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Bioscience Reports Oct 2023Radiotherapy is utilised in the treatment of ∼50% of all human cancers, which predominantly employs photon radiation. However, particle radiotherapy elicits... (Review)
Review
Radiotherapy is utilised in the treatment of ∼50% of all human cancers, which predominantly employs photon radiation. However, particle radiotherapy elicits significant benefits over conventional photons due to more precise dose deposition and increased linear energy transfer (LET) that generates an enhanced therapeutic response. Specifically, proton beam therapy (PBT) and carbon ion radiotherapy (CIRT) are characterised by a Bragg peak, which generates a low entrance radiation dose, with the majority of the energy deposition being defined within a small region which can be specifically targeted to the tumour, followed by a low exit dose. PBT is deemed relatively low-LET whereas CIRT is more densely ionising and therefore high LET. Despite the radiotherapy type, tumour cell killing relies heavily on the introduction of DNA damage that overwhelms the repair capacity of the tumour cells. It is known that DNA damage complexity increases with LET that leads to enhanced biological effectiveness, although the specific DNA repair pathways that are activated following the different radiation sources is unclear. This knowledge is required to determine whether specific proteins and enzymes within these pathways can be targeted to further increase the efficacy of the radiation. In this review, we provide an overview of the different radiation modalities and the DNA repair pathways that are responsive to these. We also provide up-to-date knowledge of studies examining the impact of LET and DNA damage complexity on DNA repair pathway choice, followed by evidence on how enzymes within these pathways could potentially be therapeutically exploited to further increase tumour radiosensitivity, and therefore radiotherapy efficacy.
Topics: Humans; DNA Damage; Radiation, Ionizing; Neoplasms; Photons; Radiation Tolerance
PubMed: 37695845
DOI: 10.1042/BSR20222586 -
Angewandte Chemie (International Ed. in... Dec 2023To interrogate neural circuits and crack their codes, in vivo brain activity imaging must be combined with spatiotemporally precise stimulation in three dimensions using...
To interrogate neural circuits and crack their codes, in vivo brain activity imaging must be combined with spatiotemporally precise stimulation in three dimensions using genetic or pharmacological specificity. This challenge requires deep penetration and focusing as provided by infrared light and multiphoton excitation, and has promoted two-photon photopharmacology and optogenetics. However, three-photon brain stimulation in vivo remains to be demonstrated. We report the regulation of neuronal activity in zebrafish larvae by three-photon excitation of a photoswitchable muscarinic agonist at 50 pM, a billion-fold lower concentration than used for uncaging, and with mid-infrared light of 1560 nm, the longest reported photoswitch wavelength. Robust, physiologically relevant photoresponses allow modulating brain activity in wild-type animals with spatiotemporal and pharmacological precision. Computational calculations predict that azobenzene-based ligands have high three-photon absorption cross-section and can be used directly with pulsed infrared light. The expansion of three-photon pharmacology will deeply impact basic neurobiology and neuromodulation phototherapies.
Topics: Animals; Zebrafish; Photons; Infrared Rays; Ligands
PubMed: 37823736
DOI: 10.1002/anie.202311181 -
Advanced Science (Weinheim,... Oct 2023Super-resolution optical imaging tools are crucial in microbiology to understand the complex structures and behavior of microorganisms such as bacteria, fungi, and...
Super-resolution optical imaging tools are crucial in microbiology to understand the complex structures and behavior of microorganisms such as bacteria, fungi, and viruses. However, the capabilities of these tools, particularly when it comes to imaging pathogens and infected tissues, remain limited. MicroMagnify (µMagnify) is developed, a nanoscale multiplexed imaging method for pathogens and infected tissues that are derived from an expansion microscopy technique with a universal biomolecular anchor. The combination of heat denaturation and enzyme cocktails essential is found for robust cell wall digestion and expansion of microbial cells and infected tissues without distortion. µMagnify efficiently retains biomolecules suitable for high-plex fluorescence imaging with nanoscale precision. It demonstrates up to eightfold expansion with µMagnify on a broad range of pathogen-containing specimens, including bacterial and fungal biofilms, infected culture cells, fungus-infected mouse tone, and formalin-fixed paraffin-embedded human cornea infected by various pathogens. Additionally, an associated virtual reality tool is developed to facilitate the visualization and navigation of complex 3D images generated by this method in an immersive environment allowing collaborative exploration among researchers worldwide. µMagnify is a valuable imaging platform for studying how microbes interact with their host systems and enables the development of new diagnosis strategies against infectious diseases.
Topics: Humans; Animals; Mice; Microscopy; Bacteria; Optical Imaging
PubMed: 37658522
DOI: 10.1002/advs.202302249 -
Physics in Medicine and Biology Jul 2023In photon counting detectors (PCDs), electric pulses induced by two or more x-ray photons can pile up and result in count losses when their temporal separation is less...
In photon counting detectors (PCDs), electric pulses induced by two or more x-ray photons can pile up and result in count losses when their temporal separation is less than the detector dead time. The correction of pulse pile-up-induced count loss is particularly difficult for paralyzable PCDs since a given value of recorded counts can correspond to two different values of true photon interactions. In contrast, charge (energy) integrating detectors work by integrating collected electric charge induced by x-rays over time and do not suffer from pile-up losses. This work introduces an inexpensive readout circuit element to the circuits of PCDs to simultaneously collect time-integrated charge to correct pile-up-induced count losses.Prototype electronics were constructed to collect time-integrated charges simultaneously with photon counts. A splitter was used to feed the electric signal in parallel to both a digital counter and a charge integrator. After recording PCD counts and integrating collected charge, a lookup table can be generated to map raw counts in the total- and high-energy bins and total charge to estimate pile-up-free true counts. Proof-of-concept imaging experiments were performed with a CdTe-based PCD array to test this method.The proposed electronics successfully recorded photon counts and time-integrated charge simultaneously, and whereas photon counts exhibited paralyzable pulse pile-up, time-integrated charge using the same electric signal as the counts measurement was linear with x-ray flux. With the proposed correction, paralyzable PCD counts became linear with input flux for both total- and high-energy bins. At high flux levels, uncorrected post-log measurements of PMMA objects severely overestimated radiological path lengths for both energy bins. After the proposed correction, the non-monotonic measurements again became linear with flux and accurately represented the true radiological path lengths. No impact on the spatial resolution was observed after the proposed correction in images of a line-pair test pattern.Time-integrated charge can be used to correct for pulse pile-up in paralyzable PCDs where analytical solutions may be difficult to use, and integrated charge can be collected simultaneously with counts using inexpensive electronics.
Topics: Cadmium Compounds; Photons; Tellurium; Quantum Dots
PubMed: 37379858
DOI: 10.1088/1361-6560/ace2a9 -
Nature Communications Dec 2023Biomolecular condensates serve as membrane-less compartments within cells, concentrating proteins and nucleic acids to facilitate precise spatial and temporal...
Biomolecular condensates serve as membrane-less compartments within cells, concentrating proteins and nucleic acids to facilitate precise spatial and temporal orchestration of various biological processes. The diversity of these processes and the substantial variability in condensate characteristics present a formidable challenge for quantifying their molecular dynamics, surpassing the capabilities of conventional microscopy. Here, we show that our single-photon microscope provides a comprehensive live-cell spectroscopy and imaging framework for investigating biomolecular condensation. Leveraging a single-photon detector array, single-photon microscopy enhances the potential of quantitative confocal microscopy by providing access to fluorescence signals at the single-photon level. Our platform incorporates photon spatiotemporal tagging, which allowed us to perform time-lapse super-resolved imaging for molecular sub-diffraction environment organization with simultaneous monitoring of molecular mobility, interactions, and nano-environment properties through fluorescence lifetime fluctuation spectroscopy. This integrated correlative study reveals the dynamics and interactions of RNA-binding proteins involved in forming stress granules, a specific type of biomolecular condensates, across a wide range of spatial and temporal scales. Our versatile framework opens up avenues for exploring a broad spectrum of biomolecular processes beyond the formation of membrane-less organelles.
Topics: Microscopy; Biomolecular Condensates; Proteins; Nucleic Acids; Spectrometry, Fluorescence
PubMed: 38086853
DOI: 10.1038/s41467-023-43969-7 -
Indian Journal of Pathology &... Apr 2024
Topics: Humans; Histocytochemistry; Male; Microscopy; Female
PubMed: 38817157
DOI: 10.4103/ijpm.ijpm_1124_21 -
RoFo : Fortschritte Auf Dem Gebiete Der... Aug 2023Photon-counting computed tomography (PCCT) is a promising new technology with the potential to fundamentally change today's workflows in the daily routine and to provide... (Review)
Review
BACKGROUND
Photon-counting computed tomography (PCCT) is a promising new technology with the potential to fundamentally change today's workflows in the daily routine and to provide new quantitative imaging information to improve clinical decision-making and patient management.
METHOD
The content of this review is based on an unrestricted literature search on PubMed and Google Scholar using the search terms "Photon-Counting CT", "Photon-Counting detector", "spectral CT", "Computed Tomography" as well as on the authors' experience.
RESULTS
The fundamental difference with respect to the currently established energy-integrating CT detectors is that PCCT allows counting of every single photon at the detector level. Based on the identified literature, PCCT phantom measurements and initial clinical studies have demonstrated that the new technology allows improved spatial resolution, reduced image noise, and new possibilities for advanced quantitative image postprocessing.
CONCLUSION
For clinical practice, the potential benefits include fewer beam hardening artifacts, radiation dose reduction, and the use of new contrast agents. In this review, we will discuss basic technical principles and potential clinical benefits and demonstrate first clinical use cases.
KEY POINTS
· Photon-counting computed tomography (PCCT) has been implemented in the clinical routine. · Compared to energy-integrating detector CT, PCCT allows the reduction of electronic image noise. · PCCT provides increased spatial resolution and a higher contrast-to-noise ratio. · The novel detector technology allows the quantification of spectral information.
CITATION FORMAT
· Stein T, Rau A, Russe MF et al. Photon-Counting Computed Tomography - Basic Principles, Potenzial Benefits, and Initial Clinical Experience. Fortschr Röntgenstr 2023; 195: 691 - 698.
Topics: Humans; Tomography, X-Ray Computed; Photons; Phantoms, Imaging
PubMed: 36863367
DOI: 10.1055/a-2018-3396 -
Journal of Biomedical Optics Sep 2023Hyperspectral microscopy grants the ability to characterize unique properties of tissues based on their spectral fingerprint. The ability to label and measure multiple...
SIGNIFICANCE
Hyperspectral microscopy grants the ability to characterize unique properties of tissues based on their spectral fingerprint. The ability to label and measure multiple molecular probes simultaneously provides pathologists and oncologists with a powerful tool to enhance accurate diagnostic and prognostic decisions. As the pathological workload grows, having an objective tool that provides companion diagnostics is of immense importance. Therefore, fast whole-slide spectral imaging systems are of immense importance for automated cancer prognostics that meet current and future needs.
AIM
We aim to develop a fast and accurate hyperspectral microscopy system that can be easily integrated with existing microscopes and provide flexibility for optimizing measurement time versus spectral resolution.
APPROACH
The method employs compressive sensing (CS) and a spectrally encoded illumination device integrated into the illumination path of a standard microscope. The spectral encoding is obtained using a compact liquid crystal cell that is operated in a fast mode. It provides time-efficient measurements of the spectral information, is modular and versatile, and can also be used for other applications that require rapid acquisition of hyperspectral images.
RESULTS
We demonstrated the acquisition of breast cancer biopsies hyperspectral data of the whole camera area within . This means that a typical biopsy can be measured in . The hyperspectral images with 250 spectral bands are reconstructed from 47 spectrally encoded images in the spectral range of 450 to 700 nm.
CONCLUSIONS
CS hyperspectral microscopy was successfully demonstrated on a common lab microscope for measuring biopsies stained with the most common stains, such as hematoxylin and eosin. The high spectral resolution demonstrated here in a rather short time indicates the ability to use it further for coping with the highly demanding needs of pathological diagnostics, both for cancer diagnostics and prognostics.
Topics: Microscopy; Physical Phenomena; Biopsy; Coloring Agents; Data Compression; Neoplasms
PubMed: 37692564
DOI: 10.1117/1.JBO.28.9.096502 -
Nature Communications Feb 2024Microwave photonics aims to overcome the limitations of radiofrequency devices and systems by leveraging the unique properties of optics in terms of low loss and power...
Microwave photonics aims to overcome the limitations of radiofrequency devices and systems by leveraging the unique properties of optics in terms of low loss and power consumption, broadband operation, immunity to interference and tunability. This enables versatile functions like beam steering, crucial in emerging applications such as the Internet of Things (IoT) and 5/6G networks. The main problem with current photonic beamforming architectures is that there is a tradeoff between resolution and bandwidth, which has not yet been solved. Here we propose and experimentally demonstrate a novel switched optical delay line beamformer architecture that is capable of achieving the desired maximum resolution (i.e., 2 pointing angles for M-bit coding) and provides broadband operation simultaneously. The concept is demonstrated by means of a compact (8 × 3 mm) 8 (5-bit) delay line Silicon Photonic chip implementation capable of addressing 32 pointing angles and offering 20 GHz bandwidth operation.
PubMed: 38365826
DOI: 10.1038/s41467-024-45743-9 -
PloS One 2023Optical microscopy is frequently used to visualize microrobotic agents (i.e., micro-agents) and physical surroundings with a relatively high spatio-temporal resolution....
Optical microscopy is frequently used to visualize microrobotic agents (i.e., micro-agents) and physical surroundings with a relatively high spatio-temporal resolution. However, the limited penetration depth of optical microscopy techniques used in microrobotics (in the order of 100 μm) reduces the capability of visualizing micro-agents below biological tissue. Two-photon microscopy is a technique that exploits the principle of two-photon absorption, permitting live tissue imaging with sub-micron resolution and optical penetration depths (over 500 μm). The two-photon absorption principle has been widely applied to fabricate sub-millimeter scale components via direct laser writing (DLW). Yet, its use as an imaging tool for microrobotics remains unexplored in the state-of-the-art. This study introduces and reports on two-photon microscopy as an alternative technique for visualizing micro-agents below biological tissue. In order to validate two-photon image acquisition for microrobotics, two-type micro-agents are fabricated and employed: (1) electrospun fibers stained with an exogenous fluorophore and (2) bio-inspired structure printed with autofluorescent resin via DLW. The experiments are devised and conducted to obtain three-dimensional reconstructions of both micro-agents, perform a qualitative study of laser-tissue interaction, and visualize micro-agents along with tissue using second-harmonic generation. We experimentally demonstrate two-photon microscopy of micro-agents below formalin-fixed tissue with a maximum penetration depth of 800 μm and continuous imaging of magnetic electrospun fibers with one frame per second acquisition rate (in a field of view of 135 × 135 μm2). Our results show that two-photon microscopy can be an alternative imaging technique for microrobotics by enabling visualization of micro-agents under in vitro and ex ovo conditions. Furthermore, bridging the gap between two-photon microscopy and the microrobotics field has the potential to facilitate in vivo visualization of micro-agents.
Topics: Microscopy, Fluorescence, Multiphoton; Imaging, Three-Dimensional; Photons; Fluorescent Dyes
PubMed: 37561749
DOI: 10.1371/journal.pone.0289725