局部亚低温对大鼠脑缺血组织钙调神经磷酸酶活性的影响

为探讨局部亚低温的脑保护作用，制备大鼠大脑中动脉脑缺血模型。分为常温组、FK－506组、亚低温组和正常对照组，测定缺血后不同时间脑组织中钙调神经磷酸酶（CaN）的活性。结果发现，常温组、FK－506组于缺血后6h CaN活性开始下降，而亚低温组CaN活性无明显变化，差异有显著意义。说明局部亚低温治疗可明显抑制缺血脑组织中CaN活性的变化，具有明确的脑保护作用。     

低温液体灌注产生亚低温的进展

低温对脑损伤的保护作用已被众多动物实验所证实,在临床方面,尤其是发现轻度和中度低温的保护作用之后,应用逐渐增多.近年来,亚低温被用于治疗新生儿缺氧性脑病、心肺复苏后脑保护、脑外伤及脑卒中等领域.目前临床及实验中所应用的低温方式主要为全身亚低温,如降温毯、冰袋等,这些方式降温效率低,不易迅速实现亚低温,而且全身低温可伴有多种并发症,如心律紊乱、凝血功能障碍等.低温液体或自体血液灌注是目前最有效的降温方式,而且局部动脉内灌注低温液体更可以快速实现局部亚低温.介入技术的进步使得快速局部动脉内低温液体灌注成为可能.我们详细回顾相关动物实验及临床应用文献,介绍低温液体灌注产生亚低温的研究进展.     

MRI of ischemic stroke in canines: applications for monitoring intraarterial thrombolysis

PURPOSE: To describe a canine embolic stroke model that is appropriate for endovascular procedure evaluations and develop local cerebral blood flow (CBF) maps to monitor the progression of stroke and thrombolysis. In the future, MR may displace X-ray imaging in some endovascular procedures, such as intraarterial (IA) thrombolysis for stroke therapy, due to increased monitoring capabilities. For MR to attain its full potential in endovascular therapy, the development of appropriate disease models and monitoring techniques is essential. MATERIALS AND METHODS: The canine stroke model uses an injection of autologous clot to produce ischemic and infarcted tissue and produces a range of stroke severities within the anterior cerebral circulation. Local CBF maps were formed by using the catheter that would be in place to deliver the thrombolytic agent for treatment to deliver the gadolinium-based contrast agent for perfusion imaging. RESULTS: After the injection of clot, changes on imaging were consistent with the progression of ischemic stroke. Local CBF maps showed perfusion changes with stroke progression and treatment. CONCLUSION: We successfully demonstrate the progression of ischemic stroke in the canine to mimic the progression of human stroke. CBF maps to show local perfusion characteristics show great potential in the evaluation of stroke therapy.     

Detecting the subregion proceeding to infarction in hypoperfused cerebral tissue: a study with diffusion and perfusion weighted MRI

Diffusion and perfusion weighted MRI have been widely used in ischaemic stroke. We studied 17 patients in whom ischaemic areas showed an ischaemic core, an area of infarct growth and hypoperfused but ultimately surviving tissue. Apparent diffusion coefficients (ADC) were measured on days 1, 2, and 8 in the three subregions and in contralateral control areas. Cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT) were measured in these regions on day 1 perfusion maps. On day 1, the ischaemic core had very low ADC and CBF and increased MTT. The ADC in the ischaemic core gradually increased during the week. The area of infarct growth on day 1 had slightly but significantly decreased ADC (96% of control, P=0.028), moderately decreased CBF and increased MTT. On day 1 the hypoperfused but surviving tissue had slightly but significantly increased ADC (103% of control, P=0.001), mildly decreased CBF and increased CBV and MTT. The ADC of the area of infarct growth decreased to the same level as in the ischaemic core on days 2 and 8. That of surviving tissue was still above normal on day 2 (103% of control), but had returned to the normal level by day 8. Measurement of ADC combined with perfusion MRI may help distinguish different subregions in acutely hypoperfused brain.     

Mismatch between iodine-123 IMP and technetium-99m HM-PAO brain perfusion imaging in a patient with meningioma

The discrepancy between three methods for cerebral perfusion imagings in the case of a man with meningioma is presented. Imaging with N-isopropyl-P-[I-123] iodoamphetamine (IMP) showed no activity in the tumor. Imaging with Tc-99m hexamethylpropyleneamine oxime (HM-PAO) and the local cerebral blood flow (LCBF) image with Xe-133 inhalation showed high tumor activity. IMP is a more accurate method for imaging the brain tissue blood flow.     

Brain perfusion CT in acute stroke: current status

Dynamic perfusion CT has become a widely accepted imaging modality for the diagnostic workup of acute stroke patients. Although compared with standard spiral CT the use of multislice CT has broadened the range from which perfusion data may be derived in a single scan run. The advent of multidetector row technology has not really overcome the limited 3D capability of this technique. Multidetector CT angiography (CTA) of the cerebral arteries may in part compensate for this by providing additional information about the cerebrovascular status. This article describes the basics of cerebral contrast bolus scanning with a special focus on optimization of contrast/noise in order to ensure high quality perfusion maps. Dedicated scan protocols including low tube voltage (80 kV) as well as the use of highly concentrated contrast media are amongst the requirements to achieve optimum contrast signal from the short bolus passage through the brain. Advanced pre and postprocessing algorithms may help reduce the noise level, which may become critical in unconscious stroke victims. Two theoretical concepts have been described for the calculation of tissue perfusion from contrast bolus studies, both of which can be equally employed for brain perfusion imaging. For each perfusion model there are some profound limitations regarding the validity of perfusion values derived from ischemic brain areas. This makes the use of absolute quantitative cerebral blood flow (CBF) values for the discrimination of the infarct core from periinfarct ischemia questionable. Multiparameter imaging using maps of CBF, cerebral blood volume (CBV), and a time parameter of the local bolus transit enables analyzing of the cerebral perfusion status in detail. Perfusion CT exceeds plain CT in depicting cerebral hypoperfusion at its earliest stage yielding a sensitivity of about 90% for the detection of embolic and hemodynamic lesions within cerebral hemispheres. Qualitative assessment of brain perfusion can be further enhanced by adding relative perfusion indices from regions of interest. Multislice CTA using a collimation of 4 x 1 mm and high pitch factors allows for isotropic scanning of the brain supplying arteries from the aortic arch to the vertex in a single run. Various image processing modalities such as multiplanar reformations, curved planar reconstructions, maximum intensity projections, and volume rendering techniques are available to deal with the extensive data and to bring out those vascular lesions, which are of relevance for individual stroke. With the advent of multidetector CT advanced stroke protocols combining plain CT, perfusion CT and CTA can routinely be accomplished within a very short timespan thus ensuring the role of CT in the diagnostic workup of acute stroke.     

脑血肿周围组织CT灌注成像研究

目的评价脑CT灌注成像对脑出血患者血肿周围组织血流动力学变化的诊断价值。方法 通过对120例脑出血患者分期单次CT灌注成像检查,分析血肿周围组织血流动力学变化规律以及与神经功能恢复之间的关系。结果四组患者灌注参数图示脑出血后MTT明显延长,7天时达高峰,后逐渐缩短;TTP的变化趋势接近MTT;rCBF7天时最低,后逐渐升高;rCBV的变化趋势接近rCBF。同一参数各组间比较及4个参数各组间经多个样本均数间的两两比较,均得出,P〈O．05,各组数据之间具有统计学差异。结论血肿周围组织血流量呈现出先降低后上升的变化趋势,与临床研究中显示的脑出血患者神经功能恢复过程相一致。脑血流的波动性改变反映了脑出血发生后血肿周围组织继发产生的病理生理学变化。动态CT脑血流灌注定量分析可提供脑组织微循环血液动力学定量信息,是一种比较理想的同时反映形态和功能的检查方法。     

Brain perfusion CT: Principles, technique and clinical applications

The imaging of brain haemodynamics and its applications are generating growing interest. By providing quantitative measurements of cerebral blood flow (CBF) and cerebral blood volume (CBV), dynamic perfusion computed tomography (p-CT) allows visualisation of cerebral autoregulation mechanisms and represents a fast, available and reliable imaging option for assessing cerebral perfusion. Thanks to its feasibility in emergency settings, p-CT is considered most useful, in combination with CT angiography, in acute ischaemic patients, as it is able to provide a fast and noninvasive assessment of cerebral perfusion impairment. In addition, p-CT can play a diagnostic role in other types of cerebrovascular disease to assess functional reserve, and in intracranial neoplasms, where it has a role in diagnosis, grading, biopsy guidance, and follow-up during treatment. This article illustrates the principles, technique and clinical applications of p-CT cerebral perfusion studies.      

Autoradiographic imaging of cerebral ischaemia using a combination of blood flow and hypoxic markers in an animal model

Current routine clinical techniques, including angiography and perfusional single-photon emission tomography, can be used to indicate problems in cerebral vascular supply and areas of cerebral hypoperfusion following a stroke, but cannot distinguish between ischaemic core and penumbra. In order to image specifically the penumbra, a method or indicator should be able to define areas with reduced blood flow, and a degree of metabolic compromise. In this context, the tissue could be regarded as hypoxic rather than ischaemic, and we have therefore chosen to investigate the potential of radio-labelled hypoxic markers in the study of ischaemia. In order to combine a hypoxic marker with a blood flow marker we used technetium-99m hexamethylpropylene amine oxime (^99mTc-HMPAO) and iodine-125 iodoazomycin arabinoside (¹²⁵I-IAZA), during cerebral ischaemia in the rat middle cerebral artery occlusion model.^99mTc-HMPAO and¹²⁵I-IAZA were injected simultaneously 2 h following occlusion of the middle cerebral artery, and 5 h before decapitation. Paired autoradiograms were produced and compared. Three distinct patterns emerged from the autoradiograms: slightly decreased perfusion with no uptake of the hypoxic marker indicating an area of misery perfusion; moderately decreased perfusion with concomitant uptake of iodoazomycin arabinoside, a region of hypoxia; and severely decreased perfusion with no retention of the hypoxic tracer. In conclusion, we present a new use for an imaging agent in the investigation of cerebral hypoxia. This agent, IAZA together with HMPAO, provides a means of separating the penumbra into regions of misery perfusion and hypoxia. The potential impact of this may be important in the clinical investigation of stroke.     

Technetium-99m-N1-(2-mercapto-2-methylpropyl)-N2-(2-propargylthio-2- methylpropyl)-1,2-benzenediamine (T691): preclinical studies of a potential new tracer of regional cerebral perfusion.

We report in vitro and in vivo preclinical studies of a new cerebral blood flow tracer, [99mTc]N1-(2-mercapto-2-methyl-propyl)-N2-(2- propargylthio-2-methylpropyl)-1,2-benzenediamine (T691). The tracer demonstrates excellent in vitro chemical stability and accumulates regionally in the brain in a pattern consistent with that of cerebral blood flow. First-pass cerebral extraction determined with the use of the brain uptake index method in the rat was 0.76. Bolus intracarotid injection in monkeys indicated a cerebral extraction of 68% and prolonged retention of 67% of the initially extracted activity. Autoradiographic studies in rats revealed a pattern characteristic of cerebral blood flow at both 1 and 60 min after systemic injection. Dynamic tomographic imaging following systemic injection in the monkey revealed peak brain activity 1 to 2 min postinjection, without significant decline over 60 min. Chromatographic studies of brain as long as 60 min following systemic injection of [99mTc]T691 showed no evidence of tracer metabolism to account for its retention. Overall, [99mTc]T691 demonstrates promise as a potential new clinical tracer of cerebral perfusion.     

犬颈内动脉内冷灌注脑选择性降温对脑保护的实验研究

目的观察颈内动脉内冷灌注犬脑选择性降温对缺血性脑组织的保护作用。方法夹闭左侧颈总动脉、双侧椎动脉、左侧颈外静脉后,自右侧颈内动脉灌入低温灌注液以选择性降低脑温。将颅脑回流的低温稀释静脉血超滤并复温至３８℃后再输入体循环。结果１８只犬中有１４只完成了脑的选择性降温：（５．０±２．０）分钟内降至２８℃,（１０．３±７．２）分钟内降至２０℃,并维持在（１９±１．０）℃达５０分钟,直肠温度保持在（３２．５±２．０）℃以上。１０只长期存活,分别于术后１,２,８,１２周处死,病理检查示犬脑无神经细胞缺血性损伤改变。另４只实验初期因降温后血压显著下降而死亡。结论颈动脉内冷灌注液灌注,可选择性快速、安全地降低脑温,防止脑组织的缺血性损伤,为开展无血手术提供了实验依据。     

Interleukin-1 exacerbates focal cerebral ischemia and reduces ischemic brain temperature in the rat.

The proinflammatory cytokine interleukin-1 (IL-1) is a key mediator of inflammation in cerebral ischemia, but its precise mechanisms of action remain elusive. Temperature is critical to outcome in brain injury and given the importance of IL-1 in pyrogenesis this has clear mechanistic implications. IL-1 exacerbates ischemia independently of core (rectal) temperature. However, it is temperature in the ischemic brain that influences outcome and rectal temperature is likely to be a poor surrogate marker. This study tested the hypothesis that IL-1 exacerbates cerebral ischemia by increasing ischemic brain temperature. Wistar rats undergoing transient middle cerebral artery occlusion received either 4 microg/kg IL-1 (n=9) or vehicle (n=10) intraperitoneally. NMR-generated maps of brain temperature, tissue perfusion, and the trace of the diffusion tensor were collected during occlusion, early reperfusion, and at 24 hr. IL-1 significantly increased ischemic damage at 24 hr by 35% but rectal temperature did not vary significantly between groups. However, ischemic brain was 1.7 degrees C cooler on reperfusion in IL-1-treated animals (vs. vehicle) and a corresponding reduction in cerebral blood flow was identified in the ischemic striatum. Contrary to the stated hypothesis, IL-1 reduced ischemic brain temperature during reperfusion and this may be due to a reduction in tissue perfusion.     

急性脑缺血脑血流变化与脑组织死亡概率间关系的实验研究

目的采用自体血栓栓塞模型计算超急性期脑缺血时脑组织的死亡概率曲线,并通过概率曲线计算缺血半暗带的阈值。材料与方法12只新西兰大白兔行自体血栓栓塞制成局灶性脑缺血模型。采用GELightspeed16层螺旋CT,于栓塞后20min和10h各行CT灌注扫描1次。以CT灌注软件绘出每个时间点的脑血流图。在脑缺血12h后,取脑标本行TTC染色,并根据血流速图和染色结果将梗死侧分为中心梗死区,半暗带区和相对正常区三部分。结果缺血20min时中心梗死区、半暗带区和相对正常区各区域pCBF均值分别为29.33%,47.86%和94.32%,对应的死亡概率分别为67%,27%和1%,缺血10h各区域pCBF均值分别为16.87%,50.17%和85.49%,对应的死亡概率分别为100%,95%和43%。各时间点梗死侧的3个区域间差别有显著的统计学意义(P<0.0001)。缺血20minP=0.5时对应的pCBF值等于31.14%,而缺血10hP=0.5时对应的pCBF值等于40.89%。结论缺血10h的脑组织死亡概率明显高于缺血20min,证明了早期诊断和治疗的重要性,提出利用概率进行半暗带判定的方法,但其有效性还需进一步研究与证实。     

Simultaneous quantitative cerebral perfusion and Gd-DTPA extravasation measurement with dual-echo dynamic susceptibility contrast MRI.

Quantification of cerebral perfusion using dynamic susceptibility contrast MRI generally relies on the assumption of an intact blood-brain barrier. The present study proposes a method to correct the tissue response function that does not require this assumption, thus, allowing perfusion studies in, for example, high-grade brain tumors. The correction for contrast extravasation in the tissue during the bolus passage is based on a two-compartment kinetic model. The method separates the intravascular hemodynamic response and the extravascular component and returns the corrected tissue response function for perfusion quantification as well as the extravasation rate constant of the vasculature. Results of simulation experiments with different degrees of contrast extravasation are presented. The clinical potential is illustrated by determination of the perfusion and extravasation of a glioblastoma multiforme. The correction scheme proves to be fast and reliable even in cases of low signal-to-noise ratio. It is applicable whether extravasation occurs or not. When extravasation is present, application of the proposed method is mandatory for accurate cerebral blood volume measurements. Magn Reson Med 43:820-827, 2000.     

The relationship between magnetic resonance diffusion imaging and autoradiographic markers of cerebral blood flow and hypoxia in an animal stroke model.

This study examined the relationship between magnetic resonance diffusion imaging and autoradiographic markers of cerebral blood flow (99mTc-hexamethylpropylene amine oxime) and cerebral hypoxia (125I-iodoazomycin arabinoside) in a rat model of stroke. Middle cerebral artery occlusion in the rat was performed using an intraluminal suture approach. Diffusion, hypoxia, and blood flow maps were acquired 2 hr following occlusion, and were compared with T2 images and histology at 7 hr. Two hours following middle cerebral artery occlusion the lesion distributions from the diffusion maps and hypoxic autoradiographs were similar. The blood flow threshold for increased uptake of the hypoxic marker was approximately 34 +/- 7% of the normal flow. The combination of diffusion or hypoxic images with perfusion maps allowed differentiation between four regions: 1) normal tissue; 2) a region of decreased perfusion but normal diffusion and normal uptake of hypoxic marker; 3) a region of decreased perfusion, decreased diffusion and increased uptake of hypoxic marker; 4) a region of decreased perfusion, decreased diffusion and low uptake of hypoxic marker. The areas for increased uptake of hypoxic marker and decreased diffusion are equivalent, indicating similar blood flow thresholds. Regions of oligaemic misery perfusion, ischaemic misery perfusion and lesion core may be delineated with the combination of diffusion or hypoxic images and perfusion maps.     

Rapid intracranial clot removal with a new device: the alligator retriever

BACKGROUND AND PURPOSE: Despite availability of an approved drug to treat acute cerebral ischemia, most patients with stroke do not realize a good outcome. A method that would rapidly increase or restore cerebral perfusion before irreversible cell death should improve patient outcomes. MATERIALS AND METHODS: We recently had the opportunity to treat 6 middle-aged-to-elderly patients who presented with signs and symptoms of acute cerebral ischemia, by mechanically removing their (predominantly) middle cerebral artery clots by using a new retrieval device that had been previously approved by the US Food and Drug Administration for intravascular retrieval of foreign bodies. During a 2-month period, the 6 patients were treated in 5 separate institutions. No patient had an unsuccessful attempt at clot removal. The cases were collected by personal communication with each operator. RESULTS: In all instances, use of the device resulted in rapid clot removal. Each patient had a large improvement in National Institutes of Health Stroke Scale score. Two of the 6 patients had experienced failure of another clot retrieval device, and 3 patients required no systemic thrombolytics, reducing the likelihood of one of the most feared complications of stroke therapy, intracranial hemorrhage. SUMMARY: We believe that use of this device may result in improved outcomes for patients with acute ischemic stroke. In our limited experience, it provided a rapid, safe, and effective means for achieving revascularization.     

Arterial input function measurements for bolus tracking perfusion imaging in the brain

Imaging of cerebral perfusion by tracking the first passage of an exogenous paramagnetic contrast agent (termed dynamic susceptibility contrast, MRI) has been used in the clinical practice for about a decade. However, the primary goal of dynamic susceptibility contrast MRI to directly quantify the local cerebral blood flow remains elusive. The major challenge of dynamic susceptibility contrast MRI is to measure the contrast inflow to the brain, i.e., the arterial input function. The measurement is complicated by the limited dynamic range of MRI pulse sequences that are optimized for a good contrast in brain tissue but are suboptimal for a much higher tracer concentration in arterial blood. In this work, we suggest a novel method for direct arterial input function quantification. The arterial input function is measured in the carotid arteries with a dedicated plug‐in to the conventional pulse sequence to enable resolution of T₂ on the order of a millisecond. The new technique is compatible with the clinical measurement protocols. Applied to the pig model (N = 13), the method demonstrates robustness of the arterial input function measurement. The cardiac output and cerebral blood volume, obtained without adjustable parameters, agree well with positron emission tomography measurements and values found in the literature. Magn Reson Med, 2013. © 2012 Wiley Periodicals, Inc.     

Clinical applications of dynamic susceptibility contrast perfusion-weighted MR imaging in brain tumours

Magnetic resonance imaging (MRI) with a dynamic susceptibility contrast perfusion-weighted imaging (DSC-PWI) sequence to study brain tumours provides information on the haemodynamic characteristics of the neoplastic tissue. Brain perfusion maps and calculation of perfusion parameters, such as relative cerebral blood flow (rCBF), relative cerebral blood volume (rCBV) and mean transit time (MTT) allow assessment of vascularity and angiogenesis within tumours of the central nervous system (CNS), thus providing additional information to conventional MRI sequences. Although DSC-PWI has long been used, its clinical use in the study of brain tumours in daily clinical practice is still to be defined. The aim of this review was to analyse the application of perfusion MRI in the study of brain tumours by summarising our personal experience and the main results reported in the literature.     

Cerebral blood flow in Sjögren's syndrome using 99Tcm-HMPAO brain SPET

Neuropsychiatric disturbances are frequent in connective tissue diseases. Little is known about the cerebral pathophysiology of Sj?gren's syndrome, including cerebral blood flow disturbances. 99Tcm-HMPAO brain SPET was performed in 21 Sj?gren's syndrome patients. We also studied 77 patients with systemic lupus erythematosus and 27 healthy individuals. Our results demonstrate the high rate of alterations in cerebral blood flow in Sj?gren's syndrome, both psychoneurologically symptomatic and asymptomatic. Focal interhemispherical perfusion deficits were seen in 17 of 21 patients (80.9%) with Sj?gren's syndrome: 13/15 symptomatic (86.6%) and 4/6 asymptomatic (66.6%). These changes were mostly localized in the prefrontal and frontal areas, occipital lobes and occipitoparietal area, and less frequently so in the temporal, parietal and central areas. Diffuse hypoperfusion of the frontal lobes (bilateral hypofrontality) was seen in 29% of patients in the Sj?gren's group. An acetazolamide stress test was performed in seven patients. There was an increase in perfusion deficits in two patients, no change in two patients, and hypoperfusion decreased in three patients compared with baseline. The results indicate that most Sj?gren's syndrome patients experience alterations in cerebral blood flow that are consistent with systemic lupus erythematosus, with heterogeneous reactivity to acetazolamide-induced hypercapnia. These alterations present as focal perfusion deficits and bilateral diffuse hypoperfusion of the lobes. The mechanism of cerebral blood flow alterations is unknown, although it might be the result of diffuse cerebral vasculitis.     

Nuclear medicine for general radiologists: clinical application of brain SPECT

Brain SPECT studies are used to evaluate the cerebral hemodynamic changes in cerebrovascular diseases and other neuro-psychiatric disorders. I-123 and Tc-99m labeled radiopharmaceuticals widely used for brain perfusion SPECT studies include I-123 IMP, Tc-99m HMPAO, and Tc-99m ECD. I-123 IMP is suitable for the quantitative evaluation of cerebral blood flow, while Tc-99m HMPAO and Tc-99m ECD have problems owing to the non-linearity between cerebral radioactivity and cerebral blood flow. In addition, Tc-99m ECD does not show cerebral blood flow in the subacute phase of cerebral infarct or other conditions. Thus, it is important to consider the characteristics of radiopharmaceuticals and the clinical aspect of brain lesions in the interpretation of brain perfusion SPECT images. In this review, some useful information on brain perfusion SPECT is presented mainly as it relates to the cerebrovascular diseases.