To investigate the validity of contrast kinetic parameter estimates from Active Contrast Encoding (ACE)-MRI against those from conventional Dynamic Contrast-Enhanced (DCE)-MRI for evaluation of tumor treatment response in mouse tumor models. Methods The ACE-MRI method that incorporates measurement of T 1 and B 1 into the enhancement curve washout region, was implemented on a 7T MRI scanner to measure tracer kinetic model parameters of 4T1 and GL261 tumors with treatment using bevacizumab and 5FU. A portion of the same ACE-MRI data was used for conventional DCE-MRI data analysis with a separately measured pre-contrast T 1 map. Tracer kinetic model parameters, such as K trans (permeability area surface product) and v e (extracellular space volume fraction), estimated from ACE-MRI were compared with those from DCE-MRI, in terms of correlation and Bland-Altman analyses. Results A threefold increase of the median K trans by treatment was observed in the flank 4T1 tumors by both ACE-MRI and DCE-MRI. In contrast, the brain tumors did not show a significant change by the treatment in either ACE-MRI or DCE-MRI. K trans and v e values of the tumors from ACE-MRI were strongly correlated with those from DCE-MRI methods with correlation coefficients of 0.92 and 0.78, respectively, for the median values of 17 tumors. The Bland-Altman plot analysis showed a mean difference of-0.01 min-1 for K trans with the 95% limits of agreement of-0.12 min-1 to 0.09 min-1 , and-0.05 with-0.37 to 0.26 for v e. Conclusion The tracer kinetic model parameters estimated from ACE-MRI and their changes by treatment closely matched those of DCE-MRI, which suggests that ACE-MRI can be used in

The purpose of the current study was to investigate the feasibility of simultaneously estimating the cellular water efflux rate ( kie), intracellular longitudinal relaxation rate ( R10i), and intracellular volume fraction ( vi) of a cell suspension using multiple samples with different gadolinium concentrations. Numerical simulation studies were conducted to assess the uncertainty in the estimation of kie, R10i, and vi from saturation recovery data using single (SC) or multiple concentrations (MC) of gadolinium‐based contrast agent (GBCA). In vitro experiments with 4 T1 murine breast cancer and SCCVII squamous cell cancer models were conducted at 11 T to compare parameter estimation using the SC protocol with that using the MC protocol. The cell lines were challenged with a Na+/K+‐ATPase inhibitor, digoxin, to assess the treatment response in terms of kie, R10i, and vi. Data analysis was conducted using the two‐compartment exchange model for parameter estimation. The simulation study data demonstrate that the MC method, compared with the SC method, reduces the uncertainty of the estimated kie by decreasing the interquartile ranges from 27.3% ± 3.7% to 18.8% ± 5.1% and the median differences from ground truth from 15.0% ± 6.3% to 7.2% ± 4.2%, while estimating R10i and vi simultaneously. In the cell studies, the MC method demonstrated reduced uncertainty in overall parameter estimation compared with the SC approach. MC method‐measured parameter changes in cells treated with digoxin increased R10i by 11.7% (p = 0.218) and kie by 5.9% (p = 0.234) for 4 T1 cells, respectively, and decreased R10i by 28.8% (p = 0.226) and kie by 1.6% (p = 0.751) for SCCVII cells, respectively. vi did not change noticeably by the treatment. The results of this study substantiate the feasibility of using saturation recovery data of multiple samples with different GBCA concentrations for simultaneous measurement of the cellular water efflux rate, intracellular volume fraction, and intracellular longitudinal relaxation rate in cancer cells.

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.

Dynamic contrast enhanced (DCE)-MRI can be used as a tool to measure intracellular water lifetime (τi) in tumor cells which can be used as a biomarker for tumor aggressiveness and treatment response. Contrast kinetic model analysis in DCE-MRI requires accurate pre-contrast T1 measurement. We used multiple flip angles for active contrast encoding of both T1 and τi during dynamic data acquisition with one injection. The present study demonstrates the feasibility of measuring T1 and τi simultaneously from the active contrast encoding (ACE) MRI data. ACE-MRI also reduces the scan time by eliminating the need of separate pre-contrast T1 measurement.

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.