title: In vivo analysis of hippocampal subfield atrophy in mild cognitive impairment via semi-automatic segmentation of T2-weighted MRI.
abstract: The measurement of hippocampal volumes using MRI is a useful in-vivo biomarker for detection and monitoring of early Alzheimer's disease (AD), including during the amnestic mild cognitive impairment (a-MCI) stage. The pathology underlying AD has regionally selective effects within the hippocampus. As such, we predict that hippocampal subfields are more sensitive in discriminating prodromal AD (i.e., a-MCI) from cognitively normal controls than whole hippocampal volumes, and attempt to demonstrate this using a semi-automatic method that can accurately segment hippocampal subfields. High-resolution coronal-oblique T2-weighted images of the hippocampal formation were acquired in 45 subjects (28 controls and 17 a-MCI (mean age: 69.5 ± 9.2; 70.2 ± 7.6)). CA1, CA2, CA3, and CA4/DG subfields, along with head and tail regions, were segmented using an automatic algorithm. CA1 and CA4/DG segmentations were manually edited. Whole hippocampal volumes were obtained from the subjects' T1-weighted anatomical images. Automatic segmentation produced significant group differences in the following subfields: CA1 (left: p = 0.001, right: p = 0.038), CA4/DG (left: p = 0.002, right: p = 0.043), head (left: p = 0.018, right: p = 0.002), and tail (left: p = 0.019). After manual correction, differences were increased in CA1 (left: p < 0.001, right: p = 0.002), and reduced in CA4/DG (left: p = 0.029, right: p = 0.221). Whole hippocampal volumes significantly differed bilaterally (left: p = 0.028, right: p = 0.009). This pattern of atrophy in a-MCI is consistent with the topography of AD pathology observed in postmortem studies, and corrected left CA1 provided stronger discrimination than whole hippocampal volume (p = 0.03). These results suggest that semi-automatic segmentation of hippocampal subfields is efficient and may provide additional sensitivity beyond whole hippocampal volumes.
authors.affiliation: Penn Image Computing and Science Laboratory, Department of Radiology, University of Pennsylvania, PA, USA. jpluta@mail.med.upenn.edu
authors.forename: John
authors.initials: J
authors.lastname: Pluta
authors.forename: Paul
authors.initials: P
authors.lastname: Yushkevich
authors.forename: Sandhitsu
authors.initials: S
authors.lastname: Das
authors.forename: David
authors.initials: D
authors.lastname: Wolk
mesh_terms: D019540:Area Under Curve; D001284:Atrophy / Q000209:etiology / Q000473:pathology; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D060825:Cognitive Dysfunction / Q000150:complications / Q000473:pathology*; D001330:Electronic Data Processing; D005260:Female; D007839:Functional Laterality; D006624:Hippocampus / Q000473:pathology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D012372:ROC Curve