Multimodal approach to assess tumour vasculature and potential treatment effect with DCE‐US and DCE‐MRI quantification in CWR22 prostate tumour xenografts

Abstract

The aim of this study was to compare intratumoural heterogeneity and longitudinal changes assessed by dynamic contrast-enhanced ultrasound (DCE-US) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in prostate tumour xenografts. In vivo DCE-US and DCE-MRI were obtained 24 h pre- (day 0) and post- (day 2) radiation treatment with a single dose of 7.5 Gy. Characterization of the tumour vasculature was determined by Brix pharmacokinetic analysis of the time-intensity curves. Histogram analysis of voxels showed significant changes (p < 0.001) from day 0 to day 2 in both modalities for kep , the exchange rate constant from the extracellular extravascular space to the plasma, and kel , the elimination rate constant of the contrast. In addition, kep and kel values from DCE-US were significantly higher than those derived from DCE-MRI at day 0 (p < 0.0001) for both groups. At day 2, kel followed the same tendency for both groups, whereas kep showed this tendency only for the treated group in intermediate-enhancement regions. Regarding kep median values, longitudinal changes were not found for any modality. However, at day 2, kep linked to DCE-US was correlated to MVD in high-enhancement areas for the treated group (p = 0.05). In contrast, correlation to necrosis was detected for the control group in intermediate-enhancement areas (p < 0.1). Intratumoural heterogeneity and longitudinal changes in tumour vasculature were assessed for both modalities. Microvascular parameters derived from DCE-US seem to provide reliable biomarkers during radiotherapy as validated by histology. Furthermore, DCE-US could be a stand-alone or a complementary technique.

Radiation treatment monitoring using multimodal functional imaging: PET/CT (18F-Fluoromisonidazole & 18F-Fluorocholine) and DCE-US

“…Earlier, 24 h after treatment with a single dose of 7.5 Gy, we detected longitudinal changes in the microvascular parameter k el derived from DCE-US as assessed by the median values [ 15 ]. In addition, MVD and necrosis were correlated to k ep for the treated group only in high intensity areas of enhancement.…”

“…A 120 min interval between tracer injection and the start of the scan was used for 18 F-FMISO. The DCE-US acquisition was performed immediately before the PET/CT acquisition, following the protocols previously described [ 15 ]. In the 18 F-FCH group, a 30 min interval was used between injection and start of the PET/CT scan.…”

“…DCE-US quantification was performed by in-house developed software using Matlab R2011b (MathWorks, Inc, Natick, MA, USA) as previously described [ 15 ]. Shortly, a region of interest (ROI) was delineated around the entire tumour using the ultrasound images excluding surrounding skin, connective and necrotic tissue.…”

“…Treated and untreated control tumours were taken for immunohistochemistry on day 3. The immunohistochemical preparation of the samples and subsequent analysis of the specimens were performed following the protocols described in detail previously [ 15 ]. The tumour vascularity was quantified by both in-house software developed in Matlab 2014b and manually by a blinded investigator.…”

Experimental imaging in orthotopic renal cell carcinoma xenograft models: comparative evaluation of high-resolution 3D ultrasonography, in-vivo micro-CT and 9.4T MRI

“…Lymph node or visceral organ metastases were not observed in our study, however their detection with hrUS seems to be feasible 14 , 15 . Beyond that, contrast-enhanced ultrasound imaging using “naked” or antibody-/ligand-conjugated microbubbles might be able to even better visualize orthotopic tumors as well as associated angiogenesis 16 and potential treatment effects 17 . A drawback of the hrUS technique is that the interpretation of the acquired images requires some expertise, yet this is also true for μCT and MRI.…”