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1.
Circulation ; 149(19): 1474-1489, 2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38533643

RESUMEN

BACKGROUND: Heart failure triggers a shift in myocardial metabolic substrate utilization, favoring the ketone body 3-hydroxybutyrate as energy source. We hypothesized that 14-day treatment with ketone ester (KE) would improve resting and exercise hemodynamics and exercise capacity in patients with heart failure with reduced ejection fraction. METHODS: In a randomized, double-blind cross-over study, nondiabetic patients with heart failure with reduced ejection fraction received 14-day KE and 14-day isocaloric non-KE comparator regimens of 4 daily doses separated by a 14-day washout period. After each treatment period, participants underwent right heart catheterization, echocardiography, and blood sampling at plasma trough levels and after dosing. Participants underwent an exercise hemodynamic assessment after a second dosing. The primary end point was resting cardiac output (CO). Secondary end points included resting and exercise pulmonary capillary wedge pressure and peak exercise CO and metabolic equivalents. RESULTS: We included 24 patients with heart failure with reduced ejection fraction (17 men; 65±9 years of age; all White). Resting CO at trough levels was higher after KE compared with isocaloric comparator (5.2±1.1 L/min versus 5.0±1.1 L/min; difference, 0.3 L/min [95% CI, 0.1-0.5), and pulmonary capillary wedge pressure was lower (8±3 mm Hg versus 11±3 mm Hg; difference, -2 mm Hg [95% CI, -4 to -1]). These changes were amplified after KE dosing. Across all exercise intensities, KE treatment was associated with lower mean exercise pulmonary capillary wedge pressure (-3 mm Hg [95% CI, -5 to -1] ) and higher mean CO (0.5 L/min [95% CI, 0.1-0.8]), significantly different at low to moderate steady-state exercise but not at peak. Metabolic equivalents remained similar between treatments. In exploratory analyses, KE treatment was associated with 18% lower NT-proBNP (N-terminal pro-B-type natriuretic peptide; difference, -98 ng/L [95% CI, -185 to -23]), higher left ventricular ejection fraction (37±5 versus 34±5%; P=0.01), and lower left atrial and ventricular volumes. CONCLUSIONS: KE treatment for 14 days was associated with higher CO at rest and lower filling pressures, cardiac volumes, and NT-proBNP levels compared with isocaloric comparator. These changes persisted during exercise and were achieved on top of optimal medical therapy. Sustained modulation of circulating ketone bodies is a potential treatment principle in patients with heart failure with reduced ejection fraction. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05161650.


Asunto(s)
Insuficiencia Cardíaca , Volumen Sistólico , Humanos , Masculino , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/fisiopatología , Femenino , Método Doble Ciego , Anciano , Volumen Sistólico/efectos de los fármacos , Persona de Mediana Edad , Estudios Cruzados , Tolerancia al Ejercicio/efectos de los fármacos , Administración Oral , Función Ventricular Izquierda/efectos de los fármacos , Resultado del Tratamiento , Ésteres/administración & dosificación , Cetonas/administración & dosificación
2.
Circulation ; 2024 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-39162035

RESUMEN

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is a major cause of morbidity and mortality in patients with type 2 diabetes (T2DM). Acute increases in circulating levels of ketone body 3-hydroxybutyrate have beneficial acute hemodynamic effects in patients without T2DM with chronic heart failure with reduced ejection fraction. However, the cardiovascular effects of prolonged oral ketone ester (KE) treatment in patients with T2DM and HFpEF remain unknown. METHODS: A total of 24 patients with T2DM and HFpEF completed a 6-week randomized, double-blind crossover study. All patients received 2 weeks of KE treatment (25 g D-ß-hydroxybutyrate-(R)-1,3-butanediol × 4 daily) and isocaloric and isovolumic placebo, separated by a 2-week washout period. At the end of each treatment period, patients underwent right heart catheterization, echocardiography, and blood samples at trough levels of intervention, and then during a 4-hour resting period after a single dose. A subsequent second dose was administered, followed by an exercise test. The primary end point was cardiac output during the 4-hour rest period. RESULTS: During the 4-hour resting period, circulating 3-hydroxybutyrate levels were 10-fold higher after KE treatment (1010±56 µmol/L; P<0.001) compared with placebo (91±55 µmol/L). Compared with placebo, KE treatment increased cardiac output by 0.2 L/min (95% CI, 0.1 to 0.3) during the 4-hour period and decreased pulmonary capillary wedge pressure at rest by 1 mm Hg (95% CI, -2 to 0) and at peak exercise by 5 mm Hg (95% CI, -9 to -1). KE treatment decreased the pressure-flow relationship (∆ pulmonary capillary wedge pressure/∆ cardiac output) significantly during exercise (P<0.001) and increased stroke volume by 10 mL (95% CI, 0 to 20) at peak exercise. KE right-shifted the left ventricular end-diastolic pressure-volume relationship, suggestive of reduced left ventricular stiffness and improved compliance. Favorable hemodynamic responses of KE treatment were also observed in patients treated with sodium-glucose transporter-2 inhibitors and glucagon-like peptide-1 analogs. CONCLUSIONS: In patients with T2DM and HFpEF, a 2-week oral KE treatment increased cardiac output and reduced cardiac filling pressures and ventricular stiffness. At peak exercise, KE treatment markedly decreased pulmonary capillary wedge pressure and improved pressure-flow relationship. Modulation of circulating ketone levels is a potential new treatment modality for patients with T2DM and HFpEF. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique Identifier: NCT05236335.

3.
Br J Haematol ; 2024 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-39161981

RESUMEN

Recently, an antibody which inhibits the glycoprotein A repetitions predominant (GARP)-mediated release of active transforming growth factor beta (TGFß) from the TGFß propeptide latency-associated peptide (LAP) showed preclinical activity in a murine model of the chronic myeloproliferative neoplasms (MPN). Consequently, we investigated the expression of the immunosuppressive molecules LAP and GARP on peripheral blood lymphocytes from 56 MPN patients and 11 healthy donors (HD). We found that lymphocytes from patients with MPN express higher levels of LAP and GARP with no strong differences found between the different MPN diagnoses. The impact of clinical parameters on the expression of LAP and GARP by lymphocytes showed that patients with calreticulin (CALR)mut MPN have increased expression compared with HD and patients with the Januskinase2 (JAK2) mutation. The fraction of lymphocytes bound to activated platelets (aPLT) strongly correlate to LAP and GARP expression suggesting that it is not the lymphocytes themselves but aPLT, which confer the increased expression of GARP and LAP on MPN patient lymphocytes. Notably, no differences in neither platelet counts nor anti-thrombotic therapy was identified between patients with JAK2- and CALRmut patients. Analysis of platelet gene expression failed to identify differences in expression of relevant genes between JAK2- and CALRmut patients.

4.
Glob Chang Biol ; 30(4): e17279, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38619007

RESUMEN

There are close links between solar UV radiation, climate change, and plastic pollution. UV-driven weathering is a key process leading to the degradation of plastics in the environment but also the formation of potentially harmful plastic fragments such as micro- and nanoplastic particles. Estimates of the environmental persistence of plastic pollution, and the formation of fragments, will need to take in account plastic dispersal around the globe, as well as projected UV radiation levels and climate change factors.


Asunto(s)
Energía Solar , Rayos Ultravioleta , Rayos Ultravioleta/efectos adversos , Cambio Climático , Contaminación Ambiental , Tiempo (Meteorología)
5.
J Exp Biol ; 227(9)2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38682690

RESUMEN

Insect performance is linked to environmental temperature, and surviving through winter represents a key challenge for temperate, alpine and polar species. To overwinter, insects have adapted a range of strategies to become truly cold hardy. However, although the mechanisms underlying the ability to avoid or tolerate freezing have been well studied, little attention has been given to the challenge of maintaining ion homeostasis at frigid temperatures in these species, despite this limiting cold tolerance for insects susceptible to mild chilling. Here, we investigated how prolonged exposure to temperatures just above the supercooling point affects ion balance in freeze-avoidant mountain pine beetle (Dendroctonus ponderosae) larvae in autumn, mid-winter and spring, and related it to organismal recovery times and survival. Hemolymph ion balance was gradually disrupted during the first day of exposure, characterized by hyperkalemia and hyponatremia, after which a plateau was reached and maintained for the rest of the 7-day experiment. The degree of ionoregulatory collapse correlated strongly with recovery times, which followed a similar asymptotical progression. Mortality increased slightly during extensive cold exposures, where hemolymph K+ concentration was highest, and a sigmoidal relationship was found between survival and hyperkalemia. Thus, the cold tolerance of the freeze-avoiding larvae of D. ponderosae appears limited by the ability to prevent ionoregulatory collapse in a manner similar to that of chill-susceptible insects, albeit at much lower temperatures. Based on these results, we propose that a prerequisite for the evolution of insect freeze avoidance may be a convergent or ancestral ability to maintain ion homeostasis during extreme cold stress.


Asunto(s)
Frío , Escarabajos , Congelación , Hemolinfa , Larva , Animales , Hemolinfa/química , Escarabajos/fisiología , Larva/fisiología , Larva/crecimiento & desarrollo , Aclimatación , Estaciones del Año , Potasio/metabolismo
6.
Pediatr Res ; 2024 Jul 28.
Artículo en Inglés | MEDLINE | ID: mdl-39068272

RESUMEN

BACKGROUND: Early biomarkers are needed to improve diagnosis and support antibiotic stewardship in neonatal sepsis. Heart rate variability (HRV) is proposed as such a biomarker. However, there is a lack of studies in term newborns. Infusion of lipopolysaccharide (LPS) from Escherichia coli induces systemic inflammation comparable to sepsis in newborns. We aimed to study the effect of systemic LPS induced inflammation on HRV in term newborn piglets. METHODS: Baseline HRV was recorded for 1 h. This control period was compared to the hourly HRV for each piglet (n = 9) during 4 h of LPS infusion. For comparison, we used a mixed-effects regression model. RESULTS: Systemic inflammation induced by LPS was found to reduce HRV. Compared to baseline, most measures of HRV decreased to lower values compared to baseline at 2 h, 3 h, and 4 h after initiation of LPS infusion. Heart rate (HR) was increased at 2 h, 3 h, and 4 h. When adjusting for HR in the mixed-effects regression model all reductions in HRV were explained by the increase in HR. CONCLUSIONS: Reduced HRV may be an early biomarker of neonatal sepsis. However, an increase in HR alone could be an already available, more accessible, and interpretable biomarker of sepsis in term neonates. IMPACT: In a term newborn piglet model, systemic inflammation induced by lipopolysaccharide from Escherichia coli reduced heart rate variability measures and increased heart rate. All reductions in heart rate variability were mediated by heart rate. While heart rate variability may be a biomarker of sepsis in term newborns, changes in heart rate alone could be a more readily available biomarker.

7.
Photochem Photobiol Sci ; 23(4): 629-650, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38512633

RESUMEN

This Assessment Update by the Environmental Effects Assessment Panel (EEAP) of the United Nations Environment Programme (UNEP) considers the interactive effects of solar UV radiation, global warming, and other weathering factors on plastics. The Assessment illustrates the significance of solar UV radiation in decreasing the durability of plastic materials, degradation of plastic debris, formation of micro- and nanoplastic particles and accompanying leaching of potential toxic compounds. Micro- and nanoplastics have been found in all ecosystems, the atmosphere, and in humans. While the potential biological risks are not yet well-established, the widespread and increasing occurrence of plastic pollution is reason for continuing research and monitoring. Plastic debris persists after its intended life in soils, water bodies and the atmosphere as well as in living organisms. To counteract accumulation of plastics in the environment, the lifetime of novel plastics or plastic alternatives should better match the functional life of products, with eventual breakdown releasing harmless substances to the environment.


Asunto(s)
Plásticos , Contaminantes Químicos del Agua , Humanos , Plásticos/toxicidad , Ecosistema , Rayos Ultravioleta , Cambio Climático , Contaminantes Químicos del Agua/análisis
8.
Radiology ; 307(2): e220989, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36648348

RESUMEN

Background The human cerebellum has a large, highly folded cortical sheet. Its visualization is important for various disorders, including multiple sclerosis and spinocerebellar ataxias. The derivation of the cerebellar cortical surface in vivo is impeded by its high foliation. Purpose To image the cerebellar cortex, including its foliations and lamination, in less than 20 minutes, reconstruct the cerebellocortical surface, and extract cortical measures with use of motion-corrected, high-spatial-resolution 7.0-T MRI. Materials and Methods In this prospective study, conducted between February 2021 and July 2022, healthy participants underwent an examination with either a 0.19 × 0.19 × 0.5-mm3, motion-corrected fast low-angle shot (FLASH) sequence (14.5 minutes) or a whole-cerebellum 0.4 × 0.4 × 0.4-mm3, motion-corrected magnetization-prepared 2 rapid gradient-echo (MP2RAGE) sequence (18.5 minutes) at 7.0 T. Four participants underwent an additional FLASH sequence without motion correction. FLASH and MP2RAGE sequences were used to visualize the cerebellar cortical layers, derive cerebellar gray and white matter segmentations, and examine their fidelity. Quantitative measures were compared using repeated-measures analyses of variance or paired t tests. Results Nine participants (median age, 36 years [IQR, 25-42 years; range, 21-62 years]; five women) underwent examination with the FLASH sequence. Nine participants (median age, 37 years [IQR, 34-42 years; range, 25-62 years]; five men) underwent examination with the MP2RAGE sequence. A susceptibility difference between the expected location of the granular and molecular cerebellar layers was visually detected in the FLASH data in all participants. The segmentations derived from the whole-cerebellum MP2RAGE sequence showed the characteristic anatomic features of the cerebellum, like the transverse fissures and splitting folds. The cortical surface area (median, 949 cm2 [IQR, 825-1021 cm2]) was 1.8 times larger, and the cortical thickness (median, 0.88 mm [IQR, 0.81-0.93 mm]) was five times thinner than previous in vivo estimates and closer to ex vivo reference data. Conclusion In vivo imaging of the cerebellar cortical layers and surface and derivation of quantitative measures was feasible in a clinically acceptable acquisition time with use of motion-corrected 7.0-T MRI. Published under a CC BY 4.0 license. Supplemental material is available for this article. See also the editorial by Dietrich in this issue.


Asunto(s)
Esclerosis Múltiple , Sustancia Blanca , Masculino , Humanos , Femenino , Adulto , Estudios Prospectivos , Imagen por Resonancia Magnética/métodos , Cerebelo/diagnóstico por imagen , Sustancia Blanca/diagnóstico por imagen , Esclerosis Múltiple/diagnóstico por imagen , Encéfalo/anatomía & histología
9.
Magn Reson Med ; 89(5): 1871-1887, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36579955

RESUMEN

PURPOSE: Dynamic glucose-enhanced (DGE) MRI relates to a group of exchange-based MRI techniques where the uptake of glucose analogues is studied dynamically. However, motion artifacts can be mistaken for true DGE effects, while motion correction may alter true signal effects. The aim was to design a numerical human brain phantom to simulate a realistic DGE MRI protocol at 3T that can be used to assess the influence of head movement on the signal before and after retrospective motion correction. METHODS: MPRAGE data from a tumor patient were used to simulate dynamic Z-spectra under the influence of motion. The DGE responses for different tissue types were simulated, creating a ground truth. Rigid head movement patterns were applied as well as physiological dilatation and pulsation of the lateral ventricles and head-motion-induced B0 -changes in presence of first-order shimming. The effect of retrospective motion correction was evaluated. RESULTS: Motion artifacts similar to those previously reported for in vivo DGE data could be reproduced. Head movement of 1 mm translation and 1.5 degrees rotation led to a pseudo-DGE effect on the order of 1% signal change. B0 effects due to head motion altered DGE changes due to a shift in the water saturation spectrum. Pseudo DGE effects were partly reduced or enhanced by rigid motion correction depending on tissue location. CONCLUSION: DGE MRI studies can be corrupted by motion artifacts. Designing post-processing methods using retrospective motion correction including B0 correction will be crucial for clinical implementation. The proposed phantom should be useful for evaluation and optimization of such techniques.


Asunto(s)
Glucosa , Procesamiento de Imagen Asistido por Computador , Humanos , Procesamiento de Imagen Asistido por Computador/métodos , Estudios Retrospectivos , Encéfalo/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Movimiento (Física) , Rotación , Artefactos
10.
J Nutr ; 153(11): 3237-3246, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37742796

RESUMEN

BACKGROUND: As a component of the thyroid hormones (THs), iodine is vital for normal neurodevelopment during early life. However, both deficient and excess iodine may affect TH production, and data on iodine status in young children are scarce. OBJECTIVES: To describe iodine nutrition (iodine status and intake) in children ≤2 y of age in Innlandet County (Norway) and to describe the associations with maternal iodine nutrition. METHODS: A cross-sectional study was performed in a representative sample of mother-child pairs selected from 30 municipalities from November 2020 until October 2021. Iodine status [child urinary iodine concentration (UIC), maternal UIC, and breast milk iodine concentration (BMIC)] was measured. Child's iodine intake was estimated using 2 24-h dietary recalls (24-HR) and a food frequency questionnaire. The Multiple Source Method was used to estimate the usual iodine intake distributions from the 24-HR assessments. RESULTS: The median UIC in 333 children was 145 µg/L, indicating adequate iodine status according to the WHO cutoff (100 µg/L). The median usual iodine intake was 83 µg/d. Furthermore, 35% had suboptimal usual iodine intakes [below the proposed Estimated average requirement (72 µg/d)], whereas <1% had excessive usual iodine intakes [above the Upper intake level (200 µg/d)]. There was a positive correlation between children's iodine intake and BMIC (Spearman rank correlation coefficient r = 0.67, P < 0.001), and between children's UIC and BMIC (r = 0.43, P < 0.001), maternal UIC (r = 0.23, P = 0.001), and maternal iodine intake (r = 0.20, P = 0.004). CONCLUSION: Despite a median UIC above the cutoff for iodine sufficiency, more than a third of the children had suboptimal usual iodine intakes. Our findings suggest that many children will benefit from iodine fortification and that risk of iodine excess in this age group is low.


Asunto(s)
Yodo , Femenino , Humanos , Preescolar , Estudios Transversales , Estado Nutricional , Leche Humana/química , Noruega
11.
J Exp Biol ; 226(18)2023 09 15.
Artículo en Inglés | MEDLINE | ID: mdl-37665251

RESUMEN

The physiology of insects is directly influenced by environmental temperature, and thermal tolerance is therefore intrinsically linked to their thermal niche and distribution. Understanding the mechanisms that limit insect thermal tolerance is crucial to predicting biogeography and range shifts. Recent studies on locusts and flies suggest that the critical thermal minimum (CTmin) follows a loss of CNS function via a spreading depolarization. We hypothesized that other insect taxa share this phenomenon. Here, we investigate whether spreading depolarization events occur in butterflies exposed to cold. Supporting our hypothesis, we found that exposure to stressful cold induced spreading depolarization in all 12 species tested. This reinforces the idea that spreading depolarization is a common mechanism underlying the insect CTmin. Furthermore, our results highlight how CNS function is tuned to match the environment of a species. Further research into the physiology underlying spreading depolarization will likely elucidate key mechanisms determining insect thermal tolerance and ecology.


Asunto(s)
Mariposas Diurnas , Animales , Insectos , Frío , Aclimatación
12.
Pediatr Res ; 93(3): 511-519, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-35681089

RESUMEN

BACKGROUND: We aimed to investigate the effect of epinephrine vs placebo on return of spontaneous circulation (ROSC) and brain magnetic resonance spectroscopy and imaging (MRS/MRI) in newborn piglets with hypoxic cardiac arrest (CA). METHODS: Twenty-five piglets underwent hypoxia induced by endotracheal tube clamping until CA. The animals were randomized to CPR + intravenous epinephrine or CPR + placebo (normal saline). The primary outcome was ROSC, and secondary outcomes included time-to-ROSC, brain MRS/MRI, and composite endpoint of death or severe brain MRS/MRI abnormality. RESULTS: ROSC was more frequent in animals treated with epinephrine than placebo; 10/13 vs 4/12, RR = 2.31 (95% CI: 1.09-5.77). We found no difference in time-to-ROSC (120 (113-211) vs 153 (116-503) seconds, p = 0.7) or 6-h survival (7/13 vs 3/12, p = 0.2). Among survivors, there was no difference between groups in brain MRS/MRI. We found no difference in the composite endpoint of death or severe brain MRS/MRI abnormality; RR = 0.7 (95% CI: 0.37-1.19). CONCLUSIONS: Resuscitation with epinephrine compared to placebo improved ROSC frequency after hypoxic CA in newborn piglets. We found no difference in time-to-ROSC or the composite endpoint of death or severe brain MRS/MRI abnormality. IMPACT: In a newborn piglet model of hypoxic cardiac arrest, resuscitation with epinephrine compared to placebo improved the rate of return of spontaneous circulation and more than doubled the 6-h survival. Brain MRS/MRI biomarkers were used to evaluate the effect of epinephrine vs placebo. We found no difference between groups in the composite endpoint of death or severe brain MRS/MRI abnormality. This study adds to the limited evidence regarding the effect and safety of epinephrine; the lack of high-quality evidence from randomized clinical trials was highlighted in the latest ILCOR 2020 guidelines, and newborn animal studies were specifically requested.


Asunto(s)
Reanimación Cardiopulmonar , Paro Cardíaco , Animales , Animales Recién Nacidos , Encéfalo/diagnóstico por imagen , Reanimación Cardiopulmonar/métodos , Epinefrina/uso terapéutico , Epinefrina/farmacología , Paro Cardíaco/tratamiento farmacológico , Hipoxia/tratamiento farmacológico , Imagen por Resonancia Magnética , Retorno de la Circulación Espontánea , Porcinos
13.
Phys Chem Chem Phys ; 25(14): 10186, 2023 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-36976569

RESUMEN

Correction for 'Atmospheric chemistry of CF3CN: kinetics and products of reaction with OH radicals, Cl atoms and O3' by Mads Peter Sulbaek Andersen et al., Phys. Chem. Chem. Phys., 2022, 24, 2638-2645, https://doi.org/10.1039/D1CP05288H.

14.
Phys Chem Chem Phys ; 25(14): 10185, 2023 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-36950873

RESUMEN

Correction for 'Atmospheric chemistry of (Z)- and (E)-1,2-dichloroethene: kinetics and mechanisms of the reactions with Cl atoms, OH radicals, and O3' by Mads P. Sulbaek Andersen et al., Phys. Chem. Chem. Phys., 2022, 24, 7356-7373, https://doi.org/10.1039/D1CP04877E.

15.
Magn Reson Med ; 88(3): 1198-1211, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35576128

RESUMEN

PURPOSE: Accuracy investigation of volumetric navigators for motion correction, with emphasis on geometric EPI distortions at ultrahigh field. METHODS: High-resolution Dixon images were collected in different head positions and reconstructed to water, fat, T2 *, and B0 maps. Resolution reduction was performed, and the T2 * and B0 maps were used to apply effects of TE and EPI distortions to simulate various volumetric water and fat navigators. Registrations of the simulated navigators were compared with registrations of the original high-resolution images. RESULTS: Increased accuracy was observed with increased spatial resolution for non-EPI navigators. When using EPI, the distortions had a negative effect on registration accuracy, which was most noticeable for high-resolution navigators. Parallel imaging helped to alleviate those caveats to a certain extent, and 5-fold acceleration gave close to similar accuracy to non-EPI in most cases. Shortening the TE by partial Fourier sampling was shown to be mostly beneficial, except for water navigators with long readout durations. The EPI blip direction had an influence on navigator accuracy, and positive blip gradient polarities (yielding mostly image stretching frontally) typically gave the best accuracy for water navigators, whereas no clear recommendation could be made for fat navigators. Generally, fat EPI navigators had lower accuracy than water EPI navigators with otherwise similar parameters. CONCLUSIONS: Echo planar imaging has been widely used for MRI navigators, but the induced distortions reduce navigator accuracy at ultrahigh field. This study can help protocol optimization and guide the complex tradeoff between resolution and EPI acceleration in navigator parameter setup.


Asunto(s)
Artefactos , Imagen Eco-Planar , Encéfalo , Imagen Eco-Planar/métodos , Interpretación de Imagen Asistida por Computador/métodos , Procesamiento de Imagen Asistido por Computador/métodos , Agua
16.
Magn Reson Med ; 87(6): 2637-2649, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35037283

RESUMEN

PURPOSE: To map T1 and the local flip angle ( B 1 + ) in human brain using a single MP3RAGE sequence with 3 rapid acquisitions of gradient echoes (RAGEs). THEORY AND METHODS: A third RAGE with a relatively high flip angle was appended to an MP2RAGE sequence. Through curve fitting and a rational approximation for small flip angles and short TR, closed form solutions for T1 and B 1 + were derived. The influence of different k-space encoding schemes on precision and whether edge enhancement artifacts could be reduced with a saturation pulse applied prior to the third RAGE were explored. Validation of T1 estimates was performed using single-slice inversion recovery (IR) and a subsequent region-of-interest-based comparison, whereas validation of B 1 + was performed using a whole brain pixelwise comparison to a DREAM flip angle mapping protocol. Lastly, MP3RAGE was compared to T1 -mapping by MP2RAGE with separate B 1 + correction. RESULTS: Whole brain maps of T1 and B 1 + at 1 mm isotropic resolution were obtained with MP3RAGE in 06:37 min. A linear-reverse centric-reverse centric phase-encoding order of the 3 RAGEs improved precision, and artifacts were successfully reduced with the saturation pulse. Estimations of T1 and B 1 + deviated +2.5 ± 3.1% and -1.7 ± 8.6% from their respective references. CONCLUSION: T1 and B 1 + can be mapped simultaneously using MP3RAGE. The approach can be thought of as combining MP2RAGE with a dual flip angle T1 -mapping protocol. Both maps can be solved for analytically and will be inherently co-registered at the high resolution associated with MPRAGE.


Asunto(s)
Encéfalo , Imagen por Resonancia Magnética , Algoritmos , Artefactos , Encéfalo/diagnóstico por imagen , Mapeo Encefálico , Humanos , Imagen por Resonancia Magnética/métodos , Fantasmas de Imagen , Reproducibilidad de los Resultados
17.
Magn Reson Med ; 88(2): 986-1001, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35468237

RESUMEN

PURPOSE: To demonstrate a novel method for tracking of head movements during MRI using electroencephalography (EEG) hardware for recording signals induced by native imaging gradients. THEORY AND METHODS: Gradient switching during simultaneous EEG-fMRI induces distortions in EEG signals, which depend on subject head position and orientation. When EEG electrodes are interconnected with high-impedance carbon wire loops, the induced voltages are linear combinations of the temporal gradient waveform derivatives. We introduce head tracking based on these signals (CapTrack) involving 3 steps: (1) phantom scanning is used to characterize the target sequence and a fast calibration sequence; (2) a linear relation between changes of induced signals and head pose is established using the calibration sequence; and (3) induced signals recorded during target sequence scanning are used for tracking and retrospective correction of head movement without prolonging the scan time of the target sequence. Performance of CapTrack is compared directly to interleaved navigators. RESULTS: Head-pose tracking at 27.5 Hz during echo planar imaging (EPI) was demonstrated with close resemblance to rigid body alignment (mean absolute difference: [0.14 0.38 0.15]-mm translation, [0.30 0.27 0.22]-degree rotation). Retrospective correction of 3D gradient-echo imaging shows an increase of average edge strength of 12%/-0.39% for instructed/uninstructed motion with CapTrack pose estimates, with a tracking interval of 1561 ms and high similarity to interleaved navigator estimates (mean absolute difference: [0.13 0.33 0.12] mm, [0.28 0.15 0.22] degrees). CONCLUSION: Motion can be estimated from recordings of gradient switching with little or no sequence modification, optionally in real time at low computational burden and synchronized to image acquisition, using EEG equipment already found at many research institutions.


Asunto(s)
Artefactos , Imagen por Resonancia Magnética , Encéfalo/diagnóstico por imagen , Imagen Eco-Planar/métodos , Electroencefalografía/métodos , Movimientos de la Cabeza , Imagen por Resonancia Magnética/métodos , Movimiento (Física) , Estudios Retrospectivos
18.
Magn Reson Med ; 88(2): 770-786, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35403247

RESUMEN

PURPOSE: Respiration-related CSF flow through the cerebral aqueduct may be useful for elucidating physiology and pathophysiology of the glymphatic system, which has been proposed as a mechanism of brain waste clearance. Therefore, we aimed to (1) develop a real-time (CSF) flow imaging method with high spatial and sufficient temporal resolution to capture respiratory effects, (2) validate the method in a phantom setup and numerical simulations, and (3) apply the method in vivo and quantify its repeatability and correlation with different respiratory conditions. METHODS: A golden-angle radial flow sequence (reconstructed temporal resolution 168 ms, spatial resolution 0.6 mm) was implemented on a 7T MRI scanner and reconstructed using compressed sensing. A phantom setup mimicked simultaneous cardiac and respiratory flow oscillations. The effect of temporal resolution and vessel diameter was investigated numerically. Healthy volunteers (n = 10) were scanned at four different respiratory conditions, including repeat scans. RESULTS: Phantom data show that the developed sequence accurately quantifies respiratory oscillations (ratio real-time/reference QR  = 0.96 ± 0.02), but underestimates the rapid cardiac oscillations (ratio QC  = 0.46 ± 0.14). Simulations suggest that QC can be improved by increasing temporal resolution. In vivo repeatability was moderate to very strong for cranial and caudal flow (intraclass correlation coefficient range: 0.55-0.99) and weak to strong for net flow (intraclass correlation coefficient range: 0.48-0.90). Net flow was influenced by respiratory condition (p < 0.01). CONCLUSIONS: The presented real-time flow MRI method can quantify respiratory-related variations of CSF flow in the cerebral aqueduct, but it underestimates rapid cardiac oscillations. In vivo, the method showed good repeatability and a relationship between flow and respiration.


Asunto(s)
Acueducto del Mesencéfalo , Imagen por Resonancia Magnética , Encéfalo/diagnóstico por imagen , Líquido Cefalorraquídeo/diagnóstico por imagen , Líquido Cefalorraquídeo/fisiología , Humanos , Imagen por Resonancia Magnética/métodos , Fantasmas de Imagen , Respiración
19.
J Exp Biol ; 225(24)2022 12 15.
Artículo en Inglés | MEDLINE | ID: mdl-36477887

RESUMEN

Most insects can acclimate to changes in their thermal environment and counteract temperature effects on neuromuscular function. At the critical thermal minimum, a spreading depolarization (SD) event silences central neurons, but the temperature at which this event occurs can be altered through acclimation. SD is triggered by an inability to maintain ion homeostasis in the extracellular space in the brain and is characterized by a rapid surge in extracellular K+ concentration, implicating ion pump and channel function. Here, we focused on the role of the Na+/K+-ATPase specifically in lowering the SD temperature in cold-acclimated Drosophila melanogaster. After first confirming cold acclimation altered SD onset, we investigated the dependency of the SD event on Na+/K+-ATPase activity by injecting the inhibitor ouabain into the head of the flies to induce SD over a range of temperatures. Latency to SD followed the pattern of a thermal performance curve, but cold acclimation resulted in a left-shift of the curve to an extent similar to its effect on the SD temperature. With Na+/K+-ATPase activity assays and immunoblots, we found that cold-acclimated flies have ion pumps that are less sensitive to temperature, but do not differ in their overall abundance in the brain. Combined, these findings suggest a key role for plasticity in Na+/K+-ATPase thermal sensitivity in maintaining central nervous system function in the cold, and more broadly highlight that a single ion pump can be an important determinant of whether insects can respond to their environment to remain active at low temperatures.


Asunto(s)
Frío , Drosophila melanogaster , Animales , Temperatura , Drosophila melanogaster/fisiología , Aclimatación/fisiología , Adenosina Trifosfatasas , ATPasa Intercambiadora de Sodio-Potasio/metabolismo
20.
Neuropediatrics ; 53(6): 423-431, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-35777661

RESUMEN

BACKGROUND: Despite therapeutic hypothermia, neonates with hypoxic-ischemic encephalopathy still develop neurological disabilities. We have previously investigated neuroprotection by remote ischemic postconditioning (RIPC) in newborn piglets following hypoxia-ischemia (HI). The aim of this study was to further investigate potential effects of RIPC on cerebral immunohistochemical markers related to edema, apoptosis, and angiogenesis. METHODS: Brain expression of aquaporin 4, caspase-3, B-cell lymphoma 2, and vascular endothelial growth factor was analyzed by immunohistochemistry in 23 piglets, randomly selected from a larger study of RIPC after HI. Twenty animals were subjected to 45 minutes of HI and randomized to treatment with and without RIPC, while three animals were randomized to sham procedures. RIPC was conducted by four conditioning cycles of 5-minute ischemia and reperfusion. Piglets were euthanized 72 hours after the HI insult. RESULTS: Piglets subjected to HI treated with and without RIPC were similar at baseline and following the HI insult. However, piglets randomized to HI alone had longer duration of low blood pressure during the insult. We found no differences in the brain expression of the immunohistochemical markers in any regions of interest or the whole brain between the two HI groups. CONCLUSION: RIPC did not influence brain expression of markers related to edema, apoptosis, or angiogenesis in newborn piglets at 72 hours after HI. These results support previous findings of limited neuroprotective effect by this RIPC protocol. Our results may have been affected by the time of assessment, use of fentanyl as anesthetic, or limitations related to our immunohistochemical methods.


Asunto(s)
Hipoxia-Isquemia Encefálica , Poscondicionamiento Isquémico , Animales , Animales Recién Nacidos , Biomarcadores , Modelos Animales de Enfermedad , Hipoxia , Hipoxia-Isquemia Encefálica/patología , Isquemia , Poscondicionamiento Isquémico/métodos , Porcinos , Factor A de Crecimiento Endotelial Vascular
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