Brain Advance Access originally published online on February 7, 2008
Brain 2008 131(3):665-680; doi:10.1093/brain/awm336
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11C PiB and structural MRI provide complementary information in imaging of Alzheimer's disease and amnestic mild cognitive impairment
1Department of Diagnostic Radiology, 2Information Services, 3Division of Biostatistics, 4Neurology Mayo Clinic and Foundation, Rochester, MN and 5University of Pittsburgh School of Medicine Pittsburgh, PA, USA
Correspondence to: Clifford R. Jack, Jr, MD, Mayo Clinic, Diagnostic Radiology, 200 First Street SW, Rochester, MN 55905, USA. E-mail: jack.clifford{at}mayo.edu
To date, most diagnostic imaging comparisons between amyloid labelling ligands and other imaging modalities have been between the use of amyloid labelling ligand 11C Pittsburgh Compound B (PiB) and FDG-PET. Our objectives were to compare cognitive performance and diagnostic group-wise discrimination between cognitively normal, amnestic mild cognitive impairment (MCI) and Alzheimer's disease subjects with MRI-based measures of hippocampal volume and PiB retention, and secondly to evaluate the topographic distribution of PiB retention and grey matter loss using 3D voxel-wise methods. Twenty cognitively normal, 17 amnestic MCI and 8 probable Alzheimer's disease subjects were imaged with both MRI and PiB. PiB retention was quantified as the ratio of uptake in cortical to cerebellar regions of interest (ROIs) 40–60 min post-injection. A global cortical PiB retention summary measure was derived from six cortical ROIs. Statistical parametric mapping (SPM) and voxel-based morphometry (VBM) were used to evaluate PiB retention and grey matter loss on a 3D voxel-wise basis. Alzheimer's disease subjects had high global cortical PiB retention and low hippocampal volume; most cognitively normal subjects had low PiB retention and high hippocampal volume; and on average amnestic MCI subjects were intermediate on both PiB and hippocampal volume. A target-to-cerebellar ratio of 1.5 was used to designate subjects with high or low PiB cortical retention. All Alzheimer's disease subjects fell above this ratio, as did 6 out of 20 cognitively normal subjects and 9 out of 17 MCI subjects, indicating bi-modal PiB retention in the latter two groups. Interestingly, we found no consistent differences in learning and memory performance between high versus low PiB cognitively normal or amnestic MCI subjects. The SPM/VBM voxel-wise comparisons of Alzheimer's disease versus cognitively normal subjects provided complementary information in that clear and meaningful similarities and differences in topographical distribution of amyloid deposition and grey matter loss were shown. The frontal lobes had high PiB retention with little grey matter loss, anteromedial temporal areas had low PiB retention with significant grey matter loss, whereas lateral temporoparietal association cortex displayed both significant PiB retention and grey matter loss. A voxel-wise SPM conjunction analysis revealed that subjects with high PiB retention shared a common PiB retention topographical pattern regardless of clinical category, and this matched that of amyloid plaque distribution from autopsy studies of Alzheimer's disease. Both global cortical PiB retention and hippocampal volumes demonstrated significant correlation in the expected direction with cognitive testing performance; however, correlations were stronger with MRI than PiB. Pair-wise inter-group diagnostic separation was significant for all group-wise pairs for both PiB and hippocampal volume with the exception of the comparison of cognitively normal versus amnestic MCI, which was not significant for PiB. PiB and MRI provided complementary information such that clinical diagnostic classification using both methods was superior to using either in isolation.
Key Words: Alzheimer's disease; mild cognitive impairment; Pittsburgh Compound B; amyloid imaging; magnetic resonance imaging; hippocampus
Abbreviations: AD, Alzheimer's disease; aMCI, amnestic mild cognitive impairment; AVLT, auditory verbal learning test; CDR-SB, Clinical Dementia Rating scale – sum of boxes; CN, cognitively normal; MMSE, Mini Mental State Exam; PiB, 11C Pittsburgh Compound; ROI, region of interest; SPM, statistical parametric mapping; STMS, Short Test of Mental Status; TPM, tissue probability maps; VBM, voxel-based morphometry; WMS-R, Wechsler Memory Scale-Revised
Received August 31, 2007. Revised November 21, 2007. Accepted December 19, 2007.