MicroCT-Based Virtual Histology Evaluation of Preclinical Medulloblastoma

Purpose 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. Procedures All animal procedures were conducted in...

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Published inMolecular imaging and biology Vol. 13; no. 3; pp. 493 - 499
Main Authors Prajapati, Suresh I., Kilcoyne, Aoife, Samano, Aislynn K., Green, Dustin P., McCarthy, Steven D., Blackman, Barron A., Brady, Michelle M., Zarzabal, Lee Ann, Tatiparthy, Arun K., Sledz, Timothy J., Duong, Timothy, Ohshima-Hosoyama, Sachiko, Giles, Francis J., Michalek, Joel E., Rubin, Brian P., Keller, Charles
Format Journal Article
LanguageEnglish
Published New York Springer-Verlag 01.06.2011
Springer Nature B.V
Subjects
Online AccessGet full text
ISSN1536-1632
1860-2002
1860-2002
DOI10.1007/s11307-010-0372-3

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Abstract Purpose 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. Procedures 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. Results 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 μm 3 for 9-μm isometric resolution microCT vs. 5,416,800 μm 3 for 400 × 111 × 122 μm resolution MRI) at a 28% cost savings ($400 vs. $555 per animal). Conclusion 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.
AbstractList 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.PURPOSEThe 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.PROCEDURESAll 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).RESULTSNine-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.CONCLUSIONThe 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.
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 μm^sup 3^ for 9-μm isometric resolution microCT vs. 5,416,800 μm^sup 3^ 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.[PUBLICATION ABSTRACT]
Purpose 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. Procedures 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. Results 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 μm 3 for 9-μm isometric resolution microCT vs. 5,416,800 μm 3 for 400 × 111 × 122 μm resolution MRI) at a 28% cost savings ($400 vs. $555 per animal). Conclusion 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.
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.
Purpose: 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. Procedures: 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. Results: 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 mu m super(3) for 9- mu m isometric resolution microCT vs. 5,416,800 mu m super(3) for 400111122 mu m resolution MRI) at a 28% cost savings ($400 vs. $555 per animal). Conclusion: 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.
Author Ohshima-Hosoyama, Sachiko
Brady, Michelle M.
McCarthy, Steven D.
Giles, Francis J.
Green, Dustin P.
Sledz, Timothy J.
Blackman, Barron A.
Michalek, Joel E.
Rubin, Brian P.
Zarzabal, Lee Ann
Keller, Charles
Prajapati, Suresh I.
Duong, Timothy
Tatiparthy, Arun K.
Kilcoyne, Aoife
Samano, Aislynn K.
AuthorAffiliation 3 Epidemiology and Biostatistics, University of Texas Health Science Center, 7703 Floyd Curl, San Antonio, TX 78229, USA
7 Cellular and Structural Biology, University of Texas Health Science Center, 7703 Floyd Curl, San Antonio, TX 78229, USA
8 Pediatrics University of Texas Health Science Center, 7703 Floyd Curl, San Antonio, TX 78229, USA
1 Greehey Children’s Cancer Research Institute, University of Texas Health Science Center, 8403 Floyd Curl Drive, MC-7784 San Antonio, TX 78229, USA
6 Department of Anatomic Pathology, Cleveland Clinic, Taussig Cancer Center and the Lerner Research Institute, Cleveland, OH, USA
2 Department of Medicine, University of Texas Health Science Center, 7703 Floyd Curl, San Antonio, TX 78229, USA
4 Microphotonics Inc., Allentown, PA, USA
5 Research Imaging Institute, University of Texas Health Science Center, 7703 Floyd Curl, San Antonio, TX 78229, USA
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/20617390$$D View this record in MEDLINE/PubMed
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Cites_doi 10.1097/00005072-199103000-00005
10.1371/journal.pgen.0020061
10.1148/rg.236035168
10.1002/pbc.21968
10.1161/CIRCULATIONAHA.108.829531
10.1182/blood-2002-08-2543
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MRI
Medulloblastoma
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Virtual histology
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References Taniguchi, Cho, Arenkiel (CR3) 2009; 53
Johnson, Hansen, Wu (CR5) 2006; 2
Koeller, Rushing (CR1) 2003; 23
Martinez, Prajapati, Estrada (CR6) 2009; 120
Hideshima, Mitsiades, Akiyama (CR8) 2003; 101
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Palombella, Dutcher (CR7) 1998; 117
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28389781 - Mol Imaging Biol. 2017 Jun;19(3):483. doi: 10.1007/s11307-017-1079-5
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Snippet Purpose 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...
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...
Purpose: 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...
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SubjectTerms Animals
Boronic Acids - pharmacology
Boronic Acids - therapeutic use
Bortezomib
Cerebellum - drug effects
Cerebellum - pathology
Imaging
Magnetic Resonance Imaging
Medicine
Medicine & Public Health
Medulloblastoma - drug therapy
Medulloblastoma - pathology
Mice
Organ Size - drug effects
Pyrazines - pharmacology
Pyrazines - therapeutic use
Radiology
Research Article
Tumor Burden - drug effects
User-Computer Interface
X-Ray Microtomography - methods
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Title MicroCT-Based Virtual Histology Evaluation of Preclinical Medulloblastoma
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