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Erschienen in:

01.09.2012 | Experimental

High accuracy of mesoscopic epi-fluorescence tomography for non-invasive quantitative volume determination of fluorescent protein-expressing tumours in mice

verfasst von: Lotfi Abou-Elkacem, Saskia Björn, Dennis Doleschel, Vasilis Ntziachristos, Ralf Schulz, Robert M. Hoffman, Fabian Kiessling, Wiltrud Lederle

Erschienen in: European Radiology | Ausgabe 9/2012

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Abstract

Objectives

To compare mesoscopic epi-fluorescence tomography (MEFT) and EPRI-illumination reflectance imaging (EPRI) for quantitative tumour size assessment in mice.

Methods

Tumour xenografts of green/red fluorescent protein (GFP/RFP)-expressing colon cancer cells were measured using MEFT, EPRI, ultrasound (US) and micro computed tomography (μCT) at day 14 post-injection (n = 6). Results from MEFT and EPRI were correlated with each other and with US and μCT (reference methods). Tumour volumes were measured ex vivo by GFP and RFP fluorescence imaging on cryoslices and compared with the in vivo measurements.

Results

High correlation and congruency were observed between MEFT, US and μCT (MEFT/US: GFP: r ² = 0.96; RFP: r ² = 0.97, both P < 0.05; MEFT/μCT: GFP: r ² = 0.93; RFP: r ² = 0.90; both P < 0.05). Additionally, in vivo MEFT data were highly correlated and congruent with ex vivo cryoslice imaging results (GFP: r ² = 0.96; RFP: r ² = 0.99; both P < 0.05). In comparison, EPRI significantly overestimated tumour volumes (P < 0.05), although there was a significant correlation with US and μCT (EPRI/US: GFP: r ² = 0.95; RFP: r ² = 0.94; both P < 0.05; EPRI/μCT GFP: r ² = 0.86; RFP: r ² = 0.86; both P < 0.05).

Conclusions

Fluorescence distribution reconstruction using MEFT affords highly accurate three-dimensional (3D) tumour volume data showing superior accuracy compared to EPRI. Thus, MEFT is a very suitable technique for quantitatively assessing fluorescence distribution in superficial tumours at high spatial resolution.

Key Points

• Mesoscopic epi-fluorescence tomography (MEFT) is an important new molecular imaging technique.

• MEFT allows accurate size determination of superficial tumours with high resolution.

• MEFT is a suitable technique for longitudinal assessment of tumour growth.

• MEFT allows 3D reconstruction and quantification of fluorescence distributions.

Graham KC, Wirtzfeld LA, MacKenzie LT et al (2005) Three-dimensional high-frequency ultrasound imaging for longitudinal evaluation of liver metastases in preclinical models. Cancer Res 65:5231–5237PubMedCrossRef

Wessels JT, Busse AC, Mahrt J, Dullin C, Grabbe E, Mueller GA (2007) In vivo imaging in experimental preclinical tumor research–a review. Cytometry 71:542–549PubMedCrossRef

Weissleder R, Pittet MJ (2008) Imaging in the era of molecular oncology. Nature 452:580–589PubMedCrossRef

Hoffman RM (2005) The multiple uses of fluorescent proteins to visualize cancer in vivo. Nat Rev Cancer 5:796–806PubMedCrossRef

Abou-Elkacem L, Gremse F, Barth S, Hoffman RM, Kiessling F, Lederle W (2011) Comparison of μCT, MRI and optical reflectance imaging for assessing the growth of GFP/RFP-expressing tumors. Anticancer Res 31:2907–2913PubMed

Ntziachristos V, Ripoll J, Wang LV, Weissleder R (2005) Looking and listening to light: the evolution of whole-body photonic imaging. Nat Biotech 23:313–320CrossRef

Björn S, Ntziachristos V, Schulz R (2010) Mesoscopic epifluorescence tomography: reconstruction of superficial and deep fluorescence in highly-scattering media. Opt Express 18:8422–8429PubMedCrossRef

Björn S, Englmeier KH, Ntziachristos V, Schulz R (2011) Reconstruction of fluorescence distribution hidden in biological tissue using mesoscopic epifluorescence tomography. J Biomed Opt 16:046005PubMedCrossRef

Jiang P, Yamauchi K, Yang M et al (2006) Tumor cells genetically labeled with GFP in the nucleus and RFP in the cytoplasm for imaging cellular dynamics. Cell Cycle 5:1198–1201PubMedCrossRef

10.

Yamamoto N, Jiang P, Yang M et al (2004) Cellular dynamics visualized in live cells in vitro and in vivo by differential dual-color nuclear-cytoplasmic fluorescent-protein expression. Cancer Res 64:4251–4256PubMedCrossRef

11.

Hoffman RM, Yang M (2006) Subcellular imaging in the live mouse. Nat Protoc 1:775–782PubMedCrossRef

12.

Cheung AMY, Brown AS, Hastie LA et al (2005) Three-dimensional ultrasound biomicroscopy for xenograft growth analysis. Ultrasound Med Biol 31:865–870PubMedCrossRef

13.

Sarantopoulos A, Themelis G, Ntziachristos V (2010) Imaging the bio-distribution of fluorescent probes using multispectral epi-illumination cryoslicing imaging. Mol Imaging Biol 13:874–885CrossRef

14.

Ntziachristos V (2010) Going deeper than microscopy: the optical imaging frontier in biology. Nat Methods 7:603–614CrossRef

15.

Vinegoni C, Pitsouli C, Razansky D, Perrimon N, Ntziachristos V (2007) In vivo imaging of Drosophila melanogaster pupae with mesoscopic fluorescence tomography. Nat Methods 5:45–47PubMedCrossRef

16.

Weissleder R, Ntziachristos V (2003) Shedding light onto live molecular targets. Nat Med 9:123–128PubMedCrossRef

17.

Crane LMA, Themelis G, Pleijhuis RG et al (2011) Intraoperative multispectral fluorescence imaging for the detection of the sentinel lymph node in cervical cancer: a novel concept. Mol Imaging Biol 13:1043–1049PubMedCrossRef

18.

van Dam GM, Themelis G, Crane LMA et al (2011) Intraoperative tumor-specific fluorescence imaging in ovarian cancer by folate receptor-α targeting: first in-human results. Nat Med 17:1315–1319PubMedCrossRef

19.

Katz MH, Takimoto S, Spivack D, Moossa AR, Hoffman RM, Bouvet M (2003) A novel red fluorescent protein orthotopic pancreatic cancer model for the preclinical evaluation of chemotherapeutics. J Surg Res 113:151–160PubMedCrossRef

20.

Deliolanis NC, Wurdinger T, Pike L et al (2011) In vivo tomographic imaging of red-shifted fluorescent proteins. Biomed Opt Express 2:887–900PubMedCrossRef

Titel: High accuracy of mesoscopic epi-fluorescence tomography for non-invasive quantitative volume determination of fluorescent protein-expressing tumours in mice
verfasst von: Lotfi Abou-Elkacem
Saskia Björn
Dennis Doleschel
Vasilis Ntziachristos
Ralf Schulz
Robert M. Hoffman
Fabian Kiessling
Wiltrud Lederle
Publikationsdatum: 01.09.2012
Verlag: Springer-Verlag
Erschienen in: European Radiology / Ausgabe 9/2012
Print ISSN: 0938-7994
Elektronische ISSN: 1432-1084
DOI: https://doi.org/10.1007/s00330-012-2462-x

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High accuracy of mesoscopic epi-fluorescence tomography for non-invasive quantitative volume determination of fluorescent protein-expressing tumours in mice