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Objectives The authors sought to elucidate the prognostic value of cardiac sympathetic nerve dysfunction as evaluated using iodine-123-labeled metaiodobenzylguanidine (123I-MIBG) single-ph...

OBJECTIVE 123I metaiodobenzylguanidine (MIBG) scintigraphy is a useful tool for the diagnosis of pheochromocytomas (PHEOs), but some PHEOs are difficult to differentiate from cortical adenoma (CA) or normal adrenal uptake by visual evaluation alone. A new semi-quantitative analysis using 123I MIBG SPECT/CT is thus expected. Herein, we introduce the tumor-to-liver count ratio (T/L) and the tumor-to-muscle count ratio (T/M). METHODS We examined the cases of 21 patients with PHEOs (10 males, 11 females; age 24-80, median 61 years) and 23 patients with CA (15 males and 8 females, age 30-78, median 58 years). The visual scoring based on 123I MIBG planar images (planar score) and SPECT images (SPECT score) was used as the conventional evaluation. Using 123I MIBG SPECT/CT findings, we calculated the semi-quantitative values of the count ratio using the maximum or mean count of the tumor and the liver or muscle as the reference organ (T/Lmax, T/Lmean, T/Mmax and T/Mmean). Each evaluation of the PHEOs and CAs was compared, and the diagnosing performance was evaluated based on an ROC analysis. RESULTS The area under curve (AUC) values were as follows: the planar score, 0.833; SPECT score, 0.813; T/Lmax, 0.986; T/Lmean, 0.975; T/Mmax, 0.955; and T/Mmean, 0.933. The AUC for T/Mmax was significantly higher than those of the planar score, and SPECT score by ROC analysis (p

PURPOSE: Planar scintigraphy with (123)I-radiolabeled metaiodobenzylguanidine ((123)I-mIBG) is an important imaging modality to evaluate neuroblastoma. In recent years, Single Photon Emission Computed Tomography combined with Computed Tomography (SPECT/CT) has revolutionized nuclear medicine. Nevertheless, the addition of the CT has increased the patients' irradiation. We aimed to evaluate the incremental benefits of (123)I-mIBG SPECT/CT over conventional planar imaging and to estimate the relative increase of radiation dose. METHODS: We retrospectively evaluated the added value of 56 SPECT/CT performed in 40 children in terms of better characterization of the lesion and its locoregional extension, better lymph node staging, detection of new lesions, and elimination of false positives by a paired comparison between the planar images and the SPECT/CT ones. Then, we calculated the percentage contribution of the additional radiation of the CT in this hybrid imagery. RESULTS: In 88% (49 out of 56) of the examinations, SPECT/CT provided additional information, which was crucial in 20% of the cases. It allowed a better characterization of the lesion and its locoregional extension in 44 cases, a better lymph node staging in 28 cases, the detection of 33 new lesions, and the elimination of 9 false positives. The CT effective dose was significantly lower than the SPECT one. The average additional radiation exposure due to CT was 12% (4–23%). CONCLUSION: (123)I-mIBG SPECT/CT has an undeniable added value that improves planar imaging interpretation and impacts patient management. These potential benefits would justify the low additional radiation induced by the CT.

To evaluate the detecting capability between planar imaging (PI) and PI combined with single-photon emission computed tomography/computed tomography (PICWS), including 123I- and 131I-labeled metaiodobenzylguanidine (mIBG) and to compare the detecting capability between 123I-mIBG and post-therapeutic 131I-mIBG scintigraphy including PI and PICWS for Curie scoring in patients with neuroblastoma. Sixty-two patients with 66 pairs of complete images with neuroblastoma were enrolled in this retrospective study. Comparing the Curie scoring between 123I-mIBG PI and PICWS and between post-therapeutic 131I-mIBG PI and PICWS, findings were concordantly negative in 28.79% and 18.18% of studies, concordantly positive in 66.67% and 74.24% of studies, and discordant in 4.54% and 7.58% of studies, respectively. PICWS was superior to PI including 123I- and 131I-mIBG in the evaluation of Curie scoring for neuroblastoma patients (both P

Objective 123I metaiodobenzylguanidine (MIBG) scintigraphy is a useful tool for the diagnosis of neuroblastoma (NB). MIBG uptake is correlated with norepinephrine transporter expression; hence, it is expected that high-MIBG tumors would be more highly differentiated and have a better prognosis than those with lower expression. We have introduced a method of assessing MIBG accumulation semi-quantitatively using SPECT/CT fusion images. The purpose of this study was to evaluate the relationship of 123I MIBG uptake measured by semi-quantitative values of SPECT/CT and early relapse of NB. Methods We studied the cases of 11 patients (5 males and 6 females, age 5–65 months, median age 20 months) with histopathologically proven NB between April 2010 and March 2015. The early-relapse group was defined as patients who had relapsed within 3 years after the first 123I MIBG SPECT/CT exam. Other patients were classified as the delay-relapse group. Uptake of MIBG was evaluated using the count ratio of tumor and muscles. T/Mmax and T/Mmean were defined as follows: T/Mmax = max count of tumor/max count of muscle, T/Mmean = mean count of tumor/mean count of muscle. Results The average T/Mmean values of the early-relapse group and delay-relapse group were 2.65 ± 0.58 and 7.66 ± 2.68, respectively. The T/Mmean values of the early-relapse group were significantly lower than those of delay-relapse group (p Conclusions Low 123I MIBG uptake using semi-quantitative SPECT/CT analysis was correlated with early relapse of NB.

This systematic review aimed to evaluate the prognostic value of Iodine123 Metaiodobenzylguanidine (123I-mIBG) SPECT myocardial imaging in patients with heart failure (HF) and to assess whether semi-quantitative SPECT scores can be useful for accurate risk stratification concerning arrhythmic event (AE) and sudden cardiac death (SCD) in this cohort. A systematic literature search of studies published until November 2020 regarding the application of 123I-mIBG SPECT in HF patients was performed, in Pubmed, Scopus, Medline, Central (Cochrane Library) and Web Of Science databases, including the words “MIBG”, “metaiodobenzylguanidine”, “heart”, “spect”, and “tomographic”. The included studies had to correlate 123I-mIBG SPECT scores with endpoints such as overall survival and prevention of AE and SCD in HF patients. According to the sixteen studies included, the analysis showed that 123I-mIBG SPECT scores, such as summed defect score (SDS), regional wash-out (rWO), and regional myocardial tracer uptake, could have a reliable prognostic value in patients with HF. An increased SDS or rWO, as well as a reduced 123I-mIBG myocardial uptake, have proven to be effective in predicting AE- and SCD-specific risk in HF patients. Despite achieved results being promising, a more reproducible standardized method for semi-quantitative analysis and further studies with larger cohort are needed for 123I-mIBG SPECT myocardial imaging to be as reliable and, thus, accepted as the conventional 123I-mIBG planar myocardial imaging.

Previous reports have found evidence that the lung uptake of iodine-123-metaiodobenzylguanidine (123I-MIBG) represents pulmonary vascular endothelial function. Therefore, it was believed that the reduced lung uptake of 123I-MIBG in patients with pulmonary artery hypertension may indicate poor pulmonary vascular endothelial function in those patients. In our previous report, we analyzed the lung uptake of 123I-MIBG in patients with pulmonary hypertension, and demonstrated that it is lower in patients with pulmonary arterial hypertension (PAH) than in those with chronic thromboembolic pulmonary hypertension and controls, suggesting that reduced uptake of 123I-MIBG in patients with PAH indicates endothelial dysfunction of the pulmonary artery. In the current report, we describe a 46-year-old woman diagnosed with scleroderma whose lung uptake of 123I-MIBG was decreased on admission, but she was not diagnosed with pulmonary artery hypertension at that time because her pulmonary artery pressure during right heart catheterization was not elevated. However, she was diagnosed with borderline PAH 2 years later. The lung uptake of 123I-MIBG was reduced before a reduction in %DLCO was observed. This report suggests that the lung uptake of 123I-MIBG may be useful for the early diagnosis of pulmonary artery hypertension.

123I-metaiodobenzylguanidine (MIBG) is a radiolabeled norepinephrine analog that can be used to investigate myocardial sympathetic innervation. 123I MIBG scintigraphy has been investigated with interest in many heart disease settings. In patients with systolic heart failure (HF), 123I MIBG scintigraphy can capture functional impairment and rarefaction of sympathetic terminals (which manifest as reduced early and late heart-to-mediastinum [H/M] ratio on planar scintigraphy), and increased sympathetic outflow (which can be visualized as high washout rate). These findings have been consistently associated with a worse outcome: most notably, a phase 3 trial found that patients with a late H/M 1.60 have a higher incidence of all-cause and cardiovascular mortality and life-threatening arrhythmias over a follow-up of less than 2years. Despite these promising findings, 123I MIBG scintigraphy has not yet been recommended by major HF guidelines as a tool for additive risk stratification, and has then never entered the stage of widespread adoption into current clinical practice. 123I MIBG scintigraphy has been evaluated also in patients with myocardial infarction, genetic disorders characterized by an increased susceptibility to ventricular arrhythmias, and several other conditions characterized by impaired sympathetic myocardial innervation. Across different disorders, scintigraphy evidence increased sympathetic outflow and a mismatch between innervation and perfusion emerged quite consistently as predictors of a worse outcome. In the present article we will summarize the state-of-the-art on cardiac 123I MIBG scintigraphy, the applications in various heart diseases, the current unresolved issues, and the possible directions of future research.

Rationale: The aim of this study was to analyse the interobserver agreement of visual and quantitative assessment of cardiac 123I-MIBG scintigraphy. Methods: Planar images were acquired using a low-energy collimator. The heart-to-mediastinal ratio (HM ratio) was adjusted for the use of a low-energy collimator, using a published formula. Interpretation was undertaken on both visual interpretation and following the addition of adjusted HM ratios. Images were classified as normal, abnormal or borderline. Results: The cohort consisted of 10 patients. On visual interpretation only, there was strong agreement on the interpretation of the scan, κ = .82, p

We report the case of a 75-year-old woman with liver metastasis as a recurrence of a pheochromocytoma resected 10 years ago, with a rare germline mutation in transmembrane protein 127, falsely negative on 18F-FDOPA and 18F-FDG PET/CT scans but strongly positive on 123I-MIBG scintigraphy and on 68Ga-DOTATOC PET/CT. Functional imaging has a key role in diagnosis of pheochromocytoma and paraganglioma, especially 18F-FDOPA shows very high sensitivity and specificity. However, 18F-FDOPA might be falsely negative in some of these tumors, depending on specific mutations, and thus MIBG or 68Ga-DOTATOC imaging could be an alternative.

Parkinson disease (PD) is a heterogeneous neurodegenerative disorder. Dopamine transporter imaging using 123I-2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl)-nortropane (FP-CIT) and noradrenergic cardiac imaging using 123I-meta-iodobenzylguanidine (MIBG) have been used in combination or separately to study PD patients. Published results regarding uptake of the 2 tracers in each motor subtype are fairly abundant and mostly in agreement. However, data on the intrasubject association between dopaminergic and noradrenergic systems in PD patients are relatively scant and vary. We aimed to assess the intrasubject relationship between striatal dopamine transporter density using a PET tracer and cardiac sympathetic innervation in tremor-dominant subtype (TD) and akinetic-rigid subtype (AR) of PD. This study has a cross-sectional design. Thirty-one patients with early PD (17 TD/14 AR) who underwent both 123I-MIBG cardiac scintigraphy and 18F-FP-CIT PET/CT were retrospectively selected. We assessed the relationship between heart-to-mediastinum ratio (H/M) of 123I-MIBG and specific (striatal)-to-nonspecific (cerebellar) dopamine transporter binding ratio (S/N) measured from 4 separate regions-of-interest (bilateral caudate nuclei and lentiform nuclei) of 18F-FP-CIT in each motor subtype. S/N of all 4 striatal regions were significantly lower in the AR subgroup than in the TD subgroup. H/M was not significantly different. There was a significant intrasubject correlation between H/M and S/N of the lentiform nucleus in AR-PD but no correlation between H/M and any of 4 S/N in TD-PD. Our data suggest a coupled degeneration of nigrostriatal dopaminergic and myocardial sympathetic denervation in AR subtype, but not in TD subtype, of early PD patients. These different results between the 2 motor subtypes likely reflects the heterogeneous pathophysiology of PD.

123I-metaiodobenzylguanidine scintigraphy is used to differentiate Lewy body disease from other neurodegenerative disorders. We identified 2 cases with remarkably changed pulmonary uptake between 2 metaiodobenzylguanidine scintigraphies; pulmonary uptake was reduced when patients were taking selective serotonin reuptake inhibitor/serotonin noradrenaline reuptake inhibitor and preserved during the medication-naive or withdrawal state, suggesting that pulmonary uptake involves not only the noradrenaline transporter, but also the serotonin transporter. Pulmonary accumulation may affect the heart-to-mediastinum ratio as the region of interest on the planner image is usually placed on the heart and includes part of the lung. Therefore, we should pay attention to the medication state of patients with decreased pulmonary uptake.

A 3-year-old boy with high-risk neuroblastoma underwent 123I-MIBG scan to evaluate the disease status after surgery and chemotherapy. 123I-MIBG SPECT/CT demonstrated liver metastasis. In addition, mildly increased uptake in the inferior left erector spinae was noted. Contrast-enhanced CT suggested intramuscular hemangioma. The 123I-MIBG accumulation in the intramuscular hemangioma persisted during the follow-up scan, whereas the abnormal activity in the liver was resolved.

131I-metaiodobenzylguanidine (131I-MIBG) is a theranostic agent useful for treatment of neuroendocrine malignancies. In this case, a child with a Curie score of 21 was administered 17.871 GBq (483 mCi) of 131I-MIBG. The elimination half-life progressively increased from 23 h to 77 h during the 11 d that the patient was hospitalized for radiation isolation. Six weeks after the posttherapy scan, a survey with an ion-chamber device yielded readings of 0.3 μSv/h (0.03 mR/h) on contact with spinal regions that had shown increased uptake on the scan. A planar image obtained using the 131I setting and a high-energy collimator did not demonstrate any focal uptake. 123I-MIBG was administered, and the 24-h scan was of diagnostic quality, without degradation from the remaining 131I-MIBG. Additional study is needed on whether the Curie score affects elimination of 131I-MIBG and on whether the period of hospitalized radiation isolation needs to be extended.

PurposeCardiac 123I-MIBG image interpretation is affected by population differences and technical factors. We recruited older adults without cognitive decline and compared their cardiac MIBG uptake with results from the literature.MethodsPhantom calibration confirmed that cardiac uptake results from Japan could be applied to our center. We recruited 31 controls, 17 individuals with dementia with Lewy bodies (DLB) and 15 with Alzheimer’s disease (AD). Images were acquired 20 minutes and four hours after injection using Siemens cameras with medium-energy low-penetration (MELP) collimators. Local normal heart-to-mediastinum (HMR) ratios were compared to Japanese results.ResultsSiemens gamma cameras with MELP collimators should give HMRs very close to the calibrated values used in Japan. However, our cut-offs with controls were lower at 2.07 for early and 1.86 for delayed images. Applying our lower cut-off to the dementia patients may increase the specificity of cardiac MIBG imaging for DLB diagnosis in a UK population without reducing sensitivity.ConclusionsOur local HMR cut-off values are lower than in Japan, higher than in a large US study but similar to those found in another UK center. UK centers using other cameras and collimators may need to use different cut-offs to apply our results.

Purpose 18F-Fluoro-L-dihydroxyphenylalanine ([18F]FDOPA) PET offers high sensitivity and specificity in the imaging of non-malignant head and neck paraganglioma (HNPGL) but lower sensitivity in metastatic disease of these neuroendocrine tumours (NET). In contrast to the radiotracer [18F]FDOPA, both 123I-meta-iodo-benzylguanidine ([123I]MIBG) and 68Ga-DOTA-Tyr3-octreotide ([68Ga]Ga-DOTA-TOC) offer valuable clinical information on norepinephrine and somatostatin (SST) receptor status for planning 131I-MIBG and radionuclide peptide therapy (PRRT), respectively. Therefore, we compared [68Ga]Ga-DOTA-TOC and [18F]FDOPA PET/CT with [123I]MIBG planar and SPECT/CT imaging, for the detection of HNPGL. Combined cross-sectional imaging was the reference standard. Methods A total of 3 men and 7 women (age range 22 to 73 years) with anatomical and/or histologically proven HNPGL were included in this study. Of these patients, 3 patients had metastatic HNPGL. Comparative evaluation included morphological imaging with CT and functional imaging with [68Ga]Ga-DOTA-TOC and [18F]FDOPA PET, including [123I]MIBG imaging. The imaging results were analysed on a per-patient and per-lesion basis. Results On a per-patient analysis, the detection rate of both [68Ga]Ga-DOTA-TOC PET/CT and [18F]FDOPA PET/CT was 100%, that of planar [123I]MIBG imaging 10.0% and that of SPECT/CT 20.0%. On a per-lesion basis and in reference to diagnostic CT, the sensitivity of [68Ga]Ga-DOTA-TOC PET/CT was 100% (McNemar, P Conclusion [68Ga]Ga-DOTA-TOC PET/CT is superior for imaging, non-malignant and metastatic HNPGL compared to [18F]FDOPA PET/CT and planar [123I]MIBG imaging, including SPECT/CT, particularly in bone lesions. Combined functional/anatomical imaging ([68Ga]Ga-DOTA-TOC PET/CT) enables excellent delineation of tumour extent in these rare tumour entities. Compared to [123I]MIBG scintigraphy, [68Ga]Ga-DOTA-TOC PET appears far more useful for planning radionuclide therapy in patients with surgically inoperable tumours or metastatic disease.

Funding Acknowledgements Type of funding sources: Public hospital(s). Main funding source(s): University Clinic Hospital of Valencia Aim The assessment of cardiac sympathetic innervation by 123I-metayodobenzylguanidine (123I-MIBG) has proved useful in patients with heart failure and neurodegenerative disorders. The standard quantification of global cardiac uptake is to obtain the heart to mediastinum (HM) ratio in planar images, while SPECT images provide better evaluation of regional extent of denervated areas. Although low energy (LE) collimator has been widely used in these patients, septal penetration of high-energy photons of 123I could affect image quality and quantification accuracy. We have compared in the same patients the effect of collimator type on image quality and quantitative assessment of HM ratio. Methods In a group of 14 patients (11 men, 57-77 y/o, 66.4 ± 5.6) submitted for cardiac sympathetic study, we obtained successive planar anterior chest images 4h after the IV administration of 10 mCi of 123I-MIBG with a low-energy-high-resolution (LEHR) and a medium-energy (ME) collimators. Images were obtained with the same gammacamera Brightview Philips for 10 min on 256x256 matrix, with 159 Kev photopeak and unchanged patient position. For quantification of HM ratio, we use in each patient the same manual heart ROI and rectangular upper mediastinum ROI in the two acquired images to obtain the corresponding HM ratio. Results The image quality was better in all the patients with ME collimator acquisition than with LEHR collimator acquisition, and the HM ratio showed higher values with ME: 1.65-2.61 (mean 2.15 ± 0.28) than with LEHR: 1.27-1.85 (mean: 1.51 ± 0.18) with a mean difference of 0.64 ± 0.15 (0.38-0.88) between ME and LEHR and a mean ratio LEHR/ME of 0.70 ± 0.04 (0.64-0.79). In 9 patients with HM ratio ≤ 1.60 obtained from LEHR collimator acquisition, the mean difference with HM ratio obtained with ME collimator was 0.61 ± 0.12 and mean ratio LEHR/ME was 0.69 ± 0.03 and in 5 patients with HM ratio(LEHR) >1.60, mean difference with HM ratio(ME) was 0.69 ± 0.19 and mean ratio LEHR/ME was 0.71 ± 0.02. Conclusion Use of a ME collimator provides better image quality than LEHR collimator in planar images and higher values of HM ratio, providing a more accurate quantification of cardiac uptake in the patients submitted for evaluation of cardiac sympathetic innervation by 123I-MIBG, and could also improve the evaluation of regional impairment and extent of denervated areas by SPECT.

Purpose of Review This narrative review reflects on the body of evidence on cardiac 123I-mIBG imaging that has accumulated since the introduction in the late 1970s and focusses on to what extent cardiac 123I-mIBG imaging has fulfilled its potential in cardiology especially. Recent Findings In contrast to the linear relationship between 123I-mIBG-derived parameters and overall prognosis in heart failure, there seems a “bell-shape” curve for 123I-mIBG-derived parameters and arrhythmic events. In addition, there is a potential clinical role for cardiac 123I-mIBG in optimizing patient selection for expensive devices (i.e., ICD and CRT). This needs of course to be established in future trials. Summary Cardiac 123I-mIBG imaging is, despite the numerous of studies, sometimes mistakenly seen as a nice to have technique rather than a must have imaging modality. Although cardiac 123I-mIBG imaging has grown and matured over the years, its full clinical potential has still not been tested to the maximum.

123I-Metaiodobenzylguanidine (MIBG) scintigraphy is a widely used functional imaging tool with a high degree of sensitivity and specificity in diagnosis of pheochromocytoma. However, rare cases of false positive reactions have been reported. A 67-year-old male patient was admitted with epigastric pain. Abdominal computed tomography (CT) revealed a heterogeneous left adrenal mass 6 cm in diameter; following hormone testing, 123I-MIBG scintigraphy was performed to determine the presence of pheochromocytoma, which confirmed eccentric uptake by a large left adrenal gland mass. Chest CT and PET-CT confirmed metastatic lymphadenopathy; therefore, endobronchial ultrasound transbronchial needle aspiration was performed. Metastatic carcinoma of unknown origin was suspected from a lymph node biopsy and surgical resection was performed for definitive diagnosis and correction of excess hormonal secretion. A final diagnosis of undifferentiated adrenal malignant tumor was rendered, instead of histologically malignant pheochromocytoma, despite the uptake of MIBG demonstrated by scintigraphy. When the degree of MIBG uptake is low-grade in relationship to a large tumor mass, then a false-positive result should be entertained, particularly in the absence of typical clinical and biochemical features of pheochromocytoma.

Funding Acknowledgements Type of funding sources: None. Introduction Cardiac 123I-mIBG SPECT imaging provides information on regional myocardial innervation. However, there is no consensus on how to use a, 17-segment based score to assess prognosis. The present study examined whether a simpler regional scoring approach for evaluation of 123I-mIBG SPECT combined with rest 99mTc-tetrofosmin SPECT myocardial perfusion imaging could be used for the prediction of arrhythmic events (AEs) in ischemic heart failure (HF). Methods 261 ischemic HF subjects (NYHA II/III, LVEF ≤35% on gated SPECT) of the ADMIRE-HF study cohort with complete cardiac 123I-mIBG and rest 99mTc-tetrofosmin SPECT studies were enrolled. Both SPECT image sets were read together by 2 experienced nuclear imagers and scored by consensus. In addition to standard 17 segments scoring, the readers classified walls (i.e. anterior, lateral, inferior, septum and apex) as normal, matched defect of innervation and perfusion, mismatched (i.e., innervation defect lager than perfusion defect) or reverse mismatched (i.e., innervation defect smaller than perfusion defect). Cox proportional hazards ratios (HR) were used to determine if the visual segmental wall classification innervation/perfusion mismatch score, 123I-mIBG summed defect scores (SDS), 99mTc-tetrofosmin SDS and innervation/perfusion mismatch SDS, age, LVEF, NYHA class, B-type natriuretic peptide (BNP) and norepinephrine (NE) plasma levels were associated with occurrence of AEs (i.e. sudden cardiac death, sustained VT, resuscitated cardiac arrest, appropriate ICD therapy). Results At 2-year median follow-up, 38 subjects (14.6%) had AEs. Subjects with 1 or 2 mismatched walls were more than twice as likely to have AEs compared with subjects with either 0 or 3-5 mismatched walls (24.0% vs 10.8%, p = 0.006). Cox regression analyses showed that the combination of the presence of visual mismatch in 1-2 walls and BNP and were the only independent predictors of AEs (HR 2.583 [1.261-5.107],p = 0.001) However, compared to the visual mismatch, the contribution of BNP is relatively small (i.e., HR 1.001 [1.000-1.001]). Conclusion In ischemic HF with LVEF ≤35 the highest risk of AEs occurs in subjects with intermediate levels of visual wall-level innervation/perfusion mismatches. Therefore, a simple visual wall-level based assessment of combined cardiac 123I-mIBG and rest 99mTc-tetrofosmin SPECT can be used to differentiate those HF patients at higher AE risk from those with relatively low AE risk. Table 1. Cox regression analysis Variable HR (95% CI) X2 change X2 p-value AE’s 1-2 mismatched segments 2.412 (1.204-4.830) 6.581 5.880 0.010 BNP 1-2 mismatched segments 1.001 (1.000-1.001) 2.538 (1.261-5.107) 13.434 4.129 0.001 Abstract Figure. Kaplan Meier curves for AEs

Background In patients with aortic valve stenosis (AS), cardiac sympathetic nervous (CSN) dysfunction and its improvement after TAVR have been reported; however, the prognostic impact of CSN function remains unclear. This study investigated the prognostic value of cardiac 123I-metaiodobenzylguanidine (MIBG) imaging for the prediction of cardiac events after transcatheter aortic valve replacement (TAVR). Methods This study was a single-center prospective observational study that enrolled patients with AS or failed surgical bioprostheses between July 2017 and May 2019. MIBG scintigraphy was performed before and after TAVR to evaluate the delayed heart–mediastinum ratio (d-H/M). Patients were classified into three pairs of groups based on the baseline and post-TAVR d-H/M (≥2.0 or Results Of 187 consecutive patients who underwent TAVR, 111 (31 men; median age: 86 years) were evaluated. Over a median follow-up of 366 days, 16 (14.4%) patients had MACE. The incidence of MACE was significantly lower in patients with d-H/M improvement and/or the high post-TAVR d-H/M (≥2.0). Post-TAVR d-H/M had significant impacts on MACE, with an adjusted hazard ratio of 1.326 (95% confidence interval, 0.139–2.515; p=0.027). Conclusions Both d-H/M improvement and high post-TAVR d-H/M were associated with better prognosis in patients who underwent TAVR. Cardiac MIBG imaging was useful for predicting cardiac events after TAVR. Funding Acknowledgement Type of funding source: None

Background Huntington’s disease (HD) patients often present with abnormal modulation of blood pressure and heart rate. We investigated whether cardiac autonomic innervation assessed by 123I-metaiodobenzylguanidine (MIBG) imaging is impaired in HD patients, in comparison with controls (Ctrl). Methods Fifteen patients (6 F and 9 M) were assessed by the motor section of the Unified HD Rating Scale, the Total Function Capacity, and the scale for outcomes in Parkinson’s disease-autonomic (SCOPA-AUT) questionnaire. All patients and 10 Ctrl (5 F and 5 M) underwent 123I-MIBG imaging. From planar images, the early and late heart-to-mediastinum (H/M) ratios and myocardial washout rates (WR) were calculated. Results We did not find significant differences in early and late H/M ratios and WR between the two groups. At individual level, three patients showed reduced early and/or late H/M ratios. The most common autonomic complaints were gastrointestinal and genitourinary disorders. SCOPA-AUT questionnaire score results positively correlated with the disease duration and WR. Conclusions Our study indicates that myocardial postganglionic sympathetic innervation is essentially preserved or only minimally involved in HD. These findings suggest that the cardiovascular dysfunction might be mainly due to the impairment of brain areas associated with the regulation and modulation of the heart function.

Purpose The aim of the study is to evaluate the impact of myocardial I-metaiodobenzylguanidine (MIBG) in the diagnosis, clinical management, and differential diagnosis of Parkinson disease (PD) and non-PD parkinsonism. Methods The study enrolled 41 patients with parkinsonism. An initial diagnosis was reached after thorough clinical and imaging evaluation. After 2 to 5 years of follow-up, a final diagnosis was established. All patients underwent, soon after their initial visit, presynaptic striatal DaT scintigraphy with I-FP-CIT (DaTscan) and I-MIBG myocardial scintigraphy. DaTscan is not specific to distinguish among different types of neurodegenerative parkinsonism. I-MIBG myocardial scintigraphy displays the functional status of cardiac sympathetic nerves, which is reduced in PD/dementia with Lewy bodies (DLB) and normal in atypical parkinsonian syndromes and secondary or nondegenerative parkinsonism. Results No patients showed adverse effects during or after both scintigraphies. A positive DaTscan was found in all patients in the PD/DLB group (17/17) and in 15 of 24 patients in the non-PD group. Myocardial I-MIBG scintigraphy was associated with lower sensitivity (82% vs 100%) but higher specificity than DaTscan (79% vs 38%) in diagnosis PD/DLB from non-PD parkinsonism. A positive scan result on both techniques, to confirm diagnosis of PD/DLB, significantly improved the specificity of DaTscan, from 38% to 75%, with no reduction in sensitivity. Conclusions Myocardial I-MIBG imaging provides complementary value to I-FP-CIT in the proper diagnosis, treatment plan, and differential diagnosis between PD and other forms of parkinsonism.

To provide reliable and reproducible heart/mediastinum (H/M) ratio cut-off values for parkinsonian disorders using two machine learning techniques, Support Vector Machines (SVM) and Random Forest (RF) classifier, applied to [123I]MIBG cardiac scintigraphy. We studied 85 subjects, 50 with idiopathic Parkinson’s disease, 26 with atypical Parkinsonian syndromes (P), and 9 with essential tremor (ET). All patients underwent planar early and delayed cardiac scintigraphy after [123I]MIBG (111 MBq) intravenous injection. Images were evaluated both qualitatively and quantitatively; the latter by the early and delayed H/M ratio obtained from regions of interest (ROIt1 and ROIt2) drawn on planar images. SVM and RF classifiers were finally used to obtain the correct cut-off value. SVM and RF produced excellent classification performances: SVM classifier achieved perfect classification and RF also attained very good accuracy. The better cut-off for H/M value was 1.55 since it remains the same for both ROIt1 and ROIt2. This value allowed to correctly classify PD from P and ET: patients with H/M ratio less than 1.55 were classified as PD while those with values higher than 1.55 were considered as affected by parkinsonism and/or ET. No difference was found when early or late H/M ratio were considered separately thus suggesting that a single early evaluation could be sufficient to obtain the final diagnosis. Our results evidenced that the use of SVM and CT permitted to define the better cut-off value for H/M ratios both in early and in delayed phase thus underlining the role of [123I]MIBG cardiac scintigraphy and the effectiveness of H/M ratio in differentiating PD from other parkinsonism or ET. Moreover, early scans alone could be used for a reliable diagnosis since no difference was found between early and late. Definitely, a larger series of cases is needed to confirm this data.

Neurodegenerative diseases occur when neurons in the central and/or peripheral nervous systems lose function over time and ultimately die. They are characterized by common cellular and molecular mechanisms including protein aggregation and inclusion body formation, categorising each type of disease. Therefore, the definitive diagnosis is at post-mortem, based on pathology. However, the development of various molecular imaging techniques has enabled pathological changes to be inferred in vivo. Decreased myocardial 123I-mIBG uptake has been reported in some patients with neurodegenerative diseases. This review is aimed to synthesise the basis, methodology and clinical role of myocardial 123I-mIBG imaging in the diagnosis of certain neurodegenerative diseases, focusing on its utility to differentiate some neurodegenerative Parkinsonisms between them, and to differentiate dementia with Lewy bodies from Alzheimer’s disease and other dementias.

Cardiac denervation is associated with progressive left ventricular (LV) dysfunction, ventricular arrhythmias, and sudden cardiac death (SCD) in heart failure (HF). In this regard, it is important to evaluate cardiac-specific sympathetic nervous system (SNS) function. The radiotracer Iodine-123 meta-iodobenzylguanidine (123I-mIBG) can noninvasively evaluate pre-synaptic SNS function. Recent multicenter trials have shown 123I-mIBG to have strong predictive value for fatal arrhythmias and cardiac death in HF. 123I-mIBG was initially developed in the USA in the 1970s. In 1992, the Japanese Ministry of Health and Labour approved 123I-mIBG for the assessment of cardiac function. Following approval, the Japanese nuclear cardiology community developed 123I-mIBG imaging services in various medical centers. Japanese groups have been trying to establish the clinical utility of 123I-mIBG and standardize parameters for data acquisition and image analysis. The US Food and Drug Administration (FDA) has approved clinical use of 123I-mIBG for cardiac and non-cardiac imaging. However, clinical use of 123I-mIBG in the US has been very limited. The number of 123I-mIBG studies in Japan has also been limited. There are similarities and differences between the two countries. To establish the clinical utility of 123I-mIBG in both countries, it is important to characterize the situations of 123I-mIBG in each.

Postischemic adaptation results in characteristic myocardial structural and functional changes in the ventricular tachycardia (VT) substrate. The aim of this study was to compare myocardial structural and functional adaptations (late gadolinium enhancement/abnormal innervation) with detailed VT mapping data to identify regional heterogeneities in postischemic changes. Methods: Fifteen patients with ischemic cardiomyopathy and drug-refractory VT underwent late gadolinium enhancement cardiac MRI (CMR), 123I-metaiodobenzylguanidine SPECT, and high-resolution bipolar voltage mapping to assess fibrosis (>3 SDs), abnormal innervation ( 0.05). However, any single modality underestimated the total VT substrate area defined as abnormal in at least 1 of the 3 modalities (76.0 cm2 [57.9-143.2 cm2]; P < 0.001). Within the total VT substrate area, regions abnormal in all 3 modalities were most common (25.2%). However, significant parts of the VT substrate had undergone heterogeneous adaptation (abnormal in

Background: Despite therapeutic improvement, the prognosis of chronic heart failure (CHF) remains unfavorable partly due to arrhythmia and sudden cardiac death (SCD). This prospective study evaluated myocardial 123I-meta-iodobenzylguanidine (123I-mIBG) scintigraphy as a predictor of arrhythmic events (AE) in CHF patients. Methods: 170 CHF patients referred for implantable cardioverter-defibrillator (ICD) implantation for both primary and secondary prevention were enrolled. All patients underwent planar and SPECT imaging. Early and late heart-to-mediastinum (H/M) ratio, 123I-mIBG washout (WO), early and late summed SPECT scores were calculated The primary endpoint was an AE: sustained ventricular tachycardia, resuscitated cardiac arrest, appropriate ICD therapy or SCD. The secondary endpoint was appropriate ICD therapy. Results: During a median follow-up of 23.3 months, 69 patients experienced an AE. Early summed score (ESS) was the only independent predictor of AE [HR 1.023 (1.003-1.043)]. Focussing on only patients with an ICD for primary prevention, ESS was the only independent predictor of AE [HR 1.028 (1.007-1.050)]. 123I-mIBG-derived parameters failed to be independent predictors of appropriate ICD therapy. However there was a “bell-shaped” relation between 123I-mIBG scintigraphy-derived parameters and AE and appropriate ICD therapy, i.e., those with intermediate 123I-mIBG abnormalities tended to be at higher risk of events. Conclusion: Although SPECT 123I-mIBG scintigraphy was associated with AE in CHF patients with ICD implantation for primary and secondary prevention, no association was found between 123I-mIBG scintigraphy-derived parameters and appropriate ICD therapy.

Previous studies have demonstrated the feasibility of absolute quantification of dynamic 123I-metaiodobenzylguanidine (123I-MIBG) SPECT imaging in humans. This work reports a simplified quantification method for dynamic 123I-MIBG SPECT using practical protocols with shortened acquisition time and voxel-by-voxel parametric imaging. Methods: Twelve healthy human volunteers underwent five 15-min dynamic SPECT scans at 0, 15, 90, 120, and 180 min after 123I-MIBG injection. List-mode SPECT data were binned into 29 frames and reconstructed with corrections for attenuation, scatter, and decay. Population-based blood-to-plasma correction and metabolite correction were applied to the image-derived input function. Likelihood estimation in graphical analysis (LEGA) was used as a simplified model to obtain volume of distribution (V T) values, which were compared with those obtained with the reversible 2-tissue (2T) compartment model. Three simplified protocols were evaluated with 2T and LEGA using a 30-min scan started simultaneously with tracer injection plus a 15-min scan at 90, 120, or 180 min after injection. Voxel-by-voxel LEGA fitting was applied to the aligned dynamic images using both the full protocol (five 15-min scans) and the simplified protocols. Results: Correlation analysis (y = 0.955x + 0.547, R 2 = 0.997) and Bland-Altman plot (mean difference, -0.8 mL/cm3; 95% limits of agreement, [-2.5, 1.0] mL/cm3; normal V T range, 29.0 ± 12.4 mL/cm3) showed that LEGA can be used as a simplified model of 2T for 123I-MIBG. High-quality V T parametric images could be obtained with LEGA. Region-of-interest (ROI) modeling and parametric imaging results were in excellent agreement as determined by correlation analysis (y = 0.999x - 1.026, R 2 = 0.982) and Bland-Altman plot (mean difference, -1.0 mL/cm3; 95% limits of agreement, [-4.2, 2.1] mL/cm3). V T correlated reasonably well between all simplified protocols and the full protocol with LEGA but not with 2T. The V T results were more reliable when there was a longer interval between the 2 acquisitions in the simplified protocols. Conclusion: For ROI-based kinetic modeling and parametric imaging, reliable quantification of dynamic 123I-MIBG SPECT can be achieved with LEGA using a simplified protocol of a 30-min scan starting with tracer injection plus a 15-min scan no earlier than 180 min after injection.

A quantitative measurement, the Heart-to-Mediastinum (H/M) ratio of counts derived from a planar acquisition approximately 4 hours after injection of 123I-mIBG, is a strong predictor of outcomes in patients with stable class II-III heart failure and LVEF ≤ 35%. This study assessed the test–retest reproducibility of the H/M ratio in such patients. 47 subjects with class II-III systolic heart failure and LVEF ≤ 35% were tested at two time intervals separated by 5 to 14 days. Subjects were imaged twice on the same camera using the same radionuclide dose. Images were sent to a core analysis lab, where three nuclear technologists independently determined the H/M ratios. The primary endpoint was test–retest H/M ratio reproducibility calculated as the absolute difference in mean value determined by the three readers. Mean subject age was 65 ± 12 years, 85% were male, and mean BMI was 29 ± 6 kg/m2. Mean injected activity was 10.18 ± 0.43 mCi for first dose and 10.09 ± 0.52 mCi for the second dose. The mean and SD values for first and repeat studies were almost identical: the 95% confidence interval of the mean test–retest difference was 0.055 to 0.076. Bland–Altman plots showed no systematic effect of the H/M ratio on the magnitude of the difference between replicate measurements. Inter-reader measurements were nearly identical. There were no serious adverse events despite exposure to 123I-mIBG on 2 occasions in a short time period. The Heart-to-Mediastinum ratio of 123I-mIBG is a consistent and highly reproducible measurement in stable Class II to III heart failure patients.

Aim. To compare the cardiovascular autonomic reflex tests (CARTs) with cardiac sympathetic innervation imaging with 123I-metaiodobenzylguanidine (MIBG) in patients with type 1 diabetes mellitus (T1DM). Patients and Methods. Forty-nine patients (29 males, mean age 36 ± 10 years, mean T1DM duration 19 ± 6 years) without cardiovascular risk factors were prospectively enrolled. Participants were evaluated for autonomic dysfunction by assessing the mean circular resultant (MCR), Valsalva maneuver (Vals), postural index (PI), and orthostatic hypotension (OH). Within one month from the performance of these tests, patients underwent cardiac MIBG imaging and the ratio of the heart to upper mediastinum count density (H/M) at 4 hours postinjection was calculated (abnormal values, H/M Results. Twenty-nine patients (59%) had abnormal CARTs, and 37 (76%) patients had an H/M_4 p=0.456). MCR, PI, Vals, and OH were abnormal in 29 (59%), 8 (16%), 5 (10%), and 11 (22%) patients, respectively. When using H/M_4 Conclusions. CARTs are not closely associated with 123I-MIBG measurements, which can detect autonomic dysfunction more efficiently than the former. In comparison to semiquantitative cardiac MIBG assessment, the recommended threshold of ≥2 abnormal CARTs to define cardiovascular autonomic dysfunction is highly sensitive but of limited specificity and is independently determined by the duration of T1DM.

According to recent studies, lung uptake of iodine-123-metaiodobenzylguanidine (123I-MIBG) is impaired in many lung diseases and low lung uptake of 123I-MIBG suggests endothelial dysfunction of the pulmonary artery. 123I-MIBG scintigraphy in patients with pulmonary hypertension (PH) has not yet been clinically evaluated. We hypothesized that the lung uptake of 123I-MIBG is reduced in patients with PH and differs among PH subtypes. The purpose of the present study was to analyze the lung uptake of 123I-MIBG in patients with PH and compare it with the data obtained by echocardiography or right heart catheterization. 123I-MIBG scintigraphy was performed in 286 consecutive patients from 2003 to 2014. We enrolled 21 patients with PH and 8 control patients. The 21 patients with PH were categorized into those with pulmonary artery hypertension (PAH, n = 12) and those with chronic thromboembolic pulmonary hypertension (CTEPH, n = 9). The mean pulmonary artery pressure was not significantly different between patients with CTEPH and PAH (37.7 ± 6.8 versus 32.3 ± 5.3 mmHg respectively; P = 0.054). There were no significant differences in any other hemodynamic parameters between the two groups. The lung uptake of 123I-MIBG in PAH patients (early image: 1.54 ± 0.18, delayed image: 1.41 ± 0.16) was significantly lower than that of CTEPH patients (early image: 2.17 ± 0.25, P < 0.0001; delayed image: 1.99 ± 0.20, P = 0.0001, adjusted for age and World Health Organization classification) and controls (early image: 2.32 ± 0.27, P = 0.0007; delayed image: 1.92 ± 0.19, P = 0.0007). In conclusion, we found for the first time that the lung uptake of 123I-MIBG in patients with PAH is lower than that in patients with CTEPH and controls.