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

ABSTRACT: 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 (p = 0.03) and increase in HV-HC (p = 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 (p = 0.01). Positive correlations were found between histological and imaging-derived habitats: HV-HC (BT-474: p = 0.03), LV-HC (MDA-MB-231: p = 0.04), LV-LC (BT-474: p = 0.04; MDA-MB-231: p < 0.01). Physiologically distinct tumor habitats associated with therapeutic response were identified with MRI and histology data in preclinical models of breast cancer.

SUBMITTER: Syed AK

PROVIDER: S-EPMC7352623 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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

Syed Anum K AK Whisenant Jennifer G JG Barnes Stephanie L SL Sorace Anna G AG Yankeelov Thomas E TE

Cancers 20200624 6

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 hist ...[more]

PMID: 32599906

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Project description:PURPOSE:In this study, we aimed to analyze the repeatability of quantitative multiparametric rectal magnetic resonance imaging (MRI) parameters with different measurement techniques. METHODS:All examinations were performed with 3 T MRI system. In addition to routine sequences for rectal cancer imaging protocol, small field-of-view diffusion-weighted imaging and perfusion sequences were acquired in each patient. Apparent diffusion coefficient (ADC) was used for diffusion analysis and ktrans was used for perfusion analysis. Three different methods were used in measurement of these parameters; measurements were performed twice by one radiologist for intraobserver and separately by three radiologists for interobserver variability analysis. ADC was measured by the lowest value, the value at maximum wall thickness, and freehand techniques. Ktrans was measured at the slice with maximum wall thickness, by freehand drawn region of interest (ROI), and at the dark red spot with maximum value. RESULTS:A total of 30 patients with biopsy-proven rectal adenocarcinoma were included in the study. The mean values of the parameters measured by the first radiologist on the first and second measurements were as follows: mean lowest ADC, 721.31±147.18 mm2/s and 718.96±135.71 mm2/s; mean ADC value on the slice with maximum wall thickness, 829.90±144.24 mm2/s and 829.48±149.23 mm2/s; mean ADC value measured by freehand ROI on the slice with maximum wall thickness, 846.56±136.31 mm2/s and 848.23±144.15 mm2/s; mean ktrans value on the slice with maximum wall thickness, 0.219±0.080 and 0.214±0.074; mean ktrans by freehand ROI technique (including as much tumoral tissue as possible), 0.208±0.074 and 0.207±0.069; mean ktrans measured from the dark red foci, 0.308±0.109 and 0.311±0.105. Intraobserver agreement was very good among diffusion and perfusion parameters obtained with all three measurement techniques. Interobserver agreement was very good, except for one of the measurement techniques. As far as interobserver variability is considered, only ADC value measured on the slice with maximum wall thickness differed significantly. CONCLUSION:Multiparametric MRI of rectum, using ADC as the diffusion and ktrans as the perfusion parameter is a repeatable technique. This technique may potentially be used in prediction and evaluation of neoadjuvant treatment response. New studies with larger patient groups are needed to validate the role of multiparametric MRI.

Project description:BackgroundThe purpose of this study was to determine whether advanced quantitative magnetic resonance imaging (MRI) can be deployed outside of large, research-oriented academic hospitals and into community care settings to predict eventual pathological complete response (pCR) to neoadjuvant therapy (NAT) in patients with locally advanced breast cancer.MethodsPatients with stage II/III breast cancer (N = 28) were enrolled in a multicenter study performed in community radiology settings. Dynamic contrast-enhanced (DCE) and diffusion-weighted (DW)-MRI data were acquired at four time points during the course of NAT. Estimates of the vascular perfusion and permeability, as assessed by the volume transfer rate (Ktrans) using the Patlak model, were generated from the DCE-MRI data while estimates of cell density, as assessed by the apparent diffusion coefficient (ADC), were calculated from DW-MRI data. Tumor volume was calculated using semi-automatic segmentation and combined with Ktrans and ADC to yield bulk tumor blood flow and cellularity, respectively. The percent change in quantitative parameters at each MRI scan was calculated and compared to pathological response at the time of surgery. The predictive accuracy of each MRI parameter at different time points was quantified using receiver operating characteristic curves.ResultsTumor size and quantitative MRI parameters were similar at baseline between groups that achieved pCR (n = 8) and those that did not (n = 20). Patients achieving a pCR had a larger decline in volume and cellularity than those who did not achieve pCR after one cycle of NAT (p < 0.05). At the third and fourth MRI, changes in tumor volume, Ktrans, ADC, cellularity, and bulk tumor flow from baseline (pre-treatment) were all significantly greater (p < 0.05) in the cohort who achieved pCR compared to those patients with non-pCR.ConclusionsQuantitative analysis of DCE-MRI and DW-MRI can be implemented in the community care setting to accurately predict the response of breast cancer to NAT. Dissemination of quantitative MRI into the community setting allows for the incorporation of these parameters into the standard of care and increases the number of clinical community sites able to participate in novel drug trials that require quantitative MRI.

Dataset Information

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

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

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