Ignasi Carrió

Use of PET and PET/CT for Radiation Therapy Planning: IAEA expert report 2006-2007

Positron Emission Tomography (PET) is a significant advance in cancer imaging with great potential for optimizing radiation therapy (RT) treatment planning and thereby improving outcomes for patients. The use of PET and PET/CT in RT planning was reviewed by an international panel. The International Atomic Energy Agency (IAEA) organized two synchronized and overlapping consultants meetings with experts from different regions of the world in Vienna in July 2006. Nine experts and three IAEA staff evaluated the available data on the use of PET in RT planning, and considered practical methods for integrating it into routine practice. For RT planning, (18)F fluorodeoxyglucose (FDG) was the most valuable pharmaceutical. Numerous studies supported the routine use of FDG-PET for RT target volume determination in non-small cell lung cancer (NSCLC). There was also evidence for utility of PET in head and neck cancers, lymphoma and in esophageal cancers, with promising preliminary data in many other cancers. The best available approach employs integrated PET/CT images, acquired on a dual scanner in the radiotherapy treatment position after administration of tracer according to a standardized protocol, with careful optimization of images within the RT planning system and carefully considered rules for contouring tumor volumes. PET scans that are not recent or were acquired without proper patient positioning should be repeated for RT planning. PET will play an increasing valuable role in RT planning for a wide range of cancers. When requesting PET scans, physicians should be aware of their potential role in RT planning.

Proposal for standardization of 123I-metaiodobenzylguanidine (MIBG) cardiac sympathetic imaging by the EANM Cardiovascular Committee and the European Council of Nuclear Cardiology

This proposal for standardization of 123I-metaiodobenzylguanidine (iobenguane, MIBG) cardiac sympathetic imaging includes recommendations for patient information and preparation, radiopharmaceutical, injected activities and dosimetry, image acquisition, quality control, reconstruction methods, attenuation, scatter and collimator response compensation, data analysis and interpretation, reports, and image display. The recommendations are based on evidence coming from original or scientific studies whenever possible and as far as possible reflect the current state-of-the-art in cardiac MIBG imaging. The recommendations are designed to assist in the practice of performing, interpreting and reporting cardiac sympathetic imaging. The proposed standardization does not include clinical indications, benefits or drawbacks of cardiac sympathetic imaging, and does not address cost benefits or cost effectiveness; however, clinical settings of potential utility are mentioned. Standardization of MIBG cardiac sympathetic imaging should contribute to increasing its clinical applicability and integration into current nuclear cardiology practice.

Cardiac 123 I-metaiodobenzylguanidine imaging allows early identification of dementia with Lewy bodies during life

PurposeDifferential diagnosis between dementia with Lewy bodies (DLB) and other neurodegenerative diseases with cognitive impairment represents a clinical challenge. Due to the overlapping of symptoms, the clinical diagnosis can be modified during the prolonged follow-up of these diseases. The purpose of this study was to assess the ability of cardiac metaiodobenzylguanidine (MIBG) imaging for early identification of DLB.Materials and methodsSince January 2003, all patients with neurodegenerative diseases with cognitive impairment at their first visit at the Memory Unit and clinical criteria of DLB were consecutively recruited and underwent a cardiac 123I-MIBG study. The heart-to-mediastinum ratio (HMR) and the washout rate (WR) of cardiac MIBG uptake were obtained.ResultsSixty-five patients were included. After a clinical follow-up of 4xa0years, the progress of the disease procured a definite diagnosis in 44 (68%) patients: 19 DLB, 12 Alzheimer disease (AD), and 13 other neurodegenerative diseases with cognitive impairment. HMR was significantly decreased in DLB with respect to the other neurodegenerative diseases. WR was only significantly different between DLB and AD. The HMR cut off point of 1.36 differentiated DLB from the other dementias with a sensitivity of 94% and a specificity of 96% with an accuracy of 95%.ConclusionsCardiac MIBG imaging performed at the time of the first clinical diagnosis of DLB can help early clinical identification or exclusion of this disease.

DMSA study performed during febrile urinary tract infection: a predictor of patient outcome?

Technetium-99m dimercaptosuccinic acid (DMSA) study has been advocated as a method for the assessment of renal sequelae after acute febrile urinary tract infection (UTI). However, it is not known whether DMSA scintigraphy performed during acute UTI has any prognostic value for outcome assessment. The objective of this study was to evaluate the usefulness of DMSA scintigraphy performed during UTI as a predictor of patient outcome, to identify children at risk of events [vesico-ureteral reflux (VUR) or recurrent UTI] that may lead to the development of progressive renal damage. One hundred and fifty-two children (including 78 girls) with a mean age of 20 months (range 1 month to 12 years) with first febrile UTI were evaluated by DMSA scintigraphy during acute UTI. After acute UTI, children were explored by voiding cysto-urethrography. Children who presented an abnormal DMSA study, or a normal DMSA study but VUR or recurrent UTI, underwent a DMSA control study 6 months after UTI. Children with VUR were followed up by direct radionuclide cystography. DMSA scintigraphy performed during acute UTI was normal in 112 children (74%). In 95 of these children, follow-up DMSA scintigraphy was not performed owing to a good clinical outcome. In the remaining 17 children, follow-up scintigraphy was normal. Forty children (26%) presented abnormal DMSA study during acute UTI. Twenty-five of them presented a normal follow-up DMSA, and 15 presented cortical lesions. Children with abnormal DMSA had a higher frequency of VUR than children with normal DMSA (48% vs 12%). It is concluded that children with normal DMSA during acute UTI have a low risk of renal damage. Children with normal follow-up DMSA and low-grade VUR have more frequent spontaneous resolution of VUR.

Comparison of sulfur hexafluoride microbubble (SonoVue)-enhanced myocardial contrast echocardiography with gated single-photon emission computed tomography for detection of significant coronary artery disease: a large European multicenter study

OBJECTIVESnThe purpose of this study was to compare sulfur hexafluoride microbubble (SonoVue)-enhanced myocardial contrast echocardiography (MCE) with single-photon emission computed tomography (SPECT) relative to coronary angiography (CA) for assessment of coronary artery disease (CAD).nnnBACKGROUNDnSmall-scale studies have shown that myocardial perfusion assessed by SonoVue-enhanced MCE is a viable alternative to SPECT for CAD assessment. However, large multicenter studies are lacking.nnnMETHODSnPatients referred for myocardial ischemia testing at 34 centers underwent rest/vasodilator SonoVue-enhanced flash-replenishment MCE, standard (99m)Tc-labeled electrocardiography-gated SPECT, and quantitative CA within 1 month. Myocardial ischemia assessments by 3 independent, blinded readers for MCE and 3 readers for SPECT were collapsed into 1 diagnosis per patient per technique and were compared to CA (reference standard) read by 1 independent blinded reader.nnnRESULTSnOf 628 enrolled patients who received SonoVue (71% males; mean age: 64 years; >1 cardiovascular [CV] risk factor in 99% of patients) 516 patients underwent all 3 examinations, of whom 161 (31.2%) had ≥70% stenosis (131 had single-vessel disease [SVD]; 30 had multivessel disease), and 310 (60.1%) had ≥50% stenosis. Higher sensitivity was obtained with MCE than with SPECT (75.2% vs. 49.1%, respectively; p < 0.0001), although specificity was lower (52.4% vs. 80.6%, respectively; p < 0.0001) for ≥70% stenosis. Similar findings were obtained for patients with ≥50% stenosis. Sensitivity levels for detection of SVD and proximal disease for ≥70% stenosis were higher for MCE (72.5% vs. 42.7%, respectively; p < 0.0001; 80% vs. 58%, respectively; p = 0.005, respectively).nnnCONCLUSIONSnSonoVue-enhanced MCE demonstrated superior sensitivity but lower specificity for detection of CAD compared to SPECT in a population with a high incidence of CV risk factors and intermediate-high prevalence of CAD. (A phase III study to compare SonoVue® enhanced myocardial echocardiography [MCE] to single photon emission computerized tomography [ECG-GATED SPECT], at rest and at peak of low-dose Dipyridamole stress test, in the assessment of significant coronary artery disease [CAD] in patients with suspect or known CAD using Coronary Angiography as Gold Standard-SonoVue MCE vs SPECT; EUCTR2007-003492-39-GR).

Use of electrical impedance tomography (EIT) for the assessment of unilateral pulmonary function

We describe a fully automatable quantification process for the assessment of unilateral pulmonary function (UPF) by means of EIT and propose a measurement protocol for its clinical implementation. Measurements were performed at the fourth and sixth intercostal levels on a first group of ten healthy subjects (5M, 5F, ages 26-48 years) to define the proper protocol by evaluating the most common postures and ventilation modes. Several off-line processing tools were also evaluated, including the use of digital filters to extract the respiratory components from EIT time series. Comparative measures were then carried out on a second group consisting of five preoperatory patients with lung cancer (4M, IF, ages 25-77 years) scheduled for radionuclide scanning. Results show that measurements were best performed with the subject sitting down, holding his arms up and breathing spontaneously. As regards data processing, it is best to extract Fourier respiratory components. The mean of the healthy subject group leads to a left-right division of lung ventilation consistent with literature values (47% left lung, 53% right lung). The comparative study indicates a good correlation (r = 0.96) between the two techniques, with a mean difference of (-0.4+/-5.4)%, suggesting that the elimination of cardiac components from the thoracic transimpedance signal leads to a better estimation of UPF.

Influence of the menstrual cycle and of menopause on the gastric emptying rate of solids in female volunteers

The aim of this study was to assess the influence of the normal menstrual cycle and of menopause on the gastric emptying rate of solids. Gastric emptying was studied in 15 premenopausal and ten postmenopausal women with an isotopic technique after the ingestion of a radiolabelled test meal. Premenopausal women were studied twice: within 1 week prior to menses and again 1 week after onset of menses. Postmenopausal women were studied only once. The emptying curves of the solid component of the meal fitted a linear model. The half-emptying time was 78±5 min during the follicular phase, 75 ± 7 min during the luteal phase and 76 ± 6 min in post-menopausal women (differences not statistically significant). The mean percentages of the meal retained in the stomach at different time intervals were also similar in the three groups. These results suggest that the menstrual cycle does not influence the gastric emptying rate of solids, which remains unchanged in relation to the follicular phase or after menopause.

Is adjuvant radiotherapy needed after curative resection of extrahepatic biliary tract cancers? A systematic review with a meta-analysis of observational studies

BACKGROUNDnThe role for adjuvant radiotherapy (ART) after curative resection in extrahepatic cholangiocarcinoma remains unclear. Due to the lack of randomized trials, available data comes from single center experiences or data-based population studies with inconclusive results.nnnOBJECTIVEnTo assess the impact of radiotherapy (with or without concurrent chemotherapy) on toxicity and survival of radically resected patients with extrahepatic bile duct cancer (extrahepatic cholangiocarcinoma, gallbladder cancer and pure ampullary cancer).nnnDATA SOURCES AND STUDY SELECTIONnEligible studies with data on survival, recurrence and toxicity were retrieved from the MEDLINE, ISI web of science, EMBASE and Cochrane databases from January 1995 to December 2008, to ensure that all ART treatments were performed with conventional 3D techniques. In the absence of randomized controlled-studies, all observational cohort studies (longitudinal and historical) were initially considered. Ten retrospective cohort studies (where the use of concurrent CT was reported only in 2), met all inclusion criteria and were enrolled for final meta-analysis. Hazard ratio (HR) had to be extracted from survival curves using the Tierney et al. methods. MIX 1.7 statistical software was used for meta-analysis.nnnRESULTSnAll studies on ART used conventional 3D-techniques. Patients in the ART cohorts were more likely to have involved surgical margins and positive lymph nodes. For extrahepatic cholangiocarcinoma location, ART significantly improved overall survival (HR 0.62; 95% CI 0.48 to 0.78, p<0.001). Meta-analysis was not feasible for gallbladder cancer and ampullary cancer locations. Late radiation-induced toxicity was low (2-9% late obstruction or GI bleeding).nnnCONCLUSIONnIn the absence of randomized controlled studies, we found in the present systematic review and meta-analysis of observational studies that, patients with extrahepatic cholangiocarcinoma treated with adjuvant RT have a significant lower risk of dying compared to patients treated with surgery alone.

Assessment of 123I-mIBG and 99mTc-tetrofosmin single-photon emission computed tomographic images for the prediction of arrhythmic events in patients with ischemic heart failure: Intermediate severity innervation defects are associated with higher arrhythmic risk

Rationale123I-mIBG planar image heart-to-mediastinum ratios effectively risk-stratify heart failure (HF) patients. The value of single-photon emission computed tomographic (SPECT) imaging for identifying increased risk of ventricular arrhythmias is less clear. This study sought to determine if findings from simultaneous interpretation of 123I-mIBG and 99mTc-tetrofosmin SPECT are predictive of arrhythmic events (ArEs).Methods123I-mIBG SPECT images from 622 patients with ischemic HF were presented in standard displays alongside 99mTc-tetrofosmin images. Consensus interpretations using a 17-segment model produced summed scores. Cox proportional hazards analyses related findings to adjudicated ArEs over 2xa0years.Results471 patients had images adequate for total 17-segment scoring. There were 48 ArEs (10.2%). Neither 123I-mIBG nor 99mTc-tetrofosmin SPECT summed scores were univariate predictors. On multivariate proportional hazards analysis, the 123I-mIBG SPECT score was independently predictive of ArEs (HR: 0.975, 95% CI 0.951-0.999, Pxa0=xa00.042), but HR<1 indicated that risk decreased with increasing score. This occurred because patients with intermediately abnormal SPECT studies had a higher likelihood of ArEs compared to patients with extensive abnormalities.ConclusionsThe presumption of a monotonic increase in ArE risk with increasing summed 123I-mIBG SPECT score may not be correct as ischemic HF patients with abnormalities of intermediate extent appear at highest risk.

Challenging the neuronal MIBG uptake by pharmacological intervention: effect of a single dose of oral amitriptyline on regional cardiac MIBG uptake

PurposeImaging with metaiodobenzylguanidine (MIBG) is used for the assessment of neuronal dysfunction in various cardiovascular disorders. Although valuable information is obtained by resting MIBG imaging, it is conceivable that competitive interference with the re-uptake mechanism would exaggerate MIBG defects and might unmask subclinical neuronal dysfunction. Tricyclic antidepressants, such as amitriptyline, have been reported to significantly increase cardiac MIBG washout and inhibit uptake into presynaptic neurons. This study was undertaken to assess whether a single oral dose of amitriptyline could influence cardiac MIBG distribution.MethodsSix patients (aged 62–81 years; four males, two females) who had demonstrated a normal cardiac MIBG scan during work-up for movement disorders were studied. The patients underwent a second 123I-MIBG study after oral administration of 25xa0mg amitriptyline within 1 week. Single-photon emission computed tomography images were acquired at 4xa0h to assess the regional distribution of MIBG, after generation of polar maps and employing a 20-segment model. Mean percentage of peak activity was calculated for each segment at rest and after amitriptyline administration.ResultsAfter amitriptyline administration, there was a decrease in regional MIBG uptake in 10±4 segments per patient [62/120 segments (52%): 37 segments with a 5–10% decrease, 25 segments with a >10% decrease]. This change was statistically significant in lateral (P=0.003), apical (P<0.0001) and inferior (P=0.03) regions.ConclusionA single oral dose of amitriptyline can induce changes in the uptake and retention of cardiac MIBG, indicating the feasibility of use of pharmacological intervention in cardiac neurotransmission imaging.