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.

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.

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.