Imaging focal reperfusion injury following global ischemia with diffusion-weighted magnetic resonance imaging and 1H-Magnetic Resonance Spectroscopy

The purpose of the study was to determine whether diffusion-weighted magnetic resonance imaging (DWI) could identify focal lesions that develop in ischemia-sensitive cerebral tissues during reperfusion following global brain ischemia. Localized ¹H-Magnetic Resonance Spectroscopy (¹H-MRS) measurements were also obtained to determine whether abnormal spectroscopic markers were associated with focal lesions and to define time correlations between DWI and metabolic changes. Brain diffusion-weighted magnetic resonance imaging measurements were made in a cat model of repetitive global cerebral ischemia and reperfusion. Five animals were exposed to three episodes of 10 min vascular occlusions at hourly intervals. Three animals were evaluated as controls. DWI, T2WI, and ¹H-MRS data were acquired for up to 12 h. Transient focal DWI hyperintensity was detected in the hippocampus, basal ganglia, and cortical watershed areas. These focal abnormalities usually appeared during the final reperfusion and eventually spread to encompass all of the gray matter. Spectroscopic measurements demonstrated the expected elevation of the lactate signal intensity during vessel occlusion, which returned to normal during early reperfusion. A subsequent rise in the lactate signal occurred approximately 3–4 h after the beginning of the third reperfusion. This late lactate elevation occurred after focal hyperintensities were identified by DWI. No significant signal changes were seen in spectroscopic metabolites other than lactate. The study illustrates that DWI and ¹H-MRS are sensitive to focal cerebral lesions that occur during reperfusion following global cerebral ischemia.     

In vivo measurement of normal rat intracellular pyruvate and lactate levels after injection of hyperpolarized [1-(13)C]alanine

Hyperpolarized technology utilizing dynamic nuclear polarization has enabled rapid and high-sensitivity measurements of ¹³C metabolism in vivo. The most commonly used in vivo agent for hyperpolarized ¹³C metabolic imaging thus far has been [1-¹³C]pyruvate. In preclinical studies, not only is its uptake detected, but also its intracellular enzymatic conversion to metabolic products including [1-¹³C]lactate and [1-¹³C]alanine. However, the ratio of ¹³C-lactate/¹³C-pyruvate measured in this data does not accurately reflect cellular values since much of the [1-¹³C]pyruvate is extracellular depending on timing, vascular properties, and extracellular space and monocarboxylate transporter activity. In order to measure the relative levels of intracellular pyruvate and lactate, in this project we hyperpolarized [1-¹³C]alanine and monitored the in vivo conversion to [1-¹³C]pyruvate and then the subsequent conversion to [1-¹³C]lactate. The intracellular lactate-to-pyruvate ratio of normal rat tissue measured with hyperpolarized [1-¹³C]alanine was 4.89±0.61 (mean±S.E.) as opposed to a ratio of 0.41±0.03 when hyperpolarized [1-¹³C]pyruvate was injected.     

In vivo C magnetic resonance spectroscopy of a human brain tumor after application of C-1-enriched glucose

Objectives

As a unique tool to assess metabolic fluxes noninvasively, ¹³C magnetic resonance spectroscopy (MRS) could help to characterize and understand malignancy in human tumors. However, its low sensitivity has hampered applications in patients. The aim of this study was to demonstrate that with sensitivity-optimized localized ¹³C MRS and intravenous infusion of [1-¹³C]glucose under euglycemia, it is possible to assess the dynamic conversion of glucose into its metabolic products in vivo in human glioma tissue.

Materials and Methods

Measurements were done at 3 T with a broadband single RF channel and a quadrature ¹³C surface coil inserted in a ¹H volume coil. A ¹H/¹³C polarization transfer sequence was applied, modified for localized acquisition, alternatively in two (50 ml) voxels, one encompassing the tumor and the other normal brain tissue.

Results

After about 20 min of [1-¹³C]glucose infusion, a [3-¹³C]lactate signal appeared among several resonances of metabolic products of glucose in MR spectra of the tumor voxel. The resonance of [3-¹³C]lactate was absent in MR spectra from contralateral tissue. In addition, the intensity of [1-¹³C]glucose signals in the tumor area was about 50% higher than that in normal tissue, likely reflecting more glucose in extracellular space due to a defective blood–brain barrier. The signal intensity for metabolites produced in or via the tricarboxylic acid (TCA) cycle was lower in the tumor than in the contralateral area, albeit that the ratios of isotopomer signals were comparable.

Conclusion

With an improved ¹³C MRS approach, the uptake of glucose and its conversion into metabolites such as lactate can be monitored noninvasively in vivo in human brain tumors. This opens the way to assessing metabolic activity in human tumor tissue.     

In vivo lactate editing in single voxel proton spectroscopy and proton spectroscopic imaging by homonuclear polarisation transfer

Volume-selective lactate editing has been performed successfully in vitro and in vivo in the brain on a clinical scanner using a PRESS-based single voxel ¹H spectroscopy and a ¹H spectroscopic imaging sequence. The PRESS sequence was made sensitive to homonuclear polarisation by replacing the standard 180° refocusing pulses with 90° pulses. Two acquisitions were made at a total echo time around 2/J (J is the coupling constant for CH and CH₃ spins in lactate ≈7 Hz) whose individual echo times differed by 5.5 ms. Subtraction of one signal from the other yielded the lactate resonance alone. The technique is an effective method of separating the overlapping signals of lactate and lipids. Furthermore this editing method can be performed without state of the art MRI scanner hardware.     

Therapeutic efficacy of a case of pyruvate dehydrogenase complex deficiency monitored by localized proton magnetic resonance spectroscopy

We experienced a case of pyruvate dehydrogenase deficiency observed by proton magnetic resonance spectroscopy(¹H MRS). This case was diagnosed as West syndrome by characteristic convulsion and the periodic hypsarrhythmia pattern of EEG. At the age of 11 months, the first examination of ¹H MRS revealed a high peak of lactate, and the high concentration of lactate and pyruvate was confirmed in sampled cerebrospinal fluid (CSF). Deficiency of pyruvate dehydrogenase complex was finally diagnosed by genetic examination. Dichloroacetate was administered to the patient as therapy. Decrease of lactate in the brain was found by ¹H MRS. Lactate and pyruvate in the CSF was also decreased. In accordance with the suspension of dichloroacetate, increase of lactate in the brain was detected and the convulsions reappeared. After readministration of dichloroacetate, the patient was almost symptom free and lactate in the brain and CSF had decreased to the normal extent. We considered that ¹H MRS provides useful information for screening metabolic disorders of infants and assessing the efficacy of therapy.     

Raman investigations of Zn1−xCoxO nanocrystals: role of starting precursors on vibrational properties

The Raman spectra of sol–gel derived Co‐doped ZnO nanoparticles (NPs) in the spectral range 100–1500 cm⁻¹ were investigated. In the sol–gel method, three different series of Co‐doped ZnO particles, i.e. Zn_1−xCo_xO (x = 0.05, 0.10, 0.15, and 0.20), were obtained using three different starting precursors, viz. cobalt chloride hexahydrate, cobalt acetate tetrahydrate, and cobalt nitrate hexahydrate, respectively. It has been observed that cobalt acetate is a better precursor in comparison to cobalt chloride and cobalt nitrate to obtain single‐phase Co‐doped ZnO NPs. As for cobalt acetate‐derived NPs, no hidden secondary phase of Co₃O₄ was observed for the lower (x = 0.05) Co concentration. The Fröhlich interaction associated with the longitudinal modes was found to be destroyed with increasing Co concentration due to structural disorder and defects induced by the dopant. In addition to ZnO and Co₃O₄ vibrational modes, a few additional modes near 550 and 715 cm⁻¹ were also observed in all cases, which could be attributed to the modes due to Co doping in ZnO. Copyright © 2011 John Wiley & Sons, Ltd.     

Assignment of symmetry-related cadmium shielding tensors to lattice positions in cadmium acetate dihydrate

An oriented single-crystal NMR experiment was carried out for a cadmium acetate dihydrate crystal having 66% ¹³C enrichment of the acetate carboxylate groups. The resulting ¹¹³Cd-¹³C direct dipole-dipole interactions give rise to an orientation-dependent modulation of ¹¹³Cd NMR linewidths for each of fdur magnetically distinguishable shielding tensors in the cadmium acetate crystal. Comparison of observed cadmium linewidths with those computed as a function of crystal orientation allows for unambiguous assignment of each of the four symmetry-related ¹¹³Cd shielding tensors to specific lattice positions in the cadmium acetate crystal. These assignments are in agreement with those made based upon empirical rules, and serve to confirm by means independent of previous assumptions the reliability of the assignment rules used previously. Confirmation of the validity and reliability of such rules is essential for the accurate interpretation of cadmium single-crystal NMR data in terms of shielding tensor-structure correlations to cadmium chemical shifts.     

Quinoline-Based “On-Off” Fluorescent Sensor for Acetate: Effect of Link Mode between Binding Sites and Fluorophore on Fluorescence Changes

ABSTRACT

A novel colorimetric and fluorescence anion sensor based on 8-nitroquinolyl-2-aldehyde phenyl-thiosemicarbazone (1) was designed and synthesized according to the approach that the binding sites were covalently linked to the signaling units. In DMSO, sensor 1 exhibited a naked-eye color change from colorless to yellow upon complexation with acetate. The association constant of 1 for acetate ion was determined to be 1.20 × 10³ M^?1 by nonlinear fitting analyses of the titration curves. The strong interactions of compound 1 with acetate ion could be rationalized on basis of not only the guest basicity but also shape complementarity between 1 and acetate. In addition, the fluorescence emission of 1 was effectively quenched upon addition of acetate ions owing to the fact that the photoinduced electron transfer (PET) was enhanced.     

Cerium isotope effects in Ce(III) malate and lactate complex formation studied by long-distance displacement chromatography

Isotope effects of cerium were observed in malate and lactate complex formations during the long-distance displacement chromatographic processes at 313 K. Heavier isotopes were found fractionated in the frontal edges of the Ce adsorption bands in both the systems, registering a preference of the heavier isotopes for the Ce(III) complexes in the solution phase over the simply hydrated Ce(III) ions in the resin phase. The fractionation coefficients ? for the ¹³⁶Ce/¹⁴⁰Ce, ¹³⁸Ce/¹⁴⁰Ce and ¹⁴²Ce/¹⁴⁰Ce isotopic pairs were 7.1 × 10^?6, 5.2 × 10^?6 and ?2.1 × 10^?6 for the malate system, and 4.8 × 10^?6, 4.5 × 10^?6 and?2.6×10^?6 for the lactate system, respectively. They all show the mass-dependent law if the deviation of ? for the ¹³⁸Ce/¹⁴⁰Ce pair was considered merely due to the isobaric interference in Ce isotopic ratio measurements, suggesting the molecular vibration, rather than the nuclear field shift, mainly contributes to the Ce isotope effects in the complex formation systems. The absolute values of ? between the two systems are comparable, suggesting no instinct difference in structural properties between Ce malate and lactate complexes involved.     

Measurement of longitudinal relaxation times in crowded 1H NMR spectra using one- and two-dimensional maximum quantum (MAXY) NMR spectroscopy

Methods for measuring longitudinal relaxation times of protons in heavily overlapped ¹H NMR spectra are introduced and exemplified using a solution of cholesteryl acetate. The methods are based on 1-dimensional and 2-dimensional maximum quantum NMR spectroscopy (MAXY), which makes possible the selective detection of CH, CH₂ and CH₃ ¹H NMR resonances. A modification of the BIRD pulse sequence to achieve selective inversion of protons bonded to either ¹²C or ¹³C is given. The approach should find application in studies of molecular dynamics where isotopic enrichment is not possible and the level of available sample dictates the use of ¹H NMR spectroscopy.     

Hydration of acetic acid and acetate ion in water studied by 1D-RISM theory

Structural and thermodynamic aspects of the hydration of acetic acid (CH₃COOH) and acetate ion (CH₃COO⁻) were studied with the 1D-RISM integral equation method. It was found that the average number of water molecules in the hydrophobic hydration shell of the CH₃ group is 8.9 for acetic acid and 10 for acetate. The average number of H-bonds formed by the COOH group is 2.5, whereas that of COO⁻ is 6, indicating that deprotonation of acetic acid leads to increased H-bonding of water molecules with the carboxylate moiety. This step involves significant reorientation of water molecules surrounding the carboxylic group. The hydration free energies and the aqueous ionization constant calculated with the set of semi-empirical corrections are in reasonable agreement with available experimental results.     

Lactate quantification by means of press spectroscopy—Influence of refocusing pulses and timing scheme

The quantitative assessment of lactic acid in tissue is an important goal for in vivo volume-selective NMR spectroscopy to aid in the noninvasive diagnosis of oxygen deficiency or other metabolic disorders. PRESS localized ¹H spectra provide comparatively high signal-to-noise ratio from small volume elements in a single acquisition mode. The quantification of lactate after multipulse excitation is not trivial due to the J-coupling characteristics which do not occur for the substances serving as references. The influence of the timing scheme and of the quality of the refocusing pulses was systematically evaluated for the lactate resonances by volume-selective measurements. Gaussian pulses, Hanning-filtered sinc pulses, and numerically optimized RE-BURP-pulses were applied for refocusing the magnetization in the PRESS sequence and the effects on the lactate AX₃ spin system were compared. For these pulses, sequence parameters are presented providing high sensitivity to lactate signals. Timing schemes are shown which provide good quantification of lactate, even in cases with B₁-inhomogeneities or slight misadjustment of the transmitter amplitude. The combination of both echo times in the double-echo sequences clearly influences the signal characteristics of lactate at overall echo times near TE = 145 and 290 ms, which may result in pure in-phase magnetization for this weakly coupled homonuclear system. Numerically optimized refocusing pulses (RE-BURP) provided up to 50% higher signal ratio of the methyl protons of lactate to uncoupled nuclei than the often used Hanning-filtered sinc pulses.     

Study on ammonium acetate salt-added polyvinyl alcohol-based solid proton-conducting polymer electrolytes

Polyvinyl alcohol (PVA) complexes with different compositions of ammonium acetate (AA) are prepared by solution cast technique. Polyvinyl alcohol crystallinity decreased with increasing ammonium acetate salt content. Molecular weight and density of polyvinyl alcohol complex increased with the addition of ammonium acetate salt. The ammonium acetate salt addition resulted in plasticization and hence decreased glass transition temperature (T _g) as well as hardness number (HV). 80PVA:20AA presented maximum conductivity (σ?=?1.3?×?10^?7S cm^?1 at 303 K) with minimum activation energy (E _a) 0.151 eV below the T _g. The proton transport number determined using EMF method found ≈0.98 for polymer complex with ammonium acetate content >15 mol%. The complex impedance is measured as a function of frequency, temperature, relative humidity, and hydrogen partial pressure. Enhanced bulk conductivity with increased H₂ partial pressure and relative humidity suggested H⁺ mobility within complex polymer electrolyte.     

Cancer recurrence monitoring using hyperpolarized [1-13C]pyruvate metabolic imaging in murine breast cancer model

The purpose of this work was to study the anatomic and metabolic changes that occur with tumor progression, regression and recurrence in a switchable MYC-driven murine breast cancer model. Serial ¹H MRI and hyperpolarized [1-¹³C]pyruvate metabolic imaging were used to investigate the changes in tumor volume and glycolytic metabolism over time during the multistage tumorigenesis. We show that acute de-induction of MYC expression in established tumors results in rapid tumor regression and significantly reduced glycolytic metabolism as measured by pyruvate-to-lactate conversion. Moreover, cancer recurrences occurring at the tumor sites independently of MYC expression were observed to accompany markedly increased lactate production.     

A novel colorimetric receptor responding AcO anions based on an azo derivative in DMSO and DMSO/water solution

A novel and efficient receptor based on the phenylhydrazone derivatives is successfully developed and applied to the acetate anion recognition, indicating that the origin of special preference for acetate (AcO⁻) anion maybe the structure well matching between the host and the guest. The sensor changes its color so obviously on addition of the acetate ions and that may make the naked-eye recognition in DMSO and even in DMSO/H₂O (95/5) solution come true. Also, the anion binding ability determinations were performed by UV-vis titration and ¹H NMR titration experiments with different anions in the solutions mentioned. The fluorescence enhancement can also be observed after the host is coordinated with the AcO⁻ anion and excited by light wavelength at 280 nm.     

Transport properties of aqueous solutions of calcium lactate in the absence and presence of β-cyclodextrin

Mutual diffusion coefficients and electrical conductivity of a well-known food additive and supplement, or excipient in pharmaceutical formulations, calcium lactate, have been measured in the absence and presence of β-cyclodextrin in aqueous solutions, at 298.15 K. The dependence of conductivity on concentration has been analysed using the Fuoss-Edelson method. The values of the Nernst diffusion coefficients, for binary solutions, derived from conductance and from diffusion experiments are in good agreement. The presence of β-cyclodextrin leads to a non-expected effect on the transport properties of the aqueous solutions of calcium lactate. These data have been justified with help of ¹H NMR spectroscopy. The effect on the water structure, reducing the hydration shell of lactate, is argued. This leads to an increase of the effective concentration of calcium lactate in solution contributing to an increase in the diffusion coefficients and a decrease in the dependence of the electrical conductance on the concentration.     

Effect of zinc salt on transport,structural, and thermal properties of PEG-based polymer electrolytes for battery application

Solid polymer polyethylene glycol (PEG)-based electrolytes composed with zinc acetate Zn(CH₃COO)₂ have been prepared by using solution blending. We proposed a scheme of PEG–zinc acetate for battery application. The structure confirmation was done by using X-ray diffraction studies detecting the phase variation. The thermal properties demonstrate the optimization of melting point (T _m) as a function of loading zinc acetate. The impedance analysis reveals that the role of ionic conductivity depends on the controlled concentration of Zn(CH₃COO)₂. Optimum ionic conductivity σ?~?1.55?×?10^?6 S?cm^?1 at room temperature (303 K) was observed for 70:30 composition. The linear variation in log σ vs 1000/T plot is based on the Arrhenius-type thermally activated process. The simultaneous discharge profile was confirmed by the solid-state electrochemical cell. Hence, the PEG–zinc acetate composition was suggested for polymer electrolyte battery application.     

ZnO:Tb纳米晶的协同发光现象

用光致发光的方法研究了掺铽的ZnO纳米晶这种新型掺杂纳米晶体系,观察到了其中的协同发光现象,指出ZnO纳米基质与掺入其中的铽中心之间存在有效的能量传递.该能量传递对稀土铽离子的特征发光起决定性的作用. 关键词： 光致发光 掺杂 纳米晶     

Cystic intracranial mass lesions: Possible role of in vivo MR spectroscopy in its differential diagnosis

Thirty-four patients showing cystic intracranial mass lesions on MR imaging were evaluated by in vivo proton MR spectroscopy (MRS) with the aim of detecting lesion-specific spectral patterns that may assist imaging in better tissue characterization. In vivo spectroscopy was performed using stimulated echo acquisition mode with echo times 20 m and 270 m in all, and spin echo with echo time 135 m in 11 patients. All primary neoplasms (intra-as well as extra-axial) showed choline (3.22 ppm) resonance along with lipid and/or lactate (1.3 ppm). It was not possible to grade cystic gliomas based on N-acetyl asparate-to-choline ratio. High-grade gliomas (n = 8) showed lipid/lactate and low-grade gliomas (n = 6) showed only lactate. Seven patients with brain abscess showed resonances only from acetate (1.92 ppm), lactate (1.3 ppm) and alanine (1.5 ppm). Two cases of metastatic adenocarcinoma showed only lipid/lactate. In 7 patients with epidermoid cyst, lactate along with an unassigned resonance at 1.8 ppm was observed and could be easily differentiated from arachnoid cyst (n = 2), which showed only minimal lactate. A case of cystic meningioma could be differentiated from cystic schowannoma by the presence of alanine in the former. It is concluded that MR imaging, when combined with in vivo MRS, may help to better characterize intracranial cystic mass lesions.