[Show abstract][Hide abstract] ABSTRACT: Background:
Mismatch between myocardial innervation and perfusion assessed with positron emission tomography (PET) is a potential risk marker for ventricular arrhythmias in patients with ischemic cardiomyopathy. This mismatch zone originates from residual viable myocardium that has sustained ischemic nerve injury. Heterogenic scar size assessed with late gadolinium-enhanced (LGE) cardiac magnetic resonance imaging (CMR) is also a risk marker of ventricular arrhythmias. These two imaging parameters may represent identical morphological tissue features. The current study explored the relation between innervation-perfusion mismatch and heterogenic scar size.
Twenty-eight patients (26 males, age 67 ± 8 years) with ischemic cardiomyopathy and a left ventricular ejection fraction below 35%, eligible for ICD implantation were included. All patients underwent both [(11)C]-hydroxyephedrine and [(15)O]-water PET studies to assess myocardial sympathetic innervation and perfusion. LGE CMR was conducted to assess total myocardial scar size, scar core size, and heterogenic scar size.
Perfusion defect size was 16.6 ± 9.9% and innervation defect size was 33.7 ± 10.8%, which resulted in an innervation-perfusion mismatch of 17.6 ± 8.9%. Total scar size, scar core size, and heterogenic scar size were 21.2 ± 8.6%, 14.7 ± 6.6%, and 6.5 ± 2.9%, respectively. No relation between scar core size and perfusion deficit size was observed (r = 0.18, P = .36). Total scar size was correlated with the innervation defect size (r = 0.52, P = .004) and the heterogenic scar zone displayed a significant correlation with the innervation-perfusion mismatch area (r = 0.67, P < .001).
Denerved residual viable myocardium in ischemic cardiomyopathy as observed with innervation-perfusion PET is related to the heterogenic scar zone as assessed with LGE CMR.
Journal of Nuclear Cardiology 11/2015; DOI:10.1007/s12350-015-0316-z · 2.94 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The physiology of brown adipose tissue (BAT) is poorly understood. In humans, the capacity to generate heat resides principally in two organs: skeletal muscle and brown adipose tissue.
[Show abstract][Hide abstract] ABSTRACT: Purpose:
The aim of this study was to investigate whether performing the late cardiac (123)I-metaiodobenzylguanidine (MIBG) scan earlier than 4 h post-injection (p.i.) has relevant impact on the late heart to mediastinum ratio (H/M ratio) in patients with heart failure (HF).
Forty-nine patients with HF (median left ventricular ejection fraction of 31 %, 51 % ischaemic HF) referred for cardiac (123)I-MIBG scintigraphy were scanned at 15 min (early) p.i. and at 1, 2, 3 and 4 h (late) p.i. of (123)I-MIBG. Late H/M ratios were calculated and evaluated using a linear mixed model with the mean late H/M ratio at 4 h p.i. as a reference. A difference in late H/M ratios of more than 0.10 between the different acquisition times in comparison with the late H/M ratio at 4 h p.i. was considered as clinically relevant.
Statistically significant mean differences were observed between the late H/M ratios at 1, 2 and 3 h p.i. compared with the late H/M ratio at 4 h p.i. (0.09, 0.05 and 0.02, respectively). However, the mean differences did not exceed the cut-off value of 0.10. On an individual patient level, compared to the late H/M ratio at 4 h p.i., the late H/M ratios at 1, 2 and 3 h p.i. differed more than 0.10 in 24 (50 %), 9 (19 %) and 2 (4 %) patients, respectively.
Variation in acquisition time of (123)I-MIBG between 2 and 4 h p.i. does not lead to a clinically significant change in the late H/M ratio. An earlier acquisition time seems to be justified and may warrant a more time-efficient cardiac (123)I-MIBG imaging protocol.
European Journal of Nuclear Medicine 10/2015; DOI:10.1007/s00259-015-3220-5 · 5.38 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Brown adipose tissue (BAT) is able to convert calories into heat rather than storing them. Therefore, activated BAT could be a potential target in the battle against obesity and type 2 diabetes. This review focuses on the role of the autonomic nervous system in the activation of human BAT. Although the number of studies focusing on BAT in humans is limited, involvement of the sympathetic nervous system (SNS) in BAT activation is evident. Metabolic BAT activity can be visualized with (18)F-fluorodeoxyglucose, whereas sympathetic activation of BAT can be visualized with nuclear-medicine techniques using different radiopharmaceuticals. Also, interruption of the sympathetic nerves leading to BAT activation diminishes sympathetic stimulation, resulting in reduced metabolic BAT activity. Furthermore, both β- and α-adrenoceptors might be important in the stimulation process of BAT, as pretreatment with propranolol or α-adrenoceptor blockade also diminishes BAT activity. In contrast, high catecholamine levels are known to activate and recruit BAT. There are several interventional studies in which BAT was successfully inhibited, whereas only one interventional study aiming to activate BAT resulted in the intended outcome. Most studies have focused on the SNS for activating BAT, although the parasympathetic nervous system might also be a target of interest. To better define the possible role of BAT in strategies to combat the obesity epidemic, it seems likely that future studies focusing on both histology and imaging are essential for identifying the factors and receptors critical for activation of human BAT.
[Show abstract][Hide abstract] ABSTRACT: Purpose:
It remains challenging to identify patients at risk of anthracycline-induced cardiotoxicity. To better understand the different risk-stratifying approaches, we evaluated (123)I-metaiodobenzylguanidine ((123)I-mIBG) scintigraphy and its interrelationship with conventional echocardiography, 2D strain imaging and several biomarkers.
We performed (123)I-mIBG scintigraphy, conventional and strain echocardiography and biomarker (NT-proBNP, TNF-α, galectin-3, IL-6, troponin I, ST-2 and sFlt-1) assessment in 59 breast cancer survivors 1 year after anthracycline treatment. Interobserver and intermethod variability was calculated on planar and SPECT (123)I-mIBG scintigraphy, using the heart/mediastinum (H/M) ratio and washout (WO). Pearson's r and multivariate analyses were performed to identify correlations and independent predictors of (123)I-mIBG scintigraphy results.
Delayed planar anterior whole-heart ROI (WH) H/M ratios and WO were the most robust (123)I-mIBG parameters. Significant correlations were observed between (123)I-mIBG parameters and several conventional echo parameters, global longitudinal and radial strain (GLS and GRS) and galectin-3. The highest Pearson's r was observed between delayed H/M ratio and GRS (Pearson's r 0.36, p = 0.01). Multivariate analysis showed that GRS was the only independent predictor of the delayed WH H/M ratio (p = 0.023).
The delayed planar H/M ratio is the most robust (123)I-mIBG parameter. It correlates with several conventional echocardiographic parameters, GLS, GRS and galectin-3. Of these, only GRS predicts the H/M ratio.
Cancer Chemotherapy and Pharmacology 09/2015; 76(5). DOI:10.1007/s00280-015-2874-9 · 2.77 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:
Renal sympathetic denervation (RSD) is currently being investigated in multiple studies of sympathetically driven cardiovascular diseases such as heart failure and arrhythmias. Our aim was to assess systemic and cardiac sympatholytic effects of RSD by the measurement of cardiac sympathetic activity and cardiovascular parameters.
A total of 21 consecutive patients with refractory hypertension (daytime ambulatory blood pressure (BP) ≥150/100mmHg despite the use of 3 or more antihypertensive drugs), no evidence for secondary hypertension and normal renovascular anatomy were included. RSD was performed with the Medtronic Symplicity renal denervation catheter with an average of 4.2 (range 3-6) ablations per renal artery. To assess cardiac sympathetic activity, (123)I-mIBG cardiac scintigraphy was performed before and 6weeks after. In addition, the effect of RSD on peripheral BP and cardiac hemodynamics were assessed non-invasively.
(123)I-mIBG uptake before and after RSD was 1.7±0.4% vs. 1.7±0.5% at 15min. and 1.4±0.4% vs. 1.5±0.5% after 4h. As a consequence, washout rate was similar before (33.7±11.7%) and after RSD (30.1±12.6%, p=0.27). In line with earlier RSD studies, a significant drop in systolic office BP (-12.2mmHg, p=0.04) was detected, whereas the decrease in ambulatory BP was not significant. No changes were seen in heart rate, stroke volume or left ventricular contractility, both in supine position and after standing.
In concert with previous reports, RSD leads to a significant drop in office BP. However, a reduction in sympathetic activity could not be demonstrated on a cardiac level.
International journal of cardiology 09/2015; 202. DOI:10.1016/j.ijcard.2015.09.025 · 4.04 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Since the publication of the European Association of Nuclear Medicine (EANM) procedural guidelines for radionuclide myocardial perfusion imaging (MPI) in 2005, many small and some larger steps of progress have been made, improving MPI procedures. In this paper, the major changes from the updated 2015 procedural guidelines are highlighted, focusing on the important changes related to new instrumentation with improved image information and the possibility to reduce radiation exposure, which is further discussed in relation to the recent developments of new International Commission on Radiological Protection (ICRP) models. Introduction of the selective coronary vasodilator regadenoson and the use of coronary CT-contrast agents for hybrid imaging with SPECT/CT angiography are other important areas for nuclear cardiology that were not included in the previous guidelines. A large number of minor changes have been described in more detail in the fully revised version available at the EANM home page: http://eanm.org/publications/guidelines/2015_07_EANM_FINAL_myocardial_perfusion_guideline.pdf .
European Journal of Nuclear Medicine 08/2015; 42(12). DOI:10.1007/s00259-015-3139-x · 5.38 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: (123)I-meta-iodobenzylguanidine ((123)I-mIBG) scintigraphy has been established as an important technique to evaluate cardiac sympathetic function and it has been shown to be of clinical value, especially for the assessment of prognosis, in many cardiac diseases. The majority of (123)I-mIBG scintigraphy studies have focused on patients with cardiac dysfunction due to hypertension, ischemic heart disease, or valvular disease. However less is known about the role of (123)I-mIBG scintigraphy in primary cardiomyopathies. This overview shows the clinical value of (123)I-mIBG scintigraphy in two types of primary cardiomyopathy: The genetic hypertrophic cardiomyopathy (HCM) and the acquired Tako-tsubo cardiomyopathy (TCM). Cardiac sympathetic activity is increased in HCM and correlates to the septal wall thickness and consequently to the LVOT obstruction. Moreover, increased cardiac sympathetic activity correlates with impaired diastolic and systolic LV function. In addition, (123)I-mIBG scintigraphy may be useful for determining the risk of developing congestive heart failure and ventricular tachycardia in these patients. In TCM (123)I-mIBG scintigraphy can be used to assess cardiac sympathetic hyperactivity. In addition, (123)I-mIBG scintigraphy may identify those patients who are prone to TCM recurrence and may help to identify responders to individual (pharmacological) therapy.
[Show abstract][Hide abstract] ABSTRACT: A 25-year-old man underwent an autotransplantation of his right kidney because of fibromuscular dysplasia-induced renal artery stenosis and subsequent hypertension. Since transplantation results in complete kidney denervation, it enabled assessment of renal sympathetic nerve activity changes using renal I-MIBG scintigraphy. Before and 2 weeks after transplantation I-MIBG, scintigraphy was performed. Uptake of I-MIBG in the left (control) kidney increased after transplantation with 4% at 15 minutes and 5% at 4 hours postinjection images, whereas I-MIBG uptake in the right transplanted kidney decreased with 21% at 15 minutes and with 29% at 4 hours, demonstrating renal I-MIBG changes after denervation.
Clinical nuclear medicine 07/2015; 40(10). DOI:10.1097/RLU.0000000000000901 · 3.93 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Over recent years moderation of renal sympathetic nerve activity by catheter-based renal sympathetic denervation (RDN) has received a considerable amount of attention as a treatment potential for therapy-resistant hypertension. However, incomplete nerve disruption is a possible factor that causes the wide inter-individual variety of blood pressure (BP) response. I-meta-iodobenzylguanidine (I-mIBG) scintigraphy enables assessment of organ specific sympathetic activity. We hypothesized that renal I-mIBG scintigraphy could be used as a measure of denervation following RDN. In addition, we explored its association with BP and plasma renin activity before and after denervation.
In patients with treatment resistant hypertension (median age 60.0 years, average 24 h BP measurement (ABPM) 160/93 mmHg), we prospectively studied I-mIBG scintigraphy, ABPM plasma- and urine-catecholamines before and 6 weeks after RDN.Planar scintigrams of the base of the skull to the upper thighs were performed at 15 min and 4 h after administration of I-mIBG. In these scintigrams, regions of interest of the kidney (specific) and muscle (non-specific) were drawn. The ratio of specific counts vs. non-specific counts represents I-mIBG uptake and washout of I-mIBG was calculated between 15 min and 4 h. Data of I-mIBG scintigraphies from six patients receiving complete denervation following renal transplantation served as control.
In 21 treatment resistant hypertensive patients no significant alterations were observed in I-mIBG readouts: uptake at 15 min before RDN was 3.08 (IQR 2.79-4.95) and 3.47 (IQR 2.26-5.53) after RDN (p = 0.289) pre-RDN washout was 41.5% and 42.7% post-RDN (p = 0.230). ABPM did not change significantly after denervation: 160/93 mmHg before RDN (IQR 151-173/84-100) to 157/92 mmHg (IQR 139-174/80-95) after RDN (p = 0.602). Post-RDN, office-based systolic BP decreased from 172 to 153 mmHg (p = 0.036) but office-based diastolic BP changed non-significantly from 97 to 90 mmHg, p = 0.531). In neither the catecholamines in plasma and urine or renin were statistical differences observed.
We observed no modifications in renal sympathetic nerve activity using renal I-mIBG scintigraphy. No changes in ABPM or catecholamines were found at six weeks after RDN, which is consistent with incomplete denervation.
[Show abstract][Hide abstract] ABSTRACT: Abnormal microvascular structure and function have been related to hypertension. Increasing evidence links Na+ to microvascular changes. Whether a chronic dietary Na+ load or an acute IV Na+ load differs in its microvascular effects is unknown. We therefore studied both effects in normotensive subjects on the microcirculation.
Twelve healthy male subjects pursued a low-sodium diet (LSD,<50 mmol Na+/d) and a high-sodium diet(HSD,>200 mmol Na+/d) for 8 days in randomized order, separated by a crossover period. On day 8 of LSD hypertonic IV saline (5mmol Na+/L body water) was administered in 30 minutes. Microvascular permeability after both diets and after IV saline was determined with transcapillary escape rate of 125I-albumin(TERalb) after IV administration of 100kBq 125I-albumin. Blood samples were drawn at fixed time points until 60 min. Plasma radioactivity was measured with an automatic γ-counter. TERalb was expressed as percentage decline in plasma radioactivity per hour (%cpm/g/h) using regression analysis. Plasma volume was determined by calculating the y-intercept of the TERalb disappearance curve, corrected for injected dose of tracer. Sublingual Sidestream Darkfield imaging was performed to assess perfused boundary region (PBR), reflecting endothelial glycocalyx thickness, and RBC filling and microvascular density as measures of microvascular perfusion (Glycocheck software). Blood pressure (BP), heart rate (HR), cardiac output (CO) and systemic vascular resistance (SVR) were measured in supine position with Nexfin.
An overview of results is presented in the table. All subjects adhered to both diets. Body weight increased significantly after HSD. TERalb and plasma volume did not differ between LSD and HSD, but increased significantly after saline infusion. PBR showed no differences between LSD and HSD, or after saline infusion. RBC filling and microvascular density did not differ between diets or after saline infusion. BP, HR, CO and SVR were similar after all conditions.(Figure is included in full-text article.) CONCLUSIONS:: Acute, but not chronic Na+ loading in healthy subjects resulted in higher microvascular permeability that coincided with increased plasma volume. These results suggest that deleterious microvascular effects of an acute Na+ load may develop by hydrostatic, or hypertonic, or direct effects of Na+ to the endothelium.
[Show abstract][Hide abstract] ABSTRACT: Background: While area detector computed tomography (ADCT) is a useful tool for coronary artery disease (CAD) evaluation, myocardial perfusion imaging (MPI) with single photon emission computed tomography is a well-established method of predicting functional relevance of CAD. Purpose: We assess the usefulness for decision making using both ADCT and MPI and discussed from the standpoint of cost for diagnostic work-up and contrast agent. Method: Between January, 2013 to September, 2014, 78 patients underwent both ADCT and MPI within two months were analyzed their therapeutic strategy. From ADCT, severity of stenosis was divided non-significant(less than 50%), moderate (over or equal to 50% and less than 75%) and severe (over or equal to 75%). Summed difference score of MPI was judged as ischemia positive.
Result: Table showed the result and executed treatment strategy. Patients with significant stenosis by ADCT were 40 patients (51.3%) and patients with ischemia positive were 25 patients (33.8%). Invasive revasculization was performed higher (82.3%, p<0.01) for the patients with significant stenosis and ischemia than moderate stenosis with ischemia (25%) or significant stenosis without ischemia (39.1%). Before taking invasive therapy, examination with ADCT and MPI saved 63700 yen and about 100ml of contrast agent in each case based study as it was compared with the case with ADCT and coronary angiography without MPI in spite of slightly higher radiation dose (4mSv). Conclusion: The combined use of ADCT and MPI could choose effectively treatment strategy of CAD with a reduction of cost and contrast agent.
European heart journal cardiovascular Imaging; 05/2015
[Show abstract][Hide abstract] ABSTRACT: The objective of this study was to determine the predictive value of C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) to a positive fluorine-18 fluorodeoxyglucose (F-FDG) PET/computed tomography (CT) result in patients with inflammation of unknown origin and fever of unknown origin.
Individual data of 498 patients were retrieved from three retrospective studies. Receiver operating characteristic derived areas under the curve were used to assess F-FDG PET/CT versus age, CRP, and ESR. The discriminative value of age, CRP, and ESR related to F-FDG PET/CT was examined using the net reclassification improvement (NRI).
A diagnosis was established in 331 patients; F-FDG PET/CT had a diagnostic accuracy of 89%. F-FDG PET/CT had the highest area under the curve (0.89, P<0.001). The addition of F-FDG PET/CT to a diagnosis prediction model including age, CRP, and ESR resulted in an NRI of 42% (P<0.001). In the same model with CRP values below 20 mg/l or ESR values below 20 mm/h, the NRI was 64% (P<0.001) and 29% (P=0.059), respectively. In 30 of 91 patients with CRP less than 10 mg/l, a diagnosis could be established; F-FDG PET/CT was 100% true negative only in patients with CRP levels less than 5 mg/l.
In patients with fever of unknown origin or inflammation of unknown origin, compared with elevated ESR levels, elevated CRP levels more often indicate a true positive F-FDG PET/CT outcome.In addition, F-FDG PET/CT, compared with CRP and ESR, shows the highest discrimination of patients with possible disabling disease.
Nuclear Medicine Communications 03/2015; 36(6). DOI:10.1097/MNM.0000000000000300 · 1.67 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The report of an imaging procedure is a critical component of an examination, being the final and often the only communication from the interpreting physician to the referring or treating physician. Very limited evidence and few recommendations or guidelines on reporting imaging studies are available; therefore, an European position statement on how to report nuclear cardiology might be useful. The current paper combines the limited existing evidence with expert consensus, previously published recommendations as well as current clinical practices. For all the applications discussed in this paper (myocardial perfusion, viability, innervation, and function as acquired by single photon emission computed tomography and positron emission tomography or hybrid imaging), headings cover laboratory and patient demographics, clinical indication, tracer administration and image acquisition, findings, and conclusion of the report. The statement also discusses recommended terminology in nuclear cardiology, image display, and preliminary reports. It is hoped that this statement may lead to more attention to create well-written and standardized nuclear cardiology reports and eventually lead to improved clinical outcome.