Joseph J. H. Ackerman

Water proton MR properties of human blood at 1.5 Tesla: Magnetic susceptibility, T1, T2, 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 1H2O 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) = So · 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°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.

Rapid vacuolar sequestration: the horseweed glyphosate resistance mechanism.

BACKGROUND Glyphosate-resistant (GR) weed species are now found with increasing frequency and threaten the critically important glyphosate weed-management system [corrected]. RESULTS The reported (31)P NMR experiments on glyphosate-sensitive (S) and glyphosate-resistant (R) horseweed, Conyza canadensis (L.) Cronq., show significantly more accumulation of glyphosate within the R biotype vacuole. CONCLUSIONS Selective sequestration of glyphosate into the vacuole confers the observed horseweed resistance to glyphosate. This observation represents the first clear evidence for the glyphosate resistance mechanism in C. canadensis.

Modeling dendrite density from magnetic resonance diffusion measurements.

Diffusion-weighted imaging (DWI) provides a noninvasive tool to probe tissue microstructure. We propose a simplified model of neural cytoarchitecture intended to capture the essential features important for water diffusion as measured by NMR. Two components contribute to the NMR signal in this model: (i) the dendrites and axons, which are modeled as long cylinders with two diffusion coefficients, parallel (D(L)) and perpendicular (D(T)) to the cylindrical axis, and (ii) an isotropic monoexponential diffusion component describing water diffusion within and across all other structures, i.e., in extracellular space and glia cells. The model parameters are estimated from 153 diffusion-weighted images acquired from a formalin-fixed baboon brain. A close correspondence between the data and the signal model is found, with the model parameters consistent with literature values. The model provides an estimate of dendrite density from noninvasive MR diffusion measurements, a parameter likely to be of value for understanding normal as well as abnormal brain development and function.

Statistical model for diffusion attenuated MR signal.

A general statistical model that can describe a rather large number of experimental results related to the structure of the diffusion‐attenuated MR signal in biological systems is introduced. The theoretical framework relies on a phenomenological model that introduces a distribution function for tissue apparent diffusion coefficients (ADC). It is shown that at least two parameters—the position of distribution maxima (ADC) and the distribution width (σ)—are needed to describe the MR signal in most regions of a human brain. A substantial distribution width, on the order of 36% of the ADC, was found for practically all brain regions examined. This method of modeling the MR diffusion measurement allows determination of an intrinsic tissue‐specific ADC for a given diffusion time independent of the strength of diffusion sensitizing gradients. The model accounts for the previously found biexponential behavior of the diffusion‐attenuated MR signal in CNS. Magn Reson Med 50:664–669, 2003.

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.

Absolute molar concentrations by NMR in inhomogeneous B1. A scheme for analysis of in vivo metabolites

The use of multiple tuned radiofrequency coils is described as a method for obtaining absolute in vivo metabolite concentrations explicitly from high resolution chemical shift spectra and zeugmatographic spin images recorded using pulse Fourier transform NMR. Further delineation to intracellular concentrations by a complimentary NMR experiment is also discussed. In instances where the alternating magnetic field distribution, B1, is determined predominantly by coil geometry, the magnitude of B1 for a multiple tuned coil will map equally over space for each coil frequency and this allows the matching of flip angles over space for each nuclide of interest. In the particular case where one of the resonances under consideration is 1H from H2O, the ratio of signal intensities for two nuclides (e.g., 31P1H) can be used to obtain the individual concentrations of each metabolite having a resonance (e.g., 31P) in the high resolution spectrum. More generally, the intensity ratio can be used to obtain a total concentration distribution for given nuclides in the spin image. This suggests a possible method for image contrast enhancement. The method is valid for uniform B1 as used in low frequency imaging (ca. ⩽ 30 MHz) and with inhomogeneous B1 as produced by surface coils at higher frequencies. A brief background development is presented along with a discussion of the practical application and its demonstration using examples employing 1H, 23Na, 31P, and 39K NMR.

Equilibrium Water Exchange Between the Intra- and Extracellular Spaces of Mammalian Brain

This report describes the measurement of water preexchange lifetimes and intra/extracellular content in intact, functioning mammalian brain. Intra‐ and extracellular water magnetic resonance (MR) signals from rat brain in vivo were quantitatively resolved in the longitudinal relaxation domain following administration of an MR relaxation agent into the extracellular space. The estimated intracellular water content fraction was 81% ± 8%, and the intra‐ to extracellular exchange rate constant was 1.81 ± 0.89 s–1 (mean ± SD, N = 9), corresponding to an intracellular water preexchange lifetime of ∼550 ms. These results provide a temporal framework for anticipating the water exchange regime (fast, intermediate, or slow) underlying a variety of compartment‐sensitive measurements. The method also supplies a means by which to evaluate membrane water permeability and intra/extracellular water content serially in intact tissue. The data are obtained in an imaging mode that permits detection of regional variations in these parameters. Magn Reson Med 50:493–499, 2003.

Evidence that both fast and slow water ADC components arise from intracellular space.

Evaluation of water diffusion in the brain has revealed both fast‐ and slow‐diffusing water populations. It has been suggested that these populations represent extra‐ and intracellular water, respectively. We have identified and characterized both populations in the intracellular space of the Xenopus oocyte. We have also determined their T1 and T2 relaxation properties. The fast and slow intracellular populations have diffusion coefficients of 1.06 ± 0.05 μm2/ms and 0.16 ± 0.02 μm2/ms, respectively, with the fast fraction representing 89% ± 1% of the total water signal. These values are quite similar to those for total water in brain and are observed in the absence of signal from the perfusate (extracellular) water population. Volumetric swelling (16% ± 4%) of the oocyte in hypoosmotic media increased the diffusion coefficients of both intracellular populations (fast = 1.27 ± 0.03 μm2/ms, slow = 0.22 ± 0.02 μm2/ms), but did not change their relative signal fractions. This phenomenon runs counter to the effects observed in brain injury, following which the apparent diffusion coefficient (ADC) decreases 30–50%. The results presented herein suggest that this ADC decrease in brain occurs despite cell swelling, which by itself would be expected to induce an increase in intracellular diffusion coefficients. Magn Reson Med 48:765–770, 2002.

Fatty liver in familial hypobetalipoproteinemia triglyceride assembly into VLDL particles is affected by the extent of hepatic steatosis

Familial hypobetalipoproteinemia (FHBL) subjects may develop fatty liver. Liver fat was assessed in 21 FHBL with six different apolipoprotein B (apoB) truncations (apoB-4 to apoB-89) and 14 controls by magnetic resonance spectroscopy (MRS). Liver fat percentages were 16.7 ± 11.5 and 3.3 ± 2.9 (mean ± SD) (P = 0.001). Liver fat percentage was positively correlated with body mass index, waist circumference, and areas under the insulin curves of 2 h glucose tolerance tests, suggesting that obesity may affect the severity of liver fat accumulation in both groups. Despite 5-fold differences in liver fat percentage, mean values for obesity and insulin indexes were similar. Thus, for similar degrees of obesity, FHBL subjects have more hepatic fat. VLDL-triglyceride (TG)-fatty acids arise from plasma and nonplasma sources (liver and splanchnic tissues). To assess the relative contributions of each, [2H2]palmitate was infused over 12 h in 13 FHBL subjects and 11 controls. Isotopic enrichment of plasma free palmitate and VLDL-TG-palmitate was determined by mass spectrometry. Non-plasma sources contributed 51 ± 15% in FHBL and 37 ± 13% in controls (P = 0.02). Correlations of liver fat percentage and percent VLDL-TG-palmitate from liver were r = 0.89 (P = 0.0001) for FHBL subjects and r = 0.69 (P = 0.01) for controls. Thus, apoB truncation-producing mutations result in fatty liver and in altered assembly of VLDL-TG.

Signal-to-noise optimization and observed volume localization with circular surface coils

Abstract Sensitivity optimization in surface coil NMR is complicated by the inhomogeneity (or shape) of the B 1 field produced by the surface coil antenna. The sensitivity and the size and location of the observed volume are dependent upon experimental conditions. Therefore, we have derived three-dimensional signal intensity maps for a single-turn, flat, circular coil operating on resonance in the single-coil mode to determine the effect of experimental conditions on the sensitivity and spatial characteristics of the observed volume. The results indicate that rapid repetition rates ( T ⪡ T 1 ) provide optimum sensitivity and contribute significant signal intensity from regions not immediately adjacent to the coil. Intermediate repetition rates ( T ∼ T 1 ) provide a significant sensitivity increase over slow repetition rates ( T ⩾ 5 T 1 ) while localizing the volume observed primarily to regions adjacent to the coil. For homogeneous samples further separated from the coil (0.2–0.4 radii), longer pulse widths provide signal from a large region of the sample with a minimum loss in sensitivity. This analysis is verified by agreement of calculated and experimental total intensities as a function of flip angle (pulse width), relaxation time ( T 1 ), and repetition rate. Furthermore, the results from 2 H (30 MHz) and 19 F (188 MHz) NMR experiments with ionic and nonionic solutions indicate that rf attenuation problems associated with conductive samples are not likely to be significant in surface coil NMR experiments that utilize small diameter coils at high fields.