Biomedical subjects

H Merkle

Publications and source records attributed to H Merkle.

At least 19 recordsLinked to original sources

PubMed2002

Different excitation and reception distributions with a single-loop transmit-receive surface coil near a head-sized spherical phantom at 300 MHz.

Calculations and experiments were used to examine the B(1) field behavior and signal intensity distribution in a 16-cm diameter spherical phantom excited by a 10-cm diameter surface coil at 300 MHz. In this simple system at this high frequency very complex RF field behavior exists, resulting in different excitation and reception distributions. Included in this work is a straightforward demonstration that coil receptivity is proportional to the magnitude of the circularly polarized component of the B(1) field that rotates in the direction opposite to that of nuclear precession. It is clearly apparent that even in very simple systems in head-sized samples at this frequency it is important to consider the separate excitation and reception distributions in order to understand the signal intensity distribution.

Head↗

PubMed2001

17O relaxation time and NMR sensitivity of cerebral water and their field dependence.

17O spin relaxation times and sensitivity of detection were measured for natural abundance H(2)(17)O in the rat brain at 4.7 and 9.4 Tesla. The relaxation times were found to be magnetic field independent (T(2) = 3.03 +/- 0.08 ms, T(*)(2) = 1.79 +/- 0.04 ms, and T(1) = 4.47 +/- 0.14 ms at 4.7T (N = 5); T(2) = 3.03 +/- 0.09 ms, T(*)(2) = 1.80 +/- 0.06 ms, and T(1) = 4.84 +/- 0.18 ms at 9.4T (N = 5)), consistent with the concept that the dominant relaxation mechanism is the quadrupolar interaction for this nucleus. The (17)O NMR sensitivity was more than fourfold higher at 9.4T than at 4.7T, for both the rat brain and a sodium chloride solution. With this sensitivity gain, it was possible to obtain localized (17)O spectra with an excellent signal-to-noise ratio (SNR) within 15 s of data acquisition despite the relatively low gyromagnetic ratio of this nucleus. Such a 15-s 2D (17)O-MRS imaging data set obtained for natural abundance H(2)(17)O in the rat brain yielded an SNR greater than 40:1 for a approximately 16 microl voxel. This approach was employed to measure cerebral blood flow using a bolus injection of H(2)(17)O via one internal carotid artery. These results demonstrate the ability of (17)O-MRS imaging to reliably map the H(2)(17)O dynamics in the brain tissue, and its potential for determining tissue blood flow and oxygen consumption rate changes in vivo. Magn Reson Med 45:543-549, 2001.

Animals↗

PubMed2001

Imaging brain function in humans at 7 Tesla.

This article describes experimental studies performed to demonstrate the feasibility of BOLD fMRI using echo-planar imaging (EPI) at 7 T and to characterize the BOLD response in humans at this ultrahigh magnetic field. Visual stimulation studies were performed in normal subjects using high-resolution multishot EPI sequences. Changes in R(*)(2) arising from visual stimulation were experimentally determined using fMRI measurements obtained at multiple echo times. The results obtained at 7 T were compared to those at 4 T. Experimental data indicate that fMRI can be reliably performed at 7 T and that at this field strength both the sensitivity and spatial specificity of the BOLD response are increased. This study suggests that ultrahigh field MR systems are advantageous for functional mapping in humans. Magn Reson Med 45:588-594, 2001.

Brain↗

PubMed2001

7T vs. 4T: RF power, homogeneity, and signal-to-noise comparison in head images.

Signal-to-noise ratio (SNR), RF field (B(1)), and RF power requirement for human head imaging were examined at 7T and 4T magnetic field strengths. The variation in B(1) magnitude was nearly twofold higher at 7T than at 4T ( approximately 42% compared to approximately 23%). The power required for a 90 degrees pulse in the center of the head at 7T was approximately twice that at 4T. The SNR averaged over the brain was at least 1.6 times higher at 7T compared to 4T. These experimental results were consistent with calculations performed using a human head model and Maxwell's equations. Magn Reson Med 46:24-30, 2001.

Brain↗

PubMed2001

In vivo 1H NMR spectroscopy of the human brain at 7 T.

In vivo 1H NMR spectra from the human brain were measured at 7 T. Ultrashort echo-time STEAM was used to minimize J-modulation and signal attenuation caused by the shorter T2 of metabolites. Precise adjustment of higher-order shims, which was achieved with FASTMAP, was crucial to benefit from this high magnetic field. Sensitivity improvements were evident from single-shot spectra and from the direct detection of glucose at 5.23 ppm in 8-ml volumes. The linewidth of the creatine methyl resonance was at best 9 Hz. In spite of the increased linewidth of singlet resonances at 7 T, the ability to resolve overlapping multiplets of J-coupled spin systems, such as glutamine and glutamate, was substantially increased. Characteristic spectral patterns of metabolites, e.g., myo-inositol and taurine, were discernible in the in vivo spectra, which facilitated an unambiguous signal assignment.

Adult↗

PubMed2001

Noninvasive measurements of transmural myocardial metabolites using 3-D (31)P NMR spectroscopy.

A completely noninvasive three-dimensional (3-D) static magnetic field magnitude spatially localized (31)P spectroscopy technique has been developed and applied to study the in vivo canine myocardium at 9.4 T. The technique incorporates both Fourier series windows and selective Fourier transform methods utilizing all three orthogonal gradients for 3-D phase encoding. The number of data acquisitions for each phase-encoding step was weighted according to the Fourier coefficients to define cylindrical voxels. Spatially localized (31)P spectra can be generated for voxels of desired location within the field of view as a postprocessing step. The quality of localization was first demonstrated by using a three-compartment phantom. The technique was then applied to in vivo canine models and yielded (31)P cardiac spectra with an excellent signal-to-noise ratio. The in vivo validation experiments, using an implanted 2-phosphoenolpyruvate-containing marker, demonstrated that the technique is capable of measuring at least two transmural layers of left ventricular myocardium representing the subepicardium and subendocardium.

Adenosine Triphosphate↗

PubMed2001

A connectivity standard for point-of-care testing.

A software standard has been designed that will facilitate the linking of all point-of-care testing (POCT) devices to information systems. This standard will replace the myriad of proprietary and incompatible solutions that currently exist. The standard is expected to be a feature of new POCT instruments by 2002.

Computer Communication Networks↗

PubMed2000

H-2(d) mice born to and reared by HBeAg-transgenic mothers do not develop T cell tolerance toward the hepatitis B virus core gene products.

The function of the secretory core gene product (HBeAg) of the human hepatitis B virus (HBV) is unknown. It has been proposed that this protein may be passed from the mother to her offspring at the perinatal stage where it might induce immune tolerance. In a previous study we have shown that the murine placenta presents an efficient barrier for the HBe protein and that H-2(b) mice born to HBeAg-positive transgenic mothers do not develop tolerance of specific cytotoxic T cells. In the present work we demonstrate that transgenic mice expressing high serum levels of HBeAg secrete only small amounts of this protein into their milk and excrete minute amounts of the viral gene product in their urine. Furthermore, it is shown that nontransgenic H-2(d) mice born to and reared by HBeAg-positive mothers exhibit a reactivity of HBc/eAg-specific CD4(+) Th cells and CD8(+) cytotoxic T cells comparable to that of normal isogenic control mice. In accordance with this observation the humoral immune responses directed against the HBeAg were comparable between these two groups of animals. This finding indicates that H-2(d) mice potentially exposed to small amounts of maternal HBeAg transferred by the transplacental, lactogenic, or renal route do not develop tolerance toward the HBV core gene products. These data challenge the hypothesis that a potential function of the HBeAg may be to operate as a tolerogen at the perinatal developmental stage.

Animals↗

PubMed2000

Hepatocytes of double-transgenic mice expressing high levels of hepatitis B virus e antigen and interferon-gamma are not injured by HBeAg specific autoantibodies.

Seroconversion from HBeAg to alphaHBe of persons chronically infected by HBV is usually associated with a transient exacerbation of liver disease and subsequent normalization of liver histology. It is speculated that these clinico-pathological features may be due to the activation of cytodestructive mechanisms by alphaHBe antibodies. The aim of the present study was to investigate the pathogenic potential of alphaHBe antibodies in a transgenic mouse model. Therefore, alphaHBe autoantibodies were elicited in double-transgenic mice expressing high amounts of HBeAg and interferon-gamma in the liver. Interferon-gamma has reviously been shown to play an important role in the development of hepatic necroinflammation associated with hepadnaviral infection, probably via tumor-necrosis-factor-alpha secreted by activated macrophages. We found no evidence that alphaHBe antibodies have the potential to destroy HBeAg-secreting hepatocytes even if the cells were predisposed to injury due to high-level interferon-gamma expression. We conclude that seroconversion from HBeAg to alphaHBe of persons chronically infected with HBV seems to be an immunological epiphenomenon without pathogenic significance.

Animals↗

PubMed2000

Functional magnetic resonance imaging with intermolecular multiple-quantum coherences.

For the first time, we demonstrate here functional magnetic resonance imaging (fMRI) using intermolecular multiple-quantum coherences (iMQCs). iMQCs are normally not observed in liquid-state NMR because dipolar interactions between spins average to zero. If the magnetic isotropy of the sample is broken through the use of magnetic field gradients, dipolar couplings can reappear, and hence iMQCs can be observed. Conventional (BOLD) fMRI measures susceptibility variations averaged over each voxel. In the experiment performed here, the sensitivity of iMQCs to frequency variations over mesoscopic and well-defined distances is exploited. We show that iMQC contrast is qualitatively and quantitatively different from BOLD contrast in a visual stimulation task. While the number of activated pixels is smaller in iMQC contrast, the intensity change in some pixels exceeds that of BOLD contrast severalfold.

Brain↗

PubMed2000

Magnetic resonance studies of brain function and neurochemistry.

In the short time since its introduction, magnetic resonance imaging (MRI) has rapidly evolved to become an indispensable tool for clinical diagnosis and biomedical research. Recently, this methodology has been successfully used for the acquisition of functional, physiological, and biochemical information in intact systems, particularly in the human body. The ability to map areas of altered neuronal activity in the brain, often referred to as functional magnetic resonance imaging (fMRI), is probably one of the most significant recent achievements that rely on this methodology. This development has permitted the examination of functional specialization in human and animal brains with unprecedented spatial resolution, as demonstrated by mapping at the level of orientation and ocular dominance columns in the visual cortex. These functional imaging studies are complemented by the ability to study neurochemistry using magnetic resonance spectroscopy, allowing the determination of metabolic processes that support neurotransmission and neurotransmission rates themselves.

Animals↗

PubMed1999

Localized in vivo 1H NMR detection of neurotransmitter labeling in rat brain during infusion of [1-13C] D-glucose.

Resolved localized nuclear magnetic resonance (NMR) signals of 1H bound to 13C label in the carbon positions of glutamate C4, C3 and glutamine C4, C3, as well as in aspartate C3, lactate C3, alanine C3, gamma-aminobutyric acid C3, and glucose C1 were simultaneously observed in spectra obtained from rat brain in vivo. Time-resolved label incorporation was measured with a new adiabatic carbon editing and decoupling (ACED) single-voxel stimulated echo acquisition mode (STEAM) sequence. Adiabatic carbon broadband decoupling of 12 kHz bandwidth was achieved in vivo, which decoupled the entire 13C spectrum at 9.4 T. Resonances from N-acetyl-aspartate and creatine were also detected, consistent with natural-abundance 13C levels. These results emphasize the potential of 1H NMR for following complex biochemical pathways in localized areas of resting rat brain as well as during focal activation using infusions of 13C-labeled glucose.

Animals↗

PubMed1999

In vitro and in vivo studies of 1H NMR visibility to detect deoxyhemoglobin and deoxymyoglobin signals in myocardium.

1H nuclear magnetic resonance (NMR) spectroscopy can be used noninvasively to detect the proximal histidyl N delta proton signals of deoxymyoglobin in the myocardium. However, the quantification of deoxymyoglobin is based on the assumption that the deoxymyoglobin signal detected is not contaminated by the deoxyhemoglobin signals contributed from the blood. The purpose of this study was to conduct in vitro and in vivo 1H NMR studies to examine the in vivo NMR visibility of deoxyhemoglobin in the myocardium. The results demonstrate that the NMR visibility of alpha and beta subunits of deoxyhemoglobin is sensitive to the pulse width for spin excitation because of short T2 relaxation times, and they are not NMR visible in the canine myocardium in vivo at 4.7 T when a 0.5-1.0 msec long Gaussian excitation pulse is used. Therefore, the resonance peak detected at approximately 72 ppm (relative to the water resonance) in the ischemic canine myocardium in vivo is dominated by deoxymyoglobin.

Animals↗

PubMed1999

Myocardial oxygenation at high workstates in hearts with left ventricular hypertrophy.

BACKGROUND: High cardiac workloads produced by catecholamine infusion result in loss of myocardial phosphocreatine (PCr) and accumulation of inorganic phosphate (Pi) which are more prominent in heart with left ventricular hypertrophy (LVH) than in normal hearts. Since ischemia can cause changes in phosphorylated compounds similar to those during catecholamine stimulation, this study tested the hypothesis that the exaggerated depletion of PCr and accumulation of Pi during high workloads in LVH is the result of impaired myocyte oxygenation. METHODS AND RESULTS: 31P- and 1H-NMR spectroscopy were used to determine myocardial high energy phosphate levels and myoglobin desaturation, respectively, in eight normal dogs and nine dogs with LVH produced by ascending aortic banding. The mean LV weight/body weight ratio was approximately twice normal in the LVH group. Infusion of dobutamine (15 and 30 micrograms/kg/min), and dobutamine + dopamine (each 20 micrograms/kg/min) caused progressive similar increases in the heart rate x systolic LV pressure product to a maximum of 57.4 +/- 3.3 x 10(3) in normal and 63.9 +/- 2.7 x 10(3) in LVH animals, while myocardial oxygen consumption increased from 0.09 +/- 0.01 to 0.24 +/- 0.04 in normals and from 0.10 +/- 0.02 to 0.25 +/- 0.03 ml/min/g in LVH. PCr/ATP ratios during basal conditions were lower in LVH hearts (1.73 +/- 0.10, 1.61 +/- 0.09 and 1.51 +/- 0.09 in subepicardium, midwall and subendocardium, respectively) as compared with normals (2.24 +/- 0.09, 2.01 +/- 0.08 and 1.89 +/- 0.07; each p < 0.01 normal vs. LVH). Catecholamine infusions caused dose-related decreases in PCr/ATP and appearance of Pi which was more marked in LVH than in normal hearts. 1H-NMR spectroscopy did not detect deoxymyoglobin in either normal or LVH hearts even during the highest workloads. In contrast, occlusion of the anterior descending coronary artery resulted in a large deoxymyoglobin signal. CONCLUSIONS: Increases of cardiac work produced by catecholamine stimulation resulted in greater decreases of PCr and greater increases of Pi in hypertrophied than in normal hearts. These abnormalities were not the result of inadequate intracellular oxygen availability and consequently cannot be ascribed to demand ischemia.

Adenosine Triphosphate↗

PubMed1999

The seismocardiogram as magnetic-field-compatible alternative to the electrocardiogram for cardiac stress monitoring.

Seismocardiography (SCG) is a methodology derived from the field of seismology to measure non-invasively compression waves generated by myocardial motion. The use of SCG is proposed here as method to monitor cardiac function during stress testing and magnetic resonance imaging (MRI). It is shown that recording of the seismocardiogram in subjects undergoing an MRI study is not compromised by flow-induced electrical voltages that can severely distort the electrocardiogram. Electromagnetic compatibility of the seismocardiograph device with the MRI scanner hardware was tested. Experiments in an animal model proved that changes in the SCG waveform during different levels of LAD stenosis correlate with the changes seen in LV function with cine MRI. The changes in the SCG waveform characteristic for the onset of ischemia were observed almost immediately after the creation of a flow-limiting stenosis. This novel application of SCG to monitor changes in peak acceleration from cardiac blood flow and wall motion may represent a solution to the long-standing and important problem of monitoring patients for signs of myocardial ischemia during MRI.

Coronary Circulation↗

PubMed1998

Lactate turnover in rat glioma measured by in vivo nuclear magnetic resonance spectroscopy.

Elevated tissue lactate concentrations typically found in tumors can be measured by in vivo nuclear magnetic resonance (NMR) spectroscopy. In this study, lactate turnover in rat C6 glioma was determined from in vivo 1H NMR measurements of [3-13C]lactate buildup during steady-state hyperglycemia with [1-13C]glucose. With this tumor model, a narrow range of values was observed for the first-order rate constant that describes lactate efflux, k2 = 0.043 +/- 0.007 (n = 12) SD min-1. For individual animals, the standard error in k2 was small (< 18%), which indicated that the NMR data fit the kinetic model well. Lactate measurements before and after infusing [1-13C]glucose showed that the majority of the tumor lactate pool was metabolically active. Signals from 13C-labeled glutamate in tumors were at least 10-fold smaller than the [3-13C]lactate signal, whereas spectra of the contralateral hemispheres revealed the expected labeling of [4-13C]glutamate, as well as [2-13C] and [3-13C]glutamate, which indicates that label cycled through the tricarboxylic acid cycle in the brain tissue. Lack of significant 13C labeling of glutamate was consistent with low respiratory metabolism in this glioma. It is concluded that lactate in rat C6 glioma is actively turning over and that the kinetics of lactate efflux can be quantified noninvasively by 1H NMR detection of 13C label. This noninvasive NMR approach may offer a valuable tool to help evaluate tumor growth and metabolic responsiveness to therapies.

Animals↗

PubMed1998

Imaging of H217O distribution in the brain of a live rat by using proton-detected 17O MRI.

Imaging of H217O has a number of important applications. Mapping the distribution of H217O produced by oxidative metabolism of 17O-enriched oxygen gas may lead to a new method of metabolic functional imaging; regional cerebral blood flow also can be measured by measuring the H217O distribution after the injection of 17O-enriched physiological saline solution. Previous studies have proposed a method for indirect detection of 17O. The method is based on the shortening of the proton T2 in H217O solutions, caused by the residual 17O-1H scalar coupling and transferred to the bulk water via fast chemical exchange. It has been shown that the proton T2 of H217O solutions can be restored to that of H216O by irradiating the resonance frequency of the 17O nucleus. The indirect 17O image thus is obtained by taking the difference between two T2-weighted spin-echo images: one acquired after irradiation of the 17O resonance and one acquired without irradiation. It also has been established that, at relatively low concentrations of H217O, the indirect method yields an image that quantitatively reflects the H217O distribution in the sample. The method is referred to as PRIMO (proton imaging of oxygen). In this work, we show in vivo proton images of the H217O distribution in a rat brain after an i.v. injection of H217O-enriched physiological saline solution. Implementing the indirect detection method in an echo-planar imaging sequence enabled obtaining H217O images with good spatial and temporal resolution of few seconds.

Animals↗

PubMed1998

Simultaneous in vivo spectral editing and water suppression.

Water suppression is typically performed in vivo by exciting the longitudinal magnetization in combination with dephasing, or by using frequency-selective coherence generation. MEGA, a frequency-selective refocusing technique, can be placed into any pulse sequence element designed to generate a Hahn spin-echo or stimulated echo, to dephase transverse water coherences with minimal spectral distortions. Water suppression performance was verified in vivo using stimulated echo acquisition mode (STEAM) localization, which provided water suppression comparable with that achieved with four selective pulses in 3,1-DRYSTEAM. The advantage of the proposed method was exploited for editing J-coupled resonances. Using a double-banded pulse that selectively inverts a J-coupling partner and simultaneously suppresses water, efficient metabolite editing was achieved in the point resolved spectroscopy (PRESS) and STEAM sequences in which MEGA was incorporated. To illustrate the efficiency of the method, the detection of gamma-aminobutyric acid (GABA) was demonstrated, with minimal contributions from macromolecules and overlying singlet peaks at 4 T. The estimated occipital GABA concentration was consistent with previous reports, suggesting that editing for GABA is efficient when based on MEGA at high field strengths.

Brain Chemistry↗