MR diffusion tensor spectroscopy and imaging.

This paper describes a new NMR imaging modality--MR diffusion tensor imaging. It consists of estimating an effective diffusion tensor, Deff, within a voxel, and then displaying useful quantities derived from it. We show how the phenomenon of anisotropic diffusion of water (or metabolites) in anisotropic tissues, measured noninvasively by these NMR methods, is exploited to determine fiber tract orientation and mean particle displacements. Once Deff is estimated from a series of NMR pulsed-gradient, spin-echo experiments, a tissue's three orthotropic axes can be determined. They coincide with the eigenvectors of Deff, while the effective diffusivities along these orthotropic directions are the eigenvalues of Deff. Diffusion ellipsoids, constructed in each voxel from Deff, depict both these orthotropic axes and the mean diffusion distances in these directions. Moreover, the three scalar invariants of Deff, which are independent of the tissue's orientation in the laboratory frame of reference, reveal useful information about molecular mobility reflective of local microstructure and anatomy. Inherently tensors (like Deff) describing transport processes in anisotropic media contain new information within a macroscopic voxel that scalars (such as the apparent diffusivity, proton density, T1, and T2) do not.     

Transmural heterogeneity of diffusion anisotropy in the sheep myocardium characterized by MR diffusion tensor imaging

The orientation of MRI-measured diffusion tensor in the myocardium has been directly correlated to the tissue fiber direction and widely characterized. However, the scalar anisotropy indexes have mostly been assumed to be uniform throughout the myocardial wall. The present study examines the fractional anisotropy (FA) as a function of transmural depth and circumferential and longitudinal locations in the normal sheep cardiac left ventricle. Results indicate that FA remains relatively constant from the epicardium to the midwall and then decreases (25.7%) steadily toward the endocardium. The decrease of FA corresponds to 7.9% and 12.9% increases in the secondary and tertiary diffusion tensor diffusivities, respectively. The transmural location of the FA transition coincides with the location where myocardial fibers run exactly circumferentially. There is also a significant difference in the midwall-endocardium FA slope between the septum and the posterior or lateral left ventricular free wall. These findings are consistent with the cellular microstructure from histological studies of the myocardium and suggest a role for MR diffusion tensor imaging in characterization of not only fiber orientation but, also, other tissue parameters, such as the extracellular volume fraction.     

Study of water migration by micro MR imaging

Magnetic Resonance (MR) microscopy is a noninvasive tool that enables high resolution imaging of water concentration in non-magnetic materials. In this study, water migration in a dense porous material (dental cement) was monitored by 1D MR microscopy. The measured concentration profiles were later analyzed via three different migration models: an imbibition model, a diffusion model and a combined model. From the best fit to the experimental data, model parameters were obtained.     

Real-time measurement of nitric oxide by luminol-hydrogen peroxide reaction in crystalloid perfused rat heart

The objective of this study was to develop an assay system that allows continuous monitoring of nitric oxide (NO) released from crystalloid perfused hearts. We utilized chemiluminescence reaction between NO and luminol-H(2)O(2) to quantify the NO level in coronary effluent. Isolated rat hearts were subjected to ordinary Langendorff's perfusion, and the right ventricle was cannulated to sample coronary effluent. After equilibration, the coronary flow rate was set constant and the hearts were paced at 300 bpm. Coronary effluent was continuously sampled and mixed with the chemiluminescent probe containing 0.018 mmol/l luminol plus 10 mmol/l H(2)O(2). Chemiluminescence from the mixture of coronary effluent and the probe was continuously measured. NO concentration was calibrated by various concentrations (0.5-400 pmol/l) of standard NO solution. The lower detection limit of NO was 1 pmol/l. Basal NO release from isolated perfused rat heart was 0.41 +/- 0.17 pmol/min/g of heart weight, and that was significantly suppressed by 0.1 mmol/l of L-NAME to 0.18 +/- 0.10 pmol/min/g of heart weight (n = 7). Application of 0.1 and 0.3 micromol/l acetylcholine increased NO level in the coronary effluent, in a concentration-dependent manner, from 6.6 +/- 1.7 in a baseline condition to 16.3 +/- 7.4 and 30.3 +/- 16.1 pmol/l at each peak, respectively. Thrombin at 1 and 10 U/ml also increased NO level from 17.6 +/- 4.3 in control to 35.5 +/- 10.4 and 48.7 +/- 8.7 pmol/l at each peak, respectively (n = 7). Thus, this assay system is applicable to the continuous real-time measurement of NO released from crystalloid perfused hearts, and it may be useful for the study of physiological or pathophysiological role of NO in coronary circulation.     

Pseudoketogenesis in the perfused rat heart

Ketogenesis is usually measured in vivo by dilution of tracers of (3R)-hydroxybutyrate or acetoacetate. We show that, in perfused working rat hearts, the specific activities of (3R)-hydroxybutyrate and acetoacetate are diluted by isotopic exchanges in the absence of net ketogenesis. We call this process pseudoketogenesis. When hearts are perfused with buffer containing 2.3 mM of [4-3H]- plus [3-14C]acetoacetate, the specific activities of [4-3H] and [3-14C]acetoacetate decrease while C-1 of acetoacetate becomes progressively labeled with 14C. This is explained by the reversibility of reactions catalyzed by mitochondrial 3-oxoacid-CoA transferase and acetoacetyl-CoA thiolase. After activation of labeled acetoacetate, the specific activity of acetoacetyl-CoA is diluted by unlabeled acetoacetyl-CoA derived from endogenous fatty acids or glucose. Acetoacetyl-CoA thiolase partially exchanges 14C between C-1 and C-3 of acetoacetyl-CoA. Finally, 3-oxoacid-CoA transferase liberates weakly labeled acetoacetate which dilutes the specific activity of extracellular acetoacetate. An isotopic exchange in the reverse direction is observed when hearts are perfused with unlabeled acetoacetate plus [1-14C]-, [13-14C]-, or [15-14C]palmitate; here also, acetoacetate becomes labeled on C-1 and C-3. Computations of specific activities of (3R)-hydroxybutyrate, acetoacetate, and acetyl-CoA yield minimal rates of pseudoketogenesis ranging from 19 to 32% of the net uptake of (3R)-hydroxybutyrate plus acetoacetate by the heart.     

Validation of Bayesian analysis of compartmental kinetic models in medical imaging

IntroductionKinetic compartmental analysis is frequently used to compute physiologically relevant quantitative values from time series of images. In this paper, a new approach based on Bayesian analysis to obtain information about these parameters is presented and validated.Materials and methodsThe closed-form of the posterior distribution of kinetic parameters is derived with a hierarchical prior to model the standard deviation of normally distributed noise. Markov chain Monte Carlo methods are used for numerical estimation of the posterior distribution. Computer simulations of the kinetics of F18-fluorodeoxyglucose (FDG) are used to demonstrate drawing statistical inferences about kinetic parameters and to validate the theory and implementation. Additionally, point estimates of kinetic parameters and covariance of those estimates are determined using the classical non-linear least squares approach.Results and discussionPosteriors obtained using methods proposed in this work are accurate as no significant deviation from the expected shape of the posterior was found (one-sided P > 0.08). It is demonstrated that the results obtained by the standard non-linear least-square methods fail to provide accurate estimation of uncertainty for the same data set (P < 0.0001).ConclusionsThe results of this work validate new methods for a computer simulations of FDG kinetics. Results show that in situations where the classical approach fails in accurate estimation of uncertainty, Bayesian estimation provides an accurate information about the uncertainties in the parameters. Although a particular example of FDG kinetics was used in the paper, the methods can be extended for different pharmaceuticals and imaging modalities.     

Importance of intracellular water apparent diffusion to the measurement of membrane permeability

The exchange of water across biological membranes is of fundamental significance to both animal and plant physiology. Diffusional membrane permeability (P(d)) for the Xenopus oocyte, an important model system for water channel investigation, is typically calculated from intracellular water pre-exchange lifetime, cell volume, and cell surface area. There is debate, however, whether intracellular water motion affects water lifetime, and thereby P(d). Mathematical modeling of water transport is problematic because the intracellular water diffusion rate constant (D) for cells is usually unknown. The measured permeability may be referred to as the apparent diffusional permeability, P, to acknowledge this potential error. Herein, we show that magnetic resonance (MR) spectroscopy can be used to measure oocyte water exchange with greater temporal resolution and higher signal-to-noise ratio than other methods. MR imaging can be used to assess both oocyte geometry and intracellular water diffusion for the same single cells. MR imaging is used to confirm the dependence of intracellular water lifetime on intracellular diffusion. A model is presented to relate intracellular lifetime to true membrane diffusional permeability. True water diffusional permeability (2.7 +/- 0.4 microm/s) is shown to be 39 +/- 6% greater than apparent diffusional permeability for 8 oocytes. This discrepancy increases with cell size and permeability (such as after water channel expression) and decreases with increasing intracellular water D.     

磁共振弥散加权成像在兔良恶性淋巴结鉴别中的价值

目的:采用动物模型研究MR弥散加权成像评价转移性淋巴结与反应增生性淋巴结的价值。方法:24只新西兰兔随机分成两组,分别制作转移性淋巴结与反应增生性淋巴结模型,比较两组淋巴结的表观弥散系数(ADC),同时在DWI图上测量并比较两组淋巴结与肌肉的相对信号强度,并进行病理结果分析。结果:两组淋巴结的DWI相对信号强度无显著性差异(P>0.05)。转移性淋巴结组ADC值大于反应性增生组ADC值,分别为0.82±0.10×10-3mm2/s和1.17±0.14×10-3mm2/s,差异有统计学意义(P<0.05)。结论:MR弥散加权成像ADC值测量有助于转移性淋巴结与反应增生性淋巴结的鉴别     

Vasoconstrictor-mediated thermogenesis present in perfused skeletal muscle but absent from perfused heart

Resting muscle thermogenesis as controlled by vasocontrictors was compared in rat hindlimb and cardiac muscle. An α-adrenergic agonist combination of phenylephrine+atenolol increased oxygen uptake and perfusion pressure in the constant flow hindlimb and neither increase was blocked by 10 μM tetrodotoxin. The same adrenergic combination also increased oxygen uptake and perfusion pressure in the perfused heart but the former along with beating was completely blocked by tetrodotoxin. Vasoconstriction by phenylephrine occurs in the heart but is not linked to thermogenic increases as in hindlimb, implying that all metabolic energy in heart is conserved for contractile activity. The findings highlight a fundamental difference between skeletal and cardiac muscle.     

Changes in water status and water distribution in maturing lupin seeds studied by MR imaging and NMR spectroscopy

The changes in water distribution in maturing lupin (Lupinus luteus L.) seeds were visualized with magnetic resonance imaging (MRI). MRI data showed local inhomogeneities of water distribution inside the seed. At the late seed-filling stage the most intense signal was detected in the seed coat and the outer parts of cotyledons in the hilum area, but during maturation drying the decline in MR image intensity was faster in the outer part of the seed than in the central part. The changes in water status were characterized by NMR spectroscopy. Analyses of T(2) relaxation times revealed a three-component water proton system in maturing lupin seeds. Three populations of protons found during seed maturation, each with a different magnetic environment causing a different relaxation rate, were correlated with three fractions of water (structural, intracellular, and extracellular) that were observed during seed germination. This study provides evidence that lupin seeds have similar states of the different water components with regard to seed moisture content at two distinct physiological stages, seed maturation and germination. The unique feature of maturing lupin seeds is the presence of the high (1)H-NMR signal in areas corresponding to the vascular bundles. Tissue localization of dehydrins showed the presence of dehydrin protein in the area of vascular tissue. An anti-dehydrin antibody detected three polypeptides in lupin embryos with molecular masses of 73, 43 and 28 kDa, respectively. The temporal pattern of dehydrin protein accumulation correlates well with seed desiccation.     

Fatty acid chain-elongation in perfused rat heart: synthesis of stearoylcarnitine from perfused palmitate

Rat hearts perfused for up to 60 min in the working mode with palmitate, but not with glucose, resulted in substantial formation of palmitoylcarnitine and stearoylcarnitine. To test whether lipolysis of endogenous lipids was responsible for the increased stearoylcarnitine content or whether some of the perfused palmitate underwent chain elongation, hearts were perfused with hexadecanoic-16,16,16-d(3) acid (M+3). The pentafluorophenacyl ester of deuterium labeled stearoylcarnitine had an M+3 (639.4 m/z) compared to the unlabeled M+0 (636.3 m/z) consistent with a direct chain elongation of the perfused palmitate. Furthermore, the near equal isotope enrichment of palmitoyl- (90.2+/-5.8%) and stearoylcarnitine (78.0+/-7.1%) suggest that both palmitoyl- and stearoyl-CoA have ready access to mitochondrial carnitine palmitoyltransferase and that most of the stearoylcarnitine is derived from the perfused palmitate.