The T1 perfusion model has worked well in brain functional studies where flow changes are measured. Using selective and nonselective inversion pulses, a new method has been developed to study steady-state brain blood flow. The authors obtained flow-sensitive images using selective inversion and flow-insensitive images using nonselective inversion. Subtraction of flow-insensitive images from flow-sensitive images gave us flow-weighted images with good gray-white flow contrast in cortical gray matter as well as in the thalamus and basal ganglia. Fitting T1s of flow-insensitive and flow-sensitive images allowed us to obtain preliminary results of brain blood flow maps. Two specific problems can seriously affect the accuracy of the brain blood flow values and the gray-white flow contrast of brain blood flow maps. These are the problems of the partial volume effect of CSF and gray matter, and the difference between blood T1 and white matter T1. The authors discuss in detail the character of these problems and present a number of approaches to manage such problems.

The image intensity in many contrast agent perfusion studies is designed to be a function of bulk tissue T1, which is, in turn, a function of the compartmental (vascular, interstitial, and cellular) T1s, and the rate of proton exchange between the compartments. The goal of this study was to characterize the compartmental tissue Gd-DTPA relaxivities and to determine the proton exchange rate between the compartments. Expressing [Gd-DTPA] as mmol/liter tissue water, the relaxivities at 8.45 T and room temperature were: saline, 3.87 +/- 0.06 (mM.s)-1 (mean +/- SE; n = 29); plasma, 3.98 +/- 0.05 (mM.s)-1 (n = 6); and control cartilage (primarily an interstitium), 4.08 +/- 0.08 (mM.s)-1 (n = 17), none of which are significantly different. The relaxivity of cartilage did not change with compression, trypsinization, or equilibration in plasma, suggesting relaxivity is not influenced by interstitial solid matrix density, charge, or the presence of plasma proteins. T1 relaxation studies on isolated perfused hearts demonstrated that the cellular-interstitial water exchange rate is between 8 and 27 Hz, while the interstitial-vascular water exchange rate is less than 7 Hz. Thus, for Gd-DTPA concentrations, which would be used clinically, the T1 relaxation rate behavior of intact hearts can be modeled as being in the fast exchange regime for cellular-interstitial exchange but slow exchange for interstitial-vascular exchange. A measured relaxivity of 3.82 +/- 0.05 (mM.s)-1 (n = 8) for whole blood (red blood cells and plasma) and 4.16 +/- 0.02 (mM.s)-1 (n = 3) for frog heart tissue (cells and interstitium) (with T1 and Gd-DTPA concentration defined from the total tissue water volume) supports the conclusion of fast cellular-extracellular exchange. Knowledge of the Gd-DTPA relaxivity and maintaining Gd-DTPA concentration in the range so as to maintain fast cellular-interstitial exchange allows for calculation of bulk Gd-DTPA concentration from bulk tissue T1 within a calculable error due to slow vascular exchange.

The contrast-enhanced magnetic resonance imaging (MRI) signal is rarely a direct measure of contrast concentration; rather it depends on the effect that the contrast agent has on the tissue water magnetization. To correctly interpret such studies, an understanding of the effects of water movement on the magnetic resonance (MR) signal is critical. In this review, we discuss how water diffusion within biological compartments and water exchange between these compartments affect MR signal enhancement and therefore our ability to extract physiologic information. The two primary ways by which contrast agents affect water magnetization are discussed: (1) direct relaxivity and (2) indirect susceptibility effects. For relaxivity agents, for which T1 effects usually dominate, the theory of relaxation enhancement is presented, along with a review of the relevant physiologic time constants for water movement affecting this relaxation enhancement. Experimental issues that impact accurate measurement of the relaxation enhancement are discussed. Finally, the impact of these effects on extracting physiologic information is presented. Susceptibility effects depend on the size and shape of the contrast agent, the size and shape of the compartment in which it resides, as well as the characteristics of the water movement through the resulting magnetic field inhomogeneity. Therefore, modeling of this effect is complex and is the subject of active study. However, since susceptibility effects can be much stronger than relaxivity effects in certain situations, they may be useful even without full quantitation.