Comparison of a novel algorithm quantitatively estimating epifascial fibrosis in three-dimensional computed tomography images to other clinical lymphedema grading methods

PLoS One. 2019 Dec 10;14(12):e0224457. doi: 10.1371/journal.pone.0224457. eCollection 2019.

Abstract

No method has yet been approved for detecting lymphedema fibrosis before its progression. This study assessed the feasibility of computed tomography-based estimation of fibrosis. This observational, cross-sectional study included patients with lymphedema affecting one limb. Three types (maximum, mean, minimum) of computed tomography reticulation indexes were digitally calculated from trans-axial images using absorptive values, and the computed tomography reticulation indexes compared with clinical scales and measurements. Of 326 patients evaluated by at least one of lymphoscintigraphy, bio-electrical impedance, and computed tomography, 24 were evaluated by all three. The mean number of computed tomography scans in these patients was 109. Sixteen patients had breast cancer, seven had gynecologic cancers, and one had primary lymphedema. Mean computed tomography reticulation index (r = 0.52, p < 0.01) and maximal computed tomography reticulation index (r = 0.45, p < 0.05) were significantly associated with time from initial limb swelling to computed tomography. Mean computed tomography reticulation index (r = 0.86, p < 0.01), minimal computed tomography reticulation index (r = 0.79, p < 0.01), and maximal computed tomography reticulation index (r = 0.68, p < 0.01) were significantly associated with International Society of Lymphedema substage. Minimal computed tomography reticulation index correlated with 1-kHz-based bio-electrical impedance ratio (r = -0.46, p < 0.05) and with standardized proximal limb circumference difference ratio (r = 0.45, p < 0.05) of both limbs. Maximal computed tomography reticulation index had a sensitivity of 0.78, specificity of 0.60, and areas under the curve of 0.66 in detecting lymphoscintigraphic stage IV. The algorithm utilizing three-dimensional computed tomography images of epifascial fibrosis may be used as a marker for lymphedema duration, limb swelling, International Society of Lymphedema substage, and interstitial lymphatic fluids of lymphedema. The current approach shows promise in providing an additional method to assist in characterizing and monitoring lymphedema patients.

Trial registration: ClinicalTrials.gov NCT03523494.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms*
  • Cohort Studies
  • Cross-Sectional Studies
  • Electric Impedance
  • Feasibility Studies
  • Female
  • Fibrosis / diagnosis*
  • Fibrosis / diagnostic imaging
  • Fibrosis / etiology
  • Humans
  • Imaging, Three-Dimensional / methods*
  • Lymphedema / complications*
  • Lymphoscintigraphy / methods
  • Male
  • Middle Aged
  • Tomography, X-Ray Computed / methods*

Associated data

  • ClinicalTrials.gov/NCT03523494

Grants and funding

This work was supported by the National Research Foundation of Korea (NRF: https://www.nrf.re.kr/index) grant funded by the Korea government (Ministry of Science, ICT & Future Planning) (NRF-2017R1A2B4011478); by the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI: https://www.htdream.kr/), funded by the Ministry of Health & Welfare, Republic of Korea (grant number : HI15C1529); CHH received both of each grant; The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.