Noninvasive assessment of tumor microenvironment using dynamic contrast-enhanced magnetic resonance imaging and 18F-fluoromisonidazole positron emission tomography imaging in neck nodal metastases

Abstract

Purpose: To assess noninvasively the tumor microenvironment of neck nodal metastases in patients with head-and-neck cancer by investigating the relationship between tumor perfusion measured using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and hypoxia measured by (18)F-fluoromisonidazole ((18)F-FMISO) positron emission tomography (PET).

Methods and materials: Thirteen newly diagnosed head-and-neck cancer patients with metastatic neck nodes underwent DCE-MRI and (18)F-FMISO PET imaging before chemotherapy and radiotherapy. The matched regions of interests from both modalities were analyzed. To examine the correlations between DCE-MRI parameters and standard uptake value (SUV) measurements from (18)F-FMISO PET, the nonparametric Spearman correlation coefficient was calculated. Furthermore, DCE-MRI parameters were compared between nodes with (18)F-FMISO uptake and nodes with no (18)F-FMISO uptake using Mann-Whitney U tests.

Results: For the 13 patients, a total of 18 nodes were analyzed. The nodal size strongly correlated with the (18)F-FMISO SUV (rho = 0.74, p < 0.001). There was a strong negative correlation between the median k(ep) (redistribution rate constant) value (rho = -0.58, p = 0.042) and the (18)F-FMISO SUV. Hypoxic nodes (moderate to severe (18)F-FMISO uptake) had significantly lower median K(trans) (volume transfer constant) (p = 0.049) and median k(ep) (p = 0.027) values than did nonhypoxic nodes (no (18)F-FMISO uptake).

Conclusion: This initial evaluation of the preliminary results support the hypothesis that in metastatic neck lymph nodes, hypoxic nodes are poorly perfused (i.e., have significantly lower K(trans) and k(ep) values) compared with nonhypoxic nodes.

Figure 1

MRI and ¹⁸F-FMISO PET images illustrating the hypoxic right neck lymph node of patient 2 (male, 62 years old, primary tonsil cancer). Coronal (A) and sagittal (B) T1-weighted and axial (C) short tau inversion recovery (STIR) images highlight the anatomy. The node is indicated with a white arrow. (D) Shows the post-contrast multi-phase spoiled gradient echo of the corresponding slice in (C). The node is outlined in yellow. The insert (E) in (D) displays the calculated parametric K^trans map of the node. In (F), the DCE-MRI signal (converted into Gd-DTPA concentrations) over the acquisition time is illustrated. The stars indicate the individual data points (averaged over the ROI), the thin black line is the fit, and the thick black line indicates the slope. Finally, in (G) the corresponding ¹⁸F-FMISO image is shown, indicating ¹⁸F-FMISO uptake in the node outlined in yellow.

Figure 2

MRI and ¹⁸F-FMISO PET images illustrating the non-hypoxic left neck lymph node of patient 1 (male, 51 years old, primary tonsil cancer). Captions for MR images A to F are similar to Figure 1 and G is the corresponding ¹⁸F-FMISO image.

Figure 3

Average distribution histogram plots for the DCE-MRI parameters K^trans (A) and k_ep (B). The mean values for the hypoxic nodes are shown with black bars, whereas the mean values for non-hypoxic nodes are shown in white. Error bars indicate the standard error of the mean. K^trans and k_ep are given in min⁻¹.

Figure 4

Box plots of the individual K^trans (A) and k_ep (b) values for nodes with and without ¹⁸F-FMISO uptake. K^trans and k_ep are given in min⁻¹. Box plots display minimum, first quartile, median, third quartile, and maximum of the distribution of the values for the nodes. * denotes p< 0.05 (Mann-Whitney U test).