Relationships between frontal metabolites and Alzheimer's disease biomarkers in cognitively normal older adults.

Elevated expression of ß-amyloid (Aß1-42) and tau are considered risk-factors for Alzheimer's disease in healthy older adults. We investigated the effect of aging and cerebrospinal fluid levels of Aß1-42 and tau on 1) frontal metabolites measured with proton magnetic resonance spectroscopy (MRS) and 2) cognition in cognitively normal older adults (n = 144; age range 50-85). Levels of frontal gamma aminobutyric acid (GABA+) and myo-inositol relative to creatine (mI/tCr) were predicted by age. Levels of GABA+ predicted cognitive performance better than mI/tCr. Additionally, we found that frontal levels of n-acetylaspartate relative to creatine (tNAA/tCr) were predicted by levels of t-tau. In cognitively normal older adults, levels of frontal GABA+ and mI/tCr are predicted by aging, with levels of GABA+ decreasing with age and the opposite for mI/tCr. These results suggest that age- and biomarker-related changes in brain metabolites are not only located in the posterior cortex as suggested by previous studies and further demonstrate that MRS is a viable tool in the study of aging and biomarkers associated with pathological aging and Alzheimer's disease.

Ionising radiation-free whole-body MRI versus (18)F-fluorodeoxyglucose PET/CT scans for children and young adults with cancer: a prospective, non-randomised, single-centre study.

BACKGROUND: Imaging tests are essential for staging of children with cancer. However, CT and radiotracer-based imaging procedures are associated with substantial exposure to ionising radiation and risk of secondary cancer development later in life. Our aim was to create a highly effective, clinically feasible, ionising radiation-free staging method based on whole-body diffusion-weighted MRI and the iron supplement ferumoxytol, used off-label as a contrast agent. METHODS: We compared whole-body diffusion-weighted MRI with standard clinical (18)F-fluorodeoxyglucose ((18)F-FDG) PET/CT scans in children and young adults with malignant lymphomas and sarcomas. Whole-body diffusion-weighted magnetic resonance images were generated by coregistration of colour-encoded ferumoxytol-enhanced whole-body diffusion-weighted MRI scans for tumour detection with ferumoxytol-enhanced T1-weighted MRI scans for anatomical orientation, similar to the concept of integrated (18)F-FDG PET/CT scans. Tumour staging results were compared using Cohen's κ statistics. Histopathology and follow-up imaging served as the standard of reference. Data was assessed in the per-protocol population. This study is registered with ClinicalTrials.gov, number NCT01542879. FINDINGS: 22 of 23 recruited patients were analysed because one patient discontinued before completion of the whole-body scan. Mean exposure to ionising radiation was 12·5 mSv (SD 4·1) for (18)F-FDG PET/CT compared with zero for whole-body diffusion-weighted MRI. (18)F-FDG PET/CT detected 163 of 174 malignant lesions at 1325 anatomical regions and whole-body diffusion-weighted MRI detected 158. Comparing (18)F-FDG PET/CT to whole-body diffusion-weighted MRI, sensitivities were 93·7% (95% CI 89·0-96·8) versus 90·8% (85·5-94·7); specificities 97·7% (95% CI 96·7-98·5) versus 99·5% (98·9-99·8); and diagnostic accuracies 97·2% (93·6-99·4) versus 98·3% (97·4-99·2). Tumour staging results showed very good agreement between both imaging modalities with a κ of 0·93 (0·81-1·00). No adverse events after administration of ferumoxytol were recorded. INTERPRETATION: Ferumoxytol-enhanced whole-body diffusion-weighted MRI could be an alternative to (18)F-FDG PET/CT for staging of children and young adults with cancer that is free of ionising radiation. This new imaging test might help to prevent long-term side-effects from radiographic staging procedures. FUNDING: Thrasher Research Fund and Clinical Health Research Institute at Stanford University.