Simple measurement of gluconeogenesis by direct 2H NMR analysis of menthol glucuronide enrichment from 2H2O.

The contribution of gluconeogenesis to fasting glucose production was determined by a simple measurement of urinary menthol glucuronide (MG) 2H enrichment from 2H2O. Following ingestion of 2H2O (0.5% body water) during an overnight fast and a pharmacological dose (400 mg) of a commercial peppermint oil preparation the next morning, 364 micromol MG was quantitatively recovered from a 2-h urine collection by ether extraction and a 125 micromol portion was directly analyzed by 2H NMR. The glucuronide 2H-signals were fully resolved and their relative intensities matched those of the monoacetone glucose derivative. The pharmacokinetics and yields of urinary MG after ingestion of 400 mg peppermint oil as either gelatin or enteric-coated capsules 1 h before breakfast were quantified in five healthy subjects. Gelatin capsules yielded 197 +/- 81 micromol of MG from the initial 2-h urine collection while enteric-coated capsules gave 238 +/- 84 micromol MG from the 2- to 4-h urine collection.     

Quantifying endogenous glucose production and contributing source fluxes from a single 2H NMR spectrum

Endogenous glucose production (EGP), gluconeogenic and glycogenolytic fluxes by analysis of a single ²H‐NMR spectrum is demonstrated with 6‐hr and 24‐hr fasted rats. Animals were administered [1‐²H, 1‐¹³C]glucose, a novel tracer of glucose turnover, and ²H₂O. Plasma glucose enrichment from both tracers was quantified by ²H‐NMR analysis of monoacetone glucose. The 6‐hr fasted group (n = 7) had EGP rates of 95.6 ± 13.3 μmol/kg/min, where 56.2 ± 7.9 μmol/kg/min were derived from PEP; 12.1 ± 2.1 μmol/kg/min from glycerol, and 32.1 ± 4.9 μmol/kg/min from glycogen. The 24‐hr fasted group (n = 7) had significantly lower EGP rates (52.8 ± 7.2 μmol/kg/min, P = 0.004 vs. 6 hr) mediated by a significantly reduced contribution from glycogen (4.7 ± 5.9 μmol/kg/min, P = 0.02 vs. 6 hr) while PEP and glycerol contributions were not significantly different (39.5 ± 3.9 and 8.5 ± 1.2 μmol/kg/min, respectively). These estimates agree with previous assays of EGP fluxes in fasted rats obtained by multinuclear NMR analyses of plasma glucose enrichment from ²H₂O and ¹³C‐glucose tracers. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.     

Sources of hepatic glucose production by 2H2O ingestion and Bayesian analysis of 2H glucuronide enrichment

The contribution of gluconeogenesis to hepatic glucose production (GP) was quantified after ²H₂O ingestion by Bayesian analysis of the position 2 and 5 ²H‐NMR signals (H2 and H5) of monoacetone glucose (MAG) derived from urinary acetaminophen glucuronide. Six controls and 10 kidney transplant (KTx) patients with cyclosporine A (CsA) immunosuppressant therapy were studied. Seven KTx patients were lean and euglycemic (BMI = 24.3 ± 1.0 kg/m²; fasting glucose = 4.7 ± 0.1 mM) while three were obese and hyperglycemic (BMI = 30.5 ± 0.7 kg/m²; fasting glucose = 7.1 ± 0.5 mM). For the 16 spectra analyzed, the mean coefficient of variation for the gluconeogenesis contribution was 10% ± 5%. This uncertainty was associated with a mean signal‐to‐noise ratio (SNR) of 79:1 and 45:1 for the MAG H2 and H5 signals, respectively. For control subjects, gluconeogenesis contributed 54% ± 7% of GP as determined by the mean and standard deviation (SD) of individual Bayesian analyses. For the lean/normoglycemic KTx subjects, the gluconeogenic contribution to GP was 62% ± 7% (P = 0.06 vs. controls), while hyperglycemic/obese KTx patients had a gluconeogenic contribution of 68% ± 3% (P < 0.005 vs. controls). These data suggest that in KTx patients, an increased gluconeogenic contribution to GP is strongly associated with obesity and hyperglycemia. Magn Reson Med 60:517–523, 2008. © 2008 Wiley‐Liss, Inc.     

A fatal clomipramine intoxication case of a chronic alcoholic patient: application of postmortem hair analysis method of clomipramine and ethyl glucuronide using LC/APCI/MS

Toxicological investigations of postmortem specimens of a 26-year-old man were performed with the use of LC/APCI/MS. They revealed in the blood of the deceased clomipramine (9.49 microg/g) and its main metabolite norclomipramine (1.10 microg/g) at concentrations explaining the fatal outcome. The presence of these xenobiotics in a 12-cm-long strand of hair (clomipramine, 7.60 ng/mg in I segment; 4.19 ng/mg in II segment; 1.86 ng/mg in III segment; norclomipramine, 5.71 ng/mg in I segment; 9.71 ng/mg in II segment; 4.13 ng/mg in III segment) confirmed the fact obtained from the medical history that the deceased had been receiving clomipramine as an antidepressant for 1 year prior to his death. The analysis demonstrated ethanol in autopsy blood (2.5mg/ml) and urine (3.2mg/ml); ethyl glucuronide as a marker of chronic alcohol abuse was detected in the deceased's hair (0.44 ng/mg in I segment; 0.07 ng/mg in II segment; n.d. in III segment). These findings may suggest the contribution of alcohol in the mechanism of drug-ethanol interaction, which in consequence might have affected the biotransformation of clomipramine in the final period of his life and evoked the ultimate toxic effect.     

Reproducibility of cerebral glucose utilization measured by PET and the [18F]-2-fluoro-2-deoxy-d-glucose method in resting,healthy human subjects

The stability of cerebral glucose utilization was examined in nine right-handed, healthy men (age, 24.88±2.93 years) using positron emission tomography (PET) and the [¹⁸F]-fluorodeoxyglucose (FDG) method. Each study was run twice at intervals of 1–12 weeks with the subject at rest. The average cerebral metabolic rate for glucose (CMRGlu) was 5.40±0.71 mg/100 g per min (coefficient of variance, 13.08). The average intraindividual variation of CMRGlu was 7.91%±15.46% (P=0.13). Metabolic indices (MI: regional/mean cortical CMRGlu) were used to determine the regional cerebral metabolic distribution. The interindividual (coefficient of variance, 7.13) and intraindividual variabilities (average variation, –0.12%±8.76%) of MI were smaller than those of metabolic rates. No reproducible significant asymmetry was observed. The FDG method used with subjects at rest thus yields low intraindividual variability of both cerebral glucose consumption and regional metabolic distribution, even at an interval of several weeks. Cerebral glucose utilization measured under such conditions may act as a reliable reference for determination of the influences of physiological (activation), pharmacological or pathological processes on cerebral glucose metabolism.Abbreviations FDG [¹⁸F]-fluorodeoxyglucose - CMRGlu cerebral metabolic rates for glucose - MI metabolic indices - EEG electroencephalogram - FWHM full width at half maximum     

健康及空腹血糖受损人群中平均血小板体积研究

目的探讨平均血小板体积(MPV)在不同血糖状态人群中的分布情况及临床意义。方法对2015年6-12月在中国医科大学附属第一医院体检中心进行健康体检的1 342名体检者的资料进行回顾性分析,详细记录其一般资料和临床生化指标。根据空腹血糖(FPG)水平,分为血糖正常组、空腹血糖受损组(IFG组)和糖尿病组。对3组研究对象的FPG和MPV水平进行分析。结果 MPV值随FPG水平升高而升高,糖尿病组的MPV值显著高于IFG组和血糖正常组,IFG组MPV值明显高于血糖正常组,差异均有统计学意义(P<0.05)。MPV值与3组的FPG水平相关,且多因素分析结果显示,MPV与FPG在各组均有独立的相关性。结论 MPV水平在不同FPG水平人群中表达存在显著差异。因此,可以通过降低MPV值,减少糖尿病并发症的发病风险,提高人群生命质量。     

Reproducibility of cerebral glucose utilization measured by PET and the [18F]-2-fluoro-2-deoxy-d-glucose method in resting, healthy human subjects

The stability of cerebral glucose utilization was examined in nine right-handed, healthy men (age, 24.88 +/- 2.93 years) using positron emission tomography (PET) and the [18F]-fluorodeoxglucose (FDG) method. Each study was run twice at intervals of 1-12 weeks with the subject at rest. The average cerebral metabolic rate for glucose (CMRGlu) was 5.40 +/- 0.71 mg/100 g per min (coefficient of variance, 13.08). The average intraindividual variation of CMRGlu was 7.91% +/- 15.46% (P = 0.13). Metabolic indices (MI: regional/mean cortical CMRGlu) were used to determine the regional cerebral metabolic distribution. The interindividual (coefficient of variance, 7.13) and intraindividual variabilities (average variation, -0.12% +/- 8.76%) of MI were smaller than those of metabolic rates. No reproducible significant asymmetry was observed. The FDG method used with subjects at rest thus yields low intraindividual variability of both cerebral glucose consumption and regional metabolic distribution, even at an interval of several weeks. Cerebral glucose utilization measured under such conditions may act as a reliable reference for determination of the influences of physiological (activation), pharmacological or pathological processes on cerebral glucose metabolism.     

Three‐point dixon method enables whole‐body water and fat imaging of obese subjects

Dixon imaging techniques derive chemical shift‐separated water and fat images, enabling the quantification of fat content and forming an alternative to fat suppression. Whole‐body Dixon imaging is of interest in studies of obesity and the metabolic syndrome, and possibly in oncology. A three‐point Dixon method is proposed where two solutions are found analytically in each voxel. The true solution is identified by a multiseed three‐dimensional region‐growing scheme with a dynamic path, allowing confident regions to be solved before unconfident regions, such as background noise. 2π‐Phase unwrapping is not required. Whole‐body datasets (256 × 184 × 252 voxels) were collected from 39 subjects (body mass index 19.8‐45.4 kg/m²), in a mean scan time of 5 min 15 sec. Water and fat images were reconstructed offline, using the proposed method and two reference methods. The resulting images were subjectively graded on a four‐grade scale by two radiologists, blinded to the method used. The proposed method was found superior to the reference methods. It exclusively received the two highest grades, implying that only mild reconstruction failures were found. The computation time for a whole‐body dataset was 1 min 51.5 sec ± 3.0 sec. It was concluded that whole‐body water and fat imaging is feasible even for obese subjects, using the proposed method. Magn Reson Med 63:1659–1668, 2010. © 2010 Wiley‐Liss, Inc.     

Fat and water separation in balanced steady-state free precession using the Dixon method.

In this work the feasibility of separating fat and water signals using the balanced steady-state free precession (SSFP) technique is demonstrated. The technique is based on the observation (Scheffler and Hennig, Magnetic Resonance in Medicine 2003;49:395-397) that at the nominal values of TE = TR/2 in SSFP imaging, phase coherence can be achieved at essentially only two orientations (0 degrees and 180 degrees ) relative to the RF pulses in the rotating frame, under the assumption of TR < T2, and independently of the SSFP angle. This property allows in-phase and out-of-phase SSFP images to be obtained by proper choices of the center frequency offset, and thus allows the Dixon subtraction method to be utilized for effective fat-water separation. The TR and frequency offset for optimal fat-water separation are derived from theories. Experimental results from healthy subjects, using a 3.0 Tesla system, show that nearly complete fat suppression can be accomplished.     

Impact of transvascular and cellular–interstitial water exchange on dynamic contrast‐enhanced magnetic resonance imaging estimates of blood to tissue transfer constant and blood plasma volume

Purpose:

To examine the effect of transvascular (k_be) and cellular–interstitial water protons exchange (k_ie) in estimates of the blood‐to‐tissue contrast agent transfer rate constant (K^trans), interstitial volume fraction (v_e), and blood plasma volume fraction (v_p) using a full three‐site two exchange (3S2X) model.

Materials and Methods:

Using the Bloch‐McConnell equations, magnetic resonance imaging (MRI) signal arising from a 3S2X system was derived for the T₁‐weighted spoiled gradient‐recalled echo (SPGR) pulse sequence. To model the effects of k_be and k_ie on estimates of R₁, the MRI‐measured arterial input function, the different sets of values of kinetic parameters: K^trans, v_e, and v_p and water protons exchange rates, k_be and k_ie, were used. To calculate the tissue water protons R₁, the signal evolving from a 3S2X model was set to a monoexponential function. By comparing the estimated K^trans, v_e, and v_p with their simulated model truth values, the impact of k_be and k_ie on K^trans, v_e, and v_p was evaluated.

Results:

v_p was strongly underestimated and K^trans and v_e were much less influenced by k_be, when k_ie was held constant. When k_be was held constant, the k_ie had a significant effect on K^trans and v_e and less effect on v_p.

Conclusion:

The full 3S2X model allows accurate estimation of K^trans, v_e, and v_p and rates of water proton exchange. J. Magn. Reson. Imaging 2013;37:435–444. © 2012 Wiley Periodicals, Inc.     

A simple method for measuring glucose utilization of insulin-sensitive tissues by using the brain as a reference

A simple method, without measurement of the plasma input function, to obtain semiquantitative values of glucose utilization in tissues other than the brain with radioactive deoxyglucose is reported. The brain, in which glucose utilization is essentially insensitive to plasma glucose and insulin concentrations, was used as an internal reference. The effects of graded doses of oral glucose loading (0.5, 1 and 2 mg/g body weight) on insulin-sensitive tissues (heart, muscle and fat tissue) were studied in the rat. By using the brain-reference method, dose-dependent increases in glucose utilization were clearly shown in all the insulin-sensitive tissues examined. The method seems to be of value for measurement of glucose utilization using radioactive deoxyglucose and positron emission tomography in the heart or other insulin-sensitive tissues, especially during glucose loading.     

水中主要毒剂GC／MS／SIM方法的研究

目的：建立同时分析水中７种主要毒剂沙林、梭曼，塔崩，ＧＦ，Ｖｘ、俄罗斯Ｖｘ和芥子气的气－质联用选择离子监测（ＧＳ／ＭＳ／ＳＩＭ）分析方法。为饮用水样的毒剂检测提供切实可行的分析手段。     

New method for the simultaneous detection of metabolites and water in localized in vivo 1H nuclear magnetic resonance spectroscopy.

A new two-scan method for localized 1H in vivo NMR spectroscopy (MRS) without water suppression (WS) is described. In one of the scans, two chemical shift selective 180 degrees pulses are applied prior to a standard localization sequence to invert all metabolite signals upfield and downfield from water, which remains unaffected. The difference spectrum records the metabolites whereas water and accompanying gradient induced artifacts are widely suppressed. The method was implemented on a 4.7-T system using point resolved spectroscopy with a short echo time of 18 ms. Phantom measurements proved the feasibility of absolute quantification using water as an internal reference. Measurements on healthy rat brain yielded comparable spectrum quality as measurements with water presaturation. The method does not require additional adjustments or sophisticated data postprocessing and scales favorably with increasing B(0) field. Therefore, the method should be useful for 1H MRS without WS. Although the two-step method doubles the minimum total measurement time, it may also be of interest for spectroscopic imaging (SI) without WS, in particular if fast SI techniques are applied.     

Fast decomposition of water and lipid using a GRASE technique with the IDEAL algorithm.

Three-point Dixon techniques achieve good lipid-water separation by estimating the phase due to field inhomogeneities. Recently it was demonstrated that the combination of an iterative algorithm (iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL)) with a fast spin-echo (FSE) three-point Dixon method yielded robust lipid-water decomposition. As an alternative to FSE, the gradient- and spin-echo (GRASE) technique has been developed for efficient data collection. In this work we present a method for lipid-water separation by combining IDEAL with the GRASE technique. An approach to correct for errors in the lipid-water decomposition caused by phase distortions due to the switching of the readout gradient polarities inherent to GRASE is presented. The IDEAL-GRASE technique is demonstrated in phantoms and in vivo for various applications, including pelvic, musculoskeletal, and (breath-hold) cardiac imaging.     

Proximal pulmonary artery blood flow characteristics in healthy subjects measured in an upright posture using MRI: the effects of exercise and age

PURPOSE: To use MRI to quantify blood flow conditions in the proximal pulmonary arteries of healthy children and adults at rest and during exercise in an upright posture. MATERIALS AND METHODS: Cine phase-contrast MRI was used to calculate mean flow and reverse flow index (RFI) in the main (MPA), right (RPA), and left (LPA) pulmonary arteries in healthy children and adults in an open-MRI magnet equipped with an upright MRI-compatible ergometer. RESULTS: From rest to exercise (150% resting heart rate), blood flow (liters/minute/m2) increased in the RPA (1.4+/-0.3 vs. 2.5+/-0.4; P<0.001), LPA (1.1+/-0.3 vs. 2.2+/-0.6; P<0.001), and MPA (2.7+/-0.5 vs. 4.9+/-0.5; P<0.001). RFI decreased in the LPA (0.040+/-0.030 vs. 0.017+/-0.018; P<0.02) and MPA (0.025+/-0.024 vs. 0.008+/-0.007; P<0.03). Adults experienced greater retrograde flow in the MPA than the children (0.042+/-0.029 vs. 0.014+/-0.012; P<0.02). CONCLUSION: It appears that at both rest and during exercise, in children and adults alike, RPA/LPA mean blood flow distribution is predominantly determined by distal vascular resistance, while retrograde flow is affected by proximal pulmonary bifurcation geometry.     

用高效液相色谱法同时测定血浆中苯妥英和卡马西平的浓度

建立了快速测定血浆或全血中苯妥英及卡马西平浓度的高效液相色谱（ＨＰＬＣ）法。样品经乙酸乙酯一步提取，用ＳｐｈｅｒｉｓｏｒｂＣ１８柱分析，流动相为甲醇一水一四氢呋喃（４５：５５：５，ｖ：ｖ：ｖ），二级管阵列检测器（ＤＡＤ）检测波长２１０±２ ｎｍ。本方法快速简便，有较好的精密度（ＲＳＤ苯妥英 １．９％～８．６％；卡马西平 ２．１％～ ７．８％）和较宽的线性范围（苯妥英 ０．４～ ４０．０ μｇ／ ｍｌ；卡马西平 ０．２～２０．０ μｇ／ ｍｌ），适合于临床血药浓度的监测和药代动力学的研究。     

Interleaved acquisition of lipid and water images of the heart using a double-inversion fast spin-echo method.

In this work we present a new method for the improved detection of lipid infiltration in the heart. The method employs a double-inversion fast spin-echo technique where the acquisition of water- and lipid-suppressed k-space data is alternated between TR periods to produce co-registered lipid and water images from data acquired in a breath hold. The lipid and water images can then be combined to generate a lipid/water image with reduced artifacts due to flow and excellent contrast between lipid and myocardium. The method is demonstrated in ex vivo tissue and in vivo. This novel method may improve the detection of lipid infiltration in the heart in pathologies such as arrhythmogenic right ventricular dysplasia.