A method for data acquisition of ¹²³I-MIBG myocardial scintigraphy was described elsewhere [24]. Briefly, after subjects have been in a supine position for 20 min, 111 MBq of ¹²³I-MIBG is injected intravenously. Anterior planar and SPECT images are obtained 20–30 min and 3–4 h after the injection as early and delayed images, respectively. On the anterior planar image, regions of interest (ROI) are set on the whole heart (H), including the left ventricle, and mediastinum (M) (Fig. 12.3), and the heart-to-mediastinum (H/M) uptake ratio is calculated as the index of cardiac MIBG uptake by dividing the count density of the ventricular ROI by that of the mediastinal ROI. The washout rate (WR) is calculated as the index of MIBG release as follows: WR (%) = 100 × (Ec − Dc)/Ec, where Ec is the early cardiac count density and Dc is the decay-corrected delayed cardiac count density (mediastinal counts are subtracted as backgrounds).

We developed software for semiautomatically measuring H/M ratio in ¹²³I-MIBG myocardial scintigraphy; using the semiautomatic method, the H/M ratio showed high reproducibility in both early and delayed imaging [25]. As different collimators and scinticameras are used for ¹²³I-MIBG myocardial scintigraphy in different institutions, standardization of the H/M ratio is necessary for correction of normal databases and for a multicenter study. For standardization of the H/M ratios, we developed the calibration phantom method which could be practically used for multicenter comparison of H/M ratios [1, 26]. To further standardize the H/M ratio with various camera-collimator combinations among institutions, a conversion coefficient for each camera-collimator system was created based on phantom studies; by using the reference H/M ratio and conversion coefficients for the system, H/M ratio in various conditions could be converted to the standard H/M ratios in a range of normal to low H/M ratios [27]. The standardized H/M ratio will be a good background to recommend universal use of MIBG study.

Cardiac diseases, metabolic or endocrine diseases, and neurological diseases with postganglionic sympathetic nerve lesions are associated with reduction of the cardiac uptake of MIBG in ¹²³I-MIBG myocardial scintigraphy (Table 12.1). The neurological diseases include neuropathies involving autonomic nerves, such as diabetic neuropathy and amyloid neuropathy, as well as LBD, such as PD, DLB, and PAF. Besides DLB (see below), reduced MIBG uptake was reported in patients with PAF, PD, and familial amyloid polyneuropathy (FAP) and a subset of patients with PSP or MSA [12–14, 28–33]. In addition, marked reduction of cardiac MIBG uptake was reported with idiopathic RBD, and an association of Lewy body pathology was suggested [34]. Thus, when ¹²³I-MIBG myocardial scintigraphy is used for the diagnosis of LBD (PD, DLB, PAF, and RBD), cardiac diseases, metabolic or endocrine diseases, and the other neurological diseases with possible postganglionic sympathetic nerve lesions need to be excluded.

Further, it should be noted that some medicines interfere with biodistribution of ¹²³I-MIBG [35]. Several mechanisms of interaction were reported: (1) inhibition of uptake, (2) inhibition of active transport into vesicles, (3) competition for transport into vesicles, (4) depletion of content of storage vesicles, (5) calcium mediated, and (6) other possible unknown mechanisms [35]. List of medicines that are known to interact with MIBG is shown in Table 12.2; it is recommended to avoid or stop treatment with such medicines [33, 35].

Since 2001, many single-center studies have reported usefulness of ¹²³I-MIBG myocardial scintigraphy to discriminate DLB from AD or other dementias since 2001 [36–45]. Our group investigated cardiac sympathetic denervation with MIBG scintigraphy in 37 patients with DLB (7 without parkinsonism and 30 with parkinsonism), 42 patients with AD, and 10 normal controls and found that, regardless of parkinsonism, delayed H/M ratio had a sensitivity of 100 %, a specificity of 100 %, and a positive predictive value of 100 % at a cutoff value of 1.68 in discrimination between DLB and AD (Fig. 12.4) [39]. In a systematic review and a meta-analysis [46], eight single-center studies were identified comprising a total of 346 patients with dementia (152 with DLB and 194 with other dementias); the pooled sensitivity of MIBG scintigraphy in detection of DLB was 98 % (95 % CI, 94–100 %); the pooled specificity of MIBG scintigraphy in differential diagnosis between DLB and other dementias was 94 % (95 % CI, 90–97 %). The data suggest that MIBG is an accurate test for differential diagnosis between DLB and other dementias.

Comparative value of MIBG myocardial scintigraphy with other diagnostic tools in distinguishing DLB from AD or other dementias has been investigated in several single-center studies. In a comparison between MIBG myocardial scintigraphy and brain perfusion SPECT with N-isopropyl-p-[¹²³I]iodoamphetamine (¹²³I-IMP) involving 19 patients with DLB and 39 patients with AD, brain perfusion SPECT failed to identify occipital hypoperfusion in five patients with DLB, while reduction of MIBG uptake was found in all the patients with DLB [41]. Some patients with probable or possible DLB showed no occipital hypoperfusion in ¹²³I-IMP SPECT, but showed low cardiac MIBG uptake [43]. Combination of brain FDG-PET with MIBG myocardial scintigraphy was useful in differentiation of DLB from AD [47]. Thus, MIBG myocardial scintigraphy would improve the sensitivity in detection of DLB in combination with brain perfusion SPECT or FDG-PET [48]. In patients with probable DLB (n = 28) studied by both ¹²³I-MIBG myocardial scintigraphy and ¹²³I-FP-CIT SPECT, cardiac MIBG uptake and FP-CIT binding in basal ganglia were reduced in parallel [49]. In differential diagnosis between DLB (n = 20) and other dementias (n = 11) using both ¹²³I-MIBG myocardial scintigraphy and ¹²³I-CIT-SPECT, the sensitivity and specificity were 90 % and 91 %, respectively, for MIBG, and were 90 % and 91 %, respectively, for FP-CIT; the same results confirmed the usefulness of both techniques in DLB diagnosis [50]. Compared with cerebrospinal fluid (CSF) tests, the diagnostic value of MIBG myocardial scintigraphy was superior to that of CSF markers including amyloid β 1–42, 181-phosphorylated tau [42], and α-synuclein [51].

Furthermore, subjects with mild cognitive impairment (MCI) and reduced cardiac uptake of MIBG were reported to later convert to probable DLB, suggesting that MIBG myocardial scintigraphy is useful for detection of DLB at MCI stage [52, 53].

To establish diagnostic value of MIBG myocardial scintigraphy, we performed a multicenter study in ten Japanese sites, 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 [1]. Three readers, unaware of the clinical diagnosis, classified the images as either normal or abnormal by visual inspection. All the institutions used standard acquisition conditions, and cross calibration of H/M ratios with the phantom studies among the institutions was performed as described elsewhere [26]. The H/M ratios were calculated using an automated region-of-interest-based system [25].

Individual values for the H/M ratio of ¹²³I-MIBG uptake and ROC analysis for discriminating probable DLB from probable AD groups are shown in Figs. 12.5 and 12.6, respectively. Using the H/M ratio calculated with the automated system, the sensitivity was 68.9 %, and the specificity was 89.1 % to differentiate probable DLB from probable AD at a cutoff value of 2.10 in both early and delayed images (Table 12.3). 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) (Figs. 12.5 and 12.6), the sensitivity and specificity were 77.4 % and 93.8 %, respectively, with the delayed H/M ratio. The moderate/severe dementia group, on the other hand, had a sensitivity of 59.6 % and a specificity of 83.3 % at a cutoff value of 2.10. No adverse events were noted during this study.