Assessment of tumor treatment response using active contrast encoding (ACE)-MRI: Comparison with conventional DCE-MRI

Abstract

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

Assessing Tumour Haemodynamic Heterogeneity and Response to Choline Kinase Inhibition Using Clustered Dynamic Contrast Enhanced MRI Parameters in Rodent Models of Glioblastoma

“…Although we observed treatment response in terms of early changes in reduction of permeability and perfusion along with reduced cell density with treatment in the F98 cases, no significant differences in these parameters was found for the GL261 tumour, indicating that the GL261 model may be highly resistant to treatment with regards to changes in vascular parameters. These findings agree with a previous study [ 31 ], where an anti-vascular agent (BEV) was used for treatment in this model. Response to treatment is associated with change in tumour volume [ 67 , 68 , 69 , 70 ].…”

“…To assess the generalizability of our methods, we performed the imaging studies on two syngeneic rodent models of GBM, the F98 GBM in rats and a GL261 models in mice, as both have been shown to recapitulate several features of human GBM and have been used previously in the DCE-MRI literature [ 2 , 3 , 30 , 31 ].…”

Metabolic changes in glioblastomas in response to choline kinase inhibition: In vivo MRS in rodent models

“…Therefore, one needs to be careful when choosing the most suitable preclinical model for the most translatable results. The models used in this study represent different phenotypic and genetic types of GBM and have all been used extensively in the MRI literature 23–26 . Furthermore, one of the main advantages of using the F98, GL261 and 9L models is that they can be implanted orthotopically in syngeneic, immune competent animals.…”

“…These models recapitulate several features of human GBM and have been used previously in the MRI literature. [23][24][25][26] Animal studies were conducted in compliance with the UK Home Office Animals (Scientific Procedures) Act 1986 and with ethical approval from the local animal welfare committee. F344 female Fischer rats (weight 100-120 g) were implanted with 50 000 F98 cells (ATCC CRL-2937™) (N = 12) or 100 000 9L cells (ATCC CRL-2200™) (N = 8) whilst C57BL6 male mice (age 8-10 weeks, weight 20-25 g, N = 10) were implanted with 500 000 GL261 cells (ATCC, Manassas, VA, USA).…”

“…To test the generalizability of our approach, three syngeneic rodent models of GBM were used in this study: the F98 and 9L GBM models in rats and the GL261 model in mice. These models recapitulate several features of human GBM and have been used previously in the MRI literature 23–26 . Animal studies were conducted in compliance with the UK Home Office Animals (Scientific Procedures) Act 1986 and with ethical approval from the local animal welfare committee.…”