Molecular bioluminescence imaging as a noninvasive tool for monitoring tumor growth and therapeutic response to MRI-guided laser ablation in a rat model of hepatocellular carcinoma

Scott M. Thompson; Matthew R. Callstrom; Bruce E. Knudsen; Jill L. Anderson; Shari L. Sutor; Kim A. Butters; Chaincy Kuo; Joseph P. Grande; Lewis R. Roberts; David A. Woodrum

doi:10.1097/RLI.0b013e31827a4a3f

Molecular bioluminescence imaging as a noninvasive tool for monitoring tumor growth and therapeutic response to MRI-guided laser ablation in a rat model of hepatocellular carcinoma

Scott M. Thompson, Matthew R. Callstrom, Bruce E. Knudsen, Jill L. Anderson, Shari L. Sutor, Kim A. Butters, Chaincy Kuo, Joseph P. Grande, Lewis R. Roberts, David A. Woodrum

Research output: Contribution to journal › Article › peer-review

17 Scopus citations

Abstract

OBJECTIVES: The objective of this study was to quantitatively compare tumor imaging by magnetic resonance imaging (MRI) and molecular bioluminescence imaging (BLI) and test the feasibility of monitoring the effect of MRI-guided laser ablation on tumor viability by 2-dimensional BLI and 3-dimensional diffuse luminescence tomography (3D DLIT) in an orthotopic rat model of hepatocellular carcinoma. MATERIALS AND METHODS: This study was approved by the animal care committee. Rats underwent injection of N1S1 cells stably transfected with an empty vector (n = 3) or a heat shock element luciferase reporter (HSE-luc; n = 4) into the liver. All rats underwent MRI to assess tumor establishment and volume and 2-dimensional BLI to assess tumor luminescence at day 7 with subsequent MRI and 2D BLI and 3D DLIT in select animals at days 14 and 21. Magnetic resonance imaging-guided laser ablation of the tumor was performed with preablation and postablation 2D BLI and/or 3D DLIT (n = 2). The tumors underwent histopathologic analysis to assess tumor viability. RESULTS: The MRI scans demonstrated hyperintense T2-weighted lesions at 3 of 3 and 4 of 4 sites in the empty vector and HSE-luc rats, respectively. Two-dimensional BLI quantitation demonstrated 23.0-fold higher radiance in the HSE-luc group compared with the empty vector group at day 7 (P < 0.01) and a significant correlation with tumor volume by MRI (r = 0.86; P < 0.03). Tumor dimensions by 3D DLIT and MRI demonstrated good agreement. Three-dimensional DLIT quantitation demonstrated better agreement with thepercentage of nonviable tumor by histopathology than did 2D BLI quantitation after the MRI-guided laser ablation. CONCLUSIONS: Bioluminescence imaging is feasible as a noninvasive, quantitative tool for monitoring tumor growth and therapeutic response to thermal ablation in a rat model of hepatocellular carcinoma.

Original language	English (US)
Pages (from-to)	413-421
Number of pages	9
Journal	Investigative radiology
Volume	48
Issue number	6
DOIs	https://doi.org/10.1097/RLI.0b013e31827a4a3f
State	Published - Jun 2013

Keywords

animal model
bioluminescence imaging
hepatocellular carcinoma
laser ablation
magnetic resonance imaging

ASJC Scopus subject areas

Radiology Nuclear Medicine and imaging

Access to Document

10.1097/RLI.0b013e31827a4a3f

Cite this

Thompson, S. M., Callstrom, M. R., Knudsen, B. E., Anderson, J. L., Sutor, S. L., Butters, K. A., Kuo, C., Grande, J. P., Roberts, L. R., & Woodrum, D. A. (2013). Molecular bioluminescence imaging as a noninvasive tool for monitoring tumor growth and therapeutic response to MRI-guided laser ablation in a rat model of hepatocellular carcinoma. Investigative radiology, 48(6), 413-421. https://doi.org/10.1097/RLI.0b013e31827a4a3f

Molecular bioluminescence imaging as a noninvasive tool for monitoring tumor growth and therapeutic response to MRI-guided laser ablation in a rat model of hepatocellular carcinoma. / Thompson, Scott M.; Callstrom, Matthew R.; Knudsen, Bruce E. et al.
In: Investigative radiology, Vol. 48, No. 6, 06.2013, p. 413-421.

Research output: Contribution to journal › Article › peer-review

Thompson, SM, Callstrom, MR, Knudsen, BE, Anderson, JL, Sutor, SL, Butters, KA, Kuo, C, Grande, JP, Roberts, LR & Woodrum, DA 2013, 'Molecular bioluminescence imaging as a noninvasive tool for monitoring tumor growth and therapeutic response to MRI-guided laser ablation in a rat model of hepatocellular carcinoma', Investigative radiology, vol. 48, no. 6, pp. 413-421. https://doi.org/10.1097/RLI.0b013e31827a4a3f

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title = "Molecular bioluminescence imaging as a noninvasive tool for monitoring tumor growth and therapeutic response to MRI-guided laser ablation in a rat model of hepatocellular carcinoma",

abstract = "OBJECTIVES: The objective of this study was to quantitatively compare tumor imaging by magnetic resonance imaging (MRI) and molecular bioluminescence imaging (BLI) and test the feasibility of monitoring the effect of MRI-guided laser ablation on tumor viability by 2-dimensional BLI and 3-dimensional diffuse luminescence tomography (3D DLIT) in an orthotopic rat model of hepatocellular carcinoma. MATERIALS AND METHODS: This study was approved by the animal care committee. Rats underwent injection of N1S1 cells stably transfected with an empty vector (n = 3) or a heat shock element luciferase reporter (HSE-luc; n = 4) into the liver. All rats underwent MRI to assess tumor establishment and volume and 2-dimensional BLI to assess tumor luminescence at day 7 with subsequent MRI and 2D BLI and 3D DLIT in select animals at days 14 and 21. Magnetic resonance imaging-guided laser ablation of the tumor was performed with preablation and postablation 2D BLI and/or 3D DLIT (n = 2). The tumors underwent histopathologic analysis to assess tumor viability. RESULTS: The MRI scans demonstrated hyperintense T2-weighted lesions at 3 of 3 and 4 of 4 sites in the empty vector and HSE-luc rats, respectively. Two-dimensional BLI quantitation demonstrated 23.0-fold higher radiance in the HSE-luc group compared with the empty vector group at day 7 (P < 0.01) and a significant correlation with tumor volume by MRI (r = 0.86; P < 0.03). Tumor dimensions by 3D DLIT and MRI demonstrated good agreement. Three-dimensional DLIT quantitation demonstrated better agreement with thepercentage of nonviable tumor by histopathology than did 2D BLI quantitation after the MRI-guided laser ablation. CONCLUSIONS: Bioluminescence imaging is feasible as a noninvasive, quantitative tool for monitoring tumor growth and therapeutic response to thermal ablation in a rat model of hepatocellular carcinoma.",

keywords = "animal model, bioluminescence imaging, hepatocellular carcinoma, laser ablation, magnetic resonance imaging",

author = "Thompson, {Scott M.} and Callstrom, {Matthew R.} and Knudsen, {Bruce E.} and Anderson, {Jill L.} and Sutor, {Shari L.} and Butters, {Kim A.} and Chaincy Kuo and Grande, {Joseph P.} and Roberts, {Lewis R.} and Woodrum, {David A.}",

year = "2013",

month = jun,

doi = "10.1097/RLI.0b013e31827a4a3f",

language = "English (US)",

volume = "48",

pages = "413--421",

journal = "Investigative radiology",

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T1 - Molecular bioluminescence imaging as a noninvasive tool for monitoring tumor growth and therapeutic response to MRI-guided laser ablation in a rat model of hepatocellular carcinoma

AU - Thompson, Scott M.

AU - Callstrom, Matthew R.

AU - Knudsen, Bruce E.

AU - Anderson, Jill L.

AU - Sutor, Shari L.

AU - Butters, Kim A.

AU - Kuo, Chaincy

AU - Grande, Joseph P.

AU - Roberts, Lewis R.

AU - Woodrum, David A.

PY - 2013/6

Y1 - 2013/6

N2 - OBJECTIVES: The objective of this study was to quantitatively compare tumor imaging by magnetic resonance imaging (MRI) and molecular bioluminescence imaging (BLI) and test the feasibility of monitoring the effect of MRI-guided laser ablation on tumor viability by 2-dimensional BLI and 3-dimensional diffuse luminescence tomography (3D DLIT) in an orthotopic rat model of hepatocellular carcinoma. MATERIALS AND METHODS: This study was approved by the animal care committee. Rats underwent injection of N1S1 cells stably transfected with an empty vector (n = 3) or a heat shock element luciferase reporter (HSE-luc; n = 4) into the liver. All rats underwent MRI to assess tumor establishment and volume and 2-dimensional BLI to assess tumor luminescence at day 7 with subsequent MRI and 2D BLI and 3D DLIT in select animals at days 14 and 21. Magnetic resonance imaging-guided laser ablation of the tumor was performed with preablation and postablation 2D BLI and/or 3D DLIT (n = 2). The tumors underwent histopathologic analysis to assess tumor viability. RESULTS: The MRI scans demonstrated hyperintense T2-weighted lesions at 3 of 3 and 4 of 4 sites in the empty vector and HSE-luc rats, respectively. Two-dimensional BLI quantitation demonstrated 23.0-fold higher radiance in the HSE-luc group compared with the empty vector group at day 7 (P < 0.01) and a significant correlation with tumor volume by MRI (r = 0.86; P < 0.03). Tumor dimensions by 3D DLIT and MRI demonstrated good agreement. Three-dimensional DLIT quantitation demonstrated better agreement with thepercentage of nonviable tumor by histopathology than did 2D BLI quantitation after the MRI-guided laser ablation. CONCLUSIONS: Bioluminescence imaging is feasible as a noninvasive, quantitative tool for monitoring tumor growth and therapeutic response to thermal ablation in a rat model of hepatocellular carcinoma.

AB - OBJECTIVES: The objective of this study was to quantitatively compare tumor imaging by magnetic resonance imaging (MRI) and molecular bioluminescence imaging (BLI) and test the feasibility of monitoring the effect of MRI-guided laser ablation on tumor viability by 2-dimensional BLI and 3-dimensional diffuse luminescence tomography (3D DLIT) in an orthotopic rat model of hepatocellular carcinoma. MATERIALS AND METHODS: This study was approved by the animal care committee. Rats underwent injection of N1S1 cells stably transfected with an empty vector (n = 3) or a heat shock element luciferase reporter (HSE-luc; n = 4) into the liver. All rats underwent MRI to assess tumor establishment and volume and 2-dimensional BLI to assess tumor luminescence at day 7 with subsequent MRI and 2D BLI and 3D DLIT in select animals at days 14 and 21. Magnetic resonance imaging-guided laser ablation of the tumor was performed with preablation and postablation 2D BLI and/or 3D DLIT (n = 2). The tumors underwent histopathologic analysis to assess tumor viability. RESULTS: The MRI scans demonstrated hyperintense T2-weighted lesions at 3 of 3 and 4 of 4 sites in the empty vector and HSE-luc rats, respectively. Two-dimensional BLI quantitation demonstrated 23.0-fold higher radiance in the HSE-luc group compared with the empty vector group at day 7 (P < 0.01) and a significant correlation with tumor volume by MRI (r = 0.86; P < 0.03). Tumor dimensions by 3D DLIT and MRI demonstrated good agreement. Three-dimensional DLIT quantitation demonstrated better agreement with thepercentage of nonviable tumor by histopathology than did 2D BLI quantitation after the MRI-guided laser ablation. CONCLUSIONS: Bioluminescence imaging is feasible as a noninvasive, quantitative tool for monitoring tumor growth and therapeutic response to thermal ablation in a rat model of hepatocellular carcinoma.

KW - animal model

KW - bioluminescence imaging

KW - hepatocellular carcinoma

KW - laser ablation

KW - magnetic resonance imaging

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Molecular bioluminescence imaging as a noninvasive tool for monitoring tumor growth and therapeutic response to MRI-guided laser ablation in a rat model of hepatocellular carcinoma

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