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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.

ABSTRACT: 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.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.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 the percentage of nonviable tumor by histopathology than did 2D BLI quantitation after the MRI-guided laser ablation.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.

SUBMITTER: Thompson SM

PROVIDER: S-EPMC3904185 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature

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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.

Thompson Scott M SM Callstrom Matthew R MR Knudsen Bruce E BE Anderson Jill L JL Sutor Shari L SL Butters Kim A KA Kuo Chaincy C Grande Joseph P JP Roberts Lewis R LR Woodrum David A DA

Investigative radiology 20130601 6

<h4>Objectives</h4>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.<h4>Materials and methods</h4>This study was approved by the animal care committee. Rats underw ...[more]

PMID: 23262791

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Project description:BackgroundPlacental dysfunction underlies numerous complications of pregnancy. A major obstacle to understanding the roles of potential mediators of placental pathology has been the absence of suitable methods for tissue-specific gene manipulation and sensitive assays for studying gene functions in the placentas of intact animals. We describe a sensitive and noninvasive method of repetitively tracking placenta-specific gene expression throughout pregnancy using lentivirus-mediated transduction of optical reporter genes in mouse blastocysts.Methodology/principal findingsZona-free blastocysts were incubated with lentivirus expressing firefly luciferase (Fluc) and Tomato fluorescent fusion protein for trophectoderm-specific infection and transplanted into day 3 pseudopregnant recipients (GD3). Animals were examined for Fluc expression by live bioluminescence imaging (BLI) at different points during pregnancy, and the placentas were examined for tomato expression in different cell types on GD18. In another set of experiments, blastocysts with maximum photon fluxes in the range of 2.0E+4 to 6.0E+4 p/s/cm(2)/sr were transferred. Fluc expression was detectable in all surrogate dams by day 5 of pregnancy by live imaging, and the signal increased dramatically thereafter each day until GD12, reaching a peak at GD16 and maintaining that level through GD18. All of the placentas, but none of the fetuses, analyzed on GD18 by BLI showed different degrees of Fluc expression. However, only placentas of dams transferred with selected blastocysts showed uniform photon distribution with no significant variability of photon intensity among placentas of the same litter. Tomato expression in the placentas was limited to only trophoblast cell lineages.Conclusions/significanceThese results, for the first time, demonstrate the feasibility of selecting lentivirally-transduced blastocysts for uniform gene expression in all placentas of the same litter and early detection and quantitative analysis of gene expression throughout pregnancy by live BLI. This method may be useful for a wide range of applications involving trophoblast-specific gene manipulations in utero.

Project description:This work explored an elementwise approach to model transcranial MRI-guided focused ultrasound (TcMRgFUS) thermal ablation, a noninvasive approach to neurosurgery. Each element of the phased array transducer was simulated individually and could be simultaneously loaded into computer memory, allowing for rapid (~2.5 s) calculation of the pressure field for different phase offsets used for beam steering and aberration correction. We simulated the pressure distribution for 431 sonications in 32 patients, applied the phase and magnitude values used during treatment, and estimated the resulting temperature rise. We systematically varied the relationship between CT (computerized tomography)-derived skull density and the acoustic attenuation and sound speed to obtain the best agreement between the predictions and MR temperature imaging (MRTI). The optimization was validated with simulations of 396 sonications from 40 additional treatments. After optimization, the predicted and measured heating agreed well (R2: 0.74 patients 1-32; 0.71 patients 33-72). The dimensions and obliquity of the heating in the simulated temperature maps were correlated with the MRTI (R2: 0.62, 0.74, respectively), but the measured heating was more spatially diffuse. The energy needed to achieve ablation varied by an order of magnitude (3.3-36.1 kJ). While this elementwise approach required more computation time up front (the combined simulation matrices were approximately 4.6 times higher than a single large simulation), it could be performed in parallel on a computing cluster. It allows for rapid calculation of the three-dimensional heating at the focus for different phase and magnitude values on the array. We also show how this approach can be used to optimize the relationship between CT-derived skull density and acoustic properties. While the relationships found here need further validation in a larger patient population, these results demonstrate the promise of this approach to model TcMRgFUS.

Project description:ObjectiveMagnetic resonance imaging (MRI)-guided laser interstitial thermal therapy (MRg-LITT) is an alternative to open epilepsy surgery. We assess safety and effectiveness of MRg-LITT for extratemporal lobe epilepsy (ETLE) in patients who are considered less favorable for open resection.MethodsWe retrospectively reviewed sequential cases of patients with focal ETLE who underwent MRg-LITT between 2012 and 2019. Epileptogenic zones were determined from standard clinical and imaging data ± stereoelectroencephalography (SEEG). Standard stereotactic techniques, MRI thermometry, and a commercial laser thermal therapy system were used for ablations. Anatomic MRI was used to calculate ablation volumes. Clinical outcomes were determined longitudinally.ResultsThirty-five patients with mean epilepsy duration of 21.3 ± 12.2 years underwent MRg-LITT for focal ETLE at a mean age 36.4 ± 12.7 years. A mean 2.59 ± 1.45 trajectories per patient were used to obtain ablation volumes of 8.8 ± 7.5 cm3 . Mean follow-up was 27.3 ± 19.5 months. Of 32 patients with >12 months of follow-up, 17 (53%) achieved good outcomes (Engel class I + II) of whom 14 (44%) were Engel class I. Subgroup analysis revealed better outcomes for patients with lesional ETLE than for those who were nonlesional, multifocal, or who had failed prior interventions (P = .02). Of 13 patients showing favorable seizure-onset patterns (localized low voltage fast activity or rhythmic spiking on SEEG) prior to ablation, 9 (69%) achieved good outcomes, whereas only 3 of 11 (27%) who show other slower onset patterns achieved good outcomes. Minor adverse events included six patients with transient sensorimotor neurologic deficits and four patients with asymptomatic hemorrhages along the fiber tract. Major adverse events included one patient with a brain abscess that required stereotactic drainage and one patient with persistent hypothalamic obesity. Three deaths-two seizure-associated and one suicide-were unrelated to surgical procedures.SignificanceMRI-guided laser interstitial thermal therapy (or MRg-LITT) was well-tolerated and yielded good outcomes in a heterogeneous group of ETLE patients. Lesional epilepsy and favorable seizure-onset patterns on SEEG predicted higher likelihoods of success.

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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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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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