Comparison of Methods to Reduce Myocardial 18F-FDG Uptake in Mice: Calcium Channel Blockers versus High-Fat Diets

Besides its application in oncology, 18F-FDG PET-CT imaging is also useful in the diagnosis of certain lung infections, inflammatory diseases, and atherosclerotic plaques. Myocardial uptake of 18F-FDG may hamper visualization of the lesions caused by these diseases. Two approaches have been proposed for reducing myocardial uptake in preclinical studies, namely, calcium channel blockers (verapamil) and high-fat diets such as commercial ketogenic diets and sunflower seed diets. The objective of this study was to compare the efficacy of these approaches in reducing myocardial uptake of 18F-FDG in mice.This research was funded in part by the Innovative Medicines Initiative Joint Undertaking under grant agreement nu115337 (www.imi.europa.eu), resources of which are composed of financial contribution from the European Union’s Seventh Framework Programme (FP7/2007-2013) and EFPIA companies’ in kind contribution, and from the Spanish MICINN (CEN-20101014) and the RIC-RETIC network, Spanish MINECO (RD12/0042/0057). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Publicad

In-line high resolution PET and 3T MRI hybrid device for preclinical multimodal imaging

Proocedings of: 3rd Conference on PET/MR and SPECT/MR (PSMR 2014). Kos, Creece, May 19-21, 2014Publicad

FDG-PET brain uptake in free moving mice

In both clinical and preclinical scenarios, 2-deoxy-2[18F]fluoro-D-glucose ([18F]FDG) is the radiotracer most widely used to study brain glucose metabolism with positron emission tomography (PET). In clinical practice, there is a worldwide standardized protocol for preparing patients for [18F]FDG-PET studies, which specifies the room lighting. However, this standard is typically not observed in the preclinical field, although it is well known that animal handling affects the biodistribution of [18F]FDG. The present study aimed to evaluate the effect of ambient lighting on brain [18F]FDG uptake in mice. Two [18F]FDG-PET studies were performed on each animal, one in light and one in dark conditions. Thermal video recordings were acquired to analyse animal motor activity in both conditions. [18F]FDG-PET images were analysed with the Statistical Parametric Mapping method. The results showed that [18F]FDG uptake is higher in darkness than in light condition in mouse nucleus accumbens, hippocampus, midbrain, hindbrain, and cerebellum. The SPM analysis also showed an interaction between the illumination condition and the sex of the animal. Mouse activity was significantly different (p = 0.01) between light conditions (632 ± 215 s of movement) and dark conditions (989 ± 200 s), without significant effect of sex (p = 0.416). We concluded that room illumination conditions during [18F]FDG uptake in mice affected the brain [18F]FDG biodistribution. Therefore, we highlight the importance to control this factor to ensure more reliable and reproducible mouse brain [18F]FDG-PET results.This work was partially supported by the Comunidad de Madrid (S2017/BMD-3867 RENIM-CM), and it was co-financed by the European Structural and Investment Fund. And by Ministerio de Ciencia e Innovación, Instituto de Salud Carlos III (PT20/00044), cofunded by European Union, European Regional Development Fund (ERDF), “A way of making Europe”. The CNIC is supported by the ISCIII, the Ministerio de Ciencia e Innovación and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (SEV-2015-0505)

Cuantificación del infarto de miocardio en imágenes PET mediante mapas polares

Actas de: XXVIII Congreso Anual de la Sociedad Española de Ingeniería Biomédica (CASEIB 2010). Madrid, 24-26 de noviembre de 2010.El análisis de la imagen de miocardio en cardiología nuclear es una herramienta muy importante para la valoración de la enfermedad coronaria, dado que permite la cuantificación objetiva de la extensión y de la intensidad del infarto de miocardio. En este trabajo se presenta una herramienta que permite realizar dicha cuantificación mediante el uso de mapas polares tanto estáticos como dinámicos, resultantes del análisis de la imagen PET que se viene realizando en los pacientes. Esta aproximación es una alternativa que permite la visualización integral del infarto en vez de requerir una segmentación (manual o asistida) de todas las rodajas tomográficas que componen el estudio.Este trabajo ha sido financiado por los proyectos del Ministerio de Ciencia e Innovación, TEC2007-64731, TEC 2008-06715-C02-1, la RETIC-RECAVA del Ministerio de Sanidad y Consumo, y el programa ARTEMIS S2009/DPI-1802 de la Comunidad de Madrid.Publicad

Multimodal assessment of myocardial infarction in rats: comparison of late gadolinium enhanced MRI and PET

[Poster] 4th European Molecular Imaging Meeting, Barcelona, Spain, May 27 - 30, 2009Myocardial infarction (Mi) size in rats has been assessed using Mri and nuclear imaging, but little information is available on the suitability and assessment of the information provided by each technique. We are running a study to compare results on the infarct size as assessed by each modality 30 days after an induced Mi in ratsThis work is supported by the reCaVa-reTiC network, Ministerio de Ciencia e innovación (TeC2008-06715-C02-01 and TeC2007-64731/TCM) and Ministerio de industria (CdTeaM, Programa CeniT)Publicad

Automatic TAC extraction from dynamic cardiac PET imaging using iterative correlation from a population template

This work describes a new iterative method for extracting time-activity curves (TAC) from dynamic imaging studies using a priori information from generic models obtained from TAC templates. Analytical expressions of the TAC templates were derived from TACs obtained by manual segmentation of three 13NH3 pig studies (gold standard). An iterative method for extracting both ventricular and myocardial TACs using models of the curves obtained as an initial template was then implemented and tested. These TACs were extracted from masked and unmasked images; masking was applied to remove the lungs and surrounding non-relevant structures. The resulting TACs were then compared with TACs obtained manually; the results of kinetic analysis were also compared. Extraction of TACs for each region was sensitive to the presence of other organs (e.g., lungs) in the image. Masking the volume of interest noticeably reduces error. The proposed method yields good results in terms of TAC definition and kinetic parameter estimation, even when the initial TAC templates do not accurately match specific tracer kinetics.This work is supported by the following grants: RD07/0014/2009, Subprograma RETICS, Ministerio de Ciencia e Innovación. S2009/DPI-1802 (ARTEMIS), Comunidad de Madrid. CEN-20101014, Programa CENIT, CDTI, Ministerio de Ciencia e Innovación. European Commission, EFPIA, INNOVATIVE MEDICINE INITIATIVE (PredDICT-TB project, 115337-1)Publicad

Radioimmune Imaging of α4β7 Integrin and TNFα for Diagnostic and Therapeutic Applications in Inflammatory Bowel Disease

Imaging using radiolabelled monoclonal antibodies can provide, non-invasively, molecular information which allows for the planning of the best treatment and for monitoring the therapeutic response in cancer, as well as in chronic inflammatory diseases. In the present study, our main goal was to evaluate if a pre-therapy scan with radiolabelled anti-α4β7 integrin or radiolabelled anti-TNFα mAb could predict therapeutic outcome with unlabelled anti-α4β7 integrin or anti-TNFα mAb. To this aim, we developed two radiopharmaceuticals to study the expression of therapeutic targets for inflammatory bowel diseases (IBD), to be used for therapy decision making. Both anti-α4β7 integrin and anti-TNFα mAbs were successfully radiolabelled with technetium-99m with high labelling efficiency and stability. Dextran sulfate sodium (DSS)-induced colitis was used as a model for murine IBD and the bowel uptake of radiolabelled mAbs was evaluated ex vivo and in vivo by planar and SPECT/CT images. These studies allowed us to define best imaging strategy and to validate the specificity of mAb binding in vivo to their targets. Bowel uptake in four different regions was compared to immunohistochemistry (IHC) score (partial and global). Then, to evaluate the biomarker expression prior to therapy administration, in initial IBD, another group of DSS-treated mice was injected with radiolabelled mAb on day 2 of DSS administration (to quantify the presence of the target in the bowel) and then injected with a single therapeutic dose of unlabelled anti-α4β7 integrin or anti-TNFα mAb. Good correlation was demonstrated between bowel uptake of radiolabelled mAb and immunohistochemistry (IHC) score, both in vivo and ex vivo. Mice treated with unlabelled α4β7 integrin and anti-TNFα showed an inverse correlation between the bowel uptake of radiolabelled mAb and the histological score after therapy, proving that only mice with high α4β7 integrin or TNFα expression will benefit of therapy with unlabelled mAb.This work has been supported by grants of Boehringer Ingelheim Pharma GmbH, & Co. KG, Biberach an der Riß, Germany. This work was partially supported by Instituto de Salud Carlos III (grant PT20/00044), co-funded by European Regional Development Fund (ERDF), “A way to make Europe” and by Comunidad de Madrid (S2022/BMD-7403 RENIM-CM), co-funded by European Structural and Investment Fund. And by the Fundación Ramón Areces

Automatic Cardiac Self-Gating of Small-Animal PET Data

Purpose: The cardiac gating signal (CGS) in positron emission tomography (PET) studies is usually obtained from an electrocardiography (ECG) monitor. In this work, we propose a method to obtain the CGS in small-animal PET using the acquired list-mode data without using any hardware or end-user input. Procedures: The CGS was obtained from the number of coincidences over time acquired in the lines-of-response connected with the cardiac region. This region is identified in the image as its value changes with frequencies in the range of 3 to 12 Hz. The procedure was tested in a study with 29 Wistar rats and 6 mice injected with 2-deoxy-2-[18F]fluoro-D-glucose, which underwent a 45-min single-bed list-mode PET scan of the heart syncronized with an ECG. The estimated signals and the reconstructed images using eight-gated frames were compared with the ones obtained using the ECG signal from the monitor. Results: The differences of the PET-based CGS with respect to the ECG relative to the duration of the heartbeats were 5.6 % in rats and 11.0 % in mice. The reconstructed gated images obtained from the proposed method do not differ qualitatively with respect to the ones obtained with the ECG. The quantitative analysis of both set of images were performed measuring the volume of the left ventricle (LV) of the rats in the end-of-systole and end-of-diastole phase. The differences found in these parameters between both methods were below 12.1 % in the ESV and 9.3 % in the EDV with a 95 % confidence interval, which are comparable to the accuracy (7 %) of the method used for segmenting the LV. Conclusion: The proposed method is able to provide a valid and accurate CGS in small-animal PET list-mode data. the ones obtained using the ECG signal from the monitor.This work was supported in part by Consejería de Educación, Juventud y Deporte de la Comunidad de Madrid (Spain) through the Madrid-MIT M+Visión Consortium, Comunidad de Madrid (S2013/MIT-3024 TOPUS-CM), UCM (Grupos UCM, 910059), CPAN (Consolider-Ingenio 2010, CSPD-2007-00042), RIC-RETIC network, Spanish MINECO (RD12/0042/0057),Ministerio de Ciencia e Innovación, Spanish Government (ENTEPRASE grant, PSE-300000-2009-5 and TEC2007-64731/TCM), and European Regional funds

Infrared-Emitting Multimodal Nanostructures for Controlled In Vivo Magnetic Hyperthermia

Deliberate and local increase of the temperature within solid tumors represents an effective therapeutic approach. Thermal therapies embrace this concept leveraging the capability of some species to convert the absorbed energy into heat. To that end, magnetic hyperthermia (MHT) uses magnetic nanoparticles (MNPs) that can effectively dissipate the energy absorbed under alternating magnetic fields. However, MNPs fail to provide real-time thermal feedback with the risk of unwanted overheating and impeding on-the-fly adjustment of the therapeutic parameters. Localization of MNPs within a tissue in an accurate, rapid, and cost-effective way represents another challenge for increasing the efficacy of MHT. In this work, MNPs are combined with state-of-the-art infrared luminescent nanothermometers (LNTh; Ag2S nanoparticles) in a nanocapsule that simultaneously overcomes these limitations. The novel optomagnetic nanocapsule acts as multimodal contrast agents for different imaging techniques (magnetic resonance, photoacoustic and near-infrared fluorescence imaging, optical and X-ray computed tomography). Most crucially, these nanocapsules provide accurate (0.2 degrees C resolution) and real-time subcutaneous thermal feedback during in vivo MHT, also enabling the attainment of thermal maps of the area of interest. These findings are a milestone on the road toward controlled magnetothermal therapies with minimal side effects.E.X. and R.M. contributed equally to this work. Work partially supported by the Ministerio de Ciencia, Innovación y Universidades (PID2019-106301RB-I00 and PID2019-105195RA-I00), by the Spanish Ministry of Economy and Competitiveness (MAT2017-85617-R, SEV-2016-0686), by the Comunidad de Madrid (RENIM-CM, B2017/BMD-3867, co-financed by the European Structural and Investment Fund; NANOMAGCOST-CM P2018/NMT-4321), by the European COST Actions CA17115 (MyWave) and CA17140 (Nano2Clinic), by the Spanish Scientific Network HiperNano (RED2018-102626-T) and by the European Commission Horizon 2020 project NanoTBTech (Grant Number: 801305). D.G.-C. acknowledges CAM for funding PEJ-2018-AI/IND-11245. A.B. acknowledges funding from Comunidad de Madrid through TALENTO grant ref. 2019-T1/IND-14014. E.X. is grateful for a Juan de la Cierva Formación scholarship (FJC2018-036734-I). R.M. acknowledges the support of the European Commission through the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie Grant agreement N 797945 (LANTERNS). A. E. acknowledges the support from Comunidad de Madrid (Talento project 2018-T1/IND-1005) and from AECC (Ideas Semilla 2019 project). P.R.S. is grateful for a Juan de la Cierva Incorporación scholarship (IJC2019-041915-I). Procedures involving animal experiments were approved by the regional authority for animal experimentation of the Comunidad de Madrid and were conducted in agreement with the Universidad Autónoma de Madrid Ethics Committee, in compliance with the European Union directives 63/2010UE and Spanish regulation RD 53/2013

Automatic Cardiac Gating of Small-animal PET from List-mode Data

Proceedings of: 11th International Meeting on Fully Three-Dimensional Image Reconstruction in Radiology and Nuclear Medicine (Fully 3D 2011). 11-15 July, 2011, Potsdam, Germany.This work presents a method to obtain automatically the cardiac gating signal in a PET study of rats, by employing the variation with time of the counts in the cardiac region, that can be extracted from list-mode data. In an initial step, the cardiac region is identified in the image space by backward-projecting a small fraction of the acquired data and studying the variation with time of the counts in each voxel inside said region, with frequencies within 2 and 8 Hz. The region obtained corresponds accurately to the left-ventricle of the heart of the rat. In a second step, the lines-of-response (LORs) connected with this region are found by forward-projecting this region. The time variation of the number of counts in these LORs contains the cardiac motion information that we want to extract. This variation of counts with time is band-pass filtered to reduce noise, and the time signal so obtained is used to create the gating signal. The result was compared with a cardiac gating signal obtained from an ECG acquired simultaneously to the PET study. Reconstructed gated images obtained from both gating information are similar. The method proposed demonstrates that valid cardiac gating signals can be obtained for rats from PET list-mode data.This work was supported in part by AMIT Project funded by CDTI (CENIT Programme), UCM (Grupos UCM, 910059), CPAN (Consolider-Ingenio 2010, CSPD-2007-00042), RECAVA-RETIC network, Comunidad de Madrid (ARTEMIS S2009/DPI-1802), Ministerio de Ciencia e Innovación, Spanish Government (ENTEPRASE grant, PSE-300000-2009-5 and TEC2007-64731/TCM) and European Regional fundsPublicad