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BACKGROUND: Pathophysiological changes of Huntington's disease (HD) can precede symptom onset by decades. Robust imaging biomarkers are needed to monitor HD progression, especially before the clinical onset. PURPOSE: To investigate iron dysregulation and microstructure alterations in subcortical regions as HD imaging biomarkers, and to associate such alterations with motor and cognitive impairments. STUDY TYPE: Prospective. POPULATION: Fourteen individuals with premanifest HD (38.0 ± 11.0 years, 9 females; far-from-onset N = 6, near-onset N = 8), 21 manifest HD patients (49.1 ± 12.1 years, 11 females), and 33 age-matched healthy controls (43.9 ± 12.2 years, 17 females). FIELD STRENGTH/SEQUENCE: 7 T, T1 -weighted imaging, quantitative susceptibility mapping, and diffusion tensor imaging. ASSESSMENT: Volume, susceptibility, fractional anisotropy (FA), and mean diffusivity (MD) within subcortical brain structures were compared across groups, used to establish HD classification models, and correlated to clinical measures and cognitive assessments. STATISTICAL TESTS: Generalized linear model, multivariate logistic regression, receiver operating characteristics with the area under the curve (AUC), and likelihood ratio test comparing a volumetric model to one that also includes susceptibility and diffusion metrics, Wilcoxon paired signed-rank test, and Pearson's correlation. A P-value <0.05 after Benjamini-Hochberg correction was considered statistically significant. RESULTS: Significantly higher striatal susceptibility and FA were found in premanifest and manifest HD preceding atrophy, even in far-from-onset premanifest HD compared to controls (putamen susceptibility: 0.027 ± 0.022 vs. 0.018 ± 0.013 ppm; FA: 0.358 ± 0.048 vs. 0.313 ± 0.039). The model with additional susceptibility, FA, and MD features showed higher AUC compared to volume features alone when differentiating premanifest HD from HC (0.83 vs. 0.66), and manifest from premanifest HD (0.94 vs. 0.83). Higher striatal susceptibility significantly correlated with cognitive deterioration in HD (executive function: r = -0.600; socioemotional function: r = -0.486). DATA CONCLUSION: 7 T MRI revealed iron dysregulation and microstructure alterations with HD progression, which could precede volume loss, provide added value to HD differentiation, and might be associated with cognitive changes. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.
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Quantitative susceptibility mapping (QSM) is a promising tool for investigating iron dysregulation in neurodegenerative diseases, including Huntington's disease (HD). Many diverse methods have been proposed to generate accurate and robust QSM images. In this study, we evaluated the performance of different dipole inversion algorithms for iron-sensitive susceptibility imaging at 7T on healthy subjects of a large age range and patients with HD. We compared an iterative least-squares-based method (iLSQR), iterative methods that use regularization, single-step approaches, and deep learning-based techniques. Their performance was evaluated by comparing: (1) deviations from a multiple-orientation QSM reference; (2) visual appearance of QSM maps and the presence of artifacts; (3) susceptibility in subcortical brain regions with age; (4) regional brain susceptibility with published postmortem brain iron quantification; and (5) susceptibility in HD-affected basal ganglia regions between HD subjects and healthy controls. We found that single-step QSM methods with either total variation or total generalized variation constraints (SSTV/SSTGV) and the single-step deep learning method iQSM generally provided the best performance in terms of correlation with iron deposition and were better at differentiating between healthy controls and premanifest HD individuals, while deep learning QSM methods trained with multiple-orientation susceptibility data created QSM maps that were most similar to the multiple orientation reference and with the best visual scores.
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Enfermedad de Huntington , Humanos , Enfermedad de Huntington/diagnóstico por imagen , Hierro , Voluntarios Sanos , Imagen por Resonancia Magnética/métodos , Procesamiento de Imagen Asistido por Computador/métodos , Encéfalo/diagnóstico por imagen , Encéfalo/fisiología , Mapeo Encefálico/métodos , AlgoritmosRESUMEN
Although combined spin- and gradient-echo (SAGE) dynamic susceptibility-contrast (DSC) MRI can provide perfusion quantification that is sensitive to both macrovessels and microvessels while correcting for T1 -shortening effects, spatial coverage is often limited in order to maintain a high temporal resolution for DSC quantification. In this work, we combined a SAGE echo-planar imaging (EPI) sequence with simultaneous multi-slice (SMS) excitation and blipped controlled aliasing in parallel imaging (blipped CAIPI) at 3 T to achieve both high temporal resolution and whole brain coverage. Two protocols using this sequence with multi-band (MB) acceleration factors of 2 and 3 were evaluated in 20 patients with treated gliomas to determine the optimal scan parameters for clinical use. ΔR2 *(t) and ΔR2 (t) curves were derived to calculate dynamic signal-to-noise ratio (dSNR), ΔR2 *- and ΔR2 -based relative cerebral blood volume (rCBV), and mean vessel diameter (mVD) for each voxel. The resulting SAGE DSC images acquired using MB acceleration of 3 versus 2 appeared visually similar in terms of image distortion and contrast. The difference in the mean dSNR from normal-appearing white matter (NAWM) and that in the mean dSNR between NAWM and normal-appearing gray matter were not statistically significant between the two protocols. ΔR2 *- and ΔR2 -rCBV maps and mVD maps provided unique contrast and spatial heterogeneity within tumors.
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Neoplasias Encefálicas/diagnóstico por imagen , Medios de Contraste/química , Imagen Eco-Planar , Glioma/diagnóstico por imagen , Procesamiento de Imagen Asistido por Computador , Perfusión , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Relación Señal-Ruido , Adulto JovenRESUMEN
PURPOSE: Although radiation therapy (RT) is a common treatment for pediatric brain tumors, it is associated with detrimental long-term effects such as impaired cognition, vascular injury, and increased stroke risk. This study aimed to develop metrics that describe vascular injury and relate them to the presence of cerebral microbleeds (CMBs) and cognitive performance scores. METHODS: Twenty-five young adult survivors of pediatric brain tumors treated with either whole-brain (n = 12), whole-ventricular (n = 7), or no RT (n = 6) underwent 7T MRI and neurocognitive testing. Simultaneously acquired MR angiography and susceptibility-weighted images were used to segment CMBs and vessels and quantify their radii and volume. RESULTS: Patients treated with whole-brain RT had significantly lower arterial volumes (p = 0.003) and a higher proportion of smaller vessels (p = 0.003) compared to the whole-ventricular RT and non-irradiated control patients. Normalized arterial volume decreased with increasing CMB count (R = - 0.66, p = 0.003), and decreasing trends were observed with time since RT and at longitudinal follow-up. Global cognition and verbal memory significantly decreased with smaller normalized arterial volume (p ≤ 0.05). CONCLUSIONS: Arterial volume is reduced with increasing CMB presence and is influenced by the total brain volume exposed to radiation. This work highlights the potential use of vascular-derived metrics as non-invasive markers of treatment-induced injury and cognitive impairment in pediatric brain tumor patients.
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Neoplasias Encefálicas , Disfunción Cognitiva , Lesiones del Sistema Vascular , Angiografía , Encéfalo/diagnóstico por imagen , Neoplasias Encefálicas/complicaciones , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/radioterapia , Hemorragia Cerebral , Disfunción Cognitiva/diagnóstico por imagen , Disfunción Cognitiva/etiología , Humanos , Imagen por Resonancia Magnética , Lesiones del Sistema Vascular/etiologíaRESUMEN
Quantitative susceptibility mapping (QSM) is a powerful MRI technique that has shown great potential in quantifying tissue susceptibility in numerous neurological disorders. However, the intrinsic ill-posed dipole inversion problem greatly affects the accuracy of the susceptibility map. We propose QSMGAN: a 3D deep convolutional neural network approach based on a 3D U-Net architecture with increased receptive field of the input phase compared to the output and further refined the network using the WGAN with gradient penalty training strategy. Our method generates accurate QSM maps from single orientation phase maps efficiently and performs significantly better than traditional non-learning-based dipole inversion algorithms. The generalization capability was verified by applying the algorithm to an unseen pathology--brain tumor patients with radiation-induced cerebral microbleeds.
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Mapeo Encefálico , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Redes Neurales de la Computación , Algoritmos , Artefactos , Encéfalo/fisiología , Mapeo Encefálico/métodos , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador/métodos , Imagen por Resonancia Magnética/métodos , MasculinoRESUMEN
PURPOSE: To develop a novel acquisition and reconstruction method for magnetization-prepared 3-dimensional multicontrast rapid gradient-echo imaging, using Hankel matrix completion in combination with compressed sensing and parallel imaging. METHODS: A random k-space shuffling strategy was implemented in simulation and in vivo human experiments at 7 T for 3-dimensional inversion recovery, T2 /diffusion preparation, and magnetization transfer imaging. We combined compressed sensing, based on total variation and spatial-temporal low-rank regularizations, and parallel imaging with pixel-wise Hankel matrix completion, allowing the reconstruction of tens of multicontrast 3-dimensional images from 3- or 6-min scans. RESULTS: The simulation result showed that the proposed method can reconstruct signal-recovery curves in each voxel and was robust for typical in vivo signal-to-noise ratio with 16-times acceleration. In vivo studies achieved 4 to 24 times accelerations for inversion recovery, T2 /diffusion preparation, and magnetization transfer imaging. Furthermore, the contrast was improved by resolving pixel-wise signal-recovery curves after magnetization preparation. CONCLUSIONS: The proposed method can improve acquisition efficiencies for magnetization-prepared MRI and tens of multicontrast 3-dimensional images could be recovered from a single scan. Furthermore, it was robust against noise, applicable for recovering multi-exponential signals, and did not require any previous knowledge of model parameters. Magn Reson Med 79:62-70, 2018. © 2017 International Society for Magnetic Resonance in Medicine.
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Encéfalo/diagnóstico por imagen , Medios de Contraste/química , Magnetismo , Algoritmos , Mapeo Encefálico/métodos , Simulación por Computador , Compresión de Datos/métodos , Difusión , Voluntarios Sanos , Humanos , Interpretación de Imagen Asistida por Computador/métodos , Imagenología Tridimensional , Modelos Estadísticos , Estudios Prospectivos , Estudios Retrospectivos , Relación Señal-RuidoRESUMEN
MR spectroscopic imaging (MRSI) at ultra-high field (≥7 T) benefits from improved sensitivity that allows the detection of low-concentration metabolites in the brain. However, optimized acquisition techniques are required to overcome inherent limitations of MRSI at ultra-high field. This work describes an optimized method for fast high-resolution 1 H-MRSI of the brain at 7 T. The proposed acquisition sequence combines precise volume localization using semi-localization by adiabatic selective refocusing, fast spatial encoding using high-bandwidth symmetric echo-planar spectroscopic imaging (EPSI), and robust water suppression with variable power and optimized relaxation delays. This showed improved robustness to B0 and B1+ inhomogeneities, eddy currents, nuisance signal contamination and system instabilities. Furthermore, a method for correction of phase inconsistencies in symmetric EPSI enabled high-bandwidth measurements at 7 T. The proposed correction effectively removed spectral ghosting using a single-shot water reference scan. This framework was tested in healthy volunteers at 7 T and spectral quality was compared with lower-spatial-resolution scans, measured at 3 T using the same methodology. A gain in the signal-to-noise ratio (SNR) per unit volume and unit time of 1.57 was achieved, keeping acquisition time short (5 min) and the specific absorption rate within the permitted limits. This SNR enhancement obtained at ultra-high field enabled high-resolution (0.25-0.375 mL) metabolite mapping of the brain within a clinically feasible scan time. The correlation of the reconstructed maps with anatomical structures was observed, showing the diagnostic potential of the technique.
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Imagen Eco-Planar , Colina/metabolismo , Creatina/metabolismo , Humanos , Procesamiento de Imagen Asistido por Computador , Espectroscopía de Resonancia Magnética , Metaboloma , Relación Señal-RuidoRESUMEN
OBJECTIVES: Our aim was to evaluate differences in metabolite levels between unmedicated patients with major depressive disorder (MDD) and healthy controls, to assess changes in metabolites in patients after they completed an 8-week course of mindfulness-based cognitive therapy (MBCT), and to exam the correlation between metabolites and depression severity. MATERIALS AND METHODS: Sixteen patients with MDD and ten age- and gender-matched healthy controls were studied using 3D short echo-time (20 ms) magnetic resonance spectroscopic imaging (MRSI) at 7 Tesla. Relative metabolite ratios were estimated in five regions of interest corresponding to insula, anterior cingulate cortex (ACC), caudate, putamen, and thalamus. RESULTS: In all cases, MBCT reduced severity of depression. The ratio of total choline-containing compounds/total creatine (tCr) in the right caudate was significantly increased compared to that in healthy controls, while ratios of N-acetyl aspartate (NAA)/tCr in the left ACC, myo-inositol/tCr in the right insula, and glutathione/tCr in the left putamen were significantly decreased. At baseline, the severity of depression was negatively correlated with my-inositol/tCr in the left insula and putamen. The improvement in depression severity was significantly associated with changes in NAA/tCr in the left ACC. CONCLUSIONS: This study has successfully evaluated regional differences in metabolites for patients with MDD who received MBCT treatment and in controls using 7 Tesla MRSI.
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Terapia Cognitivo-Conductual , Trastorno Depresivo Mayor/diagnóstico por imagen , Imagen por Resonancia Magnética , Atención Plena , Adulto , Ácido Aspártico/análogos & derivados , Ácido Aspártico/análisis , Estudios de Casos y Controles , Núcleo Caudado/diagnóstico por imagen , Corteza Cerebral/diagnóstico por imagen , Trastorno Depresivo Mayor/patología , Femenino , Giro del Cíngulo/diagnóstico por imagen , Humanos , Masculino , Putamen/diagnóstico por imagen , Tálamo/diagnóstico por imagen , Resultado del Tratamiento , Adulto JovenRESUMEN
OBJECTIVE: Zero echo time (ZTE) and ultrashort echo time (UTE) pulse sequences for MRI offer unique advantages of being able to detect signal from rapidly decaying short-T2 tissue components. In this paper, we applied 3D ZTE and UTE pulse sequences at 7T to assess differences between these methods. MATERIALS AND METHODS: We matched the ZTE and UTE pulse sequences closely in terms of readout trajectories and image contrast. Our ZTE used the water- and fat-suppressed solid-state proton projection imaging method to fill the center of k-space. Images from healthy volunteers obtained at 7T were compared qualitatively, as well as with SNR and CNR measurements for various ultrashort, short, and long-T2 tissues. RESULTS: We measured nearly identical contrast-to-noise and signal-to-noise ratios (CNR/SNR) in similar scan times between the two approaches for ultrashort, short, and long-T2 components in the brain, knee and ankle. In our protocol, we observed gradient fidelity artifacts in UTE, and our chosen flip angle and readout also resulted in shading artifacts in ZTE due to inadvertent spatial selectivity. These can be corrected by advanced reconstruction methods or with different chosen protocol parameters. CONCLUSION: The applied ZTE and UTE pulse sequences achieved similar contrast and SNR efficiency for volumetric imaging of ultrashort-T2 components. Key differences include that ZTE is limited to volumetric imaging, but has substantially reduced acoustic noise levels during the scan. Meanwhile, UTE has higher acoustic noise levels and greater sensitivity to gradient fidelity, but offers more flexibility in image contrast and volume selection.
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Imagen por Resonancia Magnética , Acústica , Algoritmos , Tobillo/diagnóstico por imagen , Artefactos , Encéfalo/diagnóstico por imagen , Mapeo Encefálico/métodos , Medios de Contraste/química , Voluntarios Sanos , Humanos , Aumento de la Imagen/métodos , Interpretación de Imagen Asistida por Computador/métodos , Procesamiento de Imagen Asistido por Computador , Rodilla/diagnóstico por imagen , Esclerosis Múltiple/diagnóstico por imagen , Esclerosis Múltiple/fisiopatología , Fantasmas de Imagen , Relación Señal-RuidoRESUMEN
This study aimed to develop a rapid, 1 mm3 isotropic resolution, whole-brain MRI technique for automatic lesion segmentation and multi-parametric mapping without using contrast by continuously applying balanced steady-state free precession with inversion pulses throughout incomplete inversion recovery in a single 6 min scan. Modified k-means clustering was performed for automatic brain tissue and lesion segmentation using distinct signal evolutions that contained mixed T1/T2/magnetization transfer properties. Multi-compartment modeling was used to derive quantitative multi-parametric maps for tissue characterization. Fourteen patients with contrast-enhancing gliomas were scanned with this sequence prior to the injection of a contrast agent, and their segmented lesions were compared to conventionally defined manual segmentations of T2-hyperintense and contrast-enhancing lesions. Simultaneous T1, T2, and macromolecular proton fraction maps were generated and compared to conventional 2D T1 and T2 mapping and myelination water fraction mapping acquired with MAGiC. The lesion volumes defined with the new method were comparable to the manual segmentations (r = 0.70, p < 0.01; t-test p > 0.05). The T1, T2, and macromolecular proton fraction mapping values of the whole brain were comparable to the reference values and could distinguish different brain tissues and lesion types (p < 0.05), including infiltrating tumor regions within the T2-lesion. Highly efficient, whole-brain, multi-contrast imaging facilitated automatic lesion segmentation and quantitative multi-parametric mapping without contrast, highlighting its potential value in the clinic when gadolinium is contraindicated.
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Introduction: This study evaluated changes in the white matter of the brain and psychological health variables, resulting from a neuroscience-based mindfulness intervention, the Training for Awareness, Resilience, and Action (TARA), in a population of healthy adolescents. Methods: A total of 100 healthy adolescents (57 female, age ranges 14-18 years) were randomized into the 12-week TARA intervention or a waitlist-control group. All participants were imaged with diffusion MRI to quantify white matter connectivity between brain regions. Imaging occurred at baseline/randomization and after 12 weeks of baseline (pre- and post-intervention in the TARA group). We hypothesized that structural connectivity in the striatum and interoceptive networks would increase following the TARA intervention, and that, this increased connectivity would relate to psychological health metrics from the Strengths and Difficulties Questionnaire (SDQ) and the Insomnia Severity Index (ISI). The TARA intervention and all assessments, except for the MRIs, were fully remotely delivered using secure telehealth platforms and online electronic data capture systems. Results: The TARA intervention showed high consistency, tolerability, safety, recruitment, fidelity, adherence, and retention. After 12 weeks, the TARA group, but not controls, also demonstrated significantly improved sleep quality (p = 0.02), and changes in the right putamen node strength were related to this improved sleep quality (r = -0.42, p = 0.006). Similarly, the TARA group, but not controls, had significantly increased right insula node strength related to improved emotional well-being (r = -0.31, p = 0.04). Finally, we used the network-based statistics to identify a white matter interoception network that strengthened following TARA (p = 0.009). Discussion: These results suggest that the TARA mindfulness-based intervention in healthy adolescents is feasible and safe, and it may act to increase structural connectivity strength in interoceptive brain regions. Furthermore, these white matter changes are associated with improved adolescent sleep quality and emotional well-being. Our results suggest that TARA could be a promising fully remotely delivered intervention for improving psychological well-being in adolescents. As our findings suggest that TARA affects brain regions in healthy adolescents, which are also known to be altered during depression in adolescents, future studies will examine the effects of TARA on depressed adolescents. Clinical trial registration: https://clinicaltrials.gov/study/NCT04254796.
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OBJECTIVE: We applied 7 Tesla phase sensitive imaging to evaluate the impact of brain iron levels on depression severity and cognitive function in individuals with major depressive disorder (MDD) treated with mindfulness-based cognitive therapy (MBCT). METHODS: Seventeen unmedicated MDD participants underwent MRI, evaluation of depression severity, and cognitive testing before and after receiving MBCT, compared to fourteen healthy controls (HC). Local field shift (LFS) values, measures of brain iron levels, were derived from phase images in the putamen, caudate, globus pallidus (GP), anterior cingulate cortex (ACC) and thalamus. RESULTS: Compared to the HC group, the MDD group had significantly lower baseline LFS (indicative of higher iron) in the left GP and left putamen and had a higher number of subjects with impairment in a test of information processing speed. In the MDD group, lower LFS values in the left and right ACC, right putamen, right GP, and right thalamus were significantly associated with depression severity; and lower LFS in the right GP was correlated with worse performance on measures of attention. All MBCT participants experienced depression relief. MBCT treatment also significantly improved executive function and attention. MBCT participants with lower baseline LFS values in the right caudate experienced significantly greater improvement in depression severity with treatment; and those with lower LFS values in the right ACC, right caudate, and right GB at baseline performed better on measures of verbal learning and memory after MBCT. CONCLUSIONS: Our study highlights the potential contribution of subtle differences in brain iron to MDD symptoms and their successful treatment.
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Terapia Cognitivo-Conductual , Trastorno Depresivo Mayor , Atención Plena , Humanos , Atención Plena/métodos , Trastorno Depresivo Mayor/diagnóstico por imagen , Trastorno Depresivo Mayor/terapia , Resultado del Tratamiento , Terapia Cognitivo-Conductual/métodos , NeuroimagenRESUMEN
Adolescence is a crucial time for social development, especially for helping (prosocial) and compassionate behaviors; yet brain networks involved in adolescent prosociality and compassion currently remain underexplored. Here, we sought to evaluate a recently proposed domain-general developmental (Do-GooD) network model of prosocial cognition by relating adolescent functional and structural brain networks with prosocial and compassionate disposition. We acquired resting state fMRI and diffusion MRI from 95 adolescents (ages 14-19 years; 46 males; 49 females) along with self-report questionnaires assessing prosociality and compassion. We then applied the Network-Based Statistic (NBS) to inductively investigate whether there is a significant subnetwork related to prosociality and compassion while controlling for age and sex. Based on the Do-GooD model, we expected that this subnetwork would involve connectivity to the ventromedial prefrontal cortex (VMPFC) from three domain-general networks, the default mode network (DMN), the salience network, and the control network, as well as from the DMN to the mirror neuron systems. NBS revealed a significant functional (but not structural) subnetwork related to prosociality and compassion connecting 31 regions (p = 0.02), showing DMN and DLPFC connectivity to the VMPFC; DMN connectivity to mirror neuron systems; and connectivity between the DMN and cerebellum. These findings largely support and extend the Do-GooD model of prosocial cognition in adolescents by further illuminating network-based relationships that have the potential to advance our understanding of brain mechanisms of prosociality.
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Background: Cognitive impairment and cerebral microbleeds (CMBs) are long-term side-effects of cranial radiation therapy (RT). Previously we showed that memory function is disrupted in young patients and that the rate of cognitive decline correlates with CMB development. However, vascular injury alone cannot explain RT-induced cognitive decline. Here we use resting-state functional MRI (rsfMRI) to further investigate the complex mechanisms underlying memory impairment after RT. Methods: Nineteen young patients previously treated with or without focal or whole-brain RT for a brain tumor underwent cognitive testing followed by 7T rsfMRI and susceptibility-weighted imaging for CMB detection. Global brain modularity and efficiency, and rsfMRI signal variability within the dorsal attention, salience, and frontoparietal networks were computed. We evaluated whether MR metrics could distinguish age- and sex-matched controls (N = 19) from patients and differentiate patients based on RT exposure and aggressiveness. We also related MR metrics with memory performance, CMB burden, and risk factors for cognitive decline after RT. Results: Compared to controls, patients exhibited widespread hyperconnectivity, similar modularity, and significantly increased efficiency (p < 0.001) and network variability (p < 0.001). The most abnormal values were detected in patients treated with high dose whole-brain RT, having supratentorial tumors, and who did not undergo RT but had hydrocephalus. MR metrics and memory performance were correlated (R = 0.34-0.53), though MR metrics were more strongly related to risk factors for cognitive worsening and CMB burden with evidence of functional recovery. Conclusions: MR metrics describing brain connectivity and variability represent promising candidate imaging biomarkers for monitoring of long-term cognitive side-effects after RT.
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Social distancing, home confinement, economic challenges, and COVID-19-related illness and deaths during the COVID-19 pandemic can significantly affect mental health in youth. One promising approach to reduce anxiety and depression in adolescents is the neuroscience-based mindfulness intervention Training for Awareness, Resilience, and Action (TARA). The objective of this individually randomized waitlist-controlled trial (RCT) was (1) to test the feasibility of TARA, delivered partially over Zoom, and (2) to assess changes in the emotional wellbeing in healthy adolescents between the ages of 14-18 years old during the COVID-19 pandemic. METHODS: Twenty-one healthy adolescents were randomized to the TARA intervention or to the waitlist control group in February 2020, just before the start of the pandemic. The TARA group intervention was delivered in person for the first five sessions and remotely over Zoom for the remaining seven sessions due to the pandemic. The participants' acceptability of TARA was assessed weekly using the Child Session Rating Scale (CSRS). The primary outcome was the emotional wellbeing measured using emotional symptoms subscale of the Strengths and Difficulties Questionnaire (SDQ) pre/post-TARA. We also explored weekly changes in TARA participants' wellbeing using the Child Outcome Rating Scale (CORS). RESULTS: The overall session rating in TARA participants improved after the switch to Zoom (Cohen's d = 1.2, p = 0.008). The results of the two-way ANOVA showed no statistically significant difference in the change of the SDQ emotional symptoms during the 12 weeks between the TARA group and waitlist-control group (timepoint × group interaction: F = 0.77, p = 0.38). The exploratory analysis using the CORS in the TARA participants showed a significant improvement in their functioning over the weeks of training. CONCLUSION: Our results support the feasibility of TARA delivered over Zoom. While our primary outcome did not provide support for the improvement of the emotional wellbeing with TARA compared to a passive control group, our exploratory analysis in the intervention group indicated an improved functioning over the weeks of TARA training. The important general positive impact of this study lies in the possibility of offering a neuroscience-based mindfulness intervention remotely to youth living in remote areas and for all youth during pandemic times.
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BACKGROUND: Radiation therapy (RT) is essential to the management of many brain tumors, but has been known to lead to cognitive decline and vascular injury in the form of cerebral microbleeds (CMBs). PURPOSE: In a subset of children, adolescents, and young adults recruited from a larger trial investigating arteriopathy and stroke risk after RT, we evaluated the prevalence of CMBs after RT, examined risk factors for CMBs and cognitive impairment, and related their longitudinal development to cognitive performance changes. METHODS: Twenty-five patients (mean 17 years, range: 10-25 years) underwent 7-Tesla MRI and cognitive assessment. Nineteen patients were treated with whole-brain or focal RT 1-month to 20-years prior, while 6 non-irradiated patients with posterior-fossa tumors served as controls. CMBs were detected on 7T susceptibility-weighted imaging (SWI) using semi-automated software, a first use in this population. RESULTS: CMB detection sensitivity with 7T SWI was higher than previously reported at lower field strengths, with one or more CMBs detected in 100% of patients treated with RT at least 1-year prior. CMBs were localized to dose-targeted brain volumes with risk factors including whole-brain RT (p = 0.05), a higher RT dose (p = 0.01), increasing time since RT (p = 0.03), and younger age during RT (p = 0.01). Apart from RT dose, these factors were associated with impaired memory performance. Follow-up data in a subset of patients revealed a proportional increase in CMB count with worsening verbal memory performance (r = -0.85, p = 0.03). CONCLUSIONS: Treatment with RT during youth is associated with the chronic development of CMBs that evolve with memory impairment over time.
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Neoplasias Encefálicas , Disfunción Cognitiva , Adolescente , Encéfalo , Neoplasias Encefálicas/complicaciones , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/radioterapia , Hemorragia Cerebral , Niño , Disfunción Cognitiva/etiología , Humanos , Imagen por Resonancia Magnética , Adulto JovenRESUMEN
Survival outcomes for patients with lower grade gliomas (LrGG) continue to improve. However, damage caused both by tumor growth and by the consequences of treatment often leads to significantly impaired cognitive function and quality of life (QoL). While neuropsychological testing is not routine, serial clinical MRIs are standard of care for patients with LrGG. Thus, having a greater understanding of MRI indicators of cognitive and QoL impairment risk could be beneficial to patients and clinicians. In this work we sought to test the hypothesis that in clinically stable LrGG patients, T2 FLAIR hyperintensity volumes at the time of cognitive assessment are associated with impairments of cognitive function and QoL and could be used to help identify patients for cognitive and QoL assessments and interventions. We performed anatomical MR imaging, cognitive testing and QoL assessments cross-sectionally in 30 clinically stable grade 2 and 3 glioma patients with subjective cognitive concerns who were 6 or more months post-treatment. Larger post-surgical T2 FLAIR volume at testing was significantly associated with lower cognitive performance, while pre-surgical tumor volume was not. Older patients had lower cognitive performance than younger patients, even after accounting for normal age-related declines in performance. Patients with Astrocytoma, IDH mutant LrGGs were more likely to show lower cognitive performance than patients with Oligodendroglioma, IDH mutant 1p19q co-deleted LrGGs. Previous treatment with combined radiation and chemotherapy was associated with poorer self-reported QoL, including self-reported cognitive function. This study demonstrates the importance of appreciating that LrGG patients may experience impairments in cognitive function and QoL over their disease course, including during periods of otherwise sustained clinical stability. Imaging factors can be helpful in identifying vulnerable patients who would benefit from cognitive assessment and rehabilitation.
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PURPOSE: Precise quantification of cerebral arteries can help with differentiation and prognostication of cerebrovascular disease. Existing image processing and segmentation algorithms for magnetic resonance angiography (MRA) are limited to the analysis of either 2D maximum intensity projection images or the entire 3D volume. The goal of this study was to develop a fully automated, hybrid 2D-3D method for robust segmentation of arteries and accurate quantification of vessel radii using MRA at varying projection thicknesses. METHODS: A novel algorithm that employs an adaptive Frangi filter for segmentation of vessels followed by estimation of vessel radii is presented. The method was evaluated on MRA datasets and corresponding manual segmentations from three healthy subjects for various projection thicknesses. In addition, the vessel metrics were computed in four additional subjects. Three synthetically generated angiographic datasets resembling brain vasculature were also evaluated under different noise levels. Dice similarity coefficient, Jaccard Index, F-score, and concordance correlation coefficient were used to measure the segmentation accuracy of manual versus automatic segmentation. RESULTS: Our new adaptive filter rendered accurate representations of vessels, maintained accurate vessel radii, and corresponded better to manual segmentation at different projection thicknesses than prior methods. Validation with synthetic datasets under low contrast and noisy conditions revealed accurate quantification of vessels without distortions. CONCLUSION: We have demonstrated a method for automatic segmentation of vascular trees and the subsequent generation of a vessel radii map. This novel technique can be applied to analyze arterial structures in healthy and diseased populations and improve the characterization of vascular integrity.
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There have been many theories about and computational models of the schizophrenic disease state. Brain imaging techniques have suggested that abnormalities of the thalamus may contribute to the pathophysiology of schizophrenia. Several studies have found the thalamus to be altered in schizophrenia, and the thalamus has connections with other brain structures implicated in the disorder. This paper describes an experiment examining thalamic levels of the metabolite N-acetylaspartate (NAA), taken from schizophrenics and controls using in vivo proton magnetic resonance spectroscopic imaging. Automatic relevance determination was performed on neural networks trained on this data, identifying NAA group differences in the pulvinar and mediodorsal nucleus, underscoring the importance of examining thalamic subregions in schizophrenia.
Asunto(s)
Mapeo Encefálico , Procesamiento de Imagen Asistido por Computador , Esquizofrenia/patología , Tálamo/patología , Ácido Aspártico/metabolismo , Colina/metabolismo , Humanos , Modelos Lineales , Espectroscopía de Resonancia Magnética , Masculino , Red Nerviosa/anatomía & histología , Red Nerviosa/fisiopatología , ProtonesRESUMEN
OBJECTIVE: Deficits in the mediodorsal and anterior nuclei of the thalamus may contribute to the psychopathological symptoms of schizophrenia. These thalamic nuclei have been found to be abnormal in schizophrenia and have close connections with other brain structures implicated in the disorder. We therefore examined schizophrenia-related alterations in brain metabolite levels specifically in the mediodorsal and anterior thalamic subregions. METHOD: We used in vivo proton magnetic resonance spectroscopic imaging ((1)H MRSI) to measure N-acetylaspartate (NAA), choline-containing compounds (Cho), and creatine+phosphocreatine (Cr) in the mediodorsal and anterior thalamus in 22 male patients with schizophrenia and 22 male controls. Magnetic resonance imaging (MRI) tissue segmentation and thalamic volume mask techniques were performed to distinguish the thalamus, extrathalamic gray and white matter, and CSF within the spectroscopic voxels. RESULTS: Compared to healthy subjects, patients with schizophrenia had significantly lower NAA in the mediodorsal and anterior thalamus bilaterally. No significant differences in Cho or Cr levels were seen. NAA was significantly higher in the left thalamus relative to the right in both groups. We found a strong negative correlation between left thalamic NAA and duration of illness, even after partialling out the effect of age. Tissue segmentation and thalamic volume mask techniques detected no group or lateralized differences in tissue type or CSF percentages, demonstrating that the metabolite reductions were not an artifact of spectroscopic voxel heterogeneity. CONCLUSIONS: These findings suggest diminished function and/or structure in the mediodorsal and anterior thalamus in male patients with schizophrenia and support earlier research demonstrating schizophrenia-related abnormalities in the thalamus and its circuitry.