SURROGATE ASSESSMENT OF TUMOR CELLULAR DENSITY AND PROLIFERATION: MAGNETIC RESONANCE SPECTROSCOPY

Abstract

<strong>Abstract</strong> Proton magnetic resonance spectroscopy (1H-MRS) exploits the unique resonant frequencies of protons within differing molecules in tissue to produce a graphical representation of the distribution of metabolites in a region of interest, expressed as a series of peaks on the horizontal axis and by the parts per million and signal amplitude on the vertical axis. Careful attention must be paid to voxel placement, minimising magnetic field inhomogeneity by shimming and adequate fat and water suppression methods to address spectral contamination and optimise results. Higher magnet strengths allow for better discrimination between metabolite peaks. The most widely accepted marker of malignancy in MRS is elevation of the metabolite choline (spectral peak 3.2 ppm), an indirect index of cell turnover and proliferation. This is often referenced to the concentrations of citrate (spectral peak 2.6 ppm) and creatine (spectral peak 3.04 ppm) as a ratio. Spectroscopy has been used in the setting of cerebral glioma to inform tumor typing and grading as well as to facilitate targeted biopsy especially when combined with 18F-FDG PET to identify representative areas of higher metabolic activity. Metabolites such as N-acetylaspartate (NAA), choline, myoinositol, choline, lipids and lactate have proven of use in the evaluation of benign and malignant neuropathology. In general, astrocytomas tend to show elevated choline with reduced NAA and creatine, whilst glioblastoma multiforme classically demonstrates a high lipid (0.9 and 1.3 ppm) and lactate peak. MRS has also been used in the assessment of prostatic malignancy. The normal peripheral zone usually demonstrates high concentrations of citrate; this decreases in the central gland due to the lower proportion of glandular tissue. A reversal of the normal choline to creatine ratio is seen in malignancy. Elevated choline/creatine ratios are also seen in breast, cervical, prostate, colorectal, lymphoma and head and neck squamous cell cancers. There may be a role for MRS in the evaluation of treatment response in several tumour types. Two studies evaluating the choline lipid ratios by 1H-MRS in a total of 94 tumours before and after transcatheter arterial chemoembolisation of hepatocellular carcinoma found a significant decrease in the ratio post-treatment. In a study of 22 patients with uterine cervical carcinoma undergoing neoadjuvant chemotherapy prior to hysterectomy, a significant drop in the triglyceride peak post treatment correlated with a reduction in tumour volume though no advantage was found in terms of survival. In a study of 80 patients with cerebral glioma, MRS, in particular the choline/ NAA ratio, was found to be equal in terms of sensitivity (81.8%) but superior to diffusion-weighted imaging in specificity (84 versus 69%), positive (81 versus 69%) and negative predictive values (81 versus 84%) in predicting disease response to treatment.