title: Combined MR, fluorescence and histology imaging strategy in a human breast tumor xenograft model.
abstract: Applications of molecular imaging in cancer and other diseases frequently require the combination of in vivo imaging modalities, such as MR and optical imaging, with ex vivo optical, fluorescence, histology and immunohistochemical imaging to investigate and relate molecular and biological processes to imaging parameters within the same region of interest. We have developed a multimodal image reconstruction and fusion framework that accurately combines in vivo MRI and MRSI, ex vivo brightfield and fluorescence microscopic imaging and ex vivo histology imaging. Ex vivo brightfield microscopic imaging was used as an intermediate modality to facilitate the ultimate link between ex vivo histology and in vivo MRI/MRSI. Tissue sectioning necessary for optical and histology imaging required the generation of a three-dimensional reconstruction module for two-dimensional ex vivo optical and histology imaging data. We developed an external fiducial marker-based three-dimensional reconstruction method, which was able to fuse optical brightfield and fluorescence with histology imaging data. The registration of the three-dimensional tumor shape was pursued to combine in vivo MRI/MRSI and ex vivo optical brightfield and fluorescence imaging data. This registration strategy was applied to in vivo MRI/MRSI, ex vivo optical brightfield/fluorescence and histology imaging datasets obtained from human breast tumor models. Three-dimensional human breast tumor datasets were successfully reconstructed and fused with this platform.
authors.affiliation: The Johns Hopkins University In Vivo Cellular and Molecular Imaging Center, Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Lu
authors.initials: L
authors.lastname: Jiang
authors.forename: Tiffany R
authors.initials: TR
authors.lastname: Greenwood
authors.forename: Erika R Amstalden
authors.initials: ER
authors.lastname: van Hove
authors.forename: Kamila
authors.initials: K
authors.lastname: Chughtai
authors.forename: Venu
authors.initials: V
authors.lastname: Raman
authors.forename: Paul T
authors.initials: PT
authors.lastname: Winnard
authors.forename: Ron M A
authors.initials: RM
authors.lastname: Heeren
authors.forename: Dmitri
authors.initials: D
authors.lastname: Artemov
authors.forename: Kristine
authors.initials: K
authors.lastname: Glunde
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis*; D001706:Biopsy / Q000379:methods*; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000378:metabolism*; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D051379:Mice; D008819:Mice, Nude; D008856:Microscopy, Fluorescence / Q000379:methods*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013382:Subtraction Technique
chemical_list: D014408:Biomarkers, Tumor