A new algorithm for automatic vascular mapping of DCE-MRI of the breast: Clinical application of a potential new biomarker

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Highlights

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    A validated algorithm quantifies breast vascularity through vascular maps (AVM).

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    Breast DCE-MR exams are analyzed before and after neoadjuvant chemotherapy (NAC).

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    Responders and non-responders show difference in vascularity before and after NAC.

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    AVMs may represent a reliable method to evaluate pathologic response after NAC.

Abstract

Background and objective

Vascularity evaluation on breast dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) has a potential diagnostic value, but it represents a time consuming procedure, affected by intra- and inter-observer variability. This study tests the application of a recently published method to reproducibly quantify breast vascularity, and evaluates if the vascular volume of cancer-bearing breast, calculated from automatic vascular maps (AVMs), may correlate with pathologic tumor response after neoadjuvant chemotherapy (NAC).

Methods

Twenty-four patients with unilateral locally advanced breast cancer underwent DCE-MRI before and after NAC, 8 responders and 16 non-responders. A validated algorithm, based on multiscale 3D Hessian matrix analysis, provided AVMs and allowed the calculation of vessel volume before the initiation and after the last NAC cycle for each breast. For cancer bearing breast, the difference in vascular volume before and after NAC was compared in responders and non-responders using the Wilcoxon two-sample test. A radiologist evaluated the vascularity on the subtracted images (first enhanced minus unenhanced), before and after treatment, assigning a vascular score for each breast, according to the number of vessels with length ≥30 mm and maximal transverse diameter ≥2 mm. The same evaluation was repeated with the support of the simultaneous visualization of the AVMs. The two evaluations were compared in terms of mean number of vessels and mean vascular score per breast, in responders and non-responders, by use of Wilcoxon two sample test. For all the analysis, the statistical significance level was set at 0.05.

Results

For breasts harboring the cancer, evidence of a difference in vascular volume before and after NAC for responders (median = 1.71 cc) and non-responders (median = 0.41 cc) was found (p = 0.003). A significant difference was also found in the number of vessels (p = 0.03) and vascular score (p = 0.02) before or after NAC, according to the evaluation supported by the AVMs.

Conclusions

The encouraging, although preliminary, results of this study suggest the use of AVMs as new biomarker to evaluate the pathologic response after NAC, but also support their application in other breast DCE-MRI vessel analysis that are waiting for a reliable quantification method.

Section snippets

Description of purpose

Solid tumors rely on blood vessels to obtain necessary nutrient and oxygen, and new vessels also offer path way for tumor expansion. Therefore, the assessment of tumor vascularity may provide useful information to characterize underlying malignancy and monitor vascular abnormalities [1]. In the past decade, microvessel density represented the most commonly used prognostic indicator for tumor vascularization in a wide range of cancers, although its quantification remained unreliable because of

Methods

The dataset was composed by 24 patients (mean age, 46 years; range 31–61) with unilateral LABC diagnosed at mammography and/or ultrasound. For each patient, DCE-MRI was performed before NAC initiation and repeated after the last NAC cycle. Breast surgery was scheduled within 3–4 weeks after the last NAC cycle. After surgery, the histopathologic response was evaluated using a 5-point assessment scale, from grade 1 (some alterations to individual malignant cells but no reduction in overall

Results

Eight patients were classified as responders: four with grade 5 response (pCR), and four with grade 4 response. For breasts harboring the cancer, considering both responders and non-responders, the median value of the difference in vascular volume before and after neoadjuvant treatment was 1.01 cc (1st–3rd quartiles 0.27–1.47 cc), while in the contralateral breasts it was 0.09 cc (1st–3rd quartiles −0.05 to 0.46 cc).

Both vascular evaluations performed by the radiologist, with and without support of

Discussion

The added diagnostic value of local and global breast vascularity has been recently investigated [9] and preliminary results have shown that breast vascular maps obtained by DCE-MRI can be considered as a new approach to evaluate the tumor response after NAC [10]. However, all studies in this realm highlight the requirement of further improvements for a higher reproducibility of vessel analysis. This study proposed the application of a validated vessel extraction algorithm [15] as a

Conclusions

The application of a validated algorithm for automatic vessel extraction on DCE-MRI of the breast is proposed to support breast vascularity evaluation, recently investigated as a potential DCE-MRI descriptor correlated with cancer diagnosis and with the effect of NAC. In particular, the method provides a standardized vascular mapping, its quantification based on vessel volume, overcoming the low reproducibility of current approaches based on human visual assessment. Taking into account the

Conflict of interest statement

F.S. received research grants from and is on the speakers’ bureau for Bracco Imaging Group and Bayer Pharma AG; L.M. was a blinded reader for Bayer Schering Pharma, was a speaker for Bracco Imaging Group. For the remaining authors, none were declared.

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