Experimental hypoxic–ischemic encephalopathy: comparison of apparent diffusion coefficients and proton magnetic resonance spectroscopy

This study aims to compare the apparent diffusion coefficients (ADCs) and proton magnetic resonance spectroscopy (¹H-MRS) in the first 24 h of acute hypoxic-ischemic brain damage (HIBD) in piglets. Twenty-five 7-day-old piglets were subjected to transient bilateral common carotid artery occlusion followed by ventilation with 4% oxygen for 1 h. Diffusion-weighted imaging (DWI) and ¹H-MRS were performed on cessation of the insult or at 3, 6, 12 or 24 h after resuscitation (all n=5). ADCs, N-acetylaspartate/choline (NAA/Cho), NAA/creatine (NAA/Cr), lactate/NAA (Lac/NAA), Lac/Cho and Lac/Cr were calculated. Cerebral injury was evaluated by pathological study and Hsp70 immunohistochemical analysis. On cessation of the insult, ADCs, NAA/Cho and NAA/Cr reduced, Lac/NAA, Lac/Cho and Lac/Cr increased. From 3 to 12 h after resuscitation, ADCs, Lac/NAA, Lac/Cho and Lac/Cr recovered, NAA/Cho and NAA/Cr reduced. Twenty-four hours after resuscitation, ADCs reduced once more, Lac/NAA, Lac/Cho and Lac/Cr increased again, whereas NAA/Cho and NAA/Cr decreased continuously. Pathological study revealed mild cerebral edema on cessation of the insult and more and more severe cerebral injury after resuscitation. No Hsp70-positive cells were detected on cessation of the insult. From 3 to 12 hours after resuscitation, Hsp70-positive cells gradually increased. Twenty-four hours after resuscitation, Hsp70-positive cells decreased. Throughout the experiment, changes in NAA/Cho and pathology had the best correlation (R=–0.729). In conclusion, NAA/Cho is the most precise ratio to reflect the pathological changes of early HIBD. Transient ADCs and Lac ratios recovery do not predict the reversal of histological damage of early HIBD. Reducing astrocytic swelling is of great clinical significance.     

Measurement of Cerebral Optical Pathlength as a Function of Oxygenation Using Near-infrared Time-resolved Spectroscopy in a Piglet Model of Hypoxia

Near-infrared spectroscopy (NIRS) has been used for measurement of changes in cerebral hemoglobin concentrations in neonates to study cerebral oxygenation and hemodynamics. In this study, measurements by time-resolved reflectance spectroscopy (TRS) were performed in a piglet model with various degrees of cerebral oxygenation to estimate the differential pathlength factor (DPF). A portable three-wavelength TRS system (TRS-10, Hamamatsu Photonics K.K.) with a probe attached to the head of a piglet was used. Eleven newborn piglets were anesthetized and respired by a ventilator to induce stepwise hypoxia loading. The DPF showed positive linear relationship with arterial hemoglobin (Hb) oxygen saturation and sagittal sinus venous Hb oxygen saturation at 761 and 795 nm. The DPF at 835 nm also showed very slight positive linear relationship with arterial hemoglobin oxygen saturation. The DPF values obtained in this study should contribute to a better understanding of noninvasive measurements by NIRS in neonates.     

High-field localized 1H NMR spectroscopy in the anesthetized and in the awake monkey

Localized cerebral in vivo ¹H NMR spectroscopy (MRS) was performed in the anesthetized as well as the awake monkey using a novel vertical 7 T/60 cm MR system. The increased sensitivity and spectral dispersion gained at high field enabled the quantification of up to 16 metabolites in 0.1- to 1-ml volumes. Quantification was accomplished by using simulations of 18 metabolite spectra and a macromolecule (MM) background spectrum consisting of 12 components. Major cerebral metabolites (concentrations >3 mM) such as glutamate (Glu), N-acetylaspartate (NAA), creatine (Cr)/phosphocreatine (PCr) and myo-inositol (Ins) were identified with an error below 3%; most other metabolites were quantified with errors in the order of 10%. Metabolite ratios were 1.39:1 for total NAA, 1.38:1 for glutamate (Glu)/glutamine (Gln) and 0.09:1 for cholines (Cho) relative to total Cr. Taurine (Tau) was detectable at concentrations lower than 1 mM, while lactate (Lac) remained below the detection limit. The spectral dispersion was sufficient to separate metabolites of similar spectral patterns, such as Gln and Glu, N-acetylaspartylglutamate (NAAG) and NAA, and PCr–Cr. MRS in the awake monkey required the development and refinement of acquisition and correction strategies to minimize magnetic susceptibility artifacts induced by respiration and movement of the mouth or body. Periods with major motion artifacts were rejected, while a frequency/phase correction was performed on the remaining single spectra before averaging. In resting periods, both spectral amplitude and line width, that is, the voxel shim, were unaffected permitting reliable measurements. The corrected spectra obtained from the awake monkey afforded the reliable detection of 6–10 cerebral metabolites of 1-ml volumes.     

Brain metabolite alterations demonstrated by proton magnetic resonance spectroscopy in diabetic patients with retinopathy

Due to the homology between retinal and cerebral microvasculatures, retinopathy is a putative indicator of cerebrovascular dysfunction. This study aimed to detect metabolite changes of brain tissue in type 2 diabetes mellitus (T2DM) patients with diabetic retinopathy (DR) using proton magnetic resonance spectroscopy (¹H-MRS). Twenty-nine T2DM patients with DR (DR group), thirty T2DM patients without DR (DM group) and thirty normal controls (NC group) were involved in this study. Single-voxel ¹H-MRS (TR: 2000 ms, TE: 30 ms) was performed at 3.0 T MRI/MRS imager in cerebral left frontal white matter, left lenticular nucleus, and left optic radiation. Our data showed that NAA/Cr ratios of the DR group were significantly lower than those of the DM group in the frontal white matter and optic radiation. In the lenticular nucleus, MI/Cr ratios were significantly higher in the DM group than those in the NC group, while MI/Cr ratios were significantly lower in the DR group than those in the DM group. In the frontal white matter, NAA/Cho ratios were found to be decreased in the DR group as compared to the NC group. Additionally, our finding indicated that NAA/Cr ratios were negatively associated with DR severity in both the frontal white matter and optic radiation. A decrease in NAA indicated neuronal loss and the likely explanation for a decrease in MI was glial loss. In conclusion, we inferred that cerebral neurons and glia cells were damaged in patients with DR. Our data support that DR is associated with brain tissue damage.     

Quantitative MRS study of Baló's concentric sclerosis lesions

Baló's concentric sclerosis (BCS) lesions display specific metabolite changes detected by magnetic resonance spectroscopy (MRS). We report on two cases of BCS lesions examined by MRS; the first case was evaluated 36 days after the onset of symptoms, whereas the second case was evaluated 9 days after the onset of symptoms. MRS data were obtained from single voxels located in the lesion and in the contralateral region. Relative to the creatine/phosphocreatine peak, BCS lesions displayed decreases of N-acetyl aspartate and increases of choline, myo-inositol (mI), glutamine/glutamate (Glx), lactate and lipid+macromolecule signals, in agreement with previous reports. In addition, previously unreported decreases of mI (-19% to -29%) and increases of Glx (+55% to +198%) were measured; these could be useful in characterizing BCS lesions.     

In vivo 31P MRS of human brain at high/ultrahigh fields: a quantitative comparison of NMR detection sensitivity and spectral resolution between 4 T and 7 T

The primary goal of this study was to establish a rigorous approach for determining and comparing the NMR detection sensitivity of in vivo ³¹P MRS at different field strengths (B₀). This was done by calculating the signal-to-noise ratio (SNR) achieved within a unit sampling time at a given field strength. In vivo ³¹P spectra of human occipital lobe were acquired at 4 and 7 T under similar experimental conditions. They were used to measure the improvement of the human brain ³¹P MRS when the field strength increases from 4 to 7 T. The relaxation times and line widths of the phosphocreatine (PCr) resonance peak and the RF coil quality factors (Q) were also measured at these two field strengths. Their relative contributions to SNR at a given field strength were analyzed and discussed. The results show that in vivo ³¹P sensitivity was significantly improved at 7 T as compared with 4 T. Moreover, the line-width of the PCr resonance peak showed less than a linear increase with increased B₀, which leads to a significant improvement in ³¹P spectral resolution. These findings indicate the advantage of high-field strength to improve in vivo ³¹P MRS quality in both sensitivity and spectral resolution. This advantage should improve the reliability and applicability of in vivo ³¹P MRS in studying high-energy phosphate metabolism, phospholipid metabolism and cerebral biogenetics in the human at both normal and diseased states noninvasively. Finally, the approach used in this study for calculating in vivo ³¹P MRS sensitivity provides a general tool in estimating the relative NMR detection sensitivity for any nuclear spin at a given field strength.     

大鼠脑缺血边缘区代谢物1H-MRS的研究

目的 利用不同的局灶性脑缺血模型，评价急性缺血后磁共振质子波谱（¹H-MRS）测定缺血后边缘区脑组织代谢和生物能量变化的时空规律. 为判定急性缺血预 后，进行有效的溶栓治疗提供有价值的生物化学信息. 方法 健康Sprague-Dawly大鼠9只，雌雄不拘，随机分为两组. A组（4只），自体血栓栓塞1 h；B组（5只），线栓法栓塞1 h. 分别 于栓塞后30、40、50、60 min进行¹HMRS检查，相对含量分析兴趣区（regio ns of interest, ROIs）氮-乙酰天门冬氨酸（NAA）、胆碱（Cho）和乳酸（Lac）等代谢产物的变化. 结果 以NAA、Cho、Lac与磷酸肌酸和肌酸（PCr+Cr）的谱峰积 分面积比值为判断标准，上述各代谢产物在兴趣区内于缺血后1 h内逐渐下降. 其中缺血后60 min，Cho/ （P Cr+Cr）、NAA/（PCr+Cr）及Lac/（PCr+Cr）的比值与缺血后50 min的比值统计学有显著性 差异（P<0.05）. 结论 ¹H-MRS技术为研究急性缺血性卒中后脑细胞代谢、生化能量状态提供了一个无创性、直接性、综合性的研究工具.     

近红外空间分辨光谱技术及其对新生猪脑缺氧缺血的检测

近红外光谱(NIRS)技术作为一种无创的组织氧检测手段,近年来在脑缺氧缺血的检测方面日益受到重视。文章介绍了自行研制的NIRS仪器(TSAH-100近红外组织血氧无损监测仪)的基本原理及用于新生猪脑氧检测时如何实现传感器与待测脑组织的最佳耦合。检测了28例新生猪在不同氧合状态下的脑组织氧饱和度(regional cerebral oxygen saturation, rSO₂),在缺氧结束后进行了有创的动脉氧饱和度及生理参数的检测。结果表明,NIRS无创测得的脑rSO₂与血气分析有创测得的动脉血氧饱和度(SaO₂)有很好的相关性(p<0.001),并且脑rSO₂与缺氧程度及缺氧后生理参数的变化一致。因此NIRS无创测得的脑rSO₂能直接判断脑氧合状态,可在一定情况下替代有创血气分析,帮助临床无创、简便地诊断脑缺氧缺血。     

基于NIRS-ICG的脑血流量无创测量

临床上脑血流量(cerebral blood flow, CBF)等脑血管血流动力学参数是脑血氧水平及脑血管储备功能诊断依据,现有检测手段存在技术复杂及相应试剂或设备不适用于所有诊断人群等缺点。为解决以上问题,利用近红外光谱技术(NIRS)结合吲哚青绿(indocyanine green, ICG)脉搏色素浓度法,研究了一种无创、快速、可重复测量的脑血流量床旁检测方法NIRS-ICG。该方法根据静脉注射ICG后脑组织及脑动脉血流中三种主要吸光色团氧合血红蛋白(oxygenated hemoglobin, HbO₂)、还原血红蛋白(reduced hemoglobin, HbR)及ICG的浓度变化情况,建立脑组织及脑动脉血流中ICG积累量及引入量模型,以获得脑血氧及CBF等脑血流动力学参数。为验证该方法的可行性,将NIRS-ICG应用于血碳酸正常及高碳酸血症病理模型的实验猪的脑血流情况检测。具体方法是：分别对四组实验猪用按0%,3%,6%,9%比例调制的CO₂和空气混合气体施行机械通气,静脉快速推注ICG后,利用NIRS-ICG方法测量CBF、脑动脉血氧饱和度(cerebral arterial oxygen saturation, SaO₂)及脑血管管床平均循环时间(mean transit time, MTT)。实验结果表明,NIRS-ICG测得的CBF随CO₂比率升高而升高,SaO₂随着CO₂比例的升高而降低,MTT并无显著变化,与生理变化一致。因此,该方法可为脑血氧及脑血管储备功能诊断提供可靠依据。     

Centrality dependence of pi(+/-), K(+/-), p,and (-)p production from sqrt[s(NN)] = 130 GeV Au + Au collisions at RHIC

Identified pi(+/-), K(+/-), p, and (-)p transverse momentum spectra at midrapidity in sqrt[s(NN)] = 130 GeV Au+Au collisions were measured by the PHENIX experiment at RHIC as a function of collision centrality. Average transverse momenta increase with the number of participating nucleons in a similar way for all particle species. Within errors, all midrapidity particle yields per participant are found to be increasing with the number of participating nucleons. There is an indication that K(+/-), p, and (-)p yields per participant increase faster than the pi(+/-) yields. In central collisions at high transverse momenta (p(T) > or =2 GeV/c), (-)p and p yields are comparable to the pi(+/-) yields.     

MRI-based quantification of cerebral edema in individual SHRSP rats using averaged criteria determined before the occurrence of edema.

This study evaluated whether it is possible with T2-weighted MRI to quantitatively relate image-outcome in a single, individual case with that of a standardized control group that did not show these pathologies. An animal model of hypertension-related cerebral damage, the salt-loaded, stroke-prone spontaneously hypertensive rat (SHRSP), was applied. Very similar values for cerebral edema were found when using either the individual or the averaged threshold. The values were positively correlated with each, as edema(averaged threshold) = 0.12 + 0.99 x edema(individual threshold) (Pearsons coefficient = 0.99, p < 0.0001). This line was virtually congruent with the line of identity. Thus, by determination of the averaged threshold in the healthy salt-loaded SHRSP, a parameter was obtained to calculate cerebral edema with the specifically used T2-weighted MRI protocol, in any rat.     

Correlation of proton MR spectroscopy and diffusion tensor imaging

Proton magnetic resonance spectroscopy ((1)H-MRS) provides indices of neuronal damage. Diffusion tensor imaging (DTI) relates to water diffusivity and fiber tract orientation. A method to compare (1)H-MRS and DTI findings was developed, tested on phantom and applied on normal brain. Point-resolved spectroscopy (T(R)/T(E)=1500/135) was used for chemical shift imaging of a supraventricular volume of interest of 8 x 8 x 2 cm(3) (64 voxels). In DTI, a segmental spin-echo sequence (T(R)/T(E)=5500/91) was used and slices were stacked to reproduce the slab used in MRS. The spatial distributions of choline and N-acetylaspartate (NAA) correlated to mean fractional anisotropy and apparent diffusion coefficient (ADC) for the inner 6 x 6=36 voxels defined in MRS, most notably NAA and ADC value (r=-.70, P<.00001; correlation across four subjects, 144 data pairs). This is the first association of neuron metabolite contents in volunteers with structure as indicated by DTI.     

Development of new population-averaged standard templates for spatial normalization and segmentation of MR images for postnatal piglet brains

Propose

To design a set of brain templates for postnatal piglet brains based on high-resolution T1-weighted imaging for voxel-based morphometric analysis.

Materials and methods

Using a 3.0 T magnetic resonance (MR) scanner, a population-based whole brain template was developed by averaging forty T1 images in the brains of postnatal piglets at 38 days of age. The templates for gray and white matter, and cerebrospinal fluid were designed based on the corresponding probability maps by adapting individual data sets using statistical parametric mapping. Anatomical labeling maps were generated from labeling propagation derived from the established Pig Brain Atlas. Differences in the coordinates from four significant structural landmarks in the template, plus an additional 12 normalized images and anatomical labeling maps were measured to validate the accuracy of the registration of the template.

Results

A whole brain template, a set of tissue-specific probability and anatomical labeling maps were developed. The location deviation of the four significant structural landmarks, including the anterior and posterior regions in the corpus callosum, and the left and right caudate nucleus, was found to be < 0.25 cm, validating the sensitivity and resolution of the template.

Conclusion

A whole brain template map and a set of tissue-specific probability and anatomical labeling maps were developed to analyze the morphometric imaging of the postnatal piglet brain, an animal model of the human infant.     

Differences between arterial occlusive and cortical photothrombosis stroke models with magnetic resonance imaging and microtubule-associated protein-2 immunoreactivity

The differences between two models of cerebral ischemia [middle cerebral arterial transection (MCAT) and cortical photothrombosis (PT)] were explored with multiparametric MRI of apparent diffusion coefficient trace (ADCtr), cerebral blood flow (CBF) and T1. Microtubule-associated protein-2 (MAP2) immunoreactivity sections aligned with the MR images in the same coronal plane were used to map the infarct and to guide region-of-interest selection. In ischemic cortex, the larger T1 increase in PT versus MCAT (42+/-7% vs. 16+/-5%) is related to the different character of edema between these models; yet, neither CBF nor ADCtr discriminated between them at 3.5 h, suggesting that different mechanisms of ischemic damage to the brain cells resulted in the same ADCtr value. CBF and ADCtr were depressed in immediately adjacent ischemic border by 27+/-7% and 47+/-10%, respectively, in MCAT but not in PT, suggesting marginal perfusion in MCAT. CBF in homotopic normal cortex in the opposite hemisphere was higher for PT compared with MCAT (199+/-20 and 134+/-10 ml/100 g/min, respectively). Different pathological processes in the two models affect CBF, ADCtr and T1 in a unique, regionally specific manner. The PT model differs substantially from the MCAT and is not a model of cortical ischemia with an appreciable border zone.     

Cerebral mucormycosis: proton MR spectroscopy and MR imaging

Proton magnetic resonance spectroscopy (MRS) was integrated with magnetic resonance imaging (MRI) in the evaluation of a case of cerebral mucormycosis. MRS showed markedly elevated lactate, depleted N-acetyl aspartate and metabolite resonances attributable to succinate and acetate. The spectroscopy profile is essentially similar to that of bacterial abscess but without the commonly seen resonances of the amino acids valine, leucine and isoleucine. Our extensive literature review did not yield any reports of MRS findings on cerebral mucormycosis. MRS prospectively limited the differential diagnoses given the otherwise nonspecific and complex MR imaging findings in our immunosuppressed patient.     

Cerebral tissue water spin-spin relaxation times in human neonates at 2.4 tesla: methodology and the effects of maturation

Using a 4-echo spin-echo sequence, cerebral T2 was measured in specific anatomic regions in eleven healthy newborn infants, whose gestational plus postnatal ages (GPAs) lay between 37 and 42 weeks. For a region in the pons, T2 was 141+/-9 ms (mean +/- standard deviation), and no significant dependence upon GPA was seen. In the thalamus mean T2 was 136+/-13 ms, and T2 demonstrated a significant negative linear dependence upon age (r = 0.690; p < 0.02). In periventricular and frontal regions, mean T2 were 217+/-33, and 228+/-32 ms respectively, and more marked negative linear correlations with age were observed (r = 0.833; p < 0.001 and r = 0.722; p < 0.02). For these regions, the rate of T2 decrease with age appeared to be related to known patterns of myelination. For the parietal region studied, mean T2 was 204+/-34 ms, no significant dependence upon GPA being seen. T2 shows promise as an objective measure of cerebral development in the perinatal period.     

Sub region-specific modulation of synchronous neuronal burst firing after a kainic acid insult in organotypic hippocampal cultures

Background  

Excitotoxicity occurs in a number of pathogenic states including stroke and epilepsy. The adaptations of neuronal circuits in response to such insults may be expected to play an underlying role in pathogenesis. Synchronous neuronal firing can be induced in isolated hippocampal slices and involves all regions of this structure, thereby providing a measure of circuit activity. The effect of an excitotoxic insult (kainic acid, KA) on Mg²⁺-free-induced synchronized neuronal firing was tested in organotypic hippocampal culture by measuring extracellular field activity in CA1 and CA3.     

Technical evaluation of in vivo abdominal fat and IMCL quantification using MRI and MRSI at 3 T

OBJECTIVES: The objectives of this study were to develop protocols that measure abdominal fat and calf muscle lipids with magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS), respectively, at 3 T and to examine the correlation between these parameters and insulin sensitivity. MATERIALS AND METHODS: Ten nondiabetic subjects [five insulin-sensitive (IS) subjects and five insulin-resistant (IR) subjects] were scanned at 3 T. Visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) were segmented semiautomatically from abdominal imaging. Intramyocellular lipids (IMCL) in calf muscles were quantified with single-voxel MRS in both soleus and tibialis anterior muscles and with magnetic resonance spectroscopic imaging (MRSI). RESULTS: The average coefficient of variation (CV) of VAT/(VAT+SAT) was 5.2%. The interoperator CV was 1.1% and 5.3% for SAT and VAT estimates, respectively. The CV of IMCL was 13.7% in soleus, 11.9% in tibialis anterior and 2.9% with MRSI. IMCL based on MRSI (3.8+/-1.2%) were significantly inversely correlated with glucose disposal rate, as measured by a hyperinsulinemic-euglycemic clamp. VAT volume correlated significantly with IMCL. IMCL based on MRSI for IR subjects was significantly greater than that for IS subjects (4.5+/-0.9% vs. 2.8+/-0.5%, P=.02). CONCLUSION: MRI and MRS techniques provide a robust noninvasive measurement of abdominal fat and muscle IMCL, which are correlated with insulin action in humans.     

MR-visible water content in human brain: A proton MRS study

In vivo measurement of metabolite concentrations in the human brain by means of proton-MRS contributes significantly to the clinical evaluation of patients with diseases of the brain. The fully relaxed water signal has been proposed as an internal standard for calibration of the MRS measurements. The major drawbacks are the necesity to make the assumptions that the water concentration in the brain and that all tissue water is MR-visible. A number of in vivo measurements were carried out to estimate the concentration of MR-visible water in the brain of healthy volunteers divided into four age groups: newborn (0–23 days), adolescents (10–15 yr), adults (22–28 yr), and elderly people (60–74 yr). The examinations were carried out using a Siemens Helicon SP 63/84 MR-scanner operating at 1.5 T. Except for the newborn, four regions were studied in each subject using stimulated echo (STEAM) sequences without water suppression. In vitro measurements on a standard phantom were used for calibration. The calculated water concentrations ranged between 35.8 and 39.6 (mean 36.9) mol·[kg wet weight]⁻¹ in the three groups, whereas it was 51.5 mol·[kg wet weight]⁻¹ in the newborn, p<.01. The observed water concentration of neither the four regions nor of the three oldest age groups were significantly different. Comparisons between the water concentrations measured and those expected based on estimation of the content of grey and white matter in the region of interest from T₁-weighted images and biochemical data published, suggest that only a small fraction (<5%) of the tissue water may be MR-invisible. The study of healthy volunteers thus shows that errors introduced by using the unsaturated water signal for calibration are less than 10%, which is comparable to expected errors when other calibration procedures are used under similar measurement conditions.