title: Detecting microvascular changes in the mouse spleen using optical computed tomography.
abstract: Methods of monitoring drug toxicity in off-target organs are very important in the development of effective and safe drugs. Standard 2-D techniques, such as histology, are prone to sampling errors and can miss important information. We demonstrate a novel application of optical computed tomography (CT) imaging to quantitatively assess, in 3-D, the response of adult murine spleen to off-target drug toxicity induced by treatment with the vascular disrupting agent ZD6126. Reconstructed images from optical CT scans sensitive to haemoglobin absorption reveal detailed, high-contrast 3-D maps of splenic structure and microvasculature. A significant difference in total splenic volume was found between vehicle and ZD6126-treated cohorts, with mean volumes of 61±3mm(3) and 44±3mm(3) respectively (both n=3, p=0.05). Textural statistics for each sample were calculated using grey-level co-occurrence matrices (GLCMs). Standard 2-D GLCM analysis was found to be slice-dependent while 3-D GLCM contrast and homogeneity analysis resulted in separation of the vehicle and ZD6126-treated cohorts over a range of length scales.
authors.affiliation: Cancer Research UK Cancer Imaging Centre, The Institute of Cancer Research, Sutton SM2 5NG, UK. Electronic address: cmcerlean@icr.ac.uk.
authors.forename: Ciara M
authors.initials: CM
authors.lastname: McErlean
authors.affiliation: Cancer Research UK Cancer Imaging Centre, The Institute of Cancer Research, Sutton SM2 5NG, UK. Electronic address: j.boult@icr.ac.uk.
authors.forename: Jessica K R
authors.initials: JK
authors.lastname: Boult
authors.affiliation: Cancer Research UK Cancer Imaging Centre, The Institute of Cancer Research, Sutton SM2 5NG, UK; Royal Marsden NHS Foundation Trust, Sutton, Surrey SM2 5PT, UK. Electronic address: d.collins@icr.ac.uk.
authors.forename: David J
authors.initials: DJ
authors.lastname: Collins
authors.affiliation: Cancer Research UK Cancer Imaging Centre, The Institute of Cancer Research, Sutton SM2 5NG, UK; Royal Marsden NHS Foundation Trust, Sutton, Surrey SM2 5PT, UK. Electronic address: m.leach@icr.ac.uk.
authors.forename: Martin O
authors.initials: MO
authors.lastname: Leach
authors.affiliation: Cancer Research UK Cancer Imaging Centre, The Institute of Cancer Research, Sutton SM2 5NG, UK. Electronic address: s.robinson@icr.ac.uk.
authors.forename: Simon P
authors.initials: SP
authors.lastname: Robinson
authors.affiliation: Cancer Research UK Cancer Imaging Centre, The Institute of Cancer Research, Sutton SM2 5NG, UK; University of Surrey, Guildford, Surrey GU2 7XH, UK. Electronic address: s.doran@icr.ac.uk.
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Doran
mesh_terms: D000818:Animals; D003287:Contrast Media / Q000737:chemistry; D005260:Female; D006454:Hemoglobins / Q000737:chemistry; D021621:Imaging, Three-Dimensional; D051379:Mice; D008807:Mice, Inbred BALB C; D008833:Microcirculation / Q000502:physiology*; D008856:Microscopy, Fluorescence; D009943:Organophosphorus Compounds / Q000737:chemistry; D013154:Spleen / Q000473:pathology*; D041623:Tomography, Optical Coherence
chemical_list: D003287:Contrast Media; D006454:Hemoglobins; C455219:N-acetylcochinol-O-phosphate; D009943:Organophosphorus Compounds
keywords: Optical computed tomography; Spleen microvasculature; Textural analysis; Toxicity; ZD6126