Micro-imaging of Brain Cancer Radiation Therapy Using Phase-contrast Computed Tomography

Barbone, Giacomo E.; Bravin, A.; Romanelli, Pantaleo; Mittone, Alberto; Bucci, Domenico; Gaaβ, Thomas; Duc, Géraldine Le; Auweter, Sigrid; Reiser, Maximilian; Kraiger, Markus; Angelis, Martin Hrabé de; Battaglia, Giuseppe; Coan, Paola

doi:10.1016/j.ijrobp.2018.03.063

Cited by 23 publications

(21 citation statements)

References 76 publications

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“…The histological appearance of the 9LGS tumor in untreated rats was consistent with that in published descriptions 20,39 . Tumors were not encapsulated with locally invasive margins ( Fig.…”

Section: Results Cell Response To Broad Synchrotron Radiation Firstsupporting

confidence: 89%

Toward personalized synchrotron microbeam radiation therapy

Engels

Davis

et al. 2020

Sci Rep

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Synchrotron facilities produce ultra-high dose rate X-rays that can be used for selective cancer treatment when combined with micron-sized beams. Synchrotron microbeam radiation therapy (MRT) has been shown to inhibit cancer growth in small animals, whilst preserving healthy tissue function. However, the underlying mechanisms that produce successful MRT outcomes are not well understood, either in vitro or in vivo. this study provides new insights into the relationships between dosimetry, radiation transport simulations, in vitro cell response, and pre-clinical brain cancer survival using intracerebral gliosarcoma (9LGS) bearing rats. As part of this groundbreaking research, a new image-guided MRT technique was implemented for accurate tumor targeting combined with a pioneering assessment of tumor dose-coverage; an essential parameter for clinical radiotherapy. Based on the results of our study, we can now (for the first time) present clear and reproducible relationships between the in vitro cell response, tumor dose-volume coverage and survival post MRT irradiation of an aggressive and radioresistant brain cancer in a rodent model. our innovative and interdisciplinary approach is illustrated by the results of the first long-term MRT pre-clinical trial in Australia. Implementing personalized synchrotron MRT for brain cancer treatment will advance this international research effort towards clinical trials.

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Section: Results Cell Response To Broad Synchrotron Radiation Firstsupporting

confidence: 89%

Toward personalized synchrotron microbeam radiation therapy

Engels

Davis

et al. 2020

Sci Rep

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“…Comparisons with classical SEM have also shown not only a perfect tissue preservation after microCT sessions but also a straightforward correspondence in co-registration analyses between the two techniques. This assessment ensures the reliability of this new technique as standard procedure in brain microstructural studies [6,20].…”

Section: Discussionmentioning

confidence: 84%

Chronic pain alters microvascular architectural organization of somatosensory cortex

Zippo

Grosso

Patera

et al. 2019

Preprint

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Chronic pain (CP) represents a complex pathology profoundly involving both neural and glial compartments of the central nervous system. While most CP studies have also investigated the macroscopic brain vascular system, its microstructural architecture still remains largely unexplored. Further, the adaptive modifications of the vascular microstructure as consequence of diseases or pathological insults did not receive adequate attention. Here we show microtomographic signs of diffuse and conspicuous microvascular neogenesis in somatosensory cortex of CP animal models already peaking at 15 days from the model instantiation.Progressive fading of this microvessel neogenesis then ensued in the next six months yet maintaining higher vascular density with a preserved small fraction of them. Due to the important consequences on the neuronglial-vessel arrangements and on the resulting metabolic and functional disorders of the local networks, novel additional scenarios of CP are thus conceivable with profound consequences of potential future CP diagnostic and therapeutic appraisals. Significance StatementChronic pain (CP) is an excruciating condition with various clinical presentations. Major signs are characterized by a rich repertoire of pain quality, intensity and length. While neuronal and glial anomalies have been associated to CP less attention has been granted to the micro-vessel and capillary compartments of the involved brain regions. Our research illustrates how the microvessel compartments of the somatosensory cortex in experimental animals present profound and long-lasting signs of extensive neogenesis (about fourfold) early within the first two weeks from the CP start, undergoing a slow and incomplete decline within six months. These results may change the CP clinical picture with potential novel therapeutic approaches to it. IntroductionAt the level of the central nervous system, Chronic Pain (CP) displays a cohort of signs and symptoms, where the percept of pain dominates within a complex morpho-functional background of anomalous neuronal and glial events. These appear variously combined and causative of a global, maladaptive condition. At large scales, brain regional anomalous activations in CP patients 1-3 , as shown by functional neuroimaging, are seemingly accompanied by metabolic dysfunctions and local macrostructural signs such as cortical thickness reductions or cortical laminar misalignments 4 . At lower cell-level scales, CP-related functional disorders have been described, in the past, mostly as gangliar, spinal or central neuronal dynamic irregularities 5-8 .These mainly included spontaneous hyper-or hypo-activities, hyper-responsiveness to non-noxious and noxious stimuli, anomalous spiking patterns, often accompanied by variable signs of local neuronal degeneration and by cortical somatotopic mapping readjustments of sensory projection fields. These signs appeared complementary and ascribed to perceptual conditions such as spontaneous pain, allodynia and hyperalgesia. A step forward was then envi...

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“…Tissue alterations in different disease states, for example neuronal loss and vascular alterations in a multiple sclerosis model (Cedola et al, 2017), or plaque formation in Alzheimer's disease models (Astolfo et al, 2016;Massimi et al, 2019) have also been addressed. This technique was also applied to ex vivo whole brain scans in view of brain tissue morphology for both normal and cancerous tissue, before and after x-ray microbeam radiation therapy (Barbone et al, 2018). A study conducted by Saiga et al (2019) evaluated the brain and spinal cord of mice with autoimmune encephalomyelitis by x-ray µCT using synchrotron radiation, demonstrating that the spinal cord of animals affected by this condition had a pronounced tissue inflammation portrayed by the observed dilated vessels and vacuolization, the latter also being found in the cerebellum (Saiga et al, 2019).…”

Section: Phase-contrast Microtomographymentioning

confidence: 99%

Illuminating the Brain With X-Rays: Contributions and Future Perspectives of High-Resolution Microtomography to Neuroscience

et al. 2021

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The assessment of three-dimensional (3D) brain cytoarchitecture at a cellular resolution remains a great challenge in the field of neuroscience and constant development of imaging techniques has become crucial, particularly when it comes to offering direct and clear obtention of data from macro to nano scales. Magnetic resonance imaging (MRI) and electron or optical microscopy, although valuable, still face some issues such as the lack of contrast and extensive sample preparation protocols. In this context, x-ray microtomography (μCT) has become a promising non-destructive tool for imaging a broad range of samples, from dense materials to soft biological specimens. It is a new supplemental method to be explored for deciphering the cytoarchitecture and connectivity of the brain. This review aims to bring together published works using x-ray μCT in neurobiology in order to discuss the achievements made so far and the future of this technique for neuroscience.

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Micro-imaging of Brain Cancer Radiation Therapy Using Phase-contrast Computed Tomography

Cited by 23 publications

References 76 publications

Toward personalized synchrotron microbeam radiation therapy

Toward personalized synchrotron microbeam radiation therapy

Chronic pain alters microvascular architectural organization of somatosensory cortex

Illuminating the Brain With X-Rays: Contributions and Future Perspectives of High-Resolution Microtomography to Neuroscience

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