Is There a Direct Correlation Between Microvascular Wall Structure and k-Trans Values Obtained From Perfusion CT Measurements in Lymphomas?

Rationale and Objectives: This study aimed to test the hypothesis that ultrastructural wall abnormalities of lymphoma vessels correlate with perfusion computed tomography (PCT) kinetics. Materials and Methods: Our local institutional review board approved this prospective study. Between February 2013 and June 2016, we included 23 consecutive subjects with newly diagnosed lymphoma, who were referred for computed tomography-guided biopsy (6 women, 17 men; mean age, 60.61 ± 12.43 years; range, 28–74 years) and additionally agreed to undergo PCT of the target lymphoma tissues. PCT was obtained for 40 seconds using 80 kV, 120 mAs, 64 × 0.6-mm collimation, 6.9-cm z-axis coverage, and 26 volume measurements. Mean and maximum k-trans (mL/100 mL/min), blood flow (BF; mL/100 mL/min) and blood volume (BV) were quantified using the deconvolution and the maximum slope + Patlak calculation models. Immunohistochemical staining was performed for microvessel density quantification (vessels/m²), and electron microscopy was used to determine the presence or absence of tight junctions, endothelial fenestration, basement membrane, and pericytes, and to measure extracellular matrix thickness. Results: Extracellular matrix thickness as well as the presence or absence of tight junctions, basal lamina, and pericytes did not correlate with computed tomography perfusion parameters. Endothelial fenestrations correlated significantly with mean BF_{deconvolution} (P =.047, r = 0.418) and additionally was significantly associated with higher mean BV_{deconvolution} (P <.005). Mean k-trans_Patlak correlated strongly with mean k-trans_{deconvolution} (r = 0.939, P =.001), and both correlated with mean BF_{deconvolution} (P =.001, r = 0.748), max BF_{deconvolution} (P =.028, r = 0.564), mean BV_{deconvolution} (P =.001, r = 0.752), and max BV_{deconvolution} (P =.001, r = 0.771). Microvessel density correlated with max k-trans_{deconvolution} (r = 0.564, P =.023). Vascular endothelial growth factor receptor-3 expression (receptor specific for lymphatics) correlated significantly with max k-trans_Patlak (P =.041, r = 0.686) and mean BF_{deconvolution} (P =.038, r = 0.695). Conclusion: k-Trans values of PCT do not correlate with ultrastructural microvessel features, whereas endothelial fenestrations correlate with increased intra-tumoral BVs.