Biomedical subjects

C S Springer

Publications and source records attributed to C S Springer.

At least 19 recordsLinked to original sources

PubMed2000

Measurements of human brain ethanol T(2) by spectroscopic imaging at 4 T.

Previous MRS measurements of ethanol in human brain have yielded a range of transverse relaxation times for ethanol methyl resonance at 1.5 T (200-380 ms). To determine the T(2) of the methyl proton resonance of ethanol in human brain, 8 x 8 spectroscopic images were acquired at 16 different TE values. A frequency-selective refocusing pulse was used to suppress J-modulation of the ethanol triplet, permitting nonintegral multiples of 1/J to be used for TE values. The measured T(2) values for the methyl resonances of ethanol, creatine, and N-acetyl aspartate in mixed tissues were 82 +/- 12, 148 +/- 20, and 227 +/- 25 ms, respectively. Regression analysis of the measured T(2) as a function of gray matter content indicates a shorter T(2) value for ethanol in pure white matter compared to that in pure gray matter. Magn Reson Med 44:35-40, 2000.

Adult↗

PubMed2000

Determination of the MRI contrast agent concentration time course in vivo following bolus injection: effect of equilibrium transcytolemmal water exchange.

For bolus-tracking studies, it is commonly assumed that CR concentration bears a linear relationship with the measured (usually longitudinal) (1)H(2)O relaxation rate constant, R*(1) identical with(T(1) *)(-1). This requires that equilibrium transcytolemmal water exchange be in the fast exchange limit (FXL). However, though systems remain in fast exchange, the FXL will not usually obtain. Here, the consequences are considered: 1) the measurement of R(1) * itself can be affected, 2) the resultant non-linear [CR]-dependence causes significant error by assuming FXL, 3) the thermodynamic [CR] (based on the space in which CR is actually distributed) can be determined, 4) transcytolemmal water permeability may be estimated, and 5) the pharmacokinetic parameters can be factored. For a 30-sec, 0.17 mmol/kg dose of GdDTPA(2-), the FXL assumption underestimates the [CR] maximum in rat thigh muscle by a factor of almost two. Similar results are obtained for a rat brain GS-9L gliosarcoma tumor model.

Animals↗

PubMed2000

Resting brain metabolic activity in a 4 tesla magnetic field.

MRI is a major tool for mapping brain function; thus it is important to assess potential effects on brain neuronal activity attributable to the requisite static magnetic field. This study used positron emission tomography (PET) and (18)F-deoxyglucose ((18)FDG) to measure brain glucose metabolism (a measure of brain function) in 12 subjects while their heads were in a 4 T MRI field during the (18)FDG uptake period. The results were compared with those obtained when the subjects were in the earth's field (PET scanner), and when they were in a simulated MRI environment in the PET instrument that imitated the restricted visual field of the MRI experiment. Whole-brain metabolism, as well as metabolism in occipital cortex and posterior cingulate gyrus, was lower in the real (4 T) and simulated (0 T) MRI environments compared with the PET. This suggests that the metabolic differences are due mainly to the visual field differences characteristic of the MRI and PET instruments. We conclude that a static magnetic field of 4 T does not in itself affect this fairly sensitive measure of brain activity.

Adult↗

PubMed2000

4.0 T water proton T1 relaxation times in normal human brain and during acute ethanol intoxication.

BACKGROUND: It has been reported that acute ethanol intoxication decreases the brain water proton magnetic resonance T1 values, an effect that has been interpreted to indicate brain dehydration during this condition. Because water macromolecular interactions largely determine tissue water T1, another possible explanation for reduced brain water proton T1 values is that the interaction between water and brain macromolecules is altered by ethanol. METHODS: A 4.0 T magnetic resonance imaging (MRI) instrument was used to measure brain water proton T1 relaxation times before, during, and after ethanol intoxication (dose, 0.75 mg/kg) in healthy controls. RESULTS: The T1 relaxation times as assessed with MRI were highly reproducible. The mean, paired ethanol-induced differences in T1 were -0.004 +/- 0.007 sec (mean +/- standard deviation) for white matter and 0.010 +/- 0.015 sec for internal gray matter structures, neither of which was significant. CONCLUSIONS: This reasonably sensitive measurement does not support the view that tissue water content or water macromolecule interactions are significantly altered in the brain during acute alcohol intoxication in otherwise healthy subjects.

Adult↗

PubMed1999

Intimate combination of low- and high-resolution image data: I. Real-space PET and (1)H(2)O MRI, PETAMRI.

Two different types of (co-registered) images of the same slice of tissue will generally have different spatial resolutions. The judicious pixel-by-pixel combination of their data can be accomplished to yield a single image exhibiting properties of both. Here, axial (18)FDG PET and (1)H(2)O MR images of the human brain are used as the low- and high-resolution members of the pair. A color scale is necessary in order to provide for separate intensity parameters from the two image types. However, not all color scales can accommodate this separability. The HSV color model allows one to choose a color scale in which the intensity of the low-resolution image type is coded as hue, while that of the high-resolution type is coded as value, a reasonably independent parameter. Furthermore, the high-resolution image must have high contrast and be quantitative in the same sense as the low-resolution image almost always is. Here, relaxographic MR images (naturally segmented quantitative (1)H(2)O spin-density components) are used. Their essentially complete contrast serves to effect an apparent editing function when encoded as the value of the color scale. Thus, the combination of (18)FDG PET images with gray-matter (GM) relaxographic (1)H(2)O images produces visually "GM-edited" (18)FDG PETAMR (positron emission tomography and magnetic resonance) images. These exhibit the high sensitivity to tracer amounts characteristic of PET along with the high spatial resolution of (1)H(2)O MRI. At the same time, however, they retain the complete quantitative measures of each of their basis images. Magn Reson Med 42:345-360, 1999. Published 1999 Wiley-Liss, Inc.

Adult↗

PubMed1999

Equilibrium transcytolemmal water-exchange kinetics in skeletal muscle in vivo.

It is commonly assumed that equilibrium transcytolemmal water exchange in tissue is sufficiently frequent as to be fast on any NMR time scale achievable with an extracellular contrast agent (CR) in vivo. A survey of literature values for cell membrane diffusional permeability coefficients (P) and cell sizes suggests that this should not really be so. To evaluate this issue experimentally, we used a programmed intravenous CR infusion protocol for the rat with several rate plateaus, each of which achieved an increased steady-state concentration of GdDTPA(2-) in the blood plasma. Interleaved rigorous measurements of (1)H(2)O inversion recoveries were made from arterial blood and from a region of homogeneous thigh muscle tissue throughout the CR infusion. We made careful relaxographic analyses for the blood and muscle (1)H(2)O longitudinal relaxation times. The combined data from several animals were evaluated with a two-site model for equilibrium transcytolemmal water exchange. An excellent fitting was achieved, with parameters that agreed very well with the relevant physiological properties available in the literature. The fraction of water in the extracellular space, 0.11, is quite consistent with published values, as well as with reported tissue CR concentrations when one accounts for the restriction of CR to this space. The derived average lifetime for a water molecule in the thigh muscle sarcoplasm, 1.1 +/- 0.4 sec, implies a sarcolemmal P of 13 x 10(-4) cm/sec, which is well within the range of literature values determined in vitro. Moreover, we find that because of the exchange, the (1)H(2)O longitudinal relaxation rate constant exhibits a decided nonlinear dependence on the tissue or thermodynamic (extracellular) concentration of GdDTPA(2-). The muscle system departs the fast-exchange limit at a [CR] value of <100 micromol/L. This has significant implications for the quantitative use of CRs as MRI tracers. Magn Reson Med 42:467-478, 1999. Published 1999 Wiley-Liss, Inc.

Animals↗

PubMed1999

Using flow relaxography to elucidate flow relaxivity.

We have investigated the theoretical and experimental linear dependence of the reciprocal of the apparent longitudinal relaxation time [(T*1)-1] of the NMR signal from spins in a flowing fluid on the volume flow rate, Fv, the so-called inflow effect. We refer to the coefficient of this dependence as the longitudinal flow relaxivity, r1F. A very simple model predicts that, under a range of conditions pertinent to modern flow studies and perfusion imaging experiments, r1F is controlled by the volume of the fluid in which the magnetization is perturbed by pulsed RF inversion or saturation, not the detection volume, and that it can be approximated as the reciprocal of half of the inversion volume. Phantom sample experiments, using a new, quantitative approach that we call flow relaxography, confirm the general predictions of this simple model. There are two intriguing implications of these findings for general NMR flow studies as well as for medical applications. It should be possible to vary the value of r1F by simply (noninvasively) adjusting the inversion slice thickness, and thus measure the value of (blood 1H2O, for example) Fv in a vessel without changing Fv, from the resultant varying T*1 values. Also, it should be possible to extrapolate to the intrinsic T1 value of the fluid signal (as if it were stationary), without altering or stopping the flow. Again, these are quite successful in phantom sample studies. Imaging versions of the flow relaxographic experiments are also possible. The twin goals of flow studies in medical MRI are the quantitative discrimination of the signals from flowing and nonflowing spins, and the accurate measurement of the flow rate of the former.

Blood Flow Velocity↗

PubMed1996

Magnetic resonance imaging (MRI) detection of the murine brain response to light: temporal differentiation and negative functional MRI changes.

Using a 9.4 T MRI instrument, we have obtained images of the mouse brain response to photic stimulation during a period between deep anesthesia and the early stages of arousal. The large image enhancements we observe (often >30%) are consistent with literature results extrapolated to 9.4 T. However, there are also two unusual aspects to our findings. (i) The visual area of the brain responds only to changes in stimulus intensity, suggesting that we directly detect operations of the M visual system pathway. Such a channel has been observed in mice by invasive electrophysiology, and described in detail for primates. (ii) Along with the typical positive response in the area of the occipital portion of the brain containing the visual cortex, another area displays decreased signal intensity upon stimulation.

Animals↗

PubMed1996

In vivo MR imaging and spectroscopy using hyperpolarized 129Xe.

Hyperpolarized 129Xe has been used to obtain gas phase images of mouse lung in vivo, showing distinct ventilation variation as a function of the breathing cycle. Spectra of 129Xe in the thorax show complex structure in both the gas phase (-4 to 3 ppm) and tissue-dissolved (190-205 ppm) regions. The alveolar gas peak shows correlated intensity and frequency oscillations, both attributable to changes in lung volume during breathing. The two major dissolved peaks near 195-200 ppm are attributed to lung parenchyma and to blood; they reach maximum intensity in 5-10 s and decay with an apparent T1 of 30 s. Another peak at 190 ppm takes 20-30 s to reach maximum; this must represent other well-vascularized tissue (e.g., heart and other muscles) in the thorax. The maximum integrated area of the tissue components reaches 30-80% of the maximum alveolar gas area, indicating that imaging at tissue frequencies can be achieved.

Animals↗

PubMed1995

What's in a name?

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Magnetic Resonance Spectroscopy↗

PubMed1994

Biological magnetic resonance imaging using laser-polarized 129Xe.

As currently implemented, magnetic resonance imaging (MRI) relies on the protons of water molecules in tissue to provide the NMR signal. Protons are, however, notoriously difficult to image in some biological environments of interest, notably the lungs and lipid bilayer membranes such as those in the brain. Here we show that 129Xe gas can be used for high-resolution MRI when the nuclear-spin polarization of the atoms is increased by laser optical pumping and spin exchange. This process produces hyperpolarized 129Xe, in which the magnetization is enhanced by a factor of about 10(5). By introducing hyperpolarized 129Xe into mouse lungs we have obtained images of the lung gas space with a speed and a resolution better than those available from proton MRI or emission tomography. As xenon (a safe general anaesthetic) is rapidly and safely transferred from the lungs to blood and thence to other tissues, where it is concentrated in lipid and protein components, images of the circulatory system, the brain and other vital organs can also be obtained. Because the magnetic behaviour of 129Xe is very sensitive to its environment, and is different from that of 1H2O, MRI using hyperpolarized 129Xe should involve distinct and sensitive mechanisms for tissue contrast.

Animals↗

PubMed1994

Relaxographic imaging.

A fundamental extension of NMR imaging is described. The distribution of relaxation times, the relaxogram, is considered as the third (or fourth) dimension of a set of 2D (or 3D) image data. There is a relaxographic dimension for each type of relaxation: longitudinal, transverse, rotating frame, etc. It is the formal inverse Laplace transform of the relaxation decay data set. Thus, combined relaxography and imaging (CRI) approaches are defined. CRI data can be displayed in two fundamental ways: localized relaxograms (relaxograms from any part of an image) or relaxographic images (images produced from discrete portions of a relaxogram). Relaxographic images are elemental components of the true spin-density image. The CRI concept is demonstrated with longitudinal relaxation data from samples of yeast cells suspended in media containing the contrast agent (CR) GdDTPA2-. This allows the discrimination of subvoxel intra- and extracellular 1H2O signals in the relaxograms from very small image voxels (about 400 nl). It is possible to isolate the intracellular 1H2O resonance from as few as a million cells. Relaxographic images are shown of the extracellular space (i.e., the distribution space of the CR) and the cytoplasmic space of a cell suspension with a cytocrit gradient. These have important potential applications in the in vivo situation. Also, the extent of equilibrium transcytolemmal water exchange can be detected and quantified.

Body Water↗

PubMed1993

Susceptibility changes following bolus injections.

The general mechanism of bulk magnetic susceptibility (BMS) induced MRI contrast following a bolus injection is elaborated. Combining radiolabeled tracer data for the first pass of a bolus injection through the human brain with the application of Wiedemann's law allows us to calculate the lower limit for the time course of the vascular BMS following the injection of any contrast agent. Superparamagnetic iron oxide particles produce a much larger effect than any mononuclear Ln(III) chelate. We also calculate the BMS changes occurring after a dilution bolus injection (of isosmolal physiological saline) subsequent to a prior slow infusion of an intravascular contrast agent. This technique bears some resemblance to the increasingly important approach that exploits changes in only the level of blood oxygenation. The calculation indicates that contrast changes after the dilution bolus injection are smaller than those following Ln(III) agent injections but larger than those due to changes in blood oxygenation and suggests a way to possibly enhance the latter. We present an in vivo study demonstrating the dilution bolus injection technique in the mouse brain, and that features its rapid repeatability. Extrapolation of these results to the human, however, indicates that the saline volumes required for venous injections, except possibly for cardiac studies, would be prohibitively large. Smaller, catheter-delivered arterial bolus injections are feasible. We also suggest a method for using an agent bolus injection to measure the parenchymal BMS, and thus the iron content, of pathologically iron-loaded tissue.

Algorithms↗

PubMed1991

A comprehensive approach to the analysis and interpretation of the resonances of spins 3/2 from living systems.

An extensive protocol for the study of tissue resonances of spin 3/2 nuclei is described. The roles of the most relevant multiple pulse experiments are indicated. Their theory is organized in terms of irreducible tensor operators and the pulse and quadrupolar relaxation transfer functions which relate them for a type c spectrum. A systematic approach to the interpretation of the temperature and/or magnetic field dependences of all six of the relaxation rate constants of the resonance of a single population of isolated spins in fast exchange, and giving rise to a type c spectrum, is presented. An experimental calibration and an application of this protocol are presented in an accompanying paper. The comprehensive method we describe has a number of practical benefits in the interpretation of the physiological spectra obtained from conventional one pulse experiments. A consideration of the appropriate transverse relaxation transfer function leads to an analytical expression for the heretofore empirical NMR visibility factor. This includes factors which account for relaxation during the receiver 'dead' time and relaxation during the pulse itself. Also, consideration of realistic transverse relaxation times likely to be observed in tissue leads to a reasonable strategy for the quantitative resolution and integration of in vivo spectra obtained in the presence of hyperfine shift reagents.

Chlorine↗

PubMed1991

The molecular environment of intracellular sodium: 23Na NMR relaxation.

The comprehensive approach described in the accompanying paper is illustrated here with the 23Na signal of a concentrated solution of bovine serum albumin (BSA) in saline and the intracellular (Nai) 23Na resonance of a dense suspension of Na(+)-loaded yeast cells. We use frequency shift reagents to discriminate the latter from the extracellular resonance. We find that the Nai signal corresponds to that of an effective single population of Na+ ions exhibiting a single type c spectrum. This is true despite the fact that the yeast protoplasm is too large and too compartmentalized for a given Na+ ion to sample its entirety on the relevant NMR timescale. Our results show clearly that, in addition to the decay of transverse magnetization, the recovery of longitudinal magnetization is biexponential. This is required for a type c spectrum but has not often been detected. The temperature dependence of the relaxation rate constants of the Nai resonance is not consistent with either a simple Debye process or a discrete exchange mechanism connecting two sites in the fast limit. We have fitted the data using an asymmetric continuous distribution of correlation times for the fluctuations of electric field gradients sensed by the Nai nuclei. The analogous distribution function for the Na+ in a 44% (w/w) BSA solution is quite similar to that of the Nai at the same temperature. This suggests that while the macromolecular environment of the Nai ions is quite congested, it is also isotropic on quite a small spatial scale. Also, one can use the correlation time distribution function, obtained from fitting the relaxation data, to calculate a relaxometry curve. This is useful because experimental 23Na relaxometry is difficult. The calculated curve may be a reasonable model for the mostly extracellular 23Na resonance encountered in vivo.

Calibration↗

PubMed1991

25Mg NMR studies of magnesium binding to erythrocyte constituents.

The binding of Mg2+ ion to ATP, ADP, AMP, 2,3-bisphosphyoglycerate (DPG), and hemoglobin has been studied by 25Mg NMR spectroscopy at 9.4 T. Addition of any of these ligands to a solution of 2 mM 25MgCl2 at pH 7.2 caused a progressive increase in linewidth, with no discernible chemical shift. ATP and ADP, which form tight 1:1 complexes with Mg2+, did not cause maximal broadening until present in several-fold excess, implying that bis(nucleotide) complexes also form. The studies showed progressively weaker Mg2+ binding to ATP, ADP, DPG, and AMP, consistent with published binding constants. Hemoglobin cause fairly little broadening, consistent with its known weak affinity for Mg2+. Competition studies determined ATP affinities for Ca2+ and H+ that were also in good agreement with published values. 25Mg NMR spectra of 2 mM bound 25Mg2+ were obtained with good signal to noise in less than 1 hr. The technique may now be a practical means for studying the binding of Mg2+ within erythrocytes and other cells.

2,3-Diphosphoglycerate↗

PubMed1990

Bulk magnetic susceptibility shifts in NMR studies of compartmentalized samples: use of paramagnetic reagents.

The bulk magnetic susceptibility (BMS) shift of a nuclear resonance frequency caused by a paramagnetic compound is of importance in vivo NMR, both magnetic resonance spectroscopy and magnetic resonance imaging. However, since it is a rather complicated phenomenon, it has been the source of many misinterpretations in the literature. We have reworked and organized the theory of the BMS shift. This includes accounting for the important effects of local susceptibility. We have conducted experiments on phantom samples in order to illustrate the principles involved. Our phantoms consist of capillaries and coaxial cylinders. They simulate the situations of blood vessels oriented parallel and perpendicular to the magnetic field and the interstitial spaces surrounding them. In most of our experiments, the paramagnetic compound was one of several different hyperfine shift reagents for cation resonances. These were chosen to cover a range of potencies, in both magnitude and sign, of the shifts they produce. However, we also used a reagent which was incapable of inducing a hyperfine shift and thus could cause only a BMS shift. Although we report only 23Na spectra in this paper, the latter samples simulate the cases where one observes the water 1H resonance in experiments employing hyperfine shift reagents for cations. There have been a number of such investigations recently reported in the literature. The principles considered in this paper allow us to offer new interpretations for the results of several experiments published in the last few years.

Electron Spin Resonance Spectroscopy↗

PubMed1990

Magnetic susceptibility shift selected imaging: MESSI.

Paramagnetic compounds are often used to enhance contrast in MRI by virtue of their increase in the kinetics of the relaxation of water 1H magnetization. Here, we demonstrate a method for contrast enhancement which is based on the resonance frequency shifts caused by the bulk magnetic susceptibility (BMS) effects of such compounds. This involves the frequency selective excitation in the absence of field gradients, during the imaging sequence, of a portion of the water 1H resonance which is rendered inhomogeneous by BMS shifts only. The image which results is of that portion of the sample which gives rise to the portion of the spectrum excited. A phantom sample which simulates some aspects of tissue, particularly blood vessels with different orientations in the magnetic field, was prepared. The contrast enhancement exhibited here avoids some of the distortions attendant to the use of paramagnetic reagents. This new approach can, in principle, utilize the natural BMS differences found in all tissue.

Animals↗