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Preclinical validation bioimaging - Services

Preclinical validation bioimaging – Services

U25-S05. Preclinical horizontal spectrometer Biospec 7T (Onsite&Remote) OUTSTANDING

Preclinical horizontal spectrometer Biospec 7T (Onsite&Remote) OUTSTANDING

7T Bruker BioSpec 70/30 USR MR system (Bruker BioSpin GmbH, Karlsruhe, Germany) equipped with a BGA12 mini-imaging gradient insert (maximum amplitude: 400 mT/m and slew rate: 5500 T/m/s). Capability for magnetic resonance imaging and spectroscopy of small animals (e.g. mouse, rat) and studies of model solutions (e.g. new contrast agents). Also capabilities for advanced imaging techniques such as diffusion and perfusion weighted images and fractional anisotropy. Coupled with anaesthetic equipment and vital signs monitoring for in vivo experiments.

Customer benefits

Noninvasive studies of anatomy and biochemical environment depending on the organ. Studies of physiological and pathological anatomy changes with a high resolution level. Magnetic resonance is not based on ionizing radiation and can be performed as many times as needed. Assessment of new therapeutic agents efficacy and novel contrast agents potential. T1, T2 and T2* maps measurement.

Target customer

Research groups or companies working with preclinical models, novel therapeutic or contrast agents, characterization of novel preclinical models based in cancer, inflammatory or neurological diseases.

References

  • Zhang S, et al. Metal-Free Radical Dendrimers as MRI Contrast Agents for Glioblastoma Diagnosis: Ex Vivo and In Vivo Approaches. Biomacromolecules. 2022 Jul 11;23(7):2767-2777. doi: 10.1021/acs.biomac.2c00088. Epub 2022 Jun 24. PMID: 35749573; PMCID: PMC9277593.
  • García-Pardo J, et al. Bioinspired Theranostic Coordination Polymer Nanoparticles for Intranasal Dopamine Replacement in Parkinson’s Disease. ACS Nano. 2021 May 25;15(5):8592-8609. doi: 10.1021/acsnano.1c00453. Epub 2021 Apr 22. PMID: 33885286; PMCID: PMC8558863.
  • Wu S, et al. Anti-tumour immune response in GL261 glioblastoma generated by Temozolomide Immune-Enhancing Metronomic Schedule monitored with MRSI-based nosological images. NMR Biomed. 2020 Apr;33(4):e4229. doi: 10.1002/nbm.4229. Epub 2020 Jan 11. PMID: 31926117.
  • Güell-Bosch J, et al. Progression of Alzheimer’s disease and effect of scFv-h3D6 immunotherapy in the 3xTg-AD mouse model: An in vivo longitudinal study using Magnetic Resonance Imaging and Spectroscopy. NMR Biomed. 2020 May;33(5):e4263. doi: 10.1002/nbm.4263. Epub 2020 Feb 17. PMID: 32067292.
  • Suárez-García S, et al. Dual T1/ T2 Nanoscale Coordination Polymers as Novel Contrast Agents for MRI: A Preclinical Study for Brain Tumor. ACS Appl Mater Interfaces. 2018 Nov 14;10(45):38819-38832. doi: 10.1021/acsami.8b15594. Epub 2018 Nov 1. PMID: 30351897.
  • Lope-Piedrafita, S. (2018). Diffusion Tensor Imaging (DTI). In: García Martín, M., López Larrubia, P. (eds) Preclinical MRI. Methods in Molecular Biology, vol 1718. Humana Press, New York, NY. doi: 10.1007/978-1-4939-7531-0_7
  • Arias-Ramos N, et al. Metabolomics of Therapy Response in Preclinical Glioblastoma: A Multi-Slice MRSI-Based Volumetric Analysis for Noninvasive Assessment of Temozolomide Treatment. Metabolites. 2017 May 18;7(2):20. doi: 10.3390/metabo7020020. PMID: 28524099; PMCID: PMC5487991.
  • Jiménez-Xarrié E, et al. Brain metabolic pattern analysis using a magnetic resonance spectra classification software in experimental stroke. BMC Neurosci. 2017 Jan 13;18(1):13. doi: 10.1186/s12868-016-0328-x. PMID: 28086802; PMCID: PMC5237280.
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U25-S06. Dynamic nuclear polarizer HyperSense® (Onsite&Remote) OUTSTANDING

Dynamic nuclear polarizer HyperSense® (Onsite&Remote) OUTSTANDING

Sheltered magnet of 3.35T. Integrated microwave source Elva-1™ VCOM-10, frequency ≈ 94 GHz. BOC Edwards™ E2M80 Series Vacuum Pump. Sample dissolution and automatic transfer system from polarizer to Bruker 600 MHz spectrometer

Customer benefits

DNP significantly boosts the sensitivity of NMR experiments, enabling the detection of nuclei present at low concentrations or in low abundance compared to conventional NMR techniques. It can be used in metabolomics studies to analyze metabolic pathways, identify metabolites, and investigate metabolic fluxes in biological samples such as tissues, cells, and biofluids. Provides real-time monitoring of chemical reactions and kinetics, providing valuable information about reaction mechanisms, intermediate species, and reaction rates.

Target customer

Researchers or companies with needs to enhance sensitivity and elucidate metabolic pathways or changes occurred during therapy, for example, changes in the glycolytic metabolism within tumor cells. Polarized samples can be used for further in vitro or in vivo experiments depending on the information needed.

References

  • Monteagudo E, Virgili A, Parella T, Pérez-Trujillo M. Chiral Recognition by Dissolution DNP NMR Spectroscopy of 13C-Labeled dl-Methionine. Anal Chem. 2017 May 2;89(9):4939-4944. doi: 10.1021/acs.analchem.7b00156. Epub 2017 Apr 21. PMID: 28394124.
  • Chavarria L, Romero-Giménez J, Monteagudo E, Lope-Piedrafita S, Cordoba J. Real-time assessment of ¹³C metabolism reveals an early lactate increase in the brain of rats with acute liver failure. NMR Biomed. 2015 Jan;28(1):17-23. doi: 10.1002/nbm.3226. Epub 2014 Oct 10. PMID: 25303736.
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U25-S07. Focused Microwave Fixation System (Onsite&Remote) OUTSTANDING

Focused Microwave Fixation System (Onsite&Remote) OUTSTANDING

Muromachi Focused Microwave Fixation System 5KW-6402C. The system is configured to mouse (TAW-174A Applicator Head for WJM-28 Mouse Holder). Capable of fast euthanization (miliseconds range) of mice, and also to halt postmortem metabolism in cell suspensions and biopsy samples, allowing further examination without the need of low temperatures to avoid postmortem changes.

Customer benefits

Halting postmortem metabolism may allow for different long-term studies such as 13C NMR (natural abundance), 2D NMR acquisitions, and also to use physiological temperatures without any postmortem deterioration. Still, the halted sample is still valid for histopathological examination if needed.

Target customer

Customers that work with systems subjected to fast postmortem changes which could make detailed studies challenging without the use of extreme, non-physiological conditions.

References

  • Delgado-Goñi T, Campo S, Martín-Sitjar J, Cabañas ME, San Segundo B, Arús C. Assessment of a 1H high-resolution magic angle spinning NMR spectroscopy procedure for free sugars quantification in intact plant tissue. Planta. 2013 Aug;238(2):397-413. doi: 10.1007/s00425-013-1924-y. Epub 2013 Jul 4. PMID: 23824526.
  • Davila M, Candiota AP, Pumarola M, Arus C. Minimization of spectral pattern changes during HRMAS experiments at 37 degrees celsius by prior focused microwave irradiation. MAGMA. 2012 Oct;25(5):401-10. doi: 10.1007/s10334-012-0303-1. PMID: 22286777.
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U25-S08. NMR consultancy for processing and interpreting data (Onsite&Remote)

NMR consultancy for processing and interpreting data (Onsite&Remote)

Possibility of requesting expert advice and guidance while processing and interpreting MR data, especially at the preclinical and clinical levels.

Customer benefits

Customers not willing to install and proceed with a learning curve for using specific software can get expert advice and guidance on metabolite significance, interpretation and meaning.

Target customer

Researchers or companies dealing with MR datasets.

References

El-Abtah ME, Wenke MR, Talati P, Fu M, Kim D, Weerasekera A, He J, Vaynrub A, Vangel M, Rapalino O, Andronesi O, Arrillaga-Romany I, Forst DA, Yen YF, Rosen B, Batchelor TT, Gonzalez RG, Dietrich J, Gerstner ER, Ratai EM. Myo-Inositol Levels Measured with MR Spectroscopy Can Help Predict Failure of Antiangiogenic Treatment in Recurrent Glioblastoma. Radiology. 2022 Feb;302(2):410-418. doi: 10.1148/radiol.2021210826. Epub 2021 Nov 9. PMID: 34751617; PMCID: PMC8805659.

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U25-S09. Access to specific software and database (Remote) OUTSTANDING

Access to specific software and database (Remote) OUTSTANDING

Possibility of access to specific software developed in-house (postprocessing of MR spectroscopy data, conversion of spectroscopic data to canonical format, software for automated classification of MR spectroscopic data, decision support systems), provided disclaimer and agreement are signed. Databases with patient MR imaging and spectroscopic data, as well as epidemiological data from two multicentric european projects.

Customer benefits

Curated databases with a high quality level data for further studies. Software no currently available in public repositories. Interaction with researchers specialized in MR data.

Target customer

Customers willing to apply automated classification to their MR spectroscopic data, or willing to apply their methods to different clinically sound datasets.

References

  • Ungan G, et al. Using Single-Voxel Magnetic Resonance Spectroscopy Data Acquired at 1.5T to Classify Multivoxel Data at 3T: A Proof-of-Concept Study. Cancers (Basel). 2023 Jul 21;15(14):3709. doi: 10.3390/cancers15143709. PMID: 37509372; PMCID: PMC10377805.
  • Hernández-Villegas Y, et al. Extraction of artefactual MRS patterns from a large database using non-negative matrix factorization. NMR Biomed. 2022 Apr;35(4):e4193. doi: 10.1002/nbm.4193. Epub 2019 Dec 2. PMID: 31793715.
  • Hellström J, et al. Evaluation of the INTERPRET decision-support system: can it improve the diagnostic value of magnetic resonance spectroscopy of the brain? Neuroradiology. 2019 Jan;61(1):43-53. doi: 10.1007/s00234-018-2129-7. Epub 2018 Nov 15. PMID: 30443796; PMCID: PMC6336758.
  • Julià-Sapé M, et al. Classification of brain tumours from MR spectra: the INTERPRET collaboration and its outcomes. NMR Biomed. 2016 Mar;29(3):371. doi: 10.1002/nbm.3483. Epub 2015 Dec 22. Erratum for: NMR Biomed. 2015 Dec;28(12):1772-87. Tate, Rosemary A [Corrected to Tate, A Rosemary]. PMID: 26915795.
  • Mocioiu V, et al. From raw data to data-analysis for magnetic resonance spectroscopy–the missing link: jMRUI2XML. BMC Bioinformatics. 2015 Nov 9;16:378. doi: 10.1186/s12859-015-0796-5. PMID: 26552737; PMCID: PMC4640235.
  • Ortega-Martorell S, et al. SpectraClassifier 1.0: a user friendly, automated MRS-based classifier-development system. BMC Bioinformatics. 2010 Feb 24;11:106. doi: 10.1186/1471-2105-11-106. PMID: 20181285; PMCID: PMC2846905.
  • Pérez-Ruiz A, et al. The INTERPRET Decision-Support System version 3.0 for evaluation of Magnetic Resonance Spectroscopy data from human brain tumours and other abnormal brain masses. BMC Bioinformatics. 2010 Nov 29;11:581. doi: 10.1186/1471-2105-11-581. PMID: 21114820; PMCID: PMC3004884.
  • Luts J, et al. A combined MRI and MRSI based multiclass system for brain tumour recognition using LS-SVMs with class probabilities and feature selection. Artif Intell Med. 2007 Jun;40(2):87-102. doi: 10.1016/j.artmed.2007.02.002. Epub 2007 Apr 26. PMID: 17466495.
  • Julià-Sapé M, et al. A multi-centre, web-accessible and quality control-checked database of in vivo MR spectra of brain tumour patients. MAGMA. 2006 Feb;19(1):22-33. doi: 10.1007/s10334-005-0023-x. Epub 2006 Feb 14. PMID: 16477436.

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U24-S02. Medical Imaging for Minimally Invasive Surgery (Onsite&Remote) OUTSTANDING

Medical Imaging for Minimally Invasive Surgery

Advancements in medical technologies have enabled the development and regular use of minimally invasive procedures, which could also be termed image-guided surgery. A platform that can integrate the different imaging techniques is pivotal to aid their development.
NANBIOSIS Unit 24 has medical grade imaging (i.e. Cardiac Magnetic Resonance including delayed enhancement, high performance ultrasound systems, flat panel fluoroscopes, intravascular optical coherence tomography) integrated in a surgical environment, so that these technologies are available for comprehensive follow up of interventions or new surgical approaches. Generally, image acquisition is performed at baseline and serially during the predetermined duration of the study in order to assess the effectiveness of these surgeries on measurable endpoints to document improvement.

Customer benefits

The studies are tailored to the needs of each specific candidate intervention, can be implemented with different follow-up times and can be performed under regulatory requirements, since the performing institution is Certified for Good Laboratory Practices.
Thus the Service can be provided as proof-of-concept studies, full safety and efficacy or under GLPs to meet regulatory agencies’ guidelines and assure clinical translation, so that the customers can take their therapy to a clinical trial faster and more efficiently, thanks to the full range of capabilities offered in this service.

Target customer

The offered service can be of interest to scientists from academia willing to test a possible surgery and perform serial follow up of its outcomes, early-stage medical professionals requiring training in minimally invasive surgery, late-stage surgeons that need to test an idea for an improved surgical approach, commercial companies that need to test the implantation of a device and its effect under GLP studies to commercialize their product.

References

  • Lucas-Cava V, Sánchez-Margallo FM, Dávila-Gómez L, Lima-Rodríguez JR, Sun F. Prostatic artery occlusion versus prostatic artery embolisation for the management of benign prostatic hyperplasia: early results in a canine model. Br J Radiol. 2022 Aug 1;95(1136):20220243. doi: 10.1259/bjr.20220243. Epub 2022 Jul 7. PMID: 35762334; PMCID: PMC10162044.
  • Sánchez-Margallo JA, Tas L, Moelker A, van den Dobbelsteen JJ, Sánchez-Margallo FM, Langø T, van Walsum T, van de Berg NJ. Block-matching-based registration to evaluate ultrasound visibility of percutaneous needles in liver-mimicking phantoms. Med Phys. 2021 Dec;48(12):7602-7612. doi: 10.1002/mp.15305. Epub 2021 Oct 31. PMID: 34665885; PMCID: PMC9298012.
  • Sánchez-Margallo FM, Veloso Brun M, Sánchez-Margallo JA. Identification of intra-abdominal lymphatics in canine carcasses by laparoscopic fluorescence lymphography with intradermal and intrapopliteal ICG administration. PLoS One. 2020 Nov 12;15(11):e0241992. doi: 10.1371/journal.pone.0241992. PMID: 33180854; PMCID: PMC7660503.
  • Sánchez-Peralta LF, Picón A, Sánchez-Margallo FM, Pagador JB. Unravelling the effect of data augmentation transformations in polyp segmentation. Int J Comput Assist Radiol Surg. 2020 Dec;15(12):1975-1988. doi: 10.1007/s11548-020-02262-4. Epub 2020 Sep 28. PMID: 32989680; PMCID: PMC7671995.
  • Crisostomo V et al. Dose-dependent improvement of cardiac function in a swine model of acute myocardial infarction after intracoronary administration of allogeneic heart-derived cells. Stem Cell Res Ther. 2019 May 31;10(1):152. doi: 10.1186/s13287-019-1237-6. PMID: 31151405; PMCID: PMC6544975.
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U23-S03. Micromanipulation and microinjection (Onsite&Remote) OUTSTANDING

Micromanipulation and microinjection oocyte; IMSI system; Embryo biopsy systems (Saturn Laser); vision systems of the mitotic spindle (Oosight system)

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U23-S02. Embryo culture media viability studies (Onsite&Remote) OUTSTANDING

Embryo selection; collection and transport for the study in animal models

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U23-S01. In vitro fertilisation studies and embryo culture media viability (Onsite&Remote) OUTSTANDING

Biopsed of blastomeres; oocyte microinjection; Oocyte and embryo cryopreservation; Implantation Studies

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U21-S01. In vivo Efficay Assays of drugs, nanomedicines, biomaterials and others (Remote) OUTSTANDING

Preclinical efficacy assays in
Preclinical evaluation of efficacy according to European Directives; In vivo models for the pilot feasibility; Biocompatibility. Animal models of human diseases: diabetes, obesity, hypercholesterolemia, hypertriglyceridemia, acute and chronic myocardial infarction, prostatic hyperplasia, ulcers, pleural adhesions, constrictive pericarditis, and abdominal aortic aneurysm among other; Animal species: rodents, rabbits, dogs, cats, pigs and sheep. Creation of different pathologies: oncological, cardiovascular, ophthalmology, transplants, assisted reproduction, cell therapy, etc.
Efficacy and safety of medical devices and biomaterials. Efficacy and toxicity studies of new molecules and pharmaceutical forms.
Murine model embryo tranfers; intracytoplasmic microinjection, oocyte vitrification, measurement and analysis of samples of Natural Killer cells (NK), seminogram and semen studies.

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