Diagnostic effectiveness of quantitative [18F]flutemetamol PET imaging for detection of fibrillar amyloid β using cortical biopsy histopathology as the standard of truth in subjects with idiopathic normal pressure hydrocephalus

Leinonen, Ville; Rinne, Juha O; Wong, Dean F; Wolk, David A; Trojanowski, John Q; Sherwin, Paul F; Smith, Adrian; Heurling, Kerstin; Su, Mandy; Grachev, Igor D

doi:10.1186/2051-5960-2-46

Table 9 Sensitivity, specificity, and exact 95% CIs for each image reading method (quantitative vs. majority BIE) by pathology SoT for all 4 studies combined

From: Diagnostic effectiveness of quantitative [¹⁸F]flutemetamol PET imaging for detection of fibrillar amyloid β using cortical biopsy histopathology as the standard of truth in subjects with idiopathic normal pressure hydrocephalus

	Cerebellum REF			Pons REF
Pathology SoT	Ipsilateral	Contralateral	Composite	Ipsilateral	Contralateral	Composite
*4G8*
Quantitative (SUVR)
Sensitivity (95% CI)	1.0000 (0.6637, 1.0000)	1.0000 (0.6637, 1.0000)	0.6667 (0.2993, 0.9251)	1.0000 (0.6637, 1.0000)	0.8889 (0.5175, 0.9972)	0.8889 (0.5175, 0.9972)
Specificity (95% CI)	0.6216* (0.4476, 0.7754)	0.6757 (0.5021, 0.8199)	0.8649 (0.7123, 0.9546)	0.5000* (0.3338, 0.6662)	0.6579* (0.4865, 0.8037)	0.6316 ^a (0.4599, 0.7819)
Sum (sensitivity + specificity)	1.6216	1.6757	1.5316	1.5000	1.5468	1.5205
BIE
Sensitivity (95% CI)	0.6667 (0.2993, 0.9251)	0.6667 (0.2993, 0.9251)	0.6667 (0.2993, 0.9251)	0.6667 (0.2993, 0.9251)	0.6667 (0.2993, 0.9251)	0.6667 (0.2993, 0.9251)
Specificity (95% CI)	0.8108* (0.6484, 0.9204)	0.8108 (0.6484, 0.9204)	0.8108 (0.6484, 0.9204)	0.8158* (0.6567, 0.9226)	0.8158* (0.6567, 0.9226)	0.8158* (0.6567, 0.9226)
Sum (sensitivity + specificity)	1.4775	1.4825	1.4775	1.4825	1.4825	1.4825
*Bielschowsky*
Quantitative (SUVR)
Sensitivity (95% CI)	1.0000 (0.6306, 1.0000)	1.0000 (0.6306, 1.0000)	1.0000 (0.6306, 1.0000)	1.0000 (0.6306, 1.0000)	1.0000 (0.6306, 1.0000)	1.0000 (0.6306, 1.0000)
Specificity (95% CI)	0.8889 (0.7084, 0.9765)	0.8889 (0.7084, 0.9765)	0.9259 (0.7571, 0.9909)	0.8214 (6311, 9394)	0.9286 (0.7650, 0.9912)	0.8571 (0.6733, 0.9597)
Sum (sensitivity + specificity)	1.8889	1.8889	1.9259	1.8214	1.9286	1.8571
BIE
Sensitivity (95% CI)	1.0000 (0.6306, 1.0000)	1.0000 (0.6306, 1.0000)	1.0000 (0.6306, 1.0000)	1.0000 (0.6306, 1.0000)	1.0000 (0.6306, 1.0000)	1.0000 (0.6306, 1.0000)
Specificity (95% CI)	0.9630 (0.8103, 0.9991)	0.9630 (0.8103, 0.9991)	0.9630 (0.8103, 0.9991)	0.9643 (0.9165, 0.9991)	0.9643 (0.8165, 0.9991)	0.9643 (0.8165, 0.9991)
Sum (sensitivity + specificity)	1.9630	1.9630	1.9630	1.9643	1.9643	1.9643
*Thioflavin S*
Quantitative (SUVR)
Sensitivity (95% CI)	0.7778 (0.3999, 0.9719)	0.8889 (0.5175, 0.9972)	1.0000 (0.6637, 1.0000)	0.8889 (0.5175, 0.9972)	0.8889 (0.5175, 0.9972)	0.8889 (0.5175, 0.9972)
Specificity (95% CI)	0.9688 (0.8378, 0.9992)	0.9063 (0.7498, 0.9802)	0.8438 (0.6721, 0.9472)	0.7576* (0.5774, 0.8891)	0.9091 (0.7567, 0.9808)	0.8485 (0.6810, 0.9489)
Sum (sensitivity + specificity)	1.7466	1.7952	1.8438	1.6465	1.7980	1.7374
BIE
Sensitivity (95% CI)	0.7778 (0.3999, 0.9719)	0.7778 (0.3999, 0.9719)	0.7778 (0.3999, 0.9719)	0.7778 (0.3999, 0.9719)	0.7778 (0.3999, 0.9719)	0.7778 (0.3999, 0.9719)
Specificity (95% CI)	0.9375 (0.7919, 0.9923)	0.9375 (0.7919, 0.9923)	0.9375 (0.7919, 0.9923)	0.9394* (0.7977, 0.9926)	0.9394 (0.7977, 0.9926)	0.9394 (0.7977, 0.9926)
Sum (sensitivity + specificity)	1.7153	1.7153	1.7153	1.7172	1.7172	1.7172
*Overall pathology*
Quantitative (SUVR)
Sensitivity (95% CI)	0.9286 (0.6613, 0.9982)	1.0000 (0.7684, 1.0000)	1.0000 (0.7684, 1.0000)	0.9286 (0.6613, 0.9982)	1.0000 (0.7684, 1.0000)	0.9286 (0.6613, 0.9982)
Specificity (95% CI)	1.0000 (0.8972, 0.1.000)	0.9706 (0.8467, 0.9993)	1.0000 (0.8972, 1.0000)	0.8571 (0.6974, 0.9519)	0.8857 (0.7326, 0.9680)	1.0000 (0.9000, 1.0000)
Sum (sensitivity + specificity)	1.9286	1.9706	2.000	1.7857	1.8857	1.9286
BIE
Sensitivity (95% CI)	0.9286 (0.6613, 0.9982)	0.9286 (0.6613, 0.9982)	0.9286 (0.6613, 0.9982)	0.9286 (0.6613, 0.9982)	0.9286 (0.6613, 0.9982)	0.9286 (0.6613, 0.9982)
Specificity (95% CI)	1.0000 (0.8972, 1.0000)	1.0000 (0.8972, 1.0000)	1.0000 (0.8972, 1.0000)	1.0000 (0.9000, 1.0000)	1.0000 (0.9000, 1.0000)	1.0000 (0.9000, 1.0000)
Sum (sensitivity + specificity)	1.9286	1.9286	1.9286	1.9286	1.9286	1.9286

BIE = blinded image examination majority read; CI = confidence interval; REF = PET imaging brain reference region; SoT = standard of truth, SUVR = standard uptake value ratio. Refer to [32] for a discussion of agreement between readers.
*Specificity was higher for BIE than for quantitative SUVR (p <0.05).

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ISSN: 2051-5960

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