Bridging the macro to micro resolution gap with angiographic optical coherence tomography and dynamic contrast enhanced MRI

W Jeffrey Zabel,Nader Allam,Warren D Foltz,I Alex Vitkin,Edward Taylor,Costel Flueraru

doi:10.1038/s41598-022-07000-1

Abstract

Dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) is emerging as a valuable tool for non-invasive volumetric monitoring of the tumor vascular status and its therapeutic response. However, clinical utility of DCE-MRI is challenged by uncertainty in its ability to quantify the tumor microvasculature (mu mathrm{m} scale) given its relatively poor spatial resolution (mm scale at best). To address this challenge, we directly compared DCE-MRI parameter maps with co-registered micron-scale-resolution speckle variance optical coherence tomography (svOCT) microvascular images in a window chamber tumor mouse model. Both semi and fully quantitative (Toft’s model) DCE-MRI metrics were tested for correlation with microvascular svOCT biomarkers. svOCT’s derived vascular volume fraction (VVF) and the mean distance to nearest vessel (overline{mathrm{DNV} }) metrics were correlated with DCE-MRI vascular biomarkers such as time to peak contrast enhancement (r=-0.81 and 0.83 respectively, P<0.0001 for both), the area under the gadolinium-time concentration curve (r=0.50 and -0.48 respectively, P<0.0001 for both) and {k}_{trans} (r=0.64 and -0.61 respectively, P<0.0001 for both). Several other correlated micro–macro vascular metric pairs were also noted. The microvascular insights afforded by svOCT may help improve the clinical utility of DCE-MRI for tissue functional status assessment and therapeutic response monitoring applications.

Highlights

Tumor cells require oxygen and nutrients to survive, which are supplied by the tumor vascular network
The vascular volume fraction (VVF) metric was measured in this analysis because it is useful, straightforward to calculate and widely c ited[6,8,11,20–24], facilitating comparison to other studies
The aggressive growth of tumor cells often leads to the formation of large avascular regions and a decrease in distances to the nearest vessel (DNV) may be associated with vascular normalization[34,35]

Summary

Introduction

Tumor cells require oxygen and nutrients to survive, which are supplied by the tumor vascular network This network is abnormal and malformed with leaky and tortuous vessels in comparison to normal tissue. The malformed nature of the tumor vasculature often results in poorly oxygenated or hypoxic regions which are more likely to metastasize and are more resistant to common cancer treatments such as radiation therapy (RT) and chemotherapy. Such characteristics of the tumor vasculature are typically highly heterogenous spatially (on the scale of ~ 100 μm or less)[1] and temporally[2]. An alternate imaging modality with deep-tissue vascular imaging capabilities must be considered for wider clinical implementation

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Conclusion