Saving lives, saving earth: hypofractionation and carbon footprint.

PURPOSE: The healthcare system contributes approximately 5% of global greenhouse gas emissions, yet the environmental impact of radiotherapy treatments remains inadequately assessed. MATERIAL AND METHODS: We selected all breast cancer patients (1959 patients) treated with adjuvant radiotherapy between 2015 and 2023 in one institution. We analyzed the CO2 emissions associated with travel. We also selected 60 patients randomly to analyze treatment-associated carbon emissions. We compared three different fractionation schemes: normofractionation (25-30 fractions, fx), hypofractionation (15-18fx), and ultra-hypofractionation (5-6fx). RESULTS: Our study revealed a significant reduction in carbon emissions within the 5-fractions group compared to the 15-fractions group (26.69kg vs 57.13kg, p < 0.001), saving approximately the CO2 emissions associated with the electricity consumption of an average Spanish household for 12 days, or the emissions of a passenger flying from Madrid to Barcelona. CONCLUSION: Most of the carbon footprint of radiotherapy is due to travel. Hypofractionation could be an appropriate solution to protect the environment.

Telemedicine Quality Improvement during the Corona Virus 2019 Pandemic Increases Pediatric Weight Management Access.

Background: The corona virus 2019 pandemic disrupted care for pediatric patients with chronic conditions, including those with childhood obesity. Lockdowns forced providers to create new ways of caring for this population. Telemedicine was a promising but previously unavailable solution. This quality improvement report details how the Healthy and Fit Children's Clinic transitioned and improved care via telemedicine. Methods: Between March 2020 and April 2021, the quality improvement project team incorporated the Model for Improvement to transition the clinic to telemedicine. The team tracked Healthy and Fit Children's Clinic appointments, no-shows, billing and reimbursement data, and noted unintended consequences or unanticipated barriers. Patients and their families were given a satisfaction survey at the end of each telemedicine encounter. Results: Compared with pre-telemedicine implementation, there was a 120% increase in completed patient clinic visits per week and a sustained positive shift above the established baseline. Telemedicine no-show rates achieved <10%, with an average sustained rate of <20%, compared with unchanged in-person no-show rates of >50% pre- and post-telemedicine implementation. There was a 74% increase in monthly billing and a sustained positive shift above the pre-telemedicine baseline. On average, patients rated all six satisfaction questions ≥92 on the 100-point scale (compared with 83 pre-telemedicine). Conclusions: This transition to telemedicine was successful and could be translatable to other clinic sites. Patients attended their clinic visits more consistently and were highly satisfied with their care. In a population where continuity of care is paramount, telemedicine shows promise as a tool to treat childhood obesity.

High Spatiotemporal Resolution Radial Encoding Single-Vessel fMRI.

High-field preclinical functional MRI (fMRI) is enabled the high spatial resolution mapping of vessel-specific hemodynamic responses, that is single-vessel fMRI. In contrast to investigating the neuronal sources of the fMRI signal, single-vessel fMRI focuses on elucidating its vascular origin, which can be readily implemented to identify vascular changes relevant to vascular dementia or cognitive impairment. However, the limited spatial and temporal resolution of fMRI is hindered hemodynamic mapping of intracortical microvessels. Here, the radial encoding MRI scheme is implemented to measure BOLD signals of individual vessels penetrating the rat somatosensory cortex. Radial encoding MRI is employed to map cortical activation with a focal field of view (FOV), allowing vessel-specific functional mapping with 50 × 50 µm2 in-plane resolution at a 1 to 2 Hz sampling rate. Besides detecting refined hemodynamic responses of intracortical micro-venules, the radial encoding-based single-vessel fMRI enables the distinction of fMRI signals from vessel and peri-vessel voxels due to the different contribution of intravascular and extravascular effects.

Reirradiation salvage radiotherapy for recurrent prostate cancer after primary low-dose brachytherapy / Radioterapia de rescate con reirradiación para el cáncer de próstata recurrente después de braquiterapia primaria de dosis baja

Purpose: Local recurrence of prostate cancer after low-dose rate brachytherapy is a clinical problem with limited salvage treatment options. This prospective study evaluated the tolerability and outcome of salvage external beam radiation therapy (S-EBRT) for locally recurrent prostate cancer after primary low-dose rate prostate brachytherapy (LDR-BT). Materials and methods: Between October 2012 and 2022, 18 patients with biopsy-proven locally recurrent prostate cancer after primary LDR-BT and received S-EBRT. We evaluated biochemical failure (BF), overall survival (OS) and acute/late gastrointestinal and urinary toxicities (CTCAE v5.0 or CTCAE v4, only before 2017). Results: Median follow-up was 32 months (range, 5–124). The median age was at S-EBRT 68 years (range 59–79). 34% (6/18) were low risk, 44% (8/18) intermediate risk, 5% (1/18) high risk, and 17% (3/18) not specified. All patients were treated with IMRT/VMAT and received 60 Gy (2.5 Gy/fraction) to the prostate and 40% (7/18) 55.2 Gy (2,3 Gy/fx) to the seminal vesicles. 56% received ADT The 3-year OS and biochemical relapse-free survival after S-EBRT were 100% and 89%, respectively, with a median PSA nadir 0,035 ng/mL (0,01–0,34). Acute cystitis was present in 72% (13/18) of patients (27% of Grade > 2). Urethritis was present in 78% (14/18) patients (16% of cases Grade > 3), and acute rectitis occurred in 22% (4/18) of patients (no cases Grade > 3). Conclusions: Our data suggest that the treatment of locally recurrent prostate cancer with S-EBRT could provide adequate disease control safely and be used as an additional treatment in the natural history of prostate cancer patients. However, the results are still early and the sample is small; larger studies with longer follow-up would be mandatory.(AU)

Reirradiation salvage radiotherapy for recurrent prostate cancer after primary low-dose brachytherapy.

PURPOSE: Local recurrence of prostate cancer after low-dose rate brachytherapy is a clinical problem with limited salvage treatment options. This prospective study evaluated the tolerability and outcome of salvage external beam radiation therapy (S-EBRT) for locally recurrent prostate cancer after primary low-dose rate prostate brachytherapy (LDR-BT). MATERIALS AND METHODS: Between October 2012 and 2022, 18 patients with biopsy-proven locally recurrent prostate cancer after primary LDR-BT and received S-EBRT. We evaluated biochemical failure (BF), overall survival (OS) and acute/late gastrointestinal and urinary toxicities (CTCAE v5.0 or CTCAE v4, only before 2017). RESULTS: Median follow-up was 32 months (range, 5-124). The median age was at S-EBRT 68 years (range 59-79). 34% (6/18) were low risk, 44% (8/18) intermediate risk, 5% (1/18) high risk, and 17% (3/18) not specified. All patients were treated with IMRT/VMAT and received 60 Gy (2.5 Gy/fraction) to the prostate and 40% (7/18) 55.2 Gy (2,3 Gy/fx) to the seminal vesicles. 56% received ADT The 3-year OS and biochemical relapse-free survival after S-EBRT were 100% and 89%, respectively, with a median PSA nadir 0,035 ng/mL (0,01-0,34). Acute cystitis was present in 72% (13/18) of patients (27% of Grade > 2). Urethritis was present in 78% (14/18) patients (16% of cases Grade > 3), and acute rectitis occurred in 22% (4/18) of patients (no cases Grade > 3). CONCLUSIONS: Our data suggest that the treatment of locally recurrent prostate cancer with S-EBRT could provide adequate disease control safely and be used as an additional treatment in the natural history of prostate cancer patients. However, the results are still early and the sample is small; larger studies with longer follow-up would be mandatory.

Characterizing brain stage-dependent pupil dynamics based on lateral hypothalamic activity.

Pupil dynamics presents varied correlation features with brain activity under different vigilant levels. The modulation of brain dynamic stages can arise from the lateral hypothalamus (LH), where diverse neuronal cell types contribute to arousal regulation in opposite directions via the anterior cingulate cortex (ACC). However, the relationship of the LH and pupil dynamics has seldom been investigated. Here, we performed local field potential (LFP) recordings at the LH and ACC, and whole-brain fMRI with simultaneous fiber photometry Ca2+ recording in the ACC, to evaluate their correlation with brain state-dependent pupil dynamics. Both LFP and functional magnetic resonance imaging (fMRI) data showed various correlations to pupil dynamics across trials that span negative, null, and positive correlation values, demonstrating brain state-dependent coupling features. Our results indicate that the correlation of pupil dynamics with ACC LFP and whole-brain fMRI signals depends on LH activity, suggesting a role of the latter in brain dynamic stage regulation.

Cortical depth-dependent human fMRI of resting-state networks using EPIK.

Introduction: Recent laminar-fMRI studies have substantially improved understanding of the evoked cortical responses in multiple sub-systems; in contrast, the laminar component of resting-state networks spread over the whole brain has been less studied due to technical limitations. Animal research strongly suggests that the supragranular layers of the cortex play a critical role in maintaining communication within the default mode network (DMN); however, whether this is true in this and other human cortical networks remains unclear. Methods: Here, we used EPIK, which offers unprecedented coverage at sub-millimeter resolution, to investigate cortical broad resting-state dynamics with depth specificity in healthy volunteers. Results: Our results suggest that human DMN connectivity is primarily supported by intermediate and superficial layers of the cortex, and furthermore, the preferred cortical depth used for communication can vary from one network to another. In addition, the laminar connectivity profile of some networks showed a tendency to change upon engagement in a motor task. In line with these connectivity changes, we observed that the amplitude of the low-frequency-fluctuations (ALFF), as well as the regional homogeneity (ReHo), exhibited a different laminar slope when subjects were either performing a task or were in a resting state (less variation among laminae, i.e., lower slope, during task performance compared to rest). Discussion: The identification of varied laminar profiles concerning network connectivity, ALFF, and ReHo, observed across two brain states (task vs. rest) has major implications for the characterization of network-related diseases and suggests the potential diagnostic value of laminar fMRI in psychiatric disorders, e.g., to differentiate the cortical dynamics associated with disease stages linked, or not linked, to behavioral changes. The evaluation of laminar-fMRI across the brain encompasses computational challenges; nonetheless, it enables the investigation of a new dimension of the human neocortex, which may be key to understanding neurological disorders from a novel perspective.

Haematological and renal toxicity of radiation therapy in neuroblastoma paediatric patients

Purpose The objective of this study was to evaluate the renal and hematologic toxicity in paediatric patients with adrenal high-risk neuroblastoma who have received radiation therapy (RT) as part of radical treatment. Material and methods Pediatric patients diagnosed with high-risk adrenal neuroblastoma who received RT as part of the definitive treatment between January 2004 and May 2020 in a single institution were selected. Complete blood counts (CBC) and creatinine clearance (CrCl) pre-RT and post-RT were compared through the Wilcoxon signed-rank test and correlated with survival analysis by Cox regression. Results Forty-two children with a median age of 3 years at diagnosis and 2.8 years of follow-up were selected. A significant and acute decrease in lymphocytes was found (p = 0.002) 1 month from RT. Patients with a drop higher than 50% of the previous value experimented a significant reduction in overall survival (55 vs 10%; p = 0.031). At the end of the follow-up, a significant increase in all blood counts was observed. With respect to renal function, an acute and significant decrease in CrCl was observed tin patients younger than 4 years who received RT (p = 0.013). However, it was not clinically relevant. Conclusion Our data suggest that acute lymphopenia occurs after RT and could be associated with a poorer prognosis. Other blood counts are reduced after RT and all of them are in physiological range at the end of follow-up. Our cohort presented excellent renal outcomes without any case of chronic renal dysfunction (AU)

Pediatric Hepatitis C Quality Improvement Project Improves Healthcare Access.

OBJECTIVES: Incidence of hepatitis C virus (HCV) infection is increasing in women of reproductive age, leading to increased prevalence of HCV infection in children via vertical transmission. This quality improvement (QI) project aimed to increase referrals to and appointments scheduled with a specialty pediatric gastroenterology HCV clinic and the number of eligible children with HCV who completed treatment. METHODS: From July 2020 to August 2021, the QI team designed a project using the Model for Improvement and completed Plan Do Study Act cycles to test change ideas to improve HCV awareness and education for medical providers and families; standardize the referral process; track patients; increase clinic capacity; and connect families with community resource care coordination. Referrals to the pediatric HCV clinic, appointments scheduled, no shows, and treatment follow-up were tracked during the project period and a comparison timeframe from July 2019 to June 2020. RESULTS: There were improvements in several measures during the project period versus the comparison timeframe, with 80 versus 48 referrals received (66% increase), 115 versus 59 scheduled clinic visits (95% increase), and 7 versus 5 treatment completers (40% increase), along with a small (7%) decline in the proportion of scheduled clinic visits that were no shows. CONCLUSION: Application of QI methodology increased medical provider and caregiver awareness and engagement in accessing HCV healthcare available for at-risk children. More QI efforts should be accelerated to identify best practices amidst a nationwide HCV epidemic.

Haematological and renal toxicity of radiation therapy in neuroblastoma paediatric patients.

PURPOSE: The objective of this study was to evaluate the renal and hematologic toxicity in paediatric patients with adrenal high-risk neuroblastoma who have received radiation therapy (RT) as part of radical treatment. MATERIAL AND METHODS: Pediatric patients diagnosed with high-risk adrenal neuroblastoma who received RT as part of the definitive treatment between January 2004 and May 2020 in a single institution were selected. Complete blood counts (CBC) and creatinine clearance (CrCl) pre-RT and post-RT were compared through the Wilcoxon signed-rank test and correlated with survival analysis by Cox regression. RESULTS: Forty-two children with a median age of 3 years at diagnosis and 2.8 years of follow-up were selected. A significant and acute decrease in lymphocytes was found (p = 0.002) 1 month from RT. Patients with a drop higher than 50% of the previous value experimented a significant reduction in overall survival (55 vs 10%; p = 0.031). At the end of the follow-up, a significant increase in all blood counts was observed. With respect to renal function, an acute and significant decrease in CrCl was observed tin patients younger than 4 years who received RT (p = 0.013). However, it was not clinically relevant. CONCLUSION: Our data suggest that acute lymphopenia occurs after RT and could be associated with a poorer prognosis. Other blood counts are reduced after RT and all of them are in physiological range at the end of follow-up. Our cohort presented excellent renal outcomes without any case of chronic renal dysfunction.

El pediatre davant un lactant amb dismorfisme cranial / El pediatra ante un lactante con dismorfia craneal / The pediatrician’s approach to an infant with cranial dysmorphism

Fonament. El dismorfisme cranial és una anomalia detectadasovint des de l’atenció primària. Els darrers anys la sevaincidència ha anat en augment a causa de la implantació dela campanya per evitar la mort sobtada dels lactants, en quèes recomana la posició en decúbit supí per dormir. Sovintaquesta troballa exploratòria és fruit de derivacions a especialistes atesa la dificultat que suposa diferenciar els dismorfismes cranials posturals dels d’origen sinostòtic, secundaris a la fusió prematura de les sutures cranials.Objectiu. Descriure la presentació clínica, l’exploració física, els possibles tractaments i el pronòstic dels diferentsdismorfismes cranials, posant un èmfasi especial en donarclaus per diferenciar els dismorfismes cranials posturalsdels sinostòtics.Mètode. Mitjançant revisió bibliogràfica, emprant les paraules clau «craniosynostosis» i «nonsynostotic plagiocephaly»a les bases de dades UpToDate i PubMed.Resultats. El tractament i el pronòstic dels dismorfismescranials varia en funció de l’etiologia i la gravetat. En lesdeformitats posicionals és primordial conèixer les mesurespreventives per evitar-los. D’altra banda, les craniosinostosis s’han de derivar a neurocirurgia i totes es tracten quirúrgicament. Operades a temps, les craniosinostosis solentenir molt bon pronòstic i se n’eviten les seqüeles.Conclusions. Té una importància vital saber diferenciar lesetiologies dels diferents dismorfismes cranials. Cal empoderar els pares de manera que puguin prevenir dismorfismes posturals i, com a pediatres, hem de ser capaços dereconèixer possibles craniosinostosis i derivar-les a la consulta especialitzada per fer un tractament precoç i millorarel pronòstic d’aquests infants. (AU)

Fundamento. Las dismorfias craneales son una anomalía detectadafrecuentemente desde la atención primaria. En los últimos años suincidencia ha ido en aumento debido a la implantación de la campaña para evitar la muerte súbita de los lactantes, donde se recomienda la posición en decúbito supino para dormir. A menudo este hallazgo exploratorio es fruto de derivaciones a especialistas dadala dificultad que supone diferenciar las dismorfias craneales posturales de las de origen sinostótico, secundarias a la fusión prematura de las suturas craneales.Objetivo. Describir la presentación clínica, la exploración física, losposibles tratamientos y el pronóstico de las diferentes dismorfiascraneales, poniendo especial énfasis en dar claves para diferenciarlas dismorfias craneales posturales de las sinostóticas.Método. Mediante revisión bibliográfica, usando las palabras clave«craniosynostosis» y «nonsynostotic plagiocephaly» en las basesde datos UpToDate y PubMed.Resultados. El tratamiento y pronóstico de las dismorfias cranealesvaría en función de su etiología y gravedad. En las deformidadesposicionales es primordial conocer las medidas preventivas paraevitarlas. Por otro lado, las craneosinostosis deben ser derivadas aneurocirugía y todas se tratan quirúrgicamente. Operadas a tiempo,las craneosinostosis suelen tener muy buen pronóstico y se evitanlas secuelas de esta entidad.Conclusiones. Es de vital importancia saber diferenciar las etiologías de las diferentes dismorfias craneales. Hay que empoderar alos padres de forma que puedan prevenir dismorfias posturales y,como pediatras, debemos ser capaces de reconocer posibles craneosinostosis y derivarlas a la consulta especializada para poderhacer un tratamiento precoz y mejorar el pronóstico de estos niños. (AU)

Background. Cranial dysmorphism is a congenital defect usuallydetected in primary care. Over the last few years, its incidence hasincreased due to the implementation of prone position for infantsduring sleep to avoid sudden death. Often, this finding results inreferrals to specialists given the difficulties in distinguishing between positional dysmorphism from those of syntostotic origin,which are secondary to premature fusion of the cranial sutures.Objective. To describe the clinical presentation, physical examination, possible treatments, and prognosis, of the different cranialdysmorphisms, and highlight the differential diagnosis betweenpositional dysmorphism and craniosynostosis.Method. Literature review of the UpToDate and PubMed databasesusing the key words “craniosynostosis” and “nonsynostotic plagiocephaly”. Results. The treatment and prognosis of cranial dysmorphism varies according to its etiology and severity. In positional deformitiesit is key to understand the possible preventive measures. Childrenwith craniosynostosis should be referred for neurosurgicaltreatment. With timely surgical correction, craniosynostosis have avery good prognosis with minimal sequelae.Conclusions. It is important to differentiate between the differentcauses of cranial dysmorphism. Parents should be educated toprevent positional deformities, and pediatricians should be able torecognize possible cases of craniosynostosis and refer them forearly treatment. (AU)

Mapping of whole-cerebrum resting-state networks using ultra-high resolution acquisition protocols.

Resting-state functional magnetic resonance imaging (fMRI) has been used in numerous studies to map networks in the brain that employ spatially disparate regions. However, attempts to map networks with high spatial resolution have been hampered by conflicting technical demands and associated problems. Results from recent fMRI studies have shown that spatial resolution remains around 0.7 × 0.7 × 0.7 mm3 , with only partial brain coverage. Therefore, this work aims to present a novel fMRI technique that was developed based on echo-planar-imaging with keyhole (EPIK) combined with repetition-time-external (TR-external) EPI phase correction. Each technique has been previously shown to be effective in enhancing the spatial resolution of fMRI, and in this work, the combination of the two techniques into TR-external EPIK provided a nominal spatial resolution of 0.51 × 0.51 × 1.00 mm3 (0.26 mm3 voxel) with whole-cerebrum coverage. Here, the feasibility of using half-millimetre in-plane TR-external EPIK for resting-state fMRI was validated using 13 healthy subjects and the corresponding reproducible mapping of resting-state networks was demonstrated. Furthermore, TR-external EPIK enabled the identification of various resting-state networks distributed throughout the brain from a single fMRI session, with mapping fidelity onto the grey matter at 7T. The high-resolution functional image further revealed mesoscale anatomical structures, such as small cerebral vessels and the internal granular layer of the cortex within the postcentral gyrus.

Pre-processing of Sub-millimeter GE-BOLD fMRI Data for Laminar Applications.

Over the past 30 years, brain function has primarily been evaluated non-invasively using functional magnetic resonance imaging (fMRI) with gradient-echo (GE) sequences to measure blood-oxygen-level-dependent (BOLD) signals. Despite the multiple advantages of GE sequences, e.g., higher signal-to-noise ratio, faster acquisitions, etc., their relatively inferior spatial localization compromises the routine use of GE-BOLD in laminar applications. Here, in an attempt to rescue the benefits of GE sequences, we evaluated the effect of existing pre-processing methods on the spatial localization of signals obtained with EPIK, a GE sequence that affords voxel volumes of 0.25 mm3 with near whole-brain coverage. The methods assessed here apply to both task and resting-state fMRI data assuming the availability of reconstructed magnitude and phase images.

Contribution of animal models toward understanding resting state functional connectivity.

Functional connectivity, which reflects the spatial and temporal organization of intrinsic activity throughout the brain, is one of the most studied measures in human neuroimaging research. The noninvasive acquisition of resting state functional magnetic resonance imaging (rs-fMRI) allows the characterization of features designated as functional networks, functional connectivity gradients, and time-varying activity patterns that provide insight into the intrinsic functional organization of the brain and potential alterations related to brain dysfunction. Functional connectivity, hence, captures dimensions of the brain's activity that have enormous potential for both clinical and preclinical research. However, the mechanisms underlying functional connectivity have yet to be fully characterized, hindering interpretation of rs-fMRI studies. As in other branches of neuroscience, the identification of the neurophysiological processes that contribute to functional connectivity largely depends on research conducted on laboratory animals, which provide a platform where specific, multi-dimensional investigations that involve invasive measurements can be carried out. These highly controlled experiments facilitate the interpretation of the temporal correlations observed across the brain. Indeed, information obtained from animal experimentation to date is the basis for our current understanding of the underlying basis for functional brain connectivity. This review presents a compendium of some of the most critical advances in the field based on the efforts made by the animal neuroimaging community.

Decoding the brain state-dependent relationship between pupil dynamics and resting state fMRI signal fluctuation.

Pupil dynamics serve as a physiological indicator of cognitive processes and arousal states of the brain across a diverse range of behavioral experiments. Pupil diameter changes reflect brain state fluctuations driven by neuromodulatory systems. Resting-state fMRI (rs-fMRI) has been used to identify global patterns of neuronal correlation with pupil diameter changes; however, the linkage between distinct brain state-dependent activation patterns of neuromodulatory nuclei with pupil dynamics remains to be explored. Here, we identified four clusters of trials with unique activity patterns related to pupil diameter changes in anesthetized rat brains. Going beyond the typical rs-fMRI correlation analysis with pupil dynamics, we decomposed spatiotemporal patterns of rs-fMRI with principal component analysis (PCA) and characterized the cluster-specific pupil-fMRI relationships by optimizing the PCA component weighting via decoding methods. This work shows that pupil dynamics are tightly coupled with different neuromodulatory centers in different trials, presenting a novel PCA-based decoding method to study the brain state-dependent pupil-fMRI relationship.

Mapping the Brain-Wide Network Effects by Optogenetic Activation of the Corpus Callosum.

Optogenetically driven manipulation of circuit-specific activity enables causality studies, but its global brain-wide effect is rarely reported. Here, we applied simultaneous functional magnetic resonance imaging (fMRI) and calcium recording with optogenetic activation of the corpus callosum (CC) connecting barrel cortices (BC). Robust positive BOLD was detected in the ipsilateral BC due to antidromic activity, spreading to the ipsilateral motor cortex (MC), and posterior thalamus (PO). In the orthodromic target, positive BOLD was reliably evoked by 2 Hz light pulses, whereas 40 Hz light pulses led to reduced calcium, indicative of CC-mediated inhibition. This presumed optogenetic CC-mediated inhibition was further elucidated by pairing light pulses with whisker stimulation at varied interstimulus intervals. Whisker-induced positive BOLD and calcium signals were reduced at intervals of 50/100 ms. The calcium-amplitude-modulation-based correlation with whole-brain fMRI signal revealed that the inhibitory effects spread to contralateral BC, ipsilateral MC, and PO. This work raises the need for fMRI to elucidate the brain-wide network activation in response to optogenetic stimulation.

Indexing brain state-dependent pupil dynamics with simultaneous fMRI and optical fiber calcium recording.

Pupillometry, a noninvasive measure of arousal, complements human functional MRI (fMRI) to detect periods of variable cognitive processing and identify networks that relate to particular attentional states. Even under anesthesia, pupil dynamics correlate with brain-state fluctuations, and extended dilations mark the transition to more arousable states. However, cross-scale neuronal activation patterns are seldom linked to brain state-dependent pupil dynamics. Here, we complemented resting-state fMRI in rats with cortical calcium recording (GCaMP-mediated) and pupillometry to tackle the linkage between brain-state changes and neural dynamics across different scales. This multimodal platform allowed us to identify a global brain network that covaried with pupil size, which served to generate an index indicative of the brain-state fluctuation during anesthesia. Besides, a specific correlation pattern was detected in the brainstem, at a location consistent with noradrenergic cell group 5 (A5), which appeared to be dependent on the coupling between different frequencies of cortical activity, possibly further indicating particular brain-state dynamics. The multimodal fMRI combining concurrent calcium recordings and pupillometry enables tracking brain state-dependent pupil dynamics and identifying unique cross-scale neuronal dynamic patterns under anesthesia.

Hematoma intraparenquimatoso asociado a vasculitis ANCA positiva / Intraparenchymal haematoma associated with an ANCA-positive vasculitis

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