title: Detection of cancer in cervical tissue biopsies using mobile lipid resonances measured with diffusion-weighted (1)H magnetic resonance spectroscopy.
abstract: The purpose of this study was to implement a diffusion-weighted sequence for visualisation of mobile lipid resonances (MLR) using high resolution magic angle spinning (HR-MAS) (1)H MRS and to evaluate its use in establishing differences between tissues from patients with cervical carcinoma that contain cancer from those that do not. A stimulated echo sequence with bipolar gradients was modified to allow T(1) and T(2) measurements and optimised by recording signal loss in HR-MAS spectra as a function of gradient strength in model lipids and tissues. Diffusion coefficients, T(1) and apparent T(2) relaxation times were measured in model lipid systems. MLR profiles were characterised in relation to T(1) and apparent T(2) relaxation in human cervical cancer tissue samples. Diffusion-weighted (DW) spectra of cervical biopsies were quantified and peak areas analysed using linear discriminant analysis (LDA). The optimised sequence reduced spectral overlap by suppressing signals originating from low molecular weight metabolites and non-lipid contributions. Significantly improved MLR visualisation allowed visualisation of peaks at 0.9, 1.3, 1.6, 2.0, 2.3, 2.8, 4.3 and 5.3 ppm. MLR analysis of DW spectra showed at least six peaks arising from saturated and unsaturated lipids and those arising from triglycerides. Significant differences in samples containing histologically confirmed cancer were seen for peaks at 0.9 (p < 0.006), 1.3 (p < 0.04), 2.0 (p < 0.03), 2.8 (p < 0.003) and 4.3 ppm (p < 0.0002). LDA analysis of MLR peaks from DW spectra almost completely separated two clusters of cervical biopsies (cancer, 'no-cancer'), reflecting underlying differences in MLR composition. Generated Receiver Operating Characteristic (ROC) curves and calculated area under the curve (0.962) validated high sensitivity and specificity of the technique. Diffusion-weighting of HR-MAS spectroscopic sequences is a useful method for characterising MLR in cancer tissues and displays an accumulation of lipids arising during tumourigenesis and an increase in the unsaturated lipid and triglyceride peaks with respect to saturated MLR.
authors.affiliation: The Institute of Cancer Research and Royal Marsden NHS Foundation Trust, Sutton, Surrey, UK. dominik.zietkowski@icr.ac.uk
authors.forename: D
authors.initials: D
authors.lastname: Zietkowski
authors.forename: R L
authors.initials: RL
authors.lastname: Davidson
authors.forename: T R
authors.initials: TR
authors.lastname: Eykyn
authors.forename: S S
authors.initials: SS
authors.lastname: De Silva
authors.forename: N M
authors.initials: NM
authors.lastname: Desouza
authors.forename: G S
authors.initials: GS
authors.lastname: Payne
mesh_terms: D001706:Biopsy; D002584:Cervix Uteri / Q000737:chemistry / Q000473:pathology*; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods*; D005260:Female; D006801:Humans; D008055:Lipids / Q000032:analysis*; D012372:ROC Curve; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis* / Q000473:pathology*
chemical_list: D008055:Lipids