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Breast Cancer Research
Published in: Breast Cancer Research 1/2022

Open Access 01-12-2022 | Ultrasound | Research

Volumetric imaging and morphometric analysis of breast tumor angiogenesis using a new contrast-free ultrasound technique: a feasibility study

Authors: Juanjuan Gu, Redouane Ternifi, Soroosh Sabeti, Nicholas B. Larson, Jodi M. Carter, Robert T. Fazzio, Mostafa Fatemi, Azra Alizad

Published in: Breast Cancer Research | Issue 1/2022

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Abstract

Background

There is a strong correlation between the morphological features of new tumor vessels and malignancy. However, angiogenic heterogeneity necessitates 3D microvascular data of tumor microvessels for more reliable quantification. To provide more accurate information regarding vessel morphological features and improve breast lesion characterization, we introduced a quantitative 3D high-definition microvasculature imaging (q3D-HDMI) as a new easily applicable and robust tool to morphologically characterize microvasculature networks in breast tumors using a contrast-free ultrasound-based imaging approach.

Methods

In this prospective study, from January 2020 through December 2021, a newly developed q3D-HDMI technique was evaluated on participants with ultrasound-identified suspicious breast lesions recommended for core needle biopsy. The morphological features of breast tumor microvessels were extracted from the q3D-HDMI. Leave-one-out cross-validation (LOOCV) was applied to test the combined diagnostic performance of multiple morphological parameters of breast tumor microvessels. Receiver operating characteristic (ROC) curves were used to evaluate the prediction performance of the generated pooled model.

Results

Ninety-three participants (mean age 52 ± 17 years, 91 women) with 93 breast lesions were studied. The area under the ROC curve (AUC) generated with q3D-HDMI was 95.8% (95% CI 0.901–1.000), yielding a sensitivity of 91.7% and a specificity of 98.2%, that was significantly higher than the AUC generated with the q2D-HDMI (p = 0.02). When compared to q2D-HDMI, the tumor microvessel morphological parameters obtained from q3D-HDMI provides distinctive information that increases accuracy in differentiating breast tumors.

Conclusions

The proposed quantitative volumetric imaging technique augments conventional breast ultrasound evaluation by increasing specificity in differentiating malignant from benign breast masses.
Appendix
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Literature
1.
2.
3.
Sharma S, Sharma M, Sarkar C. Morphology of angiogenesis in human cancer: a conceptual overview, histoprognostic perspective and significance of neoangiogenesis. Histopathology. 2005;46(5):481–9.CrossRefPubMed
4.
Christensen-Jeffries K, Couture O, Dayton PA, Eldar YC, Hynynen K, Kiessling F, O’Reilly M, Pinton GF, Schmitz G, Tang M-X. Super-resolution ultrasound imaging. Ultrasound Med Biol. 2020;46(4):865–91.CrossRefPubMedPubMedCentral
5.
Xiao X-y. Chen X, Guan X-f, Wu H, Qin W, Luo B-m. Superb microvascular imaging in diagnosis of breast lesions: a comparative study with contrast-enhanced ultrasonographic microvascular imaging. Br J Radiol. 2016;89(1066):20160546.
6.
Bayat M, Fatemi M, Alizad A. Background removal and vessel filtering of noncontrast ultrasound images of microvasculature. IEEE Trans Biomed Eng. 2018;66(3):831–42.CrossRefPubMedPubMedCentral
7.
Ghavami S, Bayat M, Fatemi M, Alizad A. Quantification of morphological features in non-contrast-enhanced ultrasound microvasculature imaging. IEEE Access. 2020;8:18925–37.CrossRefPubMedPubMedCentral
8.
Ternifi R, Wang Y, Polley EC, Fazzio RT, Fatemi M, Alizad A. Quantitative Biomarkers for Cancer Detection Using Contrast-Free Ultrasound High-Definition Microvessel Imaging: Fractal Dimension, Murray’s Deviation, Bifurcation Angle & Spatial Vascularity Pattern. IEEE Trans Med Imaging. 2021;40(12):3891–900.CrossRefPubMedPubMedCentral
9.
Ternifi R, Wang Y, Gu J, Polley EC, Carter JM, Pruthi S, Boughey JC, Fazzio RT, Fatemi M, Alizad A. Ultrasound high-definition microvasculature imaging with novel quantitative biomarkers improves breast cancer detection accuracy. Eur Radiol. 2022:1–15.
10.
Gu J, Ternifi R, Larson NB, Carter JM, Boughey JC, Stan DL, Fazzio RT, Fatemi M, Alizad A. Hybrid high-definition microvessel imaging/shear wave elastography improves breast lesion characterization. Breast Cancer Res. 2022;24(1):1–13.CrossRefPubMedPubMedCentral
11.
Sridharan A, Eisenbrey JR, Machado P, Ojeda-Fournier H, Wilkes A, Sevrukov A, Mattrey RF, Wallace K, Chalek CL, Thomenius KE. Quantitative analysis of vascular heterogeneity in breast lesions using contrast-enhanced 3-D harmonic and subharmonic ultrasound imaging. IEEE Trans Ultrason Ferroelectr Freq Control. 2015;62(3):502–10.CrossRefPubMedPubMedCentral
12.
Sridharan A, Eisenbrey JR, Stanczak M, Daecher A, Machado P, Wilkes A, Sevrukov A, Ojeda-Fournier H, Mattrey RF, Wallace K: Contrast-enhanced nonlinear 3D ultrasound imaging of breast lesions in a clinical population. In: 2016 IEEE International Ultrasonics Symposium (IUS): 2016: IEEE; 2016: 1–4
13.
Lin F, Shelton SE, Espíndola D, Rojas JD, Pinton G, Dayton PA. 3-D ultrasound localization microscopy for identifying microvascular morphology features of tumor angiogenesis at a resolution beyond the diffraction limit of conventional ultrasound. Theranostics. 2017;7(1):196.CrossRefPubMedPubMedCentral
14.
Harput S, Toulemonde M, Ramalli A, Christensen-Jeffries K, Boni E, Tortoli P, Dunsby C, Tang M-X: Quantitative microvessel analysis with 3-D super-resolution ultrasound and velocity mapping. In: 2020 IEEE International Ultrasonics Symposium (IUS): 2020: IEEE; 2020: 1–4.
15.
Shelton SE, Lee YZ, Lee M, Cherin E, Foster FS, Aylward SR, Dayton PA. Quantification of microvascular tortuosity during tumor evolution using acoustic angiography. Ultrasound Med Biol. 2015;41(7):1896–904.CrossRefPubMedPubMedCentral
16.
Yang M, Zhao L, Yang F, Wang M, Su N, Zhao C, Gui Y, Wei Y, Zhang R, Li J. Quantitative analysis of breast tumours aided by three-dimensional photoacoustic/ultrasound functional imaging. Sci Rep. 2020;10(1):1–9.
17.
Yamaga I, Kawaguchi-Sakita N, Asao Y, Matsumoto Y, Yoshikawa A, Fukui T, Takada M, Kataoka M, Kawashima M, Fakhrejahani E. Vascular branching point counts using photoacoustic imaging in the superficial layer of the breast: a potential biomarker for breast cancer. Photoacoustics. 2018;11:6–13.CrossRefPubMedPubMedCentral
18.
Zhang X-Y, Zhang L, Li N, Zhu Q-L, Li J-C, Sun Q, Wang H-Y, Jiang Y-X. Vascular index measured by smart 3-D superb microvascular imaging can help to differentiate malignant and benign breast lesion. Cancer Manag Res. 2019;11:5481.CrossRefPubMedPubMedCentral
19.
Neuschler EI, Butler R, Young CA, Barke LD, Bertrand ML, Böhm-Vélez M, Destounis S, Donlan P, Grobmyer SR, Katzen J. A pivotal study of optoacoustic imaging to diagnose benign and malignant breast masses: a new evaluation tool for radiologists. Radiology. 2018;287(2):398–412.CrossRefPubMed
20.
Li Y-J, Wen G, Wang Y, Wang D-X, Yang L, Deng Y-J, Wei H-Q, He J, Zhang X, Gu Y-S. Perfusion heterogeneity in breast tumors for assessment of angiogenesis. J Ultrasound Med. 2013;32(7):1145–55.CrossRefPubMed
21.
Frangi AF, Niessen WJ, Vincken KL, Viergever MA. Multiscale vessel enhancement filtering. In: International conference on medical image computing and computer-assisted intervention: 1998: Springer; 1998: 130–137.
22.
Lam L, Lee S-W, Suen CY. Thinning methodologies-a comprehensive survey. IEEE Trans Pattern Anal Mach Intell. 1992;14(09):869–85.CrossRef
23.
Moons KG, Altman DG, Reitsma JB, Ioannidis JP, Macaskill P, Steyerberg EW, Vickers AJ, Ransohoff DF, Collins GS. Transparent Reporting of a multivariable prediction model for Individual Prognosis or Diagnosis (TRIPOD): explanation and elaboration. Ann Intern Med. 2015;162(1):W1–73.CrossRefPubMed
24.
Sun X, Xu W. Fast implementation of DeLong’s algorithm for comparing the areas under correlated receiver operating characteristic curves. IEEE Signal Process Lett. 2014;21(11):1389–93.CrossRef
25.
26.
Heffelfinger SC, Yassin R, Miller MA, Lower E. Vascularity of proliferative breast disease and carcinoma in situ correlates with histological features. Clin Cancer Res: Off J Am Assoc Cancer Res. 1996;2(11):1873–8.
27.
Teo N, Shoker B, Jarvis C, Martin L, Sloane J, Holcombe C. Vascular density and phenotype around ductal carcinoma in situ (DCIS) of the breast. Br J Cancer. 2002;86(6):905–11.CrossRefPubMedPubMedCentral
28.
Zhang X-Y, Cai S-M, Zhang L, Zhu Q-L, Sun Q, Jiang Y-X, Wang H-Y, Li J-C. Association between vascular index measured via superb microvascular imaging and molecular subtype of breast cancer. Front Oncol. 2022, 12.
29.
King TA, Scharfenberg JC, Smetherman DH, Farkas EA, Bolton JS, Fuhrman GM. A better understanding of the term radial scar. Am J Surg. 2000;180(6):428–33.CrossRefPubMed
30.
Raman D, Boj S, Arumugam D, Chidambaram L. An assessment of angiogenesis in fibrocystic breast disease and invasive breast carcinoma. J Evol Med Dent Sci. 2017;6(78):5553–7.CrossRef
31.
Kupeli A, Kul S, Eyuboglu I, Oguz S, Mungan S. Role of 3D power Doppler ultrasound in the further characterization of suspicious breast masses. Eur J Radiol. 2016;85(1):1–6.CrossRefPubMed
32.
Weidner N. Current pathologic methods for measuring intratumoral microvessel density within breast carcinoma and other solid tumors. Breast Cancer Res Treat. 1995;36(2):169–80.CrossRefPubMed
33.
Bakkar R, Nahleh Z, Bui H, Samaan S, Sanders J, Namakydoust A, Komrokji R. A comparative analysis of angiogenesis between male and female breast cancers. J Clin Oncol. 2007;25(18_suppl):21101–21101.CrossRef
34.
Secomb TW, Dewhirst MW, Pries AR. Structural adaptation of normal and tumour vascular networks. Basic Clin Pharmacol Toxicol. 2012;110(1):63–9.CrossRefPubMed
35.
Konerding M, Fait E, Gaumann A. 3D microvascular architecture of pre-cancerous lesions and invasive carcinomas of the colon. Br J Cancer. 2001;84(10):1354–62.CrossRefPubMedPubMedCentral
36.
Du J, Li F-H, Fang H, Xia J-G, Zhu C-X. Microvascular architecture of breast lesions: evaluation with contrast-enhanced ultrasonographic micro flow imaging. J Ultrasound Med. 2008;27(6):833–42.CrossRefPubMed
37.
Oraevsky A, Clingman B, Zalev J, Stavros A, Yang W, Parikh J. Clinical optoacoustic imaging combined with ultrasound for coregistered functional and anatomical mapping of breast tumors. Photoacoustics. 2018;12:30–45.CrossRefPubMedPubMedCentral
38.
Nayak R, Kumar V, Webb J, Fatemi M, Alizad A. Non-invasive small vessel imaging of human thyroid using motion-corrected spatiotemporal clutter filtering. Ultrasound Med Biol. 2019;45(4):1010–8.CrossRefPubMedPubMedCentral
39.
Nayak R, Kumar V, Webb J, Gregory A, Fatemi M, Alizad A. Non-contrast agent based small vessel imaging of human thyroid using motion corrected power Doppler imaging. Sci Rep. 2018;8(1):1–15.CrossRef
40.
Nayak R, MacNeill J, Flores C, Webb J, Fatemi M, Alizad A. Quantitative assessment of ensemble coherency in contrast-free ultrasound microvasculature imaging. Med Phys. 2021;48(7):3540–58.CrossRefPubMed
41.
Pawar K, Chen Z, Shah NJ, Egan GF: Motion correction in MRI using deep convolutional neural network. In: Proceedings of the ISMRM Scientific Meeting & Exhibition, Paris: 2018; 2018.
42.
Küstner T, Armanious K, Yang J, Yang B, Schick F, Gatidis S. Retrospective correction of motion-affected MR images using deep learning frameworks. Magn Reson Med. 2019;82(4):1527–40.CrossRefPubMed
43.
Chen C, Hendriks GA, Fekkes S, Mann R, Menssen J, Siebers CC, De Korte CL, Hansen HH. In vivo 3D power Doppler imaging using continuous translation and ultrafast ultrasound. IEEE Trans Biomed Eng. 2021;69:1042.CrossRef
44.
Lam L, Lee SW, Suen CY. Thinning methodologies - a comprehensive survey. Ieee T Pattern Anal. 1992;14(9):869–85.CrossRef
Metadata
Title
Volumetric imaging and morphometric analysis of breast tumor angiogenesis using a new contrast-free ultrasound technique: a feasibility study
Authors
Juanjuan Gu
Redouane Ternifi
Soroosh Sabeti
Nicholas B. Larson
Jodi M. Carter
Robert T. Fazzio
Mostafa Fatemi
Azra Alizad
Publication date
01-12-2022
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 1/2022
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/s13058-022-01583-3

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