The aim of this study was to determine the metabolic changes in the transition from pre-invasive to invasive
cervical cancer using high-resolution magic angle spinning (HR-MAS) MRS. Biopsy specimens were obtained from women with histologically normal cervix (n = 5),
cervical intraepithelial neoplasia (CIN; mild, n = 5; moderate/severe, n = 40), and invasive
cancer (n = 23). (1)H HR-MAS MRS data were acquired using a Bruker Avance 11.74 T spectrometer (Carr-Purcell-Meiboom-Gill sequence; TR = 4.8 s; TE = 135 ms; 512 scans; 41 min acquisition). (31)P HR-MAS spectra were obtained from the normal subjects and
cancer patients only (as
acetic acid applied before tissue sampling in patients with CIN impaired spectral quality) using a (1)H-decoupled pulse-acquire sequence (TR = 2.82 s; 2048 scans; 96 min acquisition). Peak assignments were based on values reported in the literature. Peak areas were measured using the AMARES algorithm. Estimated metabolite concentrations were compared between patient diagnostic categories and tissue histology using independent samples t tests. Comparisons based on patient category at diagnosis showed significantly higher estimated concentrations of
choline (P = 0.0001) and
phosphocholine (P = 0.002) in tissue from patients with
cancer than from patients with high-grade dyskaryosis, but no differences between non-
cancer groups. Division by histology of the sample also showed increases in
choline (P = 0.002) and
phosphocholine (P = 0.002) in
cancer compared with high-grade CIN tissue.
Phosphoethanolamine was increased in
cancer compared with normal tissue (P = 0.0001). Estimated concentrations of
alanine (P = 0.01) and
creatine (P = 0.008) were significantly reduced in normal tissue from
cancer patients compared with normal tissue from non-
cancer patients. The estimated concentration of
choline was significantly increased in CIN tissue from
cancer patients compared with CIN tissue from non-
cancer patients (P = 0.0001). Estimated concentrations of
choline-containing metabolites increased from pre-invasive to invasive
cervical cancer. Concurrent metabolite depletion occurs in normal tissue adjacent to
cancer tissue.