Therapeutic imaging window of cerebral infarction revealed by multisequence magnetic resonance imaging An animal and clinical study

In this study, we established a Wistar rat model of right middle cerebral artery occlusion and observed pathological imaging changes （T2-weighted imaging [T2WI], T2FLAIR, and diffusion-weighted imaging [DWI]） following cerebral infarction. The pathological changes were divided into three phases： early cerebral infarction, middle cerebral infarction, and late cerebral infarction. In the early cerebral infarction phase （less than 2 hours post-infarction）, there was evidence of intracellular edema, which improved after reperfusion. This improvement was defined as the ischemic penumbra. In this phase, a high DWI signal and a low apparent diffusion coefficient were observed in the right basal ganglia region. By contrast, there were no abnormal T2WI and T2FLAIR signals. For the middle cerebral infarction phase （2-4 hours post-infarction）, a mixed edema was observed. After reperfusion, there was a mild improvement in cell edema, while the angioedema became more serious. A high DWI signal and a low apparent diffusion coefficient signal were observed, and some rats showed high T2WI and T2FLAIR signals. For the late cerebral infarction phase （4-6 hours post-infarction）, significant angioedema was visible in the infarction site. After reperfusion, there was a significant increase in angioedema, while there was evidence of hemorrhage and necrosis. A mixed signal was observed on DWI, while a high apparent diffusion coefficient signal, a high T2WI signal, and a high T2FLAIR signal were also observed. All 86 cerebral infarction patients were subjected to T2WI, T2FLAIR, and DWI. MRI results of clinic data similar to the early infarction phase of animal experiments were found in 51 patients, for which 10 patients （10/51） had an onset time greater than 6 hours. A total of 35 patients had MRI results similar to the middle and late infarction phase of animal experiments, of which eight patients （8/35） had an onset time less than 6 hours. These data suggest that defining the ＂therapeutic time window＂ as the time 6 hours after infarction may not be suitable for all patients. Integrated application of MRI sequences including T2WI, T2FLAIR, DW-MRI, and apparent diffusion coefficient mapping should be used to examine the ischemic penumbra, which may provide valuable information for identifying the ＂therapeutic time window＂.

Characters of MR diffusion tensor imaging in cerebral ischemic corticospinal tract injury

BACKGROUND： Diffusion tensor imaging （DTI） is one of the noninvasive methods to study the morphological structure of brain white matter fibrous bands in vivo, and it has been applied primarily in clinic. DTI is acknowledged as the more effective imaging method to diagnose ultra-acute and/or acute cerebral infarction.OB_3ECTIVE： To observe the anisotropic characters of cerebral white matter fibrous bands in patients with ischemic stroke by using DTI, and investigate the correlation between the damage of corticospinal tract and muscle strength in patients with ischemic stroke at acute period.DESIGN： A case-control observationSEFIING： Department of Medical Imaging, Fuzhou General Hospital of Nanjing Military Area Command of Chinese PLA.PARTICIPANTS： Nine inpatients with injury of motor function induced by acute ischemic stroke （patient group） at 6 hours to 2 weeks after the attack were selected from the Department of Neurology, Fuzhou General Hospital of Nanjing Military Area Command of Chinese PLA from September 2005 to March 2006, and they all accorded with the present diagnostic standard for cerebrovascular disease in China. There were 5 males and 4 females, aged 16-87 years. At the same time, nine healthy right-handed physical examinees matched by age and sex with the patients were taken as the control group, and they all had no nervous disease, mental diseases, cerebrovascular abnormalities and injury history, etc. All the subjects were informed with the detected items and agreed to participate in the study.METHODS： All the 9 patients with ischemic stroke at acute period and 9 healthy subjects were examined with MRI, T1 weighted imaging, T2 weighted imaging and DTI. And the data were processed offline with dTV.II software, the images of fractional anisotropy and directional encoded color （DEC） were obtained, and the three-dimensional fibrous band images of bilateral corticospinal tracts were reconstructed. In the control group, the values of fractional anisotropy of main white matter fibrous bands were measured in the region of interest （ROI） of the anterior limb, knee and posterior limb of internal capsule. In the patient group, the values of fractional anisotropy of white matter were measured in the infarcted sites and corresponding contralateral sites of the patients. The ROI was set in bilateral cerebral peduncles to reconstruct three-dimensionally the bilateral corticospinal tracts. The muscle strength of the affected hand was assessed with Brunnstorm standard in the stroke patients.MAIN OUTCOME MEASURES ： The characters of DTI and images of the value of fractional anisotropy, and the manifestations of three-dimensional corticospinal tracts were observed in the two groups.RESULTS： All the data from the 9 patients and 9 healthy volunteers were involved in the analysis of results. In the control group, the white matter and gray matter could be distinguished clearly in the image of fractional anisotropic values, the fibers of different directions were shown by different colors in DEC picture, which clearly demonstrated the normal anatomic structure and direction of white matter fibers. In the patient group, the infarctions occurred in the gray matter or white matter could be distinguished in the images of fractional anisotropic values, DEC picture could clearly show the direct influence of the infarcted site on the white matter fibers. The fractional anisotropic values in different white matter structure of the same side were significantly different in the control group （t=-3.12, P 〈 0.05）, and the reconstructed images fractional anisotropic values and DEC picture could show most of the main white matter fibrous bands. The fractional anisotropic values of the infarcted sites were significantly lower than the contralateral ones in the patient group （t=-5.570, P 〈 0.01）. ② The reconstructed bilateral corticospinal tracts showed that the anatomic forms of the contralateral corticospinal tract of the patients were almost identical to those of normal people, it started from precentral gyrus, downward to the nternal capsule, and extended to pontine and medulla oblongata, each fibrous band was continuous, and the form had good consistency. Because of the involvement of infarction of different severity, the ipsilateral corticospinal tract manifested as continuous interruption and the loss of consistent anatomic structural form. The involved severity of corticospinal tract had significant correlation with that of muscle strength of the ipsilateral hand （r=-1.30, P 〈 0.01）.CONCLUSION： ① DTI can display the direction and distribution of cerebral white matter fibrous bands.② DTI images of fractional anisotropic values and DEC can show the directions and anisotropic degree of white matter fibers in the infarcted sites of stroke patients. ③ The three-dimensional images of fibrous bands can show the conditions of pyramidal tracts more directly. ④ The damaged severity of corticospinal tracts is correlated with that of muscle strength.

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.

Needling at the Waiguan (SJ5) in healthy limbs deactivated functional brain areas in ischemic stroke patients A functional magnetic resonance imaging study

Deactivation is common in cerebral functional imaging. However, the physiological mechanisms responsible for this phenomenon remain poorly understood. The present study analyzed 12 ischemic stroke patients, who were randomly assigned to two groups： one group underwent sham needling and true needling at the Waiguan （SJ 5） in the healthy upper limb and the other group underwent sham and true needling at a sham point. Functional magnetic resonance imaging results showed no activation points in brain tissues following needling at SJ 5. However, compared with sham needling at SJ 5, true needling at SJ 5 deactivated Broadmann 4, 6, 24, and 32 areas. In addition, compared to needling at the sham point, true needling at SJ 5 deactivated bilateral hypothalamus. Results demonstrated that SJ 5 needling in the healthy upper limb resulted in specific directional brain action, as manifested by deactivation of cerebral areas related to motor （Broadmann 4 and 6）, emotion （hypothalamus）, and cognition （Broadmann 24, 32）.

EFFECT OF ACUPUNCTURE ON CEREBRAL IMAGES IN AUTISM CHILDREN

Objective: To observe the effect of acupuncture on images in autism children. Methods; A total of 27 cases of autism children were subjected into this study. By using a SPECT, the cerebral images were collected before and after acupuncture treatment and analyzed according to the recommended methods in 《Clinical Nuclear Medicine》 for assessing the state of blood flow, radioactivity quantity distribution and radioactivity count in bilateral hemispheres. 'JIN's three-needling' was employed. The acupuncture treatment was given once every other day, with 4 months being a therapeutic course and an interval of one month between two courses. Results: After acupuncture treatment, of the 22 cases, 20 had remarkable improvement and 2 had improvement in cerebral blood flow, with the total effective rate being 90.8%. Before the treatment there were significant differences between the left and right cerebrum (P<0. 001), and between the left and right frontal lobes in radioactive areas (P<0.01); however, after treatment, no differences were found between them (P>0.05). After treatment, the radioactivity count in the whole brain decreased significantly in comparison with that of pretreatment (P<0.01). It indicates the improvement of cerebral blood flow and cellular metabolism after the treatment. Conclusion: Acupuncture can significantly improve cerebral blood flow in autism children.

APPLICATION OF SINGLE PHOTON EMMISSION COMPUTED TOMOGRAPHY TO CLINICAL STUDY ON THE THERAPEUTIC EFFECT OF ACUPUNCTURE IN TREATMENT OF CHILD CEREBRAL PARALYSIS

Subjective To identify the practicability and clinical values of acupuncture in the treatment of child cerebral paralysis, try to provide visualized evidence and mechanisms for acupuncture treatment of this disease. Meth- ods: 13 cerebral palsy children including 9 cases of spasmodic type, 2 cases of ataxia type and 2 cases of mixed type, 9 males and 4 females were subjected into this study. Acupoints used were Hegu (LI 4), Quchi (LI 11), Zusanli (ST 36) and Sanyinjiao (SP 6) that were punctured and stimulated electrically with parameters of frequency 2/15 Hz, elec- tric current 5 mA, and duration of stimulation 30 min. Under monitoring of Siemens ECAM/ICON SPECT System, blood flow volumes of different brain regions were observed before, during and after elctroacupuncture (EA) stimulation of the above-mentioned acupoints. Results: SPECT revealed that in these 13 infantile patients, 18 regions of the brain in- cluding 12 in tbe frontal lobe and 6 in the temporal lobe presented insufficiency of blood perfusion and hypofunction; during EA, these cerebral regions and parietal lobe, visual cortex, thalamus, basal ganglion and cerebellum showed improvement in blood perfusion and function in different degrees. Results of the quantitative analysis on blood flow func- tion changing rate (BFCR) % showed a significant increase in 83.3% of the focal regions during EA. Conclusion: Acupuncture therapy can effectively improve cerebral blood perfusion of the focus and is of clinical value in treatment of infantile cerebral paralysis.

Aquaporin-4 gene silencing protects injured neurons after early cerebral infarction

Aquaporin-4 regulates water molecule channels and is important in tissue regulation and water transportation in the brain. Upregulation of aquaporin-4 expression is closely related to cellular edema after early cerebral infarction. Cellular edema and aquaporin-4 expression can be determined by measuring cerebral infarct area and apparent diffusion coefficient using diffusion-weighted imaging（DWI）. We examined the effects of silencing aquaporin-4 on cerebral infarction. Rat models of cerebral infarction were established by occlusion of the right middle cerebral artery and si RNA-aquaporin-4 was immediately injected via the right basal ganglia. In control animals, the area of high signal intensity and relative apparent diffusion coefficient value on T2-weighted imaging（T2WI） and DWI gradually increased within 0.5–6 hours after cerebral infarction. After aquaporin-4 gene silencing, the area of high signal intensity on T2 WI and DWI reduced, relative apparent diffusion coefficient value was increased, and cellular edema was obviously alleviated. At 6 hours after cerebral infarction, the apparent diffusion coefficient value was similar between treatment and model groups, but angioedema was still obvious in the treatment group. These results indicate that aquaporin-4 gene silencing can effectively relieve cellular edema after early cerebral infarction; and when conducted accurately and on time, the diffusion coefficient value and the area of high signal intensity on T2 WI and DWI can reflect therapeutic effects of aquaporin-4 gene silencing on cellular edema.

Acupoints combination correlates with activation of cerebral areas A functional MRI study

Acupoint combination is a method used for acupoint treatment of patients. Traditionally, acupoints are matched along the meridian distribution, which is a common rule in clinical practice, but the underlying mechanism remains unclear. Cerebral scans with functional magnetic resonance imaging （fMRI） have been used in the study of acupuncture and acupoint specifically. In this study, fMRI was used to detect the activation of the brain areas under different acupoints, matched along different meridians, to elucidate the acupoint combination via a modern medical approach. Forty healthy volunteers were randomly divided into the following groups： Waiguan point （SJ 5）, Waiguan （SJ 5） ＋ Zhigou （SJ 6） （2 acupoints come from the same meridian）, Waiguan （SJ 5） ＋ Neiguan （PC 6） （2 acupoints come from 2 meridians with the relationship of interior-exterior）, Waiguan （SJ 5） ＋ Yanglingquan （GB 34） （2 acupoints come from 2 meridians with the same name-Shaoyang Meridian）, and sham point groups （needling in different points on the right hand）. A real-time cerebral fMRI scan was simultaneously performed. The cerebral activation rate, and the number and strength of different regions of interest were compared among the groups. The fMRI cerebral imaging confirmed that there were some differences in the activation of cerebral areas by the needlings in SJ 5, and in combination with other acupoints. Needling at SJ 5 alone greatly activated the right cerebellum, while needling at both SJ 5 and different co-needling points activated different cerebral functional areas.

Acupuncture at Waiguan (TE5) influences activation/deactivation of functional brain areas in ischemic stroke patients and healthy people A functional MRI study

In the present study, 10 patients with ischemic stroke in the left hemisphere and six healthy controls were subjected to acupuncture at right Waiguan （TE5）. In ischemic stroke subjects, functional MRI showed enhanced activation in Broadmann areas 5, 6, 7, 18, 19, 24, 32, the hypothalamic inferior lobe, the mamiilary body, and the ventral posterolateral nucleus of the left hemisphere, and Broadmann areas 4, 6, 7, 18, 19 and 32 of the right hemisphere, but attenuated activation of Broadmann area 13, the hypothalamic inferior lobe, the posterior lobe of the tonsil of cerebellum, and the culmen of the anterior lobe of hypophysis, in the left hemisphere and Broadmann area 13 in the right hemisphere. In ischemic stroke subjects, a number of deactivated brain areas were enhanced, including Broadmann areas 6, 11,20, 22, 37, and 47, the culmen of the anterior lobe of hypophysis, alae lingulae cerebella, and the posterior lobe of the tonsil of cerebellum of the left hemisphere, and Broadmann areas 8, 37, 45 and 47, the culmen of the anterior lobe of hypophysis, pars tuberalis adenohypophyseos, inferior border of lentiform nucleus, lateral globus pallidus, inferior temporal gyrus, and the parahippocampal gyrus of the right hemisphere. These subjects also exhibited attenuation of a number of deactivated brain areas, including Broadmann area 7. These data suggest that acupuncture at Waiguan specifically alters brain function in regions associated with sensation, vision, and motion in ischemic stroke patients. By contrast, in normal individuals, acupuncture at Waiguan generally activates brain areas associated with insomnia and other functions.

Comparative Study of the Specificities of Needling Acupoints DU20, DU26 and HT7 in Intervening Vascular Dementia in Different Areas in the Brain on the Basis of Scale Assessment and Cerebral Functional Imaging

Objective： Using methods of clinical scale assessment and cerebral functional imaging to compare the relative specificity of needling acupoints Baihui （DU20）, Shuigou （DU26） and Shenmen （HTT） in intervening vascular dementia （VD） in different areas in the brain. Methods： Fifty patients with VD were randomized into 5 groups. Needling on conventionally used acupoints of hand and foot three Yang-meridians aiming at hemiplegia was applied to the patients in Group A, and needling on DU20 to Group B, on DU26 to Group C, on HT7 to Group D and on all the three to Group E was applied additionally. Assessments of Mini Mental State Examination （MMSE）, Activities of Daily Living （ADL） and Family Attitude Questionnaire （FAQ） were made. And the positron emission computerized tomography （PET） and single photon emission computerized tomography （SPECT） examinations were conducted in 5 selected patients from each group before and after treatment. Results： Needling on conventional acupoints plus DU20 could effect the inner temporal system, thalamencephalon system and prefrontal cortical system to improve memory and executive capacity of VD patients; conventional acupoints plus DU26 could effect more to the prefrontal cortical system to obviously elevate the executive capacity; that plus HT7 would reveal an effect similar to but rather weaker than plus DU20, and effect more to memory; and that plus all the three simultaneously could effect rather roundly multiple aspects of the nervous system related to intellectual activities, to elevate the recognition and enhance the executive capacity. Conclusion： Needling on various acupoints like DU20, DU26 and HT7 have effects on different brain areas.

A brief report on MRI investigation of experimental traumatic brain injury

Traumatic brain injury is a major cause of death and disability. This is a brief report based on a symposium presentation to the 2014 Chinese Neurotrauma Association Meeting in San Francisco, USA. It covers the work from our laboratory in applying multimodal MRI to study experimental traumatic brain injury in rats with comparisons made to behavioral tests and histology. MRI protocols include structural, perfusion, manganese-enhanced, diffusion-tensor MRI, and MRI of blood-brain barrier integrity and cerebrovascular reactivity.

Laser speckle imaging and wavelet analysis of cerebral blood flow associated with the opening of the blood–brain barrier by sound

The cerebral blood flow（CBF） alterations related to sound-induced opening of the blood–brain barrier（BBB） in adult mice are studied using laser speckle contrast imaging（LSCI） and wavelet analysis of vascular physiology.The results clearly show that the opening of the BBB is accompanied by the changes of venous but not microvessel circulation in the brain. The elevation of the BBB permeability is associated with the decrease of venous CBF and the increase of its complexity. These data suggest that the cerebral veins rather than microvessels are sensitive components of the CBF related to the opening BBB.

Positron emission tomography study of the specificity of Waiguan (SJ 5) acupoint

Functional brain imaging studies of the specificity of acupoint stimulation have revealed that needling at particular acupoints can induce activation of corresponding brain areas, examined in physiological and pathological states. The present study examined Waiguan （SJ 5） as the acupoint of interest. We tested five conditions： a true needling at true acupoint group, a sham needling at true acupoint group, a true needling at sham acupoint group, a sham needling at sham acupoint group, and a healthy control group. We examined changes in glucose metabolism in different functional cortical regions to determine the specific brain activation elicited by acupuncture at Waiguan. The results revealed that true and sham acupuncture at the same acupoint activated different brain regions. In addition, applying acupuncture at a genuine acupoint and a neighboring sham acupoint activated different brain regions. These findings suggest that acupuncture at Waiguan causes activation in some brain regions.

The clinical and imaging features of 118 patients with spontaneous cerebral arterial dissections presenting with ischemic stroke

Objective To investigate the clinical and radiologic features of patients with spontaneous cerebral arterial dissections(CADs)presenting with ischemic stroke and to explore the effect of gender and age on those features.Methods Patients admitted to our stroke center diagnosed as ischemic stroke secondary to CADs from August 2008to April 2015 were prospectively registered.

Effects of Electroacupuncture on Hippocampal and Cortical Apoptosis in A Mouse Model of Cerebral Ischemia-reperfusion Injury

Objective: To observe the effects of electroacupuncture on hippocampal and cortical apoptosis in a mouse model of cerebral ischemia-reperfusion injury. Methods: Mouse models established by repeated cerebral ischemia-reperfusion, followed by electroacupuncture at Shenshu, Geshu, and Baihui points. The control group mice were intragastrically administered Hydergine. On day 1 and 7 post-treatment, hippocampal and cortical apoptosis was detected by terminal-deoxynucleotidyl transferase mediated dUTP nick-end labeling (TUNEL), and apoptosis images in the hippocampal CA1 zone and cortical area were analyzed. Results: In the model group, apoptotic cells were detected one day after treatment and some cellular fibers were disarrayed. By day 7 post-treatment, there was an increase in the number of apoptotic cells in the hippocampal CA1 region. In addition, there were apoptotic cells in the cortical area, the cortical layers were thinner with localized neuronal loss and sieve-like lymphocyte infiltration, as well as glial cell proliferation and visible infarct lesions. However, in the Hydergine and electroacupuncture groups, there was a small number of apoptotic cells. At 7 days post-treatment in the model group, field number, numerical density on area, and surface density were increased. However, in the Hydergine and electroacupuncture groups these parameters were decreased (P<0.01), with a significant difference between the two treatment groups (P<0.01). Conclusion: Electroacupuncture treatment inhibited apoptosis and provided neuroprotection.

Specific Effects of Needling Different Acupoints of Patients with Vascular Dementia

Objective： To observe the effects of needling Baihui （GV 20）, Shuigou （GV 26） and Shenmen （HT 7） on cerebral glucose metabolism in patients with vascular dementia （VD） by cerebral functional imaging technique. Methods： Twenty-five patients with VD were divided into 5 groups （Group A, B, C, D and E） randomly. Patients in the Group A were treated by needling routine acupoints for hemiplegia （Acupoints of the three yang meridians of hand and foot）, and besides the routine acupoints, patients in the Group B were treated by needling Baihui（GV 20）, the Group C by Shuigou（GV 26）, the Group D by Shenmen（HT 7）, and the Group E by Baihui（GV 20）, Shuigou（GV 26）, and Shenmen（HT 7）. All the patients were examined by Positron Emission Tomography （PET） to detect the cerebral glucose metabolism in the bilateral frontal lobes（orbital gyri）, parietal lobes, temporal lobes（hippocampus and hippocampal gyrus）, occipital lobes, thalamus, lentiform nucleus, caudate nuclei, cingulate gyrus and cerebellum before treatments and after treatments. Results： After needling the routine acupoints for hemiplegia, glucose metabolism increased in lentiform nucleus and temporal lobe; needling Baihui（GV 20）, increased in frontal lobe, temporal lobe and lentiform nucleus; needling Shuigou（GV 26）, increased in frontal lobe, thalamus and lentiform nucleus; needling Shenmen（HT 7）, increased in parietal lobe and lentiform nucleus; and needling these three acupoints, increased in frontal lobe, temporal lobe, thalamus and lentiform nucleus. Conclusion： Needling Baihui（GV 20）, Shuigou（GV 26） and Shenmen（HT 7） affect glucose metabolism in different functional regions of the brain, and Baihui（GV 20）, Shuigou（GV26） and Shenmen（HT 7） relate to different functional regions of the brain.

Effect of acupuncture plus conventional treatment on brain activity in ischemic stroke patients: a regional homogeneity analysis

OBJECTIVE: To determine differences in cerebral activity evoked by acupuncture and conventional stroke treatment, and identify the treatment targets.METHODS: In total, 21 patients were randomly divided into two groups. Group A(11 patients) received both acupuncture and conventional treatment, while group B(10 patients) received conventional treatment only. Resting-state functional magnetic resonance imaging(f MRI) was performed on each participant before and after treatment. Regional homogeneity analysis was performed to investigate the potential mechanism of acupuncture treatment by comparing differences in cerebral activity between treatments.RESULTS: Group A showed higher Re Ho in the frontal lobe(BA6, BA46), supra-marginal gyrus(BA40),middle temporal gyrus(BA21), cerebellum, and insula. Group B showed higher Re Ho in the frontal lobe(BA6) and parietal lobe(BA3, BA7).CONCLUSION: Acupuncture and conventional treatment triggered relatively different clinical efficacy and brain responses. Acupuncture treatment more significantly improved the symptoms of stroke patients. More marked changes in sensory,emotional, and motor areas(including the frontal lobe, middle temporal gyrus, cerebellum, and insula) might reflect the specific acupuncture mechanism.