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 in | Molecular imaging and biology Vol. 13; no. 3; pp. 493 - 499 |
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Main Authors | , , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
New York
Springer-Verlag
01.06.2011
Springer Nature B.V |
Subjects | |
Online Access | Get full text |
ISSN | 1536-1632 1860-2002 1860-2002 |
DOI | 10.1007/s11307-010-0372-3 |
Cover
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 |
AuthorAffiliation_xml | – name: 2 Department of Medicine, University of Texas Health Science Center, 7703 Floyd Curl, San Antonio, TX 78229, USA – name: 6 Department of Anatomic Pathology, Cleveland Clinic, Taussig Cancer Center and the Lerner Research Institute, Cleveland, OH, USA – name: 3 Epidemiology and Biostatistics, University of Texas Health Science Center, 7703 Floyd Curl, San Antonio, TX 78229, USA – name: 7 Cellular and Structural Biology, University of Texas Health Science Center, 7703 Floyd Curl, San Antonio, TX 78229, USA – name: 5 Research Imaging Institute, University of Texas Health Science Center, 7703 Floyd Curl, San Antonio, TX 78229, USA – name: 8 Pediatrics University of Texas Health Science Center, 7703 Floyd Curl, San Antonio, TX 78229, USA – name: 4 Microphotonics Inc., Allentown, PA, USA – name: 1 Greehey Children’s Cancer Research Institute, University of Texas Health Science Center, 8403 Floyd Curl Drive, MC-7784 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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CitedBy_id | crossref_primary_10_1002_advs_202201723 crossref_primary_10_1107_S1600577518005489 crossref_primary_10_4236_ojmi_2015_53016 crossref_primary_10_1016_j_jneumeth_2019_108416 crossref_primary_10_1111_jmi_12543 crossref_primary_10_1007_s11060_011_0619_0 crossref_primary_10_1038_nprot_2017_101 crossref_primary_10_1097_MPH_0b013e3182309fe4 crossref_primary_10_1007_s11307_018_1246_3 crossref_primary_10_1159_000398781 |
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Keywords | MicroCT MRI Medulloblastoma Imaging Virtual histology Therapeutics |
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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 CR4 Palombella, Dutcher (CR7) 1998; 117 Roberts, Lynch, Jones, Hart (CR2) 1991; 50 372_CR4 T Hideshima (372_CR8) 2003; 101 372_CR7 E Taniguchi (372_CR3) 2009; 53 JT Johnson (372_CR5) 2006; 2 HG Martinez (372_CR6) 2009; 120 KK Koeller (372_CR1) 2003; 23 RO Roberts (372_CR2) 1991; 50 28389781 - Mol Imaging Biol. 2017 Jun;19(3):483. doi: 10.1007/s11307-017-1079-5 |
References_xml | – volume: 50 start-page: 134 year: 1991 end-page: 144 ident: CR2 article-title: Medulloblastoma: a population-based study of 532 cases publication-title: J Neuropathol Exp Neurol doi: 10.1097/00005072-199103000-00005 – volume: 2 start-page: e61 year: 2006 ident: CR5 article-title: Virtual histology of transgenic mouse embryos for high-throughput phenotyping publication-title: PLoS Genet doi: 10.1371/journal.pgen.0020061 – ident: CR4 – volume: 23 start-page: 1613 year: 2003 end-page: 1637 ident: CR1 article-title: From the archives of the AFIP: medulloblastoma: a comprehensive review with radiologic-pathologic correlation publication-title: Radiographics doi: 10.1148/rg.236035168 – volume: 53 start-page: 136 year: 2009 end-page: 144 ident: CR3 article-title: Bortezomib reverses a post-translational mechanism of tumorigenesis for patched1 haploinsufficiency in medulloblastoma publication-title: Pediatr Blood Cancer doi: 10.1002/pbc.21968 – volume: 120 start-page: 821 year: 2009 end-page: 822 ident: CR6 article-title: Images in cardiovascular medicine: microscopic computed tomography-based virtual histology for visualization and morphometry of atherosclerosis in diabetic apolipoprotein e mutant mice publication-title: Circulation doi: 10.1161/CIRCULATIONAHA.108.829531 – volume: 117 start-page: 455 issue: 2 year: 1998 end-page: 64 ident: CR7 article-title: Identification of the gene encoding the tryptophan synthase beta-subunit from Chlamydomonas reinhardtii publication-title: Plant Physiol. 1998 Jun – volume: 101 start-page: 1530 issue: 4 year: 2003 end-page: 1534 ident: CR8 article-title: Molecular mechanisms mediating antimyeloma activity of proteasome inhibitor PS-341 publication-title: Blood doi: 10.1182/blood-2002-08-2543 – volume: 53 start-page: 136 year: 2009 ident: 372_CR3 publication-title: Pediatr Blood Cancer doi: 10.1002/pbc.21968 – volume: 2 start-page: e61 year: 2006 ident: 372_CR5 publication-title: PLoS Genet doi: 10.1371/journal.pgen.0020061 – volume: 101 start-page: 1530 issue: 4 year: 2003 ident: 372_CR8 publication-title: Blood doi: 10.1182/blood-2002-08-2543 – ident: 372_CR4 – volume: 50 start-page: 134 year: 1991 ident: 372_CR2 publication-title: J Neuropathol Exp Neurol doi: 10.1097/00005072-199103000-00005 – ident: 372_CR7 – volume: 120 start-page: 821 year: 2009 ident: 372_CR6 publication-title: Circulation doi: 10.1161/CIRCULATIONAHA.108.829531 – volume: 23 start-page: 1613 year: 2003 ident: 372_CR1 publication-title: Radiographics doi: 10.1148/rg.236035168 – reference: 28389781 - Mol Imaging Biol. 2017 Jun;19(3):483. doi: 10.1007/s11307-017-1079-5 |
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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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