Study On Infarct Area After Stroke With Amide Proton Transfer-weighted Imaging And Muscle Of Affected Lower Limb With Phosphorus Magnetic Resonance Spectroscopy

(Part 1)Amide proton transfer-weighted imaging of the normal brain at a basal ganglia level and during acute cerebral infarction:a study on reproducibilityObjective:Amide proton transfer(APT)imaging is a novel MR imaging technique introduced in recent years that has attracted significant attention for its clinical application.Understanding its reproducibility is a prerequisite for a better use of this technique in clinical practice.However,to date there have been few reports on the reproducibility of APT imaging.Therefore,the purpose of this study was as follows:(1)to evaluate intra-and inter-observer agreement of APTw values following APT(Amide proton transfer-weighted)imaging of healthy subjects;(2)to explore the difference in APTw values at different positions of the basal ganglia;(3)To evaluate the inter-observer agreement of APTw values in patients with cerebral infarction.Patients and Methods:APT imaging was performed using Philips 3.0 T Achieva magnetic resonance imaging system and head 8-channel coil.Eleven healthy volunteers were scanned twice at two different time points(from 7 days to 30 days).Furthermore,nine patients with acute cerebral infarction(less than 24 hours)were analyzed.Image analysis was performed using the Interactive Data Language(IDL,ITT Visual Information Solutions,Boulder,CO,USA).An experienced radiologist carefully delineated the regions of interest(ROI)in the bilateral frontal cerebral white matter,lenticular nucleus,caudate nucleus,and thalamus.In addition,a second radiologist,following the same standards of measurement,evaluated the images independently at the time of the first examination.Consistency and reproducibility were evaluated using the Intra-and Interclass Correlation Coefficients(ICCs)and Bland-Altman method.The intra-and inter-observer measurements were analyzed using paired-sample t test.Comparison of the difference of APT,values among the four ROI at the basal ganglia was performed using one-way ANOVA.In addition,ICC and Bland-Altman methods were used for evaluating the reproducibility of lesions in patients with cerebral infarction.Results:The intra-observer ICC for the frontal cerebral white matter,lenticular nucleus,caudate nucleus,and thalamus correlation coefficient were 0.977(0.913-0.994),0.954(0.833-0.988),0.935(0.760-0.983),and 0.917(0.805-0.986),respectively.While the inter-observer ICC for the bilateral frontal cerebral white matter,lenticular nucleus,caudate nucleus,and thalamus correlation coefficient were 0.951(0.816-0.987),0.915(0.685-0.977),0.879(0.551-0.968),and 0.853(0.455-0961),respectively.The Bland-Altman method demonstrated good reproducibility.The intra-observer measurement had only two measures that exceeded the 95%confidence interval,while the inter-observer measurements had only three measures that exceeded the 95%confidence interval.In the intra-and inter-observer measurements of 11 healthy volunteers,the APTW values did not significantly differ.The average APTw values were(-0.174 ± 0.215)%,(0.939 ± 0.120)%,(0.980 ± 0.144)%,(1.051 ± 0.155)%in the frontal cerebral white matter,lenticular nucleus,caudate nucleus,and thalamus,respectively.The average APTW values of the frontal lobes were lower than that of the caudate nucleus,the bean-shaped nucleus,and the thalamus(P<0.001).However,there was no significant difference noted among the caudate nucleus,the bean nucleus,and the thalamus(all P>0.05).The inter-observer ICC of the lesions demonstrated good consistency,and correlation coefficients were 0.966(0.848-0.992).Good reproducibility was observed with the Bland-Altman method,with all measurements falling in the 95%confidence interval.Conclusions:The results of this preliminary study indicate that the measurement of APTw values in both healthy volunteers and patients with cerebral infarction are reproducible.The APTW values differed at different positions of the basal ganglia.(Part 2)The application of amide proton transfer magnetic resonance imaging during ischemic cerebral infarction and related influencing factorsObjective:Amide proton transfer(APT)imaging performs a noninvasive evaluation of pH changes in tissues.In addition,it accurately documents the pH change in cerebral infarction.The purpose of this study was to investigate the following:(1)the positive rate of the lesion identified by APT imaging and related influencing factors;(2)the difference in APTw values between lesions and normal appearing white matter(NAMWM)at each stage as well as the difference of APTw values among different stages;(3)the relationship between APTw values and lesion size;and(4)the relationship between APTw values and time of onset.Patients and Methods:Eighteen patients(14 males and 4 females)with cerebral infarction treated in our hospital between 2014 and 2017 were enrolled in this study.Tracking MR examination was performed at least twice on all patients.According to the time of onset,cases were divided into the following three stages:nine cases with acute stage(onset<24 h);16 cases with subacute stage(24 h to 7 d);14 cases with chronic stage(>7 d).Referring to the largest area of the lesion at DWI(diffusion weighted imaging),asymmetric magnetization transfer ratio at 3.5 PPM(MTRasym)was analyzed using APT imaging and obtained as APTw values.Five ROI were selected.APTw values were classified as follows:the largest APTw value was defined as APTw(max);the minimum APTw value was defined as APTw(min);the average APTw value was defined as APTw(ave);the difference between maximum and minimum value was defined as APTw(max-min);and the APTw value of NAWM was defined as APTw(con).The comparison between the positive rate of lesions in DWI and APT imaging was performed using Fisher's exact probability method.The differences between the values of APTw(max),APTw(min),APTw(ave),APTw(max-min),and APTw(con)were compared using the independent sample t test.The difference in APTw values between acute,subacute,and chronic stages was compared using single factor variance analysis.The relationship between APTW values,lesion size,and time of onset was analyzed using Pearson's correlation.Results:When compared with conventional images,a fraction of the lesions could not be detected using APT imaging,including two(2/9)cases in acute phase,three(3/16)cases in subacute stage,and three cases(3/14)in chronic phase.The APTw(max),APTw(min),and APTw(ave)values of the lesions were statistically significant compared with the APTw of the NAWM.Statistical differences were noted in APTw(max),APTw(min),and APTw(ave)values among the acute,subacute,and chronic phases.However,APTw(max-min)and APTw(con)values showed no statistical difference.In acute stage,there was correlation between APTw(max),APTw(min),and APTw(a,ve)values and lesion area(r = 0.792,0.809,0.849,p = 0.011,0.008,0.004).On the contrary,APTw(max-min)and APTw(con)values showed the absence of correlation with lesion area.In subacute stage,there was correlation between APTw(min)and APTw(max-min)values and lesion area(r = 0.733,0.761,p = 0.025,0.017).In contrast,APT,(max),APTw(a,ve),and APTw(con)values showed no correlation with the lesion area.In addition,in the chronic stage no correlation was observed between APT,(max),APTw(min),APTw(ave),APTw(max-min),and APTw(con)values and lesion area.Furthermore,APTw(max),APTw(min),APTw(ave),APTw(max-min)values were not correlated with the time of onset in subacute and chronic stages.Conclusion:Even though APT imaging detects cerebral infarction lesions on the basis of pH changes,a small fraction of cerebral infarction lesions could not be detected.In acute and subacute stages,the APTw value decreased compared with NAWM,which indicates the existence of tissue acidosis.With the duration of illness,the acidic environment could be alleviated.APT magnetic resonance imaging can be used in the stage of cerebral infarction.In addition,the APTw value of the lesion correlated with the lesion area in both acute and subacute stages.(Part 3)31P-MRS study of mitochondrial function of lower limbs in patients with cerebral infarction and hemiplegiaObjective:New evidence reveals significant structural and metabolic changes in skeletal muscle after stroke,and rehabilitation could improve muscle function.However,it is unknown if phosphorus magnetic resonance spectroscopy(31P-MRS)could evaluate the metabolic changes in patients with stroke.Our Objective was to investigate(1)whether hemiparetic-side muscle energy metabolism,as measured by 31P-MRS,differs from that of the unaffected side;(2)whether hemiparetic-side muscle metabolism changes,following physical rehabilitation;(3)whether metabolism measured by 31P-MRS could reflect changes of Modified Modified Asworth Scale(MMAS)and Fugl-Meyer assessment-lower extremity(FMA-LE)after rehabilitation.Patients and Methods:We enrolled thirteen patients with stroke symptoms and hemiplegia,who completed 5-6 weeks of physical rehabilitation.The unaffected leg muscle served as a within-subject internal control.31P-MRS measures included phosphocreatine(PCr),inorganic phosphate(Pi),PCr/Pi,and pH.Lower-limb motor status on affected side was evaluated by Fugl-Meyer assessment-lower extremity(FMA-LE)and Modified Modified Asworth Scale(MMAS)before and after rehabilitation.We statistically compared these measures in affected and unaffected lower leg muscle before rehabilitation,and on the affected side leg muscle before and after rehabilitation.Spearman correlational analyses was applied to determine correlations between changes of energy metabolism and changes in FMA-LE score and MMAS score after rehabilitation.Results:PCr and PCr/Pi were significantly lower in the affected muscle,compared to the unaffected muscle,however,there were no significant differences in Pi,or pH.After rehabilitation,PCr,Pi,PCr/Pi,and pH did not significantly change.However,FMA-LE and MMAS score improved significantly after rehabilitation.Changes in energy metabolism measured by 31P-MRS had no correlation with FMA-LE change after rehabilitation.However,change of PCr and PCr/Pi had correlation with change of MMAS score after rehabilitation.Conclusion:The function of mitochondrial oxidative phosphorylation of skeletal muscle in patients with cerebral infarction is impaired,and 31P-MRS can evaluate changes in muscle energy metabolism in patients with cerebral infarction.Rehabilitation therapy can improve the muscle function,however,the change of metabolism measured by 31P-MRS is not obvious.Metabolism measured by 31P-MRS could reflect changes of MMAS after rehabilitation.