Multiparametric Analysis of Longitudinal Quantitative MRI data to Identify Distinct Tumor Habitats in Preclinical Models of Breast Cancer

This study identifies physiological tumor habitats from quantitative magnetic resonance imaging (MRI) data and evaluates their alterations in response to therapy. Two models of breast cancer (BT-474 and MDA-MB-231) were imaged longitudinally with diffusion-weighted MRI and dynamic contrast-enhanced...

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Bibliographic Details
Published in:Cancers 2020-06, Vol.12 (6), p.1682
Main Authors: Syed, Anum K, Whisenant, Jennifer G, Barnes, Stephanie L, Sorace, Anna G, Yankeelov, Thomas E
Format: Article
Language:English
Subjects:
Albumin
Breast cancer
Cancer therapies
Clustering
Habitats
Magnetic resonance imaging
Monoclonal antibodies
Paclitaxel
Permeability
Physiology
Targeted cancer therapy
Trastuzumab
Tumors
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Summary:This study identifies physiological tumor habitats from quantitative magnetic resonance imaging (MRI) data and evaluates their alterations in response to therapy. Two models of breast cancer (BT-474 and MDA-MB-231) were imaged longitudinally with diffusion-weighted MRI and dynamic contrast-enhanced MRI to quantify tumor cellularity and vascularity, respectively, during treatment with trastuzumab or albumin-bound paclitaxel. Tumors were stained for anti-CD31, anti-Ki-67, and H&E. Imaging and histology data were clustered to identify tumor habitats and percent tumor volume (MRI) or area (histology) of each habitat was quantified. Histological habitats were correlated with MRI habitats. Clustering of both the MRI and histology data yielded three clusters: high-vascularity high-cellularity (HV-HC), low-vascularity high-cellularity (LV-HC), and low-vascularity low-cellularity (LV-LC). At day 4, BT-474 tumors treated with trastuzumab showed a decrease in LV-HC ( = 0.03) and increase in HV-HC ( = 0.03) percent tumor volume compared to control. MDA-MB-231 tumors treated with low-dose albumin-bound paclitaxel showed a longitudinal decrease in LV-HC percent tumor volume at day 3 ( = 0.01). Positive correlations were found between histological and imaging-derived habitats: HV-HC (BT-474: = 0.03), LV-HC (MDA-MB-231: = 0.04), LV-LC (BT-474: = 0.04; MDA-MB-231: < 0.01). Physiologically distinct tumor habitats associated with therapeutic response were identified with MRI and histology data in preclinical models of breast cancer.
ISSN:2072-6694
2072-6694
DOI:10.3390/cancers12061682