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INTRODUCTION: Cerebral blood flow (CBF) is reduced in cognitively impaired (CI) Alzheimer's disease (AD) patients. We checked the sensitivity of time-encoded arterial spin labeling (te-ASL) in measuring CBF alterations in individuals with positive AD biomarkers and associations with relevant biomarkers in cognitively unimpaired (CU) individuals. METHODS: We compared te-ASL with single-postlabel delay (PLD) ASL in measuring CBF in 59 adults across the AD continuum, classified as CU amyloid beta (Aß) negative (-), CU Aß positive (+), and CI Aß+. We sought associations of CBF with biomarkers of AD, cerebrovascular disease, synaptic dysfunction, neurodegeneration, and cognition in CU participants. RESULTS: te-ASL was more sensitive at detecting CBF reduction in the CU Aß+ and CI Aß+ groups. In CU participants, lower CBF was associated with altered biomarkers of Aß, tau, synaptic dysfunction, and neurodegeneration. DISCUSSION: CBF reduction occurs early in the AD continuum. te-ASL is more sensitive than single-PLD ASL at detecting CBF changes in AD. HIGHLIGHTS: Lower CBF can be detected in CU subjects in the early AD continuum. te-ASL is more sensitive than single-PLD ASL at detecting CBF alterations in AD. CBF is linked to biomarkers of AD, synaptic dysfunction, and neurodegeneration.
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Silent cerebral infarcts (SCI) are common in patients with sickle cell disease (SCD) and are thought to be caused by a mismatch between oxygen delivery and consumption. Functional cerebrovascular shunting is defined as reduced oxygen offloading due to the rapid transit of blood through the capillaries caused by increased flow and has been suggested as a potential mechanism underlying reduced oxygenation and SCI. We investigated the venous arterial spin labeling signal (VS) in the sagittal sinus as a proxy biomarker of cerebral functional shunting, and its association with hemodynamic imaging and hematological laboratory parameters. We included 28 children and 38 adults with SCD, and ten healthy racematched adult controls. VS, cerebral blood flow (CBF), velocity in the brain feeding arteries, oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO2) were measured before and after acetazolamide administration. VS was higher in patients with SCD compared to controls (P<0.01) and was increased after acetazolamide administration in all groups (P<0.01). VS was primarily predicted by CBF (P<0.01), but CBF-corrected VS was also associated with decreased CMRO2 (P<0.01). Additionally, higher disease severity defined by low hemoglobin and increased hemolysis was associated with higher CBF-corrected VS. Finally, CMRO2 was negatively correlated with fetal hemoglobin, and positively correlated with lactate dehydrogenase, which could be explained by changes in oxygen affinity. These findings provide evidence for cerebral functional shunting and encourage future studies investigating the potential link to aberrant capillary exchange in SCD.
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Anemia Falciforme , Imageamento por Ressonância Magnética , Adulto , Criança , Humanos , Imageamento por Ressonância Magnética/métodos , Acetazolamida , Encéfalo/irrigação sanguínea , Encéfalo/metabolismo , Oxigênio/metabolismo , Infarto Cerebral , Consumo de Oxigênio/fisiologiaRESUMO
PURPOSE: Multislice arterial spin labeling (ASL) MRI acquisitions are currently challenging in skeletal muscle because of long transit times, translating into low-perfusion SNR in distal slices when large spatial coverage is required. However, fiber type and oxidative capacity vary along the length of healthy muscles, calling for multislice acquisitions in clinical studies. We propose a new variant of flow alternating inversion recovery (FAIR) that generates sufficient ASL signal to monitor exercise-induced perfusion changes in muscle in two distant slices. METHODS: Label around and between two 7-cm distant slices was created by applying the presaturation/postsaturation and selective inversion modules selectively to each slice (split-label multislice FAIR). Images were acquired using simultaneous multislice EPI. We validated our approach in the brain to take advantage of the high resting-state perfusion, and applied it in the lower leg muscle during and after exercise, interleaved with a single-slice FAIR as a reference. RESULTS: We show that standard multislice FAIR leads to an underestimation of perfusion, while the proposed split-label multislice approach shows good agreement with separate single-slice FAIR acquisitions in brain, as well as in muscle following exercise. CONCLUSION: Split-label FAIR allows measuring muscle perfusion in two distant slices simultaneously without losing sensitivity in the distal slice.
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Circulação Cerebrovascular , Imageamento por Ressonância Magnética , Perfusão , Reprodutibilidade dos Testes , Marcadores de SpinRESUMO
Arterial spin labeling (ASL) has undergone significant development since its inception, with a focus on improving standardization and reproducibility of its acquisition and quantification. In a community-wide effort towards robust and reproducible clinical ASL image processing, we developed the software package ExploreASL, allowing standardized analyses across centers and scanners. The procedures used in ExploreASL capitalize on published image processing advancements and address the challenges of multi-center datasets with scanner-specific processing and artifact reduction to limit patient exclusion. ExploreASL is self-contained, written in MATLAB and based on Statistical Parameter Mapping (SPM) and runs on multiple operating systems. To facilitate collaboration and data-exchange, the toolbox follows several standards and recommendations for data structure, provenance, and best analysis practice. ExploreASL was iteratively refined and tested in the analysis of >10,000 ASL scans using different pulse-sequences in a variety of clinical populations, resulting in four processing modules: Import, Structural, ASL, and Population that perform tasks, respectively, for data curation, structural and ASL image processing and quality control, and finally preparing the results for statistical analyses on both single-subject and group level. We illustrate ExploreASL processing results from three cohorts: perinatally HIV-infected children, healthy adults, and elderly at risk for neurodegenerative disease. We show the reproducibility for each cohort when processed at different centers with different operating systems and MATLAB versions, and its effects on the quantification of gray matter cerebral blood flow. ExploreASL facilitates the standardization of image processing and quality control, allowing the pooling of cohorts which may increase statistical power and discover between-group perfusion differences. Ultimately, this workflow may advance ASL for wider adoption in clinical studies, trials, and practice.
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Encéfalo/diagnóstico por imagem , Processamento de Imagem Assistida por Computador/métodos , Angiografia por Ressonância Magnética/métodos , Algoritmos , Circulação Cerebrovascular/fisiologia , Humanos , Reprodutibilidade dos Testes , Razão Sinal-Ruído , Software , Marcadores de SpinRESUMO
PURPOSE: To compare cerebral blood flow (CBF) and cerebrovascular reserve (CVR) quantification from Turbo-QUASAR (quantitative signal targeting with alternating radiofrequency labeling of arterial regions) arterial spin labeling (ASL) and single post-labeling delay pseudo-continuous ASL (PCASL). METHODS: A model-based method was developed to quantify CBF and arterial transit time (ATT) from Turbo-QUASAR, including a correction for magnetization transfer effects caused by the repeated labeling pulses. Simulations were performed to assess the accuracy of the model-based method. Data from an in vivo experiment conducted on a healthy cohort were retrospectively analyzed to compare the CBF and CVR (induced by acetazolamide) measurement from Turbo-QUASAR and PCASL on the basis of global and regional differences. The quality of the two ASL data sets was examined using the coefficient of variation (CoV). RESULTS: The model-based method for Turbo-QUASAR was accurate for CBF estimation (relative error was 8% for signal-to-noise ratio = 5) in simulations if the bolus duration was known. In the in vivo experiment, the mean global CVR estimated by Turbo-QUASAR and PCASL was between 63% and 64% and not significantly different. Although global CBF values of the two ASL techniques were not significantly different, regional CBF differences were found in deep gray matter in both pre- and postacetazolamide conditions. The CoV of Turbo-QUASAR data was significantly higher than PCASL. CONCLUSION: Both ASL techniques were effective for quantifying CBF and CVR, despite the regional differences observed. Although CBF estimated from Turbo-QUASAR demonstrated a higher variability than PCASL, Turbo-QUASAR offers the advantage of being able to measure and control for variation in ATT.
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Encéfalo/irrigação sanguínea , Encéfalo/diagnóstico por imagem , Circulação Cerebrovascular/fisiologia , Interpretação de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Marcadores de Spin , Adulto JovemRESUMO
In sickle cell disease (SCD), oxygen delivery is impaired due to anemia, especially during times of increased metabolic demand, and cerebral blood flow (CBF) must increase to meet changing physiologic needs. But hyperemia limits cerebrovascular reserve (CVR) and ischemic risk prevails despite elevated CBF. The cerebral metabolic rate of oxygen (CMRO2 ) directly reflects oxygen supply and consumption and may therefore be more insightful than flow-based CVR measures for ischemic risk in SCD. We hypothesized that adults with SCD have impaired CMRO2 at rest and that a vasodilatory challenge with acetazolamide would improve CMRO2 . CMRO2 was calculated from CBF and oxygen extraction fraction (OEF), measured with arterial spin labeling and T2 -prepared tissue relaxation with inversion recovery (T2 -TRIR) MRI. We studied 36 adults with SCD without a clinical history of overt stroke, and nine healthy controls. As expected, CBF was higher in patients with SCD versus controls (mean ± SD: 74 ± 16 versus 46 ± 5 mL/100 g/min, P < .001), resulting in similar oxygen delivery (SCD: 377 ± 67 versus controls: 368 ± 42 µmol O2 /100g/min, P = .69). OEF was lower in patients versus controls (27 ± 4 versus 35 ± 4%, P < .001), resulting in lower CMRO2 in patients versus controls (102 ± 24 versus 127 ± 20 µmol O2 /100g/min, P = .002). After acetazolamide, CMRO2 declined further in patients (P < .01) and did not decline significantly in controls (P = .78), indicating that forcing higher CBF worsened oxygen utilization in SCD patients. This lower CMRO2 could reflect variation between healthy and unhealthy vascular beds in terms of dilatory capacity and resistance whereby dysfunctional vessels become more oxygen-deprived, hence increasing the risk of localized ischemia.
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Anemia Falciforme/sangue , Encéfalo/metabolismo , Hipóxia Encefálica/etiologia , Oxigênio/metabolismo , Acetazolamida/farmacologia , Acetazolamida/uso terapêutico , Adulto , Anemia Falciforme/complicações , Anemia Falciforme/tratamento farmacológico , Encéfalo/diagnóstico por imagem , Isquemia Encefálica/etiologia , Isquemia Encefálica/prevenção & controle , Circulação Cerebrovascular/efeitos dos fármacos , Estudos Transversais , Feminino , Hemoglobina Fetal/análise , Humanos , Hidroxiureia/uso terapêutico , Hipóxia Encefálica/diagnóstico por imagem , Hipóxia Encefálica/tratamento farmacológico , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neuroimagem , Consumo de Oxigênio , Falha de Tratamento , Vasodilatadores/farmacologia , Vasodilatadores/uso terapêutico , Adulto JovemRESUMO
Sickle cell disease is characterized by chronic hemolytic anemia and vascular inflammation, which can diminish the vasodilatory capacity of the small resistance arteries, making them less adept at regulating cerebral blood flow. Autoregulation maintains adequate oxygen delivery, but when vasodilation is maximized, the low arterial oxygen content can lead to ischemia and silent cerebral infarcts. We used magnetic resonance imaging of cerebral blood flow to quantify whole-brain cerebrovascular reserve in 36 adult patients with sickle cell disease (mean age, 31.9±11.3 years) and 11 healthy controls (mean age, 37.4±15.4 years), and we used high-resolution 3D FLAIR magnetic resonance imaging to determine the prevalence of silent cerebral infarcts. Cerebrovascular reserve was calculated as the percentage change in cerebral blood flow after a hemodynamic challenge with acetazolamide. Co-registered lesion maps were used to demonstrate prevalent locations for silent cerebral infarcts. Cerebral blood flow was elevated in patients with sickle cell disease compared to controls (median [interquartile range]: 82.8 [20.1] vs 51.3 [4.8] mL/100g/min, P<0.001). Cerebral blood flow was inversely associated with age, hemoglobin, and fetal hemoglobin, and correlated positively with bilirubin, and LDH, indicating that cerebral blood flow may reflect surrogates of hemolytic rate. Cerebrovascular reserve in sickle cell disease was decreased by half compared to controls (34.1 [33.4] vs 69.5 [32.4] %, P<0.001) and was associated with hemoglobin and erythrocyte count indicating anemia-induced hemodynamic adaptations. In total, 29/36 patients (81%) and 5/11 controls (45%) had silent cerebral infarcts (median volume of 0.34 vs 0.02 mL, P=0.03). Lesions were preferentially located in the borderzone. In conclusion, patients with sickle cell disease have a globally reduced cerebrovascular reserve as determined by arterial spin labeling with acetazolamide and reflects anemia-induced impaired vascular function in sickle cell disease. This study was registered at clinicaltrials.gov identifier 02824406.
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Acetazolamida/administração & dosagem , Anemia Falciforme , Circulação Cerebrovascular/efeitos dos fármacos , Hemodinâmica/efeitos dos fármacos , Angiografia por Ressonância Magnética , Adulto , Anemia Falciforme/sangue , Anemia Falciforme/diagnóstico por imagem , Anemia Falciforme/fisiopatologia , Infarto Cerebral/sangue , Infarto Cerebral/diagnóstico por imagem , Infarto Cerebral/fisiopatologia , Feminino , Hemoglobina Fetal/metabolismo , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Stroke risk in children with sickle cell disease (SCD) is currently assessed with routine transcranial Doppler ultrasound (TCD) measurements of blood velocity in the Circle of Willis (CoW). However, there is currently no biomarker with proven prognostic value in adult patients. Four-dimensional (4D) flow magnetic resonance imaging (MRI) may improve risk profiling based on intracranial haemodynamics. We conducted neurovascular 4D flow MRI and blood sampling in 69 SCD patients [median age 15 years (interquartile range, IQR: 12-50)] and 14 healthy controls [median age 21 years (IQR: 18-43)]. We measured velocity, flow, lumen area and endothelial shear stress (ESS) in the CoW. SCD patients had lower haematocrit and viscosity, and higher velocity, flow and lumen area, with lower ESS compared to healthy controls. We observed significant age-related decline in haemodynamic 4D flow parameters; velocity (Spearman's ρ = -0·36 to -0·61), flow (ρ = -0·26 to -0·52) and ESS (ρ = -0·14 to -0·54) in SCD patients. Further analysis in only adults showed that velocity values were similar in SCD patients compared to healthy controls, but that the additional 4D flow parameters, flow and lumen area, were higher, and ESS lower, in the SCD group. Our data suggest that 4D flow MRI may identify adult patients with an increased stroke risk more accurately than current TCD-based velocity.
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Anemia Falciforme/fisiopatologia , Circulação Cerebrovascular , Hemodinâmica , Imageamento por Ressonância Magnética , Adolescente , Adulto , Fatores Etários , Anemia Falciforme/sangue , Anemia Falciforme/patologia , Velocidade do Fluxo Sanguíneo , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Estudos de Casos e Controles , Criança , Feminino , Hematócrito , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Viscosidade , Adulto JovemRESUMO
INTRODUCTION: Case reports of life-threatening cardiac arrhythmias and sudden cardiac arrest (SCA) among amphetamine users have raised serious concerns about the cardiac safety of this class of drugs. This is important in light of the high prevalence of dexamphetamine (dAMPH) prescription for attention-deficit/hyperactivity disorder (ADHD), and its rising use as a recreational drug. The objective was to investigate electrocardiogram (ECG) parameters upon intravenous administration of a single dAMPH dose in habitual recreational dAMPH users (users) and healthy gender/age/ intelligence-quotient-matched controls (non-users). METHODS AND RESULTS: ECG recordings were made in 18 users and 18 non-users during administration of dAMPH (0.3 mg/kg body weight). Baseline ECG was normal in both groups. dAMPH elicited increased heart rate and corrected QT time (QTc) prolongation in both groups (all P < 0.001, QTc = 502 in one individual). QTc prolongation was attenuated in users compared to non-users, exhibiting a significant interaction effect (P = 0.04). CONCLUSION: SCA associated with amphetamine use may be related to its QTc prolonging effects, particularly during first-time use. These observations may provide a rationale for conducting ECG analysis immediately after the first-time use of amphetamines, as this could potentially unmask vulnerable individuals.
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Estimulantes do Sistema Nervoso Central/efeitos adversos , Dextroanfetamina/efeitos adversos , Síndrome do QT Longo/induzido quimicamente , Síndrome do QT Longo/fisiopatologia , Transtornos Relacionados ao Uso de Substâncias/diagnóstico por imagem , Transtornos Relacionados ao Uso de Substâncias/fisiopatologia , Eletrocardiografia/efeitos dos fármacos , Eletrocardiografia/métodos , Feminino , Humanos , Síndrome do QT Longo/diagnóstico , Masculino , Adulto JovemRESUMO
Stroke is common in children with sickle cell disease and results from an imbalance in oxygen supply and demand. Cerebral blood flow (CBF) is increased in patients with sickle cell disease to compensate for their anemia, but adequacy of their oxygen delivery has not been systematically demonstrated. This study examined the physiological determinants of CBF in 37 patients with sickle cell disease, 38 ethnicity matched control subjects and 16 patients with anemia of non-sickle origin. Cerebral blood flow was measured using phase contrast MRI of the carotid and vertebral arteries. CBF increased inversely to oxygen content (r(2) = 0.69, P < 0.0001). Brain oxygen delivery, the product of CBF and oxygen content, was normal in all groups. Brain composition, specifically the relative amounts of grey and white matter, was the next strongest CBF predictor, presumably by influencing cerebral metabolic rate. Grey matter/white matter ratio and CBF declined monotonically until the age of 25 in all subjects, consistent with known maturational changes in brain composition. Further CBF reductions were observed with age in subjects older than 35 years of age, likely reflecting microvascular aging. On multivariate regression, CBF was independent of disease state, hemoglobin S, hemoglobin F, reticulocyte count and cell free hemoglobin, suggesting that it is regulated similarly in patients and control subjects. In conclusion, sickle cell disease patients had sufficient oxygen delivery at rest, but accomplish this only by marked increases in their resting CBF, potentially limiting their ability to further augment flow in response to stress. Am. J. Hematol. 91:912-917, 2016. © 2016 Wiley Periodicals, Inc.
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Anemia Falciforme/sangue , Circulação Cerebrovascular , Oxigênio/metabolismo , Adolescente , Adulto , Fatores Etários , Anemia/sangue , Anemia Falciforme/fisiopatologia , Encéfalo/irrigação sanguínea , Estudos de Casos e Controles , Circulação Cerebrovascular/fisiologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Adulto JovemRESUMO
We discuss two potential non-invasive MRI methods to study phenomena related to subarachnoid cerebrospinal fluid (CSF) motion and perivascular fluid transport, and their association with sleep and aging. We apply diffusion-based intravoxel incoherent motion (IVIM) imaging to evaluate pseudodiffusion coefficient, D*, or CSF movement across large spaces like the subarachnoid space (SAS). We also performed perfusion-based multi-echo, Hadamard encoded arterial spin labeling (ASL) to evaluate whole brain cortical cerebral blood flow (CBF) and trans-endothelial exchange (Tex) of water from the vasculature into the perivascular space and parenchyma. Both methods were used in young adults (N = 9, 6 F, 23 ± 3 years old) in the setting of sleep and sleep deprivation. To study aging, 10 older adults (6 F, 67 ± 3 years old) were imaged after a night of normal sleep and compared with the young adults. D* in SAS was significantly (p < 0.05) reduced with sleep deprivation (0.016 ± 0.001 mm2/s) compared to normal sleep (0.018 ± 0.001 mm2/s) and marginally reduced with aging (0.017 ± 0.001 mm2/s, p = 0.029). Cortical CBF and Tex were unchanged with sleep deprivation but significantly lower in older adults (37 ± 3 ml/100 g/min, 578 ± 61 ms) than in young adults (42 ± 2 ml/100 g/min, 696 ± 62 ms). IVIM was sensitive to sleep physiology and aging, and multi-echo, multi-delay ASL was sensitive to aging.
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The blood-brain barrier (BBB) is a barrier protecting the brain and a milieu of continuous exchanges between blood and brain. There is emerging evidence that the BBB plays a major role in epileptogenesis and drug-resistant epilepsy, through several mechanisms, such as water homeostasis dysregulation, overexpression of drug transporters, and inflammation. Studies have shown abnormal water homeostasis in epileptic tissue and altered aquaporin-4 water channel expression in animal epilepsy models. This review focuses on abnormal water exchange in epilepsy and describes recent non-invasive MRI methods of quantifying water exchange. PLAIN LANGUAGE SUMMARY: Abnormal exchange between blood and brain contribute to seizures and epilepsy. The authors describe why correct water balance is necessary for healthy brain functioning and how it is impacted in epilepsy. This review also presents recent MRI methods to measure water exchange in human brain. These measures would improve our understanding of factors leading to seizures.
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Barreira Hematoencefálica , Epilepsia , Neuroimagem , Barreira Hematoencefálica/metabolismo , Humanos , Epilepsia/metabolismo , Epilepsia/diagnóstico por imagem , Epilepsia/fisiopatologia , Animais , Água/metabolismo , Imageamento por Ressonância Magnética , Encéfalo/metabolismo , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologiaRESUMO
We discuss two potential non-invasive MRI methods to cross-sectionally study two distinct facets of the glymphatic system and its association with sleep and aging. We apply diffusion-based intravoxel incoherent motion (IVIM) imaging to evaluate pseudodiffusion coefficient, D*, or cerebrospinal fluid (CSF) movement across large spaces like the subarachnoid space (SAS). We also performed perfusion-based multi-echo, Hadamard encoded multi-delay arterial spin labeling (ASL) to evaluate whole brain cortical cerebral blood flow (CBF) and transendothelial exchange (Tex) of water from the vasculature into the perivascular space and parenchyma. Both methods were used in young adults (N=9, 6F, 23±3 years old) in the setting of sleep and sleep deprivation. To study aging, 10 older adults, (6F, 67±3 years old) were imaged after a night of normal sleep only and compared with the young adults. D* in SAS was significantly (p<0.05) lesser after sleep deprivation (0.014±0.001 mm2/s) than after normal sleep (0.016±0.001 mm2/s), but was unchanged with aging. Cortical CBF and Tex on the other hand, were unchanged after sleep deprivation but were significantly lower in older adults (37±3 ml/100g/min, 476±66 ms) than young adults (42±2 ml/100g/min, 624±66 ms). IVIM was thus, sensitive to sleep physiology and multi-echo, multi-delay ASL was sensitive to aging.
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Ketamine is a promising treatment option for patients with Major Depressive Disorder (MDD) and has become an important research tool to investigate antidepressant mechanisms of action. However, imaging studies attempting to characterise ketamine's mechanism of action using blood oxygen level-dependent signal (BOLD) imaging have yielded inconsistent results- at least partly due to intrinsic properties of the BOLD contrast, which measures a complex signal related to neural activity. To circumvent the limitations associated with the BOLD signal, we used arterial spin labelling (ASL) as an unambiguous marker of neuronal activity-related changes in cerebral blood flow (CBF). We measured CBF in 21 MDD patients at baseline and 24 h after receiving a single intravenous infusion of subanesthetic ketamine and examined relationships with clinical outcomes. Our findings demonstrate that increase in thalamus perfusion 24 h after ketamine administration is associated with greater improvement of depressive symptoms. Furthermore, lower thalamus perfusion at baseline is associated both with larger increases in perfusion 24 h after ketamine administration and with stronger reduction of depressive symptoms. These findings indicate that ASL is not only a useful tool to broaden our understanding of ketamine's mechanism of action but might also have the potential to inform treatment decisions based on CBF-defined regional disruptions.
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Transtorno Depressivo Maior , Ketamina , Humanos , Ketamina/efeitos adversos , Transtorno Depressivo Maior/diagnóstico por imagem , Transtorno Depressivo Maior/tratamento farmacológico , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Tálamo/diagnóstico por imagem , Circulação Cerebrovascular , Marcadores de SpinRESUMO
PURPOSE: To investigate possible sources of quantification errors in global cerebral blood flow (CBF) measurements by comparing pseudo continuous arterial spin labeling (PCASL) and phase contrast (PC) MRI in anemic, hyperemic subjects. METHODS: All studies were performed on a Philips 3T Achieva MRI scanner. PC and PCASL CBF examinations were performed in 10 healthy, young adult subjects and 18 young adults with chronic anemia syndromes including sickle cell disease and thalassemia. CBF estimates from single and two compartment ASL kinetic models were compared. Numerical simulation and flow phantom experiments were used to explore the effects of blood velocity and B1+ on CBF quantification and labeling efficiency. RESULTS: PCASL CBF underestimated PC in both populations using a single compartment model (30.1±9.2% control, 45.2±17.2% anemia). Agreement substantially improved using a two-compartment model (-8.0±6.0% control, 11.7±12.3% anemia). Four of the anemic subjects exhibited venous outflow of ASL signal, suggestive of cerebrovascular shunt, possibly confounding PC-PCASL comparisons. Additionally, sub-study experiments demonstrated that B1+ was diminished at the labeling plane (82.9±5.1%), resulting in suboptimal labeling efficiency. Correcting labeling efficiency for diminished B1+, PCASL slightly overestimated PC CBF in controls (-15.4±6.8%) and resulted in better matching of CBF estimates in anemic subjects (0.7±10.0% without outflow, 10.5±9.4% with outflow). CONCLUSIONS: This work demonstrates that a two-compartment model is critical for PCASL quantification in hyperemic subjects. Venous outflow and B1+ under-excitation may also contribute to flow underestimation, but further study of these effects is required.
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Velocidade do Fluxo Sanguíneo/fisiologia , Circulação Cerebrovascular/fisiologia , Angiografia por Ressonância Magnética , Marcadores de Spin , Adolescente , Anemia/diagnóstico por imagem , Anemia Falciforme/diagnóstico por imagem , Artérias/diagnóstico por imagem , Feminino , Humanos , Estudos Longitudinais , Masculino , Microscopia de Contraste de Fase , Reprodutibilidade dos Testes , Adulto JovemRESUMO
Quantitative measurements of brain perfusion are influenced by perfusion-modifiers. Standardization of measurement conditions and correction for important modifiers is essential to improve accuracy and to facilitate the interpretation of perfusion-derived parameters. An extensive literature search was carried out for factors influencing quantitative measurements of perfusion in the human brain unrelated to medication use. A total of 58 perfusion modifiers were categorized into four groups. Several factors (e.g., caffeine, aging, and blood gases) were found to induce a considerable effect on brain perfusion that was consistent across different studies; for other factors, the modifying effect was found to be debatable, due to contradictory results or lack of evidence. Using the results of this review, we propose a standard operating procedure, based on practices already implemented in several research centers. Also, a theory of 'deep MRI physiotyping' is inferred from the combined knowledge of factors influencing brain perfusion as a strategy to reduce variance by taking both personal information and the presence or absence of perfusion modifiers into account. We hypothesize that this will allow to personalize the concept of normality, as well as to reach more rigorous and earlier diagnoses of brain disorders.