Water diffusion-exchange effect on the paramagnetic relaxation enhancement in off-resonance rotating frame

Abstract

The off-resonance rotating frame technique based on the spin relaxation properties of off-resonance T1rho can significantly increase the sensitivity of detecting paramagnetic labeling at high magnetic fields by MRI. However, the in vivo detectable dimension for labeled cell clusters/tissues in T1rho-weighted images is limited by the water diffusion-exchange between mesoscopic scale compartments. An experimental investigation of the effect of water diffusion-exchange between compartments on the paramagnetic relaxation enhancement of paramagnetic agent compartment is presented for in vitro/in vivo models. In these models, the size of paramagnetic agent compartment is comparable to the mean diffusion displacement of water molecules during the long RF pulses that are used to generate the off-resonance rotating frame. The three main objectives of this study were: (1) to qualitatively correlate the effect of water diffusion-exchange with the RF parameters of the long pulse and the rates of water diffusion, (2) to explore the effect of water diffusion-exchange on the paramagnetic relaxation enhancement in vitro, and (3) to demonstrate the paramagnetic relaxation enhancement in vivo. The in vitro models include the water permeable dialysis tubes or water permeable hollow fibers embedded in cross-linked proteins gels. The MWCO of the dialysis tubes was chosen from 0.1 to 15 kDa to control the water diffusion rate. Thin hollow fibers were chosen to provide sub-millimeter scale compartments for the paramagnetic agents. The in vivo model utilized the rat cerebral vasculatures as a paramagnetic agent compartment, and intravascular agents (Gd-DTPA)30-BSA were administrated into the compartment via bolus injections. Both in vitro and in vivo results demonstrate that the paramagnetic relaxation enhancement is predominant in the T1rho-weighted image in the presence of water diffusion-exchange. The T1rho contrast has substantially higher sensitivity than the conventional T1 contrast in detecting paramagnetic agents, especially at low paramagnetic agent volumetric fractions, low paramagnetic agent concentrations, and low RF amplitudes. Short pulse duration, short pulse recycle delay and efficient paramagnetic relaxation can reduce the influence of water diffusion-exchange on the paramagnetic enhancement. This study paves the way for the design of off-resonance rotating experiments to detect labeled cell clusters/tissue compartments in vivo at a sub-millimeter scale.

Figure 1

Water diffuses across a membrane that separates two compartments. (A) Schematic illustration of a phantom consists of a water compartment and a protein gel compartment. The water compartment contains the macromolecule attached paramagnetic ion chelates (the open ellipses) that cannot pass through the membrane. The water molecules (the solid dots) can diffuse into three environments with the effective diffusion coefficients denoted as D_w for the water compartment, D_m for the porous membrane, and D_g for the gel compartment. The diffusion coefficient D_m and the membrane thickness δ limit the water transfer from the water compartment to the gel compartment and vice versa. (B) Intensity profile of T_1ρ -weighted imaging at τ =0 for membrane of 0.1 kDa MWCO. The water compartment (w) contained aqueous (Gd-DTPA)₃₀-BSA at 1 mM Gd(III). The gel compartment (g) was made from 7% cross-lined BSA gel. (C) T_1ρ -weighted imaging intensity I_w, I_g and I_m as a function of pulse duration τ for the membrane of 0.1 kDa MWCO. (D) Normalized T_1ρ -weighted imaging intensity I_m as a function of pulse duration τ for various membranes. The MWCO of these membranes is 0.1, 2, 10 and 15 kDa respectively. All T_1ρ -weighted images were at 50 ×50μm² in-plane resolution, and the off-resonance pulse was irradiated at 10 kHz offset with 2 kHz RF amplitude.

Figure 2

Water diffusion-exchange in hollow fibers embedded in cross-linked protein gels. (A) Schematic illustration of a phantom contained hollow fibers (h), glass capillary (c) and protein gels (g). (B) Intensity profiles of T_1ρ -weighted images. The hollow fiber was made from polysulfone with 10 kDa MWCO and a 500 μm diameter. The glass capillary tube had a 1.5 mm diameter. Both were filled with aqueous (Gd-DTPA)₃₀-BSA at 0.1 mM Gd(III). The protein gels were made from 7% cross-lined BSA. (C) Intensity profiles of T_1ρ -weighted images. All compartments are the same as those shown in (B) except that the hollow fiber was made from regenerated cellulose esters with 13 kDa MWCO and a 150μm diameter. All T_1ρ -weighed images were at 50 ×50 μm² in-plane resolution, and the off-resonance pulse was irradiated at 10 kHz offset with 2 kHz RF amplitude. The slices were perpendicular to the longitudinal direction of the fibers and the capillary. Other imaging parameters are discussed in the text.

Figure 3

T₁ and T_1ρ -weighed images for hollow fibers embedded in cross-linked protein gels. (A) The images at 50 ×50 μm² in-plane resolution are for the slices that are parallel to the longitudinal direction of the fiber. The slice thickness is 0.5 mm and 1 mm, corresponding to the volumetric fraction of 15% and 30% respectively. The hollow fibers were made from regenerated cellulose esters with 13 kDa MWCO and a 150 μm diameter, and is filled with aqueous (Gd-DTPA)₃₀-BSA at 0.1 mM Gd(III) concentration. The gels were made from 7% cross-linked BSA. A 500 ms RF pulse with 2 kHz RF amplitude and 10 kHz frequency offset was applied in the T_1ρ -weighed imaging. (B) The imaging intensity profiles at the arrow marked locations. Other imaging parameters are discussed in the text.

Figure 3

T₁ and T_1ρ -weighed images for hollow fibers embedded in cross-linked protein gels. (A) The images at 50 ×50 μm² in-plane resolution are for the slices that are parallel to the longitudinal direction of the fiber. The slice thickness is 0.5 mm and 1 mm, corresponding to the volumetric fraction of 15% and 30% respectively. The hollow fibers were made from regenerated cellulose esters with 13 kDa MWCO and a 150 μm diameter, and is filled with aqueous (Gd-DTPA)₃₀-BSA at 0.1 mM Gd(III) concentration. The gels were made from 7% cross-linked BSA. A 500 ms RF pulse with 2 kHz RF amplitude and 10 kHz frequency offset was applied in the T_1ρ -weighed imaging. (B) The imaging intensity profiles at the arrow marked locations. Other imaging parameters are discussed in the text.

Figure 4

T₁ and T_1ρ -weighed brain images of rats injected with intravascular contrast agents (Gd-DTPA)₃₀-BSA. A 500 ms RF pulse with 2 kHz RF amplitude and 10 kHz frequency offset was applied in the T_1ρ -weighed imaging. All images have 2 mm slice thickness and 195 ×195 μm² in-plane resolution. The 0.01 mmol Gd/kg and 0.1 mmol Gd/kg dosage corresponds to the 1.3 mM and 0.13 mM Gd(III) in the blood plasma. Label 1, 2 denotes the type-1, 2 cerebral vasculature; labels 3, 4 denote the type-3 cerebral vasculatures. Their volumetric coefficients are estimated to be ∼100%, ∼10% and ∼2% respectively. Other imaging parameters are discussed in the text.

Figure 5

Imaging intensity and imaging contrast as a function of frequency offset for a 500ms pulse with 2 kHz RF amplitude. (A) T_1ρ -weighted imaging intensity for the three type vasculatures. (B) T₁ and T_1ρ -weighted imaging contrasts for the type-1 vasculature. (C) T₁ and T_1ρ -weighted imaging contrasts for the type-2 vasculature. All imaging parameters are the same as those for Fig. 4.

Figure 5

Imaging intensity and imaging contrast as a function of frequency offset for a 500ms pulse with 2 kHz RF amplitude. (A) T_1ρ -weighted imaging intensity for the three type vasculatures. (B) T₁ and T_1ρ -weighted imaging contrasts for the type-1 vasculature. (C) T₁ and T_1ρ -weighted imaging contrasts for the type-2 vasculature. All imaging parameters are the same as those for Fig. 4.

Figure 5

Imaging intensity and imaging contrast as a function of frequency offset for a 500ms pulse with 2 kHz RF amplitude. (A) T_1ρ -weighted imaging intensity for the three type vasculatures. (B) T₁ and T_1ρ -weighted imaging contrasts for the type-1 vasculature. (C) T₁ and T_1ρ -weighted imaging contrasts for the type-2 vasculature. All imaging parameters are the same as those for Fig. 4.

Figure 6

Imaging intensity and imaging contrast as a function of RF amplitude for a 500ms pulse irradiated at 5 kHz offset. (A) T_1ρ and MTC-weighted imaging intensities for the three type vasculatures, where 0db B₁ attenuation corresponds to 2 kHz RF amplitude. (B) T₁, T_1ρ and MTC-weighted imaging contrasts for the type-1 vasculature. (C) T₁, T_1ρ and MTC -weighted imaging contrasts for the type-2 vasculature. All imaging parameters are the same as those for Fig. 4. The magnetization transfer contrast (MTC) images were acquired at the off-resonance pulses set at the same parameters as the T_1ρ -weighed images, except for the 0.3 kHz RF amplitude.

Figure 6

Imaging intensity and imaging contrast as a function of RF amplitude for a 500ms pulse irradiated at 5 kHz offset. (A) T_1ρ and MTC-weighted imaging intensities for the three type vasculatures, where 0db B₁ attenuation corresponds to 2 kHz RF amplitude. (B) T₁, T_1ρ and MTC-weighted imaging contrasts for the type-1 vasculature. (C) T₁, T_1ρ and MTC -weighted imaging contrasts for the type-2 vasculature. All imaging parameters are the same as those for Fig. 4. The magnetization transfer contrast (MTC) images were acquired at the off-resonance pulses set at the same parameters as the T_1ρ -weighed images, except for the 0.3 kHz RF amplitude.

Figure 6

Imaging intensity and imaging contrast as a function of RF amplitude for a 500ms pulse irradiated at 5 kHz offset. (A) T_1ρ and MTC-weighted imaging intensities for the three type vasculatures, where 0db B₁ attenuation corresponds to 2 kHz RF amplitude. (B) T₁, T_1ρ and MTC-weighted imaging contrasts for the type-1 vasculature. (C) T₁, T_1ρ and MTC -weighted imaging contrasts for the type-2 vasculature. All imaging parameters are the same as those for Fig. 4. The magnetization transfer contrast (MTC) images were acquired at the off-resonance pulses set at the same parameters as the T_1ρ -weighed images, except for the 0.3 kHz RF amplitude.