Introduction

The presence of calcium in solid form, known as calcification, is a central feature in breast cancer (BC)¹. The detection and classification of calcification in BC holds significant prognostic value in treatment planning². Mammography, as the only current clinical radiological approach sensitive to the presence of calcification, cannot reveal the precise classification of calcification³. Ultrashort Echo Time Ultrashort Echo Time (UTE) imaging, a novel radiological method, addresses the limitation of conventional MRI to primarily soft tissue application by capturing rapid signal decay in solid state matters such as calcification. However, UTE demands non-cartesian scanning trajectory and high-performance scanner hardware to minimise the time lag between excitation and signal detection, and only became adequately robust and available on clinical scanners recently⁴. We therefore set out to examine the feasibility of UTE imaging in identifying histological characteristics of microcalcifications in freshly excised breast tumours.

Methods

Twenty breast tumour specimens were removed from female patients undergoing wide local excision, mean (range) age of 57 (35–78) years, with invasive ductal carcinoma: grade II (10)/grade III (10). The fresh specimens were immediately placed in 10% buffered solution of formalin after surgery. UTE imaging was performed to derive degree of calcification, and standard pathological analysis was conducted to determine the calcification status, Nottingham Prognostic Index (NPI) and proliferative activity marker Ki-67. The study was approved by the North West-Greater Manchester East Research Ethics Committee (REC reference number: 16/NW/0221), and signed written informed consent was obtained prior to the study.

Image Acquisition: The specimens were scanned on a 3T whole-body MRI scanner (Achieva TX, Philips Healthcare, Best, Netherlands) using a 32-channel receiver coil for high sensitivity detection and a body coil for uniform transmission. For tumour localisation, anatomical images were acquired using standard T₁-weighted and T₂-weighted sequences with conventional diffusion weighted images (2 b-values of 0 and 800 sec/mm²). The UTE images were acquired with a 3D-radial dual-echo UTE sequence, with echo times (TE1) of 0.17 ms and (TE2) 4.60 ms, repetition time (TR) of 8.5 ms, FOV of 141 × 141 mm², voxel size of 2.2 × 2.2 × 2.2 mm³. To understand the signal dynamics of calcification, two additional UTE acquisitions were performed with TE1 at 0.2 and 0.6 ms, and TE2 at 6.9 ms, and TR at 18 ms.

Image Analysis: The whole tumour was manually delineated with the reference to T₁ and T₂ anatomical images in MATLAB (MathWorks Inc., Natick, USA) (Figure 1). Subsequently, the signal intensity of the two echoes were derived as the mean of the image intensity within the whole tumour for each echo. The degree of calcification was computed as the signal difference between the two echoes normalised by the long echo.

Statistical Analysis: All statistical analysis was carried out using SPSS software (Release 27.0, SPSS Inc, IL, USA). Degree of calcification from UTE between histological calcification classes was compared using one-way ANOVA. A Tukey's HSD post hoc tests were conducted to indicate the significance of differences among the three calcification groups. Spearman’s correlation tests were performed between degree of calcification against NPI and Ki-67 scores.

Results

There was a significant difference (p = 0.012) in the degree of calcification between specimens with malignant calcification (1.054 ± 0.132) and specimens with no calcification (0.842 ± 0.091) for images acquired at TE1 of 0.17 ms (Table1). There was a significant difference in the degree of calcification between specimens with malignant calcification and specimens with no calcification for images acquired at TE1 of 0.2 ms (p = 0.048) and TE1 of 0.6ms (p = 0.014) (Figure 2). There was no significant difference (p = 0.355) in the degree of calcification between specimens with malignant calcification (1.054 ± 0.132) and benign calcification (0.951 ± 0.158) across all acquisitions. There was no significant correlation between the degree of calcification against NPI and Ki-67 scores (Figure 3).

Discussion

UTE enhances the detection of short T2* species and may have potential in the detection of solid-state signal from calcifications in breast tumours. Although UTE showed a potential in sensitivity to calcified tumours, further work is required for non-invasive differentiation of calcification classes. Malignant calcifications and benign calcifications are typically associated with different chemical composition crystal structures. Nonetheless, benign calcifications can possess crystal structures with the same chemical composition as malignant calcifications, which introduces challenges in the differentiation of solid state signals⁵. No correlation between histologic calcification classes and NPI and Ki-67 scores was found, although it is reported to have an association with calcified tumours^6,7.

Conclusion

Tumours with malignant calcification may be differentiated from tumours without calcification using UTE imaging.

Acknowledgements

This work was funded by the NHS Grampian Endowment Research Fund. Yazan Ayoub’s PhD study is supported by the Elphinstone PhD Scholarship.

References

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