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Peer-reviewedCC BY 4.0Frontiers in Oncology

IVIM-based habitat imaging for non-invasive assessment of Ki-67 proliferation status in cervical cancer

  1. 1Department of Radiology, The Fifth Affiliated Hospital of Xinjiang Medical University
  2. 2Department of Cardiovascular Surgery, People’s Hospital of Xinjiang Uygur Autonomous Region

Abstract

Objective: This study aimed to evaluate whether voxel-level IVIM-based habitat analysis supports exploratory pretreatment stratification of Ki-67 proliferation status in cervical cancer.

Materials and methods: Between January 2019 and June 2025, medical records of 149 patients with histopathologically confirmed cervical cancer were initially screened. Before image-quality assessment, 49 were excluded because IVIM MRI had been performed after chemoradiotherapy (n = 5), cervical biopsy sampling (n = 21), or lesion excision (n = 10), or because no pathological Ki-67 immunohistochemistry result was available (n = 13). Of the remaining 100 patients, 17 were excluded because of severe image artefacts (n = 11) or lesions too small for reliable ROI delineation (n = 6), leaving 83 patients for analysis. Patients were stratified into high Ki-67 (Ki-67 >70%, n = 38) and low/equal Ki-67 (Ki-67 ≤70%, n = 45) groups. Solid-tumour regions were analysed with patient-level K-means clustering using normalised D, f, and ADC features; D* was excluded from clustering because of voxel-level fitting instability. Habitat labels were harmonised according to quantitative parameter profiles and treated as image-defined phenotypes. Habitat-derived features, conventional ROI parameters, and logistic models were evaluated for Ki-67 stratification.

Results: Hab1 ADC was lower in the high- than in the low/equal-Ki-67 group (median [Q1–Q3], 0.947 [0.862–1.161] vs. 1.257 [1.113–1.455] × 10 ⁻³ mm ² /s; P < 0.001; BH q = 2.04×10 ⁻⁶ ), whereas Hab3 volume proportion was higher (0.396 [0.341–0.488] vs. 0.279 [0.190–0.390]; P = 0.002; BH q = 0.006). Hab1 ADC outperformed conventional ROI ADC for identifying high Ki-67 status [AUC, 0.826 (95% CI, 0.726–0.909) vs. 0.563 (95% CI, 0.429–0.695); paired DeLong P < 0.001]. The combined Hab1 ADC and Hab3 volume proportion model showed the numerically highest discrimination (apparent AUC, 0.877; 95% CI, 0.794–0.938), but this numerical improvement over Hab1 ADC alone was not statistically significant (paired DeLong P = 0.056). Fixed-feature leave-one-out validation of the combined model yielded an AUC of 0.855 (95% CI, 0.771–0.923) and a Brier score of 0.157 (95% CI, 0.112–0.204).

Conclusion: IVIM-based habitat analysis showed exploratory potential for non-invasive Ki-67 stratification by isolating a low-diffusivity imaging compartment otherwise obscured by conventional whole-tumour averaging. The combined habitat model should be interpreted as a research-stage imaging biomarker, not a clinical decision tool, and requires prospective external validation before clinical translation.

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BibTeX
@article{yue2026ivimbased,
  title = {{IVIM-based habitat imaging for non-invasive assessment of Ki-67 proliferation status in cervical cancer}},
  author = {Wenjing Yue and Hui Tian and Xiaofei Cai and Bofeng Yu and Yunqing Ban and Qiqi Kong},
  journal = {Frontiers in Oncology},
  year = {2026},
  month = oct,
  doi = {10.3389/fonc.2026.1885498},
  url = {https://www.frontiersin.org/articles/10.3389/fonc.2026.1885498/full},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - IVIM-based habitat imaging for non-invasive assessment of Ki-67 proliferation status in cervical cancer
AU  - Wenjing Yue
AU  - Hui Tian
AU  - Xiaofei Cai
AU  - Bofeng Yu
AU  - Yunqing Ban
AU  - Qiqi Kong
PY  - 2026
DA  - 2026/10/14
JO  - Frontiers in Oncology
DO  - 10.3389/fonc.2026.1885498
UR  - https://www.frontiersin.org/articles/10.3389/fonc.2026.1885498/full
AB  - Objective: This study aimed to evaluate whether voxel-level IVIM-based habitat analysis supports exploratory pretreatment stratification of Ki-67 proliferation status in cervical cancer.  Materials and methods: Between January 2019 and June 2025, medical records of 149 patients with histopathologically confirmed cervical cancer were initially screened. Before image-quality assessment, 49 were excluded because IVIM MRI had been performed after chemoradiotherapy (n = 5), cervical biopsy sampling (n = 21), or lesion excision (n = 10), or because no pathological Ki-67 immunohistochemistry result was available (n = 13). Of the remaining 100 patients, 17 were excluded because of severe image artefacts (n = 11) or lesions too small for reliable ROI delineation (n = 6), leaving 83 patients for analysis. Patients were stratified into high Ki-67 (Ki-67 >70%, n = 38) and low/equal Ki-67 (Ki-67 ≤70%, n = 45) groups. Solid-tumour regions were analysed with patient-level K-means clustering using normalised D, f, and ADC features; D* was excluded from clustering because of voxel-level fitting instability. Habitat labels were harmonised according to quantitative parameter profiles and treated as image-defined phenotypes. Habitat-derived features, conventional ROI parameters, and logistic models were evaluated for Ki-67 stratification.  Results: Hab1 ADC was lower in the high- than in the low/equal-Ki-67 group (median [Q1–Q3], 0.947 [0.862–1.161] vs. 1.257 [1.113–1.455] × 10 ⁻³ mm ² /s; P < 0.001; BH q = 2.04×10 ⁻⁶ ), whereas Hab3 volume proportion was higher (0.396 [0.341–0.488] vs. 0.279 [0.190–0.390]; P = 0.002; BH q = 0.006). Hab1 ADC outperformed conventional ROI ADC for identifying high Ki-67 status [AUC, 0.826 (95% CI, 0.726–0.909) vs. 0.563 (95% CI, 0.429–0.695); paired DeLong P < 0.001]. The combined Hab1 ADC and Hab3 volume proportion model showed the numerically highest discrimination (apparent AUC, 0.877; 95% CI, 0.794–0.938), but this numerical improvement over Hab1 ADC alone was not statistically significant (paired DeLong P = 0.056). Fixed-feature leave-one-out validation of the combined model yielded an AUC of 0.855 (95% CI, 0.771–0.923) and a Brier score of 0.157 (95% CI, 0.112–0.204).  Conclusion: IVIM-based habitat analysis showed exploratory potential for non-invasive Ki-67 stratification by isolating a low-diffusivity imaging compartment otherwise obscured by conventional whole-tumour averaging. The combined habitat model should be interpreted as a research-stage imaging biomarker, not a clinical decision tool, and requires prospective external validation before clinical translation.
SN  - 2234-943X
ER  -