Academic literature on the topic 'FUS imaging'
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Journal articles on the topic "FUS imaging"
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Hugon, Gaëlle, Sébastien Goutal, Ambre Dauba, Louise Breuil, Benoit Larrat, Alexandra Winkeler, Anthony Novell, and Nicolas Tournier. "[18F]2-Fluoro-2-deoxy-sorbitol PET Imaging for Quantitative Monitoring of Enhanced Blood-Brain Barrier Permeability Induced by Focused Ultrasound." Pharmaceutics 13, no. 11 (October 20, 2021): 1752. http://dx.doi.org/10.3390/pharmaceutics13111752.
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Focused ultrasound in combination with microbubbles (FUS) provides an effective means to locally enhance the delivery of therapeutics to the brain. Translational and quantitative imaging techniques are needed to noninvasively monitor and optimize the impact of FUS on blood-brain barrier (BBB) permeability in vivo. Positron-emission tomography (PET) imaging using [18F]2-fluoro-2-deoxy-sorbitol ([18F]FDS) was evaluated as a small-molecule (paracellular) marker of blood-brain barrier (BBB) integrity. [18F]FDS was straightforwardly produced from chemical reduction of commercial [18F]2-deoxy-2-fluoro-D-glucose. [18F]FDS and the invasive BBB integrity marker Evan’s blue (EB) were i.v. injected in mice after an optimized FUS protocol designed to generate controlled hemispheric BBB disruption. Quantitative determination of the impact of FUS on the BBB permeability was determined using kinetic modeling. A 2.2 ± 0.5-fold higher PET signal (n = 5; p < 0.01) was obtained in the sonicated hemisphere and colocalized with EB staining observed post mortem. FUS significantly increased the blood-to-brain distribution of [18F]FDS by 2.4 ± 0.8-fold (VT; p < 0.01). Low variability (=10.1%) of VT values in the sonicated hemisphere suggests reproducibility of the estimation of BBB permeability and FUS method. [18F]FDS PET provides a readily available, sensitive and reproducible marker of BBB permeability to noninvasively monitor the extent of BBB disruption induced by FUS in vivo.
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Bastiancich, Chiara, Samantha Fernandez, Florian Correard, Anthony Novell, Benoit Larrat, Benjamin Guillet, and Marie-Anne Estève. "Molecular Imaging of Ultrasound-Mediated Blood-Brain Barrier Disruption in a Mouse Orthotopic Glioblastoma Model." Pharmaceutics 14, no. 10 (October 19, 2022): 2227. http://dx.doi.org/10.3390/pharmaceutics14102227.
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Glioblastoma (GBM) is an aggressive and malignant primary brain tumor. The blood-brain barrier (BBB) limits the therapeutic options available to tackle this incurable tumor. Transient disruption of the BBB by focused ultrasound (FUS) is a promising and safe approach to increase the brain and tumor concentration of drugs administered systemically. Non-invasive, sensitive, and reliable imaging approaches are required to better understand the impact of FUS on the BBB and brain microenvironment. In this study, nuclear imaging (SPECT/CT and PET/CT) was used to quantify neuroinflammation 48 h post-FUS and estimate the influence of FUS on BBB opening and tumor growth in vivo. BBB disruptions were performed on healthy and GBM-bearing mice (U-87 MG xenograft orthotopic model). The BBB recovery kinetics were followed and quantified by [99mTc]Tc-DTPA SPECT/CT imaging at 0.5 h, 3 h and 24 h post-FUS. The absence of neuroinflammation was confirmed by [18F]FDG PET/CT imaging 48 h post-FUS. The presence of the tumor and its growth were evaluated by [68Ga]Ga-RGD2 PET/CT imaging and post-mortem histological analysis, showing that tumor growth was not influenced by FUS. In conclusion, molecular imaging can be used to evaluate the time frame for systemic treatment combined with transient BBB opening and to test its efficacy over time.
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Xu, Zhouyang, Samuel Pichardo, and Bingbing Cheng. "Enhancement of brain hyperthermia via transcranial magnetic resonance imaging-guided focused ultrasound and microbubbles—Heating mechanism investigation using COMSOL." Journal of the Acoustical Society of America 154, no. 4_supplement (October 1, 2023): A279. http://dx.doi.org/10.1121/10.0023523.
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Noninvasive methods for enhancing the brain drug delivery has been pursued for years. Previously we developed a new MR-guided focused ultrasound (FUS)-based technique, which can achieve targeted brain hyperthermia for heat-triggered drug release and simultaneously open the blood–brain barrier safely for drug penetration. However, the underline mechanisms were unclear. This study aimed to explore the mechanisms for the enhanced FUS brain tissue hyperthermia with microbubbles via numerical modeling in COMSOL. The acoustic wave equation was employed to describe the FUS propagation. A bubble dynamics equation was adopted for calculating the stable bubble oscillations under FUS exposures. A modified bioheat transfer equation was utilized to compute the heating, with various heating sources including FUS, microbubble acoustic emission (MAE), and viscous dissipation (VD). The microbubbles were randomly distributed within the focal region. The sonication time was 6s with an initial temperature of 41°C. The average temperature in the focal region were 41.65°C, 42.24°C, 42.98°C, and 43.59°C for FUS alone, FUS + MAE, FUS + VD, and FUS + MAE + VD, respectively. Compared with the FUS alone, both MAE and VD made significant contributions to the heating with additional temperature increases of 47.6% and 67.2%, respectively.
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Xu, Lu, Yan Gong, Chih-Yen Chien, and Hong Chen. "Shaveless focused-ultrasound-induced blood-brain barrier opening in mice." Journal of the Acoustical Society of America 153, no. 3_supplement (March 1, 2023): A140. http://dx.doi.org/10.1121/10.0018435.
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To demonstrate that focused ultrasound-induced blood-brain barrier opening (FUS-BBBO) in mice can be achieved without shaving hairs. We performed FUS-BBBO in mice by using oil as the coupling medium without shaving hairs. The hydrophobic nature of oil leads to a higher affinity to hair than water-based ultrasound gel. FUS-BBBO outcome was compared under three conditions: “oil + hairs,” “gel + hairs,” and “gel + no hairs.” T2-weighted, T1-weighted MRI, and fluorescence imaging of the ex vivo brain slices were performed to measure the quality of coupling and outcome of FUS-BBBO. Results showed that “oil + hairs” consistently achieved high-quality acoustic coupling without trapping air bubbles (Figures A & B). FUS-BBBO outcome was not significantly different between the “oil + hairs” group and the “gel + no hairs” group based on T1-weighted MRI (Figures C & D) and ex vivo fluorescence imaging (Figure E). The FUS-BBBO efficiencies for both the “oil + hairs” and “gel + no hairs” groups were significantly higher than the “gel + hairs” group. This study demonstrated that FUS-BBBO in mice could be achieved without shaving hairs. Oil provides a simple solution for achieving effective acoustic coupling for transcranial FUS procedures.
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Wang, Tony R., Aaron E. Bond, Robert F. Dallapiazza, Aaron Blanke, David Tilden, Thomas E. Huerta, Shayan Moosa, Francesco U. Prada, and W. Jeffrey Elias. "Transcranial magnetic resonance imaging–guided focused ultrasound thalamotomy for tremor: technical note." Neurosurgical Focus 44, no. 2 (February 2018): E3. http://dx.doi.org/10.3171/2017.10.focus17609.
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Although the use of focused ultrasound (FUS) in neurosurgery dates to the 1950s, its clinical utility was limited by the need for a craniotomy to create an acoustic window. Recent technological advances have enabled efficient transcranial delivery of US. Moreover, US is now coupled with MRI to ensure precise energy delivery and monitoring. Thus, MRI-guided transcranial FUS lesioning is now being investigated for myriad neurological and psychiatric disorders. Among the first transcranial FUS treatments is thalamotomy for the treatment of various tremors. The authors provide a technical overview of FUS thalamotomy for tremor as well as important lessons learned during their experience with this emerging technology.
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Gagliardo, Cesare, Roberto Cannella, Costanza D’Angelo, Patrizia Toia, Giuseppe Salvaggio, Paola Feraco, Maurizio Marrale, et al. "Transcranial Magnetic Resonance Imaging-Guided Focused Ultrasound with a 1.5 Tesla Scanner: A Prospective Intraindividual Comparison Study of Intraoperative Imaging." Brain Sciences 11, no. 1 (January 4, 2021): 46. http://dx.doi.org/10.3390/brainsci11010046.
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Background: High-quality intraoperative imaging is needed for optimal monitoring of patients undergoing transcranial MR-guided Focused Ultrasound (tcMRgFUS) thalamotomy. In this paper, we compare the intraoperative imaging obtained with dedicated FUS-Head coil and standard body radiofrequency coil in tcMRgFUS thalamotomy using 1.5-T MR scanner. Methods: This prospective study included adult patients undergoing tcMRgFUS for treatment of essential tremor. Intraoperative T2-weighted FRFSE sequences were acquired after the last high-energy sonication using a dedicated two-channel FUS-Head (2ch-FUS) coil and body radiofrequency (body-RF) coil. Postoperative follow-ups were performed at 48 h using an eight-channel phased-array (8ch-HEAD) coil. Two readers independently assessed the signal-to-noise ratio (SNR) and evaluated the presence of concentric lesional zones (zone I, II and III). Intraindividual differences in SNR and lesional findings were compared using the Wilcoxon signed rank sum test and McNemar test. Results: Eight patients underwent tcMRgFUS thalamotomy. Intraoperative T2-weighted FRFSE images acquired using the 2ch-FUS coil demonstrated significantly higher SNR (R1 median SNR: 10.54; R2: 9.52) compared to the body-RF coil (R1: 2.96, p < 0.001; R2: 2.99, p < 0.001). The SNR was lower compared to the 48-h follow-up (p < 0.001 for both readers). Intraoperative zone I and zone II were more commonly visualized using the 2ch-FUS coil (R1, p = 0.031 and p = 0.008, R2, p = 0.016, p = 0.008), without significant differences with 48-h follow-up (p ≥ 0.063). The inter-reader agreement was almost perfect for both SNR (ICC: 0.85) and lesional findings (k: 0.82–0.91). Conclusions: In the study population, the dedicated 2ch-FUS coil significantly improved the SNR and visualization of lesional zones on intraoperative imaging during tcMRgFUS performed with a 1.5-T MR scanner.
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Soloukey, S., E. Collée, L. Verhoef, D. D. Satoer, C. M. F. Dirven, E. M. Bos, J. W. Schouten, et al. "P15.07.B FUNCTIONAL BRAIN MAPPING DURING AWAKE TUMOR RESECTIONS USING ESM-FMRI CO-REGISTERED FUNCTIONAL ULTRASOUND (FUS)-IMAGING." Neuro-Oncology 25, Supplement_2 (September 1, 2023): ii110—ii111. http://dx.doi.org/10.1093/neuonc/noad137.371.
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Abstract BACKGROUND Neurosurgical resection of brain tumors resembles a balancing act between maximing extent of tumor resection (efficacy) and minimizing the risk of post-operative neurological deficits (safety). Given the difficulty of this trade-off, it is surprising how limited the neurosurgeon’s intra-operative tools are. To this day, neurosurgeons still resect brain tumors without any form of real-time volumetric functional imaging. Functional Ultrasound (fUS) shows great potential as a next-generation intra-operative functional imaging technique, combining submillimeter-subsecond spatiotemporal resolution, high-depth penetration and large fields of view. In previous work we have successfully shown fUS’ ability to map out hemodynamics-based functional brain activity during language and motor tasks during awake tumor resections. However, there has been no study comparing fUS-acquired functional maps and its gold standard counterpart of BOLD-fMRI imaging or Electrocortical Stimulation Mapping (ESM). Here we present our first results of concomitant ESM-, fMRI- and fUS-imaging in the same human subjects. MATERIAL AND METHODS In N = 3 patients undergoing awake surgery for tumor removal, we performed paired functional testing with pre-operative fMRI and intra-operative fUS and ESM. Using conventional linear ultrasound arrays (GE L8-18I-D (7.8 MHz) and GE 9L-D Logiq 9 (5.3 MHz)) interfaced with our experimental system (Vantage-256, Verasonics), we could acquire fUS-images up to 8 cm in depth with a PRF up to 800 Hz. Building on clinically available neuro-navigation software with optical tracking (Brainlab), we co-registered our intra-operative fUS-maps and ESM-hotspots to pre-operative MRI/CT-data in real-time to study spatiotemporal overlap. RESULTS In motor, language and visual tasks, we were able to demonstrate consistent spatial overlap between the fUS-based and ESM- and fMRI-based functional regions. Our fUS functional maps presented with unprecedented mesoscopic-scale precision (400 µm), even at depths of over > 5 cm. In contrast to fMRI and ESM, fUS was also able to concomitantly visualize the in-vivo microvascular morphology underlying the functional hemodynamics. The current results were only obtainable after we developed a powerful study pipeline including pre-operative fMRI-imaging and ROI-planning, intra-operative integration of experimental Doppler-data and co-registered functional analyses. CONCLUSION The work presented here is the first-ever, in-human comparison between ESM-, fMRI- and fUS-based functional data, serving as a significant milestone towards further clinical maturity of fUS as a new intra-operative tool to improve the safety and efficacy of neurosurgical brain tumor resections. Disclosure: This work was supported by the NWO-Groot grant of The Dutch Organization for Scientific Research (NWO) (Grant no. 108845).
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Sheybani, Natasha, Soumen Paul, Katelyenn McCauley, Victoria Breza, Stuart Berr, G. Wilson Miller, Kiel Neumann, and Richard Price. "472 ImmunoPET-informed sequence for focused ultrasound-targeted mCD47 blockade controls glioma." Journal for ImmunoTherapy of Cancer 8, Suppl 3 (November 2020): A502—A503. http://dx.doi.org/10.1136/jitc-2020-sitc2020.0472.
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BackgroundThe natural disease course for glioblastoma (GB) entails invariably grim outcomes for patients. Phagocytic immunotherapies, such as CD47 blockade (e.g. mCD47), have recently demonstrated promise for GB therapy. However, their efficacy is challenged by presence of the blood brain and tumor barriers (BBB/BTB). Transient disruption of the BBB/BTB via focused ultrasound (FUS) and circulating microbubbles (MB) holds promise for improving therapeutic outcomes in the context of mCD47. However, critical questions regarding the optimal protocol for therapeutic antibody delivery with FUS remain. We herein leverage immuno-PET imaging to spatiotemporally map [89Zr]-mCD47 delivery across the BBB/BTB with FUS in an orthotopic GB model. We then use these insights to design a combinatorial paradigm for mCD47 delivery with repeat FUS BBB/BTB-D.MethodsMRI-guided FUS BBB/BTB-D was performed in the presence of systemically circulating MBs in mice with orthotopically implanted GL261 tumors. Mice received i.v. [89Zr]-mCD47 either without FUS, immediately prior to FUS [FUSPRE] or following FUS [FUSPOST]. Subsequently, mice underwent serial static PET/CT imaging followed by terminal ex vivo assessment of antibody biodistribution. A therapeutic paradigm was then executed, wherein GL261-bearing mice received i.v. mCD47 (8 mg/kg) either as monotherapy or in combination with FUS BBB/BTB-D over three sessions spaced three days apart. Overall survival was monitored and tumor outgrowth was tracked via serial contrast-enhanced MRI.ResultsContrast-enhanced MRI confirmed BBB/BTB-D in GL261 tumors (figure 1A). However, PET/CT imaging revealed a lack of tumor-preferential [89Zr]-mCD47 uptake with or without FUSPRE, suggesting that neither condition improved antibody penetrance over that in naïve brain (figure 1B-C). Remarkably, FUSPOST conferred superlative [89Zr]-mCD47 uptake at the site of BBB/BTB-D, boasting between 4.3- to 6.7-fold more uptake relative to other groups (figure 1C). This elevation in uptake was sustained over the time points assessed (0–72 hours post-FUS) (figure 1C-D). Using these insights, we evaluated a rational paradigm (figure 2A) combining mCD47 with repeat FUSPOST BBB/BTB-D (figure 2B-C) for glioma therapy. FUS-mediated delivery of mCD47 across the BBB/BTB significantly constrained tumor outgrowth (figure 2D-E) and enhanced survival (figure 2F) in GL261-bearing mice.Abstract 472 Figure 1Immuno-PET monitoring of [89Zr]-mCD47 delivery(A) Representative contrast-enhanced T1-weighted MR images of GL261 tumor-bearing brain pre- and post-FUS. Enhancement in the right cerebral hemisphere on pre-FUS imaging indicates baseline barrier disruption induced by the presence of a brain tumor. Expansion of the enhanced region on post-FUS imaging reflects effective FUS-mediated BBB/BTB disruption. (B) Representative axial decay-corrected PET/CT images for each experimental group on Day 14. White arrows denote region of visibly elevated radioactivity at the tumor site targeted with FUS. (C) Whole brain standardized [89Zr]-mCD47 uptake values (SUVs) extracted from serial static PET/CT images obtained between days 14 and 16 post-implantation (0 to 2 days post-[89Zr]-mCD47 injection).%ID/mL =% injected dose per mL. **p<0.01, ****p<0.0001 vs. group(s) indicated. Significance assessed by RM mixed effects model implementing restricted maximum likelihood method, followed by Tukey multiple comparison correction. (D) Tumor-drug exposure for [89Zr]-mCD47 in naïve brain or GL261 tumors, based on integration of SUVs from decay-corrected PET/CT images collected between 0 and 48 hours after BBB/BTB-D and/or [89Zr]-mCD47 injection. Significance assessed by one-way ANOVA followed by Tukey multiple comparison correction. ****p<0.0001 vs. all other groupsAbstract 472 Figure 2Therapeutic impact of FUS-mediated mCD47 delivery(A) Overview of experimental design for evaluating mCD47 delivery to orthotopically implanted GL261 tumors in the context of repeat BBB/BTB-D with FUS. Mice received i.v. mCD47 (8 mg/kg) either alone (FUS-) or following BBB/BTB-D at 0.4 MPa (FUS+). (B) Axial contrast-enhanced T1-weighted MR images of murine GL261-tumors pre- and post-FUS. (C) Mean greyscale intensity (MGI) of contrast enhancement pre- and post-FUS over three separate BBB/BTB-D sessions conducted every three days. Calculated as fold change over contralateral brain. Mean ± SD. **p=0.0023. Significance assessed by RM 2-way ANOVA followed by Sidak’s multiple comparison test. (D) Contrast-enhanced T1-weighted MR images of GL261 tumors on days 14, 17 and 20 post-implantation. ? = image excluded due to poor quality. (E) GL261 tumor outgrowth quantified based on serial MR imaging. Mean ± SD. *p=0.0010. Significance assessed by RM mixed-effects model implementing restricted maximum likelihood method, followed by Sidak’s multiple comparison test. (F) Kaplan-Meier curve depicting overall survival of GL261-bearing mice. n=5–6 mice per group. *p=0.0008. Significance assessed by log-rank (Mantel-Cox) testConclusionsTaken together, our findings suggest that mCD47 delivery with FUS BBB/BTB-D is a promising therapeutic strategy for GB. For myriad ongoing pre-clinical and clinical evaluations of FUS-mediated immunotherapy delivery, these findings generate timely and compelling insights regarding impact of injection timing on antibody penetrance in brain tumors. This study underscores the outstanding potential role of immuno-PET imaging for rational design and monitoring of response to FUS immunotherapy approaches.AcknowledgementsThis study was supported by NIH R01CA197111, R01EB020147, R21NS118278 and the Schiff Foundation (R.J.P.). Additional support from NCI F99/K00 Predoctoral to Postdoctoral Fellow Transition Award (F99CA234954), NSF Graduate Research Fellowship and the Robert R. Wagner Fellowship (N.D.S.).Ethics ApprovalThis study was prospectively reviewed and approved by the University of Virginia Animal Care and Use Committee.ConsentN/A
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Thanou, M., and W. Gedroyc. "MRI-Guided Focused Ultrasound as a New Method of Drug Delivery." Journal of Drug Delivery 2013 (May 12, 2013): 1–12. http://dx.doi.org/10.1155/2013/616197.
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Ultrasound-mediated drug delivery under the guidance of an imaging modality can improve drug disposition and achieve site-specific drug delivery. The term focal drug delivery has been introduced to describe the focal targeting of drugs in tissues with the help of imaging and focused ultrasound. Focal drug delivery aims to improve the therapeutic profile of drugs by improving their specificity and their permeation in defined areas. Focused-ultrasound- (FUS-) mediated drug delivery has been applied with various molecules to improve their local distribution in tissues. FUS is applied with the aid of microbubbles to enhance the permeability of bioactive molecules across BBB and improve drug distribution in the brain. Recently, FUS has been utilised in combination with MRI-labelled liposomes that respond to temperature increase. This strategy aims to “activate” nanoparticles to release their cargo locally when triggered by hyperthermia induced by FUS. MRI-guided FUS drug delivery provides the opportunity to improve drug bioavailability locally and therefore improve the therapeutic profiles of drugs. This drug delivery strategy can be directly translated to clinic as MRg FUS is a promising clinically therapeutic approach. However, more basic research is required to understand the physiological mechanism of FUS-enhanced drug delivery.
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Zhang, Junhang, Chen Gong, Zihan Yang, Fan Wei, Xin Sun, Jie Ji, Yushun Zeng, et al. "Ultrasound Flow Imaging Study on Rat Brain with Ultrasound and Light Stimulations." Bioengineering 11, no. 2 (February 10, 2024): 174. http://dx.doi.org/10.3390/bioengineering11020174.
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Functional ultrasound (fUS) flow imaging provides a non-invasive method for the in vivo study of cerebral blood flow and neural activity. This study used functional flow imaging to investigate rat brain’s response to ultrasound and colored-light stimuli. Male Long-Evan rats were exposed to direct full-field strobe flashes light and ultrasound stimulation to their retinas, while brain activity was measured using high-frequency ultrasound imaging. Our study found that light stimuli, particularly blue light, elicited strong responses in the visual cortex and lateral geniculate nucleus (LGN), as evidenced by changes in cerebral blood volume (CBV). In contrast, ultrasound stimulation elicited responses undetectable with fUS flow imaging, although these were observable when directly measuring the brain’s electrical signals. These findings suggest that fUS flow imaging can effectively differentiate neural responses to visual stimuli, with potential applications in understanding visual processing and developing new diagnostic tools.
Dissertations / Theses on the topic "FUS imaging"
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Cazzanelli, Silvia. "Functional ultrasound (fUS) imaging of brain functional connectivity alterations in a mouse model of neuropathic pain : impact of nociceptive symptoms and associated comorbidities." Electronic Thesis or Diss., Université Paris sciences et lettres, 2024. http://www.theses.fr/2024UPSLS010.
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La douleur neuropathique est une sensation de douleur anormale qui persiste au-delà du cours temporel de la guérison naturelle. Elle interfère avec la qualité de vie du patient et est associée à plusieurs comorbidités telles que l'anxiété et la dépression. Des études antérieures ont suggéré que la douleur chronique pourrait résulter d’une plasticité neuronale anormale et inadaptée dans les structures connues pour être impliquées dans la perception de la douleur (Bliss et al. 2016). Cela signifie qu'une lésion nerveuse déclencherait une potentialisation à long terme de la transmission synaptique dans les aires cérébrales liées à la douleur (Zhuo et al. 2014). Comme ces régions sont également impliquées dans les aspects émotionnels de la douleur, notre hypothèse est que la plasticité inadaptée susmentionnée dans ces zones cérébrales pourrait constituer un mécanisme clé pour le développement de comorbidités, telles que l'anxiété et la dépression.Au cours de ma thèse, nous avons choisi de tester cette hypothèse de travail par l’étude des altérations de la connectivité fonctionnelle (CF) intrinsèque des réseaux cérébraux par imagerie fonctionnelle ultrasonore (fUS) dans un modèle murin de douleur neuropathique. Cette technique de neuro-imagerie relativement récente a permis de nombreuses avancées en neurosciences, grâce à sa haute résolution spatio-temporelle, à sa sensibilité, mais aussi son adaptabilité, permettant des études chez l’animal anesthésié ou éveillé.Dans une première étude, j’ai mis au point un protocole expérimental permettant d’imager le cerveau des souris éveillées de façon reproductible et avec un minimum de stress et d artefacts de mouvements et ai également été impliquée dans le développement d’un nouvel algorithme d’analyse des signaux générées par ces acquisitions. Cette première approche étant réalisée avec une sonde linéaire en mouvement qui ne permet pas de visualiser l’entièreté du cerveau, dans une seconde étude, j’ai participe au développement d’une nouvelle technologie de sonde compilées et motorisée.Fort de ces développements technologiques, j’ai alors utilisé ces nouvelles approches pour tester mon hypothèse neurobiologique. J’ai entrepris deux études en parallèle chez des animaux anesthésiés pour l’une et éveillés pour la seconde, chez lesquelles nous avons étudié le lien temporel entre les altérations de la CF cérébrale et le développement de la douleur neuropathique et/ou des comorbidités associées. Pour cela, nous avons mesuré la CF (en période de repos) chez des souris atteintes de douleur neuropathique, à trois moments différents : I) 2 semaines après l’induction de la douleur neuropathique (manchon autour du nerf sciatique) II) à 8 semaines post-induction, lorsque l'anxiété émerge et III) à 12 semaines post-induction, lorsque la dépression apparait (12W). Ce suivi longitudinal a également été réalisé en parallèle sur un groupe d’animaux contrôles.Nos résultats indiquent des changements significatifs de la CF dans les principales régions cérébrales impliquées dans la transmission ou la modulation de la sensibilité ou de la douleur, suggérant la mise en place d’une plasticité inadaptée du réseau de la douleur, suite à la lésion nerveuse. De plus, nous observons une évolution temporelle de ces altérations, potentiellement corrélée à l'apparition des comorbidités associées. Ainsi, ces mécanismes pourraient participer à la chronicisation de la douleurNeuropathic pain is an abnormal pain sensation that persists longer than the temporal course of natural healing. It interferes with the patient’s quality of life and leads to several comorbidities, such as anxiety and depression. It has been suggested that chronic pain may result from abnormal and maladaptive neuronal plasticity in the structures known to be involved in pain perception (Bliss et al. 2016). This means that nerve injury would trigger long-term potentiation of synaptic transmission in pain-related areas (Zhuo et al. 2014). Since these regions are also involved in the emotional aspects of pain, our hypothesis is that the aforementioned maladaptive plasticity in these brain areas could constitute a key mechanism for the development of comorbidities such as anxiety and depression.My PhD aimed at testing this working hypothesis, through the study of brain resting state functional connectivity (FC) using functional ultrasound imaging (fUS) in a mouse model of neuropathic pain. FUS is a relatively recent neuroimaging technique that enabled numerous advances in neuroscience, thanks to its high spatio-temporal resolution, its sensitivity, but also its adaptability, allowing studies in anesthetized or awake animals.In a first study, I developed an experimental protocol allowing the brains of awake mice to be imaged in a reproducible manner and with minimal stress and movement artifacts and was also involved in the development of a new algorithm for the analysis of the signals generated by these acquisitions. As this first approach was carried out with a moving linear probe which does not allow the entire brain to be visualized, in a second study, I participated in the development of a new compiled and motorized probe technology.Building on these technological developments, I then used these new approaches to test my neurobiological hypothesis. I undertook two parallel studies in animals anesthetized for one and awake for the second, in which we studied the temporal link between alterations in cerebral FC and the development of neuropathic pain and/or associated comorbidities. To do this, we measured the resting-state functional connectivity (FC) in anesthetized and in awake head-fixed mice, at three time points: I) 2 weeks after induction of neuropathic pain (cuff around the sciatic nerve), II) at 8 weeks post-induction during the emergence of anxiety (8W) and III) at 12 weeks post-induction during the emergence of depression. This longitudinal follow-up has been conducted concurrently on a control group.Our results show significant changes in FC in major pain-related brain regions in accordance with the development of neuropathic pain symptoms. These findings suggest that the pain network undergoes maladaptive plasticity following nerve injury which could contribute to pain chronification. Moreover, the time course of these connectivity alterations between regions of the pain network could be correlated with the subsequent apparition of associated comorbidities
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Sieu, Lim-Anna. "Exploration des réseaux épileptiques par imagerie ultrasonore et électrophysiologie." Thesis, Paris 6, 2016. http://www.theses.fr/2016PA066384/document.
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Les épilepsies sont des hyperactivités neuronales pathologiques largement distribuées au sein du système nerveux. Aborder la question de l'organisation spatiotemporelle de ces crises est un premier pas crucial vers la dissection des mécanismes qui les sous-tendent. Alors qu'il existe de nombreux modèles d'hyperactivité épileptiforme, il est plus difficile d'étudier les crises spontanées, qui sont altérées par la sédation. Dans cette thèse, j'ai développé une approche combinant l'électroencéphalogramme (EEG) avec l'imagerie fonctionnelle ultrasonore (fUS), sur le rat mobile. Ainsi, sur un modèle d'épilepsie absence, j'ai pu enregistrer simultanément la survenue des crises et les variations hémodynamiques, marqueurs du métabolisme cellulaire. Le suivi additionnel de l'activité hémodynamique n'avait pas d'effet en soi sur l'occurrence et la durée des crises épileptiques. L'analyse des enregistrements a permis de mettre en évidence des corrélations entre les activités électriques et vasculaires durant les crises. Tandis que le thalamus présentait des zones d'hyperperfusion pendant les crises, le cortex présentait des corrélats variables suivant les aires, avec une hyperémie des aires somato-sensorielles accompagnée parfois d'une baisse de perfusion des tissus adjacents. La sensibilité du fUS a révélé, à partir d'événements uniques, qu'une série de pointe-ondes observée par une électrode EEG ne s'accompagne pas toujours d'une hyperactivité vasculaire au même endroit. Ainsi, cette approche permet de délimiter le contour des aires présentant une activité vasculaire pendant les crises et montre une dichotomie partielle entre les composantes électriques et vasculaires des crisesEpilepsies consist in neuronal hyperactivities distributed across the nervous system that need first to be located in order to later decipher the mechanisms of these pathologies. While there are many models of epileptiform hyperactivity, it is more difficult to study spontaneous seizures, which are altered by sedation. In this thesis, I developed an approach that combines electroencephalography (EEG) and functional ultrasound imaging (fUS), on the mobile rat. Thus, on a model of absence epilepsy, I could record simultaneously the occurrence of seizures and the hemodynamic variations, which reflect cellular metabolism. Seizures were unaltered by the recording protocol, compared to rats with EEG alone. Correlations were observed between electric and vascular activities. The thalamus showed areas of hyperperfusion during seizures. The cortex exhibited different correlates in distinct areas, with hyperaemia in somato-sensory areas, occasionally associated with a decrease in perfusion in adjacent tissue. The sensitivity of fUS, which could resolve blood changes from single occurrences, revealed that series of spike-wave discharges recorded from an EEG electrode were not always associated with vascular hyperactivity in the same region. Thus, this approach can delimit the contour of areas presenting vascular activity during seizures and shows a partial dichotomy between the electric and vascular components of seizures
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Tiran, Elodie. "Imagerie cérébrale et étude de la connectivité fonctionnelle par échographie Doppler ultrarapide chez le petit animal éveillé et en mouvement." Thesis, Sorbonne Paris Cité, 2017. http://www.theses.fr/2017USPCC174/document.
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Mes travaux de thèse portent sur l’application de l’imagerie fUS (functional ultrasound imaging) à l’imagerie cérébrale préclinique chez le petit animal. Le but était de transformer cette technique d’imagerie cérébrale récente en un véritable outil de quantification de l’état cérébral. Les objectifs principaux ont été de démontrer la faisabilité de l’imagerie fUS chez le petit animal non anesthésié ainsi que de passer du modèle rat au modèle souris - modèle de choix en imagerie préclinique en neurosciences - de surcroît de façon non invasive. J’ai tout d’abord mis au point une nouvelle séquence d’imagerie ultrasonore ultrarapide (Multiplane Wave imaging), permettant d’améliorer le rapport signal-à-bruit des images grâce à l’augmentation virtuelle de l’amplitude du signal émis, sans diminuer la cadence ultrarapide d’acquisition. Dans un deuxième temps j’ai démontré la possibilité d’imager le cerveau de la souris et du jeune rat anesthésiés par échographie Doppler ultrarapide, de manière transcrânienne et complètement non invasive, sans chirurgie ni injection d’agents de contraste. J’ai ensuite mis au point un montage expérimental, une séquence ultrasonore et un protocole expérimental permettant de réaliser de l’imagerie fUS de manière minimalement invasive chez des souris éveillées et libres de leurs mouvements. Enfin, j’ai démontré la possibilité d’utiliser le fUS pour étudier la connectivité fonctionnelle du cerveau au repos (sans stimulus) chez des souris éveillées ou sédatées. L’imagerie fUS et la combinaison « modèle souris » + « minimalement invasif » + « animal éveillé » + « connectivité fonctionnelle » constituent un outil précieux pour la communauté des neuroscientifiques travaillant sur des modèles animaux pathologiques ou de nouvelles molécules pharmacologiquesMy work focuses on the application of fUS (functional ultrasound) imaging to preclinical brain imaging in small animals. The goal of my thesis was to turn this recent vascular brain imaging technique into a quantifying tool for cerebral state. The main objectives were to demonstrate the feasibility of fUS imaging in the non-anaesthetized small rodents and to move from rat model imaging to mouse model imaging –most used model for preclinical studies in neuroscience-, while developing the least invasive imaging protocols. First, I have developed a new ultrafast ultrasonic imaging sequence (Multiplane Wave imaging), improving the image signal-to-noise ratio by virtually increasing emitted signal amplitude, without reducing the ultrafast framerate. Then, I have demonstrated the possibility to use ultrafast Doppler ultrasound imaging to image both the mouse brain and the young rat brain, non-invasively and through the intact skull, without surgery or contrast agents injection. Next, I have developed an experimental setup, an ultrasound sequence and an experimental protocol to perform minimally invasive fUS imaging in awake and freely-moving mice. Finally, I have demonstrated the possibility to use fUS imaging to study the functional connectivity of the brain in a resting state in awake or sedated mice, still in a transcranial and minimally invasive way. fUS imaging and the combination of "mouse model" + "minimally invasive" + "awake animal" + "functional connectivity" represent a very promising tool for the neuroscientist community working on pathological animal models or new pharmacological molecules
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Lin, Qiaojin. "Axonal translation and links to neuropathies." Thesis, University of Cambridge, 2018. https://www.repository.cam.ac.uk/handle/1810/273662.
Full textAbstract:
Neurons connect to their remote targets via axons, which usually survive for the lifetime of an organism. Spatiotemporal regulation of the axonal proteome by local protein synthesis (LPS) plays a critical role in neuronal wiring and axon survival, raising the intriguing possibility that some neurological disorders involve LPS dysfunction. To visualise LPS in situ, I optimised multiple imaging techniques to investigate Netrin-1-induced translation in cultured retinal axons. Total axonal protein synthesis measured by metabolic and puromycin labelling indicates axons experience stage-dependent alterations in translation rate upon Netrin-1 stimulation. Remarkably, Netrin-1 triggers a burst of β-actin synthesis starting within 20 seconds of cue application at multiple non-repetitive sites visualised by single molecule translation imaging, an approach that allows direct visualisation of translation dynamics in response to external stimuli. Further studies have shown that local translation can occur on Rab7a-associated late endosomes, where mRNA recruitment and translation are coordinately regulated. Notably, mRNAs encoding mitochondria-related proteins are found translating on late endosomes docking in the vicinity of mitochondria, suggesting late endosomes act as ‘platforms’ for the localised synthesis of mitochondrial proteins necessary for maintaining mitochondrial integrity. Moreover, this process is affected in axons expressing the Charcot-Marie-Tooth disease type 2B (CMT2B)-related Rab7a mutants, leading to abnormal mitochondrial biogenesis and activity and compromised axon survival. Finally, attenuated de novo protein synthesis is observed in axons expressing amyotrophic lateral sclerosis (ALS)-associated fused in sarcoma (FUS) mutants and hypomethylated wild-type FUS. Live imaging reveals mislocalised mutant or hypomethylated FUS granules are transported along axons and accumulate at growth cones, possibly irreversibly trapping RNA molecules, resulting in reduced distance travelled by RNA granules in axons. Furthermore, mutant FUS expression results in defective retinal projections in vivo, highlighting the importance of RNA metabolism and local translation in axonal homeostatic mechanisms. In conclusion, aberrant translational activity in axons leads to prominent axonopathy, which recapitulates features of early stages of neurological diseases, providing the basis for novel therapeutic strategies.
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Dervishi, Elvis. "Traitement des tumeurs cérébrales par ultrasons focalisés de haute intensité - sur un modèle tumoral greffé chez le rat." Thesis, Paris 11, 2014. http://www.theses.fr/2014PA11T046.
Full textAbstract:
La thérapie par faisceaux ultrasonores focalisés de forte intensité (HIFU / High Intensity Focused Ultrasound) est une nouvelle technique d’ablation tissulaire, fondée sur la focalisation de faisceaux ultrasonores de forte intensité pour réaliser une élévation de température capable de créer une nécrose thermique. Le cerveau a été jusqu’à présent peu accessible aux ultrasons car il est protégé par la boîte crânienne. Mais de nouvelles techniques de focalisation par correction des aberrations des faisceaux ultrasonores laissent espérer des applications prochaines en intracrânien, où l’HIFU pourrait constituer une intéressante alternative à la chirurgie et à la radiothérapie stéréotaxique. Le but général de ce travail a été de tester la thérapie HIFU contrôlée par Imagerie de Résonance Magnétique (IRM) pour le traitement des tumeurs cérébrales dans un modèle petit animal in vivo de tumeur cérébrale. Nous espérons ainsi fournir des apports sur la thérapie HIFU et ses effets biologiques sur le cerveau et les tumeurs cérébrales, connaissances nécessaires avant de passer à des études cliniques chez l’homme. Le plan de ce travail est le suivant : 1) développement d’un protocole de thérapie HIFU contrôlé par IRM sur le cerveau sain et sur un modèle de tumeur RG2 greffée en intracérébral chez le rat ; 2) étude des effets biologiques de l’HIFU par l’IRM et l’examen anatomo-pathologique sur le tissu cérébral sain et la tumeur RG2 en intracérébral, montrant une sensibilité variable des tissus à l’hyperthermie ; 3) étude de sécurité (tolérance et effets indésirables), démonstration d’efficacité sur la tumeur RG2 (ralentissement de l’évolution tumorale et augmentation de la survie des animaux traités). En conclusion, l’HIFU a montré sa précision et son efficacité dans le traitement de la tumeur RG2 greffée en intracérébral chez le rat. Cette technique n’est cependant pas exempte de complications, notamment un œdème périlésionnel et des hémorragies intratumoralesHigh Intensity Focused Ultrasound (HIFU) therapy is an innovative approach for tissue ablation, based on high intensity focused ultrasound beams. At focus, HIFU induces a temperature elevation and the tissue can be thermally destroyed. For transcranial brain therapy, the skull bone is a major limitation but new adaptive techniques for focusing ultrasound through the skull are underway and in the near future HIFU therapy could be an interesting alternative to brain surgery and radiotherapy.The overall aim of this work is to test HIFU therapy guided by Magnetic Resonance Imaging (MRgHIFU) for the treatment of brain tumors in an in vivo brain tumor model in rodent in order to provide inputs for future regulatory approval for clinical trial with a clinical prototype. In this work: 1) a dedicated system for transcranial MRgHIFU in an in vivo rat brain tumor model was developed, and a full protocol was applied in healthy brain tissue of rats and in transplanted tumors; 2) the biological effects of HIFU therapy was evaluated using MRI and histology in healthy brain tissue and in RG2 brain tumor, showing a different tissue sensibility for hyperthermia; 3) tolerance and side effects were investigated and the treatment was shown to improve the animal survival time by 50%. In conclusion, HIFU therapy has proved its accuracy and efficacy in the treatment of the RG2 brain tumor transplanted intracerebral in rats. However this technique is not free of complications, in particular edema and hemorrhages
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Rykala, Adam. "Star formation studies using the Herschel-SPIRE Imaging FTS." Thesis, Cardiff University, 2011. http://orca.cf.ac.uk/19702/.
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The study of low mass star formation in our local Galaxy is particularly suited to HERSCHEL. The SPIRE spectrometer and photometer aboard the spacecraft operate in the ~ 200 - 600�m range and are well suited to probe the cold, dusty environments in molecular clouds where prestellar cores reside. The SPIRE FTS spectrometer is an interferometer, and this instrument design has strengths and weaknesses which are im- portant to understand when using data from the instrument. Herschel is set to continue groundbreaking work in the infrared, building upon earlier work from ISO, IRAS, and SPITZER, probing deep into star forming regions and improving our knowledge of the processes within. In this PhD thesis, we outline the current body of knowledge in low mass star formation. We examine the properties of the SPIRE FTS as a spectrometerusing a small, laboratory designed desktop FTS. We study the intrinsic properties of the instrument, as a way of understanding issues we are likely to see when using the SPIRE FTS in ight. With these issues firmly in mind, we examine the creation and use of SLIDE - an interactive IDL-based tool for processing SPIRE FTS data. SLIDE can extract line and continuum information from SPIRE FTS SEDs. We outline the creation, testing and use of SLIDE and provide examples of the use of SLIDE in astronomy with some examples from the literature. We then use the line information we extract from a variety of sources with the spectrometer, to examine how SED fitting from photometer data could be affected by line contamination. We simulate a wide range of greybodies with noise and line con- tamination and examine how SED fitting is affected. Our simulations conclude that line contamination is not enough to affect the recovery of temperature and spectral index B significantly. Finally we use the information we have deduced to examine SPIRE FTS SEDs of L1689B - a prestellar core located in Ophiuchus. Our SED fitting of the core confirms that this core is starless with no internal heating source, and the spectral index profile over the core morphology is consistent with an increasing density of fractal aggregrate grains towards the centre. The increase in grain density and spectral index profile is also in agreement with previous CO depletion data. Fractal grain growth of this nature is consistent with dust grain models.
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LAVIANO, FRANCESCO. "Magneto-optics: Imaging and Quantitative Analysis." Doctoral thesis, Politecnico di Torino, 2005. http://hdl.handle.net/11583/2565567.
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The work presented in this thesis deals with the magneto-optical imaging (MOI) technique, which was developed during the PhD course of the candidate, with an equipment at the international state-of-the-art. The quantitative theoretical formalism was critically reproduced and verified, along with a careful calibration procedure. A novel, big improvement was brought for all the MOI experiments, aimed at the quantitative reconstruction of the current density, by an iterative procedure (Supercond. Sci. Technol. 16, 71 (2003)). The new MOI method was then applied to study a wide class of superconducting materials and a thorough study about the electrodynamics of superconducting films was accompanied by a research in the high energy nuclear field for creating suitable nanometric-size defects. In particular: the anisotropic interaction of correlated nanostructures with vortices was verified for the first time (Phys. Rev. B 68, 014507 (2003)); controlled micro-modulations of the superconducting properties through confined high-energy heavy-ion irradiation were achieved and nonlocal electrodynamics plus new vortex matter phases were observed; the measurements of hybrid heterostructures (superconducting/ferromagnetic bi-layers) was joining the studies of macroscopic quantum physics of vortices and of the macroscopic (but localized) spin structures (interacting with vortices indeed), in the ferromagnetic film.
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ALCHERA, NICOLA. "Data harmonization in PET imaging." Doctoral thesis, Università degli studi di Genova, 2021. http://hdl.handle.net/11567/1049735.
Full textAbstract:
Medical imaging physics has advanced a lot in recent years, providing clinicians and researchers with increasingly detailed images that are well suited to be analyzed with a quantitative approach typical of hard sciences, based on measurements and analysis of clinical interest quantities extracted from images themselves. Such an approach is placed in the context of quantitative imaging.
The possibility of sharing data quickly, the development of machine learning and data mining techniques, the increasing availability of computational power and digital data storage which characterize this age constitute a great opportunity for quantitative imaging studies.
The interest in large multicentric databases that gather images from single research centers is growing year after year. Big datasets offer very interesting research perspectives, primarily because they allow to increase statistical power of studies.
At the same time, they raised a compatibility issue between data themselves. Indeed images acquired
with different scanners and protocols could be very different about quality and measures extracted from images with different quality might be not compatible with each other.
Harmonization techniques have been developed to circumvent this problem. Harmonization refers to all efforts to combine data from different sources and provide users with a comparable view of data from different studies. Harmonization can be done before acquiring data, by choosing a-priori appropriate acquisition protocols through a
preliminary joint effort between research centers, or it can be done a-posteriori i.e. images are grouped into a single dataset and then any effects on measures caused by technical acquisition factors are removed.
Although the a-priori harmonization guarantees best results, it is not often used for practical and/or technical reasons. In this thesis I will focus on a-posteriori harmonization. It is important to note that when we consider multicentric studies, in addition to the technical variability related to scanners and acquisition protocols, there may be a demographic variability that makes single centers samples not statistically equivalent to each other. The wide individual variability that characterize human beings, even more pronounced when patients are enrolled from very different geographical areas, can certainly exacerbate this issue. In addition, we must consider that biological processes are complex phenomena: quantitative imaging measures can be affected by numerous confounding demographic variables even apparently unrelated to measures themselves.
A good harmonization method should be able to preserve inter-individual variability and remove at the same time all the effects due acquisition technical factors. Heterogene ity in acquisition together with a great inter-individual variability make harmonization very hard to achieve.
Harmonization methods currently used in literature are able to preserve only the inter-subjects variability described by a set of known confounding variables, while all the unknown confounding variables are wrongly removed. This might lead to incorrect harmonization, especially if the unknown confounders play an important role. This issue
is emphasized in practice, as sometimes happens that demographic variables that are known to play a major role are unknown.
The final goal of my thesis is a proposal for an harmonization method developed in the context of amyloid Positron Emission Tomography (PET) which aim to remove the effects of variability induced by technical factors and at the same time are able to keep all the inter-individual differences. Since knowing all the demographic confounders is
almost impossible, both practically and a theoretically, my proposal does not require the knowledge of these variables.
The main point is to characterize image quality through a set of quality measures evaluated in regions of interest (ROIs) which are required to be as independent as possible from anatomical and clinical variability in order to exclusively highlight the effect of technical factors on images texture. Ideally, this allows to decouple the between-subjects variability from the technical ones: the latter can be directly removed while the former is automatically preserved.
Specifically, I defined and validated 3 quality measures based on images texture properties. In addition I used a quality metric already existing, and I considered the reconstruction matrix dimension to take into account image resolution. My work has been performed using a multicentric dataset consisting of 1001 amyloid PET images. Before dealing specifically with harmonization, I handled some important issues: I built a relational database to organize and manage data and then I developed an automated algorithm for images pre-processing to achieve registration and quantification.
This work might also be used in other imaging contexts: in particular I believe it could be applied in fluorodeoxyglucose (FDG) PET and tau PET. The consequences of harmonization I developed have been explored at a preliminary level. My proposal should be considered as a starting point as I mainly dealt with the issues of quality measures, while the harmonization of the variables in itself was done with a linear regression model.
Although harmonization through linear models is often used, more sophisticated techniques are present in literature. It would be interesting to combine them with my work. Further investigations would be desirable in future.
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Lautenschlager, Michael Allen. "Imagining the Worst: Ladislav Fuks' Contributions to Holocaust Fiction." Thesis, Virginia Tech, 2011. http://hdl.handle.net/10919/32530.
Full textAbstract:
Ladislav Fuks' works are under-recognized in English-speaking academic discourse. He is a valuable contributor not only to the Holocaust Literature genre, but also to film and literature in general. His two English-translated works, Mr. Theodore Mundstock and The Cremator, as well as the film adaptation of The Cremator, examine the role imagination can play in art that addresses atrocity, allowing for a heightened subjective impact on the audience. I critically and comparatively examine Fuks' work to establish his value to literature and Holocaust art. In the first chapter, I frame my argument with questions of art's abilities to represent atrocity and provide relevant background information relating to Fuks' and his experience in wartime Prague. In Chapter Two, I closely read Mr. Theodore Mundstock, concentrating specifically on Fuks' use of metaphor, presentation of incredulity, and commentary on the imagination's capabilities in confronting terror. Chapter Three compares Mr. Theodore Mundstock to the â Momikâ section of David Grossman's See Under: Love, focusing on similarities between the title characters. Chapter Four examines Fuks' use of the grotesque in The Cremator and its film adaptation. Chapter Five compares Fuks' works to Aharon Appelfeld's novel Badenheim 1939, emphasizing each author's reliance on the audience's retrospective prescience, which provides a significant psychological impact and avoids contributing to the over-saturation of Holocaust information on the public. I conclude that Fuks should be more highly regarded and widely recognized both academically and in popular culture, as he exhibits similar features as other, more celebrated Holocaust writers, and his innovative contributions defend the value of literature in representing atrocity.Master of Arts
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JAUBERTEAU, RAPHAËL. "Extreme events in quadratic media: application to nonlinear imaging." Doctoral thesis, Università degli studi di Brescia, 2021. http://hdl.handle.net/11379/554955.
Full textBooks on the topic "FUS imaging"
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Garcia-Alfaro, Joaquin. Foundations and Practice of Security: 5th International Symposium, FPS 2012, Montreal, QC, Canada, October 25-26, 2012, Revised Selected Papers. Berlin, Heidelberg: Springer Berlin Heidelberg, 2013.
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John Lennon Imagina que esto fue real (100 Personajes) (100 Personajes). Panamericana Editorial, 2005.
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Manaster, B. J. Diagnostic and Surgical Imaging Anatomy: Knee, Ankle, Foot: Published by Amirsys® (Diagnostic & Surgical Imaging Anatomy). Shenanigan Books, 2007.
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Manaster, B. J. Diagnostic and Surgical Imaging Anatomy: Knee, Ankle, Foot: Published by Amirsys®. Lippincott Williams & Wilkins, 2007.
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Manaster, B. J. Diagnostic and Surgical Imaging Anatomy: Knee, Ankle, Foot (International Edition): Published by Amirsys®. Lippincott Williams & Wilkins, 2007.
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Barbeau, Michel, Joaquin Garcia-Alfaro, Guang Gong, Abdelmalek Benzekri, and Romain Laborde. Foundations and Practice of Security: 12th International Symposium, FPS 2019, Toulouse, France, November 5-7, 2019, Revised Selected Papers. Springer, 2020.
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Logrippo, Luigi, Joaquin Garcia-Alfaro, Jean-Yves Marion, Abdessamad Imine, and José M. Fernandez. Foundations and Practice of Security: 10th International Symposium, FPS 2017, Nancy, France, October 23-25, 2017, Revised Selected Papers. Springer, 2018.
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Lourenço, Eduardo. El laberinto de la saudade. Psicoanálisis mítico del destino portugués. Ediciones Uniandes, 2018. http://dx.doi.org/10.51566/humalite2225.
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«Lo que yo quise hacer, sobre todo, sin querer hacerlo de una manera determinada, sino que se fue haciendo necesario poco a poco, fue una especie de tentativa de comprender cómo funciona el imaginario portugués. ¿Qué es lo que somos? Somos lo que soñamos, los mitos que construimos. ¿Cuál es la mitología portuguesa? ¿Con arreglo a qué horizonte ha funcionado la cultura portuguesa? ¿Qué tiene de particular? Eso sólo se comprende examinando sus vestigios, que son la poesía y la ficción», dice Eduardo Lourenço. Y también afirma: «El asunto propio de nuestro libro no es tanto la “preocupación por Portugal”, preocupación que está incluida por definición en todas las tentativas de autognosis, [sino] por una imagología, es decir, por el discurso crítico sobre las imágenes que [los portugueses] hemos forjado sobre nosotros mismos». Tal como Octavio Paz en El laberinto de la soledad, sobre el caso mexicano, Lourenço estudia en El laberinto de la saudade una determinada imagología. El laberinto luso es una obra crucial para captar, soñar y volver a imaginar el destino de Portugal.
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Gutmann, Flavia. Sentimentos Que Fazem Bem. Brazil Publishing, 2021. http://dx.doi.org/10.31012/978-65-5861-465-4.
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Feelings and emotions are part of our lives. Emotions are basically energy. Instinctive reactions that can’t be avoided, but their impact can be managed. Feelings, on the other hand, are the interpretation of the emotion. It can be a word, a sentence, or a description. Help our children learn vocabular to talk about their feelings is very important. The purpose of this book is to bring attention the feelings that make us feel good. Those feelings that are really good to feel. It’s a light reading that follows the alphabet and brings pleasant feelings, and examples of what we can do to feel them. A book for parents to read with their kids. For children to enhance their repertoire of feelings. To have fun with the illustrations. To exchange ideas and imagine other ways of experiencing these feelings too.
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Debbabi, Mourad, Joaquin Garcia-Alfaro, Jean Luc Danger, Jean-Yves Marion, and Nur Zincir Heywood. Foundations and Practice of Security: 6th International Symposium, FPS 2013, la Rochelle, France, October 21-22, 2013, Revised Selected Papers. Springer London, Limited, 2014.
Find full textBook chapters on the topic "FUS imaging"
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Schwille, Petra, and Jonas Ries. "Principles and Applications of Fluorescence Correlation Spectroscopy (FCS)." In Biophotonics: Spectroscopy, Imaging, Sensing, and Manipulation, 63–85. Dordrecht: Springer Netherlands, 2010. http://dx.doi.org/10.1007/978-90-481-9977-8_4.
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Montero, Vicente. "Attentional Activation of Cortico-Reticulo-Thalamic Pathways Revealed by Fos Imaging." In Plasticity in the Visual System, 97–124. Boston, MA: Springer US, 2006. http://dx.doi.org/10.1007/0-387-28190-8_6.
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Bhat, Abrar Ul Qadir, Anupama Prakash, Vijay Kumar Tayal, and Pallavi Choudekar. "Three-Phase Fault Analysis of Distributed Power System Using Fuzzy Logic System (FLS)." In Advances in Smart Communication and Imaging Systems, 615–24. Singapore: Springer Singapore, 2021. http://dx.doi.org/10.1007/978-981-15-9938-5_57.
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Nakanishi, Tomoko M. "Real-Time Element Movement in a Plant." In Novel Plant Imaging and Analysis, 109–68. Singapore: Springer Singapore, 2021. http://dx.doi.org/10.1007/978-981-33-4992-6_4.
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AbstractWe developed an imaging method utilizing the available RIs. We developed two types of real-time RI imaging systems (RRIS), one for macroscopic imaging and the other for microscopic imaging. The principle of visualization was the same, converting the radiation to light by a Cs(Tl)I scintillator deposited on a fiber optic plate (FOS). Many nuclides were employed, including 14C, 18F, 22Na, 28Mg, 32P 33P, 35S, 42K, 45Ca, 48V, 54Mn, 55Fe, 59Fe, 65Zn, 86Rb, 109Cd, and 137Cs.Since radiation can penetrate the soil as well as water, the difference between soil culture and water culture was visualized. 137Cs was hardly absorbed by rice roots growing in soil, whereas water culture showed high absorption, which could provide some reassurance after the Fukushima Nuclear Accident and could indicate an important role of soil in firmly adsorbing the radioactive cesium.28Mg and 42K, whose production methods were presented, were applied for RRIS to visualize the absorption image from the roots. In addition to 28Mg and 42K, many nuclides were applied to image absorption in the roots. Each element showed a specific absorption speed and accumulation pattern. The image analysis of the absorption of Mg is presented as an example. Through successive images of the element absorption, phloem flow in the aboveground part of the plant was analyzed. The element absorption was visualized not only in the roots but also in the leaves, a basic study of foliar fertilization.In the case of the microscopic imaging system, a fluorescence microscope was modified to acquire three images at the same time: a light image, fluorescent image, and radiation image. Although the resolution of the image was estimated to be approximately 50 μm, superposition showed the expression site of the transporter gene and the actual 32P-phosphate absorption site to be the same in Arabidopsis roots.
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Sharp, Frank R., and Stephen M. Sagar. "Mapping Sensorimotor Pathways in Rat Brain Using 2-Deoxyglucose Autoradiography and C-Fos Immunocytochemistry." In Advances in Metabolic Mapping Techniques for Brain Imaging of Behavioral and Learning Functions, 111–24. Dordrecht: Springer Netherlands, 1992. http://dx.doi.org/10.1007/978-94-011-2712-7_3.
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Martin, Lee, Jade Lee, J. C. Leapman, and Ann Rainey-Ruiz. "Making Connections: Pandemic-Era Lessons from a Maker-Centered University–Community Partnership." In University-Community Partnerships for Transformative Education, 177–89. Cham: Springer Nature Switzerland, 2024. http://dx.doi.org/10.1007/978-3-031-60583-3_9.
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AbstractBeta Lab Links connects UC Davis faculty and students with young people in the region to support them in imagining, designing, and building “maker” projects of their own choosing. The idea of “making” is broad and has a long history, but it has recently become associated with playful tinkering and design work that combines low-tech craft technologies (e.g., sewing, woodworking, and papercraft) with high-tech tools (e.g., microcontrollers, 3-D printers, software design). Advocates of maker-centered education emphasize its potential to foster STEM identity, knowledge, and skill development in a fun and inclusive environment.Typically, Beta Lab Links work in person at the schools or community centers youth already attend, using a mobile maker van to create “pop-up” making spaces. During COVID-19 closures, Beta Lab Links collaborated with the Boys & Girls Club of Greater Sacramento to distribute maker kits to families and hold weekly online sessions with upper elementary-school-aged youth. These activities focused primarily on papercraft and electronics, as these were novel, STEM-rich, and did not require additional tools.This chapter shares Beta Lab’s core pedagogical commitments and explores how the move online provided a catalyst for reflection and new insights into processes of connection and community through making.
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Takeda, Akitoshi, and Bruce Miller. "Frontotemporal dementias." In New Oxford Textbook of Psychiatry, edited by John R. Geddes, Nancy C. Andreasen, and Guy M. Goodwin, 405–13. Oxford University Press, 2020. http://dx.doi.org/10.1093/med/9780198713005.003.0041.
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Fronto-temporal dementia (FTD) is a heterogenous clinical syndrome with a progressive decline in behaviour, executive function, and language. Approximately 40% of FTD patients report a family history, and 10–15% of FTD cases show an autosomal dominant pattern of inheritance. FTD often mimics psychiatric disorders because of the prominent behavioural features, and particularly in the early stages, the only manifestation of illness may be purely behavioural. There is significant clinical, pathological, and genetic overlap between FTD and motor neuron disease/amyotrophic lateral sclerosis (FTD-ALS) and two atypical Parkinsonian syndromes—progressive supranuclear palsy (PSP) and cortico-basal degeneration (CBD). FTD is associated with non-Alzheimer’s disease pathology and the molecular aggregation of specific proteins—tau, TAR-DNA binding protein (TDP), and fused in sarcoma (FUS). Advances in clinical, imaging, and molecular characterization have increased the accuracy of FTD diagnosis. At present, appropriate management of FTD symptoms involves a combination of pharmacological therapy with techniques involving behavioural, physical, and environmental manipulation.
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Adolphe, Bruce. "Exercises to Be Done in Silence." In The Mind's Ear, 11–52. Oxford University Press, 2021. http://dx.doi.org/10.1093/oso/9780197576311.003.0002.
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The exercises in this section are performed in the mind (without the use of musical instruments) and may be done by individuals alone or by groups, such as classrooms, workshops, masterclasses, or even audiences. For individuals, who may or may not be musicians, these exercises can be fun to do at home, on trains, in waiting rooms, or just about anywhere. The exercises range from imagining visual images (as a warm-up) to imagining (in silence) ordinary sounds, scales, dynamics, instrumental timbres, harmonies, expressive performance techniques such as vibrato, and orchestration. The chapter also provides exercises that link imagining music to our other senses, and exercises that ask the participant to imagine or create sonic patterns, designs, scenarios, and compositional structures in fun and surprising ways, all in the mind’s ear.
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Schwille, Petra, Katrin Heinze, Petra Dittrich, and Elke Haustein. "Two-Photon Fluorescence Correlation Spectroscopy." In Biomedical Optical Imaging, 196–236. Oxford University PressNew York, NY, 2009. http://dx.doi.org/10.1093/oso/9780195150445.003.0008.
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Abstract Single-molecule-based fluorescence correlation spectroscopy (or FCS) is currently considered one of the most powerful complementary methods in the context of modern fluorescence microscopy. Although the information it provides is primarily of dynamic rather than spatial nature, recent FCS applications particularly in the cellular environment have raised tremendous hopes that this technique, in conjunction with confocal or two-photon imaging, can open fully new ways to investigate and understand complex biological processes on a single-molecule scale. The difference between FCS and standard microscopic techniques might be illustrated by drawing an—admittedly, rather far-fetched—parallel to wildlife observation. To learn something about, for example, animals in their natural habitat, one might either observe them from an airplane far above and take some high-resolution images or movies, or see them move around to different locations at different times to get a “big picture” about their distributions and colocalizations at certain interesting sites. One might, on the other hand, prefer to wait behind a bush or camouflage at the spots where they can be most frequently observed and take a closer look at their specific action: how fast and often they access or leave a place, how long they stay, how they interact, and how they behave as individuals. In principle, this latter approach is exactly what we want to achieve on a molecular level by applying confocal FCS analysis.
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"- Advanced Fluorescence Techniques: FLIM, FRET, and FCS." In Optical Imaging Techniques in Cell Biology, 226–45. CRC Press, 2012. http://dx.doi.org/10.1201/b12135-19.
Full textConference papers on the topic "FUS imaging"
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Maleke, Caroline, Jianwen Luo, Assimina A. Pelegri, and Elisa E. Konofagou. "Mapping of Regional Cancerous Tissue Mechanical Property Changes Using Harmonic Motion Imaging." In ASME 2007 International Mechanical Engineering Congress and Exposition. ASMEDC, 2007. http://dx.doi.org/10.1115/imece2007-42294.
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Mechanical changes in breast tissues as a result of cancer are usually detected through palpation by the physician and/or self examination. However, physicians are unable to palpate most masses under 1 cm in diameter and microscopic diseases. The goal of our study is to introduce the application of the Harmonic Motion Imaging (HMI), an acoustic radiation force technique, for reliable sensitive tumor detection and real-time monitoring of tumor ablation. Here, we applied the HMI technique using a single-element Focused Ultrasound (FUS) transducer. Due to the highly localized and harmonic nature of the response, the motion characteristics can be directly linked to the regional tissue modulus. In this experiment, a confocal transducer, combining a 4.68 MHz therapy (FUS) and a 7.5 MHz diagnostic (pulse-echo) probe, was used. The FUS beam was further modulated by a low AM continuous wave at 25 Hz. A pulser/receiver was used to drive the pulse-echo transducer at a Pulse Repetition Frequency (PRF) of 5.4 kHz. The radio-frequency (RF) signals were acquired using a standard pulse echo technique. The intensity amplitudes of the FUS beam at the focus (Ispta) were 231 W/cm2 for tumor detection and 1086 W/cm2 for FUS ablation. An analog bandpass filter was used to remove the spectrum of the FUS beam prior to displacement estimation. The resulting axial tissue displacement (i.e., HMI displacement) was estimated using an RF-based speckle tracking technique based on 1D cross-correlation. For tumor mapping, a harmonic radiation force was applied using a 2D raster-scan technique. The 3D HMI image was obtained by combining multiple 2D planes at different depths. The 2D and 3D HMI images in ex vivo breast tissues could detect a benign tumor (2×5×5mm3) surrounded by normal tissue, and a malignant tumor (8×7×5mm3) embedded in glandular and fat tissues. For FUS therapy, temperature measurements and RF signals were acquired during thermal ablation. HMI images during FUS ablation showed lower displacements, indicating thus tissue hardening due to lesion formation at temperatures higher than 50°C. A finite-element model (FEM) simulation was also used to analyze the findings of the experimental results. In conclusion, this technique demonstrates feasibility of the HMI technique for tumor detection and characterization, as well as real-time monitoring of tissue ablation based on the associated tissue elasticity changes.
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Li, Xiaoyue J., Niloufar Saharkhiz, Yangpei Liu, Md Murad Hossain, M.-Sharjeel Ansari, Bret Taback, and Elisa E. Konofagou. "Real-time lesion monitoring during FUS ablation using interleaved harmonic motion imaging guided FUS (Interleaved-HMIgFUS) in in vivo mouse and humans." In 2022 IEEE International Ultrasonics Symposium (IUS). IEEE, 2022. http://dx.doi.org/10.1109/ius54386.2022.9957857.
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Maleke, Caroline, Elisa E. Konofagou, and Emad S. Ebbini. "Real-time Focused Ultrasound Surgery (FUS) Monitoring Using Harmonic Motion Imaging (HMI)." In 8TH INTERNATIONAL SYMPOSIUM ON THERAPEUTIC ULTRASOUND. AIP, 2009. http://dx.doi.org/10.1063/1.3131420.
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Soloukey, S., B. S. Harhangi, B. S. Generowicz, J. P. H. Slenter, C. I. De Zeeuw, P. Kruizinga, and S. K. E. Koekkoek. "Towards High-Resolution functional Ultrasound (fUS) Imaging of the Murine Spinal Cord." In 2019 IEEE International Ultrasonics Symposium (IUS). IEEE, 2019. http://dx.doi.org/10.1109/ultsym.2019.8926243.
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Gesnik, Marc, Kevin Blaize, Alexandre Dizeux, Jose-Alain Sahel, Mathias Fink, Thomas Deffieux, Jean-Luc Gennisson, Serge Picaud, and Mickael Tanter. "Spatiotemporal response of rat visual cortex during moving stimuli using Functional Ultrasound (fUS) imaging." In 2016 IEEE International Ultrasonics Symposium (IUS). IEEE, 2016. http://dx.doi.org/10.1109/ultsym.2016.7728612.
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Aubier, Tom, Ivan M. Suarez Castellanos, Magali Perier, Alexandre Carpentier, and W. Apoutou N'Djin. "Mixed Focused UltraSound (FUS) / fluorescence imaging platform for characterization of the spatial-temporal dynamics of FUS-evoked calcium fluxes in an in vitro human cell model." In 2021 IEEE International Ultrasonics Symposium (IUS). IEEE, 2021. http://dx.doi.org/10.1109/ius52206.2021.9593676.
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Maleke, Caroline. "Real-Time Monitoring Of Regional Tissue Elasticity During FUS Focused Ultrasound Therapy Using Harmonic Motion Imaging." In THERAPEUTIC ULTRASOUND: 5th International Symposium on Therapeutic Ultrasound. AIP, 2006. http://dx.doi.org/10.1063/1.2205460.
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Bakshi, Saurabh, Sijia Guo, and Xiaoning Jiang. "Multi-Frequency Focused Ultrasound for Tissue Ablation." In ASME 2011 International Mechanical Engineering Congress and Exposition. ASMEDC, 2011. http://dx.doi.org/10.1115/imece2011-64076.
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In this study, the effectiveness of tissue ablation was investigated using multi-frequency high intensity focused ultrasound (HIFU) transducers (950 kHz, 1.5 MHz). Temperature rise and lesion volume were recorded when chicken tissue was ablated by focused ultrasound (FUS) with controlled ultrasound power and exposure time using single frequency and multi-frequency modes. It was found that multi-frequency tissue ablation gives a higher maximum temperature accompanied by a faster rise, and a larger ablation lesion volume, compared with single frequency ablation, under the same input conditions of electrical power, exposure time and depth of focus. Also, it was concluded that the same desired tissue temperature and ablation lesion conditions can be attained by using less power for the multi-frequency ablation. These findings are promising because the multi-frequency ultrasound ablation using FUS with a greater frequency difference could result in promising imaging guided effective therapy using one multi-frequency probe.
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Liu, Yangpei, Niloufar Saharkhiz, Murad Hossain, and Elisa E. Konofagou. "Effects of tracking beam dimensions on Harmonic Motion Imaging (HMI) with electronic beam steering of focused ultrasound (FUS)." In 2022 IEEE International Ultrasonics Symposium (IUS). IEEE, 2022. http://dx.doi.org/10.1109/ius54386.2022.9958475.
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Friedl-Vallon, Felix. "Airborne / Balloonborne Imaging FTS." In Fourier Transform Spectroscopy. Washington, D.C.: OSA, 2009. http://dx.doi.org/10.1364/fts.2009.ftha1.
Full textReports on the topic "FUS imaging"
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Lee, W. S., Victor Alchanatis, and Asher Levi. Innovative yield mapping system using hyperspectral and thermal imaging for precision tree crop management. United States Department of Agriculture, January 2014. http://dx.doi.org/10.32747/2014.7598158.bard.
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Original objectives and revisions – The original overall objective was to develop, test and validate a prototype yield mapping system for unit area to increase yield and profit for tree crops. Specific objectives were: (1) to develop a yield mapping system for a static situation, using hyperspectral and thermal imaging independently, (2) to integrate hyperspectral and thermal imaging for improved yield estimation by combining thermal images with hyperspectral images to improve fruit detection, and (3) to expand the system to a mobile platform for a stop-measure- and-go situation. There were no major revisions in the overall objective, however, several revisions were made on the specific objectives. The revised specific objectives were: (1) to develop a yield mapping system for a static situation, using color and thermal imaging independently, (2) to integrate color and thermal imaging for improved yield estimation by combining thermal images with color images to improve fruit detection, and (3) to expand the system to an autonomous mobile platform for a continuous-measure situation. Background, major conclusions, solutions and achievements -- Yield mapping is considered as an initial step for applying precision agriculture technologies. Although many yield mapping systems have been developed for agronomic crops, it remains a difficult task for mapping yield of tree crops. In this project, an autonomous immature fruit yield mapping system was developed. The system could detect and count the number of fruit at early growth stages of citrus fruit so that farmers could apply site-specific management based on the maps. There were two sub-systems, a navigation system and an imaging system. Robot Operating System (ROS) was the backbone for developing the navigation system using an unmanned ground vehicle (UGV). An inertial measurement unit (IMU), wheel encoders and a GPS were integrated using an extended Kalman filter to provide reliable and accurate localization information. A LiDAR was added to support simultaneous localization and mapping (SLAM) algorithms. The color camera on a Microsoft Kinect was used to detect citrus trees and a new machine vision algorithm was developed to enable autonomous navigations in the citrus grove. A multimodal imaging system, which consisted of two color cameras and a thermal camera, was carried by the vehicle for video acquisitions. A novel image registration method was developed for combining color and thermal images and matching fruit in both images which achieved pixel-level accuracy. A new Color- Thermal Combined Probability (CTCP) algorithm was created to effectively fuse information from the color and thermal images to classify potential image regions into fruit and non-fruit classes. Algorithms were also developed to integrate image registration, information fusion and fruit classification and detection into a single step for real-time processing. The imaging system achieved a precision rate of 95.5% and a recall rate of 90.4% on immature green citrus fruit detection which was a great improvement compared to previous studies. Implications – The development of the immature green fruit yield mapping system will help farmers make early decisions for planning operations and marketing so high yield and profit can be achieved.
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Rohan, Hana. Análisis de la Situación: Enfermedad por el Virus de Marburg en Guinea Ecuatorial y Tanzania. Institute of Development Studies, May 2023. http://dx.doi.org/10.19088/sshap.2023.013.
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Este informe proporciona una imagen global de los brotes de la enfermedad por el virus de Marburg en Guinea Ecuatorial y Tanzania, así como los factores coyunturales a tener en cuenta para implementar medidas de respuesta en ambos países. Ha sido redactado por Hana Rohan (asesora independiente) con la colaboración de Juliet Bedford (Anthrologica). Fue publicado el 10 de mayo de 2023 bajo la responsabilidad de la SSHAP.
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Cunningham, Stuart, Marion McCutcheon, Greg Hearn, Mark David Ryan, and Christy Collis. Australian Cultural and Creative Activity: A Population and Hotspot Analysis: Gold Coast. Queensland University of Technology, August 2020. http://dx.doi.org/10.5204/rep.eprints.203691.
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The Gold Coast has one of the strongest and most resilient city brands in Australia. Monikers such as the ‘glitter strip’, ‘Sin City’, ‘Australia’s playground’ and ‘famous for fun’ have variously been applied to brand the Gold Coast, with its identity long touted as revolving around ‘sun, surf and sand’. Belinda McKay (2005, p. 68) observes that the Gold Coast is often seen as a place to escape to, ‘where new possibilities can be imagined and enacted’: this sense of escape from the ordinary remains a strong element of the Gold Coast’s place identity.
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Karki, Shanta. Applying the River of Life Method to Support Reflection and Learning in Terre des hommes Nepal. Institute of Development Studies, September 2023. http://dx.doi.org/10.19088/clarissa.2023.005.
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The RoL method is a visual narrative method that helps people tell stories of the past, present, and future. Individuals can use this method to introduce themselves in a fun and descriptive way. A group can use it to understand and reflect on the past and imagine the future of a project. Besides, it can also be used to build a shared view of a process over time while acknowledging different and perhaps contradictory perspectives. The method uses drawings rather than text, making it useful in groups that do not share a common language. Metaphors from a river are used to explore aspects of a story – such as whirlpools depicting challenges or lakes suggesting a sense of calm etc. When used in a group, it is an active method, engaging people in the process of storytelling and listening through visualising their experiences and using metaphors to explore in depth. In CLARISSA, we adapted the RoL method to document our collective understanding of the story of implementation of the programme as part of the programme’s monitoring, evaluation and learning component. The purpose was to surface the details of our process of the systemic Action Research that we are undertaking with children in the worst forms of child labour and business owners. We used the same river metaphors as is often applied when the method is used with individuals.
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La transición energética en el Reino Unido. Universidad de Deusto, 2020. http://dx.doi.org/10.18543/ajky4025.
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El objetivo del presente estudio consiste en ofrecer una imagen del sistema energético británico y los retos a los que se enfrenta para acometer la transición energética del país. Para ello, en primer lugar, se contextualiza el territorio, debido a sus peculiaridades tanto geográficas como políticas. A continuación, se realiza un análisis de la evolución histórica del sector energético, que viene acompañada, en el siguiente capítulo por la situación del mix energético del país y del impacto medioambiental de la actividad energética de Reino Unido. Debido a la importancia de la energía como factor de competitividad y bienestar de la población, se incluye un apartado relativo a los precios de la energía. Posteriormente, se trata de recoger los principales desarrollos legislativos sobre los que se apoya la transición del sector y un apartado sobre el desarrollo industrial. En último lugar, un capítulo recoge las principales conclusiones del estudio. Todo el análisis se realiza teniendo en cuenta el actual contexto del Brexit, que fue cambiando a lo largo del propio estudio.