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

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.

Hyperpolarized 13C-Pyruvate Metabolism as a Surrogate for Tumor Grade and Poor Outcome in Renal Cell Carcinoma-A Proof of Principle Study.

Differentiating aggressive clear cell renal cell carcinoma (ccRCC) from indolent lesions is challenging using conventional imaging. This work prospectively compared the metabolic imaging phenotype of renal tumors using carbon-13 MRI following injection of hyperpolarized [1-13C]pyruvate (HP-13C-MRI) and validated these findings with histopathology. Nine patients with treatment-naïve renal tumors (6 ccRCCs, 1 liposarcoma, 1 pheochromocytoma, 1 oncocytoma) underwent pre-operative HP-13C-MRI and conventional proton (1H) MRI. Multi-regional tissue samples were collected using patient-specific 3D-printed tumor molds for spatial registration between imaging and molecular analysis. The apparent exchange rate constant (kPL) between 13C-pyruvate and 13C-lactate was calculated. Immunohistochemistry for the pyruvate transporter (MCT1) from 44 multi-regional samples, as well as associations between MCT1 expression and outcome in the TCGA-KIRC dataset, were investigated. Increasing kPL in ccRCC was correlated with increasing overall tumor grade (ρ = 0.92, p = 0.009) and MCT1 expression (r = 0.89, p = 0.016), with similar results acquired from the multi-regional analysis. Conventional 1H-MRI parameters did not discriminate tumor grades. The correlation between MCT1 and ccRCC grade was confirmed within a TCGA dataset (p < 0.001), where MCT1 expression was a predictor of overall and disease-free survival. In conclusion, metabolic imaging using HP-13C-MRI differentiates tumor aggressiveness in ccRCC and correlates with the expression of MCT1, a predictor of survival. HP-13C-MRI may non-invasively characterize metabolic phenotypes within renal cancer.

Sodium MRI with 3D-cones as a measure of tumour cellularity in high grade serous ovarian cancer.

The aim of this study was to assess the feasibility of rapid sodium MRI (23Na-MRI) for the imaging of peritoneal cancer deposits in high grade serous ovarian cancer (HGSOC) and to evaluate the relationship of 23Na-MRI with tumour cellularity. 23Na-MRI was performed at 3 T on twelve HGSOC patients using a 3D-cones acquisition technique. Tumour biopsies specimens were collected after imaging and cellularity was measured from histology. Total 23Na-MRI scan time for each patient was approximately 11 min. At an isotropic resolution of 5.6 mm, signal-to-noise ratios (SNRs) of 82.2 ± 15.3 and 15.1 ± 7.1 (mean ± standard deviation) were achieved for imaging of tumour tissue sodium concentration (TSC) and intracellular weighted sodium concentration (IWS) respectively. Tumour TSC and IWS concentrations were: 56.8 ± 19.1 mM and 30.8 ± 9.2 mM respectively and skeletal muscle TSC and IWS concentrations were 33.2 ± 16.3 mM and 20.5 ± 9.9 mM respectively. There were significant sodium concentration differences between cancer and skeletal muscle, Wilcoxon signed-rank test, P < 0.001 for TSC and P = 0.01 for IWS imaging. Tumour cellularity displayed a strong negative correlation with TSC, Spearman's rho = -0.92, P < 0.001, but did not correlate with IWS. This study demonstrates that 23Na-MRI using 3D-cones can rapidly assess sodium concentration in peritoneal deposits of HGSOC and that TSC may serve as a biomarker of tumour cellularity.