Tavarekere N Nagaraja1, Rasha Elmghirbi2, Stephen L Brown3, Lonni R Schultz4, Ian Y Lee5, Kelly A Keenan5, Swayamprava Panda6, Glauber Cabral6, Tom Mikkelsen7, James R Ewing8. 1. Dept. of Neurosurgery, Henry Ford Hospital, Detroit, MI, USA. Electronic address: tnagara1@hfhs.org. 2. Dept. of Neurology, Henry Ford Hospital, Detroit, MI, USA; Dept. of Physics, Oakland University, Rochester, MI, USA. 3. Dept. of Radiation Oncology, Henry Ford Hospital, Detroit, MI, USA. 4. Dept. of Neurosurgery, Henry Ford Hospital, Detroit, MI, USA; Dept. of Public Health Sciences, Henry Ford Hospital, Detroit, MI, USA. 5. Dept. of Neurosurgery, Henry Ford Hospital, Detroit, MI, USA. 6. Dept. of Neurology, Henry Ford Hospital, Detroit, MI, USA. 7. Dept. of Neurosurgery, Henry Ford Hospital, Detroit, MI, USA; Ontario Brain Institute, Toronto, ON, Canada. 8. Dept. of Neurology, Henry Ford Hospital, Detroit, MI, USA; Dept. of Physics, Oakland University, Rochester, MI, USA; Dept. of Neurology, Wayne State University, Detroit, MI, USA.
Abstract
PURPOSE: The objective was to study temporal changes in tumor vascular physiological indices in a period of 24h in a 9L gliosarcoma rat model. METHODS: Fischer-344 rats (N=14) were orthotopically implanted with 9L cells. At 2weeks post-implantation, they were imaged twice in a 24h interval using dynamic contrast enhanced magnetic resonance imaging (DCE-MRI). Data-driven model-selection-based analysis was used to segment tumor regions with varying vascular permeability characteristics. The region with the maximum number of estimable parameters of vascular kinetics was chosen for comparison across the two time points. It provided estimates of three parameters for an MR contrast agent (MRCA): i) plasma volume (vp), ii) forward volumetric transfer constant (Ktrans) and interstitial volume fraction (ve, ratio of Ktrans to reverse transfer constant, kep). In addition, MRCA extracellular distribution volume (VD) was estimated in the tumor and its borders, along with tumor blood flow (TBF) and peritumoral MRCA flux. Descriptors of parametric distributions were compared between the two times. Tumor extent was examined by hematoxylin and eosin (H&E) staining. Picrosirus red staining of secreted collagen was performed as an additional index for 9L cells. RESULTS: Test-retest differences between population summaries for any parameter were not significant (paired t and Wilcoxon signed rank tests). Bland-Altman plots showed no apparent trends between the differences and averages of the test-retest measures for all indices. The intraclass correlation coefficients showed moderate to almost perfect reproducibility for all of the parameters, except vp. H&E staining showed tumor infiltration in parenchyma, perivascular space and white matter tracts. Collagen staining was observed along the outer edges of main tumor mass. CONCLUSION: The data suggest the relative stability of these MR indices of tumor microenvironment over a 24h duration in this gliosarcoma model.
PURPOSE: The objective was to study temporal changes in tumor vascular physiological indices in a period of 24h in a 9L gliosarcomarat model. METHODS: Fischer-344 rats (N=14) were orthotopically implanted with 9L cells. At 2weeks post-implantation, they were imaged twice in a 24h interval using dynamic contrast enhanced magnetic resonance imaging (DCE-MRI). Data-driven model-selection-based analysis was used to segment tumor regions with varying vascular permeability characteristics. The region with the maximum number of estimable parameters of vascular kinetics was chosen for comparison across the two time points. It provided estimates of three parameters for an MR contrast agent (MRCA): i) plasma volume (vp), ii) forward volumetric transfer constant (Ktrans) and interstitial volume fraction (ve, ratio of Ktrans to reverse transfer constant, kep). In addition, MRCA extracellular distribution volume (VD) was estimated in the tumor and its borders, along with tumor blood flow (TBF) and peritumoral MRCA flux. Descriptors of parametric distributions were compared between the two times. Tumor extent was examined by hematoxylin and eosin (H&E) staining. Picrosirus red staining of secreted collagen was performed as an additional index for 9L cells. RESULTS: Test-retest differences between population summaries for any parameter were not significant (paired t and Wilcoxon signed rank tests). Bland-Altman plots showed no apparent trends between the differences and averages of the test-retest measures for all indices. The intraclass correlation coefficients showed moderate to almost perfect reproducibility for all of the parameters, except vp. H&E staining showed tumor infiltration in parenchyma, perivascular space and white matter tracts. Collagen staining was observed along the outer edges of main tumor mass. CONCLUSION: The data suggest the relative stability of these MR indices of tumor microenvironment over a 24h duration in this gliosarcoma model.
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Authors: Tavarekere N Nagaraja; Rasha Elmghirbi; Stephen L Brown; Julian A Rey; Lonni Schultz; Abir Mukherjee; Glauber Cabral; Swayamprava Panda; Ian Y Lee; Malisa Sarntinoranont; Kelly A Keenan; Robert A Knight; James R Ewing Journal: NMR Biomed Date: 2021-04-04 Impact factor: 4.044