| First Author | Zhang Y | Year | 2023 |
| Journal | Magn Reson Imaging | Volume | 103 |
| Pages | 92-101 | PubMed ID | 37353182 |
| Mgi Jnum | J:353884 | Mgi Id | MGI:7715011 |
| Doi | 10.1016/j.mri.2023.06.008 | Citation | Zhang Y, et al. (2023) Immune cell identity behind the K(trans) mapping of mouse glioblastoma. Magn Reson Imaging 103:92-101 |
| abstractText | Dynamic contrast-enhanced MR imaging (DCE-MRI) can assess the integrity of the blood brain barrier (BBB) and has been used in GBM patients to determine glioma grade, predict prognosis, evaluate treatment response, and differentiate treatment-induced effect from recurrence. The volume transfer constant K(trans) is the most frequently used metric in tumor assessment. Based on previous studies that a higher WHO grade of brain tumor was associated with greater impairments of immunity and that K(trans) value was associated with the pathological grading, the relationship between differential composition of immune cells in GBM tissue and dynamic changes in K(trans) mapping was anticipated in this study. The present study utilized an orthotopic allograft model of GBM in which mouse GL26 cells are implanted into Ccr2(RFP/wt)Cx3cr1(GFP/wt) mice on a C57 background. The brain tumors exhibited heterogenous K(trans) values with the coefficients of variation (CV) above 75%, or relatively homogeneous K(trans) maps with CV values below 50%. The K(trans) values of homogeneous tumors ranged between 0.02/min-0.32/min with a median value of 0.10/min. The immune cell composition defined by quantitative immunohistochemistry and cell sorting was compared between the tumors with K(trans) values above 0.10/min (higher K(trans)) or below 0.10/min (lower K(trans)). Histological analysis showed that tumors with higher K(trans) values exhibited greater numbers of CCR2(pos) cells (257.60 +/- 16.42/mm(2) vs 203.23 +/- 12.20/mm(2), p = 0.04) and an increased ratio of CCR2(pos) cells to CX3CR1(pos) cells (1.20 +/- 0.02 vs 0.38 +/- 0.04, p = 0.001), the numbers of CX3CR1(pos) cells did not differ significantly based on K(trans) values (219.70 +/- 16.20/mm(2) vs 250.38 +/- 21.20/mm(2), p = 0.19). Flowcytometry analysis showed that tumors with higher K(trans) values (above 0.1/min) were associated with greater numbers of both overall monocytes (54.93 +/- 6.81% vs 29.75 +/- 3.54%, p = 0.01) and inflammatory monocytes (72.38 +/- 1.49% vs 59.52 +/- 2.44%, p = 0.001). In contrast, tumors with lower K(trans) values (below 0.1/min) exhibited greater numbers of patrolling monocytes (75.65 +/- 4.14% vs 63 +/- 6.94%, p = 0.05). In the tumors with lower K(trans) values, all three types of tumor associated cells, including patrolling monocytes, inflammatory monocytes, and microglia cells possessed a higher proportion of cells at pro-inflammatory status (41.77 +/- 6.13% vs 25.06 +/- 6.72%, p = 0.05; 27.50 +/- 2.11% vs 20.62 +/- 1.87%, p = 0.03; and 55.80 +/- 9.88% vs 31.12 +/- 7.31%, p = 0.05), inflammatory monocytes showed fewer anti-inflammatory cells (1.25 +/- 0.62% vs 3.16 +/- 3.56%, p = 0.04). Taken together, differences in K(trans) values were associated with differential immune cell phenotypes and polarizations. K(trans) mapping may therefore represent a novel approach for defining the immune status of GBM. |
