Jeffrey L. Evelhoch

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.

NMR T1 measurements in inhomogeneous B1 with surface coils

Abstract Spin-lattice relaxation measurements with surface coils used in the single coil mode on stationary samples will produce accurate T 1 values if a three-parameter exponential fit is employed. A further sufficient requirement is that the T 1 measurement method (pulse sequence) conform to the following three criteria at all points in the sensitive volume of the surface coil. (i) The Z magnetization is consistently prepared to a nonequilibrium value at time zero. This initial condition must be the same at the start of every evolution period. (ii) After preparation, the magnetization is allowed to return toward thermal equilibrium during variable evolution periods τ. (iii) A constant fraction of the Z magnetization must then be sampled (observed) at the end of the evolution period. The inversion recovery, modified fast inversion recovery, and pulse-burst saturation recovery methods meet criteria (i)-(iii) and produce accurate T 1 values with a surface coil. A brief survey of surface coil T 1 measurements suggests that the greatest dynamic range is provided by using the inversion recovery or modified fast inversion recovery method, the pulse-burst saturation recovery method provides accurate T 1 measurements in a minimum amount of time, and the use of composite pulses does not significantly improve the accuracy of the measurement.

Correlations between 31P NMR spectroscopy and 15O perfusion measurements in the RIF-1 murine tumor in vivo.

The tumor physiological environment is one of the least understood and most important factors in determining the response of solid tumors to cancer therapy. To examine several important characteristics of the tumor physiological environment we have used in situ photon activation-15O decay measurements (perfusion characteristics) and 31P surface coil-NMR spectroscopy (metabolic characteristics) to observe in vivo subcutaneous RIF-1 tumors grown in female C3H/Anf mice. The following correlations between the 15O perfusion characteristics and the 31P NMR metabolic characteristics in individual tumors were observed: a negative correlation between pH, as measured by NMR (pHNMR), and the inorganic phosphate to nucleosides triphosphate peak height ratio (Pi:NTP); for the well-perfused fraction of the tumor there is a positive correlation with both pHNMR and the phosphocreatine to nucleosides triphosphate peak height ratio (PCr:NTP), and a negative correlation with Pi:NTP. These correlations are interpreted as evidence for a direct relationship between the distribution of cellular physiological environments and the tumor metabolic state. Because these physiological characteristics affect tumor response to various therapeutic modalities and both measurements can be made on humans, it is suggested that these techniques may be of prognostic value in the clinical management of human cancer.

Deuterium NMR tissue perfusion measurements using the tracer uptake approach: I. Optimization of methods.

This paper considers potential problems encountered when using the Kety approach to measure perfusion in small laboratory animals with nuclear magnetic resonance (NMR) tracer uptake methods: a) the need to measure the arterial input function (AIF) in each animal; b) sensitivity to perfusion heterogeneity; c) sensitivity to low signal‐to‐noise ratio (SNR); and d) influence of changes in the AIF. A method to estimate the AIF in rats is presented that derives an AIF from the time course of a tracer passing through a carotid chamber. The results of computer simulations indicate that a common AIF obtained in one set of animals can be used for perfusion estimations in another set of animals if the tracer is delivered as a dose and that optimal data analysis (fitting data vs. integration approach) is dictated by SNR and perfusion heterogeneity. Experimental strategies are suggested to minimize the effects of changes in the individual AIF that could distort perfusion estimates. Magn Reson Med 42:42–52, 1999.

The surface-coil NMR receiver in the presence of homogeneous B1 excitation

Abstract The signal intensity and inherent spatial localization in a single-pulse steady-state experiment using a circular surface receiver coil in the presence of a homogeneous rf excitation magnetic field ( B 1 ) is examined theoretically by computer simulation assuming zero interaction between the transmission-coil and the surface-coil radiofrequency circuits. The theoretical analysis is verified by NMR experiments employing appropriate “phantom” samples with the surface coil orthogonal to the transmitter coil to minimize interaction between the two. Under slow pulse repetition conditions the signal intensity of the homogeneous B 1 transmission-surface-coil reception experiment is essentially the same as that obtained in the single-coil configuration surface-coil experiment and is independent of the orientation of the homogeneous B 1 with respect to the surface coil. A significant consequence of this result is that the optimum performance of multiple-pulse sequences which require specific flip angles over the whole sample should be attained while retaining the spatially restrictive sensitivity profile of the surface coil. The homogeneous B 1 transmission-surface-coil reception sensitive volume penetrates deeper into the sample than the surface-coil single-coil configuration sensitive volume, and therefore may be a more appropriate shape for in vivo NMR spectroscopy. The homogeneous B 1 transmission actually induces more xy magnetization than surface-coil transmission does, but differences in signal phase from different regions of the sample result in an incoherent addition when the signal from all parts of the sample are summed together. In imaging experiments, each volume element of the sample is uniquely characterized by its Larmor frequency and phase, thus, signal reduction due to phase differences is absent.

Deuterium NMR tissue perfusion measurements using the tracer uptake approach: II. comparison with microspheres in tumors

Whole‐volume tumor perfusion measured using nuclear magnetic resonance (NMR) observation of deuterated water uptake after intravenous injection and a common arterial input function (AIF) derived from AIF estimates in a small set of animals was compared with perfusion measured by the commonly used microsphere method in rat 9L gliosarcomas. Tumor perfusion estimated with this optimized NMR technique using an appropriate common AIF (i.e., taking into account the duration of anesthesia) correlates highly (n = 13, P = 0.001) with that measured by the microsphere method, yielding no significant differences (P = 0.5, paired Students t‐test). Thus, the optimized NMR method can be used for repeatable, non‐invasive, and quantitative measurements of tumor perfusion. Magn Reson Med 42:240–247, 1999.

Magnetic Resonance in Experimental and Clinical Oncology

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Defining the pHi-Hyperthermia Sensitivity Relationship for the RIF-1 Tumor In Vivo: A 31P MR Spectroscopy Study

Abstract Spees, W. M., Evelhoch, J. L., Thompson, P. A., Sloop, D. J. and Ackerman, J. J. H. Defining the pHi-Hyperthermia Sensitivity Relationship for the RIF-1 Tumor In Vivo: A 31P MR Spectroscopy Study. Radiat. Res. 164, 86–99 (2005). This study quantifies the enhancement of the therapeutic efficacy of hyperthermia resulting from an acutely acidified and accurately monitored intracellular pH (pHi) in a mouse tumor model in vivo. Metabolic manipulation of the physiology of RIF-1 tumor (subcutaneous, on the hind flanks of female C3H/HeJ mice) achieved by i.p. bolus injection of glucose (glycolytic tumor acidification) or 3-O-methylglucose (non-glycolytic tumor acidification) was monitored by 31P magnetic resonance (31P MR) prior to, during and up to 1 h after localized hyperthermia. The pre-hyperthermia 31P MR-observable metabolic parameter that correlates most strongly with thermal sensitivity is pHi. Thermal sensitivity increases linearly with decreasing pHi regardless of the mechanism (glycolytic or non-glycolytic) of metabolic manipulation. The quantitative relationship is described by log10(SF)/EQ43 = 0.0079 pHi,preHT −0.0606 (R = 0.63, P < 0.0001), where EQ43 is the thermal heat dose delivered to the tumor (in units of equivalent minutes at 42.5°C), pHi,preHT is the intracellular pH immediately prior to hyperthermia, and SF is the surviving fraction. The therapeutic enhancement is not as dramatic as expected based upon previously reported in vitro studies but is generally consistent with other in vivo studies. The method still represents a viable strategy for enhancing the therapeutic efficacy of hyperthermia, especially when used in combination with other therapeutic modalities.

31P and 2H MRS Studies of Flavone Acetic Acid and Analogues

Flavone acetic acid [FAA, NSC-347512, LM-975 (LIPHA Pharmaceuticals; Lyon, France); see Figure 1] is a novel antitumor agent with unique therapeutic characteristics. FAA is broadly active against murine transplantable solid tumors growing subcutaneously (s.c.) including several which are insensitive to standard chemo-therapeutic agents (1–5; see Table 1). Conversely, FAA has no activity against murine leukemias or lymphomas generally sensitive to the agents currently used clinically (see Table 1). In both humans and animals treated with non-lethal doses of FAA, no long-term toxic effects are evident (4,5,7–9). Toxicities observed include transient sedation (reversible in minutes to a few hours), reversible gastrointestinal and nervous system effects, and hypotension. In mice, there is a narrow therapeutic range and activity is markedly reduced for split doses (2,3). These effects appear to be due to non-linear pharmacokinetics associated with elimination and plasma protein binding (10,11).