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Multicenter Study
. 2015 Mar 20;10(3):e0120540.
doi: 10.1371/journal.pone.0120540. eCollection 2015.

Diagnostic accuracy of 123I-meta-iodobenzylguanidine myocardial scintigraphy in dementia with Lewy bodies: a multicenter study

Affiliations
Multicenter Study

Diagnostic accuracy of 123I-meta-iodobenzylguanidine myocardial scintigraphy in dementia with Lewy bodies: a multicenter study

Mitsuhiro Yoshita et al. PLoS One. .

Abstract

Background and purpose: Dementia with Lewy bodies (DLB) needs to be distinguished from Alzheimer's disease (AD) because of important differences in patient management and outcome. Severe cardiac sympathetic degeneration occurs in DLB, but not in AD, offering a potential system for a biological diagnostic marker. The primary aim of this study was to investigate the diagnostic accuracy, in the ante-mortem differentiation of probable DLB from probable AD, of cardiac imaging with the ligand 123I-meta-iodobenzylguanidine (MIBG) which binds to the noradrenaline reuptake site, in the first multicenter study.

Methods: We performed a multicenter study in which we used 123I-MIBG scans to assess 133 patients with clinical diagnoses of probable (n = 61) or possible (n = 26) DLB or probable AD (n = 46) established by a consensus panel. Three readers, unaware of the clinical diagnosis, classified the images as either normal or abnormal by visual inspection. The heart-to-mediastinum ratios of 123I-MIBG uptake were also calculated using an automated region-of-interest based system.

Results: Using the heart-to-mediastinum ratio calculated with the automated system, the sensitivity was 68.9% and the specificity was 89.1% to differentiate probable DLB from probable AD in both early and delayed images. By visual assessment, the sensitivity and specificity were 68.9% and 87.0%, respectively. In a subpopulation of patients with mild dementia (MMSE ≥ 22, n = 47), the sensitivity and specificity were 77.4% and 93.8%, respectively, with the delayed heart-to-mediastinum ratio.

Conclusions: Our first multicenter study confirmed the high correlation between abnormal cardiac sympathetic activity evaluated with 123I-MIBG myocardial scintigraphy and a clinical diagnosis of probable DLB. The diagnostic accuracy is sufficiently high for this technique to be clinically useful in distinguishing DLB from AD, especially in patients with mild dementia.

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Conflict of interest statement

Competing Interests: Mitsuhiro Yoshita, Kenji Wada and Seigo Nakano received honoraria for sponsored lectures from Fujifilm RI Pharma Co. Ltd. Takashi Asada and Shouhei Yamashina received honoraria for sponsored lectures and research grant from Fujifilm RI Pharma Co. Ltd. and Nihon Medi-Physics Co. Ltd. Haruo Hanyu, Junichi Taki and Takahiko Tokuda received honoraria for sponsored lectures from Nihon Medi-Physics Co. Ltd. Eizo Iseki received honoraria for consultancies, sponsored lectures, and presiding at lecture meetings from Nihon Medi-Physics Co. Ltd. Osamu Iizuka received honoraria and travel costs from Nihon Medi-Physics Co. Ltd. Kenji Kosaka received honoraria for sponsored lectures, writing, and editing from Fujifilm RI Pharma Co. Ltd., and honoraria for sponsored lectures from Nihon Medi-Physics Co. Ltd. Etsuo Mori and Katsuya Urakami received research grant from Fujifilm RI Pharma Co. Ltd., and honoraria for sponsored lectures from Nihon Medi-Physics Co. Ltd. Hirotaka Maruno received honoraria for sponsored lectures and travel costs from Fujifilm RI Pharma Co. Ltd. and Nihon Medi-Physics Co. Ltd. Kenichi Nakajima has collaborative research works with Fujifilm RI Pharma Co. Ltd., and received research funds for joint researches, honoraria for lectures and writing, and pending application for a patent on software development unrelated to this study; the title is "Image processing method and computer program” and the number is No. JP 2012–78088. Kenji Nakashima received sponsored scholarship and honoraria for presiding at lecture meetings from Fujifilm RI Pharma Co. Ltd. Satoshi Orimo received honoraria for sponsored lectures from Fujifilm RI Pharma Co. Ltd. and Nihon Medi-Physics Co. Ltd. Junichi Yamasaki received sponsored scholarship, honoraria for sponsored lectures, and travel costs from Fujifilm RI Pharma Co. Ltd., and honoraria for sponsored lectures and research grant from Nihon Medi-Physics Co. Ltd. Masahito Yamada received honoraria for sponsored lectures and research grant from Fujifilm RI Pharma Co. Ltd. Heii Arai, Hiroyuki Arai, Tetsuaki Arai, Hiroshige Fujishiro, Eizo Iseki, Kenichi Kashihara, Katsuyoshi Mizukami, Yoshikuni Mizuno, Hiroyuki Nakamura, Seigo Nakano, Yoshiyuki Nishio, Miharu Samuraki, Akira Takahashi, Kumiko Utsumi, Kenji Wada, and Yukihiko Washimi declare that they have no conflicts of interest. There are no further patents, products in development or marketed products to declare. This does not alter the authors’ adherence to all the PLOS ONE policies on sharing data and materials.

Figures

Fig 1
Fig 1. Normal and abnormal planar image of 123I-MIBG cardiac scintigraphy.
Fig 2
Fig 2. Flow diagram of the eligible patients and the enrolling process of the study.
Fig 3
Fig 3. Individual values for the H/M ratio of 123I-MIBG uptake.
Significant reductions in early and delayed H/M ratios were observed in probable DLB compared with probable AD group of all cases, mild dementia cases (MMSE ≥ 22), and moderate/severe dementia cases (MMSE ≤ 21) (see text). Green lines indicate the mean value of H/M ratio. AD: Alzheimer’s disease; DLB: dementia with Lewy bodies.
Fig 4
Fig 4. ROC curves for the detection of probable DLB from probable AD based on H/M ratio of each group.
The area under the ROC curve of the early H/M ratio was 0.805 (p < 0.001) for the all patients group, 0.901 (p < 0.0001) for the mild dementia group, and 0.732 (p = 0.001) for the moderate/severe dementia group, whereas that for the delayed H/M ratio was 0.817 (p < 0.001), 0.942 (p < 0.0001), and 0.747 (p = 0.007), respectively. ROC: receiver operating characteristic. AUC: area under the curve.

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