123I-MIBG Uptake Research Articles

Development of an 123I-metaiodobenzylguanidine Myocardial Three-Dimensional Quantification Method for the Diagnosis of Lewy Body Disease.

Objective(s):We recently developed a new uptake index method for 123I-metaiodobenzylguanidine (123I-MIBG) heart uptake measurements by using planar images (radioisotope angiography and planar image) for the diagnosis of Lewy body disease (LBD), including Parkinson’s disease (PD) and dementia with Lewy bodies (DLB). However, the diagnostic accuracy of the uptake index was approximately equal to that of the heart-to-mediastinum ratio (H/M) for the discrimination of the LBD and non-LBD patients. A simple and pain-free uptake index method using 123I-MIBG SPECT images by modifying the uptake index method may show better diagnostic accuracy than the planar uptake index method. We hypothesized that the development of a new uptake index method for the determination of 123I-MIBG using single-photon emission computed tomography (SPECT) imaging would provide a reliable and reproducible diagnostic tool for clinical application. Regarding this, the purpose of this study was to develop a new uptake index method with a simple protocol to determine 123I-MIBG uptake on SPECT.Methods:The 123I-MIBG input function was determined from the input counts of the pulmonary artery, assessed by analyzing the pulmonary artery time-activity curves. The 123I-MIBG output function was obtained from 123I-MIBG SPECT counts on the polar map. The uptake index was calculated through dividing the output function by the input function (SPECT uptake method). For the purpose of the study, 77 patients underwent 123I-MIBG SPECT, with an average of 31.5 min after clinical assessment and injection of the tracer. The H/M values, as well as planar and SPECT uptake indices were calculated, and then correlated with clinical features. Results:According to the results, values obtained for LBD were significantly lower than those for non-LBD in all analyses (P<0.01). The overlap of the H/M values between the LBD and non-LBD cases ranged from 2.06 to 2.50. Furthermore, the overlap in uptake index values between LBD and non-LBD cases in planar image analysis was 1.05-1.29. The SPECT uptake index method showed the least overlap of 1.23-1.25, with the highest value for LBD patients clearly distinguished from the lowest value for the non-LBD patients.Conclusion:The new 123I-MIBG SPECT quantification method, developed by the input counts of the pulmonary artery, clearly distinguished LBD from non-LBD. Therefore, this method may be appropriate for routine clinical study.

Variability in Heart-to-Mediastinum Ratio from Planar 123I-MIBG Images of a Thorax Phantom for 6 Common γ-Camera Models.

A heart-to-mediastinum (H/M) ratio of 1.6 or greater on planar 123I-iobenguane (123I-MIBG) images identifies heart failure patients at low risk of experiencing an adverse cardiac event. This phase-4 study used standardized phantoms to assess the intercamera, intracamera, and interhead variability in H/M ratio determinations from planar cardiac 123I-MIBG imaging using commercially available, dual-head γ-cameras. Methods: A fillable thorax phantom was developed to simulate the typical uptake of 123I-MIBG. The phantom had a nominal H/M ratio of 1.6 on the reference camera. Commercial cameras used in the study were dual-head and capable of 90° configuration for cardiac imaging. The target sample size was 8 units (examples) per camera model. Two imaging technologists independently analyzed planar images of simulated 123I-MIBG uptake from the thorax phantom. H/M was the ratio of the average counts per pixel of the heart and mediastinum regions of interest. The primary endpoint, intercamera variability in H/M ratio from head 1, was determined for each camera model via comparison with the H/M ratio on the reference camera. Only cameras with at least 8 units tested (n ≥ 8) were included in the primary analysis. Intracamera and interhead variability in the H/M ratio were also evaluated. Results: Nine camera models were studied. The mean H/M ratio ranged from 1.342 to 1.677. The primary analysis (6 camera models) using a mixed-model, repeated-measures analysis showed no significant difference in H/M ratio between any camera model and the reference camera. Intracamera variability (head 1) in the H/M ratio among camera models with 8 units or more was high, with SDs ranging from 0.0455 to 0.1193. Interhead variability was low (SDs of the interhead difference, 0.017-0.074). Conclusion: Commonly used γ-cameras produced H/M ratios from simulated 123I-MIBG phantom images that were not significantly different from those on the reference camera. This finding indicates that the results of previous clinical trials of 123I-MIBG, involving many different clinical sites and camera models, are valid. The assessment of the performance of a given camera unit using an 123I planar phantom before H/M results from 123I-MIBG imaging are used for classifying risk in heart failure patients is encouraged.

Normal 123 I-MIBG uptake areas may be associated with hyperinnervation and arrhythmia risk in phenol model rabbit hearts.

Iodine-123 metaiodobenzylguanidine (123 I-MIBG) is useful for detecting sympathetic innervation in the heart, and has been closely associated with fatal arrhythmias. However, such imaging is typically calibrated to the area of highest uptake and thus is unable to identify areas of hyperinnervation. We hypothesized that normal 123 I-MIBG uptake regions in the denervated heart would demonstrate nerve sprouting and correlate with the potential for arrhythmogenesis. Twenty New Zealand white rabbits treated with phenol or sham were prepared under anesthesia. Sympathetic innervation was quantified using autoradiography and immunostaining 4weeks after phenol application, and electrophysiological study was performed. 123 I-MIBG revealed maximal local differences in isotope uptake in the border zone between areas with attenuated and abundant MIBG compared with that seen between adjacent regions within the lowest uptake areas. On immunostaining, heterogeneous and decreased expressions of growth-associated protein 43 signal were observed in the MIBG-attenuated areas; however, abundant signals were recognized in the MIBG-abundant areas. Upregulation of the tyrosine hydroxylase signal was observed at the part of the MIBG-abundant area. In electrophysiological study, the dispersion of activation recovery interval (ARI) was increased in the phenol-applied areas by norepinephrine infusion. Stellate stimulation exacerbated the ARI dispersion in both the phenol-applied and nonapplied areas, and was associated with increased inducibility of ventricular tachycardia and ventricular fibrillation. The presence of hyperinnervation in the nondenervated regions of denervated rabbit hearts suggests that heterogeneous neural remodeling occurs in regions with seemingly normal 123 I-MIBG uptake and contributes to electrical instability.

Determination of the Heart-to-Mediastinum Ratio of 123I-MIBG Uptake Using Dual-Isotope (123I-MIBG/99mTc-Tetrofosmin) Multipinhole Cadmium-Zinc-Telluride SPECT in Patients with Heart Failure.

The aim of this retrospective study was to compare the heart-to-mediastinum ratio (HMR) of 123I-metaiodobenzylguanidine (123I-MIBG) uptake obtained using a multipinhole cadmium-zinc-telluride (CZT) camera with that obtained using conventional planar imaging. Methods: Forty consecutive heart failure patients underwent planar acquisition 4 h after 123I-MIBG injection (191 ± 41 [mean ± SD] MBq). To localize the heart using the CZT camera, 99mTc-tetrofosmin (358 ± 177 MBq) was administered and dual-isotope acquisition was performed. The HMRs were calculated with conventional planar imaging (HMRplanar), with anterior reprojection images using the CZT camera (HMRreproj), and with transaxial reconstructed images using the CZT camera (HMRtransaxial). In a phantom study, we estimated a linear model fitting the CZT camera data to the planar data, and we applied it to provide corrected CZT camera-determined HMRs in patients (cHMRreproj and cHMRtransaxial). Results: Thirty-four men and 6 women (71 ± 9 y old) with ischemic (22 patients) and nonischemic (18 patients) heart failure completed the study. For 22 of the 40 patients (55%), the New York Heart Association classification was class II and the ejection fraction was 35% ± 9%. HMRreproj (1.12 ± 0.19) and HMRtransaxial (1.35 ± 0.34) were lower than HMRplanar (1.44 ± 0.14) (P < 0.0001 and P < 0.01, respectively). cHMRreproj (1.54 ± 0.09) and cHMRtransaxial (1.45 ± 0.14) were significantly different (P < 0.0001). Lin concordance correlation and Bland-Altman analysis demonstrated an almost perfect concordance and a high agreement between HMRplanar and cHMRtransaxial (P was not significant) but not between HMRplanar and cHMRreproj (P < 0.0001). Conclusion: This study demonstrated that determination of the late HMR of cardiac 123I-MIBG uptake using dual-isotope (123I and 99mTc) acquisition on a multipinhole CZT camera was feasible in patients with heart failure. However, this determination should be performed using transaxial reconstructed images and linear correction based on phantom data acquisitions.

123I-ioflupane brain SPECT and 123I-MIBG cardiac planar scintigraphy combined use in uncertain parkinsonian disorders.

We evaluated the clinical usefulness of the combined use of 123I-ioflupane brain single photon emission computed tomography (SPECT) and 123I-metaiodobenzylguanidine (MIBG) cardiac scintigraphy in discriminating uncertain parkinsonism with vascular lesions in striatal nuclei at magnetic resonance imaging (MRI). Forty-three consecutive patients with uncertain parkinsonism and vascular lesions at MRI in striatal nuclei were retrospectively evaluated; the uncertain differential diagnosis was between Parkinson's disease and vascular parkinsonism (PD/VP) in 22 patients, between PD and other neurodegenerative parkinsonism (PD/PS) in 11 patients and between Lewy body dementia and Alzheimer disease (LBD/AD) in the remaining 10 cases. All patients underwent 123I-ioflupane SPECT with striatal dopaminergic activity determination as binding potentials (BP; cut-off: 3.3). 123I-MIBG cardiac planar scintigraphy was performed 2 weeks later, in early (15 minutes) and delayed (240 minutes) phases also calculating heart to mediastinum (H/M) ratio (cut-off: 1.56). 123I-Ioflupane uptake was normal in 9 patients with BP values >3.3, while it was reduced in 34/43 cases with BP values <3.3 at least in one of the striatal nuclei. 123I-MIBG uptake was normal in 21/43 patients (5 of whom with normal and 16 with 123I-ioflupane striatal defects) showing the H/M ratio >1.56 in all cases; the uptake was reduced in 22/43 cases, (4 of whom were normal and 18 were with 123I-ioflupane striatal defects) with the H/M ratio <1.56 in all cases. No statistical differences were found when early and delayed H/M ratios were mutually compared. Combining the 2 radioisotopic procedures, a more reliable diagnosis was achieved in 39/43 cases properly classifying 13 PD, 10 VP, 7 PS, 5 LBD, and 4 AD. However, the diagnosis remained uncertain in four patients with normal 123I-ioflupane and reduced 123I-MIBG uptake. The results of the present study confirmed that in uncertain parkinsonian syndromes associated with vascular lesions in striatal nuclei, brain 123I-ioflupane SPECT alone did not prove able to discriminate between the different forms of disease. Only the association with 123I-MIBG cardiac scintigraphy, also with the early acquisition alone, allowed the most appropriate diagnosis in 90.7% of our cases. However, patients with normal 123I-ioflupane and reduced 123I-I-MIBG uptakes need a close clinical and instrumental follow-up as sympathetic damage could precede striatal disorders in the early stage of PD and LBD.

Beta blocker dose and markers of sympathetic activation in heart failure patients: interrelationships and prognostic significance.

AimsExtent of cardiac sympathetic activation can be estimated from physiological parameters, blood biomarkers, and imaging findings. This study examined the prognostic value of three markers of sympathetic activity and their relationship to beta blocker dose in heart failure patients.Methods and resultsA post hoc analysis of 858 heart failure subjects in the ADMIRE‐HF trial was performed. Variables related to sympathetic activity were plasma norepinephrine, baseline heart rate, the heart to mediastinum (H/M) ratio of 123I‐mIBG uptake, and beta blocker dose. Univariate and multivariate analyses for occurrence of mortality (all‐cause and cardiac) and arrhythmic events were performed. Beta blocker dose was significantly related to age, heart rate, b‐type natriuretic peptide (negatively), body mass index, body weight and plasma norepinephrine. Univariate predictors of all‐cause and cardiac mortality were baseline heart rate (χ 2 = 4.5, P = 0.029 and χ 2 = 5 .2, P = 0.022, respectively), plasma norepinephrine level (χ 2 = 8.9, P = 0.0006 and χ 2 = 8.6, P = 0.003, respectively), and H/M (χ = 22.4, P < 0.0001 and χ 2 = 17.8, P < 0.0001, respectively). In multivariate analyses, carvedilol‐equivalent dose (P = 0.017), plasma norepinephrine (P = 0.002), and H/M (P = 0.0001) were significant predictors of all‐cause mortality. In separate analyses using multiple measurements of heart rate, mean heart rate >67 b.p.m. was associated with significantly higher cardiac mortality.ConclusionsHigher beta blocker dose was associated with lower mortality, but of the variables associated with sympathetic activity examined, cardiac 123I‐mIBG uptake was the most powerful prognostic marker in heart failure patients. Elevated heart rate was associated with greater risk for cardiac death.

Persistent positive metaiodobenzylguanidine scans after autologous peripheral blood stem cell transplantation may indicate maturation of stage 4 neuroblastoma

ABSTRACTMetaiodobenzylguanidine (MIBG) scans are sensitive testing tools for neuroblastoma. Persistent positive MIBG scans in patients with stage 3 neuroblastoma have previously been found to indicate maturation rather than regression. We assessed the significance of this finding in stage 4 neuroblastoma in the present study. Fifteen consecutive pediatric patients with stage 4 neuroblastoma treated between 2004 and 2014 at the Kagoshima University Hospital were retrospectively examined. Treatment involved a combination of multiagent chemotherapy, resection, autologous peripheral blood stem cell transplantation (PBSCT), radiotherapy, and maintenance therapy with retinoic acid. The MIBG uptake in each patient during treatment was assessed using a Curie score. The 5-year event-free and overall survival rates in 15 patients were 38.9% and 58.7%, respectively. Four patients with persistent positive MIBG scans who underwent autologous PBSCT but experienced decreased 123I-MIBG uptake during the clinical course survived without progression, and their event-free survival (EFS) was significantly superior to that of patients who showed negative MIBG scans after PBSCT (5-year EFS rate: 18.2%, p = 0.0176). Therefore, persistent positive MIBG scans with gradually decreased uptake after PBSCT do not always indicate neuroblastoma progression, and may instead indicate tumor maturation in some selected cases, if not all cases, of stage 4 neuroblastoma.

Uptake Index of 123I-metaiodobenzylguanidine Myocardial Scintigraphy for Diagnosing Lewy Body Disease.

Objective(s):Iodine-123 metaiodobenzylguanidine (123I-MIBG) myocardial scintigraphy has been used to evaluate cardiac sympathetic denervation in Lewy body disease (LBD), including Parkinson’s disease (PD) and dementia with Lewy bodies (DLB). The heart-to-mediastinum ratio (H/M) in PD and DLB is significantly lower than that in Parkinson’s plus syndromes and Alzheimer’s disease. Although this ratio is useful for distinguishing LBD from non-LBD, it fluctuates depending on the system performance of the gamma cameras. Therefore, a new, simple quantification method using 123I-MIBG uptake analysis is required for clinical study. The purpose of this study was to develop a new uptake index with a simple protocol to determine 123I-MIBG uptake on planar images.Methods:The 123I-MIBG input function was obtained from the input counts of the pulmonary artery (PA), which were assessed by analyzing the PA time-activity curves. The heart region of interest used for determining the H/M was used for calculating the uptake index, which was obtained by dividing the heart count by the input count.Results:Forty-eight patients underwent 123I-MIBG chest angiography and planar imaging, after clinical feature assessment and tracer injection. The H/M and 123I-MIBG uptake index were calculated and correlated with clinical features. Values for LBD were significantly lower than those for non-LBD in all analyses (P<0.001). The overlapping ranges between non-LBD and LBD were 2.15 to 2.49 in the H/M method, and 1.04 to 1.22% in the uptake index method. The diagnostic accuracy of the uptake index (area under the curve (AUC), 0.98; sensitivity, 96%; specificity, 91%; positive predictive value (PPV), 90%; negative predictive value (NPV), 93%; and accuracy, 92%) was approximately equal to that of the H/M (AUC, 0.95; sensitivity, 93%; specificity, 91%; PPV, 90%; NPV, 93%; and accuracy, 92%) for discriminating patients with LBD and non-LBD.Conclusion:A simple uptake index method was developed using 123I-MIBG planar imaging and the input counts determined by analyzing chest radioisotope angiography images of the PA. The diagnostic accuracy of the uptake index was approximately equal to that of the H/M for discriminating patients with LBD and non-LBD.

Correlation of Somatostatin Receptor-2 Expression with Gallium-68-DOTA-TATE Uptake in Neuroblastoma Xenograft Models.

Peptide-receptor imaging and therapy with radiolabeled somatostatin analogs such as 68Ga-DOTA-TATE and 177Lu-DOTA-TATE have become an effective treatment option for SSTR-positive neuroendocrine tumors. The purpose of this study was to evaluate the correlation of somatostatin receptor-2 (SSTR2) expression with 68Ga-DOTA-TATE uptake and 177Lu-DOTA-TATE therapy in neuroblastoma (NB) xenograft models. We demonstrated variable SSTR2 expression profiles in eight NB cell lines. From micro-PET imaging and autoradiography, a higher uptake of 68Ga-DOTA-TATE was observed in SSTR2 high-expressing NB xenografts (CHLA-15) compared to SSTR2 low-expressing NB xenografts (SK-N-BE(2)). Combined autoradiography-immunohistochemistry revealed histological colocalization of SSTR2 and 68Ga-DOTA-TATE uptake in CHLA-15 tumors. With a low dose of 177Lu-DOTA-TATE (20 MBq/animal), tumor growth inhibition was achieved in the CHLA-15 high SSTR2 expressing xenograft model. Although, in vitro, NB cells showed variable expression levels of norepinephrine transporter (NET), a molecular target for 131I-MIBG therapy, low 123I-MIBG uptake was observed in all selected NB xenografts. In conclusion, SSTR2 expression levels are associated with 68Ga-DOTA-TATE uptake and antitumor efficacy of 177Lu-DOTA-TATE. 68Ga-DOTA-TATE PET is superior to 123I-MIBG SPECT imaging in detecting NB tumors in our model. Radiolabeled DOTA-TATE can be used as an agent for NB tumor imaging to potentially discriminate tumors eligible for 177Lu-DOTA-TATE therapy.

Cardiac parasympathetic dysfunction in the early phase of Parkinson's disease.

Cardiac parasympathetic function is strongly affected by aging. Although sympathetic dysfunction has been well documented in Parkinson's disease (PD), cardiac parasympathetic dysfunction has not been well studied. The objective of this study was to clarify the development of cardiac parasympathetic dysfunction in the early phase of PD and to explore the age-corrected correlation between cardiac parasympathetic dysfunction and cardiac sympathetic dysfunction. We reviewed 25 healthy controls and 56 patients with idiopathic PD of Hoehn and Yahr stages I-III. We evaluated cardiac parasympathetic function using the Valsalva ratio, the baroreflex sensitivity (BRS) and the coefficient of variation of RR intervals in the resting state (resting-CVRR) and during deep breathing (DB-CVRR). In addition, we measured cardiac 123I-metaiodobenzylguanidine (MIBG) uptake to investigate the relationship between cardiac sympathetic and parasympathetic dysfunction in PD. Compared with healthy controls, patients with PD showed significantly decreased cardiac parasympathetic parameters (resting-CVRR 2.8±1.3 vs. 1.7±0.6%, p<0.001; DB-CVRR 5.8±2.3 vs. 3.8±1.7%, p<0.001; Valsalva ratio 1.52±0.26 vs. 1.34±0.17, p<0.01; BRS 10.6±9.5 vs. 5.0±5.4ms/mmHg, p<0.01). In particular, resting-CVRR and DB-CVRR were significantly decreased in the early phase of PD. In age-corrected analyses, none of the parasympathetic indices correlated with the delayed cardiac 123I-MIBG uptake. These observations indicate that cardiac parasympathetic dysfunction occurs in the early phase of PD, but not necessarily in parallel with cardiac sympathetic dysfunction.

Persistence of 123I-mIBG Prognostic Capability in Relation to Medical Therapy in Heart Failure (from the ADMIRE-HF Trial)

123I-mIBG imaging has been evaluated to assess sympathetic function and prognosis in heart failure (HF). However, the effect of combined HF medical therapies on 123I-mIBG uptake and its prognostic significance has not been previously examined. This analysis examined the relation between the intensity of guideline-directed HF medical therapy and global 123I-mIBG cardiac uptake in the AdreView Myocardial Imaging for Risk Evaluation in Heart Failure (ADMIRE-HF) database. A second objective was to investigate whether this guideline-based therapy, measured by total medication doses, had the expected effect on outcome, that is, that patients with higher 123I-mIBG cardiac uptake and more intensive medical therapy had the fewest outcome events. Three HF cardiologists developed an HF Medication Score (HFMS) to quantify adequacy of dosages of β blockers, angiotensin-converting enzyme inhibitors, and angiotensin II receptor blockers and mineralocorticoid receptor antagonists. A Cox model was used to investigate the predictive ability of the HFMS for mortality events during median 17months follow-up. Multiple regression and Cox models assessed the usefulness of the HFMS relative to the planar heart/mediastinum ratio (H/Mp) from 123I-mIBG imaging in prediction of an event and to characterize the interaction of HFMS and H/M in predicting an event. HFMS was not a significant predictor of all-cause or cardiac death in either univariate or multivariate Cox models; H/Mp was highly significant for both event categories (p <0.0001). Mean H/Mp did not differ among HFMS ranges 0 to 3, 4 to 6, and 7 to 9. However, within each category, the mean H/Mp for subjects with events was significantly lower than that of subjects without events, with the exception of cardiac mortality in those with highest scores. In conclusion, intensity of medical therapy is not predictive of short-term mortality in HF patients. H/Mp is a good predictor for both cardiac and overall mortality regardless of medical therapy levels.

123I-mIBG scintigraphy in neuroblastoma: development of a SIOPEN semi-quantitative reporting ,method by an international panel

PurposeA robust method is required to standardise objective reporting of diagnostic 123I-mIBG images in neuroblastoma. Prerequisites for an appropriate system are low inter- and intra-observer error and reproducibility across a broad disease spectrum. We present a new reporting method, developed and tested for SIOPEN by an international expert panel.MethodPatterns of abnormal skeletal 123I-mIBG uptake were defined and assigned numerical scores [0–6] based on disease extent within 12 body segments. Uptake intensity was excluded from the analysis. Data sets from 82 patients were scored independently by six experienced specialists as unblinded pairs (pre- and post-induction chemotherapy) and in random order as a blinded study. Response was defined as ≥50 % reduction in post induction score compared with baseline.ResultsIn total, 1968 image sets were reviewed individually. Response rates of 88 % and 82 % were recorded for patients with baseline skeletal scores ≤23 and 24-48 respectively, compared with 44 % response in patients with skeletal scores >48 (p = 0.02). Reducing the number of segments or extension scale had a small but statistically negative impact upon the number of responses detected. Intraclass correlation coefficients [ICCs] calculated for the unblinded and blinded study were 0.95 at diagnosis and 0.98 and 0.99 post-induction chemotherapy, respectively.ConclusionsThe SIOPEN mIBG score method is reproducible across the full spectrum of disease in high risk neuroblastoma. Numerical assessment of skeletal disease extent avoids subjective evaluation of uptake intensity. This robust approach provides a reliable means with which to examine the role of 123I mIBG scintigraphy as a prognostic indicator in neuroblastoma.

Impact of aging on cardiac sympathetic innervation measured by 123I-mIBG imaging in patients with systolic heart failure.

Sympathetic nervous system (SNS) hyperactivity is a salient characteristic of chronic heart failure (HF) and contributes to the progression of the disease. Iodine-123 meta-iodobenzylguanidine (123I-mIBG) imaging has been successfully used to assess cardiac SNS activity in HF patients and to predict prognosis. Importantly, SNS hyperactivity characterizes also physiological ageing, and there is conflicting evidence on cardiac 123I-mIBG uptake in healthy elderly subjects compared to adults. However, little data are available on the impact of ageing on cardiac sympathetic nerve activity assessed by 123I-mIBG scintigraphy, in patients with HF. We studied 180 HF patients (age = 66.1 ± 10.5years [yrs]), left ventricular ejection fraction (LVEF = 30.6 ± 6.3%) undergoing cardiac 123I-mIBG imaging. Early and late heart to mediastinum (H/M) ratios and washout rate were calculated in all patients. Demographic, clinical, and echocardiographic data were also collected. Our study population consisted of 53 patients aged >75years (age = 77.7 ± 4.0year), 67 patients aged 62-72years (age = 67.9 ± 3.2years) and 60 patients aged ≤61year (age = 53.9 ± 5.6years). In elderly patients, both early and late H/M ratios were significantly lower compared to younger patients (p < 0.05). By multivariate analysis, H/M ratios (both early and late) and washout rate were significantly correlated with LVEF and age. Our data indicate that, in a population of HF patients, there is an independent age-related effect on cardiac SNS innervation assessed by 123I-mIBG imaging. This finding suggests that cardiac 123I-mIBG uptake in patients with HF might be affected by patient age.

PR Prolongation Is Correlated with Reduced Cardiac 123I-MIBG Uptake in Parkinson’s Disease (P6.374)

PR Prolongation Is Correlated with Reduced Cardiac 123I-MIBG Uptake in Parkinson’s Disease (P6.374)

NOVEL DIAGNOSTIC TOOL OF PAH: LUNG 123I-MIBG SCINTIGRAPHY

Recent studies reported that lung 123I-MIBG uptake was impaired in many lung diseases and low uptake of lung 123I-MIBG is suggested to indicate the pulmonary endothelial dysfunction of pulmonary artery (PA). However, the clinical validation of 123I-MIBG scintigraphy for patients with pulmonary

NORMAL LIMITS OF HEART-TO-MEDIASTINUM RATIO (HMR) OF I-123 MIBG UPTAKE QUANTIFIED FROM HIGH-SENSITIVITY (HS) AND HIGH-RESOLUTION (HR) SPECT/CT

Assessment of I-123 MIBG uptake usually relies on HMR based on 2-D planar imaging. While the more quantitative 3-D SPECT approach to MIBG may provide more precise risk stratification, lower limit of normal (LLN) of HMR derived from HS and HR SPECT is unknown. We have developed a new SPECT

(123)I-Meta-iodobenzylguanidine Sympathetic Imaging: Standardization and Application to Neurological Diseases.

123I-meta-iodobenzylguanidine (MIBG) has become widely applied in Japan since its introduction to clinical cardiology and neurology practice in the 1990s. Neurological studies found decreased cardiac uptake of 123I-MIBG in Lewy-body diseases including Parkinson's disease and dementia with Lewy bodies. Thus, cardiac MIBG uptake is now considered a biomarker of Lewy body diseases. Although scintigraphic images of 123I-MIBG can be visually interpreted, an average count ratio of heart-to-mediastinum (H/M) has commonly served as a semi-quantitative marker of sympathetic activity. Since H/M ratios significantly vary according to acquisition and processing conditions, quality control should be appropriate, and quantitation should be standardized. The threshold H/M ratio for differentiating Lewy-body disease is 2.0-2.1, and was based on standardized H/M ratios to comparable values of medium-energy collimators. Parkinson's disease can be separated from various types of parkinsonian syndromes using cardiac 123I-MIBG, whereas activity is decreased on images of Lewy-body diseases using both 123I-ioflupane for the striatum and 123I-MIBG. Despite being a simple index, the H/M ratio of 123I-MIBG uptake is reproducible and can serve as an effective tool to support a diagnosis of Lewy-body diseases in neurological practice.

Differences in Sympathetic Nervous Stimulation of Brown Adipose Tissue Between the Young and Old, and the Lean and Obese.

Brown adipose tissue (BAT) could facilitate weight loss by increasing energy expenditure. Cold is a potent stimulator of BAT, activating BAT primarily through the sympathetic nervous system (SNS). Older or overweight individuals have less metabolic BAT activity than the lean and young, but the role of the SNS in this decline is unknown. We aimed to determine whether this lower metabolic BAT activity in older or overweight individuals can be explained by a lower SNS response to cold. This was a prospective observational study. We included 10 young obese, 11 old lean, and 14 young lean healthy men. All subjects underwent (18)F-FDG PET/CT and (123)I-meta-iodobenzylguanidine ((123)I-mIBG) SPECT/CT after an overnight fast and 2 h of cold exposure. Metabolic BAT activity was expressed as volume and as SUVmax of (18)F-FDG. BAT SNS activity was expressed as volume and as the ratio between (123)I-mIBG uptake in BAT and a reference region (SQUVmax of (123)I-mIBG). SUVmax, BAT volume, and SQUVmax were significantly different between young and old (SUVmax, 7.9 [range, 4.2-17.3] vs. 2.9 [range, 0.0-4.0]; volume, 124.8 [range, 10.9-338.8] vs. 3.4 [range, 0.0-10.9]; and SQUVmax, 2.7 [range, 1.9-4.7] vs. 0.0 [range, 0.0-2.2], respectively) (all P < 0.01) but not between lean and obese (SUVmax, 7.9 [range, 4.2-17.3] vs. 4.0 [range, 0.0-13.5] [P = 0.69]; volume, 124.8 [range, 10.9-338.8] vs. 11.8 [range, 0.0-190.2] [P = 0.64]; and SQUVmax, 2.7 [range, 1.9-4.7] vs. 1.7 [range, 0-3.5] [P = 0.69], respectively). We found a strong positive correlation between BAT activity measured with (18)F-FDG and (123)I-mIBG in the whole group of BAT-positive subjects (ρ = 0.82, P < 0.01). Both sympathetic drive and BAT activity are lower in older but not in obese men.

Prognostic significance of (123)I-mIBG SPECT myocardial imaging in heart failure: differences between patients with ischaemic and non-ischaemic heart failure.

The purpose of this study was to examine the prognostic significance of uptake patterns on quantitative myocardial (123)I-mIBG and (99m)Tc-tetrofosmin SPECT imaging in heart failure (HF) subjects and to assess the differences between patients with ischaemic and non-ischaemic HF. Results of quantitative analyses of (123)I-mIBG myocardial SPECT, alone and in combination with (99m)Tc tetrofosmin SPECT, were studied in 619 ischaemic (I) and 319 non-ischaemic (NI) HF subjects from the ADMIRE-HF trial. Cardiac and all-cause mortality data for 2-year follow-up were collected in the extension study (ADMIRE-HFX) and were examined in relation to extent and severity of voxel-based defects, the number of myocardial segments with significant dysinnervation (derived score ≥2), and (123)I-mIBG/(99m)Tc tetrofosmin mismatch quantitation. Cox proportional hazards and survival analyses were used to identify higher and lower risk groups and to define thresholds for optimal discrimination between the two. Two-year all-cause and cardiac mortality were not significantly different between IHF and NIHF subjects. Mortality was higher in patients with dysinnervation involving >50% of the myocardium. Highest cardiac mortality risk for IHF subjects was seen with perfusion defects involving 20-40% of the myocardium. By comparison, NIHF subjects with smaller perfusion abnormalities (<20% of myocardium), but with a large discrepancy between (123)I-mIBG and (99m)Tc tetrofosmin defect sizes, were at highest risk of cardiac death. Prognostic significance of patterns of (123)I-mIBG and MPI uptake differ between IHF and NIHF subjects. SPECT imaging may provide new insights into underlying disease processes in HF, including the degree of dysinnervation in areas with preserved myocardial perfusion in non-ischaemic HF patients.

PR Prolongation and Cardiac 123I-MIBG Uptake Reduction in Parkinson's Disease

Background: Cardiac ¹²³I-metaiodobenzylguanidine scintigraphy (MIBG) previously demonstrated an uptake reduction in patients with Parkinson's disease (PD). However, epidemiologic research showed that electrocardiography (ECG) abnormalities occurred prior to motor signs in PD. Here we investigated whether the electrical conduction system of the heart was impaired in PD. Methods: Clinical features, ECG and MIBG parameters were analyzed in 191 patients with PD, 42 with multiple system atrophy (MSA) and 124 normal controls (NL). Results: The PR interval was significantly longer in patients with PD than in NL. The PR interval was significantly negatively correlated with early and delayed heart-to-mediastinum ratios in MIBG scintigraphy in PD and MSA patients. In 19 PD patients with PR prolongation, 17 patients also had abnormal MIBG findings, and the other 2 showed normal MIBG. Conclusions: The PR prolongation must show some sympathetic system abnormality because it is mainly controlled by the sympathetic nervous system. PR prolongation supports the objective biomarker value of MIBG for PD diagnosis.