颅脑创伤近红外实时监测技术研究

采用一套专门设计的由微创光纤探头组成的光纤光谱仪生物组织光学参数测试系统,对颅脑创伤的大鼠创伤侧和对照侧进行近红外光谱检测及脑水含量(brain water content:BWC)测定.通过采用Feeney's自由落体撞击法建立大鼠急性局灶性脑挫裂伤模型,以近红外光谱技术和干湿比重法监测伤后脑水肿的变化.实验发现:伤后1 h,伤侧脑组织已发生水肿,伤后24～72 h,伤侧脑水肿达高峰,随后逐渐下降;用脱水剂后,脑水肿情况逐渐好转,随着药物失效,水肿又一次发生.生物组织优化散射系数(Reduced Scat-tering Coefficient:μ's)与Bwc的变化规律一致,有很好的线性相关性,能够较好的反映脑组织水肿程度以及药物脱水效果.证实近红外光谱技术用于颅脑创伤实时监测的可行性,为颅脑创伤的研究提出了一种新技术.     

X射线显微CT用于大鼠骨小梁结构分析的研究

应用X射线显微CT(X-μCT)对正常及骨质疏松大鼠的骨小梁结构进行了分析,并与骨组织形态计量法的测量值进行了比较,探讨了X射线光谱技术在骨结构分析中的应用。实验对大鼠骨样品进行X-μCT扫描,扫描条件为 80 kVp,80 μA,360°旋转,帧平均4帧,角度增益 0.4°,分辨率14 μm。三维重建并分析了骨小梁结构,结构参数包括骨体积分数(BV/TV)、骨小梁厚度(Tb.Th)、骨小梁数量(Tb.N)以及骨小梁间隔(Tb.Sp)。结果表明,采用X-μCT分析不同组大鼠的骨小梁结构参数值之间存在显著差异(P<0.05),测定值与传统骨组织形态计量法的测定值显著相关,其中胫骨骨小梁BV/TV,Tb.Th,Tb.N,Tb.Sp的相关系数r分别为0.984,0.960,0.995,0.988,腰椎骨小梁各结构参数的相关系数分别为0.938,0.968,0.877,0.951。因此,X-μCT可以较好地呈现并区分正常骨组织、骨质疏松骨组织以及经雌激素治疗后骨组织的微观结构,可以实现对骨小梁结构参数的分析测定,与骨组织形态计量法相比是一种更精确、立体、快速且无损测量骨微结构和评价骨质量的方法。     

血液可见吸收光谱与血氧参数神经网络估算法

总血红蛋白浓度和血氧饱和度是两个基本的血氧参数。文章提出了利用内置双光纤微创探头在位测量大鼠脑组织血氧参数的新方法。首先,利用悬乳液(Intralipid)和全血配置不同总血红蛋白浓度的混合溶液,模拟生物组织模型,用光纤光谱仪测试系统测量组织模型在加氧和去氧时的实时吸收光谱,同时用血氧分析仪(OXI meter)对血氧参数定标,建立测试光谱和定标数据样本集。然后,利用人工神经网络建立血液吸收光谱与血氧参数的神经网络模型,训练后的网络模型能根据吸收光谱输出生物组织的血氧参数值,总血红蛋白浓度和血氧饱和度的平均输出误差分别为±4μmol·L-1和±5%。最后,利用神经网络模型对大鼠脑组织血氧参数进行了在位测试实验,测得脑灰质的血氧饱和度为0.60~0.70,脑白质血氧饱和度为0.45~0.55;总血红蛋白浓度在脑皮层(深度1mm)附近最高,平均110μmol·L-1,其余深度脑组织的总血红蛋白浓度为70~90μmol·L-1。这种方法对脑外科微创手术中实时在位测试脑组织血氧参数具有重要的参考意义。     

大鼠脑组织含磷代谢物随年龄变化的NMR研究

随着人口老龄化的不断加剧,衰老相关疾病已成为全球关注的问题.神经系统功能的退行性改变居于衰老相关疾病的首位,其机制尚不明了.该文旨在通过核磁共振磷谱(~(31)P NMR)检测不同月龄大鼠脑组织中小分子物质的改变,明确能量相关的含磷化合物随大鼠年龄增长的变化,从而揭示脑组织中年龄相关代谢物的变化规律.该研究萃取了不同年龄(幼年、中年及老年)Sprague-Dawley(SD)大鼠脑组织中的小分子物质,进行了~(31)P NMR检测分析.结果显示:老年大鼠脑组织中能量代谢相关物质——磷酸肌酸的含量显著升高,而磷脂酰胆碱及磷酸肌醇含量显著降低,并且出现了磷酸化葡萄糖.这一发现有助于理解衰老相关的脑结构和功能下调,为神经退行性疾病的发生提供依据.     

同步辐射显微红外光谱研究6-OHDA诱导帕金森病大鼠海马

利用同步辐射红外显微光谱研究6-hydroxydopamine(6-OHDA)毁损内侧前脑束所致帕金森病大鼠脑海马区神经元的生物化学成分改变。研究样本为6-OHDA诱导的帕金森大鼠模型海马区神经元。与正常大鼠海马区神经元比较,PD大鼠样品在属于脂类的CH2反对称和对称伸缩振动的2 924和2 850cm-1的振动吸收积分面积以及在峰值位于1 736cm-1的伸缩振动吸收积分强度比正常大鼠都有增加,提示PD样品脂质含量升高,而在属于核酸的PO2反对称伸缩振动和对称伸缩振动的强度比正常大鼠样品下降,提示PD样品中核酸的含量比正常样品减少。蛋白质的振动没有发现异常。该研究表明帕金森病大鼠模型海马神经元存在生物化学成分改变,这种改变可能与神经元的病理改变密切相关。     

基于二比特自旋压缩模型中的热纠缠研究

利用Concurrence判据,讨论了基态和有限温度下二比特自旋压缩模型中的量子热纠缠性质.探究了自旋压缩参量μ、外磁场Ω以及温度T对系统纠缠性质的影响.结果发现,首先,Concurrence随着耦合参量μ(或Ω)的增大先增大到最大值,然后逐渐衰减到零,Concurrence的最大值随参数μ(或Ω)的增大而增大;Concurrence的衰减率会随参数μ(或Ω)的增大而减小,从而可以在较大的范围内得到体系热纠缠.其次,较大的耦合参量取值可以提升Concurrence存在的温度范围.最后,在有限温度条件下,当参数μ(或Ω)取值较小时,体系的纠缠保持为零,即存在纠缠"死亡间隔"现象;然而随着参量μ(或Ω)的取值增大到一定值时,Concurrence会突然产生,即存在纠缠瞬间产生("Sudden birth")现象,值得注意的是:纠缠的"死亡间隔"会随着参数μ(或Ω)的增大而减小.     

基于修正脉搏色素谱的循环血量检测方法

循环血量(CBV)作为主要的血流动力学参数,在心血管疾病的病情评估和手术监护中具有重要的临床应用价值。将吲哚菁绿色素(ICG)作为示踪剂的脉搏色素谱法,通过建立ICG稀释排泄的色素谱曲线,实现CBV的在体无创测量。在实际临床应用中,由于受到血氧波动和环境背景光等干扰因素的影响,脉搏色素谱法测量CBV的准确度低于预期值。为解决这一问题,研究了一种基于修正脉搏色素谱的循环血量检测方法。具体操作是,在患者的肘静脉处注入吲哚菁绿试剂,利用光电传感器分别采集特征波长点的透射光谱信号和背景光电信号,采用差分算法消除血氧波动和环境背景光的干扰影响,建立准确的ICG色素谱曲线,从而计算CBV等血流动力学参数。与131I同位素“金标准法”相比较的试验结果表明,该研究提出的基于修正脉搏色素谱的循环血量检测方法,将CBV测量的平均相对误差从6.85%降低为4.53%,显著提高了其测量准确度。     

RP-3航空煤油热辐射物性参数的透射法测量

建立了填充半透明液体光学腔光谱透射比的正问题计算模型,提出了一种基于填充液体光学腔的透射光谱反演其液态介质光学常数的IDTM模型,通过测量填充水光学腔的透射光谱并反演水的光学常数进行了模型验证.采用Bruke V70傅里叶红外光谱仪实验测量了填充RP-3航空煤油光学腔在波长2~15μm的透射光谱,基于新模型反演得到RP-3航空煤油光学常数,进而计算得到了其部分波段区域热辐射物性参数.研究结果表明:1)IDTM模型反演液体光学常数精度同MCDTM模型基本一致,且明显高于SODTM模型和SDTM模型.2)RP-3航空煤油在波长2~15μm范围透光性能较差,其中存在2.4μm、3.4μm、6.9μm、7.3μm和13.8μm等5个强吸收区域.3)RP-3航空煤油的光学常数和热辐射物性参数光谱选择性很强,在不同波段其值差距较大.     

利用宇宙线直接测量结果对初级宇宙线能谱参数的调整

由JACEE?,RUNJOB和SOKOL等宇宙线直接测量结果和刚度截断模型,对于10¹⁴—10¹⁶eV能区的初级宇宙线微分能谱参数进行调整.利用调整后的能谱与选取QGSJET模型的CORSIKA程序进行EAS模拟,同HD,PD谱进行对比研究.采用相同的标准对模拟数据与实验数据进行分析.结果表明,调整后的谱和HD谱的模拟结果与甘巴拉山乳胶室实验结果符合较好,而PD谱的模拟结果与实验结果偏离较大.     

大鼠创伤性脑水肿模型中近红外光有效检测深度研究

采用近红外光谱技术实现颅脑损伤的无损监测过程中,存在着检测深度不明确的问题.利用Monte Carlo模拟光子在生物组织中的传输过程,建立有效检测深度模型,对光纤探头在大鼠创伤性脑水肿模型中的有效检测深度规律进行了研究.采用不依赖于模板的阈值分割和窄带水平集分割方法,将大鼠头部MRI图像分为头皮、头骨、脑脊液、灰质和白质五部分,建立真实的大鼠脑组织三维模型,使Monte Carlo仿真结果更加准确.改进复杂组织光场分布仿真的tMCimg软件,使其能够实时记录光子在组织中的位置和光子被检测器接收时的能量,从而计算出探头在组织中的有效检测深度.分析了不同光源和检测器的中心距、光源芯径对有效检测深度的影响,结果表明光在大鼠脑组织中的有效检测深度小于或者等于光源和检测器中心距的一半,并随光源芯径的增大逐渐增大.建立大鼠脑水肿模型,验证了仿真结果的正确性.研究结果对于无创脑水肿模型的光纤探头的设计和脑水肿区域的判定有着重要的意义.     

Impaired functionality of reperfused brain tissue following short transient focal ischemia in rats

Functional magnetic resonance imaging (fMRI) has been applied to study the consequences of transient focal ischemia on neuronal excitability in the rat brain. The experimental paradigm consisted of measuring the changes in local cerebral blood volume (CBV) induced by systemic infusion of the GABA(A) antagonist bicuculline after occlusion of the middle cerebral artery (MCA) for durations of 5, 15, 30 and 60 min using the intraluminal thread model. fMRI studies were carried out 60 min after successful reperfusion of the ischemic territory. Bicuculline-induced dynamic changes in local CBV were assessed in three brain regions: Parietal cortex, caudate putamen and thalamus. The measured CBV response was negatively correlated with the ischemia duration. Additionally, the three regions showed different vulnerability to the transient MCA occlusion, caudate being the most susceptible followed by parietal cortex and thalamus. The fMRI signals weakly correlated with basal CBF and CBV following reperfusion. Our results indicate that fMRI is a sensitive method to assess functional integrity of the brain. Activation maps allow to quantitatively assess the functionally compromized territory at an early stage following the ischemic event prior to the manifestation of pathomorphological changes.     

Assessment of a combined spin- and gradient-echo (SAGE) DSC-MRI method for preclinical neuroimaging

The goal of this study was to optimize and validate a combined spin- and gradient-echo (SAGE) sequence for dynamic susceptibility-contrast magnetic resonance imaging to obtain hemodynamic parameters in a preclinical setting. The SAGE EPI sequence was applied in phantoms and in vivo rat brain (normal, tumor, and stroke tissue). Partial and full Fourier encoding schemes were implemented and characterized. Maps of cerebral blood volume (CBV), cerebral blood flow (CBF), mean transit time (MTT), vessel size index (VSI), volume transfer constant (K^trans), and volume fraction of the extravascular extracellular space (v_e) were obtained. Partial Fourier encoding provided shortened echo times with acceptable signal-to-noise ratio and temporal stability, thus enabling reliable characterization of T₂, T₂^? and T₁ in both phantoms and rat brain. The hemodynamic parameters CBV, CBF, and MTT for gradient-echo and spin-echo contrast were determined in tumor and stroke; VSI, K^trans, and v_e were also computed in tumor tissue. The SAGE EPI sequence allows the acquisition of multiple gradient- and spin-echoes, from which measures of perfusion, permeability, and vessel size can be obtained in a preclinical setting. Partial Fourier encoding can be used to minimize SAGE echo times and reliably quantify dynamic T₂ and T₂^? changes. This acquisition provides a more comprehensive assessment of hemodynamic status in brain tissue with vascular and perfusion abnormalities.     

Near-infrared spectroscopy extended with indocyanine green dye dilution for cerebral blood flow measurement: Median values in healthy volunteers

The cerebral blood flow (CBF) is an important vital parameter in neurointensive care. Currently, there is no non-invasive method for its measurement that can easily be applied at the bedside. A new tool to determine CBF is based on near-infrared spectroscopy (NIRS) applied together with indocyanine green (ICG) dye dilution. From a bilateral measurement on selected regions on the head of infrared (IR) absorption at various wavelengths during the dilution maneuver, the vascular perfusion characteristics of the two brain hemispheres can be determined in terms of mean transit time (mtt) of ICG, cerebral blood volume (CBV) and CBF. So far, on nine healthy volunteers, NIRS ICG dye dilution bihemispheric measurements were performed, which yielded to mtt given as median (range) of 9.3 s (5.1–16.3 s), CBV of 3.5 ml/100 g (1.7–4.1 ml/100 g), and CBF of 18.2 ml/(100 g×min) [11.1–48.6 ml/(100 g×min)]. Additionally, the blood flow index (BFI) was calculated with BFI= 13.8 mg/(100 g×s) [6.6–15.2 mg/(100 g×s)]. The Spearman rank correlation coefficient between CBF and BFI was R_S = 0.76. However, as the Bland & Altman plot between CBFNIRS and the CBF_BFI documents, the limits of agreement are rather wide (21.9±6.7). Under physiological conditions in healthy volunteers, no differences could be detected between the hemispheres.     

A multimodality investigation of cerebral hemodynamics and autoregulation in pharmacological MRI

Pharmacological MRI (phMRI) methods have been widely applied to assess the central hemodynamic response to pharmacological intervention as a surrogate for changes in the underlying neuronal activity. However, many psychoactive drugs can also affect cardiovascular parameters, including arterial blood pressure (BP). Abrupt changes in BP or the anesthetic agents used in preclinical phMRI may impair cerebral blood flow (CBF) autoregulation mechanisms, potentially introducing confounds in the phMRI response. Moreover, relative cerebral blood volume (rCBV), often measured in small-animal phMRI studies, may be sensitive to BP changes even in the presence of intact autoregulation. We applied laser Doppler flowmetry and MRI to measure changes in CBF and microvascular CBV induced by increasing doses of intravenous norepinephrine (NE) challenge in the halothane-anesthetized rat. NE is a potent vasopressor that does not cross the blood-brain barrier and mimics the rapid BP changes typically observed with acute drug challenges. We found that CBF autoregulation was maintained over a BP range of 60-120 mmHg. Under these conditions, no significant central rCBV responses were observed, suggesting that microvascular rCBV changes in response to abrupt changes in perfusion pressure are negligible within the autoregulatory range. Larger BP responses were accompanied by significant changes in both CBV and CBF that might confound the interpretation of phMRI results.     

Study of cerebrovascular reserve capacity by magnetic resonance perfusion weighted imaging and photoacoustic imaging

The aim of this work was to assess the feasibility of photoacoustic imaging (PAI) and MR imaging for evaluating the cerebrovascular reserve capacity (CVRC) in animal models. Wistar-Kyoto (WKY) rats and spontaneous hypertensive rats (SHR) were used for MRI. BALB/c mice were used for PAI. MR perfusion weighted imaging (PWI) was performed on a 1.5-T whole-body MR system before and after oral administration of acetazolamide (ACZ). The region of interest (ROI) was chosen in the bilateral frontal lobe for measuring regional cerebral blood flow (rCBF), regional cerebral blood volume (rCBV) and mean transit time (MTT). The vessel diameters of the superficial layer of the cortex were measured by PAI in the resting and ACZ-activated mice. The results showed that there was a statistical difference between the resting and ACZ-activated animals in vessel diameter, rCBV and rCBF values. The increments in rCBV and rCBF of WKY rats between resting and ACZ test states were significantly higher than that of SHR. The pathological findings of small arterial walls and lumen of the brain were also different between WKY and SHR rats. The diameters of blood vessels in the superficial layer of the brain measured by PAI were enlarged after the ACZ tolerance test. This result was also observed in the MRI CBV map, where the signal of the vessel in the superficial layer of the cortex became redder after the ACZ stimulation, suggesting the increase of blood flow. It can be concluded that MR PWI and PAI combined with the ACZ test might be useful in evaluating the CVRC and revealing the pathologic changes in cerebral vessels.     

固体进样石墨炉原子吸收光谱技术在测定大鼠脑铁含量中的应用

石墨炉原子吸收光谱法是测定动物脑组织Fe含量的常用方法,然而由于传统的液体进样方法中,样品前处理阶段用硝酸消解周期长,成本高耗时长,限制了原子吸收光谱技术在测定动物组织中Fe含量的应用。文章以SD大鼠脑部海马、纹状体、皮层为实验材料,采用固体进样器进样,利用石墨炉原子吸收光谱技术对各组织中的Fe含量进行了测定,并与传统法方法——硝酸消解样品后,液体进样的石墨炉原子吸收光谱测定结果做了比较,结果表明这两种方法所测结果无显著性差异,但应用固体进样法,样品前处理阶段明显简单,显著节省了样品准备时间,降低了工作量,使测定时间明显缩短,成本明显降低,并且能够有效避免外界因素对测定结果的影响,为固体进样法的进一步应用奠定了基础。     

Perfusion parameters derived from MRI for preoperative prediction of IDH mutation and MGMT promoter methylation status in glioblastomas

PurposeTo investigate the feasibility for preoperative prediction of IDH mutation and MGMT promoter methylation status in glioblastomas(GBMs) by intravoxel incoherent motion(IVIM) and dynamic susceptibility contrast(DSC).MethodsPreoperative IVIM and DSC images of 71 patients(IDH mutation:45, IDH wildtype: 26; MGMT methylation: 31, MGMT unmethylation:40) with glioblastomas were analyzed retrospectively. Perfusion parameters including microcirculation perfusion coefficient(D*), perfusion fraction(f), cerebral blood volume(CBV) and cerebral blood flow(CBF) were measured. Corrected perfusion parameters containing corrected perfusion coefficient(ADC_perf) and simplified perfusion fraction(SPF) were from the simplified IVIM with 3 b values. Correlations among parameters were analyzed by Spearman correlation. All parameters were compared with Mann-Whitney U test. Univariate and multivariate logistic regression models were constructed. The receiver operating characteristic(ROC) curve was analyzed.ResultsThe IVIM parameters showed merely moderate correlations with CBV and showed no correlation with CBF. IDH mutation GBMs showed lower D*, ADC_perf, SPF, CBV and higher f than IDH wildtype GBMs(all p < 0.05). D* was the independent predictor for IDH mutation with the highest AUC of 0.912(95%CI: 0.821–0.966). The D*, ADC_perf, SPF and CBV of MGMT promoter methylation GBMs were lower than unmethylation GBMs while f was higher(all p < 0.05). Multivariate model showed the highest prediction efficacy for MGMT promoter methylation with an AUC of 0.915(95%CI: 0.824–0.968). The CBF was not useful in distinguishing IDH mutation and MGMT promoter methylation status(p = 0.055, 0.215).ConclusionIDH mutation and MGMT promoter methylation status in GBMs can be assessed effectively by IVIM and DSC. Besides, D* was the independent predictor of IDH mutation status.     

Measurement of relative cerebral blood volume using BOLD contrast and mild hypoxic hypoxia

Relative cerebral blood volume (CBV) was estimated using a mild hypoxic challenge in humans, combined with BOLD contrast gradient-echo imaging at 3 T. Subjects breathed 16% inspired oxygen, eliciting mild arterial desaturation. The fractional BOLD signal change induced by mild hypoxia is expected to be proportional to CBV under conditions in which there are negligible changes in cerebral perfusion. By comparing the regional BOLD signal changes arising with the transition between normoxia and mild hypoxia, we calculated CBV ratios of 1.5±0.2 (mean±S.D.) for cortical gray matter to white matter and 1.0±0.3 for cortical gray matter to deep gray matter.     

Mismatch between Cerebral Blood Volume and Flow Index during Transient Focal Ischemia Studied with MRI and Gd-BOPTA

We investigated the regional and temporal changes in cerebral blood volume (CBV), cerebral blood flow (CBF), and vascular transit time in seven mongrel cats during 30 min transient focal ischemia, caused by occlusion of the middle cerebral artery. Dynamic susceptibility contrast magnetic resonance imaging was done at 4.7 T, using fast gradient echo T₂¹ weighted imaging and intravenous injection of gadolinium-BOPTA/Dimeglumine. During occlusion, the areas showing a blood volume change were predominantly within the middle cerebral artery territory and could be divided into areas showing either CBV increases or decreases. The area with decreased blood volume also had decreased blood flow as measured by our flow-based index (p < 0.05) and was located in the central territory of the middle cerebral artery. Peripheral to this region was an area showing increased blood volume but without significant CBF changes (p > 0.05). During reperfusion, the CBF increased in the entire zone showing changes in blood volume during occlusion, and remained significantly elevated until 45 min post-occlusion, while CBV remained elevated in the hyperemic rim for at least 2 h. The presence of a peri-ischemic zone showing flow/volume mismatch identified a region wherein baseline CBF is maintained by means of compensatory vasodilatation, but where the ratio of CBF to CBV is decreased. Dynamic susceptibility contrast magnetic resonance imaging with gadolinium-BOPTA/Dimeglumine may be a valuable technique for the investigation of regional and temporal perturbations of hemodynamics during ischemia and reperfusion.