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Background: With the advent of electronic nicotine delivery systems, the use of nicotine and tobacco products (NTPs) among adolescents and young adults remains high in the US. Use of e-cigarettes additionally elevates the risk of problematic use of other substances like cannabis, which is often co-used with NTPs. However, their effects on brain health, particularly the hippocampus, and cognition during this neurodevelopmental period are poorly understood. Methods: Healthy late adolescents/young adults (N = 223) ages 16-22 completed a structural MRI to examine right and left hippocampal volumes. Memory was assessed with the NIH Toolbox Picture Sequence Memory Test (PSMT) and Rey Auditory Verbal Learning Test (RAVLT). Cumulative 6-month NTP and cannabis episodes were assessed and modeled continuously on hippocampal volumes. Participants were then grouped based on 6-month NTP use to examine relationships with the hippocampus and memory: current users (CU) endorsed weekly or greater use; light/abstinent users (LU) endorsed less than weekly; and never users (NU). Results: NTP use predicted larger hippocampal volumes bilaterally while cannabis use had no impact nor interacted with NTP use. For memory, larger left hippocampal volumes were positively associated with PSMT performance, RAVLT total learning, short delay and long delay recall for the NU group. In contrast, there was a negative relationship between hippocampal volumes and performances for LU and CU groups. No differences were detected between NTP-using groups. Conclusion: These results suggest that the hippocampus is sensitive to NTP exposure during late adolescence/young adulthood and may alter typical hippocampal morphometry in addition to brain-behavior relationships underlying learning and memory processes.
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In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time.
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PURPOSE: To develop a generalized signal model for dual-module velocity-selective arterial spin labeling (dm-VSASL) that can integrate arbitrary saturation and inversion profiles. THEORY AND METHODS: A recently developed mathematical framework for single-module VSASL is extended to address the increased complexity of dm-VSASL and to model the use of realistic velocity-selective profiles in the label-control and vascular crushing modules. Expressions for magnetization difference, arterial delivery functions, labeling efficiency, and cerebral blood flow (CBF) estimation error are presented. Sources of error are examined and timing requirements to minimize quantification errors are derived. RESULTS: For ideal velocity-selective profiles, the predicted signals match those of prior work. With realistic profiles, a CBF-dependent estimation error can occur when velocity-selective inversion (VSI) is used for the labeling modules and velocity-selective saturation (VSS) is used for the vascular crushing module. The error reflects a mismatch between the leading and trailing edges of the delivery function for the second bolus and can be minimized by choosing a nominal labeling cutoff velocity that is lower than the nominal saturation cutoff velocity. In the presence of B 0 $$ {\mathrm{B}}_0 $$ and B 1 $$ {\mathrm{B}}_1 $$ inhomogeneities, the labeling efficiency of dual-module VSI is more attenuated than that of dual-module VSS. CONCLUSION: The proposed signal model will enable researchers to more accurately assess and compare the performance of realistic dm-VSASL implementations and improve the quantification of dm-VSASL CBF measures.
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PURPOSE: To mitigate the B0/B1 + sensitivity of velocity-selective inversion (VSI) pulse trains for velocity-selective arterial spin labeling (VSASL) by implementing adiabatic refocusing. This approach aims to achieve artifact-free VSI-based perfusion imaging through single-pair label-control subtractions, reducing the need for the currently required four-pair dynamic phase-cycling (DPC) technique when using a velocity-insensitive control. METHODS: We introduce a Fourier-transform VSI (FT-VSI) train that incorporates sinc-modulated hard excitation pulses with MLEV-8-modulated adiabatic hyperbolic secant refocusing pairs. We compare performance between this train and the standard composite refocusing train, including with and without DPC, for dual-module VSI VSASL. We evaluate (1) simulated velocity-selective profiles and subtraction fidelity across a broad B0/B1 + range, (2) subtraction fidelity in phantoms, and (3) image quality, artifact presence, and gray-matter perfusion heterogeneity (as measured by the spatial coefficient of variation) in healthy human subjects. RESULTS: Adiabatic refocusing significantly improves FT-VSI robustness to B0/B1 + inhomogeneity for a single label-control subtraction. Subtraction fidelity is dramatically improved in both simulation and phantoms compared with composite refocusing without DPC, and is similar compared with DPC methods. In humans, marked artifacts seen with the non-DPC composite refocusing approach are eliminated, corroborated by significantly reduced gray-matter heterogeneity (via lower spatial coefficient of variation values). CONCLUSION: A novel VSASL labeling train using adiabatic refocusing pulses for VSI was found to reduce artifacts related to B0/B1 + inhomogeneity, thereby providing an alternative to DPC and its associated limitations, which include increased vulnerability to physiological noise and motion, reduced functional MRI applicability, and suboptimal data censoring.
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Algoritmos , Artefactos , Procesamiento de Imagen Asistido por Computador , Fantasmas de Imagen , Marcadores de Spin , Humanos , Procesamiento de Imagen Asistido por Computador/métodos , Encéfalo/diagnóstico por imagen , Encéfalo/irrigación sanguínea , Adulto , Análisis de Fourier , Masculino , Femenino , Circulación Cerebrovascular/fisiología , Imagen por Resonancia Magnética/métodos , Simulación por Computador , Angiografía por Resonancia Magnética/métodos , Sustancia Gris/diagnóstico por imagenRESUMEN
INTRODUCTION: Despite evidence suggesting deleterious effects of cannabis and nicotine tobacco product (NTP) use on white matter integrity, there have been limited studies examining white matter integrity among users of both cannabis and nicotine. Further, updated white matter methodology provides opportunities to investigate use patterns on neurite orientation dispersion and density (NODDI) indices and subtle tissue changes related to the intra- and extra-neurite compartment. We aimed to investigate how cannabis and NTP use among adolescents and young adults interacts to impact the white matter integrity microstructure. MATERIALS AND METHODS: A total of 221 participants between the ages of 16 and 22 completed the Customary Drinking and Drug Use Record (CDDR) to measure substance use, and underwent a magnetic resonance imaging (MRI) session. Participants were divided into NTP-control and NTP groupings and cannabis-control and cannabis groupings (≥26 NTP/cannabis uses in past 6 months). Tract-Based Spatial Statistics (TBSS) and two-way between-subjects ANOVA investigated the effects of NTP use group, cannabis use group, and their interaction on fractional anisotropy (FA) and NODDI indices while controlling for age and biological sex. RESULTS: NTP use was associated with decreased FA values and increased orientation dispersion in the left anterior capsule. There were no significant effects of cannabis use or the interaction of NTP and cannabis use on white matter outcomes. DISCUSSION: NTP use was associated with altered white matter integrity in an adolescent and young adult sample. Findings suggest that NTP-associated alterations may be linked to altered fiber tract geometry and dispersed neurite structures versus myelination, as well as differential effects of NTP and cannabis use on white matter structure. Future work is needed to investigate how altered white matter is related to downstream behavioral effects from NTP use.
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PURPOSE: To present a theoretical framework that rigorously defines and analyzes key concepts and quantities for velocity selective arterial spin labeling (VSASL). THEORY AND METHODS: An expression for the VSASL arterial delivery function is derived based on (1) labeling and saturation profiles as a function of velocity and (2) physiologically plausible approximations of changes in acceleration and velocity across the vascular system. The dependence of labeling efficiency on the amplitude and effective bolus width of the arterial delivery function is defined. Factors that affect the effective bolus width are examined, and timing requirements to minimize quantitation errors are derived. RESULTS: The model predicts that a flow-dependent negative bias in the effective bolus width can occur when velocity selective inversion (VSI) is used for the labeling module and velocity selective saturation (VSS) is used for the vascular crushing module. The bias can be minimized by choosing a nominal labeling cutoff velocity that is lower than the nominal cutoff velocity of the vascular crushing module. CONCLUSION: The elements of the model are specified in a general fashion such that future advances can be readily integrated. The model can facilitate further efforts to understand and characterize the performance of VSASL and provide critical theoretical insights that can be used to design future experiments and develop novel VSASL approaches.
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Arterias , Angiografía por Resonancia Magnética , Marcadores de Spin , Arterias/diagnóstico por imagen , Modelos Teóricos , Aceleración , Circulación Cerebrovascular/fisiología , Velocidad del Flujo Sanguíneo/fisiologíaRESUMEN
Nicotine and tobacco product (NTP) use remains prevalent in adolescence/young adulthood. The effects of NTPs on markers of brain health during this vulnerable neurodevelopmental period remain largely unknown. This report investigates associations between NTP use and gray matter cerebral blood flow (CBF) in adolescents/young adults. Adolescent/young adult (16-22 years-old) nicotine users (NTP; N = 99; 40 women) and non-users (non-NTP; N = 95; 56 women) underwent neuroimaging sessions including anatomical and optimized pseudo-continuous arterial spin labeling scans. Groups were compared on whole-brain gray matter CBF estimates and their relation to age and sex at birth. Follow-up analyses assessed correlations between identified CBF clusters and NTP recency and dependence measures. Controlling for age and sex, the NTP vs. non-NTP contrast revealed a single cluster that survived thresholding which included portions of bilateral precuneus (voxel-wise alpha < 0.001, cluster-wise alpha < 0.05; ≥7 contiguous voxels). An interaction between NTP group contrast and age was observed in two clusters including regions of the left posterior cingulate (PCC)/lingual gyrus and right anterior cingulate cortex (ACC): non-NTP exhibited positive correlations between CBF and age in these clusters, whereas NTP exhibited negative correlations between CBF and age. Lower CBF from these three clusters correlated with urine cotinine (rs=-0.21 - - 0.16; ps < 0.04) and nicotine dependence severity (rs=-0.16 - - 0.13; ps < 0.07). This is the first investigation of gray matter CBF in adolescent/young adult users of NTPs. The results are consistent with literature on adults showing age- and nicotine-related declines in CBF and identify the precuneus/PCC and ACC as potential key regions subserving the development of nicotine dependence.
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Sustancia Gris , Tabaquismo , Recién Nacido , Adulto Joven , Humanos , Adolescente , Femenino , Adulto , Sustancia Gris/diagnóstico por imagen , Nicotina , Imagen por Resonancia Magnética/métodos , Tabaquismo/diagnóstico por imagen , Encéfalo/fisiología , Circulación Cerebrovascular/fisiologíaRESUMEN
Nanographene materials are promising building blocks for the growing field of low-dimensional materials for optics, electronics and biophotonics applications. In particular, bottom-up synthesized 0D graphene quantum dots show great potential as single quantum emitters. To fully exploit their exciting properties, the graphene quantum dots must be of high purity; the key parameter for efficient purification being the solubility of the starting materials. Here, we report the synthesis of a family of highly soluble and easily processable rod-shaped graphene quantum dots with fluorescence quantum yields up to 94%. This is uncommon for a red emission. The high solubility is directly related to the design of the structure, allowing for an accurate description of the photophysical properties of the graphene quantum dots both in solution and at the single molecule level. These photophysical properties were fully predicted by quantum-chemical calculations.
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The authors discovered an error in the primary analysis and have withdrawn the results from this version of the investigation.
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Importance: Whether protein risk scores derived from a single plasma sample could be useful for risk assessment for atherosclerotic cardiovascular disease (ASCVD), in conjunction with clinical risk factors and polygenic risk scores, is uncertain. Objective: To develop protein risk scores for ASCVD risk prediction and compare them to clinical risk factors and polygenic risk scores in primary and secondary event populations. Design, Setting, and Participants: The primary analysis was a retrospective study of primary events among 13â¯540 individuals in Iceland (aged 40-75 years) with proteomics data and no history of major ASCVD events at recruitment (study duration, August 23, 2000 until October 26, 2006; follow-up through 2018). We also analyzed a secondary event population from a randomized, double-blind lipid-lowering clinical trial (2013-2016), consisting of individuals with stable ASCVD receiving statin therapy and for whom proteomic data were available for 6791 individuals. Exposures: Protein risk scores (based on 4963 plasma protein levels and developed in a training set in the primary event population); polygenic risk scores for coronary artery disease and stroke; and clinical risk factors that included age, sex, statin use, hypertension treatment, type 2 diabetes, body mass index, and smoking status at the time of plasma sampling. Main Outcomes and Measures: Outcomes were composites of myocardial infarction, stroke, and coronary heart disease death or cardiovascular death. Performance was evaluated using Cox survival models and measures of discrimination and reclassification that accounted for the competing risk of non-ASCVD death. Results: In the primary event population test set (4018 individuals [59.0% women]; 465 events; median follow-up, 15.8 years), the protein risk score had a hazard ratio (HR) of 1.93 per SD (95% CI, 1.75 to 2.13). Addition of protein risk score and polygenic risk scores significantly increased the C index when added to a clinical risk factor model (C index change, 0.022 [95% CI, 0.007 to 0.038]). Addition of the protein risk score alone to a clinical risk factor model also led to a significantly increased C index (difference, 0.014 [95% CI, 0.002 to 0.028]). Among White individuals in the secondary event population (6307 participants; 432 events; median follow-up, 2.2 years), the protein risk score had an HR of 1.62 per SD (95% CI, 1.48 to 1.79) and significantly increased C index when added to a clinical risk factor model (C index change, 0.026 [95% CI, 0.011 to 0.042]). The protein risk score was significantly associated with major adverse cardiovascular events among individuals of African and Asian ancestries in the secondary event population. Conclusions and Relevance: A protein risk score was significantly associated with ASCVD events in primary and secondary event populations. When added to clinical risk factors, the protein risk score and polygenic risk score both provided statistically significant but modest improvement in discrimination.
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Aterosclerosis , Enfermedades Cardiovasculares , Proteómica , Femenino , Humanos , Masculino , Aterosclerosis/epidemiología , Aterosclerosis/genética , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/epidemiología , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Estudios Retrospectivos , Accidente Cerebrovascular , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/mortalidad , Enfermedades Cardiovasculares/terapia , Medición de Riesgo , Adulto , Persona de Mediana Edad , Anciano , Islandia/epidemiología , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
OBJECTIVES: Physical activity (PA) may help maintain brain structure and function in aging. Since the intensity of PA needed to effect cognition and cerebrovascular health remains unknown, we examined associations between PA and cognition, regional white matter hyperintensities (WMH), and regional cerebral blood flow (CBF) in older adults. METHOD: Forty-three older adults without cognitive impairment underwent magnetic resonance imaging (MRI) and comprehensive neuropsychological assessment. Waist-worn accelerometers objectively measured PA for approximately one week. RESULTS: Higher time spent in moderate to vigorous PA (MVPA) was uniquely associated with better memory and executive functioning after adjusting for all light PA. Higher MVPA was also uniquely associated with lower frontal WMH volume although the finding was no longer significant after additionally adjusting for age and accelerometer wear time. MVPA was not associated with CBF. Higher time spent in all light PA was uniquely associated with higher CBF but not with cognitive performance or WMH volume. CONCLUSIONS: Engaging in PA may be beneficial for cerebrovascular health, and MVPA in particular may help preserve memory and executive function in otherwise cognitively healthy older adults. There may be differential effects of engaging in lighter PA and MVPA on MRI markers of cerebrovascular health although this needs to be confirmed in future studies with larger samples. Future randomized controlled trials that increase PA are needed to elucidate cause-effect associations between PA and cerebrovascular health.
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Disfunción Cognitiva , Ejercicio Físico , Humanos , Anciano , Ejercicio Físico/fisiología , Cognición/fisiología , Encéfalo/diagnóstico por imagen , Acelerometría/métodosRESUMEN
BACKGROUND: Extensive research suggests that physical activity (PA) is important for brain and cognitive health and may help to delay or prevent Alzheimer's disease and related dementias. Most PA interventions designed to improve brain health in older adults have been conducted in laboratory, gym, or group settings that require extensive resources and travel to the study site or group sessions. Research is needed to develop novel interventions that leverage mobile health (mHealth) technologies to help older adults increase their engagement in PA in free-living environments, reducing participant burden and increasing generalizability of research findings. Moreover, promoting engagement in moderate-to-vigorous PA (MVPA) may be most beneficial to brain health; thus, using mHealth to help older adults increase time spent in MVPA in free-living environments may help to offset the burden of Alzheimer's disease and related dementias and improve quality of life in older age. OBJECTIVE: We developed a novel PA intervention that leverages mHealth to help older adults achieve more minutes of MVPA independently. This pilot study was a 12-week randomized controlled trial to investigate the feasibility of providing just-in-time (JIT) feedback about PA intensity during free-living exercise sessions to help older adults meet current PA recommendations (150 minutes per week of MVPA). METHODS: Participants were eligible if they were cognitively healthy English speakers aged between 65 and 80 years without major cardiovascular, neurologic, or mental health conditions; could ambulate independently; and undergo magnetic resonance imaging. Enrollment occurred from October 2017 to March 2020. Participants randomized to the PA condition received an individualized exercise prescription and an mHealth device that provided heart rate-based JIT feedback on PA intensity, allowing them to adjust their behavior in real time to maintain MVPA during exercise sessions. Participants assigned to the healthy aging education condition received a reading prescription consisting of healthy aging topics and completed weekly quizzes based on the materials. RESULTS: In total, 44 participants were randomized to the intervention. A follow-up manuscript will describe the results of the intervention as well as discuss screening, recruitment, adverse events, and participants' opinions regarding their participation in the intervention. CONCLUSIONS: The long-term goal of this intervention is to better understand how MVPA affects brain and cognitive health in the real world and extend laboratory findings to everyday life. This pilot randomized controlled trial was conducted to determine the feasibility of using JIT heart rate zone feedback to help older adults independently increase time spent in MVPA while collecting data on the plausible mechanisms of change (frontal and medial temporal cerebral blood flow and cardiorespiratory fitness) that may affect cognition (memory and executive function) to help refine a planned stage 2 behavioral trial. TRIAL REGISTRATION: ClinicalTrials.gov NCT03058146; https://clinicaltrials.gov/ct2/show/NCT03058146. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/42980.
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In multi-echo fMRI (ME-fMRI), two metrics have been widely used to measure the performance of various acquisition and analysis approaches. These are temporal SNR (tSNR) and differential contrast-to-noise ratio (dCNR). A key step in ME-fMRI is the weighted combination of the data from multiple echoes, and prior work has examined the dependence of tSNR and dCNR on the choice of weights. However, most studies have focused on only one of these two metrics, and the relationship between the two metrics has not been examined. In this work, we present a geometric view that offers greater insight into the relation between the two metrics and their weight dependence. We identify three major regimes: (1) a tSNR robust regime in which tSNR is robust to the weight selection with most weight variants achieving close to optimal performance, whereas dCNR shows a pronounced dependence on the weights with most variants achieving suboptimal performance; (2) a dCNR robust regime in which dCNR is robust to the weight selection with most weight variants achieving close to optimal performance, while tSNR exhibits a strong dependence on the weights with most variants achieving significantly lower than optimal performance; and (3) a within-type robust regime in which both tSNR and dCNR achieve nearly optimal performance when the form of the weights are variants of their respective optimal weights and exhibit a moderate decrease in performance for other weight variants. Insight into the behavior observed in the different regimes is gained by considering spherical representations of the weight dependence of the components used to form each metric. For multi-echo acquisitions, dCNR is shown to be more directly related than tSNR to measures of CNR and signal-to-noise ratio (SNR) for task-based and resting-state fMRI scans, respectively.
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Encéfalo , Imagen por Resonancia Magnética , Benchmarking , Encéfalo/diagnóstico por imagen , Imagen Eco-Planar , Humanos , Cintigrafía , Relación Señal-RuidoRESUMEN
Transcutaneous auricular vagus nerve stimulation (taVNS), a non-invasive alternative to vagus nerve stimulation (VNS) with implantable devices, has shown promise in treating disorders such as depression, migraine, and insomnia. Studies of these disorders with resting-state functional magnetic resonance imaging (MRI) (rsfMRI) have found sustained changes in resting-state functional connectivity (rsFC) in patients treated with low frequency (1-20 Hz) taVNS. A recent study has reported reductions in pain scores in patients with rheumatoid arthritis after a 12-week treatment of high-frequency (20 kHz) sub-threshold taVNS. However, no studies to date have examined the effects of high-frequency sub-threshold taVNS on rsFC. The objective of this study was to determine whether high-frequency sub-threshold taVNS induces changes in rsFC using seed regions from the cingulate cortex and insula, brain regions that play a key role in interoception and processing of pain. With a single-blind placebo-controlled repeated measures experimental design, rsfMRI scans were acquired before and after 15 min of either sub-threshold taVNS treatment or a sham control. Significant taVNS-related changes in functional connections to the cingulate cortex were detected between the anterior cingulate cortex and right superior temporal gyrus and between the midcingulate cortex and right inferior parietal lobule. In addition, significant changes in functional connections to the insula were detected between the posterior insula and right precuneus and between the anterior insula and right cuneus gyrus. These results suggest that high-frequency sub-threshold taVNS can lead to sustained effects on the rsFC of brain regions involved in interoception and processing of pain in a cohort of healthy subjects. This study lays the foundation for future rsfMRI studies of high-frequency sub-threshold taVNS in clinical populations.
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Atomically precise graphene quantum dots synthesized by bottom-up chemistry are promising versatile single emitters with potential applications for quantum photonic technologies. Toward a better understanding and control of graphene quantum dot (GQD) optical properties, we report on single-molecule spectroscopy at cryogenic temperature. We investigate the effect of temperature on the GQDs' spectral linewidth and vibronic replica, which we interpret building on density functional theory calculations. Finally, we highlight that the vibronic signatures are specific to the GQD geometry and can be used as a fingerprint for identification purposes.
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OBJECTIVE: Co-use of cannabis and nicotine and tobacco products (NTPs) in adolescence/young adulthood is common and associated with worse outcomes than the use of either substance in isolation. Despite this, little is known about the unique contributions of co-use to neurostructural microstructure during this neurodevelopmentally important period. This study sought to investigate the interactive effects of nicotine and cannabis co-use on white matter fiber tract microstructure in emerging adulthood. METHOD: A total of 111 late adolescent (16-22 years old) nicotine (NTP; n = 55, all past-year cannabis users) and non-nicotine users (non-NTP; n = 56, 61% reporting cannabis use in the past year) completed demographic and clinical interviews and a neuroimaging session comprising anatomical and diffusion-weighted imaging scans. Group connectometry analysis identified white matter tracts significantly associated with the interaction between nicotine group and past-year cannabis use according to generalized fractional anisotropy (GFA). RESULTS: Nicotine Group × Cannabis Use interactions were observed in the right and left cingulum and left fornix tracts (false discovery rate = 0.053), where greater cannabis use was associated with increased GFA in the cingulum and left fornix, but only when co-used with nicotine. CONCLUSIONS: This report represents the first group connectometry analysis in late adolescent/young adult cannabis and/or NTP users. Results suggest that co-use of cannabis and NTPs results in a structurally distinct white matter phenotype as compared with cannabis use only, although to what extent this may change over time with more chronic nicotine and cannabis use remains to be examined in future work.
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Cannabis , Alucinógenos , Sustancia Blanca , Adolescente , Adulto , Anisotropía , Humanos , Neuroimagen , Nicotina , Sustancia Blanca/diagnóstico por imagen , Adulto JovenRESUMEN
Graphene quantum dots, atomically precise nanopieces of graphene, are promising nano-objects with potential applications in various domains such as photovoltaics, quantum light emitters and bio-imaging. Despite their interesting prospects, precise reports on their photophysical properties remain scarce. Here, we report on a study of the photophysics of C96H24(C12H25) graphene quantum dots. A combination of optical studies down to the single molecule level with advanced molecular modelling demonstrates the importance of coupling to vibrations in the emission process. Optical fingerprints for H-like aggregates are identified. Our combined experimental-theoretical investigations provide a comprehensive description of the light absorption and emission properties of nanographenes, which not only represents an essential step towards precise control of sample production but also paves the way for new exciting physics focused on twisted graphenoids.