Study of the impact of tissue density heterogeneities on 3-dimensional abdominal dosimetry: comparison between dose kernel convolution and direct monte carlo methods.

Dose kernel convolution (DK) methods have been proposed to speed up absorbed dose calculations in molecular radionuclide therapy. Our aim was to evaluate the impact of tissue density heterogeneities (TDH) on dosimetry when using a DK method and to propose a simple density-correction method. METHODS: This study has been conducted on 3 clinical cases: case 1, non-Hodgkin lymphoma treated with (131)I-tositumomab; case 2, a neuroendocrine tumor treatment simulated with (177)Lu-peptides; and case 3, hepatocellular carcinoma treated with (90)Y-microspheres. Absorbed dose calculations were performed using a direct Monte Carlo approach accounting for TDH (3D-RD), and a DK approach (VoxelDose, or VD). For each individual voxel, the VD absorbed dose, D(VD), calculated assuming uniform density, was corrected for density, giving D(VDd). The average 3D-RD absorbed dose values, D(3DRD), were compared with D(VD) and D(VDd), using the relative difference Δ(VD/3DRD). At the voxel level, density-binned Δ(VD/3DRD) and Δ(VDd/3DRD) were plotted against ρ and fitted with a linear regression. RESULTS: The D(VD) calculations showed a good agreement with D(3DRD). Δ(VD/3DRD) was less than 3.5%, except for the tumor of case 1 (5.9%) and the renal cortex of case 2 (5.6%). At the voxel level, the Δ(VD/3DRD) range was 0%-14% for cases 1 and 2, and -3% to 7% for case 3. All 3 cases showed a linear relationship between voxel bin-averaged Δ(VD/3DRD) and density, ρ: case 1 (Δ = -0.56ρ + 0.62, R(2) = 0.93), case 2 (Δ = -0.91ρ + 0.96, R(2) = 0.99), and case 3 (Δ = -0.69ρ + 0.72, R(2) = 0.91). The density correction improved the agreement of the DK method with the Monte Carlo approach (Δ(VDd/3DRD) < 1.1%), but with a lesser extent for the tumor of case 1 (3.1%). At the voxel level, the Δ(VDd/3DRD) range decreased for the 3 clinical cases (case 1, -1% to 4%; case 2, -0.5% to 1.5%, and -1.5% to 2%). No more linear regression existed for cases 2 and 3, contrary to case 1 (Δ = 0.41ρ - 0.38, R(2) = 0.88) although the slope in case 1 was less pronounced. CONCLUSION: This study shows a small influence of TDH in the abdominal region for 3 representative clinical cases. A simple density-correction method was proposed and improved the comparison in the absorbed dose calculations when using our voxel S value implementation

A031 Développement d’un peptido-mimétique de la glycorpotein VI plaquettaire comme outil d’imagerie de la fibrose

ObjectifLa glycoprotéine VI est le récepteur d’activation des plaquettes par les collagènes de type I et de type III. Nous avons émis l’hypothèse que nous pourrions développer une sonde spécifique du collagène basée sur la spécificité de GPVI et que cette sonde permettrait de visualiser la fibrose in vivo par une méthode non invasive.MéthodesUn anticorps bloquant la liaison de GPVI au collagène a été utilisé pour cribler une banque peptidique permettant d’identifier un motif peptidique cyclique. La capacité du peptide à mimer la GPVI a été analysée par des études de liaison et de compétition en phase solide. La liaison au collagène tissulaire a été analysée par histochimie. L’imagerie in vivo a été réalisée par injection du peptide-marqué au Tc-99m dans un modèle de fibrose cicatricielle sur infarctus du myocarde chez le rat, scintigraphie et autoradiographieRésultatsLe peptide, nommé collagelin, se lie de manière spécifique à l’anticorps anti GPVI 9O12.2 et aux collagènes I et III in vitro et la liaison est inhibée par GPVI indiquant que le peptide mime GPVI. Cependant le collagelin n’inhibe pas l’agrégation des plaquettes induite par le collagène. Les études d’histochimie montrent que le collagelin se lie au collagène tissulaire sur coupe d’aorte et de queue de rat indiquant que le collagelin se comporte comme un traceur du collagène. Dans le modèle d’infarctus cicatriciel, une accumulation du collagelin radiomarqué est observée dans la zone cardiaque par scintigraphie planaire et tomographie chez les animaux avec MI mais pas chez les animaux contrôles ni avec un peptide contrôle. L’accumulation du traceur dans les zones de fibrose a été mise en évidence ex vivo par superposition des images d’autoradiographies et d’histologie sur coupes congelées.ConclusionNous avons produit un peptide qui mime en partie le site de liaison de GPVI au collagène. Ce peptide se comporte comme un traceur spécifique du collagène in vitro et in vivo. Nous proposons que ce traceur pourrait être utile pour le diagnostic et le suivi évolutif de la fibrose dans un grand nombre de pathologies

Cost-effectiveness analysis of stand-alone or combined non-invasive imaging tests for the diagnosis of stable coronary artery disease: results from the EVINCI study

Aim: This study aimed at evaluating the cost-effectiveness of different non-invasive imaging-guided strategies for the diagnosis of obstructive coronary artery disease (CAD) in a European population of patients from the Evaluation of Integrated Cardiac Imaging in Ischemic Heart Disease (EVINCI) study. Methods and results: Cost-effectiveness analysis was performed in 350 patients (209 males, mean age 59 ± 9 years) with symptoms of suspected stable CAD undergoing computed tomography coronary angiography (CTCA) and at least one cardiac imaging stress-test prior to invasive coronary angiography (ICA) and in whom imaging exams were analysed at dedicated core laboratories. Stand-alone stress-tests or combined non-invasive strategies, when the first exam was uncertain, were compared. The diagnostic end-point was obstructive CAD defined as > 50% stenosis at quantitative ICA in the left main or at least one major coronary vessel. Effectiveness was defined as the percentage of correct diagnosis (cd) and costs were calculated using country-specific reimbursements. Incremental cost-effectiveness ratios (ICERs) were obtained using per-patient data and considering “no-imaging” as reference. The overall prevalence of obstructive CAD was 28%. Strategies combining CTCA followed by stress ECHO, SPECT, PET, or stress CMR followed by CTCA, were all cost-effective. ICERs values indicated cost saving from − 969€/cd for CMR-CTCA to − 1490€/cd for CTCA-PET, − 3092€/cd for CTCA-SPECT and − 3776€/cd for CTCA-ECHO. Similarly when considering early revascularization as effectiveness measure. Conclusion: In patients with suspected stable CAD and low prevalence of disease, combined non-invasive strategies with CTCA and stress-imaging are cost-effective as gatekeepers to ICA and to select candidates for early revascularization

Arrhythmogenic right ventricular cardiomyopathy/dysplasia

Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is a heart muscle disease clinically characterized by life-threatening ventricular arrhythmias. Its prevalence has been estimated to vary from 1:2,500 to 1:5,000. ARVC/D is a major cause of sudden death in the young and athletes. The pathology consists of a genetically determined dystrophy of the right ventricular myocardium with fibro-fatty replacement to such an extent that it leads to right ventricular aneurysms. The clinical picture may include: a subclinical phase without symptoms and with ventricular fibrillation being the first presentation; an electrical disorder with palpitations and syncope, due to tachyarrhythmias of right ventricular origin; right ventricular or biventricular pump failure, so severe as to require transplantation. The causative genes encode proteins of mechanical cell junctions (plakoglobin, plakophilin, desmoglein, desmocollin, desmoplakin) and account for intercalated disk remodeling. Familiar occurrence with an autosomal dominant pattern of inheritance and variable penetrance has been proven. Recessive variants associated with palmoplantar keratoderma and woolly hair have been also reported. Clinical diagnosis may be achieved by demonstrating functional and structural alterations of the right ventricle, depolarization and repolarization abnormalities, arrhythmias with the left bundle branch block morphology and fibro-fatty replacement through endomyocardial biopsy. Two dimensional echo, angiography and magnetic resonance are the imaging tools for visualizing structural-functional abnormalities. Electroanatomic mapping is able to detect areas of low voltage corresponding to myocardial atrophy with fibro-fatty replacement. The main differential diagnoses are idiopathic right ventricular outflow tract tachycardia, myocarditis, dialted cardiomyopathy and sarcoidosis. Only palliative therapy is available and consists of antiarrhythmic drugs, catheter ablation and implantable cardioverter defibrillator. Young age, family history of juvenile sudden death, QRS dispersion ≥ 40 ms, T-wave inversion, left ventricular involvement, ventricular tachycardia, syncope and previous cardiac arrest are the major risk factors for adverse prognosis. Preparticipation screening for sport eligibility has been proven to be effective in detecting asymptomatic patients and sport disqualification has been life-saving, substantially declining sudden death in young athletes

Early detection of recurrence by 18FDG-PET in the follow-up of patients with colorectal cancer

We assessed the potential benefits of including systematic 18fluorodeoxyglucose positron emission tomography (FDG-PET) for detecting tumour recurrence in a prospective randomised trial. Patients (N=130) who had undergone curative therapy were randomised to undergo either conventional (Con) or FDG-PET procedures during follow-up. The two groups were matched at baseline. Recurrence was confirmed histologically. ‘Intention-to-treat' analysis revealed a recurrence in 46 patients (25 in the FDG-PET group, and 21 in the Con group; P=0.50), whereas per protocol analysis revealed a recurrence in 44 out of 125 patients (23 and 21, respectively; P=0.60). In another three cases, PET revealed unexpected tumours (one gastric GIST, two primary pulmonary cancers). Three false-positive cases of FDG-PET led to no beneficial procedures (two laparoscopies and one liver MRI that were normal). We failed to identify peritoneal carcinomatosis in two of the patients undergoing FDG-PET. The overall time in detecting a recurrence from the baseline was not significantly different in the two groups. However, recurrences were detected after a shorter time (12.1 vs 15.4 months; P=0.01) in the PET group, in which recurrences were also more frequently (10 vs two patients) cured by surgery (R0). Regular FDG-PET monitoring in the follow up of colorectal cancer patients may permit the earlier detection of recurrence, and influence therapy strategies

Cost-effectiveness analysis of stand-alone or combined non-invasive imaging tests for the diagnosis of stable coronary artery disease: results from the EVINCI study

Aim: This study aimed at evaluating the cost-effectiveness of different non-invasive imaging-guided strategies for the diagnosis of obstructive coronary artery disease (CAD) in a European population of patients from the Evaluation of Integrated Cardiac Imaging in Ischemic Heart Disease (EVINCI) study.Methods and results: Cost-effectiveness analysis was performed in 350 patients (209 males, mean age 59 ± 9 years) with symptoms of suspected stable CAD undergoing computed tomography coronary angiography (CTCA) and at least one cardiac imaging stress-test prior to invasive coronary angiography (ICA) and in whom imaging exams were analysed at dedicated core laboratories. Stand-alone stress-tests or combined non-invasive strategies, when the first exam was uncertain, were compared. The diagnostic end-point was obstructive CAD defined as > 50% stenosis at quantitative ICA in the left main or at least one major coronary vessel. Effectiveness was defined as the percentage of correct diagnosis (cd) and costs were calculated using country-specific reimbursements. Incremental cost-effectiveness ratios (ICERs) were obtained using per-patient data and considering “no-imaging” as reference. The overall prevalence of obstructive CAD was 28%. Strategies combining CTCA followed by stress ECHO, SPECT, PET, or stress CMR followed by CTCA, were all cost-effective. ICERs values indicated cost saving from − 969€/cd for CMR-CTCA to − 1490€/cd for CTCA-PET, − 3,09 €/cd for CTCA-SPECT and − 3776€/cd for CTCA-ECHO. Similarly when considering early revascularization as effectiveness measure.Conclusion: In patients with suspected stable CAD and low prevalence of disease, combined non-invasive strategies with CTCA and stress-imaging are cost-effective as gatekeepers to ICA and to select candidates for early revascularization.</p

Dose optimization a major challenge for acceptability of nuclear medicine

International audience[No abstract available

Dosimétrie cellulaire en médecine nucléaire diagnostique : influence des émissions électroniques

Les radio-nucléides utilisés en diagnostic présentent des émissions photoniques utilisées pour l'imagerie, mais également des émissions électroniques de faible énergie, responsables d'une hétérogénéité de dose à l'échelon cellulaire. La dose moyenne délivrée au noyau par les émissions électroniques du 99mTc, de l'123I, de l'111In, du 67Ga, et du 201Tl, a été calculée, en tenant compte de localisations nucléaires, cytoplasmiques et membranaires de la radioactivité. Ce modèle tient compte de la contribution de la dose due à la radioactivité présente dans la cellule cible elle-même, et de la contribution des cellules voisines. Les résultats de la dosimétrie cellulaire (Dcel) ont été comparés à ceux trouvés en dosimétrie conventionnelle (Dconv), en supposant une activité identique dans toutes les cellules. Le modèle cellulaire montre que pour des localisations membranaires et cytoplasmiques, la principale source d'irradiation électronique vient des cellules voisines. Pour des localisations nucléaires, la contribution de la cellule cible n'est plus négligeable et peut même devenir la principale contribution. La comparaison entre les modèles cellulaire et conventionnel montre que Dcel/Dconv varie entre 0,61 et 0,89 pour des localisations cytoplasmiques et membranaires de la radioactivité, suivant le radio-nucléide et les dimensions cellulaires. Ainsi, la dosimétrie conventionnelle surestime faiblement la dose au noyau. Par contre, Dcel/Dconv varie entre 1,1 et 75 pour une localisation purement nucléaire. La dosimétrie conventionnelle peut alors sous-estimer notablement la dose au noyau. Cette étude montre qu'en médecine nucléaire diagnostique, la dosimétrie cellulaire peut conduire à une radioprotection accrue du patient et une meilleure évaluation des risques radiobiologiques liés à l'administration d'un radiopharmaceutique.