MicroCT-based virtual histology evaluation of preclinical medulloblastoma.
The purpose of this paper is to validate a rapid and cost-effective ex vivo technique, microCT-based virtual histology, as an alternative to MRI imaging for assessing the therapeutic response in genetically engineered mouse models of cancer.



All animal procedures were conducted in accordance with the Guidelines for the Care and Use of Laboratory Animals and were approved by the Institutional Animal Care and Use Committee (IACUC) at the University of Texas Health Science Center at San Antonio. MRI imaging was performed on 6-week-old, bortezomib-treated genetically engineered Patched1, p53 mice that recapitulate the characteristics of human medulloblastoma. After MRI scans, the same mice were euthanized to collect brain or spine samples for virtual histology staining followed by microCT scanning.



Nine-micrometer resolution ex vivo micro X-ray computed tomography (microCT)-based virtual histology images were qualitatively reflective of high-field live animal images obtained with magnetic resonance imaging (MRI) and histopathology. Cerebellar volumes on microCT-based virtual histology correlated closely with MRI cerebellar volumes (R = 0.998). MRI and microCT-based virtual histology both indicated a significant difference between cerebellar volumes of untreated and treated mice (p = 0.02 and p = 0.04, respectively). The ex vivo microCT method also allowed a 7,430-fold improvement in voxel resolution (voxel volume of 729 μm³ for 9-μm isometric resolution microCT vs. 5,416,800 μm³ for 400 × 111 × 122 μm resolution MRI) at a 28% cost savings ($400 vs. $555 per animal).



The ex vivo, en bloc technique of microCT-based virtual histology matched MRI in reflecting histopathology. MicroCT-based virtual histology proved to be a more cost-effective technique and less labor-intensive. On the other hand, MRI provides ability to perform in vivo imaging, faster scanning and lower radiation dose by sacrificing the spatial resolution. Thus, both in vivo MRI and ex vivo microCT-based virtual histology are effective means of quantitatively evaluating therapeutic response in preclinical models of cerebellar tumors including the childhood cancer, medulloblastoma.
Prajapati
Suresh I
SI
Greehey Children's Cancer Research Institute, University of Texas Health Science Center, 8403 Floyd Curl Drive, MC-7784, San Antonio, TX, 78229, USA.
Kilcoyne
Aoife
A
Greehey Children's Cancer Research Institute, University of Texas Health Science Center, 8403 Floyd Curl Drive, MC-7784, San Antonio, TX, 78229, USA.|Department of Medicine, University of Texas Health Science Center, 7703 Floyd Curl, San Antonio, TX, 78229, USA.
Samano
Aislynn K
AK
Greehey Children's Cancer Research Institute, University of Texas Health Science Center, 8403 Floyd Curl Drive, MC-7784, San Antonio, TX, 78229, USA.
Green
Dustin P
DP
Greehey Children's Cancer Research Institute, University of Texas Health Science Center, 8403 Floyd Curl Drive, MC-7784, San Antonio, TX, 78229, USA.
McCarthy
Steven D
SD
Greehey Children's Cancer Research Institute, University of Texas Health Science Center, 8403 Floyd Curl Drive, MC-7784, San Antonio, TX, 78229, USA.
Blackman
Barron A
BA
Greehey Children's Cancer Research Institute, University of Texas Health Science Center, 8403 Floyd Curl Drive, MC-7784, San Antonio, TX, 78229, USA.
Brady
Michelle M
MM
Greehey Children's Cancer Research Institute, University of Texas Health Science Center, 8403 Floyd Curl Drive, MC-7784, San Antonio, TX, 78229, USA.
Zarzabal
Lee Ann
LA
Epidemiology and Biostatistics, University of Texas Health Science Center, 7703 Floyd Curl, San Antonio, TX, 78229, USA.
Tatiparthi
Arun K
AK
Microphotonics Inc., Allentown, PA, USA.
Sledz
Timothy J
TJ
Microphotonics Inc., Allentown, PA, USA.
Duong
Timothy
T
Research Imaging Institute, University of Texas Health Science Center, 7703 Floyd Curl, San Antonio, TX, 78229, USA.
Ohshima-Hosoyama
Sachiko
S
Greehey Children's Cancer Research Institute, University of Texas Health Science Center, 8403 Floyd Curl Drive, MC-7784, San Antonio, TX, 78229, USA.
Giles
Francis J
FJ
Department of Medicine, University of Texas Health Science Center, 7703 Floyd Curl, San Antonio, TX, 78229, USA.
Michalek
Joel E
JE
Epidemiology and Biostatistics, University of Texas Health Science Center, 7703 Floyd Curl, San Antonio, TX, 78229, USA.
Rubin
Brian P
BP
Department of Anatomic Pathology, Cleveland Clinic, Taussig Cancer Center and the Lerner Research Institute, Cleveland, OH, USA.
Keller
Charles
C
Greehey Children's Cancer Research Institute, University of Texas Health Science Center, 8403 Floyd Curl Drive, MC-7784, San Antonio, TX, 78229, USA. keller@ohsu.edu.|Cellular and Structural Biology, University of Texas Health Science Center, 7703 Floyd Curl, San Antonio, TX, 78229, USA. keller@ohsu.edu.|Pediatrics University of Texas Health Science Center, 7703 Floyd Curl, San Antonio, TX, 78229, USA. keller@ohsu.edu.
D000818:Animals; D001897:Boronic Acids / Q000494:pharmacology / Q000627:therapeutic use; D000069286:Bortezomib; D002531:Cerebellum / Q000187:drug effects / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008527:Medulloblastoma / Q000188:drug therapy / Q000473:pathology*; D051379:Mice; D009929:Organ Size / Q000187:drug effects; D011719:Pyrazines / Q000494:pharmacology / Q000627:therapeutic use; D047368:Tumor Burden / Q000187:drug effects; D014584:User-Computer Interface; D055114:X-Ray Microtomography / Q000379:methods*
D001897:Boronic Acids; D011719:Pyrazines; D000069286:Bortezomib