Use Of Rotating Frame(T1?)and Apparent Diffusion Coefficient(ADC)Obtained From MRI With T1 Relaxation Time To Estimate Cerebral Ischemia Evolution&Preliminary Research Of Ischemic Penumbra In Subacute Stroke Combinating Use Of Amide Proton Transfer(APT)wi

Part One Use of Rotating Frame(T1p)and Apparent Diffusion Coefficient(ADC)Obtained from MRI with T1 Relaxation Time to Estimate Cerebral Ischemia EvolutionBackgroud and purposeThe key factor for appropriate treatment strategies for ischemia patients is its onset timing.We aimed to evaluate the diagnostic accuracy of T1 relaxation time in rotating frame(T1?)and apparent diffusion coefficient(ADC)from magnetic resonance imaging(MRI)to estimate ischemia stagesMaterials and methods:1.Research subjects This study was approved by the Medical Ethics Committee Hospital.University and was compliant with the Health Insurance Portability and Accountability Act.All patients provided informed consent.We reviewed our prospectively collected database for patients who were admitted to our center between March 2015 and February 2017.Patients were included if:Clinically,suspected for a cerebral stroke.Patients were excluded if:i)they had a history of neurological disorders,including multiple sclerosis,brain tumor,vasculitis,prematurity,seizure disorders,traumatic brain injury,infection;?)confirmation of hemorrhage by CT;?)any cranial procedure and any ischemic stroke therapy.Seventy-three patients(66 males,aged 29-78 years and 41 females,aged 22-94 years)with ischemia were imaged with multiparametric MRI during the post-ischemic period.Ischemic parenchyma included tissue with elevated signal areas on diffusion-weighted imaging(DWI)and correlative hypo-intense areas on ADC maps.2.MR images acquisitionThe MRI experiments were performed on a Philips Achieva TX 3.0-T scanner,using an eight-channel head coil.Conventional MR plain scanning included axial T1-weighted imaging,T2-weighted lamging,FLAIR sequence and sagettal T1-weighted imaging to eliminate brain disorders.T1?-weighted images were acquired using a whole brain fluid suppressed 3D turbo spin echo(TSE)technique,spin lock frequency = 500 Hz;spin lock time = 0,20,40,60,80,and 100 ms,giving a total acquisition time of approximately 12 min.Additionally,a diffusion-weighted scan was acquired using a spineecho(SE)echo-planar-imaging(EPI)sequence Data from three gradient directions with different diffusion weiglhting(b-values of 0 and 1000 s/mm2)were acquired,and the scan time was 50 seconds.An ADC map was calculated with a mono-exponential model.3.Post-processing of MRI data.3.1 TlP imaging post-processingThe main steps are listed as follows:(1)Format conversion.(2)Corretion,normalization.(3)Choice of interest area and Extraction of T1? values in each brain region of each subject.A T1? relaxation map was generated by fitting different spin lock data with a mono-exponential decaying function.3.2 diffusion-weighted imaging post-processingThe main steps are listed as follows:(1)The generation of the ADC mapping and Format conversion.(2)Choice of interest area and Extraction of ADC values in each brain region of each subject.An ADC map was calculated with a mono-exponential model.4.Statiscal analysisStatistical analysis was performed using SPSS version 20.0 or MATLAB 2015a workstation.The statistically significant differences was set at Inspection level?=0.05,P<0.05.Statistical significance was estimated using One-Way-ANOVA and repeated measures for MR pararmetric results(ATlp,AADC,Tlpipsi and ADCipsi)between each stage.To characterize and compare all values of different stages during ischemia,the sensitivity of different MR paranmetric results to the duration of ischemia was quantified by analyzing respective correlations,.and linear regression was used to calculate the linear fits.To assess the differences in T1? and ADC,correlation coefficients(R2)were calculated.The 95%confidence interval(Cl)for each mean was calculated as follows:mean± tval x SEM,where tval is the Student t-value for the 95%interval and SEM is the standard error of mean.All values are shown as mean ±SEM.ResultsThe study prospectively included 66 males(aged 29-78 years,56.8± 12.2 years)and 41 females(aged 22-94 years,59.8± 14.4 years).The stage of ischemia was clinically defined according to timing of ischemia onset:there were 15 hyperacute cases,16 acute-stage cases,41 early subacute cases,20 late subacute cases,and 15 chronic cases.The sensitivity of variables to ischemia time was quantified by analyzing the respective correlations of these values with onset time.?T1?(ipsilateral-contralateral differences in T1p)(R2=0.955,F=357.087)and T1?ipsi(ipsilateral ischemia T1?values)(R2=0.941,F=339.155)were elevated in all ischemic lesions;these values increased linearly as a function of time,unlike AADC(ipsilateral-contralateral differences in ADC)(R2=0.441)and ADCipsi(ipsilateral ischemia ADC values)(R2-0.471).ATIp and Tlpipsi were significantly different between all stages(P<0.01),except the acute and hyperacute stages((p=0.103 for ?T1?,p=0.010 for Tlpipsi),but AADC and ADCipsi only between the late subacute and early subacute stages and the late subacute and chronic stages(P<0.01).ConclusionsThese data suggest that Tip can provide estimates for the ischemic time in patients.Tip has the potential to outperform diffusion for single-time-point examination because the T1p change during strokes is positive and linear.If patients with suspected stroke are scanned by MRI within the appropriate time frame,Tip may provide tools for evaluating stroke onset,potentially aiding in treatment strategies.Part Two Preliminary Research of ischemic penumbra in subacute stroke combinating use of amide proton transfer(APT)with arterial spin-labeling(ASL)Objective:Currently,many clinicians require imaging methods to be able to comfirm the existence of ischemic penumbra in the later ischemic stroke(onset time>24h,subacute stroke)or the stroke patients with unknown time of symptom onset,as a result of heterogeneity of ischemia tissue injury,the regions of ischemic penumbra in this part of patients that may be outside the approved time window for the rt-PA intravenous thrombolysis treatment may still recover function.PWI(perfusion-weighted imaging)and DWI(diffusion-weighted imaging)can identify regions of hypoperfusion and ischemia core,respectively.However it often remains unclear whether a PWI-DWI mismatch corresponds to benign oligemia or a true ischemic penumbra(IP).The purpose of the preliminary researcha is to investigate the feasibility of APT?weighted MRI in the clinical identiflication and definition of IP in subacute stroke.Patients and Methods:80 subjects were enrolled from Nanfang Hospital,including 40 patients of subacute(stroke onset time:ld-14d)ischemic stroke(stroke group,28 male,12 femal,aged ranging 37-87y,average age 58.3±13.7y,stroke onset time 5.9±3.2d),and 40age/gender-matchedheanlthyvolunteers(healthyvolunteergroup,25 male,15 femal,aged ranging 40-85y,average age 59.8±11.4y).All participants were performed head MRI on a 3T Philips Achieva 3TX system.The imaging protocol included the following sequences:T2WI(T2-weighted imaging),T1WI(T1-weighted imaging),FLAIR(fluid-attenuated-inversion-recovery),ASL(arterial spin labeling),APTWI(amide proton transfe-weighted imaging).The final infarct size was assessed by follow-up FLAIR on 25 subacute stroke patients after 10-14d.DWI,ASL-CBF,APT mapping,follow-up FLAIR were imported into the post-processing improved brain perfusion protocol to compare the largest area ratio between the lesion regions.The APTW values of the lesion regions and the contralateral normal appearance white matter regions were measured on the APT mappings.In the healthy volunteers,the slice of basal ganglia was selected to acquire the APT mappings and the APTW values of the bilateral temporal lobe were measured.The differences of APTW values between the contralateral normal regions of the subacute stroke group and the temporal lobe white matter of healthy volunteers were compared by Independent-sample t test.The differences of APTW values between all lesion regions and contralateral normal regions in the subacute stroke group were compared with the paired t test.ANOVA and repeated measures ANOVA were used for APTW values of multiple region of interest comparisons.Result:In the subacute stroke,areas of APTWI deficits,were always larger than or equal to DWI deficits and smaller than or equal to ASL-CBF deficits.Group analysis showed that ATPWI deficits during this phase coincided with the resulting infarct area at follow-up endpoint.Final infarcts were smaller than CBF deficits and larger than or equal to subacute DWI deficits.Conclusion:1.The ischemic penumbra still exists around the infarct core in the subacute stroke.2.These data suggest that the outer boundary of the hypoperfused area showing a decrease in APTW without DWI abnormality may correspond to the outer boundary of the ischemic penumbra,while the hypoperfused region at normal APTW may correspond to benign oligemia.3.These first results show that APT can provide information complementary on cell metabolism to ASL-CBF and DWI in the delineation of ischemic tissue.4.Clinically,no matter what stage of stroke(hyperacute,aeute,subacute),as long as the presence of ischemic penumbra in ischemic tissue is confirmed by image methods,that tissue is still active in spite of ischemia and can still recover its function after treatment,aggressive therapy decisions should be taken.