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Assessment of candidate elements for development of spectral photon-counting CT specific contrast agents.

ABSTRACT: Spectral photon-counting computed tomography (SPCCT) is a rapidly emerging imaging modality that provides energy-dependent information on individual x-ray photons, leading to accurate material decomposition and simultaneous quantification of multiple contrast generating materials. Development of SPCCT-specific contrast agents is needed to overcome the issues with currently used iodinated contrast agents, such as difficulty in differentiation from calcified structures, and yield SPCCT's full promise. In this study, the contrast generation of different elements is investigated using a prototype SPCCT scanner based on a modified clinical CT system and suitable elements for novel contrast agent development for SPCCT imaging are identified. Furthermore, nanoparticles were synthesized from tantalum as a proof of concept spectral photon-counting CT agent and tested for their in vitro cytotoxicity and contrast generation to provide insight into the feasibility of nanoparticle contrast agent development from these elements. We found that gadolinium, ytterbium and tantalum generate high contrast in spectral photon-counting CT imaging and may be suitable elements for contrast agent development for this modality. Our proof of concept results with tantalum-based nanoparticles underscore this conclusion due to their detectability with spectral photon-counting CT, as well as their biocompatibility.

SUBMITTER: Kim J

PROVIDER: S-EPMC6092324 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Assessment of candidate elements for development of spectral photon-counting CT specific contrast agents.

Kim Johoon J Bar-Ness Daniel D Si-Mohamed Salim S Coulon Philippe P Blevis Ira I Douek Philippe P Cormode David P DP

Scientific reports 20180814 1

Spectral photon-counting computed tomography (SPCCT) is a rapidly emerging imaging modality that provides energy-dependent information on individual x-ray photons, leading to accurate material decomposition and simultaneous quantification of multiple contrast generating materials. Development of SPCCT-specific contrast agents is needed to overcome the issues with currently used iodinated contrast agents, such as difficulty in differentiation from calcified structures, and yield SPCCT's full prom ...[more]

PMID: 30108247

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Project description:Photon-counting micro computed tomography (micro-CT) offers new potential in preclinical imaging, particularly in distinguishing materials. It becomes especially helpful when combined with contrast agents, enabling the differentiation of tumors from surrounding tissues. There are mainly two types of contrast agents in the market for micro-CT: small molecule-based and nanoparticle-based. However, despite their widespread use in liver tumor studies, there is a notable gap in research on the application of these commercially available agents for photon-counting micro-CT in breast and ovarian tumors. Herein, we explored the effectiveness of these agents in differentiating tumor xenografts from various origins (AU565, MDA-MB-231, and SKOV-3) in nude mice, using photon-counting micro-CT. Specifically, ISOVUE-370 (a small molecule-based agent) and Exitrone Nano 12000 (a nanoparticle-based agent) were investigated in this context. To improve tumor visualization, we proposed a novel color visualization method for photon-counting micro-CT, which changes color tones to highlight contrast media distribution, offering a robust alternative to traditional material decomposition methods with less computational demand. Our in vivo experiments confirm its effectiveness, showing distinct enhancement characteristics for each contrast agent. Qualitative and quantitative analyses suggested that Exitrone Nano 12000 provides superior vasculature enhancement and better quantitative consistency across scans, while ISOVUE-370 gives more comprehensive tumor enhancement but with a significant variance between scans due to its short blood half-time. This variability leads to high sensitivity to timing and individual differences among mice. Further, a paired t-test on mean and standard deviation values within tumor volumes showed significant differences between the AU565 and SKOV-3 tumor models with the nanoparticle-based (p-values < 0.02), attributable to their distinct vascularity, as confirmed by immunohistochemistry. These findings underscore the utility of photon-counting micro-CT in non-invasively assessing the morphology and anatomy of different tumor xenografts, which is crucial for tumor characterization and longitudinal monitoring of tumor development and response to treatments.

Project description: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.

Project description:ObjectiveEvaluation of image characteristics at ultra-low radiation dose levels of a first-generation dual-source photon-counting computed tomography (PCCT) compared to a dual-source dual-energy CT (DECT) scanner.MethodsA multi-energy CT phantom was imaged with and without an extension ring on both scanners over a range of radiation dose levels (CTDIvol 0.4-15.0 mGy). Scans were performed in different modes of acquisition for PCCT with 120 kVp and DECT with 70/Sn150 kVp and 100/Sn150 kVp. Various tissue inserts were used to characterize the precision and repeatability of Hounsfield units (HUs) on virtual mono-energetic images between 40 and 190 keV. Image noise was additionally investigated at an ultra-low radiation dose to illustrate PCCT's ability to remove electronic background noise.ResultsOur results demonstrate the high precision of HU measurements for a wide range of inserts and radiation exposure levels with PCCT. We report high performance for both scanners across a wide range of radiation exposure levels, with PCCT outperforming at low exposures compared to DECT. PCCT scans at the lowest radiation exposures illustrate significant reduction in electronic background noise, with a mean percent reduction of 74% (p value ~ 10-8) compared to DECT 70/Sn150 kVp and 60% (p value ~ 10-6) compared to DECT 100/Sn150 kVp.ConclusionsThis paper reports the first experiences with a clinical dual-source PCCT. PCCT provides reliable HUs without disruption from electronic background noise for a wide range of dose values. Diagnostic benefits are not only for quantification at an ultra-low dose but also for imaging of obese patients.Key pointsPCCT scanners provide precise and reliable Hounsfield units at ultra-low dose levels. The influence of electronic background noise can be removed at ultra-low-dose acquisitions with PCCT. Both spectral platforms have high performance along a wide range of radiation exposure levels, with PCCT outperforming at low radiation exposures.

Project description:ObjectiveThe aim of the current study was, first, to assess the coronary artery calcium (CAC) scoring potential of spectral photon-counting CT (SPCCT) in comparison with computed tomography (CT) for routine clinical protocols. Second, improved CAC detection and quantification at reduced slice thickness were assessed.MethodsRaw data was acquired and reconstructed with several combinations of reduced slice thickness and increasing strengths of iterative reconstruction (IR) for both CT systems with routine clinical CAC protocols for CT. Two CAC-containing cylindrical inserts, consisting of CAC of different densities and sizes, were placed in an anthropomorphic phantom. A specific CAC was detectable when 3 or more connected voxels exceeded the CAC scoring threshold of 130 Hounsfield units (HU). For all reconstructions, total CAC detectability was compared between both CT systems. Significant differences in CAC quantification (Agatston and volume scores) were assessed with Mann-Whitney U tests. Furthermore, volume scores were compared with the known CAC physical.ResultsCAC scores for routine clinical protocols were comparable between SPCCT and CT. SPCCT showed 34% and 4% higher detectability of CAC for the small and large phantom, respectively. At reduced slice thickness, CAC detection increased by 142% and 169% for CT and SPCCT, respectively. In comparison with CT, volume scores from SPCCT were more comparable with the physical volume of the CAC.ConclusionCAC scores using routine clinical protocols are comparable between conventional CT and SPCCT. The increased spatial resolution of SPCCT allows for increased detectability and more accurate CAC volume estimation.Key points• Coronary artery calcium scores using routine clinical protocols are comparable between conventional CT and spectral photon-counting CT. • In comparison with conventional CT, increased coronary artery calcium detectability was shown for spectral photon-counting CT due to increased spatial resolution. • Volumes scores were more accurately determined with spectral photon-counting CT.

Project description:ObjectiveTo evaluate the image quality of an ultra-low contrast medium and radiation dose CT pulmonary angiography (CTPA) protocol for the diagnosis of acute pulmonary embolism using a clinical photon-counting detector (PCD) CT system and compare its performance to a dual-energy-(DE)-CTPA protocol on a conventional energy-integrating detector (EID) CT system.MethodsSixty-four patients either underwent CTPA with the novel scan protocol on the PCD-CT scanner (32 patients, 25 mL, CTDIvol 2.5 mGy·cm) or conventional DE-CTPA on a third-generation dual-source EID-CT (32 patients, 50 mL, CTDIvol 5.1 mGy·cm). Pulmonary artery CT attenuation, signal-to-noise ratio, and contrast-to-noise-ratio were assessed as objective criteria of image quality, while subjective ratings of four radiologists were compared at 60 keV using virtual monoenergetic imaging and polychromatic standard reconstructions. Interrater reliability was determined by means of the intraclass correlation coefficient (ICC). Effective dose was compared between patient cohorts.ResultsSubjective image quality was deemed superior by all four reviewers for 60-keV PCD scans (excellent or good ratings in 93.8% of PCD vs. 84.4% of 60 keV EID scans, ICC = 0.72). No examinations on either system were considered "non-diagnostic." Objective image quality parameters were significantly higher in the EID group (mostly p < 0.001), both in the polychromatic reconstructions and at 60 keV. The ED (1.4 vs. 3.3 mSv) was significantly lower in the PCD cohort (p < 0.001).ConclusionsPCD-CTPA allows for considerable reduction of contrast medium and radiation dose in the diagnosis of acute pulmonary embolism, while maintaining good to excellent image quality compared to conventional EID-CTPA.Clinical relevance statementClinical PCD-CT allows for spectral assessment of pulmonary vasculature with high scan speed, which is beneficial in patients with suspected pulmonary embolism, frequently presenting with dyspnea. Simultaneously PCD-CT enables substantial reduction of contrast medium and radiation dose.Key points• The clinical photon-counting detector CT scanner used in this study allows for high-pitch multi-energy acquisitions. • Photon-counting computed tomography allows for considerable reduction of contrast medium and radiation dose in the diagnosis of acute pulmonary embolism. • Subjective image quality was rated best for 60-keV photon-counting scans.

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Assessment of candidate elements for development of spectral photon-counting CT specific contrast agents.

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Assessment of candidate elements for development of spectral photon-counting CT specific contrast agents.

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