MRI-Compatible and Cost-Effective Clipping of Breast Carcinoma Using Titanium-Based Surgical Ligating Clips

By Rana Bilal Idrees, Mariam Malik, Zeeshan Rashid Mirza, Faisal Ehsan Cheema, Jawairia Arif, Sadia Anwar

Affiliations

1. Department of Radiology, INMOL Cancer Hospital, Lahore, Pakistan

doi: 10.29271/jcpsp.2025.08.1050

ABSTRACT
The MRI compatibility, safety, and effectiveness of titanium-based surgical ligating clips (TBC) were evaluated in breast cancer patients. In a prospective study conducted at the Department of Radiology, INMOL Cancer Hospital, Lahore, Pakistan, from August 2022 to 2023, ten female patients diagnosed with Stage I or II unifocal breast carcinoma, with no prior history of breast cancer recurrence, were included. Patients with advanced tumours (Stage III or IV), disease progression during neoadjuvant chemotherapy (NAC), or contraindications to MRI were excluded from the study. TBC were placed under ultrasound guidance, and their visibility was assessed using mammography, ultrasound, and MRI before and after NAC. Mammography and ultrasound performed immediately after the clip placement confirmed the clip visibility in all cases. The MRI showed no significant artefacts or adverse effects. These findings suggest that TBC is cost-effective, MRI-compatible, and reliable method for breast tumour localisation during NAC. This technique may be particularly beneficial in settings with limited resources.

Key Words: MRI compatibility, Breast clips, Neoadjuvant chemotherapy, Artefacts.

INTRODUCTION

Breast cancer is the most common malignancy among women worldwide, necessitating advancements in both diagnostics and treatment.^1-3 Neoadjuvant chemotherapy (NAC) improves survival, facilitates breast-conserving surgery, and provides insights into tumour biology and treatment response.⁴

Tumour bed localisation post-NAC is challenging, especially in cases of complete clinical and radiological response. Pre-NAC clip placement ensures the identification of accurate surgical site. Commercial breast tissue markers (CBTM) are MRI-compatible but are costly (26,000 PKR or 84.8 USD, Figure 1). Metallic clips made from 25-gauge needles are more cost-effective but are not MRI-compatible and cause artefacts. Titanium-based clips (TBC) offer a cost-effective alternative (1,000 PKR or 3.264 USD), but their MRI compatibility remains unstudied in Pakistan. This is crucial as patients may require post-NAC MRI for assessing tumour burden, treatment response or recurrence.

This study evaluates the MRI compatibility, safety, and cost- effectiveness of TBC by assessing artefact formation, migration risk, and heating under magnetisation, using CBTM as the standard reference.
 

It also examines TBC visibility on ultrasound and mammography, particularly in cases of complete radiological response post-NAC.

METHODOLOGY

A prospective study was conducted at the Department of Radiology, INMOL Cancer Hospital, Lahore, Pakistan, from August 2022 to 2023. This study included ten female patients with histopathologically confirmed BIRADS VI breast cancer (TNM Stages I and II) scheduled for NAC. Patients with advanced tumours, disease progression, or contraindications to MRI were excluded.

Ethical approval from the Institutional Review Board and patient informed consent were obtained. Under ultrasound guidance, a 16-gauge lumbar puncture (LP) needle was used to deploy TBC. Post-placement mammography confirmed clip positioning, followed by an MRI to assess safety, artefacts, and compatibility. After NAC, preoperative wire localisation was guided by TBC in patients with complete tumour regression. Post-lumpectomy x-rays confirmed TBC and localisation wire within the tumour bed (Figure 2).

The ultrasound assessed TBC visibility immediately after placement and post-NAC. Displacement was defined as movement >1 cm. Data analysis was performed using SPSS version 20.0, and a p-value of <0.05 was considered as significant.

RESULTS

Patients were aged 35-60 years (mean: 46.8 ± 2.69 years). A total of 30 TBCs (3 per patient) were inserted. Six patients had a complete response, while four had a partial response.

Figure 1: (A) CBTM in Ribbon configuration (B) Ultrasound image (C) Mammo- gram (D) MRI T1W sagittal (E) MRI T1W axial with lesion (green arrow) and clip inside the lesion (red arrow).

Figure 2: (A) Ultrasound image (B) Mammogram image (C) Axial MRI T1WI and (D) T1 Fat saturated post contrast images. Lesion (green arrow) and TBC inside the lesion (red arrow) are shown (E) Post-lumpectomy surgical specimen x-rays, demonstrating pre-surgical localisation wire inside the lesion (green arrow) and intralesional TBC (red arrow).

Table I: Data of post-TBC placement mammography and ultrasound of patients in the immediate TBC placement period and after completion of NAC, the qualitative analysis and p-value of post-TBC placement assessments, data of post-TBC placement MRI of patients, and the qualitative analysis and p-value of post-clip placement assessments.
 

Total patients	TBC visualisation on mammography in the immediate post-clipping period	TBC visualisation on sonomammography in the immediate post TBC period	Assessment of lesion morphology post-TBC on ultrasound / effect of TBC artefact on lesion visualisation	TBC visualisation on mammography after completion of NAC / TBC artefact effect on the visualisation of the lesion	TBC visualisation on sonomammography after completion of NAC
10	10	10	10	10	7
	TBC visualisation on mammography in an immediate post-clipping period	TBC visualisation on sonomammography in an immediate post-clipping period	Assessment of lesion morphology post-TBC on ultrasound / effect of TBC artifact on lesion visualisation	TBC visualisation on mammography after completion of NAC / clip artifact effect on the visualisation of lesion	TBC visualisation on sonomammography after completion of NAC
Yes	100% (n = 10)	100% (n = 10)	0% (n = 0)	100% (n = 10)	70% (n = 7)
No	0% (n = 0)	0% (n = 0)	100% (n = 10)	0% (n = 0)	30% (n = 3)
No. of patients for MRI assessment	TBC visualised as a signal void	No Effect on the pattern of enhancement	No TBC artefact limiting the evaluation of the lesion	No adverse effect on skin (burns or erythema)	Displacement (significant if more than 1 cm)
10	10	10	10	10	1
	TBC signal void	Effect on the pattern of enhancement	Adverse effect on skin (burns or erythema)	TBC artefact limiting the evaluation of the lesion	Displacement (significant if more than 1 cm)
Yes (significant)	100% (n = 10)	0% (n = 10)	0% (n = 0)	0% (n = 0)	10% (n = 1)
No  (not significant)	0% (n = 0)	100% (n = 0)	100% (n = 10)	100% (n = 10)	90% (n = 9)
p-value	<0.001	<0.001	<0.001	<0.001	<0.001

There was 100% visibility on immediate mammography and sonomammography, and 70% visibility post-NAC on sono-mammography. No MRI artefacts were observed affecting the lesion evaluation. There were no adverse effects (burns/ erythema) during the MRI. There was 10% displacement (>1 cm) post-NAC. Cost savings approximated at 10,000 PKR (32.64 USD) for TBC vs. 260,000 PKR (848.61 USD) for CBTM for the total of ten patients collectively. Minimal compli-cations were observed, including mild pain in two patients and haematoma formation in one patient. Results are tabulated in Table I.

DISCUSSION

Treatment response was assessed using the RECIST criteria and classified as complete response, partial response, or disease progression.⁵ Clip placement before NAC was crucial for tumour bed localisation during surgery, particularly in complete response cases. The National Comprehensive Cancer Network (NCCN) guidelines emphasised the use of breast markers in breast-conserving surgery to prevent unnecessary mastectomies.⁶

In low-resource settings such as Pakistan, finding cost-effective alternatives are necessary. While metallic clips from 25-gauge injection needles are economical (20 PKR 0.07 USD),⁷ their MRI-incompatibility causes artefacts that compromise image interpretation. The present study demonstrated that TBC provides an affordable, MRI-compatible solution with minimal artefacts and at a fraction of the cost of CBTM.

The 10–15 minute ultrasound-guided TBC placement was safe with minimal complications. No significant displace-ment occurred within 24 hours. The MRI showed no heat effects or artefacts interfering with lesion assessment.

A complete radiological response was observed in six patients, altering the measured distance of TBC from the skin due to tumour regression. This was not a true migration but an effect of tumour shrinkage, as noted in previous studies.⁸ TBC placement in solid tumour components prevented displacement. Some studies suggested higher migration rates in fatty breast tissue, though findings were inconsistent.^7,9 Apart from the pain in two patients and haematoma in one patient, no significant complications were identified, consistent with the previous literature.³

TBC was visible on ultrasound immediately after placement (100%) but reduced the post-NAC (70%). This decline was due to tumour regression, making TBC difficult to distin-guish from echogenic fat, as observed in the prior studies.¹⁰ The MRI showed a subtle perifocal hypointense haze on T1/T2 sequences due to paramagnetic effects, but lesion characterisation remained unaffected. A longer time-to-echo (TE) resulted in a more visible artefact; hence, the haze was more evident on T2 than T1 sequences.

CONCLUSION

TBC is a cost-effective, MRI-compatible alternative to CBTM, providing reliable localisation for breast tumour surgery in resource-limited settings.

COMPETING  INTEREST:
The authors declared no conflict of interest.

AUTHORS’  CONTRIBUTION:
RBI: Data acquisition, methodology, drafting, and editing.
MM: Methodology, writing of the original draft, and editing.
ZRM: Conceptualisation, formal analysis, and supervision.
FEC: Conceptualisation, investigation, and formal analysis.
JA, SA: Investigation, drafting, and editing.
All authors approved the final version of the manuscript to be published.
 

REFERENCES

1. Lukasiewicz S, Czeczelewski M, Forma A, Baj J, Sitarz R, Stanisławek A. Breast cancer-epidemiology, risk factors, classification, prognostic markers, and current treatment strategies - An updated review. Cancers (Basel) 2021; 13(17):4287. doi: 10.3390/cancers13174287.
2. Hassan SA, Osman MA. Cost-effectiveness of ultrasound-guided surgical clips placement for breast cancer localisation prior to neoadjuvant chemotherapy. Egypt J Radiol Nucl Med 2018; 49(4):1163-8. doi: 10.1016/j. ejrnm.2018.06.010.
3. Young I, Choi SH, Kook SH, Choi YJ, Park CH, Park YL, et al. Ultrasonography-guided surgical clip placement for tumour localisation in patients undergoing neoadjuvant chemo-therapy for breast cancer. J Breast Cancer 2015; 18(1): 44-9. doi: 10.4048/jbc.2015.18.1.44.
4. Abdelfatah NOS, Abdallah RH, Ibrahim SF, Ahmed AI. Assessment of low-cost surgical metallic clip placement for tumour localisation in BIRDAS VI breast cancer patients undergoing neoadjuvant chemo-therapy. Egypt J Radiol Nucl Med 2022; 53:71. doi: 10. 1186/s43055-022-00740-0.
5. Masroor I, Zeeshan S, Afzal S, Sufian SN, Ali M, Khan S, et al. Outcome and cost-efectiveness of ultrasono-graphically guided surgical clip placement for tumour localisation in patients undergoing neoadjuvant chemotherapy for breast cancer. Asian Pac J Cancer Prev 2016; 16(18):8339-43. doi: 10.7314/apjcp.2015.16.18. 8339.
6. Kaufmann M, von Minckwitz G, Mamounas EP, Cameron D, Carey LA, Cristofanilli M, et al. Recommendations from an international consensus conference on the current status and future of neoadjuvant systemic therapy in primary breast cancer. Ann Surg Oncol 2012; 19(5): 1508-16. doi: 10.1245/s10434-011-2108-2.
7. Margolin FR, Kaufman L, Denny SR, Jacobs RP, Schrumpf JD. Metallic marker placement after stereo-tactic core biopsy of breast calcifications: comparison of two clips and deploy-ment techniques. AJR Am J Roentgenol 2003; 181(6):1685-90. doi: 10.2214/ajr. 181.6.1811685.
8. Lee SG, Piccoli CW, Hughes JS. Displacement of micro-calcifications during stereotactic 11-gauge directional vacuum-assisted biopsy with marking clip placement: Case report. Radiology 2001; 219(2):495-7. doi: 10.1148/radiology.219.2.r01ma04495.
9. Madeley CR, Kessell MA, Madeley CJ, Taylor DB, Wylie EJ. Radiographer technique: Does it contribute to the question of clip migration? J Med Imaging Radiat Oncol 2015; 59(5):564-70. doi: 10.1111/1754-9485.12327.
10. Kim WH, Kim HJ, Kim SH, Jung JH, Park HY, Lee J, et al. Ultrasound-guided dual-localisation for axillary nodes before and after neoadjuvant chemotherapy with clip and activated charcoal in breast cancer patients: A feasibility study. BMC Cancer 2019; 19(1):859. doi: 10.1186/s12885-019-6095-1.