the full-emission spectrum of a fluorescent sample. We will describe a computational hyperspectral light sheet microscope inspired from Hadamard spectroscopy. We generate structured light sheets using a digital micromirror device and focus the fluorescence signal onto the entrance slit of an imaging spectrometer. Then, we reconstruct the full hypercube from the raw data acquired for multiple structured light patterns. Our technique enjoys excellent spectral resolution and allows resolving overlapping fluorophores with up to nanometer resolution. Furthermore, the Hadamard patterns used for illumination allow maximizing the collected signal compared to previous hyperspectral SPIM setups. To reduce the acquisition time, we consider undersampled measurements for which we will present reconstruction results obtained using an algorithm based on a deep convolutional network.

Instrumentation for on-line monitoring of hadrontherapy treatments Localization of the dose deposited in the patient is a key point for the hadrontherapy cancer treatment. Different modalities of on-line control are explored, motivating acquisition systems and detectors developments, such as a Compton gamma camera, a proton trajectometer and a beam hodoscope.

Gliomas are infiltrative brain tumors with a margin difficult to identify. 5-ALA induced PpIX fluorescence measurements are a clinical standard, but expert-based classification models still lack sensitivity and specificity. Here a fully automatic clustering method is proposed to discriminate glioma margin. This is obtained from spectroscopic fluorescent measurements acquired with a recently introduced intraoperative set up. We describe a data-driven selection of best spectral features and show how this improves results of margin prediction from healthy tissue by comparison with the standard biomarker-based prediction. This pilot study based on 10 patients and 50 samples shows promising results with a best performance of 77% of accuracy in healthy tissue prediction from margin tissue.

The two-photon excited fluorescence (TPEF) cross-section of Protoporphyrin IX (PpIX) in solution is determined at different excitation wavelengths. Maxima observed at 620 and 634 nm are associated with two different forms of PpIX already observed in one-photon excited fluorescence studies. In order to further provide insights into these two forms, first hyperpolarizabilities are also reported for these two forms with corresponding depolarization ratio further demonstrating the existence of specific symmetry differences. The static and the frequency dependent first hyperpolarizability were also calculated using Gaussian 09 and compared to the experimental data. This work shows that PpIX can exhibit two forms that might be targeted in applications like oncology clinical agents.

Gliomas are diffuse brain tumors still hardly curable due to the difficulties to identify margins. 5-ALA induced PpIX fluorescence measurements enable to gain in sensitivity but are still limited to discriminate margin from healthy tissue. In this fluorescence spectroscopic study, we compare an expert-based model assuming that two states of PpIX contribute to total fluorescence and machine learning-based models. We show that machine learning retrieves the main features identified by the expert approach. We also show that machine learning approach slightly overpasses expert-based model for the identification of healthy tissues. These results might help to improve fluorescence-guided resection of gliomas by discriminating healthy tissues from tumor margins.

Biopolymers represent natural, renewable and abundant materials. Their use is steadily growing in various areas (food, health, building.) but, in lithography, despite some works, resists, solvents and developers are still oil-based and hazardous chemicals. In this work, we replaced synthetic resist by chitosan, a natural, abundant and hydrophilic polysaccharide. High resolution sub-micron patterns were obtained through chitosan films as water developable, chemically unmodified, positive tone mask resist for an eco-friendly electron beam and deep-UV (193 nm) lithography process. Sub-micron patterns were also successfully obtained using a 248 nm photomasker thanks to the addition of bio-sourced photoactivator, riboflavin. Patterns were then transferred by plasma etching into silica even for high resolution patterns.

We report the use of the Second Harmonic Generation response from a riboflavin doped chitosan film as a characterization method of the film morphology. This film is of particular interest in the development of new and bio-sourced material for eco-friendly UV lithography. The method allows us to determine how riboflavin is distributed as a function of film depth in the sample. This possibility is of importance in order to have a better understanding of the riboflavin influence in chitosan films during the lithography process. On the contrary, linear optical techniques provide no information beyond the mere confirmation of the riboflavin presence.

Ion beam therapy enables a highly accurate dose conformation delivery to the tumor due to the finite range of charged ions in matter (i.e. Bragg peak (BP)). Consequently, the dose profile is very sensitive to patients anatomical changes as well as minor mispositioning, and so it requires improved dose control techniques. Proton interaction vertex imaging (IVI) could offer an online range control in carbon ion therapy. In this paper, a statistical method was used to study the sensitivity of the IVI technique on experimental data obtained from the Heidelberg Ion-Beam Therapy Center. The vertices of secondary protons were reconstructed with pixelized silicon detectors. The statistical study used the [Formula: see text] test of the reconstructed vertex distributions for a given displacement of the BP position as a function of the impinging carbon ions. Different phantom configurations were used with or without bone equivalent tissue and air inserts. The inflection points in the fall-off region of the longitudinal vertex distribution were computed using different methods, while the relation with the BP position was established. In the present setup, the resolution of the BP position was about 4-5 mm in the homogeneous phantom under clinical conditions (106 incident carbon ions). Our results show that the IVI method could therefore monitor the BP position with a promising resolution in clinical conditions.

The transmission of protons in planar channeling or in the regime of crystal reflection in bent crystals is now routinely used at high energy. We used the property that channeling critical angle increases as the incident particle momentum decreases, to explore the region of moderate energies (100MeV–1GeV). Indeed, such energies are particularly interesting since medical applications such as particle therapy have to face the constraints of being compatible with hospital-based accelerators. Therefore, replacing tens- or even hundreds-tons gantries by bent crystals would – if feasible – meet societal applications.

Light leaking from a bent optical fiber shares many properties with synchrotron radiation : in ray optics, both lights are emitted tangentially to a light cylinder; in wave optics, the emission mechanism involves a tunnel effect. The angular distributions of these two radiations are studied in parallel and found to be similar. The same is done for the impact parameter distributions. The latter show interference fringes of the Airy function type. The far field escaped from the fiber is calculated with the Volume Current Method. An optical system observing the impact parameter profile is proposed.

Purpose:The purpose of this study was to experimentally assess the possibility to monitor carbon ion range variations—due to tumor shift and/or elongation or shrinking—using prompt‐gamma (PG) emission with inhomogeneous phantoms. Such a study is related to the development of PG monitoring techniques to be used in a carbon ion therapy context.Methods:A 95 MeV/u carbon ion beam was used to irradiate phantoms with a variable density along the ion path to mimic the presence of bone and lung in homogeneous humanlike tissue. PG profiles were obtained after a longitudinal scan of the phantoms. A setup comprising a narrow single‐slit collimator and two detectors placed at 90° with respect to the beam axis was used. The time of flight technique was applied to allow the selection between PG and background events.Results:Using the positions at 50% entrance and 50% falloff of the PG profiles, a quantity called prompt‐gamma profile length (PGPL) is defined. It is possible to observe shifts in the PGPL when there are absolute ion range shifts as small as 1–2 mm. Quantitatively, for an ion range shift of −1.33 ± 0.46 mm (insertion of a Teflon slab), a PGPL difference of −1.93 ± 0.58 mm and −1.84 ± 1.27 mm is obtained using a BaF2 and a NaI(Tl) detector, respectively. In turn, when an ion range shift of 4.59 ± 0.42 mm (insertion of a lung‐equivalent material slab) is considered, the difference is of 4.10 ± 0.54 and 4.39 ± 0.80 mm for the same detectors.Conclusions:Herein, experimental evidence of the usefulness of employing PG to monitor carbon ion range using inhomogeneous phantoms is presented. Considering the homogeneous phantom as reference, the results show that the information provided by the PG emission allows for detecting ion range shifts as small as 1–2 mm. When considering the expected PG emission from an energy slice in a carbon ion therapy scenario, the experimental setup would allow to retrieve the same PGPL as the high statistics of the full experimental dataset in 58% of the times. However, this success rate increases to 93% when using a better optimized setup by means of Monte Carlo simulations.

This paper gives a short review of the past and recent activities of the Atomic Collisions in Solids Lyon-group, in collaboration with other groups, in the field of high energy channelling. The ion-channelling programme was performed at GANIL-Caen and at GSI-Darmstadt. The electron-channelling programme started at ALS-Saclay for relativistic incident energies and was then extended to SPS-CERN for ultra-relativistic energies. The last part of this paper presents the electron-channelling experiments performed originally at ALS-Saclay, then at BTF-Frascati and more recently at LS-Saga, in order to observe the electron “internal clock” predicted in 1924 by L. de Broglie.