Nanoparticle imaging probes for molecular imaging with computed tomography and application to cancer imaging

Roeder, Ryan K.; Curtis, Tyler E.; Nallathamby, Prakash D.; Irimata, Lisa E.; McGinnity, Tracie L.; Cole, Lisa E.; Vargo-Gogola, Tracy; Dahl, Karen D. Cowden

doi:10.1117/12.2255688

Cited by 14 publications

(18 citation statements)

References 11 publications

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“…This result suggests that spectral CT may be used to decompose and quantify low concentrations of contrast agents that are spatially coincident with mineralized tissues, 33 such as breast microcalcifications, 34,35 atherosclerotic plaque, 15 and bone. 36,37 The ability to decompose and quantify spatially coincident gadolinium and iodine further suggests that spectral CT may be used for multicontrast imaging, [23][24][25]38 including perfusion, angiography, colonography, and/or tumor targeting.…”

Section: Discussionmentioning

confidence: 99%

Quantification of multiple mixed contrast and tissue compositions using photon-counting spectral computed tomography

Curtis

Roeder

2019

J. Med. Imag.

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Quantitative material decomposition of multiple mixed, or spatially coincident, contrast agent (gadolinium and iodine) and tissue (calcium and water) compositions is demonstrated using photon-counting spectral computed tomography (CT). Material decomposition is performed using constrained maximum likelihood estimation (MLE) in the image domain. MLE is calibrated by multiple linear regression of all pure material compositions, which exhibits a strong correlation (R 2 > 0.91) between the measured x-ray attenuation in each photon energy bin and known concentrations in the calibration phantom. Material decomposition of mixed compositions in the sample phantom provides color material concentration maps that clearly identify and differentiate each material. The measured area under the receiver operating characteristic curve is >0.95, indicating highly accurate material identification. Material decomposition also provides accurate quantitative estimates of material concentrations in mixed compositions with a root-mean-squared error <12% of the maximum concentration for each material. Thus, photon-counting spectral CT enables quantitative molecular imaging of multiple spatially coincident contrast agent (gadolinium and iodine) and tissue (calcium and water) compositions, which is not possible with current clinical molecular imaging modalities, such as nuclear imaging and magnetic resonance imaging.

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Section: Discussionmentioning

confidence: 99%

Quantification of multiple mixed contrast and tissue compositions using photon-counting spectral computed tomography

Curtis

Roeder

2019

J. Med. Imag.

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“…The scanner has physiological support and monitoring capabilities for in vivo studies but does not provide gating. Nevertheless, as detailed in the Spectral micro-CT section of this review, PCD-based scanners provide improved material discrimination [5 6] and allow the use of nanoparticle contrast agents that can be functionalized for molecular x-ray imaging [7].…”

Section: State-of-the-art Commercial Micro-ct Scannersmentioning

confidence: 99%

Advances in micro-CT imaging of small animals

Clark

Badea

2021

Physica Medica

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Micron-scale computed tomography (micro-CT) imaging is a ubiquitous, cost-effective, and non-invasive three-dimensional imaging modality. We review recent developments and applications of micro-CT for preclinical research. Methods: Based on a comprehensive review of recent micro-CT literature, we summarize features of state-of-theart hardware and ongoing challenges and promising research directions in the field. Results: Representative features of commercially available micro-CT scanners and some new applications for both in vivo and ex vivo imaging are described. New advancements include spectral scanning using dual-energy micro-CT based on energy-integrating detectors or a new generation of photon-counting x-ray detectors (PCDs). Beyond two-material discrimination, PCDs enable quantitative differentiation of intrinsic tissues from one or more extrinsic contrast agents. When these extrinsic contrast agents are incorporated into a nanoparticle platform (e.g. liposomes), novel micro-CT imaging applications are possible such as combined therapy and diagnostic imaging in the field of cancer theranostics. Another major area of research in micro-CT is in x-ray phase contrast (XPC) imaging. XPC imaging opens CT to many new imaging applications because phase changes are more sensitive to density variations in soft tissues than standard absorption imaging. We further review the impact of deep learning on micro-CT. We feature several recent works which have successfully applied deep learning to micro-CT data, and we outline several challenges specific to micro-CT. Conclusions: All of these advancements establish micro-CT imaging at the forefront of preclinical research, able to provide anatomical, functional, and even molecular information while serving as a testbench for translational research.

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“…Hafnium oxide (HfO 2 ) nanoparticles (NPs) have gained recent interest in biomedicine as a radiosensitizer, 1‐5 radiographic contrast agent, 6‐9 mid‐infrared biosensor, 6,10 and photoluminescent biosensor or radioluminescent scintillator 11‐14 . HfO 2 is a highly stable compound exhibiting a high melting point (2758°C), high dielectric constant ( ε = 25), high density (9.7 g/cm 3 ), high atomic number ( Z = 72), wide band gap (5.3–5.9 eV), and high index of refraction.…”

Section: Introductionmentioning

confidence: 99%

“…HfO 2 is a highly stable compound exhibiting a high melting point (2758°C), high dielectric constant ( ε = 25), high density (9.7 g/cm 3 ), high atomic number ( Z = 72), wide band gap (5.3–5.9 eV), and high index of refraction. The high atomic number and electron density of hafnium enables strong absorption of X‐rays, which can be leveraged as a radiosensitizer in radiotherapy 1‐5 and a radiographic contrast agent for diagnostic X‐ray imaging 6‐9 . A commercialized HfO 2 radiosensitizer (NBTXR3, Nanobiotix, Paris, France) recently gained regulatory approval in the United States and European Union for the treatment of various cancers 15 .…”

Section: Introductionmentioning

confidence: 99%

Colloidal stability, cytotoxicity, and cellular uptake of HfO₂ nanoparticles

et al. 2021

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The colloidal stability, cytotoxicity, and cellular uptake of hafnium oxide (HfO2) nanoparticles (NPs) were investigated in vitro to assess safety and efficacy for use as a deliverable theranostic in nanomedicine. Monoclinic HfO2 NPs, ~60–90 nm in diameter and ellipsoidal in shape, were directly prepared without calcination by a hydrothermal synthesis at 83% yield. The as‐prepared, bare HfO2 NPs exhibited colloidal stability in cell culture media for at least 10 days without significant agglomeration or settling. The viability (live/dead assay) of human epithelial cells (HeLa) and monocyte‐derived macrophages (THP‐1) did not fall below 95% of untreated cells after up to 24 h exposure to HfO2 NPs at concentrations up to 0.80 mg/ml. Similarly, the mitochondrial activity (MTT assay) of HeLa and THP‐1 cells did not fall below 80% of untreated cells after up to 24 h exposure to HfO2 NPs at concentrations up to 0.40 mg/ml. Cellular uptake was confirmed and visualized in both HeLa and THP‐1 cells by fluorescence microscopy of HfO2 NPs labeled with Cy5 and transmission electron microscopy (TEM) of bare HfO2 NPs. TEM micrographs provided direct observation of macropinocytosis and endosomal compartmentalization within 4 h of exposure. Thus, the HfO2 NPs in this study exhibited colloidal stability, cytocompatibility, and cellular uptake for potential use as a deliverable theranostic in nanomedicine.

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Nanoparticle imaging probes for molecular imaging with computed tomography and application to cancer imaging

Cited by 14 publications

References 11 publications

Quantification of multiple mixed contrast and tissue compositions using photon-counting spectral computed tomography

Quantification of multiple mixed contrast and tissue compositions using photon-counting spectral computed tomography

Advances in micro-CT imaging of small animals

Colloidal stability, cytotoxicity, and cellular uptake of HfO₂ nanoparticles

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Nanoparticle imaging probes for molecular imaging with computed tomography and application to cancer imaging

Cited by 14 publications

References 11 publications

Quantification of multiple mixed contrast and tissue compositions using photon-counting spectral computed tomography

Quantification of multiple mixed contrast and tissue compositions using photon-counting spectral computed tomography

Advances in micro-CT imaging of small animals

Colloidal stability, cytotoxicity, and cellular uptake of HfO2 nanoparticles

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Product

Resources

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Colloidal stability, cytotoxicity, and cellular uptake of HfO₂ nanoparticles