Can Realistic Liver Tissue Surrogates Accurately Quantify the Impact of Reduced-kV Imaging on Attenuation and Contrast of Parenchyma and Lesions?

RATIONALE AND OBJECTIVES: To assess if a liquid tissue surrogate for the liver (LTSL) can emulate contrast-enhanced liver parenchyma and lesions and quantify the impact of reduced-kV imaging as a function of lesion contrast, phase of enhancement, and phantom size. MATERIALS AND METHODS: First, CT attenuation of LTSL- and water-iodine solutions were measured as a function of iodine concentration and tube potential. For each solution, the iodine concentration was determined to emulate liver parenchyma at 120 kV. CT attenuation for both solutions was predicted for different tube potentials and compared to published patient data. Second, liver parenchyma in late arterial phase (LA: +92 HU at 120 kV) and portal venous phase (PV: +112 HU at 120 kV) was emulated using LTSL-iodine and a two-size phantom. Fourteen setups of hyper- and hypoattenuating lesions (lesion-to-parenchyma contrast (CLP) = -50 to +50HU) were created. Each combination of CLP, phase, and size was imaged at 80, 100, 120, and 140 kV at constant radiation dose. CT attenuation, CLP, and lesion-to-parenchyma contrast-to-noise ratio (CNRLP) were assessed and compared to a theoretical model. RESULTS: LTSL-iodine more accurately emulated the CT attenuation of liver parenchyma across different tube potentials compared to water-iodine solutions. The theoretical model was confirmed by the empirical measurements using LTSL-iodine solutions: attenuation, CLP, and CNRLP increased when the tube potential decreased (p < 0.001). This trend was independent of lesion contrast, phase, and size. The absolute improvement in CLP and CNRLP, however, was inversely related to the magnitude of CLP at 140kV. CONCLUSION: LTSL accurately emulated the energy-dependent CT attenuation characteristics of contrast-enhanced liver parenchyma and lesions. The relative improvement in CLP and CNRLP by applying reduced-kV imaging was independent of lesion contrast, phase, and size while the absolute improvement decreased for low-contrast lesions.

An Intravascular Tantalum Oxide-based CT Contrast Agent: Preclinical Evaluation Emulating Overweight and Obese Patient Size.

Purpose To compare the CT imaging performance of a carboxybetaine zwitterionic-coated tantalum oxide (TaCZ) nanoparticle CT contrast agent with that of a conventional iodinated contrast agent in a swine model meant to simulate overweight and obese patients. Materials and Methods Four swine were evaluated inside three different-sized adipose-equivalent encasements emulating abdominal girths of 102, 119, and 137 cm. Imaging was performed with a 64-detector row CT scanner at six scan delays after intravenous injection of 240 mg element (Ta or I) per kilogram of body weight of TaCZ or iopromide. For each time point, contrast enhancement of the aorta and liver were measured by using regions of interest. Two readers independently recorded the clarity of vasculature using a five-point Likert scale. Findings were compared by using paired t tests and Wilcoxon signed-rank tests. Results Mean peak enhancement was higher for TaCZ than for iopromide in the aorta (270 HU [σ = 24.5] vs 199 HU [σ = 10.2], P < .001) and liver (61.3 HU [σ = 11.7] vs 45.2 HU [σ = 8], P < .001). Vascular clarity was higher for TaCZ than for iopromide in 63% (132 of 208), 82% (170 of 208), and 86% (178 of 208) of the individual vessels at the 102-, 119-, and 137-cm girths, respectively (P < .01). Arterial clarity scores were higher for TaCZ than for iopromide in 62% (208 of 336) of vessels. Venous clarity scores were higher for TaCZ than for iopromide in 89% (128 of 144) of the veins in the venous phase and in 100% (144 of 144) of veins in the delayed phase (P < .01). No vessel showed higher clarity score with iopromide than with TaCZ. Conclusion An experimental tantalum nanoparticle-based contrast agent showed greater contrast enhancement compared with iopromide in swine models meant to simulate overweight and obese patients. © RSNA, 2018.

Liquid tissue surrogates for X-ray and CT phantom studies.

PURPOSE: To develop a simple method for producing liquid-tissue-surrogate (LTS) materials that accurately represent human soft tissues in terms of density and X-ray attenuation coefficient. METHODS AND MATERIALS: We evaluated hypothetical mixtures of water, glycerol, butanol, methanol, sodium chloride, and potassium nitrate; these mixtures were intended to emulate human adipose, blood, brain, kidney, liver, muscle, pancreas, and skin. We compared the hypothetical densities, effective atomic numbers (Zeff ), and calculated discrete-energy CT attenuation [Hounsfield Units (HU)] of the proposed materials with those of human tissue elemental composition as specified in International Commission on Radiation Units (ICRU) Report 46. We then physically produced the proposed LTS materials for adipose, liver, and pancreas tissue, and we measured the polyenergetic CT attenuation (also expressed as HU) of these materials within a 32 cm phantom using a 64-slice clinical CT scanner at 80 kVp, 100 kVp, 120 kVp, and 140 kVp. RESULTS: The predicted densities, Zeff , and calculated discrete-energy CT attenuation of our proposed formulations generally agreed with those of ICRU within < 1% or < 10 HU. For example, the densities of our hypothetical materials agreed precisely with ICRU's reported values and were 0.95 g/mL for adipose tissue, 1.04 g/mL for pancreatic tissue, and 1.06 g/mL for liver tissue; the discrete-energy CT attenuation at 60 keV of our hypothetical materials (and ICRU-specified compositions) were -107 HU (-113 HU) for adipose #3, -89 HU (-90 HU) for adipose #2, 56 HU (55 HU) for liver tissue, and 31 HU (31 HU) for pancreatic tissue. The densities of our physically produced materials (compared to ICRU-specified compositions) were 0.947 g/mL (0.0%) for adipose #2, 1.061 g/mL (+2.0%) for pancreatic tissue, and 1.074 g/mL (+1.3%) for liver tissue. The empirical polyenergetic CT attenuation measurements of our LTS materials (and the discrete-energy HU of the ICRU compositions at the mean energy of each spectrum) at 80 kVp were -104 HU (-113 HU) for adipose #3, -87 HU (-90 HU) for adipose #2, 59 HU (55 HU) for liver tissue, and 33 HU (31 HU) for pancreatic tissue; at 120 kVp, these were -83 HU (-83 HU) for adipose #3, -68 HU (-63 HU) for adipose #2, 55 HU (52 HU) for liver tissue, and 35 HU (33 HU) for pancreatic tissue. CONCLUSION: Our method for formulating tissue surrogates allowed straightforward production of solutions with CT attenuation that closely matched the target tissues' expected CT attenuation values and trends with kVp. The LTSs' inexpensive and widely available constituent chemicals, combined with their liquid state, should enable rapid production and versatile use among different phantom and experiment types. Further study is warranted, such as the inclusion of contrast agents. These liquid tissue surrogates may potentially accelerate development and testing of advanced CT imaging techniques and technologies.

Opportunities for new CT contrast agents to maximize the diagnostic potential of emerging spectral CT technologies.

The introduction of spectral CT imaging in the form of fast clinical dual-energy CT enabled contrast material to be differentiated from other radiodense materials, improved lesion detection in contrast-enhanced scans, and changed the way that existing iodine and barium contrast materials are used in clinical practice. More profoundly, spectral CT can differentiate between individual contrast materials that have different reporter elements such that high-resolution CT imaging of multiple contrast agents can be obtained in a single pass of the CT scanner. These spectral CT capabilities would be even more impactful with the development of contrast materials designed to complement the existing clinical iodine- and barium-based agents. New biocompatible high-atomic number contrast materials with different biodistribution and X-ray attenuation properties than existing agents will expand the diagnostic power of spectral CT imaging without penalties in radiation dose or scan time.

The Effect of Patient Diameter on the Dual-Energy Ratio of Selected Contrast-Producing Elements.

OBJECTIVES: The aim of this study was to assess whether the low- to high-kVp computed tomography (CT) number ratio at dual-energy CT is affected by changes in patient diameter. METHODS: Seven contrast-producing elements were housed sequentially within an abdomen phantom. Fat rings enlarged the phantom diameter from 26 to 44 cm. The phantom was scanned using single-energy CT at tube potentials of 80 and 140 kVp and rapid-kVp-switching dual-energy CT. RESULTS: CT numbers decreased proportionally (∼20% CT number reduction for smallest to largest phantom diameters) for low- and high-energy acquisitions but resulted in consistent dual-energy ratios for each contrast element. For 17 of 21 material pair combinations, the dual-energy ratio ranges of the two elements did not overlap, implying that discrimination should remain possible for these material pairs at all patient sizes. CONCLUSIONS: The dual-energy ratio for different contrast materials is largely unaffected by changes in phantom diameter. This should allow for robust separation of most contrast material combinations irrespective of patient size.

Fast analytical approach of application specific dose efficient spectrum selection for diagnostic CT imaging and PET attenuation correction.

Computed tomography (CT) has been used for a variety of applications, two of which include diagnostic imaging and attenuation correction for PET or SPECT imaging. Ideally, the x-ray tube spectrum should be optimized for the specific application to minimize the patient radiation dose while still providing the necessary information. In this study, we proposed a projection-based analytic approach for the analysis of contrast, noise, and bias. Dose normalized contrast to noise ratio (CNRD), inverse noise normalized by dose (IND) and bias are used as evaluation metrics to determine the optimal x-ray spectrum. Our simulation investigated the dose efficiency of the x-ray spectrum ranging from 40 kVp to 200 kVp. Water cylinders with diameters of 15 cm, 24 cm, and 35 cm were used in the simulation to cover a variety of patient sizes. The effects of electronic noise and pre-patient copper filtration were also evaluated. A customized 24 cm CTDI-like phantom with 13 mm diameter inserts filled with iodine (10 mg ml-1), tantalum (10 mg ml-1), water, and PMMA was measured with both standard (1.5 mGy) and ultra-low (0.2 mGy) dose to verify the simulation results at tube voltages of 80, 100, 120, and 140 kVp. For contrast-enhanced diagnostic imaging, the simulation results indicated that for high dose without filtration, the optimal kVp for water contrast is approximately 100 kVp for a 15 cm water cylinder. However, the 60 kVp spectrum produces the highest CNRD for bone and iodine. The optimal kVp for tantalum has two selections: approximately 50 and 100 kVp. The kVp that maximizes CNRD increases when the object size increases. The trend in the CTDI phantom measurements agrees with the simulation results, which also agrees with previous studies. Copper filtration improved the dose efficiency for water and tantalum, but reduced the iodine and bone dose efficiency in a clinically-relevant range (70-140 kVp). Our study also shows that for CT-based attenuation correction applications for PET or SPECT, a higher-kVp spectrum with copper filtration is preferable. This method is developed based on filter back projection and does not require image reconstruction or Monte Carlo dose estimates; thus, it could potentially be used for patient-specific and task-based on-the-fly protocol optimization.

A Proposed Computed Tomography Contrast Agent Using Carboxybetaine Zwitterionic Tantalum Oxide Nanoparticles: Imaging, Biological, and Physicochemical Performance.

OBJECTIVES: The aim of this study was to produce and evaluate a proposed computed tomography (CT) contrast agent based on carboxybetaine zwitterionic (CZ)-coated soluble tantalum oxide (TaO) nanoparticles (NPs). We chose tantalum to provide superior imaging performance compared with current iodine-based clinical CT contrast agents. We developed the CZ coating to provide biological and physical performance similar to that of current iodinated contrast agents. In addition, the aim of this study was to evaluate the imaging, biological, and physicochemical performance of this proposed contrast agent compared with clinically used iodinated agents. MATERIALS AND METHODS: We evaluated CT imaging performance of our CZ-TaO NPs compared with that of an iodinated agent in live rats, imaged centrally located within a tissue-equivalent plastic phantom that simulated a large patient. To evaluate vascular contrast enhancement, we scanned the rats' great vessels at high temporal resolution during and after contrast agent injection. We performed several in vivo CZ-TaO NP studies in healthy rats to evaluate tolerability. These studies included injecting the agent at the anticipated clinical dose (ACD) and at 3 times and 6 times the ACD, followed by longitudinal hematology to assess impact to blood cells and organ function (from 4 hours to 1 week). Kidney histological analysis was performed 48 hours after injection at 3 times the ACD. We measured the elimination half-life of CZ-TaO NPs from blood, and we monitored acute kidney injury biomarkers with a kidney injury assay using urine collected from 4 hours to 1 week. We measured tantalum retention in individual organs and in the whole carcass 48 hours after injection at ACD. Carboxybetaine zwitterionic TaO NPs were synthesized and analyzed in detail. We used multidimensional nuclear magnetic resonance to determine surface functionality of the NPs. We measured NP size and solution properties (osmolality and viscosity) of the agent over a range of tantalum concentrations, including the high concentrations required for standard clinical CT imaging. RESULTS: Computed tomography imaging studies demonstrated image contrast improvement of approximately 40% to 50% using CZ-TaO NPs compared with an iodinated agent injected at the same mass concentration. Blood and organ analyses showed no adverse effects after injection in healthy naive rats at 3 times the ACD. Retention of tantalum at 48 hours after injection was less than 2% of the injected dose in the whole carcass, which very closely matched the reported retention of existing commercial iodine-based contrast agents. Urine analysis of sensitive markers for acute kidney injury showed no responses at 1 week after injection at 3 times the ACD; however, a moderate response in the neutrophil gelatinase-associated lipocalin biomarker was measured at 24 and 48 hours. Compared with other TaO NPs reported in the literature, CZ-TaO NPs had relatively low osmolality and viscosity at concentrations greater than 200 mg Ta/mL and were similar in these physical properties to dimeric iodine-based contrast agents. CONCLUSIONS: We found that a CZ-TaO NP-based contrast agent is potentially viable for general-purpose clinical CT imaging. Our results suggest that such an agent can be formulated with clinically viable physicochemical properties, can be biologically safe and cleared rapidly in urine, and can provide substantially improved image contrast at CT compared with current iodinated agents.

CT Image Contrast of High-Z Elements: Phantom Imaging Studies and Clinical Implications.

PURPOSE: To quantify the computed tomographic (CT) image contrast produced by potentially useful contrast material elements in clinically relevant imaging conditions. MATERIALS AND METHODS: Equal mass concentrations (grams of active element per milliliter of solution) of seven radiodense elements, including iodine, barium, gadolinium, tantalum, ytterbium, gold, and bismuth, were formulated as compounds in aqueous solutions. The compounds were chosen such that the active element dominated the x-ray attenuation of the solution. The solutions were imaged within a modified 32-cm CT dose index phantom at 80, 100, 120, and 140 kVp at CT. To simulate larger body sizes, 0.2-, 0.5-, and 1.0-mm-thick copper filters were applied. CT image contrast was measured and corrected for measured concentrations and presence of chlorine in some compounds. RESULTS: Each element tested provided higher image contrast than iodine at some tube potential levels. Over the range of tube potentials that are clinically practical for average-sized and larger adults-that is, 100 kVp and higher-barium, gadolinium, ytterbium, and tantalum provided consistently increased image contrast compared with iodine, respectively demonstrating 39%, 56%, 34%, and 24% increases at 100 kVp; 39%, 66%, 53%, and 46% increases at 120 kVp; and 40%, 72%, 65%, and 60% increases at 140 kVp, with no added x-ray filter. CONCLUSION: The consistently high image contrast produced with 100-140 kVp by tantalum compared with bismuth and iodine at equal mass concentration suggests that tantalum could potentially be favorable for use as a clinical CT contrast agent.

Complementary contrast media for metal artifact reduction in dual-energy computed tomography.

Metal artifacts have been a problem associated with computed tomography (CT) since its introduction. Recent techniques to mitigate this problem have included utilization of high-energy (keV) virtual monochromatic spectral (VMS) images, produced via dual-energy CT (DECT). A problem with these high-keV images is that contrast enhancement provided by all commercially available contrast media is severely reduced. Contrast agents based on higher atomic number elements can maintain contrast at the higher energy levels where artifacts are reduced. This study evaluated three such candidate elements: bismuth, tantalum, and tungsten, as well as two conventional contrast elements: iodine and barium. A water-based phantom with vials containing these five elements in solution, as well as different artifact-producing metal structures, was scanned with a DECT scanner capable of rapid operating voltage switching. In the VMS datasets, substantial reductions in the contrast were observed for iodine and barium, which suffered from contrast reductions of 97% and 91%, respectively, at 140 versus 40 keV. In comparison under the same conditions, the candidate agents demonstrated contrast enhancement reductions of only 20%, 29%, and 32% for tungsten, tantalum, and bismuth, respectively. At 140 versus 40 keV, metal artifact severity was reduced by 57% to 85% depending on the phantom configuration.

Optimal kVp Selection for Contrast CT Imaging Based on a Projection-domain Method.

Computed Tomography (CT) has been in clinical use for several decades. The number of CT scans has increased significantly worldwide, which results in increased radiation dose delivered to the general population. Many technologies have been developed to minimize the dose from CT scans, including scanner hardware improvements, task-specific protocol design and advanced reconstruction algorithms. In this study, we focused on selection of X-ray tube voltage and filtration to achieve optimal dose efficiency given required image quality, more specifically the contrast to noise ratio. Our approach differs from previous studies in two aspects. Typically, Monte-Carlo simulation is used to estimate dose in simulations, but this is computationally costly. We instead use a projection-domain dose estimation method. No image reconstruction is required for the projection-domain method, which further simplifies the analysis. This study also includes tantalum, a new contrast agent, in addition to soft tissue (water), bone and iodine contrast. Optimal tube voltages and filtration are identified as a function of phantom size. The simulation analysis is confirmed with a limited phantom study.

Biological performance of a size-fractionated core-shell tantalum oxide nanoparticle x-ray contrast agent.

OBJECTIVES: Metal-containing nanoparticles show great promise as x-ray contrast media and could enable reduced radiation dose, increased contrast, and the visualization of smaller anatomic features. In this study, we report progress toward these goals using a size-fractionated core-shell tantalum oxide nanoparticle contrast agent. MATERIALS AND METHODS: A core-shell tantalum oxide nanoparticle contrast agent was synthesized and size fractionated for preclinical investigation of biodistribution, blood half-life, organ retention, and histopathology. Fractionated agent was injected at anticipated clinical dose and at 3 times the anticipated clinical dose to evaluate biological performance. Computed tomography (CT) imaging studies were also performed to evaluate short-term clearance kinetics and new imaging applications. RESULTS: Improved control of 2-diethylphosphatoethylsilane-TaO nanoparticle size resulted in significantly reduced retention of injected tantalum. In vivo and in vitro CT imaging studies demonstrated short-term biodistribution differences in the kidney between small-molecule iodinated contrast media and fractionated 2-diethylphosphatoethylsilane-TaO, as well as preliminary data about new "Ta-only" imaging applications using multienergy CT image acquisition. CONCLUSIONS: Size-fractionated core-shell tantalum oxide nanoparticles with a well-defined particle size distribution have several key features required of clinically viable vascular imaging compounds and may be used in developing multienergy CT imaging applications.

Synthesis, characterization, and computed tomography imaging of a tantalum oxide nanoparticle imaging agent.

Water-soluble ≤6 nm tantalum oxide nanoparticles have been synthesized and characterized in solution using HPLC-ICP, DLS, and multinuclear NMR. Nanoparticle formulation permitted intravenous injection, in vivo imaging, and subsequent renal clearance. A clinical CT scanner provided excellent resolution following agent injection, and distribution to the arterial system was visualized. In vitro CT imaging studies indicated that at equal molar concentration of tantalum and iodine, tantalum produced greater image contrast than iodine across the diagnostic X-ray spectrum with contrast benefit increasing with peak X-ray energy.