An FMRI Study On "Juci" Waiguan(SJ5) In Ischemic Stroke Patients

Background:Ischemic stroke is the ischemic necrosis or softening of localized brain tissue caused by the brain blood circulation disorders, ischemia, hypoxia, is the most common type of stroke, accounting for60%to80%of the total stroke."Juci" is one of the "nine needling method" of ancient acupuncture, is first contained in "Nei Jing", is a needling method of according the illness needs to selecting point on left-side for treating disease in right-side, selecting point on right-side for treating disease in left-side, and selecting in the opposite side of the disease. In recent years, the "Juci" is took attention by many physicians in the clinical, especially in the rehabilitation therapy of stroke patients plays an important role.Waiguan(SJ5) is one of the eight-extrameridian Points, belongs to Sanjiao Meridian of Hand-Shaoyang and connects Yangwei meridian. It’s indications are fever, headache, buccal pain, deafness, tinnitus, conjunctival congestion, pain flank, shoulder and arm pain, adverse brachiumflexion and extension, finger pain and hand tremor etc. Waiguan(SJ5) is the common points for clinical treatment of the stroke sequela.The specilific of acpoints is relative to other points or sham points. The acupuncture has the relative specificity in morphology, biophysics, reflect disease and therapeutic effect. Recently, the study of the specilific of acpoints by functional magnetic resonance imaging (fMRI) is gradually being carried out. Scholars researched the specilific of acpoints on physiological status by functional magnetic resonance imaging. Xinsheng Lai observed the cerebral activating effects of needling/shallow needling at Waiguan(SJ5) of12cases of youth volunteer by fMRI. Guifeng Zhang observed the cerebral activating effects of needling/sham needling at acupuncture point of18cases of healthy people by PET. Tongjun Zeng observed the cerebral activating effects of needling at Waiguan(SJ5)/sham point of12cases of youth volunteer by functional magnetic resonance imaging(fMRI). They all found that the activating cerebral functional araes by needling acupuncture point are closely related with the therapeutic effects of the point, to a certain extent confirmed the "Meiridian specificity-the brain related to the doctrine" by Professor Xin-Sheng Lai.BOLD-fMRI imaging technology is first proposed by Ogawa in1990. This method is based on the different influence degree of the local oxygen consumption and brain serum by the neurons activities, to change the relative content of local oxygen-oxygen hemoglobin, leading to the changes of local magnetic field properties principle, according to different nature of the magnetic field of the two hemoglobin to determine changes of blood flow of the local brain tissue by imaging method, which indirectly reflect the neural electrical activity. Testing brain functional areas of the specific activities, its relatively high resolution on time and spatial, is the one of the best tools on study brain activity by far. In recent years, domestic and foreign researchers have used the fMRI technology to research the effects of the central nervous system by needling, and have achieved some results outputs.Based on the previous studies, the group puts forward the hypothesis "Treating the ischemic stroke by’Juci’at Waiguan (SJ5) can relatively active the brain specific functional areas", thinks human body as the biology, the reaction and adjust action of the body cause by acupuncture signal must go through the brain as central to recuperate and integration, and than act on target organs, thus present the acupuncture effect, this effect is relate to brain areas activated by peripheral acupuncture signal, activate the same brain areas produce the same acupuncture effects, relatively the cerebral central speaking, the afferent pathway and the process is up the secondary role. Plans to using functional magnetic resonance imaging (fMRI) brain imaging analysis technology as the research means,"Waiguan"(SJ5) as the research object, and observe the effect of four factor, like "Juci" at SJ5, sham needling "Juci" at SJ5,"Juci" at sham point and sham needling "Juci" at sham point under the human pathologic state (ischemic stroke patients with hemiplegia).Through the scientific and reasonable comprehensive design, striving to objective scientific directly explain the specificity of "Waiguan" from the visual level, to distinguish the meridian acupoints and sham point, to solve the meridian specificity and nature of acupoints play an improving role.Objective:Observe the effect of four factor, like "Juci" at SJ5, sham needling "Juci" at SJ5,"Juci" at sham point and sham needling "Juci" at sham point under the human pathologic state (ischemic stroke patients with hemiplegia) by functional magnetic resonance imaging (fMRI) brain imaging analysis technology as the research means,"Waiguan"(SJ5), and discuss the specificity of "Waiguan", to confirmed "Meiridian specificity-the brain related to the doctrine". This as the preliminary exploration of specilific of points by "Juci".Methods:Time:the experiment begins in October2010and ends in May2011, for a total of8months to complete.Location:Imaging Center in South hospital.Patients’data:12cases of ischemic stroke in right basales nuclei, all come from First Affiliated Hospital of Guangzhou University of Chinese Medicine.8male and4female, age39-67years old, course of disease1-24months, were randomized divided into2groups, each group of6, one received sham needling "Juci" and "Juci" at SJ5, another received sham needling "Juci" and "Juci" at a sham point. The age and disease course of two groups of patients are homogeneity of variance and are no statistical difference (P>0.001).Experiment process:All patients were required to have a rest for10minutes in a closed case of audio-visual before they were inspected.12cases of ischemic stroke patients are needled at right upper limbs. Acupuncture is operated by one acupuncturist.Needling at the SJ5acupoint:The SJ5acupoint of the right upper limb was sterilized, and the needle was inserted by tube insertion method (tube was purchased from Dongbang AcuPrime, Exeter, UK; silver needle,0.3×40mm, was purchased from Zhongyan Taihe, Beijing, China). After removing the tube, the needle was inserted to a depth of15±2mm using the mild reinforcing-reducing method. The needle was twirled for±180°for60times/min. The stimulation program was designed using a block method:twirling for30seconds, followed by rest for30seconds. This process was repeated for a total of six minutes. Needling at the sham point:The sham point (at the midpoint of the SJ5and the Small Intestine Meridian of hand Taiyang) of the right upper limb was sterilized, other method is liked needling at the SJ5. Sham needling at the SJ5acupoint:SJ5of the right upper limb was sterilized, and the sham needle was inserted. The needle tip,1mm out of the tube, touched the skin. The stimulation program was designed using the block method:touching for30seconds, followed by lifting the needle handle for30seconds. This process was repeated six times for a total of6minutes (Figure5). Sham needling at the sham point: The sham point (at the midpoint of the SJ5and the Small Intestine Meridian of hand Taiyang) of the right upper limb was sterilized, other method is liked sham needling at the SJ5.Cranial fMRI scanning was performed using a3.0T MRI system (GE Healthcare, Fairfield, Connecticut, USA) and a standard head coil. After vision and audition were blocked (ear plug, Aearo, Chickasha, OK, US; eyeshade, Hanjiang Xinhua Tourism Supplies Factory, Yangzhou, Jiangsu, China), the subjects rested in the bed for5-10minutes. MR anatomy images were acquired using T1-weighted three-dimensional gradient echo-pulse sequences prior to needling, and blood oxygenation level-dependent fMRI imaging was performed during needling. Tl transverse scanning was completed using FSE sequences for three minutes, with the following parameters:OAXT1FLAIR, repetition time of2300/echo time21, TI920, slice thickness6.0mm/gap1.0mm, for20slices, field of view FOV24×18/Z,320×256/2NEX, echo train length9, band width50; BOLD scanning utilized gradient echo and echo planar imaging. Functional images of identical slices in combination with anatomy images were collected:GR/EPI/90, TR3000ms/20/FE, flip angle90, FOV24×24/Z, slice thickness6.0mm/gap1.0mm,96×96/1.00NEX, phase per location:130,2600for6.5minutes. Data were analyzed using functional neuroimaging analysis software on a MRI workstation. The time course of pixel signal intensity represented the ideal reference waveform, and the time intensity curve of each pixel was compared with the reference waveform. A pixel with P<0.001and K>30correlated with the tasks and was regarded as significant activity to produce a functional image. Finally, the functional image was overlaid with a corresponding anatomy image to determine the anatomic location of brain activity.Data processing:Data post-processing was performed using statistical parametric mapping (SPM2, download from http://www.fil.ion.ac.uk). SPM2software was utilized with MATLAB platform, and the fMRI module was selected. realine (a procedure of SPM2Software) was run first to adjust for head micro-movements, and the values were standardized to the brain template in the MNI space, followed by Gaussian noise reduction and pixel analysis based on generalized linear model. Data were analyzed using two-sample one-sided t-test (SPM software), and the t-value corresponding to each pixel was calculated. A statistical parameter map composed of t-values was drawn (statistical significance:P<0.001, uncorrected, K>30). Brain areas with significant differences were fused to standard structure images, i.e., differences in reactions following needling in each brain area between stimulating and controlling conditions were displayed. Brain areas with changes were overlaid with a mean brain template that comprised the subject structure image. The red area represented activation/deactivation.Results:Through to the data processing and analysis, we initially found:1."Juci" at SJ5had activated at Broadmann(BA)18, BA19, BA20, BA21, BA22, BA37, BA39, BA46, cerebellum posterior lobe, tonsild and slope, and concentrate in right cerebral area, deactivated at BA3, BA4, BA9, BA10, BA11, BA18, BA19, BA21, BA36, BA38, BA46, BA47and cerebellum posterior lobe pyramis, and concentrate in left cerebral area.2. sham "Juci" at SJ5had non-activated cerebral area, but could deactivate BA7and BA19.3."Juci" sham point had activated BA19, BA22, BA31, BA35, BA39, BA40, left cerebellum posterior lobe slope and left limbic lobe parahippocampal gyrus, and concentrate in left cerebral area, deactivated BA1, BA2, BA3, BA4, BA5, BA6, BA7, BA10, BA40, right cerebral anterior lobe and posterior lobe slope, and concentrate in right cerebral area.4. Sham "Juci" at sham point could activate BA8and left cerebellum posterior lobe, and could deactivate BA10.5. Compared to sham "Juci" at sham point,"Juci" at SJ5had non-activated cerebral area, deactivated BA4, BA6, BA24, BA32, and concentrate in left cerebral area.6. Compared to "Juci" at sham point,"Juci" at SJ5had non-activated cerebral area, but could deactivate hypothalamus.Conclusion:Through the fMRI study on "Juci" at Waiguan(SJ5) of ischemic stroke patients,preliminary affirmed the effect of brain regions blood flow state by "Juci", and find that SJ5directionally affected brain areas related to motor, emotion, and cognition. By the comparings showed that there are difference between "Waiguan" and sham point.