Autopsy Validation of the Diagnostic Accuracy of 123 I-Metaiodobenzylguanidine Myocardial Scintigraphy for Lewy Body Disease

Figures

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  Figure 1. Flowchart of Participant Selection BBAR = Brain Bank for Aging Research; H/M = heart-to-mediastinum ratio; 123I-MIBG = 123I-meta-iodobenzyl-guanidine; LBD = Lewy body disease.

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  Figure 2. Individual Values for H/M Ratio and Washout Rate of 123I-MIBG Uptake in the Pathologically Diagnosed LBD and Non-LBD Groups Early (A) and delayed (B) heart-to-mediastinum (H/M) ratios of 123I-meta-iodobenzyl-guanidine (123I-MIBG) uptake show significant reductions in the Lewy body disease (LBD) group. Washout rate (C) shows a significant increase in the LBD group. Boxplot indicates the median and 25% and 75% quartiles, with whiskers representing 1.5 times the interquartile range. Early and delayed H/M ratios of 123I-MIBG uptake (D) are shown for each of the following subgroups: motor symptoms, dementia, or autonomic failure, according to their initial complaints, further divided into 2 subgroups based on the time from symptom onset to scintigraphy (<3 or ≥3 years). *p < 0.001.

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  Figure 3. ROC Curves for Detecting LBDs From the H/M Ratios and Washout Rate Receiver operating characteristic (ROC) curves based on the early (A [red], B) and delayed (A [blue], C) heart-to-mediastinum (H/M) ratios and washout rate (A [green], D). Bars indicate 95% CIs at representative points. AUC = area under the ROC curve; LBD = Lewy body disease. *Optimal cutoff point at which the sensitivity is maximized with the lower limit of the CI for a specificity of ≥0.80.

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  Figure 4. Correlation Between the Proportion of TH-Immunoreactive Residual Cardiac Sympathetic Fibers and Cardiac 123I-MIBG Uptake Scatterplots show the relationship between the proportion of residual tyrosine hydroxylase (TH)–immunoreactive sympathetic fibers in the anterior wall of the left ventricle and the cardiac 123I-meta-iodobenzyl-guanidine (123I-MIBG) uptake in the early (A) and delayed (B) heart-to-mediastinum (H/M) ratios.

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  Figure 5. Typical Microscopic Images of True-Positive, False-Positive, and False-Negative Cases of 123I-MIBG Myocardial Scintigraphy True-positive case with Lewy body disease (LBD) and abnormal 123I-meta-iodobenzyl-guanidine (123I-MIBG) myocardial scintigraphy presents with marked denervation of tyrosine hydroxylase (TH)–immunoreactive sympathetic fibers (A) and accumulation of α-synuclein (D) in the heart. Accumulation of α-synuclein is also identified in the sympathetic ganglion (G). False-negative case with LBD and normal 123I-MIBG myocardial scintigraphy presents with obscure denervation of TH-immunoreactive sympathetic fibers (B) and adequate accumulation of α-synuclein (E) in the heart. Only a small amount of α-synuclein accumulation is observed in the sympathetic ganglion (H). False-positive case without LBD and with abnormal 123I-MIBG myocardial scintigraphy presents with generally preserved TH-immunoreactive sympathetic fibers but sparse in some nerve fascicles (C), without accumulation of α-synuclein in the heart (F) or sympathetic ganglion (I). Counterstain is hematoxylin. Scale bar represents 50 µm (A–I).