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1.
Magn Reson Imaging ; 73: 111-117, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32717203

RESUMO

PURPOSE: Arterial spin labeling MRI can quantify the cerebral blood flow (CBF) without exogenous tracer. However, the variation of arterial transit time across different brain regions introduces bias for measuring local CBF, especially for those subjects with long arterial transit time (ATT). Long post-labeling delay (PLD) or multi-PLD methods could mitigate the problem of heterogenous ATT at the expense of the signal-to-noise ratio (SNR). Long-label ASL might address the low SNR problem by increasing the amount of labeled arterial blood. Thus, we hypothesized that with the same relatively long PLD, long-label pCASL may be more robust and reproducible than standard-label pCASL in population with potentially prolonged ATT. The purpose of the study was to investigate the reliability and reproducibility of long-label pCASL in the whole brain and vascular regions of interest in an elderly population, compared with standard-label pCASL. METHOD: Twenty adult volunteers (14 males, 6 females; age, 56.6 ± 17.2 years) were scanned twice on one 3.0 T scanner by standard-label pCASL (label duration (LD) = 1500 ms, PLD = 2000 ms) and long-label pCASL (LD = 3500 ms, PLD = 2000 ms). The intraclass correlation coefficient (ICC), within-subject coefficient of variation (wsCV), random noise and signal coefficient of variation(CoV) were used to assess global and regional reliability and reproducibility. Measurement agreement and difference were compared in different brain regions using correlation coefficient plots and Bland-Altman plots respectively. RESULTS: CBF value measured by long-label pCASL was overall higher than standard-label pCASL in all ROIs. Long-label pCASL had higher ICC than standard-label pCASL in most ROIs, and lower wsCV, random noise and CoV in all ROIs. Regardless of ASL method used, anterior circulation flow territories (ICC, 0.93-0.97; wsCV, 0.03-0.06) had higher CBF reliability and reproducibility than posterior circulation flow territories (ICC, 0.89; wsCV, 0.06-0.08). In all ROIs, the correlation analysis showed higher test-retest agreement (rlong-label > rstandard-label) and the Bland-Altman plots demonstrated lower measurement difference in long-label pCASL. CONCLUSION: The study demonstrated good reliability and reproducibility of long-label pCASL in anterior brain regions in the elderly population. To further improve CBF quantification in a long-ATT population while proper PLD is already used, increasing the label duration may help.


Assuntos
Encéfalo/irrigação sanguínea , Circulação Cerebrovascular/fisiologia , Processamento de Imagem Assistida por Computador/métodos , Imagem por Ressonância Magnética/métodos , Encéfalo/diagnóstico por imagem , Encéfalo/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valores de Referência , Reprodutibilidade dos Testes , Razão Sinal-Ruído , Marcadores de Spin
2.
Neuroradiol J ; 33(5): 368-373, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32666873

RESUMO

Central nervous system involvement in severe acute respiratory syndrome caused by coronavirus disease 2019 (COVID-19) has increasingly been recognised in the literature, and possible mechanisms of neuroinvasion, neurotropism and neurovirulence have been described. Neurological signs have been described in 84% of COVID-19 intensive care unit patients, and haemostatic abnormalities in such patients may play an important role, with a broad spectrum of neuroimaging findings. This report describes the magnetic resonance imaging neurovascular findings in an acutely ill patient with COVID-19, including perfusion abnormalities depicted in the arterial spin labelling technique.


Assuntos
Encéfalo/diagnóstico por imagem , Circulação Cerebrovascular , Infecções por Coronavirus/diagnóstico por imagem , Pneumonia Viral/diagnóstico por imagem , Hemorragia Subaracnóidea/diagnóstico por imagem , Idoso , Betacoronavirus , Encéfalo/irrigação sanguínea , Infecções por Coronavirus/complicações , Infecções por Coronavirus/fisiopatologia , Corpo Caloso , Lobo Frontal , Humanos , Hemorragias Intracranianas , Imagem por Ressonância Magnética , Masculino , Pandemias , Lobo Parietal , Imagem de Perfusão , Pneumonia Viral/complicações , Pneumonia Viral/fisiopatologia , Marcadores de Spin , Hemorragia Subaracnóidea/complicações , Tálamo
3.
PLoS One ; 15(7): e0236512, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32706796

RESUMO

OBJECTIVE: To identify abnormalities of regional cerebral blood flow (rCBF) in individuals with obsessive-compulsive disorder (OCD) by conducting a voxel-based analysis of pseudo-continuous arterial spin labeling (pCASL) perfusion images. MATERIALS AND METHODS: This prospective study included 23 OCD patients (nine males, 14 females; age 21-62 years; mean ± SD 37.2 ± 10.7 years) diagnosed based on DSM-IV-TR criteria and 64 healthy controls (27 males, 37 females; age 20-64 years; mean ± SD 38.3 ± 12.8 years). Subjects were recruited from October 2011 to August 2017. Imaging was performed on a 3T scanner. Quantitative rCBF maps generated from pCASL images were co-registered and resliced with the three-dimensional T1-weighted images, and then spatially normalized to a brain template and smoothed. We used statistical nonparametric mapping to assess the differences in rCBF and gray matter volume between the OCD and control groups. The significance level was set at the p-value <0.05 with family-wise error rate correction for multiple comparisons. RESULTS: Compared to the control group, there were significant rCBF reductions in the right putamen, right frontal operculum, left midcingulate cortex, and right temporal pole in the OCD group. There were no significant between-group differences in the gray matter volume. CONCLUSION: The pCASL imaging noninvasively detected physiologically disrupted areas without structural abnormalities in OCD patients. The rCBF reductions observed in these regions in OCD patients could be associated with the pathophysiology of OCD.


Assuntos
Artérias/química , Circulação Cerebrovascular/fisiologia , Imagem por Ressonância Magnética/métodos , Transtorno Obsessivo-Compulsivo/fisiopatologia , Adulto , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico , Estudos de Casos e Controles , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Imageamento Tridimensional , Masculino , Pessoa de Meia-Idade , Transtorno Obsessivo-Compulsivo/diagnóstico por imagem , Estudos Prospectivos , Marcadores de Spin , Adulto Jovem
4.
Chem Biol Interact ; 329: 109210, 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-32726580

RESUMO

Cigarette smoke is a complex mixture capable of triggering inflammation and oxidative damage in animals at pulmonary and systemic levels. Tempol (4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl) reduces tissue injury associated with inflammation in vivo by mechanisms that are not completely understood. Here we evaluated the effect of tempol on inflammation and oxidative damage induced by acute exposure to cigarette smoke in vivo. Male C57BL/6 mice (n = 32) were divided into 4 groups (n = 8 each): 1) control group exposed to ambient air (GC), 2) animals exposed to cigarette smoke for 5 days (CSG), mice treated 3) prior or 4) concomitantly with tempol (50 mg/kg/day) and exposed to cigarette smoke for 5 days. The results showed that the total number of leukocytes and neutrophils increased in the respiratory tract and lung parenchyma of mice exposed to cigarette smoke. Likewise, MPO levels and activity as well as lipid peroxidation and lung protein nitration and carbonylation also increased. Administration of tempol before or during exposure to cigarette smoke inhibited all the above parameters. Tempol also reduced the pulmonary expression of the inflammatory cytokines Il-6, Il-1ß and Il-17 to basal levels and of Tnf-α by approximately 50%. In contrast, tempol restored Il-10 and Tgf-ß levels and enhanced the expression of Nrf2-associated genes, such as Ho-1 and Gpx2. Accordingly, total GPx activity increased in lung homogenates of tempol-treated animals. Taken together, our results show that tempol protects mouse lungs from inflammation and oxidative damage resulting from exposure to cigarette smoke, likely through reduction of leukocyte infiltration and increased transcription of some of the Nrf2-controlled genes.


Assuntos
Óxidos N-Cíclicos/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/metabolismo , Infiltração de Neutrófilos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Fumar/efeitos adversos , Animais , Líquido da Lavagem Broncoalveolar/química , Interleucina-10/genética , Interleucina-10/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Pulmão/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fator 2 Relacionado a NF-E2/genética , Nitritos/análise , Peroxidase/metabolismo , Carbonilação Proteica/efeitos dos fármacos , Marcadores de Spin , Fator de Crescimento Transformador beta/genética , Fator de Crescimento Transformador beta/metabolismo
5.
Medicine (Baltimore) ; 99(22): e20503, 2020 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-32481470

RESUMO

To investigate the feasibility of 3D arterial spin labeling (ASL) as an alternative to dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) for the qualitative and quantitative evaluation of nasopharyngeal carcinoma (NPC) perfusion.Fifty-two newly diagnosed NPC patients underwent 3D ASL and DCE-MRI scans on a 3.0-T MRI system. The visual qualitative evaluation of the NPC perfusion level was scored from 0 to 3 (0 = no contrast to normal peripheral soft tissue, 3 = pronounced contrast to normal peripheral soft tissue). The visual evaluation of the NPC outline was scored from 0 to 2 (0 = very vague outline, 2 = clear outline). Comparisons of the ASL-derived blood flow (BF) with the DCE-MRI-derived positive enhancement integral, maximum slope of increase, maximum slope of decrease, and time to peak (TTP) were conducted between NPC and non-NPC areas with independent samples t-tests. The diagnostic performance of these parameters was assessed by receiver operating characteristic curve analysis. The correlations between ASL BF and DCE parameters were assessed by Spearman correlation analysis.There was no difference in the visual scores of the NPC perfusion level between the 2 perfusion methods (P= .963). ASL had a lower visual score for describing the outline of NPC than DCE-MRI (P < .001). The ASL and DCE parameters of the NPC areas were significantly different from those of the non-NPC areas (P < .001). The ASL BF showed the largest area under the receiver operating characteristic curve (AUC) of 0.936 for identifying NPC. When all NPC and non-NPC areas were taken into account, significant correlations were observed between the ASL BF and the DCE parameters positive enhancement integral (r = 0.503, P < .001), maximum slope of increase (r = 0.616, P < .001), maximum slope of decrease (r = 0.380, P < .001), and TTP (r = -0.601, P < .001).3D ASL could reveal the hyperperfusion of NPC in a qualitative and quantitative manner without using contrast agent. Additionally, the ASL BF correlated significantly with the semiquantitative DCE-MRI parameters.


Assuntos
Angiografia por Ressonância Magnética/métodos , Imagem por Ressonância Magnética/métodos , Carcinoma Nasofaríngeo/diagnóstico por imagem , Neoplasias Nasofaríngeas/diagnóstico por imagem , Adolescente , Adulto , Idoso , Meios de Contraste , Estudos de Viabilidade , Feminino , Gadolínio DTPA , Humanos , Interpretação de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Marcadores de Spin
6.
Clin Imaging ; 66: 127-132, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32480267

RESUMO

PURPOSE: To probe the utility of diffusion-weighted imaging (DWI) and 3D arterial spin labeling (ASL) in assessing the clinical stage of nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: This prospective study included sixty-five newly diagnosed NPC patients who underwent DWI and 3D ASL scans on a 3.0-T magnetic resonance imaging (MRI) system. The apparent diffusion coefficient (ADC) and the tumor blood flow (TBF) of NPC were measured. Tumors were classified as low or high T, N and American Joint Committee on Cancer (AJCC) stages. Student's t-test was used to evaluate the differences between tumors with low and high clinical stages. Pearson correlation analyses were performed to determine the correlation between MRI parameters and clinical stages. Receiver operating characteristic (ROC) curves were then used to evaluate diagnostic capability. RESULTS: High T stage (T3/4) NPC showed significantly lower ADCmin (P = 0.000) and higher TBFmax (P = 0.003) and TBFmean (P = 0.008) values than low T stage (T1/2) NPC. High N stage (N2/3) NPC showed significantly lower ADCmin values (P = 0.023) than low N stage (N0/1) NPC. High AJCC stage (III/IV) NPC showed significantly lower ADCmin (P = 0.000) and higher TBFmax (P = 0.005) and TBFmean (P = 0.011) values than low AJCC stage (I/II) NPC. ADCmin values showed moderate negative correlations with T stage (r = -0.512, P = 0.000), N stage (r = -0.281, P = 0.023), and AJCC stage (r = -0.494, P = 0.000). TBFmax values showed moderate positive correlations with T stage (r = 0.369, P = 0.003) and AJCC stage (r = 0.346, P = 0.005). Compared with ADCmin and TBFmax alone, the combination of ADCmin and TBFmax improved the accuracy from 72.3% and 75.4% to 78.5%, respectively, for T staging, as well as from 72.3% and 69.2% to 83.1% for AJCC staging. CONCLUSIONS: ADCmin and TBFmax values in patients with NPC could help evaluate clinical stages. ADCmin and TBFmax values combined could clearly improve the accuracy in the assessment of AJCC stage.


Assuntos
Carcinoma Nasofaríngeo/diagnóstico por imagem , Neoplasias Nasofaríngeas/diagnóstico por imagem , Estadiamento de Neoplasias , Adulto , Idoso , Imagem de Difusão por Ressonância Magnética/métodos , Feminino , Humanos , Imagem por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Neoplasias Nasofaríngeas/patologia , Estudos Prospectivos , Curva ROC , Marcadores de Spin
7.
Nan Fang Yi Ke Da Xue Xue Bao ; 40(1): 1-5, 2020 Jan 30.
Artigo em Chinês | MEDLINE | ID: mdl-32376558

RESUMO

OBJECTIVE: To retrospectively analyze the outcomes of wake-up stroke (WUS) patients with occlusion of large vessel occlusion (LVO), who were selected for mechanical thrombectomy according to the mismatch of Alberta Stroke Program Early CT Score (ASPECTS) based on arterial spin labeling (ASL) and diffusion-weighted image (DWI) on admission magnetic resonance (MR) scans. METHODS: Twelve consecutive WUS patients with acute LVO of the anterior circulation undergoing MR scans with ASL and DWI prior to thrombectomy were retrospectively evaluated. The mismatch of ASPECTS was defined as the difference between ASL-ASPECTS and DWI-ASPECTS, and a higher score indicates a greater mismatch. RESULTS: The procedures led to successful reperfusion in all the cases (Thrombolysis in Cerebral Infarction Grade 2b-3). Eleven patients (91.7%) had significantly decreased National Institute of Health Stroke scale (NIHSS) score at discharge.AmRS score of ≤2 at 90 days was achieved in 8 of the 12 patients (66.7%). CONCLUSIONS: The mismatch between ASPECTS assessed based on ASL and DWI can detect a true mismatch in patients with acute LVO of the anterior circulation, and can be used for rapid screening of patients eligible for thrombectomy.


Assuntos
Isquemia Encefálica/diagnóstico por imagem , Acidente Vascular Cerebral/diagnóstico por imagem , Trombectomia , Adulto , Idoso , Idoso de 80 Anos ou mais , Isquemia Encefálica/cirurgia , Imagem de Difusão por Ressonância Magnética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Marcadores de Spin , Acidente Vascular Cerebral/cirurgia , Resultado do Tratamento
8.
Nan Fang Yi Ke Da Xue Xue Bao ; 40(1): 56-60, 2020 Jan 30.
Artigo em Chinês | MEDLINE | ID: mdl-32376566

RESUMO

OBJECTIVE: To study the behavioral changes of inositol 1, 4, 5-trisphosphate receptor type 2 knockout (Itpr2-/- mice) and investigate the blood perfusion changes in the hippocampus using three-dimensional arterial spin labeling (3D-ASL). METHODS: 28 Itpr2-/- mice and 20 wild-type mice were assessed for depressive phenotype using behavioral tests (including sucrose consumption test, tail suspension test, forced swimming test and open field test). 15 Itpr2-/- mice and 14 wild-type mice were randomly selected for 3D-T2WI imaging of the whole brain and 3D-ASL imaging of the middle hippocampal layer, and cerebral blood flow (CBF) of the middle hippocampal layer was calculated. ITK-SNAP was used to delineate the bilateral hippocampal area and measure the average CBF value. RESULTS: Compared with the wild-type mice, Itpr2-/- mice exhibited a distinct depressive phenotype with significantly decreased sucrose preference (P < 0.05) and increased immobile time in tail suspension test (P < 0.05) and forced swimming test (P < 0.01), without obvious changes in the performance in open field test (P > 0.05). Significantly decreased mean CBF values were found in the left and right hippocampus of Itpr2-/- mice as compared with the wild-type mice (left: 73.30 ±5.609 vs 95.77±5.095; right: 73.53±5.700 vs 100.5±4.696; bilateral means: 73.42±5.607 vs98.12±4.754; P < 0.01). CONCLUSIONS: Itpr2 deficiency can cause depressive phenotype and affect the cerebral blood flow in the hippocampus of mice.


Assuntos
Circulação Cerebrovascular , Depressão/genética , Hipocampo/diagnóstico por imagem , Imageamento Tridimensional , Animais , Hipocampo/irrigação sanguínea , Receptores de Inositol 1,4,5-Trifosfato/genética , Camundongos , Camundongos Knockout , Imagem de Perfusão , Marcadores de Spin
9.
Life Sci ; 254: 117819, 2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32442451

RESUMO

AIMS: Vascular dysfunction plays a key role in sepsis but the role of perivascular adipose tissue (PVAT) in this condition is relatively unknown. MAIN METHODS: Sepsis was induced by cecal ligation and puncture (CLP). The responses of the aorta and superior mesenteric artery to norepinephrine in the presence or absence of PVAT were evaluated. Fluorescent probes measured the production of nitric oxide (NO) and reactive oxygen species (ROS). NO synthases (NOS) and ß3-adrenoceptor expression were detected by immunofluorescence and S-nitrosylation by the biotin switch assay. KEY FINDINGS: Aorta and superior mesenteric arteries from septic animals with intact PVAT showed a worsened response to the vasoconstrictor compared to vessels without PVAT. PVAT from the aorta (APVAT) produced NO and ROS whereas PVAT from the superior mesenteric artery (MPVAT) produced only ROS. Septic APVAT exhibited a higher density of NOS-1 and NOS-3. S-nitrosylation was found in APVAT. Donor (PVAT obtained from normal or septic rats):Host (normal vessel without PVAT) experiments showed that L-NAME, ODQ and ß3-adrenergic receptor antagonist blocked the septic APVAT anti-contractile effect. None of these compounds affected MPVAT; tempol, but not apocynin, blocked its anti-contractile effect. SIGNIFICANCE: PVAT contributes to the anti-contractile effect in the aorta and mesenteric artery of septic rats through different pathways. ß3-Adrenergic receptor and NO appear to be key mediators of this effect in APVAT, but not in MPVAT where ROS seem to be a relevant mediator. Therefore, PVAT is a relevant player of sepsis vascular dysfunction.


Assuntos
Aorta/metabolismo , Artérias Mesentéricas/metabolismo , Óxido Nítrico/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Receptores Adrenérgicos beta 3/fisiologia , Sepse/fisiopatologia , Acetofenonas/farmacologia , Tecido Adiposo/metabolismo , Agonistas de Receptores Adrenérgicos beta 3/farmacologia , Animais , Óxidos N-Cíclicos/farmacologia , Feminino , NG-Nitroarginina Metil Éster/farmacologia , Óxido Nítrico Sintase/metabolismo , Norepinefrina/farmacologia , Oxidiazóis/farmacologia , Fenótipo , Quinoxalinas/farmacologia , Ratos , Receptores Adrenérgicos beta 3/biossíntese , Marcadores de Spin , Vasoconstrição/efeitos dos fármacos , Vasoconstrição/fisiologia
10.
Clin Imaging ; 64: 92-96, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32388003

RESUMO

OBJECTIVE: Carbon monoxide (CO) poisoning is one of the most common poisonings worldwide. The affinity of hemoglobin for CO is significantly higher than that for oxygen, and the formation of carboxy-hemoglobin leads to a decrease in the capacity of blood to transport oxygen to tissues, tissue hypoxia, and early perfusion changes in the affected tissue. This study aimed to investigate the utility of arterial spin labeling perfusion imaging (ASL-PI) in revealing cerebral vascular hemodynamic changes in patients presenting to the emergency room with CO poisoning and to compare findings with those from diffusion-weighted imaging (DWI). METHOD: This study was conducted between November 2016 and May 2019 and was approved by the local ethics committee. DWI and ASL-PI examinations were performed in 83 patients who presented to the emergency room with CO poisoning. Four regions-the cerebral cortex, basal ganglia, cerebral white matter, and cerebellum-were evaluated for alterations in perfusion and diffusion, and findings from DWI and ASL-PI were compared. RESULTS: The study group included 39 (50.6%) females and 38 (49.4%) males, with a mean (±SD) age of 40.08 ± 20.41 years (range, 7-86 years). DWI revealed restricted diffusion in 10 regions in 6 (7.8%) patients, including the basal ganglia (n = 2), cerebral white matter (n = 2), cerebral cortex (n = 3), and the cerebellum (n = 3). ASL-PI revealed hypo-perfusion in 64 regions in 36 (46.8%) patients, including the basal ganglia (n = 21), cerebral white matter (n = 12), cerebral cortex (n = 23), and cerebellum (n = 7). CONCLUSION: ASL-PI provided additional information when used to identify perfusion changes in the brains of individuals who experienced CO poisoning and was superior to DWI as it revealed early changes in the brain. Considering its limitations, ASL-PI can be routinely used with DWI in cases of CO poisoning.


Assuntos
Encéfalo/diagnóstico por imagem , Intoxicação por Monóxido de Carbono/diagnóstico por imagem , Adulto , Artérias , Córtex Cerebral , Circulação Cerebrovascular , Imagem de Difusão por Ressonância Magnética/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Perfusão , Imagem de Perfusão/métodos , Marcadores de Spin , Substância Branca
11.
Br J Radiol ; 93(1110): 20190830, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32208976

RESUMO

OBJECTIVES: To compare the performance of arterial spin labelling (ASL) in evaluating arteriovenous malformations (AVMs) against the current gold standard of catheter angiography. METHODS: We systematically reviewed the published literature using EMBASE and Medline. We included studies that compared ASL to catheter angiography in the assessment of AVMs in three outcome domains: detection, angioarchitectural and haemodynamic features. RESULTS: From 314 unique citations, 19 studies representing 289 patients with intracranial AVMs met our inclusion criteria. We did not pool data due to marked heterogeneity in study outcome measures. Seven studies showed high diagnostic performance of ASL in identifying arterial feeders, with sensitivity ranging from 84.6 to 100% and specificity ranging from 93.3 to 100%. Six studies showed strong ability in detecting arteriovenous shunting, with sensitivity ranging from 91.7 to 100% and specificity ranging from 90 to 100%. Seven studies demonstrated that ASL could identify nidal location and size as well as catheter angiography, while five studies showed relatively poorer performance in delineating venous drainage. Two studies showed 100% sensitivity of ASL in the identification of residual or obliterated AVMs following stereotactic radiosurgery. CONCLUSIONS: Despite limitations in the current evidence base and technical challenges, this review suggests that ASL has a promising role in the work-up and post-treatment follow-up of AVMs. Larger scale prospective studies assessing the diagnostic performance of ASL are warranted. ADVANCES IN KNOWLEDGE: ASL demonstrates overall validity in the evaluation of intracranial AVMs.


Assuntos
Angiografia Cerebral/métodos , Malformações Arteriovenosas Intracranianas/diagnóstico por imagem , Angiografia por Ressonância Magnética/métodos , Cateterismo/métodos , Circulação Cerebrovascular , Humanos , Sensibilidade e Especificidade , Marcadores de Spin
12.
Arch Biochem Biophys ; 684: 108323, 2020 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-32126206

RESUMO

Electron Paramagnetic Resonance is a spectroscopic technique which, in combination with site-directed spin-labeling, provides structural and dynamic information about proteins in conditions similar to those of their physiological environment. The information is sequence-resolved, as it is based on probing the local dynamics of a paramagnetic label incorporated as a side chain of a selected amino acid. EPR does not impose a limit on the size of the protein or protein complex, as long as it is amenable to site-directed mutagenesis, and is able to obtain reliable distance distributions between two or more labels (identical or different).. The mean value, width and shape of distance distributions, as well as their dependence upon the state of the protein or interactions with physiological partners, provide insight into order-disorder transitions and the roles of protein flexibility. The main potentialities and limitations of the technique are revised and illustrated with examples of proteins for which order-disorder play an important role.


Assuntos
Espectroscopia de Ressonância de Spin Eletrônica/métodos , Proteínas Intrinsicamente Desordenadas/química , Marcadores de Spin , Óxidos N-Cíclicos/química , Cisteína/química , Maleabilidade , Conformação Proteica
13.
AJNR Am J Neuroradiol ; 41(3): 430-436, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32115416

RESUMO

BACKGROUND AND PURPOSE: Arterial spin-labeling-derived CBF values may be affected by arterial transit time artefacts. Thus, our aim was to assess to what extent arterial spin-labeling-derived CBF and cerebrovascular reserve capacity values in major vascular regions are overestimated due to the arterial transit time artifacts in patients with Moyamoya disease. MATERIALS AND METHODS: Eight patients with Moyamoya disease were included before or after revascularization surgery. CBF maps were acquired using a 3D pseudocontinuous arterial spin-labeling sequence, before and 5, 15, and 25 minutes after an IV acetazolamide injection and were registered to each patient's 3D-T1-weighted images. Vascular regions were defined by spatial normalization to a Montreal Neurological Institute-based vascular regional template. The arterial transit time artifacts were defined as voxels with high signal intensity corresponding to the right tail of the histogram for a given vascular region, with the cutoff selected by visual inspection. Arterial transit time artifact maps were created and applied as masks to exclude arterial transit time artifacts on CBF maps, to create corrected CBF maps. The cerebrovascular reserve capacity was calculated as CBF after acetazolamide injection relative to CBF at baseline for corrected and uncorrected CBF values, respectively. RESULTS: A total of 16 examinations were analyzed. Arterial transit time artifacts were present mostly in the MCA, whereas the posterior cerebral artery was generally unaffected. The largest differences between corrected and uncorrected CBF and cerebrovascular reserve capacity values, reported as patient group average ratio and percentage point difference, respectively, were 0.978 (95% CI, 0.968-0.988) and 1.8 percentage points (95% CI, 0.3-3.2 percentage points). Both were found in the left MCA, 15 and 5 minutes post-acetazolamide injection, respectively. CONCLUSIONS: Arterial transit time artifacts have negligible overestimation effects on calculated vascular region-based CBF and cerebrovascular reserve capacity values derived from single-delay 3D pseudocontinuous arterial spin-labeling.


Assuntos
Artefatos , Circulação Cerebrovascular/fisiologia , Interpretação de Imagem Assistida por Computador/métodos , Doença de Moyamoya/diagnóstico por imagem , Imagem de Perfusão/métodos , Adulto , Algoritmos , Feminino , Humanos , Imageamento Tridimensional/métodos , Imagem por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Marcadores de Spin
14.
Phys Med Biol ; 65(10): 10NT01, 2020 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-32160593

RESUMO

Arterial spin labeling (ASL) is a non-contrast enhanced method for perfusion measurements. The obtained information is in general a snap-shot of the whole-brain perfusion. Image acquisition is performed after a certain delay time after the labeling of the arterial blood. Time-resolved information alongside flow territory mapping of individual arteries can become useful for the collection of important information such as arterial crossflow, and revascularization. Therefore, a method is presented that combines time-resolved flow territory mapping within a single scan based on encoding of the acquisition cycle using a ternary matrix approach. The super-selective tagging process is divided in individual blocks following a ternary matrix encoding scheme. In each block, the position of the labeling focus changes its position to each of the major brain feeding arteries. Contrary to conventional ASL approaches, no control condition is acquired and the individual flow territories are calculated by combining the label images only. The method was successfully evaluated in healthy volunteers. Each flow territory could be visualized over several post labeling delays within a single scan of approximately five minutes. Comparison of signal intensity (relative perfusion) did not show statistically significant differences between the methods. Encoding super-selective ASL using a ternary matrix allows for the vessel-selective and time-resolved acquisition of perfusion territories within a single scan.


Assuntos
Artérias/diagnóstico por imagem , Artérias/fisiologia , Circulação Cerebrovascular , Imagem Molecular , Marcadores de Spin , Adulto , Algoritmos , Encéfalo/irrigação sanguínea , Feminino , Voluntários Saudáveis , Humanos , Processamento de Imagem Assistida por Computador , Masculino
15.
Nucleic Acids Res ; 48(6): 2830-2840, 2020 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-32052020

RESUMO

The determination of distances between specific points in nucleic acids is essential to understanding their behaviour at the molecular level. The ability to measure distances of 2-10 nm is particularly important: deformations arising from protein binding commonly fall within this range, but the reliable measurement of such distances for a conformational ensemble remains a significant challenge. Using several techniques, we show that electron paramagnetic resonance (EPR) spectroscopy of oligonucleotides spin-labelled with triazole-appended nitroxides at the 2' position offers a robust and minimally perturbing tool for obtaining such measurements. For two nitroxides, we present results from EPR spectroscopy, X-ray crystal structures of B-form spin-labelled DNA duplexes, molecular dynamics simulations and nuclear magnetic resonance spectroscopy. These four methods are mutually supportive, and pinpoint the locations of the spin labels on the duplexes. In doing so, this work establishes 2'-alkynyl nitroxide spin-labelling as a minimally perturbing method for probing DNA conformation.


Assuntos
DNA/química , Marcadores de Spin , Sequência de Bases , Cristalografia por Raios X , DNA/síntese química , Espectroscopia de Ressonância de Spin Eletrônica , Espectroscopia de Ressonância Magnética , Simulação de Dinâmica Molecular
16.
J Phys Chem Lett ; 11(5): 1848-1858, 2020 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-32062966

RESUMO

A method for fitting ab initio determined spin-orbit coupling interactions, in the Breit-Pauli approximation, based on quasidiabatic representations using neural network fits is reported. The algorithm generalizes our recently reported neural network approach for representing the dipole interaction. The S0, S1, and T1 states of formaldehyde are used as an example. First, the two singlet states S0 and S1 are diabatized with a modified Boys Localization diabatization method. Second, the spin-orbit coupling between singlet and triplet states is transformed to the diabatic representation. This removes the discontinuities in the adiabatic representation. The diabatized spin-orbit couplings are then fit with smooth neural network functions. The analytic representation of spin-orbit coupling interactions in a diabatic basis by neural networks will make accurate full-dimensional quantum dynamical treatment of both internal conversion and intersystem crossing possible, which will help us to gain better understanding of both processes.


Assuntos
Algoritmos , Formaldeído/química , Teoria Quântica , Marcadores de Spin
17.
Phys Chem Chem Phys ; 22(9): 4875-4879, 2020 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-32072999

RESUMO

Structural studies on proteins directly in their native environment are required for a comprehensive understanding of their function. Electron paramagnetic resonance (EPR) spectroscopy and in particular double electron-electron resonance (DEER) distance determination are suited to investigate spin-labeled proteins directly in the cell. The combination of intracellular bioorthogonal labeling with in-cell DEER measurements does not require additional purification or delivery steps of spin-labeled protein to the cells. In this study, we express eGFP in E. coli and use copper-catalyzed azide-alkyne cycloaddition (CuAAC) for the site-directed spin labeling of the protein in vivo, followed by in-cell EPR distance determination. Inter-spin distance measurements of spin-labeled eGFP agree with in vitro measurements and calculations based on the rotamer library of the spin label.


Assuntos
Espectroscopia de Ressonância de Spin Eletrônica , Escherichia coli/metabolismo , Proteínas de Fluorescência Verde/química , Alquinos/química , Azidas/química , Catálise , Cobre/química , Reação de Cicloadição , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Óxidos de Nitrogênio/química , Marcadores de Spin
18.
PLoS One ; 15(2): e0229444, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32101567

RESUMO

Clinical interpretation of arterial spin labeling (ASL) perfusion MRI in cerebrovascular disease remains challenging mainly because of the method's sensitivity to concomitant contributions from both intravascular and tissue compartments. While acquisition of multi-delay images can differentiate between the two contributions, the prolonged acquisition is prone to artifacts and not practical for clinical applications. Here, the utility of the spatial coefficient of variation (sCoV) of a single-delay ASL image as a marker of the intravascular contribution was evaluated by testing the hypothesis that sCoV can detect the effects of differences in label arrival times between ipsi- and contra-lateral hemispheres even in the absence of a hemispheric difference in CBF. Hemispheric lateralization values for sCoV and CBF were computed from ASL images acquired on 28 patients (age 73.9 ± 10.2 years, 8 women) with asymptomatic unilateral carotid occlusion. The results showed that sCoV lateralization predicted the occluded side with 96.4% sensitivity, missing only 1 patient. In contrast, the sensitivity of the CBF lateralization was 71.4%, with 8 patients showing no difference in CBF between hemispheres. The findings demonstrate the potential clinical utility of sCoV as a cerebrovascular correlate of large vessel disease. Using sCoV in tandem with CBF, vascular information can be obtained in image processing without the need for additional scan-time.


Assuntos
Arteriopatias Oclusivas/diagnóstico , Encéfalo/irrigação sanguínea , Doenças das Artérias Carótidas/diagnóstico , Circulação Cerebrovascular , Processamento de Imagem Assistida por Computador/métodos , Imagem por Ressonância Magnética/métodos , Marcadores de Spin , Idoso , Feminino , Humanos , Masculino
19.
Food Chem ; 315: 126237, 2020 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-32014666

RESUMO

Lipid derived free radical in soymilks were studied by combining 5,5-dimethyl-pyrroline-l-oxide (DMPO) spin trap, chloroform-methanol extraction and electron spin resonance (ESR) spectroscopy. Five lipid derived free radical adducts: DMPO-X, DMPO-L, DMPO-R, DMPO-LOO, and DMPO-RO were presented in soymilks. The total amounts of spins increased as the soaking temperature increased from 4 °C to 50 °C and the soaking pH increased from 3 to 9 and in paralleled with the diffusion of soybean exudates to soaking water. Prolonged soaking of soybean at 50 °C resulted in a higher signal intensity of DMPO-R than that of DMPO-LOO. Soybean lipoxygenases (LOXs) were responsible for the formation of lipid derived free radicals in soymilks. Soybean exudates affected the total amounts of lipid radicals in linoleic acid (LA) - LOX model system. The relative signal intensities of DMPO-R and DMPO-LOO were depended on the contents of soybean exudates in the system.


Assuntos
Radicais Livres/química , Lipídeos/química , Leite de Soja/química , Óxidos N-Cíclicos/química , Espectroscopia de Ressonância de Spin Eletrônica/métodos , Concentração de Íons de Hidrogênio , Ácido Linoleico/química , Soja/química , Marcadores de Spin , Temperatura
20.
Am J Respir Cell Mol Biol ; 62(6): 732-746, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32048876

RESUMO

Pulmonary vasoconstriction resulting from intermittent hypoxia (IH) contributes to pulmonary hypertension (pHTN) in patients with sleep apnea (SA), although the mechanisms involved remain poorly understood. Based on prior studies in patients with SA and animal models of SA, the objective of this study was to evaluate the role of PKCß and mitochondrial reactive oxygen species (mitoROS) in mediating enhanced pulmonary vasoconstrictor reactivity after IH. We hypothesized that PKCß mediates vasoconstriction through interaction with the scaffolding protein PICK1 (protein interacting with C kinase 1), activation of mitochondrial ATP-sensitive potassium channels (mitoKATP), and stimulated production of mitoROS. We further hypothesized that this signaling axis mediates enhanced vasoconstriction and pHTN after IH. Rats were exposed to IH or sham conditions (7 h/d, 4 wk). Chronic oral administration of the antioxidant Tempol or the PKCß inhibitor LY-333531 abolished IH-induced increases in right ventricular systolic pressure and right ventricular hypertrophy. Furthermore, scavengers of O2- or mitoROS prevented enhanced PKCß-dependent vasoconstrictor reactivity to endothelin-1 in pulmonary arteries from IH rats. In addition, this PKCß/mitoROS signaling pathway could be stimulated by the PKC activator PMA in pulmonary arteries from control rats, and in both rat and human pulmonary arterial smooth muscle cells. These responses to PMA were attenuated by inhibition of mitoKATP or PICK1. Subcellular fractionation and proximity ligation assays further demonstrated that PKCß acutely translocates to mitochondria upon stimulation and associates with PICK1. We conclude that a PKCß/mitoROS signaling axis contributes to enhanced vasoconstriction and pHTN after IH. Furthermore, PKCß mediates pulmonary vasoconstriction through interaction with PICK1, activation of mitoKATP, and subsequent mitoROS generation.


Assuntos
Hipertensão Pulmonar/fisiopatologia , Hipóxia/fisiopatologia , Mitocôndrias/fisiologia , Proteína Quinase C beta/fisiologia , Artéria Pulmonar/fisiopatologia , Vasoconstrição/fisiologia , Animais , Proteínas de Transporte/antagonistas & inibidores , Proteínas de Transporte/metabolismo , Células Cultivadas , Óxidos N-Cíclicos/farmacologia , Proteínas do Citoesqueleto/antagonistas & inibidores , Proteínas do Citoesqueleto/metabolismo , Depuradores de Radicais Livres/farmacologia , Humanos , Hipertensão Pulmonar/etiologia , Hipóxia/complicações , Hipóxia/enzimologia , Indóis/farmacologia , Masculino , Maleimidas/farmacologia , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Artérias Mesentéricas/efeitos dos fármacos , Artérias Mesentéricas/fisiopatologia , Miócitos de Músculo Liso/efeitos dos fármacos , Miócitos de Músculo Liso/enzimologia , Proteínas Nucleares/antagonistas & inibidores , Proteínas Nucleares/metabolismo , Canais de Potássio/metabolismo , Mapeamento de Interação de Proteínas , Artéria Pulmonar/enzimologia , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais , Síndromes da Apneia do Sono/fisiopatologia , Marcadores de Spin , Acetato de Tetradecanoilforbol/farmacologia
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