Intravoxel incoherent motion (IVIM) imaging at different magnetic field strengths: What is feasible?

Background

Due to limited SNR the cerebral applications of the intravoxel incoherent motion (IVIM) concept have been sparse. MRI hardware developments have resulted in improved SNR and this may justify a reassessment of IVIM imaging for non-invasive quantification of the cerebral blood volume (CBV) as a first step toward determining the optimal field strength.

Purpose

To investigate intravoxel incoherent motion imaging for its potential to assess cerebral blood volume (CBV) at three different MRI field strengths.

Materials and methods

Four volunteers were scanned twice at 1.5 T, 3 T as well as 7 T. By correcting for field-strength-dependent effects of relaxation, estimates of corrected CBV (cCBV) were obtained in deep gray matter (DGM), frontal gray matter (FGM) and frontal white matter (FWM), using Bayesian analysis. In addition, simulations were performed to facilitate the interpretation of experimental data.

Results

In DGM, FGM and FWM we obtained cCBV estimates of 2.2 ml/100 ml, 2.7 ml/100 ml, 1.4 ml/100 ml at 1.5 T; 3.7 ml/100 ml, 5.0 ml/100 ml, 3.2 ml/100 ml at 3 T and 15.5 ml/100 ml, 20.3 ml/100 ml, 7.0 ml/100 ml at 7 T.

Conclusion

Quantitative cCBV values obtained at 1.5 T and 3 T corresponded better to physiological reference values, while 7 T showed the largest deviation from expected values. Simulations of synthetic tissue voxels indicated that the discrepancy at 7 T can partly be explained by SNR issues. Results were generally more repeatable at 7 T (intraclass correlation coefficient, ICC = 0.84) than at 1.5 T (ICC = 0.68) and 3 T (ICC = 0.46).     

A metabonomic approach applied to predict patients with cerebral infarction

Cerebral infarction is always of sudden onset, and usually leading to serious consequence. It is of therapeutic significance to develop fast and accurate diagnosis methods for cerebral infarction so that patients can be treated timely and properly. A metabonomic approach was then proposed to investigate the potential biomarkers and metabolic pathways associated with cerebral infarction and also establish a prediction model of cerebral infarction for the fast diagnosis. Serum metabolic profiling of sixty-seven cerebral infarction patients and sixty-two controls was obtained using UPLC-TOF MS. The resulting data were then processed by multivariate statistical analysis to graphically demonstrate metabolic variations. The PLS-DA model was validated with cross validation and permutation tests to assure the model's reliability, and significant difference was obtained between the original and hypothetical models (p < 0.0001). A series of endogenous metabolites in the one-carbon cycle, such as folic acid, cysteine, S-adenosyl homocysteine and oxidized glutathione, were determined as potential biomarkers of cerebral infarction. A prediction model developed using PLS-KNN algorithm was established to differentiate cerebral infarction patients from controls, and an average accuracy of 100% was obtained. In conclusion, metabonomic approach is a powerful tool to investigate the pathogenesis of stroke and is expected to be developed as a useful method for the fast diagnosis.     

Application of comprehensive two-dimensional gas chromatography with time-of-flight mass spectrometry method to identify potential biomarkers of perinatal asphyxia in a non-human primate model

Perinatal asphyxia is a leading cause of brain injury in infants, occurring in 2-4 per 1000 live births. The clinical response to asphyxia is variable and difficult to predict with current diagnostic tests. Reliable biomarkers are needed to help predict the timing and severity of asphyxia, as well as response to treatment. Two-dimensional gas chromatography-time-of-flight-mass spectrometry (GC×GC-TOFMS) was used herein, in conjunction with chemometric data analysis approaches for metabolomic analysis in order to identify significant metabolites affected by birth asphyxia. Blood was drawn before and after 15 or 18 min of cord occlusion in a Macaca nemestrina model of perinatal asphyxia. Postnatal samples were drawn at 5 min of age (n=20 subjects). Metabolomic profiles of asphyxiated animals were compared to four controls delivered at comparable gestational age. Fifty metabolites with the greatest change pre- to post-asphyxia were identified and quantified. The metabolic profile of post-asphyxia samples showed marked variability compared to the pre-asphyxia samples. Fifteen of the 50 metabolites showed significant elevation in response to asphyxia, ten of which remained significant upon comparison to the control animals. This metabolomic analysis confirmed lactate and creatinine as markers of asphyxia and discovered new metabolites including succinic acid and malate (intermediates in the Krebs cycle) and arachidonic acid (a brain fatty acid and inflammatory marker) as potential biomarkers. GC×GC-TOFMS coupled with chemometric data analysis are useful tools to identify acute biomarkers of brain injury. Further study is needed to correlate these metabolites with severity of disease, and response to treatment.     

Anatomical and functional MR imaging in the macaque monkey using a vertical large-bore 7 Tesla setup

Functional magnetic resonance imaging (MRI) in the nonhuman primate promises to provide a much desired link between brain research in humans and the large body of systems neuroscience work in animals. We present here a novel high field, large-bore, vertical MR system (7 T/60 cm, 300 MHz), which was optimized for neuroscientific research in macaque monkeys. A strong magnetic field was applied to increase sensitivity and spatial resolution for both MRI and spectroscopy. Anatomical imaging with voxel sizes as small as 75×150×300 μm³ and with high contrast-to-noise ratios permitted the visualization of the characteristic lamination of some neocortical areas, e.g., Baillarger lines. Relaxation times were determined for different structures: at 7 T, T1 was 2.01/1.84/1.54 s in GM/GM-V1/WM, T2 was 59.1/54.4 ms in GM/WM and T2* was 29 ms. At 4.7 T, T1 was 25% shorter, T2 and T2* 18% longer compared to 7T. Spatiotemporally resolved blood-oxygen-level-dependent (BOLD) signal changes yielded robust activations and deactivations (negative BOLD), with average amplitudes of 4.1% and −2.4%, respectively. Finally, the first high-resolution (500 μm in-plane) images of cerebral blood flow in the anesthetized monkey are presented. On functional activation we observed flow increases of up to 38% (59 to 81 ml/100 g/min) in the primary visual cortex, V1. Compared to BOLD maps, functional CBF maps were found to be localized entirely within the gray matter, providing unequivocal evidence for high spatial specificity. The exquisite sensitivity of the system and the increased specificity of the hemodynamic signals promise further insights into the relationship of the latter to the underlying physiological activity.     

活体心肌缺血再灌自由基产生和清除的ESR研究

ESR和自旅捕捉技术用于研究活体动物犬心肌缺血再灌产生的自由基,PBN从冠状静脉血液中捕捉到了OH自由基,直接地证实了缺血再灌细胞膜损伤的活性氧自由基作用机制;实验还看到一种甾体皂甙药物具有保护心肌细胞,防止自由基损伤的功能.     

Possibility of Targeting Treatment for Ischemic Heart Disease With Liposome (Ⅰ)

This paper reports the basic research on the possibility of using targeting treatment for ischemic heart disease with liposome as drug carrier. Studies have been performed on isolated rat cardiomyocytes, or isolated perfused rat and rabbit hearts. Results show that cardiomyocytes may interact with liposome through fusion, endocytosis, adsorption and molecular exchange of phospholipid. Forms of cellular uptake of liposome depend chiefly on the physicochemical properties of liposomes. Anoxia changes the pattern of liposome uptake by cardiomyocytes and increases uptake of liposomes. Uptake of liposomes, especially of positively charged liposomes by ischemic myocardium is significantly increased. The quantity of increase of liposome uptake is in the following order: ischemia-reperfusion area>peripheral area of the infarct>non-ischemic area>infarcted area. The above results indicate that liposome as drug carrier might promote the delivery of drug into ischemic myocardium and cardiomyocytes.     

Kinetic distribution of paeoniflorin in cortex of normal and cerebral ischemia-reperfusion rats after intravenous administration of Paeoniae Radix extract

The time course of paeoniflorin in the cortex of normal and cerebral ischemia-reperfusion rats, following intravenous administration of Paeoniae Radix extract at a dose of 60 mg/kg of paeoniflorin, was determined using high-performance liquid chromatographic (HPLC) assay. The results showed that paeoniflorin could penetrate through the blood-brain barrier to reach the cortex, and that the injuries of ischemia-reperfusion could play an important role in pharmacokinetic process of paeoniflorin in the cortex after intravenous administration of Paeoniae Radix extract. The cortex concentrations of paeoniflorin in cerebral ischemia-reperfusion rats were lower 5 min after dosing and declined more slowly than that in normal control.     

Validation study of a pulsed arterial spin labeling technique by comparison to perfusion computed tomography

Abnormalities in cerebral blood flow (CBF) are believed to play a significant role in the development of major neonatal neuropathologies. One approach that would appear ideal for measuring CBF in this fragile age group is arterial spin labeling (ASL) since ASL techniques are noninvasive and quantitative. The purpose of this study was to assess the accuracy of a pulsed ASL method implemented on a 3-T scanner dedicated to neonatal imaging. Cerebral blood flow was measured in nine neonatal piglets, the ASL–CBF measurements were acquired at two inversion times (TI) (1200 and 1700 ms), and CBF was measured by perfusion computed tomography (pCT) for validation. Perfusion CT also provided images of cerebral blood volume, which were used to identify large blood vessels, and contrast arrival time, which were used to assess differences in arterial transit times between gray and white matter. Good agreement was found between gray matter CBF values from pCT (76±1 ml/min per 100 g) and ASL at TI=1700 ms (73±1 ml/min per 100 g). At TI=1200 ms, ASL overestimated CBF (91±2 ml/min per 100 g), which was attributed to substantial intravascular signal. No significant differences in white matter CBF from pCT and ASL were observed (average CBF=60±1 ml/min per 100 g), nor was there any difference in contrast arrival times for gray and white matter (0.95±0.04 and 0.99±0.03 s, respectively), which suggests that the arterial transit times for ASL were the same in this animal model. This study verified the accuracy of the implemented ASL technique and showed the value of using pCT to study other factors that can affect ASL–CBF measurements.     

Spectral-luminescent manifestation of the damaging action of brain ischemia on blood serum components

With the aid of spectral-luminescent analysis, our hypothesis on the determining role of free-radical oxidation in damage of blood serum components (low-density lipoproteins) in ischemia has been confirmed. An increase in the luminescence intensity of the blood serum of animals that suffered from brain ischemia as against that of healthy animals is registered. Lipoperoxide free-radical damage of phospholipids of the amphipathic layer of low-density lipoproteins after an ischemic procedure has also been confirmed by fluorescent probes (rhodamine 6G and Nile Blue). __________ Translated from Zhurnal Prikladnoi Spektroskopii, Vol. 72, No. 6, pp. 827–831, November–December, 2005.     

Measurement of polyunsaturated fatty acids of myocardial lipids by high performance liquid chromatography

Summary This report describes a modified method for the separation and analysis of polyunsaturated fatty acids such as 20:4, 20:5, and 22:6, using HPLC. The results show that these fatty acids are well separated from the saturated acids. Since the unsaturated fatty acids elute earlier than saturated acids, and this method does not require the fractionation of free fatty acids using thin layer chromatography, a necessary step for the gas chromatographic analysis, the recoveries of polyunsaturated fatty acids were significantly higher as compared to those from gas chromatography. Furthermore, HPLC and gas chromatographic methods gave identical results for the acyl chain composition of phosphatidylserine. The advantages of using HPLC over gas chromatography in determining the acyl chain composition of free fatty acids and phospholipids are also discussed.