Introduction and objectives The biology of Malignant Pleural Mesothelioma (MPM) is poorly understood, reflected in inexplicable heterogeneity in survival and therapeutic responses. Tumour angiogenesis has been identified as a therapeutic target and high tumour vascularity-to-stroma ratio is a poor prognosis marker. We report preliminary results of a pilot study conducted to establish and validate dynamic contrast-enhanced (CE) magnetic resonance imaging (MRI) methodology for the non-invasive assessment of MPM tumour vascularity.
Methods 15 patients with suspected MPM were recruited prospectively. All had Pleural MRI (3T Siemens) 3–5 days prior to Medical Thoracoscopy (MT). Imaging protocols were developed utilising patients 1–6. In the remaining 9, T1-weighted VIBE images were acquired (single isotropic volume in the coronal plane) at baseline and 4.5, 9 and 13.5 min post-injection of Gadolinium contrast (0.1 mmol/kg). Signal Intensity (SI) was measured within 15 regions of interest containing representative pleural tissue at each time point and summarised as Mean (+/-SD).
Pleural biopsies were obtained at MT in 8/9 patients who underwent complete CE-MRI. Paraffin-embedded tissue was available for 6/8 and stained with Factor VIII and CD34 immunostains. Blood vessel numbers and total vessel area were measured using quantitative image-analysis software (Leica Biosystems, U. K.) and correlated against contrast kinetic parameters (early SI increment (0–4.5 min) and peak SI), using Spearman’s test. Patients were followed-up in a specialist pleural clinic and survival recorded.
Results Mean age was 75 years (+/- 7). 93% (n = 14) were male. Final diagnoses were: MPM (n = 6), lung adenocarcinoma (n = 1), breast adenocarcinoma (n = 1), renal cell carcinoma (n = 1), Benign Asbestos Pleural Effusion (n = 4), rheumatoid arthritis-related effusion (n = 1) and haemothorax (n = 1).
Figure 1 demonstrates relationships identified between contrast kinetic parameters and tissue vascularity. Mean follow-up was 267 (+/- 149) days, over which time mortality for MPM patients exhibiting early peak CE was 100% (n = 2/2) vs. 0% (n = 0/1) for late peak CE (log rank p = 0.2).
Conclusions We have established a functional MRI protocol for use in MPM. Within the limitations of this pilot study, early CE kinetics appear to reflect pleural tissue vascularity. Further work is ongoing to fully assess the diagnostic, prognostic and predictive value of this imaging biomarker.
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