Molecular Imaging, vol. 12

2. 3D Fusion Framework for Infarction and Angiogenesis Analysis in a Myocardial Infarct Minipig Model

   Xu Zhenzhen, PhD¹, Bo Tao, PhD, MD², Yu Li, MSc¹, Jun Zhang, PhD¹, Xiaochao Qu, PhD¹, Feng Cao, PhD², Jimin Liang, PhD¹
   Molecular Imaging, vol. 16, First Published May 11, 2017.
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   Abstract

   The combination of different modality images can provide detailed and comprehensive information for the prognostic assessment and therapeutic strategy of patients with ischemic heart disease. In this study, a 3D fusion framework is designed to integrate coronary computed tomography (CT) angiography (CTA), 2-deoxy-2-[¹⁸F]fluoro-D-glucose ([¹⁸F]DG) positron emission tomography (PET)/CT, and [⁶⁸Ga]-1,4,7-triazacyclononane-1,4,7-triacetic acid-(Arg-Gly-Asp)2 ([⁶⁸Ga]-NOTA-PRGD2) PET/CT images of the myocardial infarction model in minipigs. First, the structural anatomy of the heart in coronary CTA and CT is segmented using a multi-atlas-based method. Then, the hearts are registered using the B-spline-based free form deformation. Finally, the [¹⁸F]DG and [⁶⁸Ga]-NOTA-PRGD2 signals are mapped into the heart in coronary CTA, which produces a single fusion image to delineate both the cardiac structural anatomy and the functional information of myocardial viability and angiogenesis. Heart segmentation demonstrates high accuracy with good agreement between manual delineation and automatic segmentation. The fusion result intuitively reflects the extent of the [¹⁸F]DG uptake defect as well as the location where the [⁶⁸Ga]-NOTA-PRGD2 signal appears. The fusion result verified the occurrence of angiogenesis based on the in vivo noninvasive molecular imaging approach. The presented framework is helpful in facilitating the study of the relationship between infarct territories and blocked coronary arteries as well as angiogenesis.
    
3. 

   Whole-Body Distribution of Leukemia and Functional Total Marrow Irradiation Based on FLT-PET and Dual-Energy CT

   Taiki Magome, PhD¹², Jerry Froelich, MD³, Shernan G. Holtan, MD⁴, Yutaka Takahashi, PhD²⁵, Michael R. Verneris, MD⁴, Keenan Brown, PhD⁶, Kathryn Dusenbery,MD⁷, Jeffrey Wong, MD⁸, Susanta K. Hui, PhD²⁷⁸
   Molecular Imaging, vol. 16, First Published September 26, 2017.
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   Abstract

   This report describes a multimodal whole-body 3′-deoxy-3′[(18)F]-fluorothymidine positron emission tomography (FLT-PET) and dual-energy computed tomography (DECT) method to identify leukemia distribution within the bone marrow environment (BME) and to develop disease- and/or BME-specific radiation strategies. A control participant and a newly diagnosed patient with acute myeloid leukemia prior to induction chemotherapy were scanned with FLT-PET and DECT. The red marrow (RM) and yellow marrow (YM) of the BME were segmented from DECT using a basis material decomposition method. Functional total marrow irradiation (fTMI) treatment planning simulations were performed combining FLT-PET and DECT imaging to differentially target irradiation to the leukemia niche and the rest of the skeleton. Leukemia colonized both RM and YM regions, adheres to the cortical bone in the spine, and has enhanced activity in the proximal/distal femur, suggesting a potential association of leukemia with the BME. The planning target volume was reduced significantly in fTMI compared with conventional TMI. The dose to active disease (standardized uptake value >4) was increased by 2-fold, while maintaining doses to critical organs similar to those in conventional TMI. In conclusion, a hybrid system of functional–anatomical–physiological imaging can identify the spatial distribution of leukemia and will be useful to both help understand the leukemia niche and develop targeted radiation strategies.
    
4. 

   Vulnerable Plaque Detection and Quantification with Gold Particle–Enhanced Computed Tomography in Atherosclerotic Mouse Models

   David De Wilde, Bram Trachet, Carole Van der Donckt, Bert Vandeghinste, Benedicte Descamps, Christian Vanhove, Guido R. Y. De Meyer, Patrick Segers
   Molecular Imaging, vol. 14, 6, First Published June 1, 2015.
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   Abstract

   Recently, an apolipoprotein E–deficient (ApoE^−/−) mouse model with a mutation (C1039G+/−) in the fibrillin-1 (Fbn1) gene (ApoE^−/−Fbn1^C1039G+/− mouse model) was developed showing vulnerable atherosclerotic plaques, prone to rupture, in contrast to the ApoE^−/− mouse model, where mainly stable plaques are present. One indicator of plaque vulnerability is the level of macrophage infiltration. Therefore, this study aimed to measure and quantify in vivo the macrophage infiltration related to plaque development and progression. For this purpose, 5-weekly consecutive gold nanoparticle–enhanced micro–computed tomography (microCT) scans were acquired. Histology confirmed that the presence of contrast agent coincided with the presence of macrophages. Based on the microCT scans, regions of the artery wall with contrast agent present were calculated and visualized in three dimensions. From this information, the contrast-enhanced area and contrast-enhanced centerline length were calculated for the branches of the carotid bifurcation (common, external, and internal carotid arteries). Statistical analysis showed a more rapid development and a larger extent of plaques in the ApoE^−/−Fbn1^C1039G+/− compared to the ApoE^−/−mice. Regional differences between the branches were also observable and quantifiable. We developed and applied a methodology based on gold particle–enhanced microCT to visualize the presence of macrophages in atherosclerotic plaques in vivo.
    
5. 

   Complementary Use of Bioluminescence Imaging and Contrast-Enhanced Micro—Computed Tomography in an Orthotopic Brain Tumor Model

   Sanaz Yahyanejad, Patrick V. Granton, Natasja G. Lieuwes, Lesley Gilmour, Ludwig Dubois, Jan Theys, Anthony J. Chalmers, Frank Verhaegen, Marc Vooijs
   Molecular Imaging, vol. 13, 4, First Published January 1, 2015.
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   Abstract

   Small animal models are crucial to link molecular discoveries and implementation of clinically relevant therapeutics in oncology. Using these models requires noninvasive imaging techniques to monitor disease progression and therapy response. Micro–computed tomography (CT) is less studied for the in vivo monitoring of murine intracranial tumors and traditionally suffers from poor soft tissue contrast, whereas bioluminescence imaging (BLI) is known for its sensitivity but is not frequently employed for quantifying tumor volume. A widely used orthotopic glioblastoma multiforme (GBM) tumor model was applied in nude mice, and tumor growth was evaluated by BLI and contrast-enhanced microCT imaging. A strong correlation was observed between CT volume and BLI-integrated intensity (Pearson coefficient (r) = .85, p = .0002). Repeated contouring of contrast-enhanced microCT-delineated tumor volumes achieved an intraobserver average pairwise overlap ratio of 0.84 and an average tumor volume coefficient of variance of 0.11. MicroCT-delineated tumor size was found to correlate with tumor size obtained via histologic analysis (Pearson coefficient (r) = .88, p = .005). We conclude that BLI intensity can be used to derive tumor volume but that the use of both contrast-enhanced microCT and BLI provides complementary tumor growth information, which is particularly useful for modern small animal irradiation devices that make use of microCT and BLI for treatment planning, targeting, and monitoring.
    
6. 

   Development and Validation of a Complete GATE Model of the Siemens Inveon Trimodal Imaging Platform

   Sanghyeb Lee, Jens Gregor, Dustin Osborne
   Molecular Imaging, vol. 12, 7, First Published October 1, 2013.
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   Abstract

   This article presents and validates a newly developed GATE model of the Siemens Inveon trimodal imaging platform. Fully incorporating the positron emission tomography (PET), single-photon emission computed tomography (SPECT), and computed tomography (CT) data acquisition subsystems, this model enables feasibility studies of new imaging applications, the development of reconstruction and correction algorithms, and the creation of a baseline against which experimental results for real data can be compared. Model validation was based on comparing simulation results against both empirical and published data. The PET modality was validated using the NEMA NU-4 standard. Validations of SPECT and CT modalities were based on assessment of model accuracy compared to published and empirical data on the platform. Validation results show good agreement between simulation and empirical data of approximately ± 5%.
    
7. 

   Use of eXIA 160 XL for Contrast Studies in Micro–Computed Tomography: Experimental Observations

   Inneke Willekens, Nico Buls, Michel De Maeseneer, Tony Lahoutte, Johan de Mey
   Molecular Imaging, vol. 12, 6, First Published September 1, 2013.
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   Abstract

   The purpose of this study was to evaluate the time course of contrast enhancement of spleen, liver, and blood using eXIA 160 XL in healthy mice. eXIA 160 XL was intravenously injected in C57bl/6 mice (n = 12) at a dose of 0.1 mL/20 g (16 mg iodine [I]/20 g) (n = 6) or 0.2 mL/20 g (32 mg I/20 g) (n = 6). The distribution was analyzed by repeated micro–computed tomographic scans up to 48 hours after contrast administration. Images were analyzed using Amidesoftware. Regions of interest were drawn in the spleen, liver, and left ventricle. Contrast enhancement was measured and expressed as a function of time. Peak contrast enhancement of the spleen was reached at 30 minutes, and peak contrast enhancement of the liver occurred 45 minutes after 16 mg I/20 g. Given that this contrast was found to be rather low in the spleen in comparison with former eXIA 160 products, experiments were done at a higher dose. However, the 32 mg I/20 g dose was lethal for mice. Enhancement inside the heart lasts for 1 hour. Administration of eXIA 160 XL results in long-lasting blood pool contrast with higher contrast enhancement in heart and liver in comparison with eXIA 160; however, the administered dose should be limited to 16 mg I/20 g.
    
8. 

   Comparison of Computed Tomography– and Optical Image–Based Assessment of Liposome Distribution

   Huang Huang, Michael Dunne, John Lo, David A. Jaffray, Christine Allen
   Molecular Imaging, vol. 12, 3, First Published May 1, 2013.
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   Abstract

   The use of multimodal imaging as a tool to assess the in vivo pharmacokinetics and biodistribution of nanocarriers is important in understanding the nature of their in vivo transport. The current study reports the development of a nano-sized liposomal computed tomographic (CT)/optical imaging probe carrying iohexol and Cy5.5 and its use in micro-CT and optical imaging to quantitatively assess the whole-body (macroscopic), intratumoral, and microscopic distribution over a period of 8 days. These multimodal liposomes have a vascular half-life of 30.3 ± 8.9 hours in mice bearing subcutaneous H520 non-small cell lung cancer tumors, with the maximum liposome accumulation in tumor achieved 48 hours postinjection. The in vivo liposome distribution and stability were quantitatively assessed using both micro-CT and fluorescence molecular tomography. The combination of CT and optical imaging enables visualization of the liposomes at the whole-body, tumor, and cellular scales with high sensitivity. Such noninvasive tracking of therapeutic vehicles at the macro- and microscale is important for informed and rational development of novel nanocarrier systems.