Core facilities

Preclinical Imaging

Head

Antonio Esposito

The main goal of the Preclinical Imaging Facility is to develop and validate non-invasive or minimally invasive imaging approaches to visualize pathological processes in pre-clinical mouse models. The Facility was created on the model of technology and expertise sharing, collecting tools and skills necessary to provide a state-of-the-art service of small animal Magnetic Resonance (MRI), Ultrasound (US), Optical Imaging (OI),Radioherapy (RT), Computed Tomography (μCT) and Optical coherence tomography (OCT) to biomedical research groups of OSR, as well as to all external researchers. Moreover, the Facility is equipped with a state of the art image guided small animal irradiator, which allows to mimic all aspects of radiotherapy (RT) treatment in small animal models. Using this technology we can assess the response of tumours and normal tissues to different RT or combined therapeutic strategies. In addition, tailored image analysis and post processing techniques are developed in order to extract data and features from images.

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Services

Non-invasive preclinical imaging represents an essential tool to develop a modern and translational biomedical research. From this perspective, the imaging tools included in the Facility provide a wide range of multidimensional information on tissue physiology combined with traditional anatomic images. Therefore, it is possible to functionally and structurally characterize the phenotype of mouse disease models and genetically modified mouse models, gaining insights into disease pathogenesis and development. Moreover, these preclinical imaging approaches provide the unique opportunity to perform longitudinal studies of the same animal, minimizing experimental variability and number of animals per study.

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Fees

Equipments	Fee per user
7 Tesla MRI	Internal: 110 € External (no profit/ for profit): 150/250 €
MRI contrast agents	Market price
Vevo 2100 user operated	Internal user: 40 € External (no profit/ for profit): 65/100 €
Vevo 2100 core operated	Internal user: 65 € External (no profit/ for profit): 104/160 €
Vevo 2100 contrast enhanced studies	Market price
IVIS SpectrumCT user operated (2d mode only)	Internal user: 49 € External (no profit/ for profit): 78/120 €
IVIS SpectrumCT core operated	Internal user: 73 € External (no profit/ for profit): 117/180 €
IVIS SpectrumCT reagents	Market price
Preclinical Radiotherapy	Internal user: 126 € External (no profit/ for profit): 196/280 €
Retinal Fluorangiography - OCT	Internal user: 45 € External (no profit/ for profit): 75/120 €
Retinal Fluorangiography - OCT core operated	Internal user: 68 € External (no profit/ for profit): 113/180 €
Image analysis	Internal user: 65 € External (no profit/ for profit): 80/80 €

The Facility has an internal animal housing service to accommodate mice undergoing long-term follow-up with imaging. This service is managed by the central Animal Facility (dr. Enzo Oriani, dr. Sofia Ghiandoni) at a cost of 1,35€/per cage/per day.

Selected publications

Dugnani E, Pasquale V, Marra P, Liberati D, Canu T, Perani L, De Sanctis F, Ugel S, Invernizzi F, Citro A, Venturini M, Doglioni C, Esposito A, Piemonti L. Four-class tumor staging for early diagnosis and monitoring of murine pancreatic cancer using magnetic resonance and ultrasound. Carcinogenesis. 2018 Sep 21;39(9):1197-1206.

Casella G, Colombo F, Finardi A, Descamps H, Ill-Raga G, Spinelli A, Podini P, Bastoni M, Martino G, Muzio L, Furlan R. Extracellular Vesicles Containing IL-4 Modulate Neuroinflammation in a Mouse Model of Multiple Sclerosis. Mol Ther. 2018 Sep 5;26(9):2107-2118.

Calcinotto A, Spataro C, Zagato E, Di Mitri D, Gil V, Crespo M, De Bernardis G, Losa M, Mirenda M, Pasquini E, Rinaldi A, Sumanasuriya S, Lambros MB, Neeb A, Lucianò R, Bravi CA, Nava-Rodrigues D, Dolling D, Prayer-Galetti T, Ferreira A, Briganti A, Esposito A, Barry S, Yuan W, Sharp A, de Bono J, Alimonti A.IL-23 secreted by myeloid cells drives castration-resistant prostate cancer. Nature. 2018 Jul;559(7714):363-369.

Adamiano A, Iafisco M, Sandri M, Basini M, Arosio P, Canu T, Sitia G, Esposito A, Iannotti V, Ausanio G, Fragogeorgi E, Rouchota M, Loudos G, Lascialfari A, Tampieri A.On the use of superparamagnetic hydroxyapatite nanoparticles as an agent for magnetic and nuclear in vivo imaging. Acta Biomater. 2018 Jun;73:458-469.

Pisani C, Strimpakos G, Gabanella F, Di Certo MG, Onori A, Severini C, Luvisetto S, Farioli-Vecchioli S, Carrozzo I, Esposito A, Canu T, Mattei E, Corbi N, Passananti C. Utrophin up-regulation by artificial transcription factors induces muscle rescue and impacts the neuromuscular junction in mdx mice. Biochim Biophys Acta Mol Basis Dis. 2018 Apr;1864(4 Pt A):1172-1182.

Belloli S, Zanotti L, Murtaj V, Mazzon C, Di Grigoli G, Monterisi C, Masiello V, Iaccarino L, Cappelli A, Poliani PL, Politi LS, Moresco RM. 18F-VC701-PET and MRI in the in vivo neuroinflammation assessment of a mouse model of multiple sclerosis. J Neuroinflammation. 2018 Feb 5;15(1):33.

Buccarello L, Sclip A, Sacchi M, Castaldo A M, Bertani I, ReCecconi A, Maestroni S, Zerbini G, Nucci P, Borsello T. The c-jun N-terminal kinase plays a key role in ocular degenerative changes in a mouse model of Alzheimer disease suggesting a correlation between ocular and brain pathologies. Oncotarget. 2017 Oct 10; 8(47): 83038–83051.

Locafaro G, Andolfi G, Russo F, Cesana L, Spinelli A, Camisa B, Ciceri F, Lombardo A, Bondanza A, Roncarolo MG, Gregori S. IL-10-Engineered Human CD4(+) Tr1 Cells Eliminate Myeloid Leukemia in an HLA Class I-Dependent Mechanism. Mol Ther. 2017 Oct 4;25(10):2254-2269.

Corti A, Gasparri AM, Ghitti M, Sacchi A, Sudati F, Fiocchi M, Buttiglione V, Perani L, Gori A, Valtorta S, Moresco RM, Pastorino F, Ponzoni M, Musco G, Curnis F. Glycine N-methylation in NGR-Tagged Nanocarriers Prevents Isoaspartate formation and Integrin Binding without Impairing CD13 Recognition and Tumor Homing. Adv Funct Mater. 2017 Sep 26;27(36).

Zaccagnini G, Maimone B, Fuschi P, Maselli D, Spinetti G, Gaetano C, Martelli F. Overexpression of miR-210 and its significance in ischemic tissue damage. Sci Rep. 2017 Aug 25;7(1):9563.

Mastaglio S, Genovese P, Magnani Z, Ruggiero E, Landoni E, Camisa B, Schiroli G, Provasi E, Lombardo A, Reik A, Cieri N, Rocchi M, Oliveira G, Escobar G, Casucci M, Gentner B, Spinelli A, Mondino A, Bondanza A, Vago L, Ponzoni M, Ciceri F, Holmes MC, Naldini L, Bonini C. NY-ESO-1 TCR single edited stem and central memory T cells to treat multiple myeloma without graft-versus-host disease. Blood. 2017 Aug 3;130(5):606-618.

Dugnani E, Pasquale V, Liberati D, Citro A, Cantarelli E, Pellegrini S, Marra P, Canu T, Balzano G, Scavini M, Esposito A, Doglioni C, Piemonti L. Modeling the Iatrogenic Pancreatic Cancer Risk After Islet Autotransplantation in Mouse. Am J Transplant. 2017 Oct;17(10):2720-2727. doi: 10.1111/ajt.14360. Epub 2017 Jun 12.

Lidonnici MR, Aprile A, Frittoli MC, Mandelli G, Paleari Y, Spinelli A, Gentner B, Zambelli M, Parisi C, Bellio L, Cassinerio E, Zanaboni L, Cappellini MD, Ciceri F, Marktel S, Ferrari G. Plerixafor and G-CSF combination mobilizes hematopoietic stem and progenitors cells with a distinct transcriptional profile and a reduced in vivo homing capacity compared to plerixafor alone. Haematologica. 2017 Apr;102(4):e120-e124.

Curnis F, Dallatomasina A, Bianco M, Gasparri A, Sacchi A, Colombo B, Fiocchi M, Perani L, Venturini M, Tacchetti C, Sen S, Borges R, Dondossola E, Esposito A, Mahata SK, Corti A. Regulation of tumor growth by circulating full-length chromogranin A. Oncotarget. 2016 Nov 8;7(45):72716-72732.

Cappato S, Tonachini L, Giacopelli F, Tirone M, Galietta LJ, Sormani M, Giovenzana A, Spinelli AE, Canciani B, Brunelli S, Ravazzolo R, Bocciardi R. High-throughput screening for modulators of ACVR1 transcription: discovery of potential therapeutics for fibrodysplasia ossificans progressiva. Dis Model Mech. 2016 Jun 1;9(6):685-96.

Migliavacca J, Percio S, Valsecchi R, Ferrero E, Spinelli A, Ponzoni M, Tresoldi C, Pattini L, Bernardi R, Coltella N. Hypoxia inducible factor-1α regulates a pro-invasive phenotype in acute monocytic leukemia. Oncotarget. 2016 Aug 16;7(33):53540-53557.

Saita D, Ferrarese R, Foglieni C, Esposito A, Canu T, Perani L, Ceresola ER, Visconti L, Burioni R, Clementi M, Canducci F.Adaptive immunity against gut microbiota enhances apoE-mediated immune regulation and reduces atherosclerosis and western-diet-related inflammation. Sci Rep. 2016 Jul 7;6:29353.

Greco S, Zaccagnini G, Perfetti A, Fuschi P, Valaperta R, Voellenkle C, Castelvecchio S, Gaetano C, Finato N, Beltrami AP, Menicanti L, Martelli F. Long noncoding RNA dysregulation in ischemic heart failure. J Transl Med. 2016 Jun 18;14(1):183.

Cottone L, Capobianco A, Gualteroni C, Monno A, Raccagni I, Valtorta S, Canu T, Di Tomaso T, Lombardo A, Esposito A, Moresco RM, Maschio AD, Naldini L, Rovere-Querini P, Bianchi ME, Manfredi AA. Leukocytes recruited by tumor-derived HMGB1 sustain peritoneal carcinomatosis. Oncoimmunology. 2016 Jan 8;5(5):e1122860.

Mezzapelle R, Rrapaj E, Gatti E, Ceriotti C, Marchis FD, Preti A, Spinelli AE, Perani L, Venturini M, Valtorta S, Moresco RM, Pecciarini L, Doglioni C, Frenquelli M, Crippa L, Recordati C, Scanziani E, de Vries H, Berns A, Frapolli R, Boldorini R, D'Incalci M, Bianchi ME, Crippa MP. Human malignant mesothelioma is recapitulated in immunocompetent BALB/c mice injected with murine AB cells. Sci Rep. 2016 Mar 10;6:22850.

Catarinella M, Monestiroli A, Escobar G, Fiocchi A, Tran NL, Aiolfi R, Marra P, Esposito A, Cipriani F, Aldrighetti L, Iannacone M, Naldini L, Guidotti LG, Sitia G. IFNα gene/cell therapy curbs colorectal cancer colonization of the liver by acting on the hepatic microenvironment. EMBO Mol Med. 2016 Feb 1;8(2):155-70.

Zaccagnini G, Palmisano A, Canu T, Maimone B, Lo Russo FM, Ambrogi F, Gaetano C, De Cobelli F, Del Maschio A, Esposito A, Martelli F.Magnetic Resonance Imaging Allows the Evaluation of Tissue Damage and Regeneration in a Mouse Model of Critical Limb Ischemia. PLoS One. 2015 Nov 10;10(11):e0142111.

Chiaravalli M, Rowe I, Mannella V, Quilici G, Canu T, Bianchi V, Gurgone A, Antunes S, D'Adamo P, Esposito A, Musco G, Boletta A. 2-Deoxy-d-Glucose Ameliorates PKD Progression. J Am Soc Nephrol. 2016 Jul;27(7):1958-69.

Catucci M, Zanoni I, Draghici E, Bosticardo M, Castiello MC, Venturini M, Cesana D, Montini E, Ponzoni M, Granucci F, Villa A. Wiskott-Aldrich syndrome protein deficiency in natural killer and dendritic cells affects antitumor immunity. Eur J Immunol. 2014 Apr;44(4):1039-45.

Instrumentation

The facility is equipped with a 7 Tesla small-bore Magnetic Resonance (MR) scanner (Bruker BioSpec® 70/30), a high-resolution digital Ultrasound system (Vevo® 2100, Visualsonic) and a small animal Optical-CT scanner (IVIS SpectrumCT®, Perkin Elmer) and a Micron IV Retinal Imaging Microscope (Phoenix Reasearch Labs), which are managed by a team of Radiologists, Technicians, Physicists and Biologists who developed a deep experience in preclinical research after a wide clinical training.

7 Tesla small-bore Magnetic Resonance (MR) scanner (Bruker BioSpec® 70/30)

High-resolution digital Ultrasound system (Vevo® 2100, Visualsonic)

Small animal Optical-CT scanner (IVIS SpectrumCT® Perkin Elmer)

Micron IV Retinal Imaging Microscope and Image-guided OCT (Phoenix Research Labs, Pleasanton, CA, USA)

Small animal image guided precision irradiator for radiotherapy (XRAD225Cx SmART, Precision x-ray)

This organization provides an open platform suitable for the development of tailored imaging protocols based on the specific needs of each research group. The Facility includes also two rooms for animal housing dedicated to mice and rats undergoing to longitudinal imaging experiments (about 5000 mice), connected to an animal preparation/microsurgery room. Imaging laboratories are equipped with gas anesthesia systems and physiologic monitoring that allows gated imaging.