Value Of Neuro Gam Software Analysis In Single Photon Emission Computed Tomography Localization Diagnosis Of Epilepsy In Interictal Stage

Part one The added diagnostic value of detecting epilepsy in syncope patients by Neuro Gam software analysisObjective: Syncope is a transient loss of consciousness(TLOC)due to transient cerebral hypoperfusion characterized by rapid onset,short duration,and complete spontaneous recovery.Syncope may result in untoward consequences,such as physical injury,and has serious effects on the quality of life of the patient.Objective and accurate evaluation of regional cerebral blood flow(r CBF)is,therefore,critical for patients with syncope.The changes in r CBF and regional metabolism can be assessed by radionuclide imaging,especially single photon emission computed tomography(SPECT)and positron emission tomography(PET).Brain perfusion SPECT is a well-established and reliable method for evaluating brain function through the measurement of r CBF.In clinical practice,visual inspection is the most used method for analyzing r CBF SPECT images despite its limitations.Quantification of r CBF images has its natural place in clinical neuropsychiatric research,and the Neuro Gam software,which was used for 3-dimensional(3D)voxel-by-voxel analysis of brain perfusion SPECT,provided the possibility of analysis in strictly defined cortical functional areas,like the Brodmann(Br)functional areas.Quantitative analysis as a complement to visual assessment will probably make the assessment of functional abnormalities more reliable and the interpretations more objective.This study aims to explore the importance of Neuro Gam software in the analysis of syncope,and the relationship between epilepsy and the image findings of the brain SPECT.Methods: Twenty-three patients(10 men and 13 women;mean age±SD,50.2±14.7 years)were enrolled in this study.The cases included 7 cases of reflex,6 cases of cardiac,3 cases of orthostatic hypotension,and 7 cases of unexplained syncope.As a control group,17 healthy volunteers(8 men,9 women;mean age±SD,53.1±11.9 years)without any history of neurologic or cardiac disease were also enrolled after they underwent neurologic examination(the Mini-Mental State Examination)and other neuropsychological tests with normal results.SPECT studies were performed when the patients were free of syncopal episodes for at least 72 hours.Brain perfusion SPECT scanning was performed 30 min after intravenous injections of 555 MBq 99 m Tc-ethylcysteinate dimmer(99m Tc-ECD)(99m Tc,HTA Co.,Ltd;ECD,Beijing Shihong Pharma Centre,China)in a dimly lit,quiet room with the patients lying in a supine position with eyes closed.The SPECT images were visually inspected by two experienced nuclear medicine physicians who were blinded to the patients’ clinical data.Based on the transaxial plane,and with reference to the coronal and sagittal plane,positive lesions were confirmed by decreased or lack of radioactive uptake,which appeared in consecutive views(≥2 in the same plane)in more than 2 planes.The reconstructed data of the images were elaborated by Neuro Gam software(GE medical system,Segami Corp.,Columbia,MD,USA),which is one of the statistical analysis methods for automated diagnosis of brain perfusion SPECT images.After anatomical standardization and voxel normalization to cerebellum mean values,the Talairach technique normalized the brain volume to facilitate a voxel-by-voxel comparison of the ECD uptake in the brain cortex with a normal database of subjects also corrected volumetrically.The z-score maps are displayed either in the standard cuts or by overlay on a 3D anatomical topographic representation by means of a specific color scale.Results: Only 4 cases of the 23 patients with syncope showed abnormal results with brain perfusion imaging;the positive rate was 17.4%(4/23).Abnormal lesions of 3 cases,including one of each of the reflex,orthostatic hypotension,and unexplained syncope,were not localized clearly due to decreased or scattered distribution of the images of r CBF.The remaining case,which was a reflex syncope,with abnormal lesion showed a partial decrease in r CBF and was localized in the temporal lobe.Fourteen out of the 23 patients [60.9%(14/23)] with syncope showed abnormal brain perfusion imaging.The patients included 4 cases of reflex,2 cases of cardiac,1 cases of orthostatic hypotension,and 7 case of unexplained syncope.The abnormal lesions of 6 cases were not clear due to decreased or scattered distribution of images of r CBF,which showed in 2 case of reflex,2 cases of cardiac,1 cases of orthostatic hypotension syncope,and 1 case of unexplained syncope.Abnormal lesions of the 14 cases were localized in 8 patients [57.1%(8/14)].Qualitative and semi-quantitative analyses were performed on these 8 patients using the Neuro Gam software.The patients included 2 cases of reflex and 6 case of unexplained syncope.A total of 5 patients with unexplained syncope were evaluated clinically and 5 patients were diagnosed with epilepsy.The 5 patients showed partially decreased r CBF involving the frontal lobe,the temporal lobe,the insular lobes,and the cerebellum.By comparing with the reference data of healthy crowd database of the Neuro Gam software,the abnormal lesions were displayed further in the following Br areas: Br 12(both),Br 13(right),Br 37(both),Br 38(both),and Br 44(left).Z-scores in the r CBF-decreased Br 12,44(frontal),Br 38(temporal),Br 13(insular)and Br 37(occipitotemporal),were-2.9±0.8,-3.2±1.1,-3.6±0.9,-3.4±0.7,and-3.1±1.2 respectively.Conclusions: Abnormalities of brain perfusion in patients with syncope can be observed by Neuro Gam software analysis using 99Tcm-ECD brain SPECT.Neuro Gam software analysis demonstrates a higher positive rate than the traditional methods and showed different performances in various syncope as observed in our study,suggesting that different types of syncope,especially epilepsy,can be differentiated by this method.Neuro Gam software analysis is useful in presenting and locating the abnormal areas of r CBF and in assessing these alterations in syncope.The use of Neuro Gam software analysis may have practical implications for further studies.The Neuro Gam software analysis is useful for clinical medicine.Part two The comparison of Neuro Gam software analysis with several clinical routine methods for diagnosis of epilepsy.Objective: To explore the value of Neuro Gam software analysis in localization diagnosis of epilepsy by 99Tcm-ethylcysteinate dimmer(ECD)brain imaging.Methods: 52 cases of epilepsy proved by clinic were performed by 99Tcm-ECD brain imaging,and were analyzed by Neuro Gam software.The results were compared with EEG and MRI,and the positive rates and localization rates to epileptic foci by these different methods were analyzed.Results: Neuro Gam software results showed that forty-two of 52 epilepsy cases were abnormal detected by 99Tcm-ECD brain imaging,the positive rate was 80.8%(42/52).36 cases of 42 patients can be showed abnormal area clearly,the rate was 85.7%(36/42).Both were higher than that of brain perfusion SPECT visual assessment and the consistency of these two methods results was 64.5%(34/52).30 cases of 36 patients showed decreased regional cerebral blood flow(r CBF)in single lobe of brain,which showed in frontal lobe 18 cases,temporal lobe 20 cases,parietal lobe 2cases,respectively;4 cases of 36 patients showed decreased r CBF in multiple lobes,which showed in frontal lobe and temporal lobe;2 cases of 36 patients showed increased r CBF in temporal lobe and parietal lobe.Application Neuro Gam software analysis can be further show that the abnormal area is located in a different brain function partition and the Z value by semi-quantitative analysis.29 cases of 52 patients were abnormal detected by EEG,the positive rate was 55.8%(29/52),16 cases of patients can be showed abnormal area clearly,the rate was 55.2%(16/29).17 cases of 43 patients were abnormal detected by MRI,the positive rate was 39.5%(17/43),9 cases of patients can be showed abnormal area clearly,the rate was 52.9%(9/17).The consistency of Neuro Gam software analysis and EEG,MRI were 48.1%(25/52),34.9%(15/43),respectively.Conclusion: Neuro Gam software analysis is a simple,objective and effective method to locate epileptic foci,which the sensitivity of detecting abnormal areas is better than EEG and MRI,and it is a powerful tool of 99Tcm-ECD brain imaging.Part three Added value of Neuro Gam Software analysis in single photon emission computed tomography localization diagnosis of epilepsy in interictal stageObjective: The localization value of single photon emission computed tomography(SPECT)on epileptogenic zone has been widely recognized.However,owing to the rapid spread in the epileptic seizure,it is challenging to capture the epileptogenic zone,which requires precise timing of the injection of the imaging agent.Therefore,the routine SPECT examination in the ictal phase of seizures is greatly limited.The sensitivity and specificity of SPECT in locating the epileptogenic zone during interictal phase are lower than that during the ictal phase.The brain function analysis software can restore the deficiency and analyze the brain SPECT data based on the voxel level.This approach is advantageous with respect to objectivity and repeatability.The present study used Neuro Gam brain function analysis software,and performed localization analysis of the epileptogenic zone during the interictal phase of seizures based on the SPECT cerebral blood flow perfusion image.In addition,the method investigated added value of the localization ability of the conventional visual analysis.Methods: A retrospective analysis of patients diagnosed with epilepsy,by neurological physicians,was conducted at the Third Hospital of Hebei Medical University,Shijiazhuang,Hebei Province,China,from April 2006–2016.Finally,67 cases(36 males and 31 females aged 23–61 years,mean 42.2±10.7 years)were enrolled.99Tcm-ethyl cysteinate dimer(ECD)cerebral blood perfusion imaging was performed.The image reconstruction was performed on the transverse,coronal,and sagittal sections in parallel with the orbitomeatal(OM)line,respectively.The films were visually inspected and interpreted by two experienced nuclear medicine physicians.The localization of epileptogenic zone was divided into three grades including clear,uncertain,and unable to locate.The clear location for the focal lesions was visually recognizable,the uncertain location was scattered around or uneven cerebral perfusion changes were observed,and the unable to locate grade indicated clinically diagnosed epileptic patients with negative SPECT results in visual analysis.Neuro Gam software was used for the data analysis of image reconstruction.By affine registration of the data blocks,the raw data of 99Tcm-ECD cerebral blood flow perfusion imaging was mapped to Talairach standard space.After normalization of the image,standardization was performed with the cerebellum as a reference area in qualitative analysis.The local cerebral blood flow perfusion was represented by the continuous tone from orange to blue.In the semi-quantitative analysis,the normal database on the identical age and gender provided by the software was used as control and analyzed independently;the computer program calculated the Z values of each voxel using the following formula: Z value =(average value of the control group in the database-individual value)/ standard deviation of the control group in the database.The Z value in different regions was represented as x±s.The difference of more than 2-fold of the standard deviation was considered as the abnormal value,and the Z value was represented using special color gradation.In order to accurately locate the abnormal perfusion area,the functional areas of the cerebral cortex were analyzed using the Brodmann area.The localizations of epileptogenic zone were divided into three grades including clear,uncertain,and unable to locate.The clear location comprised of the hypoperfusion focal lesions with Z-value ≥2-fold of the standard deviation;the uncertain location represented the multiple scattered or uneven cerebral perfusion changes with the Z-value <1-2-fold of the standard deviation,and the unable to locate comprised of clinically diagnosed epileptic patients with negative results in the analysis by Neuro Gam software.The diagnosis and analysis of the final location of the epileptogenic zone were conducted by two experienced neurological physicians according to the clinical manifestations,EEG,imaging data,and follow-up results of the patients.The positive predictive rate(PPV),negative predictive rate(NPV),accuracy(Ac),sensitivity(Se),specificity(Sp),and uncertainty rate were calculated by visual analysis and Neuro Gam software analysis methods.The receiver operating characteristic curve(ROC)was plotted,and the area under curve(AUC)and 95% confidence intervals(CI)were computed for the evaluation of diagnostic efficiency.Results: Through the final clinical diagnostic comprehensive localization,among 67 epilepsy patients,the epileptogenic zone in 51 cases could be located distinctly,and those in 16 cases could not be located.Compared to the visual analysis,the Neuro Gam software analysis was more sensitive in the location of epileptogenic zone(χ2=4.876,P=0.027).The area under the ROC curve(AUC)and 95% confidence interval(CI)of the Neuro Gam software and visual analyses was 0.760 and 0.689,(0.613,0.908)and(0.547,0.832),respectively.However,the consistency of the two methods was poor(Kappa=0.367,P=0.001).Compared to visual analysis,the Neuro Gam software analysis exerted more advantages in the localization diagnosis of the epileptogenic zone(P<0.001).Conclusion: In the location diagnosis of brain perfusion,single photon emission computed tomography(SPECT)epileptogenic zone was used in interictal phase of seizures,and Neuro Gam software analysis exerted a distinct added value for visual analysis.Conclusions:1.Neuro Gam software analysis is useful in presenting and locating the abnormal areas of r CBF and in assessing these alterations in syncope.2.Neuro Gam software analysis is a simple,objective and effective method to locate epileptic foci3.Neuro Gam software analysis exerted a distinct added value for visual analysis.