Micro-CT emerges as a promising tool for real-time breast cancer margin checks

Breast-conserving surgery has become the standard of care for most women with early-stage breast cancer, offering survival rates equivalent to mastectomy while sparing patients the physical and psychological toll of losing a breast. Yet the procedure carries a persistent problem that has frustrated surgeons for decades: determining whether the tumor has been removed with clear margins. Because final margin status traditionally requires over a day of specimen processing, surgeons often close the incision without knowing whether cancer cells remain at the edge of the excision. A new systematic review and meta-analysis published in Frontiers in Medical Engineering suggests that micro-computed tomography, a high-resolution three-dimensional X-ray imaging technique, could change that calculus by allowing surgeons to assess margins in real time.

The research team, led by Seyed Mostafa Meshkati Yazd of Tehran University of Medical Sciences and Mahtab Vasigh, with contributions from surgical oncologists at Fox Chase Cancer Center and imaging scientists at the University of Southampton, systematically searched Scopus, EMBASE, and PubMed for studies evaluating micro-CT for intraoperative margin assessment. Out of 2,921 initially retrieved articles, eight studies met the eligibility criteria and collectively scanned 988 specimens and margins. The scanning times ranged from 4 to 30 minutes, with most studies reporting acquisition and reconstruction within 10 minutes, a window that fits comfortably within the natural surgical pause between specimen excision and wound closure.

The pooled diagnostic indices from a hierarchical summary receiver operating characteristics analysis revealed a sensitivity of 63 percent, a specificity of 78 percent, and an overall accuracy of 77 percent compared to the gold standard of histopathological evaluation. In practical terms, this means that micro-CT correctly identified roughly six out of ten positive margins while correctly clearing about eight out of ten negative ones. The diagnostic odds ratio of approximately 6 indicates that when a margin was truly positive, micro-CT was six times more likely to yield a true positive than a false positive result. The authors note that these figures represent an improvement over a previous meta-analysis that reported a specificity of only 69 percent based on four studies and 260 samples.

The clinical significance of these numbers becomes apparent when considering the current landscape of breast-conserving surgery. Positive margin rates after lumpectomy range from 5 to 30 percent depending on tumor histology, and re-excision rates under the modern “no tumor on ink” consensus guidelines stand at approximately 14 percent, with 4 percent of patients converting to mastectomy. Each additional surgery carries an estimated average cost of over 16,000 dollars in the United States, alongside increased psychological burden and potential delays in adjuvant radiation therapy. If micro-CT could reliably detect positive margins intraoperatively, allowing targeted additional excision during the same operation, the authors estimate that reoperation rates could decrease substantially.

Micro-CT works by capturing hundreds to thousands of X-ray radiographs at numerous projection angles, either by rotating the specimen around a fixed axis or by rotating the X-ray source and detector around a stationary sample. Specialized algorithms then reconstruct the internal structure into a three-dimensional volumetric grid expressed in grayscale, with brighter voxels indicating higher X-ray attenuation. The technique achieves voxel sizes in the micrometer range, enabling visualization of breast cancer cells, which typically measure 10 to 20 microns across. Most studies in the meta-analysis used SkyScan scanner models operating at energies between 40 and 130 kilovolts, with voxel sizes ranging from 4 to 200 micrometers.

The technology offers several practical advantages over existing intraoperative methods. Frozen section analysis, the current gold standard for real-time margin assessment, achieves higher sensitivity and specificity at 86 and 96 percent respectively, but requires a mean of nearly 28 minutes, skilled personnel, specialized equipment, and substantial laboratory resources. Micro-CT scanning, by contrast, costs approximately 130 dollars per specimen compared to 327 dollars per patient for frozen section in the Netherlands. Moreover, frozen sections provide only two-dimensional slices that sample a small proportion of the tissue and are prone to artifacts in fatty breast tissue, whereas micro-CT delivers non-destructive three-dimensional imaging of the entire excised specimen.

Beyond margin assessment, the systematic review identified eleven studies exploring additional clinical applications of micro-CT in breast cancer management. The technique has demonstrated the highest correlation with pathologic tumor size compared to MRI, enabling accurate T-stage classification particularly in invasive ductal carcinomas. Micro-CT can also visualize microcalcification structures in high resolution, distinguishing benign from malignant appearances based on morphometric features such as size, roundness, and surface area to volume ratio. Preliminary data suggest the modality may even evaluate sentinel lymph nodes intraoperatively by revealing the internal architecture and vasculature of excised nodes, with benign nodes showing regular oval contours and homogeneous interiors while malignant nodes display irregular shapes and heterogeneous structures.

Despite the encouraging results, the authors caution that the evidence remains of low certainty according to the GRADE framework, owing to heterogeneity among the included studies, small sample sizes, and variability in imaging protocols and margin definitions. Conventional X-ray attenuation-based imaging also faces a fundamental challenge in fresh breast specimens: the similarity in attenuation between fibroglandular tissue and tumor makes reliable distinction difficult, sometimes leading to misidentification of fibrous tissues as tumors or tumor size overestimation. Advanced techniques such as X-ray phase-contrast micro-CT, photon-counting CT, dual-energy imaging, and contrast agents may help address this limitation by enhancing soft tissue contrast without staining or dehydration.

Practical barriers to clinical integration also persist. Metal markers and wires used to localize non-palpable tumors generate starvation, hardening, and scattering artifacts that can interfere with image interpretation, though strategies such as two-stage scanning protocols and metal artifact reduction algorithms offer potential solutions. Reader training represents another hurdle, as radiologists and pathologists must develop familiarity with histology-level volumetric X-ray data. The authors point to a three-phase study by Janssen and colleagues demonstrating that implementation guidelines improved sensitivity and positive predictive value, suggesting that structured training and consensus atlases could accelerate adoption. The most effective deployment model may involve collaboration between radiologists experienced in volumetric data and pathologists skilled in high-resolution tissue interpretation.

The research team emphasizes that adequately powered clinical trials are now warranted to investigate re-excision and local recurrence rates following micro-CT-based margin assessment. Future directions include dedicated spiral breast CT with photon-counting detectors, X-ray phase-contrast imaging, and hybrid modalities such as micro-PET/CT, which has already demonstrated substantially higher sensitivity of 90 percent in preliminary studies. Coupling micro-CT with optical scatter imaging or spatial frequency-domain imaging may further improve differentiation of collagen-rich fibrous tissues at resection margins. While the technology cannot compensate for suboptimal surgical planning, the accumulated evidence positions micro-CT as a promising complement to the existing framework for breast-conserving surgery, one that could transform the operating room from a place of uncertainty into one of informed, real-time decision-making.

Subject of Research: The role of micro-CT in breast cancer management: a systematic review on the clinical applications of micro-CT in breast cancer and a diagnostic accuracy meta-analysis on intraoperative margin assessment

Article Title: The role of micro-CT in breast cancer management: a systematic review on the clinical applications of micro-CT in breast cancer and a diagnostic accuracy meta-analysis on intraoperative margin assessment

Article References: Meshkati Yazd, S. M., Vasigh, M., Papazoglou, A. S., Liatsos, A. C., Ranjbar, K., Williams, A. D., Bleicher, R. J., Katsamenis, O. L., Pierotti, M. L., Cruz Pico, C. X., Theocharis, S., Tsolaki, F., Leff, D. R., & Michaelson, J. S. (2025). The role of micro-CT in breast cancer management: a systematic review on the clinical applications of micro-CT in breast cancer and a diagnostic accuracy meta-analysis on intraoperative margin assessment. Frontiers in Medical Engineering, 3, Article 1571528. https://doi.org/10.3389/fmede.2025.1571528

Image Credits: AI Generated

DOI: 10.3389/fmede.2025.1571528

Keywords: role, micro-CT, breast, cancer, management, systematic, review, clinical, applications, diagnostic, accuracy, meta-analysis