Noninvasive prediction of axillary lymph node breast cancer metastasis using morphometric analysis of nodal tumor microvessels in a contrast-free ultrasound approach

Abstract Purpose Changes in microcirculation of axillary lymph nodes (ALNs) may indicate metastasis. Reliable noninvasive imaging technique to quantify such variations is lacking. We aim to develop and investigate a contrast-free ultrasound quantitative microvasculature imaging technique for detecti...

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Main Authors: Giulia Ferroni, Soroosh Sabeti, Tasneem Abdus-Shakur, Lorenzo Scalise, Jodi M. Carter, Robert T. Fazzio, Nicholas B. Larson, Mostafa Fatemi, Azra Alizad
Format: Article
Language:English
Published: BMC 2023-06-01
Series:Breast Cancer Research
Subjects:
Online Access:https://doi.org/10.1186/s13058-023-01670-z
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author Giulia Ferroni
Soroosh Sabeti
Tasneem Abdus-Shakur
Lorenzo Scalise
Jodi M. Carter
Robert T. Fazzio
Nicholas B. Larson
Mostafa Fatemi
Azra Alizad
author_facet Giulia Ferroni
Soroosh Sabeti
Tasneem Abdus-Shakur
Lorenzo Scalise
Jodi M. Carter
Robert T. Fazzio
Nicholas B. Larson
Mostafa Fatemi
Azra Alizad
author_sort Giulia Ferroni
collection DOAJ
description Abstract Purpose Changes in microcirculation of axillary lymph nodes (ALNs) may indicate metastasis. Reliable noninvasive imaging technique to quantify such variations is lacking. We aim to develop and investigate a contrast-free ultrasound quantitative microvasculature imaging technique for detection of metastatic ALN in vivo. Experimental design The proposed ultrasound-based technique, high-definition microvasculature imaging (HDMI) provides superb images of tumor microvasculature at sub-millimeter size scales and enables quantitative analysis of microvessels structures. We evaluated the new HDMI technique on 68 breast cancer patients with ultrasound-identified suspicious ipsilateral axillary lymph nodes recommended for fine needle aspiration biopsy (FNAB). HDMI was conducted before the FNAB and vessel morphological features were extracted, analyzed, and the results were correlated with the histopathology. Results Out of 15 evaluated quantitative HDMI biomarkers, 11 were significantly different in metastatic and reactive ALNs (10 with P << 0.01 and one with 0.01 < P < 0.05). We further showed that through analysis of these biomarkers, a predictive model trained on HDMI biomarkers combined with clinical information (i.e., age, node size, cortical thickness, and BI-RADS score) could identify metastatic lymph nodes with an area under the curve of 0.9 (95% CI [0.82,0.98]), sensitivity of 90%, and specificity of 88%. Conclusions The promising results of our morphometric analysis of HDMI on ALNs offer a new means of detecting lymph node metastasis when used as a complementary imaging tool to conventional ultrasound. The fact that it does not require injection of contrast agents simplifies its use in routine clinical practice.
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spelling doaj.art-8b7c5477e6d549809d536891968c8a332023-06-11T11:28:58ZengBMCBreast Cancer Research1465-542X2023-06-0125111110.1186/s13058-023-01670-zNoninvasive prediction of axillary lymph node breast cancer metastasis using morphometric analysis of nodal tumor microvessels in a contrast-free ultrasound approachGiulia Ferroni0Soroosh Sabeti1Tasneem Abdus-Shakur2Lorenzo Scalise3Jodi M. Carter4Robert T. Fazzio5Nicholas B. Larson6Mostafa Fatemi7Azra Alizad8Department of Physiology and Biomedical Engineering, Mayo Clinic College of Medicine and ScienceDepartment of Physiology and Biomedical Engineering, Mayo Clinic College of Medicine and ScienceDepartment of Radiology, Mayo Clinic College of Medicine and ScienceDepartment of Industrial Engineering and Mathematical Science, Marche Polytechnic UniversityDepartment of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine and ScienceDepartment of Radiology, Mayo Clinic College of Medicine and ScienceDepartment of Quantitative Health Sciences, Mayo Clinic College of Medicine and ScienceDepartment of Physiology and Biomedical Engineering, Mayo Clinic College of Medicine and ScienceDepartment of Physiology and Biomedical Engineering, Mayo Clinic College of Medicine and ScienceAbstract Purpose Changes in microcirculation of axillary lymph nodes (ALNs) may indicate metastasis. Reliable noninvasive imaging technique to quantify such variations is lacking. We aim to develop and investigate a contrast-free ultrasound quantitative microvasculature imaging technique for detection of metastatic ALN in vivo. Experimental design The proposed ultrasound-based technique, high-definition microvasculature imaging (HDMI) provides superb images of tumor microvasculature at sub-millimeter size scales and enables quantitative analysis of microvessels structures. We evaluated the new HDMI technique on 68 breast cancer patients with ultrasound-identified suspicious ipsilateral axillary lymph nodes recommended for fine needle aspiration biopsy (FNAB). HDMI was conducted before the FNAB and vessel morphological features were extracted, analyzed, and the results were correlated with the histopathology. Results Out of 15 evaluated quantitative HDMI biomarkers, 11 were significantly different in metastatic and reactive ALNs (10 with P << 0.01 and one with 0.01 < P < 0.05). We further showed that through analysis of these biomarkers, a predictive model trained on HDMI biomarkers combined with clinical information (i.e., age, node size, cortical thickness, and BI-RADS score) could identify metastatic lymph nodes with an area under the curve of 0.9 (95% CI [0.82,0.98]), sensitivity of 90%, and specificity of 88%. Conclusions The promising results of our morphometric analysis of HDMI on ALNs offer a new means of detecting lymph node metastasis when used as a complementary imaging tool to conventional ultrasound. The fact that it does not require injection of contrast agents simplifies its use in routine clinical practice.https://doi.org/10.1186/s13058-023-01670-zBreast cancerUltrasound microvessel imagingAxillary lymph node metastasisFlow imagingVessel morphological biomarkers
spellingShingle Giulia Ferroni
Soroosh Sabeti
Tasneem Abdus-Shakur
Lorenzo Scalise
Jodi M. Carter
Robert T. Fazzio
Nicholas B. Larson
Mostafa Fatemi
Azra Alizad
Noninvasive prediction of axillary lymph node breast cancer metastasis using morphometric analysis of nodal tumor microvessels in a contrast-free ultrasound approach
Breast Cancer Research
Breast cancer
Ultrasound microvessel imaging
Axillary lymph node metastasis
Flow imaging
Vessel morphological biomarkers
title Noninvasive prediction of axillary lymph node breast cancer metastasis using morphometric analysis of nodal tumor microvessels in a contrast-free ultrasound approach
title_full Noninvasive prediction of axillary lymph node breast cancer metastasis using morphometric analysis of nodal tumor microvessels in a contrast-free ultrasound approach
title_fullStr Noninvasive prediction of axillary lymph node breast cancer metastasis using morphometric analysis of nodal tumor microvessels in a contrast-free ultrasound approach
title_full_unstemmed Noninvasive prediction of axillary lymph node breast cancer metastasis using morphometric analysis of nodal tumor microvessels in a contrast-free ultrasound approach
title_short Noninvasive prediction of axillary lymph node breast cancer metastasis using morphometric analysis of nodal tumor microvessels in a contrast-free ultrasound approach
title_sort noninvasive prediction of axillary lymph node breast cancer metastasis using morphometric analysis of nodal tumor microvessels in a contrast free ultrasound approach
topic Breast cancer
Ultrasound microvessel imaging
Axillary lymph node metastasis
Flow imaging
Vessel morphological biomarkers
url https://doi.org/10.1186/s13058-023-01670-z
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