Regional tumor oxygen tension: fluorine echo planar imaging of hexafluorobenzene reveals heterogeneity of dynamics.

PURPOSE: Therapeutic success could be enhanced if therapy were tailored to the characteristics of specific tumors. We have been developing novel approaches to measuring tumor oxygen tension in vivo, and recently reported a method based on 19F nuclear magnetic resonance (NMR) spin lattice echo planar imaging (EPI) relaxometry of hexafluorobenzene (HFB). We have now examined the feasibility of monitoring dynamic changes in regional tumor oxygenation in response to respiratory challenge. Preliminary data in one tumor show distinct differences before and subsequent to irradiation. METHODS AND MATERIALS: Dunning prostate adenocarcinoma R3327-AT1 was grown in the form of pedicles on the foreback of male Copenhagen rats. When the tumors reached approximately 1 cm diameter, HFB (40 microl) was administered by direct intratumoral injection deliberately dispersed to interrogate both central and peripheral regions. Local pO2 was determined using pulse burst saturation recovery 19F NMR EPI on the basis of the spin lattice relaxation rate. RESULTS: Interrogation of both central and peripheral regions of tumors showed bimodal distribution for oxygenation, including many voxels with pO2 < 15 torr. Altering the inspired gas to 100% O2 produced significant elevation for regions with initially high pO2 (P < 0.01), but the temporal course of dynamic changes varied for each voxel. Many voxels with low pO2 showed little response. Following irradiation (20 Gy), tumor oxygenation was significantly elevated and remained high for at least 10 h. CONCLUSION: We believe this method provides a valuable new approach to investigate tumor oximetry that may extend our understanding of tumor physiology, and could have prognostic value.

Regional tumor oxygen dynamics: 19F PBSR EPI of hexafluorobenzene.

We demonstrate a novel approach to measuring regional tumor oxygen tension using 19F pulse burst saturation recovery echo planar imaging (EPI) relaxometry of hexafluorobenzene. Hexafluorobenzene offers exceptional sensitivity to changes in oxygen tension, and has a single resonance making it ideal for imaging studies. By combining a pulse burst saturation recovery preparation sequence with EPI, the relaxation experiments were performed in approximately 20 min facilitating measurements of dynamic changes in pO2 accompanying interventions. Direct intratumoral administration of hexafluorobenzene permitted labeling of specific regions of interest, and imaging provided maps of pO2, confirming distinct intra tumoral heterogeneity. For a group of three Dunning prostate adenocarcinoma R3327-AT1 tumors interrogation of the central tumor region showed skewed pO2 distributions with considerable radiobiological hypoxia (approximately 90% voxels had pO2 < 15 torr) when rats breathed 33% O2. Altering the inspired gas to pure oxygen caused distributions to shift towards increased pO2 with significant increases in mean oxygen tension (p < 0.05) in two cases. Interrogation of both central and peripheral regions in a fourth tumor showed bimodal distribution for tumor oxygenation including approximately 75% voxels with pO2 > 15 torr. EPI allows the fate of individual voxels to be traced: upon altering the inspired gas to pure oxygen those voxels with baseline pO2 > 30 torr showed significant changes (p < 0.05), whereas those with pO2 < 16 torr showed minimal response. The precision of the measurements, together with the ability to simultaneously examine dynamic changes in multiple regions should provide a useful technique for investigating tumor hypoxia with respect to therapy.

Oxygen tension mapping with F-19 echo-planar MR imaging of sequestered perfluorocarbon.

The authors used fluorine-19 inversion-recovery (IR) echo-planar imaging (EPI) to map oxygen tension on the basis of the spin-lattice relaxation rate (R1) of sequestered perfluorocarbon. R1 measured with IR-EPI varied as a linear function of oxygen tension and temperature, and the relationship agreed well with earlier spectroscopic findings. Oxygen tension maps of a mouse that had received a dose of perflubron emulsion were acquired before, during, and after the mouse breathed pure oxygen. Results showed low liver oxygen tension during air breathing, which increased during breathing of pure oxygen, with distinct regional heterogeneity, to 8-17% atm (60-130 torr [8.0-17.3 kPa]).

Echo planar imaging of perfluorocarbons.

Emulsions of perfluorotributylamine (FTBA) and perflubron were evaluated for their utility in 19F echo planar imaging. Fluorine images of the emulsions were obtained in a phantom and two mice that had been predosed. Both agents, but particularly perflubron, show potential for fluorine echo planar studies because of the long spin-spin relaxation times of the CF3 resonances. High resolution thin slice images obtained in as little as 26.6 ms are presented.

A MRI gradient waveform model for automated sequence calibration.

In order to set up magnetic resonance imaging (MRI) procedures of arbitrary voxel dimensions, slice orientation, and sequence timing in a reasonable time, some form of automatic gradient pulse calibration is required. One such method, involving simulation of gradient waveforms, is presented. Waveforms are modeled based on measurements of the step response. The model used divides each transition into three time regions: a "start" region in the first 0.3 ms, a "slew" region, and a "tail" region representing decay of the eddy current compensation error. In the "slew" region, the time derivative of the gradient, G' (t), is expressed as a function of G(t). The first two regions are nonlinear with respect to demand. The mean error in the simulated gradient is generally less than 0.04 mT m-1 in spin echo sequences. Image signal/noise ratios resulting from sequences calibrated using the model are within 5% of those of empirically calibrated sequences.

Absence of exercise-induced MRI enhancement of skeletal muscle in McArdle's disease.

To assess the role of glycogenolysis in mediating exercise-induced increases in muscle water as monitored by changes in muscle proton relaxation times on magnetic resonance imaging (MRI) and cross-sectional area (CSA), five patients with myophosphorylase deficiency (MPD) were compared with seven controls. Absolute and relative work loads were matched during ischemic handgrip and graded cycling, respectively. Relaxation times of active muscle did not increase after handgrip in MPD (T1: 1 +/- 14%, P greater than 0.1; T2: 4 +/- 4%, P greater than 0.1) but did in controls (T1: 59 +/- 30%, P less than 0.005; T2: 26 +/- 9%, P less than 0.005). The volume of exercised muscles, estimated by CSA, increased in both groups after handgrip (controls: 13.8 +/- 3.5%, n = 7, P less than 0.0001; MPD: 7.5 +/- 1.5%, n = 4, P less than 0.005), but the change was greater in controls (P less than 0.02). Ischemic handgrip in controls resulted in a large increase in finger flexor signal intensity (SI) on short tau-inversion recovery images (25 +/- 7%, n = 3; P less than 0.005 compared with preexercise) and a further increase with subsequent reflow (43 +/- 11%, n = 3; P less than 0.001 compared with rest); in MPD, SI did not increase. The ratio of active to inactive muscle SI did not increase from rest to maximal cycle exercise in MPD (0 +/- 20%, n = 2, P greater than 0.1) but did in normals (73 +/- 36%, n = 3; P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Lipid/water ratio of bone marrow measured by phase-encoded proton nuclear magnetic resonance spectroscopy.

Proton NMR spectroscopy (spatially resolved) at 0.7 Tesla with a whole body superconducting magnet was performed on bone marrow from human lumbar spine to measure the lipid/water ratio. Phase-encoded proton spectroscopy was performed by using (1) a spin-echo sequence with selective 90 degrees and 180 degrees rf pulses on the Z and X axes; (2) 64 different phase encodes along the Y axis; and (3) echo acquisition with no gradient. The lipid/water ratios also were measured by the Folch chemical extraction technique. The set of phase-encoded spectra obtained from the spine demonstrates the chemical difference between the vertebral disk (large water peak and no lipid peak) and the marrow (smaller water peak and detectable lipids). Lipid/water ratios were lower than the chemically measured ratios. The phase-encoded proton spectroscopic technique presented in this study allowed rapid acquisition of localized spectra from the bone marrow in each of three vertebral bodies of the intact human spine. This technique provided a measure of the mobile lipid/water ratio weighted by relaxation times.