Cerebral perfusion in patients with unilateral internal carotid artery occlusion by dual post-labeling delays arterial spin labeling imaging

BACKGROUND Global and regional cerebral blood flow(CBF)changes in patients with unilateral internal carotid artery occlusion(ICAO)are unclear when the dual post-labeling delays(PLD)arterial spin labeling(ASL)magnetic resonance imaging(MRI)technique is used.Manual delineation of regions of interest for CBF measurement is time-consuming and laborious.AIM To assess global and regional CBF changes in patients with unilateral ICAO with the ASL-MRI perfusion technique.METHODS Twenty hospitalized patients with ICAO and sex-and age-matched controls were included in the study.Regional CBF was measured by Dr.Brain's ASL software.The present study evaluated differences in global,middle cerebral artery(MCA)territory,anterior cerebral artery territory,and Alberta Stroke Program Early Computed Tomography Score(ASPECTS)regions(including the caudate nucleus,lentiform nucleus,insula ribbon,internal capsule,and M1-M6)and brain lobes(including frontal,parietal,temporal,and insular lobes)between ICAO patients and controls at PLD 1.5 s and PLD 2.5 s.RESULTS When comparing CBF between ICAO patients and controls,the global CBF in ICAO patients was lower at both PLD 1.5 s and PLD 2.5 s;the CBF on the occluded side was lower in 15 brain regions at PLD 1.5 s,and it was lower in 9 brain regions at PLD 2.5 s;the CBF in the contralateral hemisphere was lower in the caudate nucleus and internal capsule at PLD 1.5 s and in M6 at PLD 2.5 s.The global CBF in ICAO patients was lower at PLD 1.5 s than at PLD 2.5 s.The ipsilateral CBF at PLD 1.5 s was lower than that at PLD 2.5 s in 15 regions,whereas the contralateral CBF was lower at PLD 1.5 s than at PLD 2.5 s in 12 regions.The ipsilateral CBF was lower than the contralateral CBF in 15 regions at PLD 1.5 s,and in M6 at PLD 2.5 s.CONCLUSION Unilateral ICAO results in hypoperfusion in the global and MCA territories,especially in the ASPECTS area.Dual PLD settings prove more suitable for accurate CBF quantification in ICAO.

Three-dimensional-arterial spin labeling perfusion correlation with diabetes-associated cognitive dysfunction and vascular endothelial growth factor in type 2 diabetes mellitus rat

BACKGROUND Type 2 diabetes mellitus(T2DM) has been strongly associated with an increased risk of developing cognitive dysfunction and dementia.The mechanisms of diabetes-associated cognitive dysfunction(DACD) have not been fully elucidated to date.Some studies proved lower cerebral blood flow(CBF) in the hippocampus was associated with poor executive function and memory in T2DM.Increasing evidence showed that diabetes leads to abnormal vascular endothelial growth factor(VEGF) expression and CBF changes in humans and animal models.In this study,we hypothesized that DACD was correlated with CBF alteration as measured by three-dimensional(3D) arterial spin labeling(3D-ASL) and VEGF expression in the hippocampus.AIM To assess the correlation between CBF(measured by 3D-ASL and VEGF expression) and DACD in a rat model of T2DM.METHODS Forty Sprague-Dawley male rats were divided into control and T2DM groups.The T2DM group was established by feeding rats a high-fat diet and glucose to induce impaired glucose tolerance and then injecting them with streptozotocin to induce T2DM.Cognitive function was assessed using the Morris water maze experiment.The CBF changes were measured by 3D-ASL magnetic resonance imaging.VEGF expression was determined using immunofluorescence.RESULTS The escape latency time significantly reduced 15 wk after streptozotocin injection in the T2DM group.The total distance traveled was longer in the T2DM group;also,the platform was crossed fewer times.The percentage of distance in the target zone significantly decreased.CBF decreased in the bilateral hippocampus in the T2DM group.No difference was found between the right CBF value and the left CBF value in the T2DM group.The VEGF expression level in the hippocampus was lower in the T2DM group and correlated with the CBF value.The escape latency negatively correlated with the CBF value.The number of rats crossing the platform positively correlated with the CBF value.CONCLUSION Low CBF in the hippocampus and decreased VEGF expression might be crucial in DACD.CBF measured by 3D-ASL might serve as a noninvasive imaging biomarker for cognitive impairment associated with T2DM.

Pulsed arterial spin labeling effectively and dynamically observes changes in cerebral blood flow after mild traumatic brain injury

Cerebral blood flow is strongly associated with brain function, and is the main symptom and diagnostic basis for a variety of encephalopathies. However, changes in cerebral blood flow after mild traumatic brain injury remain poorly understood. This study sought to observe changes in cerebral blood flow in different regions after mild traumatic brain injury using pulsed arterial spin labeling. Our results demonstrate maximal cerebral blood flow in gray matter and minimal in the white matter of patients with mild traumatic brain injury. At the acute and subacute stages, cerebral blood flow was reduced in the occipital lobe, parietal lobe, central region, subcutaneous region, and frontal lobe. Cerebral blood flow was restored at the chronic stage. At the acute, subacute, and chronic stages, changes in cerebral blood flow were not apparent in the insula. Cerebral blood flow in the temporal lobe and limbic lobe diminished at the acute and subacute stages, but was restored at the chronic stage. These findings suggest that pulsed arterial spin labeling can precisely measure cerebral blood flow in various brain regions, and may play a reference role in evaluating a patient＇s condition and judging prognosis after traumatic brain injury.

Three-dimensional arterial spin labeling and diffusion kurtosis imaging in evaluating perfusion and infarct area size in acute cerebral ischemia

BACKGROUND Early thrombolytic therapy is crucial to treat acute cerebral infarction,especially since the onset of thrombolytic therapy takes 1-6 h.Therefore,early diagnosis and evaluation of cerebral infarction is important.AIM To investigate the diagnostic value of magnetic resonance multi-delay threedimensional arterial spin labeling(3DASL)and diffusion kurtosis imaging(DKI)in evaluating the perfusion and infarct area size in patients with acute cerebral ischemia.METHODS Eighty-four patients who experienced acute cerebral ischemia from March 2019 to February 2021 were included.All patients in the acute stage underwent magnetic resonance-based examination,and the data were processed by the system’s own software.The apparent diffusion coefficient(ADC),average diffusion coefficient(MD),axial diffusion(AD),radial diffusion(RD),average kurtosis(MK),radial kurtosis(fairly RK),axial kurtosis(AK),and perfusion parameters post-labeling delays(PLD)in the focal area and its corresponding area were compared.The correlation between the lesion area of cerebral infarction under MK and MD and T2-weighted imaging(T2WI)was analyzed.RESULTS The DKI parameters of focal and control areas in the study subjects were compared.The ADC,MD,AD,and RD values in the lesion area were significantly lower than those in the control area.The MK,RK,and AK values in the lesion area were significantly higher than those in the control area.The MK/MD value in the infarct lesions was used to determine the matching situation.MK/MD<5 mm was considered matching and MK/MD≥5 mm was considered mismatching.PLD1.5s and PLD2.5s perfusion parameters in the central,peripheral,and control areas of the infarct lesions in MK/MD-matched and-unmatched patients were not significantly different.PLD1.5s and PLD2.5s perfusion parameter values in the central area of the infarct lesions in MK/MD-matched and-unmatched patients were significantly lower than those in peripheral and control areas.The MK and MD maps showed a lesion area of 20.08±5.74 cm^(2) and 22.09±5.58 cm^(2),respectively.T2WI showed a lesion area of 19.76±5.02 cm^(2).There were no significant differences in the cerebral infarction lesion areas measured using the three methods.MK,MD,and T2WI showed a good correlation.CONCLUSION DKI parameters showed significant difference between the focal and control areas in patients with acute ischemic cerebral infarction.3DASL can effectively determine the changes in perfusion levels in the lesion area.There was a high correlation between the area of the infarct lesions diagnosed by DKI and T2WI.

Neural plasticity secondary to carpal tunnel syndrome: a pseudo-continuous arterial spin labeling study

Conventional neuroimaging techniques cannot truly reflect the change of regional cerebral blood flow in patients with carpal tunnel syndrome.Pseudo-continuous arterial spinning labeling(pCASL)as an efficient non-invasive neuroimaging technique can be applied to directly quantify the neuronal activities of individual brain regions that show the persistent symptoms owing to its better spatial resolution and increased signal-to-noise ratio.Therefore,this prospective observational study was conducted in 27 eligible female carpal tunnel syndrome,aged 57.7±6.51 years.Psychometric tests,nerve conduction studies and pCASL neuroimaging assessment were performed.The results showed that the relevant activated brain regions in the cortical,subcrotical,and cerebral regions were correlated with numbness,pain,functionality,median nerve status and motor amplitude of median nerve(K=21–2849,r=–0.77–0.76,P<0.05).There was a tendency of pain processing which shifted from the nociceptive circuitry to the emotional and cognitive one during the process of chronic pain caused by carpal tunnel syndrome.It suggests the necessity of addressing the ignored cognitive or emotional state when managing patients with carpal tunnel syndrome.Approval for this study was obtained from the Institutional Review Board of The University of Hong Kong/Hospital Authority Hong Kong West,China(HKU/HA HKW IRB,approval No.UW17-129)on April 11,2017.This study was registered in Clinical Trial Registry of The University of Hong Kong,China(registration number:HKUCTR-2220)on April 24,2017.

Arterial spin labeling perfusion MRI applications in drug‑resistant epilepsy and epileptic emergency

Epilepsy affects all age groups and is one of the most common and disabling neurological disorders worldwide.Drug-resistant epilepsy(DRE),status epilepticus(SE),and sudden unexpected death in epilepsy(SUDEP),which are associated with considerable healthcare costs and mortality,have always been difficult to address and become the focus of clinical research.The rapid identification of seizure onset and accurate localization of epileptic foci are crucial for the treatment and prognosis of people with DRE,SE,or near-SUDEP.However,most of the conventional neuroimaging techniques for assessing cerebral blood flow of people with epilepsy are restricted by time consumption,limited resolution,and ionizing radiation.Arterial spin labeling(ASL)is a newly powerful non-contrast magnetic resonance imaging technique that enables the quantitative evaluation of brain perfusion,characterized by its unique advantages of reproducibility and easy accessibility.Recent studies have demonstrated the potential advantages of ASL for the diagnosis and evaluation of epilepsy.Therefore,in this review,we discussed the complementary value of ASL in evaluating and characterizing the basic substrates underlying refractory epilepsy and epileptic emergencies.

Quantitative assessment of acute kidney injury by noninvasive arterial spin labeling perfusion MRI:a pilot study

The kidneys are essential for maintaining homeostasis,are responsible for the reabsorption of water,glucose and amino acids,and filter the blood by removing waste.Acute kidney injury(AKI) is a syndrome characterized by the rapid loss of renal excretory function and the accumulation of end metabolic products of urea and creatinine.AKI is associated with the later development of chronic kidney disease and end-stage kidney disease,and may eventually be fatal.Early diagnosis of AKI and assessments of the effects of treatment,however,are challenging.The pathophysiological mechanism of AKI is thought to be the imbalance between oxygen supply and demand in the kidneys.We have assessed the ability of arterial spin labeling(ASL) perfusion magnetic resonance imaging(MRI),without the administration of contrast media,to quantify renal blood flow(RBF) non-invasively.We found that RBF was significantly lower in AKI patients than in healthy volunteers.These results suggest that ASL perfusion MRI,a noninvasive measurement of RBF,may be useful in the early diagnosis of AKI.

Structural characteristics of the hydrophobic patch of azurin and its interaction with p53: a site-directed spin labeling study

Site-directed spin labeling (SDSL) is a powerful tool for monitoring protein structure, dynamics and conformational changes. In this study, the domain-specific properties of azurin and its interaction with p53 were studied using this technique. Mutations of six residues, that are located in the hydrophobic patch of azurin, were prepared and spin labeled. Spectra of the six azurin mutants in solution showed that spin labeled residues 45 and 63 are in a very restricted environment, residues 59 and 65 are in a spacious environment and have free movement, and residues 49 and 51 are located in a relatively closed pocket. Polarity experiments confirmed these results. The changes observed in the spectra of spin labeled azurin upon interaction with p53 indicate that the hydrophobic patch is involved in this interaction. Our results provide valuable insight into the topographic structure of the hydrophobic domain of azurin, as well as direct evidence of its interaction with p53 in solution via the hydrophobic patch. Cytotoxicity studies of azurin mutants showed that residues along the hydrophobic patch are important for its cytotoxicity.

Predicting Acute Mountain Sickness Using Regional Sea-Level Cerebral Blood Flow

Objective To investigate the role of sea-level cerebral blood flow(CBF)in predicting acute mountain sickness(AMS)using three-dimensional pseudo-continuous arterial spin labeling(3D-pCASL).Methods Forty-eight healthy volunteers reached an altitude of 3,650 m by air after undergoing a head magnetic resonance imaging(MRI)including 3D-pCASL at sea level.The CBF values of the bilateral anterior cerebral artery(ACA),middle cerebral artery(MCA),posterior cerebral artery(PCA),and posterior inferior cerebellar artery(PICA)territories and the laterality index(LI)of CBF were compared between the AMS and non-AMS groups.Statistical analyses were performed to determine the relationship between CBF and AMS,and the predictive performance was assessed using receiver operating characteristic(ROC)curves.Results The mean cortical CBF in women(81.65±2.69 mL/100 g/min)was higher than that in men(74.35±2.12 mL/100 g/min)(P<0.05).In men,the cortical CBF values in the bilateral ACA,PCA,PICA,and right MCA were higher in patients with AMS than in those without.Cortical CBF in the right PCA best predicted AMS(AUC=0.818).In women,the LI of CBF in the ACA was different between the AMS and non-AMS groups and predicted AMS with an AUC of 0.753.Conclusion Although the mechanism and prediction of AMS are quite complicated,higher cortical CBF at sea level,especially the CBF of the posterior circulatory system,may be used for prediction in male volunteers using non-invasive 3D-pCASL.

The Antioxidization Effects of TP-5, Thy(1[Lys23] and Their Spin Labeled Derivatives

TP-5 and Thy(1, synthesized by solid phase synthesis, have the effect to restrain the formation of superoxide anion in xanthine oxidase system in vitro. The formations of lipid peroxide in several organs (such as liver, brain and thymus) of the mice treated with TP-5, TP-5(R, active fragment of Thy(1 and active fragment of Thy(1(R of 10 (g(kg(d-1 for 10 d were decreased. That means these peptides possess the capability of antioxidezation.

Study on the synthesis of spin labeled poly(styrene-co-maleic acid)s and their segmental motion

Study of the segmental mobility of polymer chains is important when the polymer is used as drag reduction agents of crude oil.Electron spin resonance(ESR)spectroscopy can provide important information about segmental dynamics of polymer chains,which is related to their microenvironment.In this article,we employed an amphiphilic polymer to study the effect of hydrophilic/hydrophobic balance of the polymers on the segmental motion of polymer chains.Poly(styrene-co-maleic acid)(PSMA)was spin labeled with 4-amino TEMPO radicals by increasing the concentration of radical moiety on the polymer chains.The PSMA and spin labeled-PSMAs(SL-PSMAs)were characterized by nuclear magnetic resonance(NMR),Fourier transform infrared(FT-IR)spectroscopy,Cyclic voltammetry(CV)and ESR techniques.Inter-polymer complexes(IPCs)of SL-PSMA-2 were prepared by employing polyethylene glycols(PEGs)of varying molecular weights.The results showed that the increased hydrophobic interactions of nitroxide radicals on the SLPSMAs’chains reduced the rotational mobility of spin labels and the random coil-toglobular transition of polymer chains occurred at higher pH value for SL-PSMAs,which showed a slow motion component in the ESR spectra of SL-PSMAs.Further,by increasing the molecular weight of PEGs in IPCs the complexation was increased,which also reduced the rotational motion of spin labels due to interpolymer hydrogen bonding causing a slow motion component in the ESR spectra.©2021 The Authors.

Advances in arterial spin labeled cerebral perfusion imaging in cerebrovascular diseases

Cerebrovascular disease is a disease with high morbidity,disability and mortality rates,which seri-ously affects the daily life of patients and is a heavy burden on families and society.Arterial spin labeling(ASL)is a magnetic resonance imaging(MRI)technology that uses the magnetic labeling of hydrogen atoms in arterial blood as tracers to noninvasively evaluate brain blood flow.ASL does not require injection of an exogenous contrast agent,and has the advantages of no radiation,simplicity and low cost.In cerebrovascular diseases,ASL can evaluate the collateral cerebrovascular circulation and abnormal perfusion of brain tissue,which can provide a reliable basis for early diagnosis and clinical decision-making.This study reviewed ASL and its application in the diagnosis,treatment and prognosis of cerebrovascular diseases.

Hyperperfusion of Multiple Sclerosis Plaques Characterized by 3D FSE Arterial Spin Labelling

MULTIPLE sclerosis （MS） is a common inflammatory demyelinating disorder of central nervous system, and the disease burder could be well evaluated by conven-tional magnetic resonance imaging （MRI）,1 including T2-weighted, fluid-attenuatd inversion recovery, and postcontrast Tl-weighted sequences. 2 We investigated the perfusion state of MS plaques using brain perfusion imaging in a 12-year-old boy with MS.

Synthesis of Novel Spin Labeled Daunomycin Derivatives

Three spin labeled daunomycin derivatives 2-4 were synthesized and their biological activities were tested against mouse leukemia L1210 and human liver cancer BEL-7402 cells in vitro.

Abnormal volumetric brain morphometry and cerebral blood flow in adolescents with depression

BACKGROUND Prior research has demonstrated that the brains of adolescents with depression exhibit distinct structural alterations.However,preliminary studies have documented the pathophysiological changes in certain brain regions,such as the cerebellum,highlighting a need for further research to support the current understanding of this disease.AIM To study brain changes in depressed adolescents.METHODS This study enrolled 34 adolescents with depression and 34 age-,sex-,and education-level-matched healthy control(HC)individuals.Structural and functional alterations were identified when comparing the brains of these two participant groups through voxel-based morphometry and cerebral blood flow(CBF)analysis,respectively.Associations between identified brain alterations and the severity of depressive symptoms were explored through Pearson correlation analyses.RESULTS The cerebellum,superior frontal gyrus,cingulate gyrus,pallidum,middle frontal gyrus,angular gyrus,thalamus,precentral gyrus,inferior temporal gyrus,superior temporal gyrus,inferior frontal gyrus,and supplementary motor areas of adolescents with depression showed an increase in brain volume compared to HC individuals.These patients with depression further presented with a pronounced drop in CBF in the left pallidum(group=98,and peak t=-4.4324),together with increased CBF in the right percental gyrus(PerCG)(group=90,and peak t=4.5382).In addition,17-item Hamilton Depression Rating Scale scores were significantly correlated with the increased volume in the opercular portion of the left inferior frontal gyrus(r=-0.5231,P<0.01).CONCLUSION The right PerCG showed structural and CBF changes,indicating that research on this part of the brain could offer insight into the pathophysiological causes of impaired cognition.

Current and future applications of magnetic resonance imaging and spectroscopy of the brain in hepatic encepha-lopathy

Hepatic encephalopathy （HE） is a common neuropsychiatric abnormality, which complicates the course of patients with liver disease and results from hepatocellular failure and/or portosystemic shunting. The manifestations of HE are widely variable and involve a spectrum from mild subclinical disturbance to deep coma. Research interest has focused on the role of circulating gut-derived toxins, particularly ammonia, the development of brain swelling and changes in cerebral neurotransmitter systems that lead to global CNS depression and disordered function. Until recently the direct investigation of cerebral function has been difficult in man. However, new magnetic resonance imaging （MRI） techniques provide a non-invasive means of assessment of changes in brain volume （coregistered MRI） and impaired brain function （fMRI）, while proton magnetic resonance spectroscopy （^1H MRS） detects changes in brain biochemistry, including direct measurement of cerebral osmolytes, such as myoinositol, glutamate and glutamine which govern processes intrinsic to cellular homeostasis, including the accumulation of intracellular water. The concentrations of these intracellular osmolytes alter with hyperammonaemia. MRS-detected metabolite abnormalities correlate with the severity of neuropsychiatric impairment and since MR spectra return towards normal after treatment, the technique may be of use in objective patient monitoring and in assessing the effectiveness of various treatment regimens.

Effects of r-HuEPO on the biophysical characteristics of erythrocyte membrane in patients with anemia of chronic renal failure

Using electron spin resonance (ESR) spin labeling technique, we have studied the conformation of sulfhydryl groups(-SH) binding sites in membrane proteins and membrane fluidity of red blood cells (RBCs) from two groups of patients with anemia of chronic renal failure (ACRF). One of the groups is composed of patients who were untreated with recombinant human erythropoietin(r-HuEPO), and the other is composed of patients who were treated with r-HuEPO. The results indicated: 1) the conformation of SH group binding site in RBC membrane proteins from former group was different from those of health people. 2)the fluidity in the region near the surface of RBC membrane from former group was lower than those of healthy people. 3) However, the above biophysical properties of RBC membrane from later group were normal. We concluded that RBC membrane in patients with ACRF was abnormal, and the treatment of r-HuEPO may promote the production of normal RBCs, thus ameliorate the biophysical properties of RBCs from the patients with ACRF.

Comparative Study of DSC-PWI and 3D-ASL in Ischemic Stroke Patients

Summary： The purpose of this study was to quantitatively analyze the relationship between three di- mensional arterial spin labeling （3D-ASL） and dynamic susceptibility contrast-enhanced perfusion weighted imaging （DSC-PWI） in ischemic stroke patients. Thirty patients with ischemic stroke were in- cluded in this study. All subjects underwent routine magnetic resonance imaging scanning, diffusion weighted imaging （DWI）, magnetic resonance angiography （MRA）, 3D-ASL and DSC-PWI on a 3.0T MR scanner. Regions of interest （ROIs） were drawn on the cerebral blood flow （CBF） maps （derived from ASL） and multi-parametric DSC perfusion maps, and then, the absolute and relative values of ASL-CBF, DSC-derived CBF, and DSC-derived mean transit time （MTT） were calculated. The rela- tionships between ASL and DSC parameters were analyzed using Pearson＇s correlation analysis. Re- ceiver operative characteristic （ROC） curves were performed to define the thresholds of relative value of ASL-CBF （rASL） that could best predict DSC-CBF reduction and MTT prolongation. Relative ASL better correlated with CBF and MTT in the anterior circulation with the Pearson correlation coefficients （R） values being 0.611 （P〈0.001） and-0.610 （P〈0.001） respectively. ROC curves demonstrated that when rASL 〈0.585, the sensitivity, specificity and accuracy for predicting ROIs with rCBF〈0.9 were 92.3%, 63.6% and 76.6% respectively. When rASL 〈0.952, the sensitivity, specificity and accuracy for predicting ROIs rMTT〉I.0 were 75.7%, 89.2% and 87.8% respectively. ASL-CBF map has better linear correlations with DSC-derived parameters （DSC-CBF and MTT） in anterior circulation in ischemic stroke patients. Additionally, when rASL is lower than 0.585, it could predict DSC-CBF decrease with moderate accuracy. IfrASL values range from 0.585 to 0.952, we just speculate the prolonged MTT.

The neuroimaging of neurodegenerative and vascular disease in the secondary prevention of cognitive decline

Structural brain changes indicative of dementia occur up to 20 years before the onset of clinical symptoms. Efforts to modify the disease process after the onset of cognitive symptoms have been unsuccessful in recent years. Thus, future trials must begin during the preclinical phases of the disease before symptom onset. Age related cognitive decline is often the result of two coexisting brain pathologies: Alzheimer's disease(amyloid, tau, and neurodegeneration) and vascular disease. This review article highlights some of the common neuroimaging techniques used to visualize the accumulation of neurodegenerative and vascular pathologies during the preclinical stages of dementia such as structural magnetic resonance imaging, positron emission tomography, and white matter hyperintensities. We also describe some emerging neuroimaging techniques such as arterial spin labeling, diffusion tensor imaging, and quantitative susceptibility mapping. Recent literature suggests that structural imaging may be the most sensitive and cost-effective marker to detect cognitive decline, while molecular positron emission tomography is primarily useful for detecting disease specific pathology later in the disease process. Currently, the presence of vascular disease on magnetic resonance imaging provides a potential target for optimizing vascular risk reduction strategies, and the presence of vascular disease may be useful when combined with molecular and metabolic markers of neurodegeneration for identifying the risk of cognitive impairment.