Magnetization transfer imaging of ovarian cancer: initial experiences of correlation with tissue cellularity and changes following neoadjuvant chemotherapy

Abstract

Objectives: To investigate the relationship between magnetization transfer (MT) imaging and tissue macromolecules in high-grade serous ovarian cancer (HGSOC) and whether MT ratio (MTR) changes following neoadjuvant chemotherapy (NACT).

Methods: This was a prospective observational study. 12 HGSOC patients were imaged before treatment. MTR was compared to quantified tissue histology and immunohistochemistry. For a subset of patients (n = 5), MT imaging was repeated after NACT. The Shapiro-Wilk test was used to assess for normality of data and Spearman's rank-order or Pearson's correlation tests were then used to compare MTR with tissue quantifications. The Wilcoxon signed-rank test was used to assess for changes in MTR after treatment.

Results: Treatment-naïve tumour MTR was 21.9 ± 3.1% (mean ± S.D.). MTR had a positive correlation with cellularity, rho = 0.56 (p < 0.05) and a negative correlation with tumour volume, ρ = -0.72 (p = 0.01). MTR did not correlate with the extracellular proteins, collagen IV or laminin (p = 0.40 and p = 0.90). For those patients imaged before and after NACT, an increase in MTR was observed in each case with mean MTR 20.6 ± 3.1% (median 21.1) pre-treatment and 25.6 ± 3.4% (median 26.5) post-treatment (p = 0.06).

Conclusion: In treatment-naïve HGSOC, MTR is associated with cellularity, possibly reflecting intracellular macromolecular concentration. MT may also detect the HGSOC response to NACT, however larger studies are required to validate this finding.

Advances in knowledge: MTR in HGSOC is influenced by cellularity. This may be applied to assess for cell changes following treatment.

Figure 1.

Flowchart of patient recruitment and progression through study.

Figure 2.

Example axial images from a 63-year-old participant. The tumour is outlined in blue. (A) MT_off; (B) MT_on; (C) MTR map, scale bar represents MTR in percent; (D) T ₂ weighted image. MT = magnetization transfer; MTR = magnetization transfer ratio.

Figure 3.

High-grade serous ovarian cancer histology and IHC from a 63-year-old patient at 20x magnification. (A) Collagen IV IHC: the brown stain represents positive expression, and the blue stain represents the hematoxylin background counterstain. (B) Automated segmentation of the collagen IV staining: yellow segmentation represents staining with OD 0.270–0.355 and red segmentation represents staining with OD >0.355. (C) Laminin IHC: the brown stain represents positive expression, and the blue stain represents the hematoxylin background counterstain. (D) Automated segmentation of the laminin staining: yellow segmentation represents staining with OD = 0.270–0.355 and red segmentation represents staining with OD >0.355. (E) Box-plots showing the distribution of percentage slide area with positive collagen IV and laminin staining. IHC = immunohistochemistry; OD = optical density.

Figure 4.

Comparison of cell density, tumour volume and IHC with MT imaging in HGSOC patients. (A) MTR compared to cell density; (B) MTR compared to tumour volume; (C) percentage positive collagen IV tissue area compared to tumour MTR; (D) percentage positive laminin tissue area compared to tumour MTR. HGSOC = high-grade serous ovarian cancer; MTR = magnetization transfer ratio.

Figure 5.

(A) Line graphs showing the change in MTR before and after three cycles of neoadjuvant chemotherapy treatment for five patients undergoing repeat imaging; (B) example MTR map of a HGSOC tumour before treatment; and (C) after treatment. HGSOC = high-grade serous ovarian cancer; MTR = magnetization transfer ratio.