Biomedical subjects

J J Ackerman

Publications and source records attributed to J J Ackerman.

At least 19 recordsLinked to original sources

PubMed2001

Water proton MR properties of human blood at 1.5 Tesla: magnetic susceptibility, T(1), T(2), T*(2), and non-Lorentzian signal behavior.

Accurate knowledge of the magnetic properties of human blood is required for the precise modeling of functional and vascular flow-related MRI. Herein are reported determinations of the relaxation parameters of blood, employing in vitro samples that are well representative of human blood in situ. The envelope of the blood (1)H(2)O free-induction decay signal magnitude during the first 100 msec following a spin echo at time TE is well- described empirically by an expression of the form, S(t) = S(o). exp[-R(*)(2). (t - TE) - AR*. (t - TE)(2)]. The relaxation parameters AR* and R(*)(2) increase as a function of the square of the susceptibility difference between red blood cell and plasma and depend on the spin-echo time. The Gaussian component, AR*, should be recognized in accurate modeling of MRI phenomena that depend upon the magnetic state of blood. The magnetic susceptibility difference between fully deoxygenated and fully oxygenated red blood cells at 37 degrees C is 0.27 ppm, as determined independently by MR and superconducting quantum interference device (SQUID) measurements. This value agrees well with the 1936 report of Pauling and Coryell (Proc Natl Acad Sci USA 1936;22:210-216), but is substantially larger than that frequently used in MRI literature. Magn Reson Med 45:533-542, 2001.

Blood↗

PubMed2001

Extracellular apparent diffusion in rat brain.

The apparent diffusion coefficients (ADCs) of a series of markers concentrated in the extracellular space of normal rat brain were measured to evaluate, by inference, the ADC of water in the extracellular space. The markers (mannitol, phenylphosphonate, and polyethylene glycols) are defined as "compartment selective" because tissue culture experiments demonstrate some leakage into the intracellular space, making them less "compartment specific" than commonly believed. These primarily extracellular markers have ADCs similar to those of intracellular metabolites of comparable hydrodynamic radius, suggesting that water ADC values in the intra- and extracellular spaces are similar. If this is the case, then it is unlikely that a net shift of water from the extra- to the intracellular space contributes significantly to the reduction in water ADC detected following brain injury. Rather, this reduction is more likely due primarily to a reduction of the ADC of intracellular water associated with injury.

Analysis of Variance↗

PubMed2001

Water and lipid MRI of the Xenopus oocyte.

Oocytes of Xenopus laevis are large, single cells that provide a promising model system for the exploration of the MR biophysics fundamental to more complex living systems. Previous studies have generally employed 2D spin-echo sequences with an image slice thickness greater than the thickness of the cellular volumes of interest. Also, the large cytoplasmic lipid signal has typically been ignored. This study describes separate, high-resolution 3D measurements of the water and lipid spin densities, T(1) and T(2) relaxation time constants, and the water apparent diffusion rate constant (ADC) in the Xenopus oocyte without significant partial volume artifacts. The lipid spin-density and values for water MR properties varied monotonically from the vegetal to animal poles, indicating that the border between the poles is not sharply demarcated. Regional water MR property values correlated with lipid signal intensity. Lipid-specific imaging is shown for which water suppression is achieved via high diffusion weighting in the imaging sequence.

Animals↗

PubMed2001

Impaired prostate tumorigenesis in Egr1-deficient mice.

The transcription factor early growth response protein 1 (EGR1) is overexpressed in a majority of human prostate cancers and is implicated in the regulation of several genes important for prostate tumor progression. Here we have assessed the effect of Egr1 deficiency on tumor development in two transgenic mouse models of prostate cancer (CR2-T-Ag and TRAMP). Using a combination of high-resolution magnetic resonance imaging and histopathological and survival analyses, we show that tumor progression was significantly impaired in Egr1-/- mice. Tumor initiation and tumor growth rate were not affected by the lack of Egr1; however, Egr1 deficiency significantly delayed the progression from prostatic intra-epithelial neoplasia to invasive carcinoma. These results indicate a unique role for Egr1 in regulating the transition from localized, carcinoma in situ to invasive carcinoma.

Animals↗

PubMed2001

Direct, longitudinal comparison of (1)H and (23)Na MRI after transient focal cerebral ischemia.

BACKGROUND AND PURPOSE: (23)Na MRI may offer new insight into the evaluation of tissue injury. We performed a direct, longitudinal, morphological comparison of (1)H T2 relaxation, (1)H apparent diffusion coefficient (ADC), (23)Na content, and histopathology after cerebral ischemia to address the hypotheses that (a) (23)Na MRI is unique in comparison to (1)H MRI, and (b) accumulation of (23)Na is an unambiguous marker for dead tissue. METHODS: Rats underwent 30 minutes of focal ischemia. MRIs of (1)H T2, (1)H ADC, and (23)Na content were acquired from 12 hours up to 1, 2, or 14 days after reperfusion. On excision, brains were stained with triphenyltetrazolium chloride (TTC). RESULTS: In all cases, the region of abnormality increased in size for 2 days. On day 5, both (1)H T2 and ADC temporarily appeared normal despite the presence of TTC-defined infarction. By comparison, the volume of tissue exhibiting abnormally intense (23)Na signal mirrored the TTC-defined infarct at all time points. CONCLUSIONS: Regions of high (23)Na content correlate well with the TTC-defined infarct and may be a quantitative in vivo marker for dead tissue. In contrast, the dynamics of the (1)H T2 and ADC make it difficult to interpret these images without additional information because they may appear normal despite infarction. Neither type of (1)H image delineates dead tissue, and none of these methods predicts the potential infarct size at early time points.

Animals↗

PubMed2000

Coupling between changes in human brain temperature and oxidative metabolism during prolonged visual stimulation.

A fundamental discovery of modern human brain imaging with positron-emission tomography that the blood flow to activated regions of the normal human brain increases substantially more than the oxygen consumption has led to a broad discussion in the literature concerning possible mechanisms responsible for this phenomenon. Presently no consensus exists. It is well known that oxygen delivery is not the only function of systemic circulation. Additional roles include delivery of nutrients and other required substances to the tissue, waste removal, and temperature regulation. Among these other functions, the role of regional cerebral blood flow in local brain temperature regulation has received scant attention. Here we present a theoretical analysis supported by empirical data obtained with functional magnetic resonance suggesting that increase in regional cerebral blood flow during functional stimulation can cause local changes in the brain temperature and subsequent local changes in the oxygen metabolism. On average, temperature decreases by 0.2 degrees C, but individual variations up to +/-1 degrees C were also observed. Major factors contributing to temperature regulation during functional stimulation are changes in the oxygen consumption, changes in the temperature of incoming arterial blood, and extensive heat exchange between activated and surrounding brain tissue.

Body Temperature↗

PubMed2000

Left ventricular torsion is equal in mice and humans.

Global cardiac function has been studied in small animals with methods such as echocardiography, cine-magnetic resonance imaging (MRI), and cardiac catheterization. However, these modalities make little impact on delineation of pathophysiology at the tissue level. The advantage of tagged cine-MRI technique is that the twisting motion of the ventricle, referred to as torsion, can be measured noninvasively, reflecting the underlying shearing motion of individual planes of myofibrils that generate wall thickening and ventricular ejection. Thus we sought to determine whether the mechanism of ventricular ejection, as measured by torsion, was the same in both humans and mice. Nine mice and ten healthy humans were studied with tagged cine-MRI. The magnitude and systolic time course of ventricular torsion were equivalent in mouse and humans, when normalized for heart rate and ventricular length. The end-systolic torsion angle was 12.7 +/- 1.7 degrees in humans vs. 2.0 +/- 1.5 degrees in mice unnormalized and 1.9 +/- 0.3 degrees /cm vs. 2.7 +/- 2.3 degrees /cm when normalized for ventricular length). These results support the premise that ventricular torsion may be a uniform measure of normal ventricular ejection across mammalian species and heart sizes.

Adult↗

PubMed1999

Transient magnetic resonance without RF pulses: fast field switching.

An unusual strategy for performing magnetic resonance experiments is demonstrated. Instead of employing conventional radiofrequency transmitter fields to perturb spin state populations away from equilibrium, as is the basis of most magnetic resonance spectrometers today, technological advances now make possible fast switching of the magnetic field orientation to achieve the same effect. This is demonstrated with an electron spin resonance experiment where the magnetic field is switched 90 degrees nonadiabatically with a dead time of a few tens of nanoseconds and an electron free induction decay observed.

Magnetic Resonance Spectroscopy↗

PubMed1999

Sepsis increases intracellular free calcium in brain.

Using magnetic resonance methods and a clinically relevant rodent model of sepsis, we have made in vivo measurements of increased intracellular calcium in a pathologic state in the CNS. The intracellular calcium concentration was increased nearly twofold in septic rat brain compared with controls (p < 0.0001). This result, in a fully intact functioning mammalian system, ties together a previous spectrum of indirect evidence from numerous laboratories suggesting an important role for elevated intracellular calcium in sepsis. In addition, levels of the proinflammatory cytokine tumor necrosis factor-a were elevated threefold in septic rat brain (p < 0.02), and electron microscopic examination revealed scattered injury in approximately 0.25% of glial cells. These findings are discussed in light of the current understanding of the pathophysiology of sepsis.

Animals↗

PubMed1998

Homonuclear J coupling effects in volume localized NMR spectroscopy: pitfalls and solutions.

It has been observed that the signal amplitude of multiplet resonances such as the 1H doublet resonance of lactate varies with pulse sequence timing when echo-driven volume selective methods such as point resolved spectroscopy are used. Herein a standard vectorial description is presented for the mechanism of this artifact, which results from the chemical shift between homonuclear scalar-coupled (i.e., J coupled) nuclei. The chemical shift causes the extent of a signal phase modulation to vary for different spatial regions of the excited voxel. This variation results in spatial interference effects that can lead to marked loss of signal intensity as well as corruption of the size and shape of the voxel from which signal is obtained. The phenomenon is substantial at an imaging field of 1.5 T and becomes especially pronounced at higher field strengths. Several strategies to avoid the artifact are provided.

Humans↗

PubMed1998

Evaluation of extra- and intracellular apparent diffusion in normal and globally ischemic rat brain via 19F NMR.

The biophysical mechanism(s) underlying diffusion-weighted MRI contrast following brain injury remains to be elucidated. Although it is generally accepted that water apparent diffusion coefficient (ADC) decreases after brain injury, it is unknown whether this is associated with a decrease in intracellular or extracellular water displacement, or both. To address this question, 2-[19F]luoro-2-deoxyglucose-6-phosphate (2FDG-6P) was employed as a compartment-specific marker in normal and globally ischemic rat brain. Through judicious choice of routes of administration, 2FDG-6P was confined to the intra- or extracellular space. There was no statistical difference between intra- and extracellular 2FDG-6P ADCs in normal or in globally ischemic brain (P > 0.16), suggesting that water ADCs in both compartments are similar. However, ischemia did result in a 40% ADC decrease in both compartments (P < 0.001). Assuming that 2FDG-6P reflects water motion, this study shows that water ADC decreases in both spaces after ischemia, with the reduction of intracellular water motion being the primary source of diffusion-weighted contrast.

Animals↗

PubMed1997

Quantification of ion transport in perfused rat heart: 133Cs+ as an NMR active K+ analog.

Proper ion balance between intra- and extracellular compartments is necessary for normal physiological function. Conversely, alterations in membrane ion transport occur in numerous pathological states. As a noninvasive, nondestructive spectroscopic technique, nuclear magnetic resonance (NMR) offers a powerful approach to the study of ion balance in intact biological systems. Unfortunately, rare NMR active nuclides that are isotopes of the 100% naturally abundant 23Na+ and 39K+ are not available for tracer kinetic studies of Na1 and K+ transport. However, Cs is a biologically active analog of K+, and the 100% naturally abundant NMR active 133Cs+ nuclide can be employed to examine K+ transport (Davis, D. G., E. Murphy, and R. E. London. Biochemistry 27: 3547-3551, 1988). The distinguishing feature of 133Cs+ is that it naturally gives two separate well-resolved NMR resonances for intra- and extra-cellular 133Cs+, permitting study of the time course changes of either of these compartments independent of the other. In this report, the experimental procedures and compartmental modeling formalism are developed that allow quantitative analysis of Cs+ membrane transport in the perfused rat heart. Intracellular 133Cs+ is shown to be 100% visible by solution-state NMR methods and its influx transport to be markedly inhibited by ouabain, a confirmation of findings previously reported by others. Intracellular 133Cs+ spin-lattice and spin-spin relaxation times at 7 T were determined to be 2.1 +/- 0.3 (SD)s (n = 8) and 0.065 +/- 0.007 (SD) s (n = 8), respectively, for T1 and T2. The rate constant for Na(+)-K(+)-ATPase pump dominated intracellular influx was measured to be 0.25 +/- 0.07 (SD) min-1 (n = 27) and that for efflux 0.005 +/- 0.001 (SD) min-1 (n = 14). The rate constant for 133Cs+ equilibration in the extracellular space at supraphysiological perfusate flow rate (20 ml/min) was found to be 4.6 +/- 0.9 (SD) min-1 (n = 20). Thus extracellular diffusion limitations do not dominate the 133Cs+ transport measurements.

Animals↗

PubMed1997

Inhibition of ion transport in septic rat heart: 133Cs+ as an NMR active K+ analog.

Sepsis, the systemic response to severe infection, and the resulting multiorgan failure it induces are major contributors to intensive care unit morbidity and mortality. A number of abnormalities in ion transport processes and intracellular free Na+ ([Na+]i) and K+ ([K+]i) concentrations have been reported to occur during sepsis/endotoxemia. An effect of sepsis on the NA(+)-K(+)-ATPase may be an important contribution to changes in intracellular ion balance and the resultant pathophysiology of the disorder. The purpose of this study was to examine the effect of sepsis on the Na(+)-K(+)-ATPase in the isolated perfused rat heart using 133Cs+ nuclear magnetic resonance (NMR). Cs+ is a K+ analog, and 133Cs-NMR offers the opportunity to examine Na(+)-K(+)-ATPase activity in the intact organ via tracer kinetics. Sepsis was induced in halothane-anesthetized male Sprague-Dawley rats using the cecal ligation and perforation (CLP) model. Twenty-four to thirty-six hours after surgery, hearts from CLP or sham-operated rats were perfused with Krebs-Henseleit buffer containing 1.25 mM Cs+. The influx rate constant for Cs+ was decreased by 24% in septic rat hearts, i.e., 0.25 +/- 0.08 (SD) min 1 for controls and 0.19 +/- 0.04 (SD) min-1 for septic animals (P = 0.003). There was no difference for Cs+ efflux [0.005 +/- 0.001 (SD) min-1 for controls and 0.005 +/- 0.002 (SD) min-1 for septic animals; P = 0.8]. These results are consistent with an inhibition of the Na(+)-K(+)-ATPase pump during sepsis/endotoxemia. A decrease in the activity of the Na(+)-K(+)-ATPase pump may be responsible for or contribute to the changes in [Na+]i and [K+]i during the disorder.

Animals↗

PubMed1996

Evaluation of intracellular diffusion in normal and globally-ischemic rat brain via 133Cs NMR.

The question of whether the apparent diffusion coefficient (ADC) of intracellular water changes after brain injury was addressed by using 133Cs as an indicator to report on the state of the intracellular environment. Cesium is an NMR-detectable potassium analog that accumulates in the intracellular space and is detectable in rat brain after being added to the animal's diet. The ADC of cesium was measured before and after the death of the rat. The cesium ADC fell from 0.91 +/- 0.05 x 10(-3) mm2/s (mean +/- SEM, n=5) in the alive rat to 0.71 +/- 0.05 x 10(-3) mm2/s within 20 min (the best time resolution of the experiment) of the death of the animal and stayed at this value for at least 3 h (p < 0.001). Assuming that the ADC of cesium reflects motion in the intracellular environment, these results support the idea that there are changes associated with cell injury that would cause a reduction in the ADC of intracellular water. Hence, one factor contributing to the decrease in water ADC after brain injury is a change in the ADC of intracellular water.

Animals↗

PubMed1996

The NMR chemical shift pH measurement revisited: analysis of error and modeling of a pH dependent reference.

A standard differential calculus-based propagation of error treatment is applied to the traditional chemical-exchange Henderson-Hasselbalch NMR pH model in which the reference shift is pH independent. It is seen naturally from this analysis that (i) the error minimum in derived pH occurs in the region where pH and indicator pKa are equal and that (ii) the dynamic range, or difference between the limiting chemical shifts of acid and base forms of indicator species, determines the insensitivity of the technique to propagation of errors. To extend the useful pH range and utility of NMR pH determination methodology, a more general model is developed in which the internal reference species is also considered as having a pH-dependent chemical shift. Data from standard solution pH titrations are fitted to both models and parameters are estimated for the normally observed family of ionizable phosphorus metabolites (ATP, inorganic phosphate, phosphoethanolamine and phosphocholine) and the xenometabolite 2-deoxyglucose-6-phosphate with either phosphocreatine, the alpha-phosphate of ATP, or H2O taken as the 31P or 1H chemical shift internal reference species as well as with an external reference.

Hydrogen-Ion Concentration↗

PubMed1996

Tumor 31P NMR pH measurements in vivo: a comparison of inorganic phosphate and intracellular 2-deoxyglucose-6-phosphate as pHnmr indicators in murine radiation-induced fibrosarcoma-1.

Uncertainty regarding the intracellular/extracellular distribution of inorganic phosphate (P(i)) in tumors has raised concerns that pH calculated from the tumor P(i) chemical shift may not accurately represent the intracellular pH (pHin). This issue was addressed in subcutaneously transplanted murine radiation induced fibrosarcoma-1 by directly comparing pH measured via P(i) with pH measured via the in situ generated intracellular xenometabolite 2-deoxyglucose-6-phosphate (2DG6P). In 131 comparative measurements employing eight tumor-bearing mice under both control and hyperglycemic conditions (the latter to extend the range of tumor pH examined), the pH as derived from either 2DG6P or P(i) showed only a small, but statistically significant, difference (0.07 +/- 0.11 SD; P = 0.0001). Scatter in the comparative analysis over the pH range examined (ca. 5.5-7.5) was not uniform. Above pH 6.6, 2DG6P indicated a pH lower than that of P(i) by 0.088 +/- 0.105 SD (n = 107, P = 0.0001); below pH 6.6, 2DG6P indicated a pH essentially identical to and not statistically different from that of P(i) (mean difference 0.003 +/- 0.128 SD (n = 24, P = 0.92)). Evidence is presented in support of this differential arising from a systematic measurement error due to peak overlap between 2DG6P and endogenous phosphomonoester species. These results support the use of P(i) as a tumor 31P NMR pHin indicator, at least in RIF-1 tumors under control and hyperglycemic conditions.

Animals↗

PubMed1995

On the use of 133Cs as an NMR active probe of intracellular space in vivo.

Data are presented from 133Cs NMR studies on both excised and in situ tissues from rats fed a regular diet and administered i.p. CsCI in aqueous solution for 6 to 14 days. Cesium is an NMR-active potassium analog which accumulates in the intracellular spaces of tissues [Davies et al., Biochemistry 27, 3547 (1988); Shehan, B.P. et al., Magn. Reson. Med. 30,573 (1993)]. Chemical shifts, relaxation properties, sensitivity and detectability of cesium in tissues were investigated. Consistent with previous reports, two resonances (representing intra- and extracellular cesium) were detected in blood. Only one resonance was detected in brain, kidney, and muscle tissue. Efforts to resolve intra- and extracellular components by T1 and T2 relaxation discrimination were not successful. Following i.p. administration, cesium accumulates intracellularly with a brain-to-cerebrospinal fluid concentration (mumol/g) ratio of 9:1 and a thigh muscle-to-plasma concentration ratio of 40:1. Considering the small extracellular volume in these tissues (ca 18% and 10%, respectively), the net content differences between intra- and extracellular cesium are approximately 40-fold in brain and 360-fold in muscle. The concentration ratio of cesium in brain to cesium in cerebrosinal fluid decreased to 3:1 1 h after death, indicating a relatively slow rate of leakage of cesium from the intra- to extracellular space in the face of bioenergetic failure. These data suggest that the cesium signal is dominated by the intracellularly located cesium and, thus, cesium may be useful as a probe of the intracellular environment despite an inability to resolve and directly observe distinct resonances from intra- and extracellular spaces.

Animals↗

PubMed1995

Model-based maximum-likelihood estimation for phase- and frequency-encoded magnetic-resonance-imaging data.

A maximum-likelihood (ML)-based magnetic-resonance-imaging (MRI) reconstruction algorithm is established, based on frequency- and phase-encoded data. The model on which the ML method is based is a superposition of exponentially decaying, sinc-modulated sinusoids, arising from the basic Bloch equations for MR spectroscopy, modified to account for the distribution of resonance frequencies and phases used for spatial localization in the image field. Spatial-localizing gradients are assumed to be known linear functions of spatial coordinate position, with the x-encode (frequency) gradient applied continuously during the full duration of data collection, and the y-encode (phase) gradient applied during varying time periods before data collection. A single-voxel emitter becomes sinc-modulated in the x, y directions at rates proportional to voxel size and gradient strengths in the x-encode and y-encode directions. The full two-dimensional MRI signal becomes a superposition of sinc-modulated, exponentially decaying, single-sinusoid emitters, one for each voxel. The ML estimation of spin-density and spin-spin relaxation decay time images becomes a nonlinear least-squares optimization problem; it is solved using an iterative expectation-maximization algorithm for estimating multiple modulated sinusoids in noise. Phantom studies are presented, demonstrating the accuracy of the model and the application of the algorithm to spin-density and spin-spin relaxation decay time profiles.

Algorithms↗