Functional imaging of tumor vasculature using iodine and gadolinium-based nanoparticle contrast agents: A comparison of spectral micro-CT using energy integrating and photon counting detectors
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Abstract Advances in computed tomography (CT) hardware have propelled the development of novel CT contrast agents. In particular, the spectral capabilities of x-ray CT can facilitate simultaneous imaging of multiple contrast agents. This approach is particularly useful for functional imaging of solid tumors by simultaneous visualization of multiple targets or architectural features that govern cancer development and progression. Nanoparticles are a promising platform for contrast agent development. While several novel imaging moieties based on high atomic number elements are being explored, iodine (I) and gadolinium (Gd) are particularly attractive because of their existing approval for clinical use. In this work, we investigate the in vivo discrimination of I and Gd nanoparticle contrast agents using both dual energy micro-CT with energy integrating detectors (DE-EID) and photon counting detector (PCD)-based spectral micro-CT. Simulations and phantom experiments were performed using varying concentrations of I and Gd to determine the imaging performance with optimized acquisition parameters. Quantitative spectral micro-CT imaging using liposomal-iodine (Lip-I) and liposomal-Gd (Lip-Gd) nanoparticle contrast agents was performed in sarcoma bearing mice for anatomical and functional imaging of tumor vasculature. Iterative reconstruction provided high sensitivity to detect and discriminate relatively low I and Gd concentrations. According to the Rose criterion applied to the experimental results, the detectability limits for I and Gd were approximately 2.5 mg ml −1 for both DE-EID CT and PCD micro-CT, even if the radiation dose was approximately 3.8 times lower with PCD micro-CT. The material concentration maps confirmed expected biodistributions of contrast agents in the blood, liver, spleen and kidneys. The PCD provided lower background signal and better simultaneous visualization of tumor vasculature and intratumoral distribution patterns of nanoparticle contrast agent compared to DE-EID decompositions. Preclinical spectral CT systems such as this could be useful for functional characterization of solid tumors, simultaneous quantitative imaging of multiple targets and for identifying clinically-relevant applications that benefit from the use of spectral imaging. Additionally, it could aid in the development nanoparticles that show promise in the developing field of cancer theranostics (therapy and diagnostics) by measuring vascular tumor biomarkers such as fractional blood volume and the delivery of liposomal chemotherapeutics.
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DCE-CT is beneficial for identifying patients expected to respond to liposomal drug therapy.
“Thus, DCE-CT is beneficial for identifying patients expected to respond to liposomal drug therapy [134].”
From Approaches to Improve EPR-Based Drug Delivery for Cancer Therapy and Diagnosis (2023) · cites this paper as [134]
The Discussion and conclusions (page unavailable) says preclinical spectral micro-CT can measure tumor vascularity and nanoparticle accumulation, with the latter serving as a surrogate for the intratumoral distribution of liposomal chemotherapeutics. It does not establish that DCE-CT identifies patients likely to respond to liposomal drug therapy; the Results describe imaging in sarcoma-bearing mice, not patient selection or treatment response. (LLM, conf=0.85)
Experimental — accuracy not yet measuredBLI is used to assess nanodrug efficiency based on endogenic luminescence of tumors to confirm NPs diagnostics or theranostic prospects and to integrate with other imaging modalities.
“BLI is used to assess nanodrug efficiency based on the endogenic luminescence of tumors to confirm NPs diagnostics or theranostic prospects and to integrate with other imaging modalities [19,134,135,136].”
From Approaches to Improve EPR-Based Drug Delivery for Cancer Therapy and Diagnosis (2023) · cites this paper as [134]
The Introduction and Discussion and conclusions describe spectral micro-CT imaging of nanoparticle contrast agents and its potential for cancer theranostics. Our copy does not address BLI, tumor luminescence, or using BLI to assess nanodrug efficiency or integrate imaging modalities (searched: bioluminescence, BLI, luminescence, and optical imaging). (LLM, conf=0.76)
Experimental — accuracy not yet measured
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Basic Principles and Clinical Applications of Photon-Counting CT
Flohr, T. G., Petersilka, M., Ulzheimer, S., Schmidt, B. T., Erhard, K., Brendel, B., Villien, M., Coulon, P., Si-Mohamed, S. A., & Boccalini, S. (2022) · Medical radiology · doi:10.1007/978-3-030-96285-2_6 · Cited by 3 · see citing works
Neue Kontrastmittel für die photonenzählende Computertomographie
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Liu, K., Zuo, R., Yu, Y., Chen, X., Wang, T., Xie, L., Sun, H., Niu, M., & Wang, H. (2025) · Molecular Pharmaceutics · doi:10.1021/acs.molpharmaceut.5c00527 · Cited by 2 · see citing works
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Nadkarni, R., Allphin, A. J., Clark, D. P., Qi, Y., Han, Z. Y., Ghaghada, K. B., Badea, A., & Badea, C. T. (2025) · PLoS ONE · doi:10.1371/journal.pone.0339293 · Cited by 2 · see citing works
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Photon counting micro-CT for imaging Cisplatin
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Self-citationVirtual photon-counting micro-CT platform for simulation of head and neck cancer imaging in mice
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- Authors
- Badea, C. T., Clark, D. P., Holbrook, M., Srivastava, M., Mowery, Y., & Ghaghada, K. B.
- Affiliations
- Duke University (US)
- Texas Children's Hospital (US)
- Corresponding author
- Badea, C T
- Venue
- Physics in Medicine & Biology
- Publisher
- IOP Publishing
- Published
- 2019-03-01
- Volume
- 64
- Issue
- 6
- Pages
- 065007
- ISSN
- 0031-9155 (ISSN-L)
- 1361-6560
- PMC
- PMC6607440
- OpenAlex
- W2914136035
- Cited by
- 74
- References
- 36
- Citations by year
- 2026: 6 · 2025: 11 · 2024: 13 · 2023: 12 · 2022: 10 · 2021: 7 · 2020: 13 · 2019: 2
- FWCI
- 2.82
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Physics in Medicine and Biology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Center for Scientific Review (R01 CA196667)
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › Advanced X-ray and CT Imaging
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Medical Imaging Techniques and Applications
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Cardiac Imaging and Diagnostics
- Keywords
- liposomal contrast agents, tumor vasculature, photon counting detectors, energy-integrating detector, sarcoma, iterative reconstruction, cancer theranostics, fractional blood volume, radiation dose reduction
- MeSH terms
- Animals, Contrast Media, Gadolinium, Humans, Iodine, Magnetic Resonance Imaging, Mice, Inbred C57BL, Neovascularization, Pathologic, Sarcoma, Tomography Scanners, X-Ray Computed, Photons, Phantoms, Imaging, Mice, Nanoparticles, X-Ray Microtomography
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