Impact of transvascular and cellular–interstitial water exchange on dynamic contrast‐enhanced magnetic resonance imaging estimates of blood to tissue transfer constant and blood plasma volume

Purpose:

To examine the effect of transvascular (k_be) and cellular–interstitial water protons exchange (k_ie) in estimates of the blood‐to‐tissue contrast agent transfer rate constant (K^trans), interstitial volume fraction (v_e), and blood plasma volume fraction (v_p) using a full three‐site two exchange (3S2X) model.

Materials and Methods:

Using the Bloch‐McConnell equations, magnetic resonance imaging (MRI) signal arising from a 3S2X system was derived for the T₁‐weighted spoiled gradient‐recalled echo (SPGR) pulse sequence. To model the effects of k_be and k_ie on estimates of R₁, the MRI‐measured arterial input function, the different sets of values of kinetic parameters: K^trans, v_e, and v_p and water protons exchange rates, k_be and k_ie, were used. To calculate the tissue water protons R₁, the signal evolving from a 3S2X model was set to a monoexponential function. By comparing the estimated K^trans, v_e, and v_p with their simulated model truth values, the impact of k_be and k_ie on K^trans, v_e, and v_p was evaluated.

Results:

v_p was strongly underestimated and K^trans and v_e were much less influenced by k_be, when k_ie was held constant. When k_be was held constant, the k_ie had a significant effect on K^trans and v_e and less effect on v_p.

Conclusion:

The full 3S2X model allows accurate estimation of K^trans, v_e, and v_p and rates of water proton exchange. J. Magn. Reson. Imaging 2013;37:435–444. © 2012 Wiley Periodicals, Inc.     

Three‐compartment T1 relaxation model for intracellular paramagnetic contrast agents

The goal of this work was to elaborate a model describing the effective longitudinal relaxation rate constant R₁ for ¹H₂O in three cellular compartments experiencing possible equilibrium water exchange, and to apply this model to explain the effective R₁ dependence on the overall concentration of a cell‐internalized Gd³⁺‐based contrast agent (CA). The model voxel comprises three compartments representing extracellular, cytoplasmic, and vesicular (e.g., endosomal, lysosomal) subcellular spaces. Relaxation parameters were simulated using a modified Bloch–McConnell equation including magnetization exchange between the three compartments. With the model, several possible scenarios for internalized CA distribution were evaluated. Relaxation parameters were calculated for contrast agent restricted to the cytoplasmic or vesicular compartments. The size or the number of CA‐loaded vesicles was varied. The simulated data were then separately fitted with empirical mono‐ and biexponential inversion recovery expressions. The voxel CA‐concentration dependencies of R₁ can be used to qualitatively and quantitatively understand a number of different experimental observations reported in the literature. Most important, the simulations reproduced the relaxivity “quenching” for cell‐internalized contrast agent that has been observed. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.     

Manganese-enhanced magnetic resonance imaging (MEMRI) of rat brain after systemic administration of MnCl2: changes in T1 relaxation times during postnatal development

PURPOSE: To measure regional T(1) changes in the postnatal rat brain following systemic administration of the contrast agent manganese chloride (MnCl(2)). MATERIALS AND METHODS: MnCl(2) (120 mM) was administered intravenously (i.v.) at 1.25 mL/hour to a dose of 175 mg/kg body weight. MRI experiments were performed on anaesthetized animals (32 male Wistar rats, postnatal days (PDs) 11, 16, 21, and 31) at 2.0 T. Regions of interest (ROIs) were drawn in sagittal slices and placed over five brain regions: olfactory bulb, cerebellum, cortex, thalamus, and hypothalamus. The signal intensities of each ROI were measured and fitted to a three-parameter function to estimate T(1) values. RESULTS: In the brains of animals who did not receive the contrast agent (control group), we observed a consistent age-dependent decrease in T(1) values. In the brains of manganese-infused animals (manganese group), however, T(1) values were significantly lower than in the control group, indicating the uptake of manganese, but no dependence of T(1) on age was found. CONCLUSION: Our T(1) measurements indicate that the relative Mn(2+) concentrations are higher in neonates and decrease with brain development. An estimate of the relative cortical concentration of manganese shows a two-fold drop from PD 11 to PD 31.     

A longitudinal study of R2* and R2 magnetic resonance imaging relaxation rate measurements in murine liver after a single administration of 3 different iron oxide-based contrast agents

OBJECTIVE: The objective of this study was to investigate the duration of R2* and R2 enhancement in murine liver in vivo after administration of a single dose of 3 different iron oxide-based contrast agents. MATERIALS AND METHODS: Murine liver R2* and R2 were quantified longitudinally postadministration of 2.5 mgFe/kg ferumoxides, 2.5 mgFe/kg ferumoxytol, 2.5 or 5 mgFe/kg feruglose, or saline over 50 days. Changes in R2* and R2 were evaluated histologically using Perl's staining and by atomic absorption spectrometry. RESULTS: All 3 contrast agents significantly increased liver R2* and R2 4 hours after challenge. After 10 days, R2* and R2 for both the ferumoxides and ferumoxytol cohorts had recovered to saline control levels, whereas the faster R2* and R2 of the feruglose cohort was sustained and significantly faster than control at day 50. Histology revealed feruglose in both Kupffer and endothelial cells, whereas both ferumoxides and ferumoxytol were associated with the Kupffer cells. CONCLUSION: Compared with ferumoxides and ferumoxytol, feruglose exhibits prolonged R2* and R2 enhancement of murine liver.     

Cellular‐interstitial water exchange and its effect on the determination of contrast agent concentration in vivo: Dynamic contrast‐enhanced MRI of human internal obturator muscle

The purpose of this study was to assess the effects of cellular‐interstitial water exchange on estimates of tracer kinetics parameters obtained using rapid dynamic contrast‐enhanced (DCE) MRI. Data from the internal obturator muscle of six patients were examined using three models of water exchange: no exchange (NX), fast exchange limit (FXL), and intermediate rate (shutter‐speed [SS]). In combination with additional multiple flip angle (FA) data, a full two‐pool exchange model was also used. The results obtained using the NX model (transfer constant, K^trans = 0.049 ± 0.027 min^–1, apparent interstitial volume, v_e = 0.14 ± 0.04) were marginally higher than those obtained using the FXL model (K^trans = 0.045 ± 0.025 min^–1, v_e = 0.13 ± 0.04), but the error bars overlapped in two‐thirds of these parameter estimate pairs. Estimates of K^trans and v_e obtained using the SS model exceeded those obtained using the NX model in half the patients, and many estimates, including all those of intracellular residence time of water, t_i, were imprecise. Results obtained using the full two‐pool model fell between those obtained using FXL and NX models, and estimates of t_i were also imprecise. The results suggest that data obtained using clinically relevant DCE‐MRI are exchange‐insensitive and unsuitable for the assessment of cellular‐interstitial water exchange. Magn Reson Med 60:1011–1019, 2008. © 2008 Wiley‐Liss, Inc.