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BRIEF RESEARCH REPORT article

Front. Oncol.

Sec. Radiation Oncology

This article is part of the Research TopicDeciphering Hidden Biology Through Mathematical Techniques for Precision Radiation OncologyView all articles

Intra-voxel incoherent motion biomarker repeatability in healthy volunteers and sensitivity to chemoradiotherapy-induced changes in patients with uterine cervical cancer

Provisionally accepted
Damien  J McHughDamien J McHugh1,2*Anubhav  DattaAnubhav Datta2,3Michael  J DubecMichael J Dubec2,4David  L BuckleyDavid L Buckley4,5Ross  A LittleRoss A Little2Michael  BerksMichael Berks2Susan  CheungSusan Cheung2Kate  HaslettKate Haslett6Lisa  BarracloughLisa Barraclough6Catharine  M L WestCatharine M L West2Ananya  ChoudhuryAnanya Choudhury2,6Peter  HoskinPeter Hoskin2,6James  P B O'ConnorJames P B O'Connor2,3,7
  • 1The Christie NHS Foundation Trust, Manchester, United Kingdom
  • 2Division of Cancer Sciences, The University of Manchester, Manchester, United Kingdom
  • 3Clinical Radiology, The Christie NHS Foundation Trust, Manchester, United Kingdom
  • 4Christie Medical Physics and Engineering, The Christie NHS Foundation Trust, Manchester, United Kingdom
  • 5Biomedical Imaging, University of Leeds, Leeds, United Kingdom
  • 6Clinical Oncology, The Christie NHS Foundation Trust, Manchester, United Kingdom
  • 7Division of Radiotherapy and Imaging, Institute of Cancer Research, London, United Kingdom

The final, formatted version of the article will be published soon.

Intra-voxel incoherent motion (IVIM) biomarkers require validation for translation into clinical practice. This work evaluates repeatability and sensitivity to treatment of IVIM biomarkers in the uterine cervix, and assesses suitability of the IVIM model. Six healthy volunteers underwent two scans to evaluate repeatability. Eight patients with stage IIB-IVA cervical squamous cell carcinoma were scanned pre-treatment, and at weeks 3 and 5 into treatment. IVIM and apparent diffusion coefficient (ADC) model fits were compared using the corrected Akaike information criterion (AICc). Tissue diffusion coefficient, D, perfusion signal fraction, f, and pIVIM, the fraction of voxels better described by the IVIM model, were measured. ADCs calculated with minimum b-values of 0 (ADCb0) and 150 s/mm2 (ADCb150) were compared with f to assess sensitivity to perfusion. Model preference maps qualitatively reflected physiological characteristics of different tissues. Healthy cervix within-subject coefficients of variation were 8% (D), 15% (f), and 12% (pIVIM). Tumour D increased from baseline to week 3 (p=0.02). Baseline pIVIM showed large inter-patient variability (range: 0.13-0.68), which persisted throughout treatment. The difference between ADCb0 and ADCb150 correlated with f (repeated measures correlation coefficient r=0.76, p=0.002). IVIM biomarkers are repeatable in healthy cervix tissue. Tumour D is sensitive to early therapy-induced changes. The IVIM model is not favoured in all tumour voxels, indicating the presence of heterogeneous tumour microenvironments. ADC calculated using b=0 s/mm2 can be influenced by a perfusion-dependent bias. Not all tumour voxels are best described by the IVIM model. ADC in cervical tumours can suffer from perfusion-dependent bias.

Keywords: biomarkers, Diffusion Magnetic Resonance Imaging, image processing, intra-voxelincoherent motion, Model Comparison, Uterine Cervical Neoplasms, Radiotherapy

Received: 22 May 2025; Accepted: 07 Nov 2025.

Copyright: © 2025 McHugh, Datta, Dubec, Buckley, Little, Berks, Cheung, Haslett, Barraclough, West, Choudhury, Hoskin and O'Connor. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Damien J McHugh, damien.mchugh@nhs.net

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