The aim of this study was to investigate the feasibility of using 2 flip angles (FAs) with an ultrashort echo time during dynamic contrast-enhanced (DCE)-magnetic resonance imaging (MRI) for estimation of plasma gadolinium (Gd) concentration without using a precontrast longitudinal relaxation time T 1 (T 10 ) measurement. Methods: T 1 -weighted DCE-MRI experiments were carried out with C57BL/6J mice using the scan protocol with 2 FAs over 3 sequential segments during 1 scan. The data with 2 FAs were used to estimate T 10 (T 1T ) during conversion of a timeintensity curve to the time-concentration curve. Three dosages of gadoliniumbased contrast agent were used to achieve a wide range of variability in Gd concentrations when measured at 10 minutes postinjection: 0.05 mmol/kg (n = 6), 0.1 mmol/kg (n = 11), and 0.15 mmol/kg (n = 7). For comparison, the signalto-concentration conversion was also conducted using the T 10 measured from the precontrast scan (T 1M ) as well as a constant T 10 (2.1 seconds) from the literature (T 1C ). The Gd concentrations ([Gd]) estimated using DCE-MRI data for the time of retro-orbital blood collection ([Gd] T1T , [Gd] T1M , and [Gd] T1C , respectively) were compared against the [Gd] of the blood samples measured by inductively coupled plasma mass spectrometry ([Gd] MS ). In addition, contrast kinetic model analysis was conducted on mice with GL261 brain tumors (n = 5) using the 3 different methods for T 10 . Results: T 1T strongly correlated with T 1M (r = 0.81). [Gd] T1M and [Gd] T1T were significantly different from [Gd] T1C . [Gd] T1M and [Gd] T1T were in good agreement with [Gd] MS with strong correlations (mean percentage error ± standard deviation) of r = 0.70 (16% ± 56%) and r = 0.85 (15% ± 44%), respectively. In contrast, [Gd] T1C had a weak correlation of r = 0.52 with larger errors of 33% ± 24%. The contrast kinetic model parameters of GL261 brain tumors using T 1T were not significantly different from those using T 1M . Conclusions: This study substantiates the feasibility of using the 2-FA approach during DCE-MRI scan to estimate [Gd] in the plasma without using an extra scan to perform precontrast T 1 measurements.

This manuscript aims to evaluate the robustness and significance of the water efflux rate constant (kio) parameter estimated using the two flip-angle Dynamic Contrast-Enhanced (DCE) MRI approach with a murine glioblastoma model at 7 T. The repeatability of contrast kinetic parameters and kio measurement was assessed by a test–retest experiment (n = 7). The association of kio with cellular metabolism was investigated through DCE-MRI and FDG-PET experiments (n = 7). Tumor response to a combination therapy of bevacizumab and fluorouracil (5FU) monitored by contrast kinetic parameters and kio (n = 10). Test–retest experiments demonstrated compartmental volume fractions (ve and vp) remained consistent between scans while the vascular functional measures (Fp and PS) and kio showed noticeable changes, most likely due to physiological changes of the tumor. The standardized uptake value (SUV) of tumors has a linear correlation with kio (R2 = 0.547), a positive correlation with Fp (R2 = 0.504), and weak correlations with ve (R2 = 0.150), vp (R2 = 0.077), PS (R2 = 0.117), Ktrans (R2 = 0.088) and whole tumor volume (R2 = 0.174). In the treatment study, the kio of the treated group was significantly lower than the control group one day after bevacizumab treatment and decreased significantly after 5FU treatment compared to the baseline. This study results support the feasibility of measuring kio using the two flip-angle DCE-MRI approach in cancer imaging.

Gadolinium (Gd) based contrast agents (GBCAs) are widely used in magnetic resonance imaging (MRI) and are paramount to cancer diagnostics and tumor pharmacokinetic analysis. Accurate quantification of gadolinium concentration is essential to monitoring the biodistribution, clearance, and pharmacodynamics of GBCAs. However, current methods of quantifying gadolinium in blood or plasma (biological media) are both low throughput and clinically unavailable. Here, we have demonstrated the use of a sensitized gadolinium chelate, Gd[DTPA-cs124], as an MRI contrast agent that can be used to measure the concentration of gadolinium via luminescence quantification in biological media following transmetalation with a terbium salt. Gd[DTPA-cs124] was synthesized by conjugating carbostyril-124 (cs124) to diethylenetriaminepentaacetic acid (DTPA) and chelating to gadolinium. We report increases in both stability and relaxivity compared to the clinically approved analog Gd[DTPA] (gadopentetic acid or Magnevist). In vivo MRI experiments were conducted using C57BL6 mice in order to further illustrate the performance of Gd[DTPA-cs124] as an MRI contrast agent in comparison to Magnevist. Our results indicate that similar chemical modification to existing clinically approved GBCA may likewise provide favorable property changes, with the ability to be used in a gadolinium quantification assay. Furthermore, our assay provides a straightforward and high-throughput method of measuring gadolinium in biological media using a standard laboratory plate reader.

Measurement of gadolinium concentration in DCE-MRI is a significant step but remains challenging. In this study, we developed a novel Gd-based contrast agent Gd-DOTA-coumarin that can directly quantify gadolinium concentration through florescence measurement using a plate reader. The preliminary results shows that the longitudinal relaxivity in plasma at 7T is 8.6 mM-1s-1 and the limit of detection for the fluorescence measurement is 100 µM in blood. This new agent has also been successfully used for in vivo MRI experiments.

This study explores two different approachs of measuring subtle BBB disruption. To induce different levels of BBB disruption, we used a focused ultrasound (FUS) sonication with intravenously injected microbubbles with an animal model. Each animal underwent FUS procedure with different acoustic power levels. We compared the changes measured using DCE-MRI with Gadolinium-based contrast agent for volume transfer rate constant and Ferumoxytol-based ACE-MRI to measure transendotheliel water exchange rate. Our results suggest that both the water exchange rate and the contrast exchange rate show sensitive detection of subtle BBB disruption, which could shed light on understanding different permeability changes in BBB.