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Background Characterizing cerebrovascular hemodynamics in older adults is important for identifying disease and understanding normal neurovascular aging. Four-dimensional (4D) flow MRI allows for a comprehensive assessment of cerebral hemodynamics in a single acquisition. Purpose To establish reference intracranial blood flow and pulsatility index values in a large cross-sectional sample of middle-aged (45-65 years) and older (>65 years) adults and characterize the effect of age and sex on blood flow and pulsatility. Materials and Methods In this retrospective study, patients aged 45-93 years (cognitively unimpaired) underwent cranial 4D flow MRI between March 2010 and March 2020. Blood flow rates and pulsatility indexes from 13 major arteries and four venous sinuses and total cerebral blood flow were collected. Intraobserver and interobserver reproducibility of flow and pulsatility measures was assessed in 30 patients. Descriptive statistics (mean ± SD) of blood flow and pulsatility were tabulated for the entire group and by age and sex. Multiple linear regression and linear mixed-effects models were used to assess the effect of age and sex on total cerebral blood flow and vessel-specific flow and pulsatility, respectively. Results There were 759 patients (mean age, 65 years ± 8 [SD]; 506 female patients) analyzed. For intra- and interobserver reproducibility, median intraclass correlation coefficients were greater than 0.90 for flow and pulsatility measures across all vessels. Regression coefficients ß ± standard error from multiple linear regression showed a 4 mL/min decrease in total cerebral blood flow each year (age ß = -3.94 mL/min per year ± 0.44; P < .001). Mixed effects showed a 1 mL/min average annual decrease in blood flow (age ß = -0.95 mL/min per year ± 0.16; P < .001) and 0.01 arbitrary unit (au) average annual increase in pulsatility over all vessels (age ß = 0.011 au per year ± 0.001; P < .001). No evidence of sex differences was observed for flow (ß = -1.60 mL/min per male patient ± 1.77; P = .37), but pulsatility was higher in female patients (sex ß = -0.018 au per male patient ± 0.008; P = .02). Conclusion Normal reference values for blood flow and pulsatility obtained using four-dimensional flow MRI showed correlations with age. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Steinman in this issue.
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Arterias Cerebrales , Circulación Cerebrovascular , Senos Craneales , Hemodinámica , Imagen por Resonancia Magnética , Humanos , Persona de Mediana Edad , Envejecimiento , Anciano , Velocidad del Flujo Sanguíneo/fisiología , Imagen por Resonancia Magnética/métodos , Estudios Transversales , Masculino , Femenino , Anciano de 80 o más Años , Estudios Retrospectivos , Senos Craneales/diagnóstico por imagen , Arterias Cerebrales/diagnóstico por imagenRESUMEN
There has been extensive growth in both the technical development and the clinical applications of MRI, establishing this modality as one of the most powerful diagnostic imaging tools. However, long examination and image interpretation times still limit the application of MRI, especially in emergent clinical settings. Rapid and abbreviated MRI protocols have been developed as alternatives to standard MRI, with reduced imaging times, and in some cases limited numbers of sequences, to more efficiently answer specific clinical questions. A group of rapid MRI protocols used at the authors' institution, referred to as FAST (focused abbreviated survey techniques), are designed to include or exclude emergent or urgent conditions or screen for specific entities. These FAST protocols provide adequate diagnostic image quality with use of accelerated approaches to produce imaging studies faster than traditional methods. FAST protocols have become critical diagnostic screening tools at the authors' institution, allowing confident and efficient confirmation or exclusion of actionable findings. The techniques commonly used to reduce imaging times, the imaging protocols used at the authors' institution, and future directions in FAST imaging are reviewed to provide a practical and comprehensive overview of FAST MRI for practicing neuroradiologists. ©RSNA, 2023 Quiz questions for this article are available in the supplemental material.
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Imagen por Resonancia Magnética , Columna Vertebral , Humanos , Imagen por Resonancia Magnética/métodos , Columna Vertebral/diagnóstico por imagen , Encéfalo/diagnóstico por imagen , Literatura de Revisión como AsuntoRESUMEN
The COVID-19 pandemic highlighted the challenges delivering face-to-face patient care across healthcare systems. In particular the COVID-19 pandemic challenged the imaging community to provide timely access to essential diagnostic imaging modalities while ensuring appropriate safeguards were in place for both patients and personnel. With increasing vaccine availability and greater prevalence of vaccination in communities worldwide we are finally emerging on the other side of the COVID-19 pandemic. As we learned from our institutional and healthcare system responses to the pandemic, maintaining timely access to MR imaging is essential. Radiologists and other imaging providers partnered with their referring providers to ensure that timely access to advanced MR imaging was maintained. On behalf of the International Magnetic Resonance in Medicine (ISMRM) Safety Committee, this white paper is intended to serve as a guide for radiology departments, imaging centers, and other imaging specialists who perform MR imaging to refer to as we prepare for the next pandemic. Lessons learned including strategies to triage and prioritize MR imaging research during a pandemic are discussed. LEVEL OF EVIDENCE: 5 TECHNICAL EFFICACY: Stage 5.
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COVID-19 , Pandemias , Humanos , Imagen por Resonancia Magnética/efectos adversos , Pandemias/prevención & controlRESUMEN
This study investigated differences in retrospective cognitive trajectories between amyloid and tau PET biomarker stratified groups in initially cognitively unimpaired participants sampled from the Wisconsin Registry for Alzheimer's Prevention. One hundred and sixty-seven initially unimpaired individuals (baseline age 59 ± 6 years; 115 females) were stratified by elevated amyloid-ß and tau status based on 11C-Pittsburgh compound B (PiB) and 18F-MK-6240 PET imaging. Mixed effects models were used to determine if longitudinal cognitive trajectories based on a composite of cognitive tests including memory and executive function differed between biomarker groups. Secondary analyses investigated group differences for a variety of cross-sectional health and cognitive tests, and associations between 18F-MK-6240, 11C-PiB, and age. A significant group × age interaction was observed with post hoc comparisons indicating that the group with both elevated amyloid and tau pathophysiology were declining approximately three times faster in retrospective cognition compared to those with just one or no elevated biomarkers. This result was robust against various thresholds and medial temporal lobe regions defining elevated tau. Participants were relatively healthy and mostly did not differ between biomarker groups in health factors at the beginning or end of study, or most cognitive measures at study entry. Analyses investigating association between age, MK-6240 and PiB indicated weak associations between age and 18F-MK-6240 in tangle-associated regions, which were negligible after adjusting for 11C-PiB. Strong associations, particularly in entorhinal cortex, hippocampus and amygdala, were observed between 18F-MK-6240 and global 11C-PiB in regions associated with Braak neurofibrillary tangle stages I-VI. These results suggest that the combination of pathological amyloid and tau is detrimental to cognitive decline in preclinical Alzheimer's disease during late middle-age. Within the Alzheimer's disease continuum, middle-age health factors likely do not greatly influence preclinical cognitive decline. Future studies in a larger preclinical sample are needed to determine if and to what extent individual contributions of amyloid and tau affect cognitive decline. 18F-MK-6240 shows promise as a sensitive biomarker for detecting neurofibrillary tangles in preclinical Alzheimer's disease.
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Encéfalo/diagnóstico por imagen , Disfunción Cognitiva/diagnóstico por imagen , Placa Amiloide/diagnóstico por imagen , Anciano , Enfermedad de Alzheimer/diagnóstico por imagen , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/fisiopatología , Enfermedad de Alzheimer/psicología , Péptidos beta-Amiloides/metabolismo , Compuestos de Anilina , Encéfalo/metabolismo , Radioisótopos de Carbono , Disfunción Cognitiva/metabolismo , Disfunción Cognitiva/fisiopatología , Disfunción Cognitiva/psicología , Femenino , Radioisótopos de Flúor , Humanos , Isoquinolinas , Estudios Longitudinales , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Ovillos Neurofibrilares/metabolismo , Pruebas Neuropsicológicas , Placa Amiloide/metabolismo , Tomografía de Emisión de Positrones , Síntomas Prodrómicos , Tiazoles , Proteínas tau/metabolismoRESUMEN
After five positive randomized controlled trials showed benefit of mechanical thrombectomy in the management of acute ischemic stroke with emergent large-vessel occlusion, a multi-society meeting was organized during the 17th Congress of the World Federation of Interventional and Therapeutic Neuroradiology in October 2017 in Budapest, Hungary. This multi-society meeting was dedicated to establish standards of practice in acute ischemic stroke intervention aiming for a consensus on the minimum requirements for centers providing such treatment. In an ideal situation, all patients would be treated at a center offering a full spectrum of neuroendovascular care (a level 1 center). However, for geographical reasons, some patients are unable to reach such a center in a reasonable period of time. With this in mind, the group paid special attention to define recommendations on the prerequisites of organizing stroke centers providing medical thrombectomy for acute ischemic stroke, but not for other neurovascular diseases (level 2 centers). Finally, some centers will have a stroke unit and offer intravenous thrombolysis, but not any endovascular stroke therapy (level 3 centers). Together, these level 1, 2, and 3 centers form a complete stroke system of care. The multi-society group provides recommendations and a framework for the development of medical thrombectomy services worldwide.
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Accidente Cerebrovascular/terapia , Isquemia Encefálica/complicaciones , Isquemia Encefálica/terapia , Procedimientos Endovasculares/métodos , Humanos , Accidente Cerebrovascular/etiología , Trombectomía/métodosRESUMEN
Purpose To develop and evaluate a retrospective method to minimize motion artifacts in structural MRI. Materials and Methods The motion-correction strategy was developed for three-dimensional radial data collection and demonstrated with MPnRAGE, a technique that acquires high-resolution volumetric magnetization-prepared rapid gradient-echo, or MPRAGE, images with multiple tissue contrasts. Forty-four pediatric participants (32 with autism spectrum disorder [mean age ± standard deviation, 13 years ± 3] and 12 age-matched control participants [mean age, 12 years ± 3]) were imaged without sedation. Images with and images without retrospective motion correction were scored by using a Likert scale (0-4 for unusable to excellent) by two experienced neuroradiologists. The Tenengrad metric (a reference-free measure of image sharpness) and statistical analyses were performed to determine the effects of performing retrospective motion correction. Results MPnRAGE T1-weighted images with retrospective motion correction were all judged to have good or excellent quality. In some cases, retrospective motion correction improved the image quality from unusable (Likert score of 0) to good (Likert score of 3). Overall, motion correction improved mean Likert scores from 3.0 to 3.8 and reduced standard deviations from 1.1 to 0.4. Image quality was significantly improved with motion correction (Mann-Whitney U test; P < .001). Intraclass correlation coefficients for absolute agreement of Tenengrad scores with reviewers 1 and 2 were 0.92 and 0.88 (P < .0005 for both), respectively. In no cases did the retrospective motion correction induce severe image degradation. Conclusion Retrospective motion correction of MPnRAGE data were shown to be highly effective for consistently improving image quality of T1-weighted MRI in unsedated pediatric participants, while also enabling multiple tissue contrasts to be reconstructed for structural analysis. © RSNA, 2018 Online supplemental material is available for this article.
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Artefactos , Trastorno del Espectro Autista , Encéfalo/diagnóstico por imagen , Interpretación de Imagen Asistida por Computador/métodos , Imagenología Tridimensional/métodos , Imagen por Resonancia Magnética/métodos , Adolescente , Niño , Femenino , Humanos , Masculino , Movimiento (Física) , Neuroimagen/métodos , Reproducibilidad de los Resultados , Estudios RetrospectivosRESUMEN
Gadolinium-based contrast agents (GBCAs) have revolutionized MRI, enabling physicians to obtain crucial life-saving medical information that often cannot be obtained with other imaging modalities. Since initial approval in 1988, over 450 million intravenous GBCA doses have been administered worldwide, with an extremely favorable pharmacologic safety profile; however, recent information has raised new concerns over the safety of GBCAs. Mounting evidence has shown there is long-term retention of gadolinium in human tissues. Further, a small subset of patients have attributed a constellation of symptoms to GBCA exposure, although the association of these symptoms with GBCA administration or gadolinium retention has not been proven by scientific investigation. Despite evidence that macrocyclic GBCAs show less gadolinium retention than linear GBCAs, the safety implications of gadolinium retention are unknown. The mechanism and chemical forms of gadolinium retention, as well as the biologic activity and clinical importance of these retained gadolinium species, remain poorly understood and underscore the need for additional research. In February 2018, an international meeting was held in Bethesda, Md, at the National Institutes of Health to discuss the current literature and knowledge gaps about gadolinium retention, to prioritize future research initiatives to better understand this phenomenon, and to foster collaborative standardized studies. The greatest priorities are to determine (a) if gadolinium retention adversely affects the function of human tissues, (b) if retention is causally associated with short- or long-term clinical manifestations of disease, and (c) if vulnerable populations, such as children, are at greater risk for experiencing clinical disease. The purpose of the research roadmap is to highlight important information that is not known and to identify and prioritize needed research. ©RSNA, 2018 Online supplemental material is available for this article .
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Medios de Contraste/efectos adversos , Medios de Contraste/farmacocinética , Gadolinio/efectos adversos , Gadolinio/farmacocinética , Investigación , Animales , Humanos , National Institutes of Health (U.S.) , Radiología , Sociedades Médicas , Estados UnidosRESUMEN
The ability to detect preclinical Alzheimer's disease is of great importance, as this stage of the Alzheimer's continuum is believed to provide a key window for intervention and prevention. As Alzheimer's disease is characterized by multiple pathological changes, a biomarker panel reflecting co-occurring pathology will likely be most useful for early detection. Towards this end, 175 late middle-aged participants (mean age 55.9 ± 5.7 years at first cognitive assessment, 70% female) were recruited from two longitudinally followed cohorts to undergo magnetic resonance imaging and lumbar puncture. Cluster analysis was used to group individuals based on biomarkers of amyloid pathology (cerebrospinal fluid amyloid-ß42/amyloid-ß40 assay levels), magnetic resonance imaging-derived measures of neurodegeneration/atrophy (cerebrospinal fluid-to-brain volume ratio, and hippocampal volume), neurofibrillary tangles (cerebrospinal fluid phosphorylated tau181 assay levels), and a brain-based marker of vascular risk (total white matter hyperintensity lesion volume). Four biomarker clusters emerged consistent with preclinical features of (i) Alzheimer's disease; (ii) mixed Alzheimer's disease and vascular aetiology; (iii) suspected non-Alzheimer's disease aetiology; and (iv) healthy ageing. Cognitive decline was then analysed between clusters using longitudinal assessments of episodic memory, semantic memory, executive function, and global cognitive function with linear mixed effects modelling. Cluster 1 exhibited a higher intercept and greater rates of decline on tests of episodic memory. Cluster 2 had a lower intercept on a test of semantic memory and both Cluster 2 and Cluster 3 had steeper rates of decline on a test of global cognition. Additional analyses on Cluster 3, which had the smallest hippocampal volume, suggest that its biomarker profile is more likely due to hippocampal vulnerability and not to detectable specific volume loss exceeding the rate of normal ageing. Our results demonstrate that pathology, as indicated by biomarkers, in a preclinical timeframe is related to patterns of longitudinal cognitive decline. Such biomarker patterns may be useful for identifying at-risk populations to recruit for clinical trials.
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Envejecimiento , Enfermedad de Alzheimer , Péptidos beta-Amiloides/líquido cefalorraquídeo , Disfunción Cognitiva , Hipocampo/diagnóstico por imagen , Sustancia Blanca/diagnóstico por imagen , Anciano , Envejecimiento/líquido cefalorraquídeo , Envejecimiento/patología , Enfermedad de Alzheimer/líquido cefalorraquídeo , Enfermedad de Alzheimer/diagnóstico por imagen , Enfermedad de Alzheimer/fisiopatología , Atrofia/patología , Biomarcadores , Análisis por Conglomerados , Disfunción Cognitiva/líquido cefalorraquídeo , Disfunción Cognitiva/diagnóstico por imagen , Disfunción Cognitiva/fisiopatología , Femenino , Humanos , Estudios Longitudinales , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Fragmentos de Péptidos/líquido cefalorraquídeoRESUMEN
Whole brain radiotherapy (WBRT) is associated with memory dysfunction. As part of NRG Oncology RTOG 0933, a phase II study of WBRT for brain metastases that conformally avoided the hippocampal stem cell compartment (HA-WBRT), memory was assessed pre- and post-HA-WBRT using both traditional and computerized memory tests. We examined whether the computerized tests yielded similar findings and might serve as possible alternatives for assessment of memory in multi-institution clinical trials. Adult patients with brain metastases received HA-WBRT to 30 Gy in ten fractions and completed Hopkins Verbal Learning Test-Revised (HVLT-R), CogState International Shopping List Test (ISLT) and One Card Learning Test (OCLT), at baseline, 2 and 4 months. Tests' completion rates were 52-53 % at 2 months and 34-42 % at 4 months. All baseline correlations between HVLT-R and CogState tests were significant (p ≤ 0.003). At baseline, both CogState tests and one component of HVLT-R differentiated those who were alive at 6 months and those who had died (p ≤ 0.01). At 4 months, mean relative decline was 7.0 % for HVLT-R Delayed Recall and 18.0 % for ISLT Delayed Recall. OCLT showed an 8.0 % increase. A reliable change index found no significant changes from baseline to 2 and 4 months for ISLT Delayed Recall (z = -0.40, p = 0.34; z = -0.68, p = 0.25) or OCLT (z = 0.15, p = 0.56; z = 0.41, p = 0.66). Study findings support the possibility that hippocampal avoidance may be associated with preservation of memory test performance, and that these computerized tests also may be useful and valid memory assessments in multi-institution adult brain tumor trials.
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Neoplasias Encefálicas/psicología , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/secundario , Memoria/efectos de la radiación , Pruebas Neuropsicológicas , Traumatismos por Radiación/psicología , Femenino , Humanos , Masculino , Recuerdo Mental/efectos de la radiación , Persona de Mediana Edad , Aprendizaje Verbal/efectos de la radiaciónRESUMEN
OBJECTIVES: The purpose of this study was to assess whether age-related differences in white matter microstructure are associated with altered task-related connectivity during episodic recognition. METHODS: Using functional magnetic resonance imaging and diffusion tensor imaging from 282 cognitively healthy middle-to-late aged adults enrolled in the Wisconsin Registry for Alzheimer's Prevention, we investigated whether fractional anisotropy (FA) within white matter regions known to decline with age was associated with task-related connectivity within the recognition network. RESULTS: There was a positive relationship between fornix FA and memory performance, both of which negatively correlated with age. Psychophysiological interaction analyses revealed that higher fornix FA was associated with increased task-related connectivity amongst the hippocampus, caudate, precuneus, middle occipital gyrus, and middle frontal gyrus. In addition, better task performance was associated with increased task-related connectivity between the posterior cingulate gyrus, middle frontal gyrus, cuneus, and hippocampus. CONCLUSIONS: The findings indicate that age has a negative effect on white matter microstructure, which in turn has a negative impact on memory performance. However, fornix microstructure did not significantly mediate the effect of age on performance. Of interest, dynamic functional connectivity was associated with better memory performance. The results of the psychophysiological interaction analysis further revealed that alterations in fornix microstructure explain-at least in part-connectivity among cortical regions in the recognition memory network. Our results may further elucidate the relationship between structural connectivity, neural function, and cognition.
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Mapeo Encefálico , Lóbulo Frontal/diagnóstico por imagen , Lóbulo Frontal/fisiología , Memoria Episódica , Vías Nerviosas/fisiología , Reconocimiento en Psicología/fisiología , Adulto , Factores de Edad , Anciano , Imagen de Difusión Tensora , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Vías Nerviosas/diagnóstico por imagen , Pruebas Neuropsicológicas , Estimulación Luminosa , Estadística como Asunto , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/fisiologíaAsunto(s)
Angiografía Cerebral/métodos , Uso Excesivo de los Servicios de Salud/prevención & control , Accidente Cerebrovascular/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , Triaje/métodos , Encéfalo/diagnóstico por imagen , Encéfalo/cirugía , Angiografía por Tomografía Computarizada , Humanos , Reproducibilidad de los Resultados , Accidente Cerebrovascular/cirugía , Trombectomía/métodos , TiempoRESUMEN
INTRODUCTION: The present study investigated the relationship between beta-amyloid (Aß) and cognition in a late middle-aged cohort at risk for Alzheimer's disease (AD). METHODS: One eighty-four participants (mean age = 60; 72% parental history of AD) completed a [C-11]Pittsburgh compound B positron emission tomography scan and serial cognitive evaluations. A global measure of Aß burden was calculated, and composite scores assessing learning, delayed memory, and executive functioning were computed. RESULTS: Higher Aß was associated with classification of psychometric mild cognitive impairment (MCI) at follow-up (P < .01). Linear mixed effects regression results indicated higher Aß was associated with greater rates of decline in delayed memory (P < .01) and executive functioning (P < .05). Apolipoprotein E (APOE) ε4 status moderated the relationship between Aß and cognitive trajectories (P values <.01). DISCUSSION: In individuals at risk for AD, greater Aß in late middle age is associated with increased likelihood of MCI at follow-up and steeper rates of cognitive decline.
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Enfermedad de Alzheimer/metabolismo , Péptidos beta-Amiloides/metabolismo , Disfunción Cognitiva/metabolismo , Anciano , Encéfalo/metabolismo , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Pruebas Neuropsicológicas/estadística & datos numéricos , Tomografía de Emisión de Positrones/métodos , Síntomas Prodrómicos , Sistema de Registros , WisconsinAsunto(s)
Astrocitoma/diagnóstico por imagen , Núcleos Cerebelosos , Medios de Contraste , Gadolinio , Globo Pálido , Adolescente , Núcleos Cerebelosos/diagnóstico por imagen , Núcleos Cerebelosos/patología , Femenino , Globo Pálido/diagnóstico por imagen , Globo Pálido/patología , Humanos , Imagen por Resonancia Magnética/métodosRESUMEN
Cerebral blood flow (CBF) provides an indication of the metabolic status of the cortex and may have utility in elucidating preclinical brain changes in persons at risk for Alzheimer's disease (AD) and related diseases. In this study, we investigated CBF in 327 well-characterized adults including patients with AD (n = 28), patients with amnestic mild cognitive impairment (aMCI, n = 23), older cognitively normal (OCN, n = 24) adults, and asymptomatic middle-aged adults (n = 252) with and without a family history (FH) of AD. Compared with the asymptomatic cohort, AD patients displayed significant hypoperfusion in the precuneus, posterior cingulate, lateral parietal cortex, and the hippocampal region. Patients with aMCI exhibited a similar but less marked pattern of hypoperfusion. Perfusion deficits within the OCN adults were primarily localized to the inferior parietal lobules. Asymptomatic participants with a maternal FH of AD showed hypoperfusion in hippocampal and parietofrontal regions compared with those without a FH of AD or those with only a paternal FH of AD. These observations persisted when gray matter volume was included as a voxel-wise covariate. Our findings suggest that having a mother with AD might confer a particular risk for AD-related cerebral hypoperfusion in midlife. In addition, they provide further support for the potential utility of arterial spin labeling for the measurement of AD-related neurometabolic dysfunction, particularly in situations where [18F]fluorodeoxyglucose imaging is infeasible or clinically contraindicated.
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Enfermedad de Alzheimer/patología , Encéfalo/fisiopatología , Circulación Cerebrovascular/fisiología , Hijo de Padres Discapacitados , Relaciones Madre-Hijo , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/genética , Apolipoproteína E4/genética , Mapeo Encefálico , Disfunción Cognitiva/genética , Disfunción Cognitiva/patología , Femenino , Humanos , Imagenología Tridimensional , Imagen por Resonancia Magnética , Masculino , Persona de Mediana EdadRESUMEN
The relative influence of amyloid burden, neuronal structure and function, and prior cognitive performance on prospective memory decline among asymptomatic late middle-aged individuals at risk for Alzheimer's disease (AD) is currently unknown. We investigated this using longitudinal cognitive data from 122 middle-aged adults (21 "Decliners" and 101 "Stables") enrolled in the Wisconsin Registry for Alzheimer's Prevention who underwent multimodality neuroimaging [11C-Pittsburgh Compound B (PiB), 18F-fluorodeoxyglucose (FDG), and structural/functional magnetic resonance imaging (fMRI)] 5.7 ± 1.4 years (range = 2.9-8.9) after their baseline cognitive assessment. Covariate-adjusted regression analyses revealed that the only imaging measure that significantly distinguished Decliners from Stables (p = .027) was a Neuronal Function composite derived from FDG and fMRI. In contrast, several cognitive measures, especially those that tap episodic memory, significantly distinguished the groups (p's<.05). Complementary receiver operating characteristic curve analyses identified the Brief Visuospatial Memory Test-Revised (BVMT-R) Total (.82 ± .05, p < .001), the BVMT-R Delayed Recall (.73 ± .06, p = .001), and the Reading subtest from the Wide-Range Achievement Test-III (.72 ± .06, p = .002) as the top three measures that best discriminated the groups. These findings suggest that early memory test performance might serve a more clinically pivotal role in forecasting future cognitive course than is currently presumed.
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Enfermedad de Alzheimer/complicaciones , Enfermedad de Alzheimer/patología , Amiloide/metabolismo , Encéfalo/metabolismo , Encéfalo/patología , Trastornos del Conocimiento/etiología , Adulto , Anciano , Enfermedad de Alzheimer/genética , Análisis de Varianza , Apolipoproteína E4/genética , Encéfalo/irrigación sanguínea , Encéfalo/diagnóstico por imagen , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Neuroimagen , Pruebas Neuropsicológicas , Oxígeno/sangre , Curva ROC , Cintigrafía , Estudios Retrospectivos , Factores de RiesgoRESUMEN
BACKGROUND AND PURPOSE: The goal of the Stroke Treatment Academic Industry Roundtable (STAIR) meetings is to advance the development of stroke therapies. At STAIR VIII, consensus recommendations were developed for clinical trial strategies to demonstrate the benefit of endovascular reperfusion therapies for acute ischemic stroke. SUMMARY OF REVIEW: Prospects for success with forthcoming endovascular trials are robust, because new neurothrombectomy devices have superior reperfusion efficacy compared with earlier-generation interventions. Specific recommendations are provided for trial designs in 3 populations: (1) patients undergoing intravenous fibrinolysis, (2) early patients ineligible for or having failed intravenous fibrinolysis, and (3) wake-up and other late-presenting patients. Among intravenous fibrinolysis-eligible patients, key principles are that CT or MRI confirmation of target arterial occlusions should precede randomization; endovascular intervention should be pursued with the greatest rapidity possible; and combined intravenous and neurothrombectomy therapy is more promising than neurothrombectomy alone. Among patients ineligible for or having failed intravenous fibrinolysis, scientific equipoise was affirmed and the need to randomize all eligible patients emphasized. Vessel imaging to confirm occlusion is mandatory, and infarct core and penumbral imaging is desirable in later time windows. Additional STAIR VIII recommendations include approaches to test multiple devices in a single trial, utility weighting of disability end points, and adaptive designs to delineate time and tissue injury thresholds at which benefits from intervention no longer accrue. CONCLUSIONS: Endovascular research priorities in acute ischemic stroke are to perform trials testing new, highly effective neuro thrombectomy devices rapidly deployed in patients confirmed to have target vessel occlusions.
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Isquemia Encefálica/cirugía , Ensayos Clínicos como Asunto , Proyectos de Investigación , Accidente Cerebrovascular/cirugía , Trombectomía/instrumentación , Isquemia Encefálica/tratamiento farmacológico , Fibrinolíticos/uso terapéutico , Humanos , Accidente Cerebrovascular/tratamiento farmacológico , Terapia Trombolítica/métodosRESUMEN
Sinovenous thrombosis (SVT) is a well-recognized and serious complication in children treated for acute leukemia. This frequently occurs during or immediately upon completion of induction therapy and is commonly attributed to asparaginase therapy.Headache is the first and most common clinical symptom to occur during the early development of SVT. With advancement of the thrombosis, the clinical symptoms can progress to increased sleepiness, focal neurological deficit, seizures, and altered consciousness. We report the case of a 4-year-old girl who presented after several days of headaches and anorexia, which then progressed to seizures, left-sided weakness, and altered consciousness. She was later found to have a widespread and occlusive SVT with right cerebral hemorrhagic infarction. This case is notable for the extensive nature of the cerebral SVT and the child's complete clinical recovery from the neurological event. The report discusses the relation of the thrombosis and leukemia and also emphasizes the importance of early recognition and prompt management, while incorporating a collaborative multidisciplinary approach to prevent long-term consequences.
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Infarto Encefálico/etiología , Hemorragias Intracraneales/etiología , Leucemia-Linfoma Linfoblástico de Células T Precursoras/complicaciones , Leucemia-Linfoma Linfoblástico de Células T Precursoras/terapia , Trombosis de los Senos Intracraneales/etiología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Infarto Encefálico/terapia , Preescolar , Resultado Fatal , Femenino , Humanos , Hemorragias Intracraneales/terapia , Imagen por Resonancia Magnética , Trombosis de los Senos Intracraneales/terapiaRESUMEN
Introduction: Age-related changes in cerebral hemodynamics are controversial and discrepancies may be due to experimental techniques. As such, the purpose of this study was to compare cerebral hemodynamics measurements of the middle cerebral artery (MCA) between transcranial Doppler ultrasound (TCD) and four-dimensional flow MRI (4D flow MRI). Methods: Twenty young (25 ± 3 years) and 19 older (62 ± 6 years) participants underwent two randomized study visits to evaluate hemodynamics at baseline (normocapnia) and in response to stepped hypercapnia (4% CO2, and 6% CO2) using TCD and 4D flow MRI. Cerebral hemodynamic measures included MCA velocity, MCA flow, cerebral pulsatility index (PI) and cerebrovascular reactivity to hypercapnia. MCA flow was only assessed using 4D flow MRI. Results: MCA velocity between the TCD and 4D flow MRI methods was positively correlated across the normocapnia and hypercapnia conditions (r = 0.262; p = 0.004). Additionally, cerebral PI was significantly correlated between TCD and 4D flow MRI across the conditions (r = 0.236; p = 0.010). However, there was no significant association between MCA velocity using TCD and MCA flow using 4D flow MRI across the conditions (r = 0.079; p = 0.397). When age-associated differences in cerebrovascular reactivity using conductance were compared using both methodologies, cerebrovascular reactivity was greater in young adults compared to older adults when using 4D flow MRI (2.11 ± 1.68 mL/min/mmHg/mmHg vs. 0.78 ± 1.68 mL/min/mmHg/mmHg; p = 0.019), but not with TCD (0.88 ± 1.01 cm/s/mmHg/mmHg vs. 0.68 ± 0.94 cm/s/mmHg/mmHg; p = 0.513). Conclusion: Our results demonstrated good agreement between the methods at measuring MCA velocity during normocapnia and in response to hypercapnia, but MCA velocity and MCA flow were not related. In addition, measurements using 4D flow MRI revealed effects of aging on cerebral hemodynamics that were not apparent using TCD.
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Cognitive decline in Alzheimer's disease and other dementias typically begins long before clinical impairment. Identifying people experiencing subclinical decline may facilitate earlier intervention. This study developed cognitive trajectory clusters using longitudinally based random slope and change point parameter estimates from a Preclinical Alzheimer's disease Cognitive Composite and examined how baseline and most recently available clinical/health-related characteristics, cognitive statuses and biomarkers for Alzheimer's disease and vascular disease varied across these cognitive clusters. Data were drawn from the Wisconsin Registry for Alzheimer's Prevention, a longitudinal cohort study of adults from late midlife, enriched for a parental history of Alzheimer's disease and without dementia at baseline. Participants who were cognitively unimpaired at the baseline visit with ≥3 cognitive visits were included in trajectory modelling (n = 1068). The following biomarker data were available for subsets: positron emission tomography amyloid (amyloid: n = 367; [11C]Pittsburgh compound B (PiB): global PiB distribution volume ratio); positron emission tomography tau (tau: n = 321; [18F]MK-6240: primary regions of interest meta-temporal composite); MRI neurodegeneration (neurodegeneration: n = 581; hippocampal volume and global brain atrophy); T2 fluid-attenuated inversion recovery MRI white matter ischaemic lesion volumes (vascular: white matter hyperintensities; n = 419); and plasma pTau217 (n = 165). Posterior median estimate person-level change points, slopes' pre- and post-change point and estimated outcome (intercepts) at change point for cognitive composite were extracted from Bayesian Bent-Line Regression modelling and used to characterize cognitive trajectory groups (K-means clustering). A common method was used to identify amyloid/tau/neurodegeneration/vascular biomarker thresholds. We compared demographics, last visit cognitive status, health-related factors and amyloid/tau/neurodegeneration/vascular biomarkers across the cognitive groups using ANOVA, Kruskal-Wallis, χ2, and Fisher's exact tests. Mean (standard deviation) baseline and last cognitive assessment ages were 58.4 (6.4) and 66.6 (6.6) years, respectively. Cluster analysis identified three cognitive trajectory groups representing steep, n = 77 (7.2%); intermediate, n = 446 (41.8%); and minimal, n = 545 (51.0%) cognitive decline. The steep decline group was older, had more females, APOE e4 carriers and mild cognitive impairment/dementia at last visit; it also showed worse self-reported general health-related and vascular risk factors and higher amyloid, tau, neurodegeneration and white matter hyperintensity positive proportions at last visit. Subtle cognitive decline was consistently evident in the steep decline group and was associated with generally worse health. In addition, cognitive trajectory groups differed on aetiology-informative biomarkers and risk factors, suggesting an intimate link between preclinical cognitive patterns and amyloid/tau/neurodegeneration/vascular biomarker differences in late middle-aged adults. The result explains some of the heterogeneity in cognitive performance within cognitively unimpaired late middle-aged adults.
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BACKGROUND AND PURPOSE: The DIAS-2 study was the only large, randomized, intravenous, thrombolytic trial that selected patients based on the presence of ischemic penumbra. However, DIAS-2 did not confirm the positive findings of the smaller DEDAS and DIAS trials, which also used penumbral selection. Therefore, a reevaluation of the penumbra selection strategy is warranted. METHODS: In post hoc analyses we assessed the relationships of magnetic resonance imaging-measured lesion volumes with clinical measures in DIAS-2, and the relationships of the presence and size of the diffusion-perfusion mismatch with the clinical effect of desmoteplase in DIAS-2 and in pooled data from DIAS, DEDAS, and DIAS-2. RESULTS: In DIAS-2, lesion volumes correlated with National Institutes of Health Stroke Scale (NIHSS) at both baseline and final time points (P<0.0001), and lesion growth was inversely related to good clinical outcome (P=0.004). In the pooled analysis, desmoteplase was associated with 47% clinical response rate (n=143) vs 34% in placebo (n=73; P=0.08). For both the pooled sample and for DIAS-2, increasing the minimum baseline mismatch volume (MMV) for inclusion increased the desmoteplase effect size. The odds ratio for good clinical response between desmoteplase and placebo treatment was 2.83 (95% confidence interval, 1.16-6.94; P=0.023) for MMV >60 mL. Increasing the minimum NIHSS score for inclusion did not affect treatment effect size. CONCLUSIONS: Pooled across all desmoteplase trials, desmoteplase appears beneficial in patients with large MMV and ineffective in patients with small MMV. These results support a modified diffusion-perfusion mismatch hypothesis for patient selection in later time-window thrombolytic trials. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique Identifiers: NCT00638781, NCT00638248, NCT00111852.