Article Figures & Data
Figures
- FIGURE 1.
Regions for visual read are outlined and overlaid on T1-weighted MR images for anatomic reference.
- FIGURE 2.
18F-MK-6240 PET in CN volunteer, AD patient, and patient with non-AD tauopathy. “Positive, atypical AD” was added in refined algorithm. Non-AD tauopathy patterns with only subcortical (cluster 3) and no cortical uptake (clusters 1 and 2), as would be expected in progressive supranuclear palsy (PSP), were not encountered in this primarily MCI/AD dataset.
- FIGURE 3.
Difficult case showing bilateral anterior mesial temporal uptake, which can be confused with off-target uptake in meninges and floor of calvarium. Fused axial image of MK-6240 with the participant’s T1-weighted MR image (top left), fused coronal image of MK-6240 with the participant’s T1-weighted MR image (bottom left); axial (top right) and coronal (bottom right) views of MRI only.
- FIGURE 4.
SUVr for different regional VOIs parsed by visual read of negative or positive. Jack VOI = VOI regions of Jack et al. (15).
Tables
Brain area Included regions Visual rating No. regions Rationale Cluster 1, temporal lobes Hippocampus; mesial temporal; inferior temporal; lateral temporal No uptake (0%); uptake 1%–25%; extension 26%–75%; >75% extension 8 regions: 4 each in left and right hemispheres Earliest cortical regions involved in AD per Braak staging Cluster 2, extratemporal neocortex Occipital; posterior cingulate; parietal; frontal No uptake (0%); uptake 1%–25%; extension 26%–75%; >75% extension 8 regions: 4 each in left and right hemispheres Next regions involved in AD Cluster 3, subcortical area Striatum-globus; thalamus; dentate nucleus; pons; midbrain Presence or absence 5 regions May be positive in non-AD tauopathies Development dataset Test dataset Sex (n) Sex (n) Group n Age (y) M F n Age (y) M F AD 29 72.4 (9.9) 20 9 24 70.4 (10.7) 12 12 MCI 17 71.2 (7.1) 11 6 21 69.9 (8.0) 12 9 CN 52 66.4 (12.1) 25 27 45 68.6 (7.5) 18 27 Other 4 63.3 (4.6) 0 4 12 65.9 (9.4) 5 7 Age is mean followed by SD in parentheses.
Regional binary agreement on positive or negative Complete agreement on spatial extent scoring Agreement Region Fleiss κ Agreement Region Fleiss κ Almost perfect Right parietal 0.945 Substantial Right lateral temporal 0.748 Right frontal 0.929 Left lateral temporal 0.716 Right lateral temporal 0.907 Right posterior cingulate 0.702 Left parietal 0.906 Left posterior cingulate 0.678 Left posterior cingulate 0.904 Right parietal 0.655 Left lateral temporal 0.888 Left parietal 0.621 Right posterior cingulate 0.87 Right frontal 0.618 Substantial Left frontal 0.801 Left frontal 0.602 Left occipital 0.801 Moderate Right inferior temporal 0.597 Left hippocampus 0.783 Left inferior temporal 0.576 Right inferior temporal 0.782 Right hippocampus 0.552 Right occipital 0.759 Right mesial temporal 0.552 Right hippocampus 0.756 Left hippocampus 0.551 Left inferior temporal 0.753 Left mesial temporal 0.545 Right mesial temporal 0.742 Right occipital 0.537 Left mesial temporal 0.726 Left occipital 0.503 Overall binary assessment, κ = 0.912.
- TABLE 4.
Sensitivity and Specificity of MK-6240 Visual Reads and SUVr Analyses Using Clinical Diagnosis as Standard of Truth
Method Sensitivity Specificity Youden index Visual read Reader 0 0.79 0.93 0.72 Reader 1 0.75 0.93 0.68 Reader 2 0.79 0.91 0.70 Consensus 0.81 0.93 0.74 Visual VRES (cutoff, 1.5) 0.742 0.890 0.63 SUVr Braak 1–2 (cutoff, 1.4) 0.649 0.888 0.54 Braak 3–4 (cutoff, 1.3) 0.645 0.963 0.61 Braak 5–6 (cutoff, 1.2) 0.611 0.960 0.57 Jack VOI (cutoff, 1.4) 0.650 0.880 0.53 Jack VOI = VOI regions of Jack et al. (15).
Scan assessment Original algorithm Refined algorithm Reason for adjustment Negative No more than one region positive in cortex All clusters negative Allowing one region to be positive was to prevent interpretation of scans as positive when meningeal uptake near inferolateral temporal lobes could be misread as positive region; this was dropped with improved methods or instructions to identify this confounder Positive, AD pattern Evidence of increased uptake in two cortical regions with at least one region in temporal lobes At least one cluster 1 region positive and no cluster 3 regions positive Revision was made after observation of multiple cases with isolated cluster 1 abnormality in just one region Positive, atypical AD pattern Not assessed Increased uptake in one or more regions in cluster 2 but not in clusters 1 or 3 This rare pattern was noted from review of other MK-6240 datasets and was expected pattern based on published literature on other tau PET tracers Positive, non-AD pattern Any positive scan not fitting AD criteria Increased uptake in one or more regions in clusters 1–3, with at least one region in cluster 3 Adjustment was made after formalized uniform assessment for regions involved in non-AD tauopathies
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