SSQ17-01

Hippocampus MRI T1 Texture's Relation to Established Alzheimer's Disease Biomarkers and Prediction of Progression

Thursday, Dec. 3 10:30AM - 10:40AM Location: N229



FDA Discussions may include off-label uses.

Mads Nielsen, PhD, Copenhagen, Denmark (Presenter) Stockholder, Biomediq A/S Research Grant, Nordic Bioscience A/S Research Grant, SYNARC Inc Research Grant, AstraZeneca PLC
Lauge Sorensen, Copenhagen, Denmark (Abstract Co-Author) Research funded, Biomediq A/S
Akshay Pai, Copenhagen, Denmark (Abstract Co-Author) Nothing to Disclose
Christian Igel, Copenhagen, Denmark (Abstract Co-Author) Research funded, Biomediq A/S
Martin Lillholm, PhD, Copenhagen, Denmark (Abstract Co-Author) Employee, Biomediq A/S Shareholder, Biomediq A/S
PURPOSE

The hippocampus texture as recorded in T1 MRI has been shown to be a strong predictor of conversion from MCI to probable AD and has been suggested for enrichment of AD trials. We investigate the relation of the hippocampal texture to CSF amyloid and tau load, and glucose metabolism of the hippocampus and it's potential prediction of conversion in amyloid and tau positive subject respectively.

METHOD AND MATERIALS

The study dataset consisted of the 504 subjects from the "complete annual year 2 visits" standardized Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset including 234 baseline MCI subjects. MRI analysis consisted of segmenting the hippocampi using cross-sectional FreeSurfer (v.5.1.0), computation of the baseline hippocampal fraction (HF, hippocampal volume divided by intra-cranial volume), hippocampal atrophy (baseline, 12 month, 24 month regression percentage volume loss), and texture scoring of the hippocampus using our in-house method. CSF amyloid (AΒ42 ), respectively total tau (t-tau), and tau phosphorylated at the threonine 118 position (p-tau) were defined as positive by AΒ42 <= 192 pg/ml, t-tau >= 93 pg/ml, and p-tau >= 23 pg/ml. Normalized FDG-PET measurements constrained to the hippocampus were averaged over left and right hippocampus. Age and gender adjustment was performed.

RESULTS

The subpopulations having available amyloid, tau, and FDG-PET measurements did not significantly differ from the full 504 subjects in age, gender, MMSE, or HF. Hippocampal texture predicted conversion from MCI to AD in 12 months with an AUC of 0.71. In AΒ42, p-tau and t-tau positive subjects, the AUC of MCI to AD conversion were respectively 0.71, 0.72, and 0.69 (not significantly different from the whole population). The Pearson's R between hippocampus texture and AΒ42, p-tau, t-tau, FDG-PET, and hippocampal atrophy was respectively -0.32, 0.31, 0.28, -0.62, and 0.50. All AUC's and R's remained significant after decorrelation using HF.

CONCLUSION

Hippocampal texture predicts MCI-to-AD conversion independent of AΒ42, p-tau, t-tau. It relates weakly to AΒ42, p-tau, t-tau and strongly to glucose metabolism and future hippocampal atrophy.

CLINICAL RELEVANCE/APPLICATION

Hippocampus MRI T1 texture is a promising marker for prediction of fast Alzheimer's progression and enrichment of clinical trials.