Countering Calcium Blooming With Personalized Contrast Media Injection Protocols: The 1-2-3 Rule for Photon-Counting Detector CCTA.

OBJECTIVE: Photon-counting detector computed tomography (PCD-CT) enables spectral data acquisition of CT angiographies allowing for reconstruction of virtual monoenergetic images (VMIs) in routine practice. Specifically, it has potential to reduce the blooming artifacts associated with densely calcified plaques. However, calcium blooming and iodine attenuation are inversely affected by energy level (keV) of the VMIs, creating a challenge for contrast media (CM) injection protocol optimization. A pragmatic and simple rule for calcium-dependent CM injection protocols is investigated and proposed for VMI-based coronary CT angiography with PCD-CT. MATERIALS AND METHODS: A physiological circulation phantom with coronary vessels including calcified lesions (maximum CT value >700 HU) with a 50% diameter stenosis was injected into at iodine delivery rates (IDRs) of 0.3, 0.5, 0.7, 1.0, 1.5, 2.0, 2.5, and 3.0 g I/s. Images were acquired using a first-generation dual-source PCD-CT and reconstructed at various VMI levels (between 45 and 190 keV). Iodine attenuation in the coronaries was measured at each IDR for each keV, and blooming artifacts from the calcified lesions were assessed including stenosis grading error (as % overestimation vs true lumen). The IDR to achieve 300 HU at each VMI level was then calculated and compared with stenosis grading accuracy to establish a general rule for CM injection protocols. RESULTS: Plaque blooming artifacts and intraluminal iodine attenuation decreased with increasing keV. Fixed windowing (representing absolute worst case) resulted in stenosis overestimation from 77% ± 4% at 45 keV to 5% ± 2% at 190 keV, whereas optimized windowing resulted in overestimation from 29% ± 3% at 45 keV to 4% ± 1% at 190 keV. The required IDR to achieve 300 HU showed a strong linear correlation to VMI energy (R2 = 0.98). Comparison of this linear plot versus stenosis grading error and blooming artifact demonstrated that multipliers of 1, 2, and 3 times the reference IDR for theoretical clinical regimes of no, moderate, and severe calcification density, respectively, can be proposed as a general rule. CONCLUSIONS: This study provides a proof-of-concept in an anthropomorphic phantom for a simple pragmatic adaptation of CM injection protocols in coronary CT angiography with PCD-CT. The 1-2-3 rule demonstrates the potential for reducing the effects of calcium blooming artifacts on overall image quality.

Tungsten-Based Contrast Agent for Photon-Counting Detector CT Angiography in Calcified Coronaries: Comparison to Iodine in a Cardiovascular Phantom.

OBJECTIVES: Calcified plaques induce blooming artifacts in coronary computed tomography angiography (CCTA) potentially leading to inaccurate stenosis evaluation. Tungsten represents a high atomic number, experimental contrast agent with different physical properties than iodine. We explored the potential of a tungsten-based contrast agent for photon-counting detector (PCD) CCTA in heavily calcified coronary vessels. MATERIALS AND METHODS: A cardiovascular phantom exhibiting coronaries with calcified plaques was imaged on a first-generation dual-source PCD-CT. The coronaries with 3 different calcified plaques were filled with iodine and tungsten contrast media solutions equating to iodine and tungsten delivery rates (IDR and TDR) of 0.3, 0.5, 0.7, 1.0, 1.5, 2.0, 2.5, and 3.0 g/s, respectively. Electrocardiogram-triggered sequential acquisitions were performed in the spectral mode (QuantumPlus). Virtual monoenergetic images (VMIs) were reconstructed from 40 to 190 keV in 1 keV increments. Blooming artifacts and percentage error stenoses from calcified plaques were quantified, and attenuation characteristics of both contrast media were recorded. RESULTS: Blooming artifacts from calcified plaques were most pronounced at 40 keV (78%) and least pronounced at 190 keV (58%). Similarly, percentage error stenoses were highest at 40 keV (48%) and lowest at 190 keV (2%), respectively. Attenuation of iodine decreased monotonically in VMIs from low to high keV, with the strongest decrease from 40 keV to 100 keV (IDR of 2.5 g/s: 1279 HU at 40 keV, 187 HU at 100 kV, and 35 HU at 190 keV). The attenuation of tungsten, on the other hand, increased monotonically as a function of VMI energy, with the strongest increase between 40 and 100 keV (TDR of 2.5 g/s: 202 HU at 40 keV, 661 HU at 100 kV, and 717 HU at 190 keV). For each keV level, the relationship between attenuation and IDR/TDR could be described by linear regressions (R2 ≥ 0.88, P < 0.001). Specifically, attenuation increased linearly when increasing the delivery rate irrespective of keV level or contrast medium. Iodine exhibited the highest relative increase in attenuation values at lower keV levels when increasing the IDR. Conversely, for tungsten, the greatest relative increase in attenuation values occurred at higher keV levels when increasing the TDR. When high keV imaging is desirable to reduce blooming artifacts from calcified plaques, IDR has to be increased at higher keV levels to maintain diagnostic vessel attenuation (ie, 300 HU), whereas for tungsten, TDR can be kept constant or can be even reduced at high keV energy levels. CONCLUSIONS: Tungsten's attenuation characteristics in relation to VMI energy levels are reversed to those of iodine, with tungsten exhibiting high attenuation values at high keV levels and vice versa. Thus, tungsten shows promise for high keV imaging CCTA with PCD-CT as-in distinction to iodine-both high vessel attenuation and low blooming artifacts from calcified plaques can be achieved.

Gadolinium Presence in Rat Skin: Assessment of Histopathologic Changes Associated with Small Fiber Neuropathy.

Background The presence of gadolinium traces in the skin after administration of gadolinium-based contrast agents (GBCAs) raised safety concerns regarding a potential association with small fiber neuropathy (SFN). Purpose To investigate signs of SFN in rat foot pads by quantification of the intraepidermal nerve fiber density (IENFD) after multiple GBCA administrations and to evaluate gadolinium concentration, chemical species, and clearance. Materials and Methods Fifty rats received eight intravenous injections of either gadodiamide, gadobutrol, gadoterate, gadoteridol (8 × 0.6 mmol per kilogram of body weight), or saline (1.2 mL per kilogram of body weight), within 2 weeks and were sacrificed 5 days or 5 weeks after the last injection. IENFD was determined with protein gene product (PGP) 9.5 immunofluorescent staining and blinded and automated image analysis. The gadolinium and GBCA concentrations were measured with inductively coupled plasma mass spectrometry (ICP-MS), laser ablation ICP-MS, and matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI). P values were calculated using linear contrasts of model analysis. Results The IENFD (measured as geometric mean [SD] and in number of nerve fibers per millimeter of epidermis) was not significantly altered after 5 days (saline, 8.4 [1.1]; gadobutrol, 9.7 [1.2]; gadoterate, 9.2 [1.2]; gadoteridol, 9.9 [1.3]; gadodiamide, 10.5 [1.2]) or 5 weeks (saline, 19.7 [1.4]; gadobutrol, 16.4 [1.6]; gadoterate, 14.3 [1.6]; gadoteridol, 22.2 [1.8]; gadodiamide, 17.9 [1.4]). Gadolinium skin concentrations were highest for gadodiamide after 5 days (16.0 nmol/g [1.1]) and 5 weeks (10.6 nmol/g [1.2], -33%). Macrocyclic agents were lower at 5 days (gadoteridol, 2.6 nmol/g [1.2]; gadobutrol, 2.7 nmol/g [1.1]; and gadoterate, 2.3 nmol/g [1.2]) and efficiently cleared after 5 weeks (gadoteridol, -95%; gadobutrol and gadoterate, -96%). The distribution of gadolinium and IENF did not visually overlap. For macrocyclic agents, gadolinium was found in sweat glands and confirmed to be intact chelate. Conclusion There were no signs of SFN in rat foot pads using multiple dosing regimens at two time points after administration of GBCAs. Macrocyclic GBCAs exhibited lower levels of gadolinium in the skin and were effectively eliminated within 5 weeks compared with linear gadodiamide, and intact macrocyclic GBCA was detected in sweat glands. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Clement in this issue.

AI as a New Frontier in Contrast Media Research: Bridging the Gap Between Contrast Media Reduction, the Contrast-Free Question and New Application Discoveries.

ABSTRACT: Artificial intelligence (AI) techniques are currently harnessed to revolutionize the domain of medical imaging. This review investigates 3 major AI-driven approaches for contrast agent management: new frontiers in contrast agent dose reduction, the contrast-free question, and new applications. By examining recent studies that use AI as a new frontier in contrast media research, we synthesize the current state of the field and provide a comprehensive understanding of the potential and limitations of AI in this context. In doing so, we show the dose limits of reducing the amount of contrast agents and demonstrate why it might not be possible to completely eliminate contrast agents in the future. In addition, we highlight potential new applications to further increase the radiologist's sensitivity at normal doses. At the same time, this review shows which network architectures provide promising approaches and reveals possible artifacts of a paired image-to-image conversion. Furthermore, current US Food and Drug Administration regulatory guidelines regarding AI/machine learning-enabled medical devices are highlighted.

Comprehensive Analysis of the Spatial Distribution of Gadolinium, Iron, Manganese, and Phosphorus in the Brain of Healthy Rats After High-Dose Administrations of Gadodiamide and Gadobutrol.

OBJECTIVES: After the administration of gadolinium-based contrast agents (GBCAs), residual gadolinium (Gd) has been detected in a few distinct morphological structures of the central nervous system (CNS). However, a systematic, comprehensive, and quantitative analysis of the spatial Gd distribution in the entire brain is not yet available. The first aim of this study is to provide this analysis in healthy rats after administration of high GBCA doses. The second aim is to assess the spatial distributions and possible Gd colocalizations of endogenous iron (Fe), manganese (Mn), and phosphorus (P). In addition, the presence of Gd in proximity to blood vessels was assessed by immunohistochemistry. MATERIALS AND METHODS: Male rats were randomly assigned to 3 groups (n = 3/group): saline (control), gadodiamide (linear GBCA), and gadobutrol (macrocyclic GBCA) with cumulative Gd doses of 14.4 mmol/kg of body mass. Five weeks after the last administration, the brains were collected and cryosectioned. The spatial distributions of Gd, Fe, Mn, and P were analyzed in a total of 130 sections, each covering the brain in 1 of the 3 perpendicular anatomical orientations, using laser ablation coupled with inductively coupled plasma mass spectrometry. Quantitative spatial element maps were generated, and the concentrations of Gd, Fe, and Mn were measured in 31 regions of interest covering various distinct CNS structures. Correlation analyses were performed to test for possible colocalization of Gd, Fe, and Mn. The spatial proximity of Gd and blood vessels was studied using metal-tagged antibodies against von Willebrand factor with laser ablation coupled with inductively coupled plasma mass spectrometry. RESULTS: After administration of linear gadodiamide, high Gd concentrations were measured in many distinct structures of the gray matter. This involved structures previously reported to retain Gd after linear GBCA, such as the deep cerebellar nuclei or the globus pallidus, but also structures that had not been reported so far including the dorsal subiculum, the retrosplenial cortex, the superior olivary complex, and the inferior colliculus. The analysis in all 3 orientations allowed the localization of Gd in specific subregions and layers of certain structures, such as the hippocampus and the primary somatosensory cortex. After macrocyclic gadobutrol, the Gd tissue concentration was significantly lower than after gadodiamide. Correlation analyses of region of interest concentrations of Gd, Fe, and Mn revealed no significant colocalization of Gd with endogenous Fe or Mn in rats exposed to either GBCA. Immunohistochemistry revealed a colocalization of Gd traces with vascular endothelium in the deep cerebellar nuclei after gadobutrol, whereas the majority of Gd was found outside the vasculature after gadodiamide. CONCLUSIONS: In rats exposed to gadodiamide but not in rats exposed to gadobutrol, high Gd concentrations were measured in various distinct CNS structures, and structures not previously reported were identified to contain Gd, including specific subregions and layers with different cytoarchitecture and function. Knowledge of these distinct spatial patterns may pave the way for tailored functional neurological testing. Signs for the localization of the remaining Gd in the vascular endothelium were prominent for gadobutrol but not gadodiamide. The results also indicate that local transmetalation with endogenous Fe or Mn is unlikely to explain the spatial patterns of Gd deposition in the brain, which argues against a general role of these metals in local transmetalation and release of Gd ions in the CNS.

Individualized scan protocols for CT angiography: an animal study for contrast media or radiation dose optimization.

BACKGROUND: We investigated about optimization of contrast media (CM) dose or radiation dose in thoracoabdominal computed tomography angiography (CTA) by automated tube voltage selection (ATVS) system configuration and CM protocol adaption. METHODS: In six minipigs, CTA-optimized protocols were evaluated regarding objective (contrast-to-noise ratio, CNR) and subjective (6 criteria assessed by Likert scale) image quality. Scan parameters were automatically adapted by the ATVS system operating at 90-kV semi-mode and configured for standard, CM saving, or radiation dose saving (image task, quality settings). Injection protocols (dose, flow rate) were adapted manually. This approach was tested for normal and simulated obese conditions. RESULTS: Radiation exposure (volume-weighted CT dose index) for normal (obese) conditions was 2.4 ± 0.7 (5.0 ± 0.7) mGy (standard), 4.3 ± 1.1 (9.0 ± 1.3) mGy (CM reduced), and 1.7 ± 0.5 (3.5 ± 0.5) mGy (radiation reduced). The respective CM doses for normal (obese) settings were 210 (240) mgI/kg, 155 (177) mgI/kg, and 252 (288) mgI/kg. No significant differences in CNR (normal; obese) were observed between standard (17.8 ± 3.0; 19.2 ± 4.0), CM-reduced (18.2 ± 3.3; 20.5 ± 4.9), and radiation-saving CTAs (16.0 ± 3.4; 18.4 ± 4.1). Subjective analysis showed similar values for optimized and standard CTAs. Only the parameter diagnostic acceptability was significantly lower for radiation-saving CTA compared to the standard CTA. CONCLUSIONS: The CM dose (-26%) or radiation dose (-30%) for thoracoabdominal CTA can be reduced while maintaining objective and subjective image quality, demonstrating the feasibility of the personalization of CTA scan protocols. KEY POINTS: • Computed tomography angiography protocols could be adapted to individual patient requirements using an automated tube voltage selection system combined with adjusted contrast media injection. • Using an adapted automated tube voltage selection system, a contrast media dose reduction (-26%) or radiation dose reduction (-30%) could be possible.

New Contrast Media for K-Edge Imaging With Photon-Counting Detector CT.

ABSTRACT: The recent technological developments in photon-counting detector computed tomography (PCD-CT) and the introduction of the first commercially available clinical PCD-CT unit open up new exciting opportunities for contrast media research. With PCD-CT, the efficacy of available iodine-based contrast media improves, allowing for a reduction of iodine dosage or, on the other hand, an improvement of image quality in low contrast indications. Virtual monoenergetic image reconstructions are routinely available and enable the virtual monoenergetic image energy to be adapted to the diagnostic task.A key property of PCD-CT is the ability of spectral separation in combination with improved material decomposition. Thus, the discrimination of contrast media from intrinsic or pathological tissues and the discrimination of 2 or more contrasting elements that characterize different tissues are attractive fields for contrast media research. For these approaches, K-edge imaging in combination with high atomic number elements such as the lanthanides, tungsten, tantalum, or bismuth plays a central role.The purpose of this article is to present an overview of innovative contrast media concepts that use high atomic number elements. The emphasis is on improving contrast enhancement for cardiovascular plaque imaging, stent visualization, and exploring new approaches using 2 contrasting elements. Along with the published research, new experimental findings with a contrast medium that incorporates tungsten are included.Both the literature review and the new experimental data demonstrate the great potential and feasibility for new contrast media to significantly increase diagnostic performance and to enable new clinical fields and indications in combination with PCD-CT.

Contrast Agent Dose Reduction in MRI Utilizing a Generative Adversarial Network in an Exploratory Animal Study.

OBJECTIVES: The aim of this study is to use virtual contrast enhancement to reduce the amount of hepatobiliary gadolinium-based contrast agent in magnetic resonance imaging with generative adversarial networks (GANs) in a large animal model. METHODS: With 20 healthy Göttingen minipigs, a total of 120 magnetic resonance imaging examinations were performed on 6 different occasions, 50% with reduced (low-dose; 0.005 mmol/kg, gadoxetate) and 50% standard dose (normal-dose; 0.025 mmol/kg). These included arterial, portal venous, venous, and hepatobiliary contrast phases (20 minutes, 30 minutes). Because of incomplete examinations, one animal had to be excluded. Randomly, 3 of 19 animals were selected and withheld for validation (18 examinations). Subsequently, a GAN was trained for image-to-image conversion from low-dose to normal-dose (virtual normal-dose) with the remaining 16 animals (96 examinations). For validation, vascular and parenchymal contrast-to-noise ratio (CNR) was calculated using region of interest measurements of the abdominal aorta, inferior vena cava, portal vein, hepatic parenchyma, and autochthonous back muscles. In parallel, a visual Turing test was performed by presenting the normal-dose and virtual normal-dose data to 3 consultant radiologists, blinded for the type of examination. They had to decide whether they would consider both data sets as consistent in findings and which images were from the normal-dose study. RESULTS: The pooled dynamic phase vascular and parenchymal CNR increased significantly from low-dose to virtual normal-dose (pooled vascular: P < 0.0001, pooled parenchymal: P = 0.0002) and was found to be not significantly different between virtual normal-dose and normal-dose examinations (vascular CNR [mean ± SD]: low-dose 17.6 ± 6.0, virtual normal-dose 41.8 ± 9.7, and normal-dose 48.4 ± 12.2; parenchymal CNR [mean ± SD]: low-dose 20.2 ± 5.9, virtual normal-dose 28.3 ± 6.9, and normal-dose 29.5 ± 7.2). The pooled parenchymal CNR of the hepatobiliary contrast phases revealed a significant increase from the low-dose (22.8 ± 6.2) to the virtual normal-dose (33.2 ± 6.1; P < 0.0001) and normal-dose sequence (37.0 ± 9.1; P < 0.0001). In addition, there was no significant difference between the virtual normal-dose and normal-dose sequence. In the visual Turing test, on the median, the consultant radiologist reported that the sequences of the normal-dose and virtual normal-dose are consistent in findings in 100% of the examinations. Moreover, the consultants were able to identify the normal-dose series as such in a median 54.5% of the cases. CONCLUSIONS: In this feasibility study in healthy Göttingen minipigs, it could be shown that GAN-based virtual contrast enhancement can be used to recreate the image impression of normal-dose imaging in terms of CNR and subjective image similarity in both dynamic and hepatobiliary contrast phases from low-dose data with an 80% reduction in gadolinium-based contrast agent dose. Before clinical implementation, further studies with pathologies are needed to validate whether pathologies are correctly represented by the network.

Third-Generation Cardiovascular Phantom: The Next Generation of Preclinical Research in Diagnostic Imaging.

OBJECTIVE: Different types of preclinical research tools used in the field of diagnostic imaging such as dynamic flow circulation phantoms have built the foundation for optimization and advancement of clinical procedures including new imaging techniques. The objective was to introduce a third-generation phantom, building on the limitations of earlier versions and unlocking new opportunities for preclinical investigation. MATERIAL AND METHODS: A third-generation phantom was designed and constructed comprising physiological vascular models from head to toe, including a 4-chamber heart with embedded heart valves and a controllable electromechanical pump. The models include modular segments, allowing for interchangeability between healthy and diseased vessels. Clinical sanity checks were performed using the phantom in combination with a dual-head power injector on a third-generation dual-source computed tomography scanner. Contrast media was injected at 1.5 g I/s, and the phantom was configured with a cardiac output of 5.3 L/min. Measurements of mean transit times between key vascular landmarks and peak enhancement values in Hounsfield units (HUs) were measured to compare with expected in vivo results estimated from literature. RESULTS: Good agreement was obtained between literature reference values from physiology and measured results. Contrast arrival between antecubital vein and right ventricle was measured to be 13.1 ± 0.3 seconds. Transit time from right ventricle to left ventricle was 12.0 ± 0.2 seconds, from left internal carotid artery to left internal jugular vein 7.7 ± 0.4 seconds, and 2.9 ± 0.2 seconds from aortic arch to aortic bifurcation. The peak enhancement measured in the regions of interest was between 336 HU and 557 HU. CONCLUSIONS: The third-generation phantom demonstrated the capability of simulating physiologic in vivo conditions with accurate contrast media transport timing, good repeatability, and expected enhancement profiles. As a nearly complete cardiovascular system including a functioning 4-chamber heart and interchangeable disease states, the third-generation phantom presents new opportunities for the expansion of preclinical research in diagnostic imaging.

Preclinical Profile of Gadoquatrane: A Novel Tetrameric, Macrocyclic High Relaxivity Gadolinium-Based Contrast Agent.

OBJECTIVES: The aim of this report was to characterize the key physicochemical, pharmacokinetic (PK), and magnetic resonance imaging (MRI) properties of gadoquatrane (BAY 1747846), a newly designed tetrameric, macrocyclic, extracellular gadolinium-based contrast agent (GBCA) with high relaxivity and stability. MATERIALS AND METHODS: The r1-relaxivities of the tetrameric gadoquatrane at 1.41 and 3.0 T were determined in human plasma and the nuclear magnetic relaxation dispersion profiles in water and plasma. The complex stability was analyzed in human serum over 21 days at pH 7.4 at 37°C and was compared with the linear GBCA gadodiamide and the macrocyclic GBCA (mGBCA) gadobutrol. In addition, zinc transmetallation assay was performed to investigate the kinetic inertness. Protein binding and the blood-to-plasma ratio were determined in vitro using rat and human plasma. The PK profile was evaluated in rats (up to 7 days postinjection). Magnetic resonance imaging properties were investigated using a glioblastoma (GS9L) rat model. RESULTS: The new chemical entity gadoquatrane is a macrocyclic tetrameric Gd complex with one inner sphere water molecule per Gd ( q = 1). Gadoquatrane showed high solubility in buffer (1.43 mol Gd/L, 10 mM Tris-HCl, pH 7.4), high hydrophilicity (logP -4.32 in 1-butanol/water), and negligible protein binding. The r1-relaxivity of gadoquatrane in human plasma per Gd of 11.8 mM -1 ·s -1 (corresponding to 47.2 mM -1 ·s -1 per molecule at 1.41 T at 37°C, pH 7.4) was more than 2-fold (8-fold per molecule) higher compared with established mGBCAs. Nuclear magnetic relaxation dispersion profiles confirmed the more than 2-fold higher r1-relaxivity in human plasma for the clinically relevant magnetic field strengths from 0.47 to 3.0 T. The complex stability of gadoquatrane at physiological conditions was very high. The observed Gd release after 21 days at 37°C in human serum was below the lower limit of quantification. Gadoquatrane showed no Gd 3+ release in the presence of zinc in the transmetallation assay. The PK profile (plasma elimination, biodistribution, recovery) was comparable to that of gadobutrol. In MRI, the quantitative evaluation of the tumor-to-brain contrast in the rat glioblastoma model showed significantly improved contrast enhancement using gadoquatrane compared with gadobutrol at the same Gd dose administered (0.1 mmol Gd/kg body weight). In comparison to gadoterate meglumine, similar contrast enhancement was reached with gadoquatrane with 75% less Gd dose. In terms of the molecule dose, this was reduced by 90% when compared with gadoterate meglumine. Because of its tetrameric structure and hence lower number of molecules per volume, all prepared formulations of gadoquatrane were iso-osmolar to blood. CONCLUSIONS: The tetrameric gadoquatrane is a novel, highly effective mGBCA for use in MRI. Gadoquatrane provides favorable physicochemical properties (high relaxivity and stability, negligible protein binding) while showing essentially the same PK profile (fast extracellular distribution, fast elimination via the kidneys in an unchanged form) to established mGBCAs on the market. Overall, gadoquatrane is an excellent candidate for further clinical development.

Effect of Contrast Agent Dose Reduction on Vascular Enhancement and Image Quality in Thoracoabdominal Dynamic 3-Dimensional Magnetic Resonance Angiography: A Systematic Intraindividual Analysis in Pigs.

OBJECTIVE: High spatial and temporal resolution contrast-enhanced magnetic resonance angiography (MRA) with gadolinium-based contrast agents (GBCAs) at standard dose offers both detailed anatomic information on both arterial and venous vessels and hemodynamic characteristics. Several preclinical and clinical dynamic 3-dimensional (3D) MRA studies that focused on arterial vessels only proposed that high image quality may also be achieved with significantly reduced GBCA doses, calling into question the need to use standard doses. A systematic analysis of GBCA doses and resulting image quality for both arteries and veins has not yet been performed. The purpose of this study was therefore to systematically analyze dose-dependent vascular enhancements in dynamic 3D-MRA of the thoracoabdominal vasculature at 1.5 T in an animal model to determine the optimal contrast agent protocol for optimized vascular assessment. MATERIALS AND METHODS: The vascular enhancement in thoracoabdominal dynamic 3D-MRA (time-resolved angiography with interleaved stochastic trajectories, TWIST at 1.5 T) was interindividually and intraindividually compared in 5 anesthetized Göttingen minipigs using gadobutrol at the standard dose (0.1 mmol/kg body weight, ie, 0.1 mL/kg) and at reduced doses (0.08, 0.06, 0.04, 0.02 mmol/kg) in a randomized order. All injections were performed at 2 mL/s followed by 20 mL saline. Images were quantitatively analyzed, measuring signal intensities in 5 regions that covered the passage of the GBCA through the body at different representative stages of circulation (pulmonary, arterial, and venous system). The evaluation of GBCA dose-dependent signal intensity changes in the different vascular regions was performed by linear regression analysis.The qualitative image analysis of dynamic 3D-MRA by 3 independent radiologists included the visibility of 25 arterial and venous vessel segments at different stages of GBCA passage. Possible quality losses were statistically tested by comparing image quality ratings at the reduced dose with that of the standard dose using Friedman test followed by Dunn post hoc test for multiple comparison. Significance was stated at P < 0.05. RESULTS: Quantitative analysis revealed shorter time-to-peak intervals and bolus durations in line with decreasing GBCA dose and volume in all vessels. Although the peak signal was almost independent of the administered GBCA dose at the level of the pulmonary trunk, a linear signal decrease in the abdominal aorta ( r2 = 0.96), the renal arteries ( r2 = 0.99), the inferior vena cava ( r2 = 0.99), and the portal vein ( r2 = 0.97) was observed. Cumulative analysis of arterial segments revealed significantly lower image quality at doses below 40% of the standard dose, whereas in venous segments, significantly lower image quality was observed at doses below 60% of the standard dose. CONCLUSIONS: In dynamic 3D-MRA at 1.5 T, dose reduction leads to a signal loss that is most pronounced in the venous system and results in significantly lower image quality according to the dose and vessels of interest. Careful dose reduction is thus required according to the specific diagnostic needs. For dynamic 3D-MRA of the arterial and venous system, GBCA doses of at least 60% of the standard dose up to the full dose are preferable, whereas 40% of the standard dose seems feasible if only the arterial system is to be imaged.

Contrast Media Reduction in Computed Tomography With Deep Learning Using a Generative Adversarial Network in an Experimental Animal Study.

OBJECTIVE: This feasibility study aimed to use optimized virtual contrast enhancement through generative adversarial networks (GAN) to reduce the dose of iodine-based contrast medium (CM) during abdominal computed tomography (CT) in a large animal model. METHODS: Multiphasic abdominal low-kilovolt CTs (90 kV) with low (low CM, 105 mgl/kg) and normal contrast media doses (normal CM, 350 mgl/kg) were performed with 20 healthy Göttingen minipigs on 3 separate occasions for a total of 120 examinations. These included an early arterial, late arterial, portal venous, and venous contrast phase. One animal had to be excluded because of incomplete examinations. Three of the 19 animals were randomly selected and withheld for validation (18 studies). Subsequently, the GAN was trained for image-to-image conversion from low CM to normal CM (virtual CM) with the remaining 16 animals (96 examinations). For validation, region of interest measurements were performed in the abdominal aorta, inferior vena cava, portal vein, liver parenchyma, and autochthonous back muscles, and the contrast-to-noise ratio (CNR) was calculated. In addition, the normal CM and virtual CM data were presented in a visual Turing test to 3 radiology consultants. On the one hand, they had to decide which images were derived from the normal CM examination. On the other hand, they had to evaluate whether both images are pathological consistent. RESULTS: Average vascular CNR (low CM 6.9 ± 7.0 vs virtual CM 28.7 ± 23.8, P < 0.0001) and parenchymal (low CM 1.5 ± 0.7 vs virtual CM 3.8 ± 2.0, P < 0.0001) CNR increased significantly by GAN-based contrast enhancement in all contrast phases and was not significantly different from normal CM examinations (vascular: virtual CM 28.7 ± 23.8 vs normal CM 34.2 ± 28.8; parenchymal: virtual CM 3.8 ± 2.0 vs normal CM 3.7 ± 2.6). During the visual Turing testing, the radiology consultants reported that images from normal CM and virtual CM were pathologically consistent in median in 96.5% of the examinations. Furthermore, it was possible for the examiners to identify the normal CM data as such in median in 91% of the cases. CONCLUSIONS: In this feasibility study, it could be demonstrated in an experimental setting with healthy Göttingen minipigs that the amount of CM for abdominal CT can be reduced by approximately 70% by GAN-based contrast enhancement with satisfactory image quality.

The Effect of Gadolinium-Based Contrast Agents on Longitudinal Changes of Magnetic Resonance Imaging Signal Intensities and Relaxation Times in the Aging Rat Brain.

OBJECTIVES: The aim of the study was to investigate the possible influence of changes in the brain caused by age on relaxometric and relaxation time-weighted magnetic resonance imaging (MRI) parameters in the deep cerebellar nuclei (DCN) and the globus pallidus (GP) of Gd-exposed and control rats over the course of 1 year. MATERIALS AND METHODS: Twenty-five Wistar-Han rats were equally subdivided into 5 groups and initially received 8 injections on 4 consecutive days per week of either 3.6 mL/kg body weight saline (group I-III) or 1.8 mmol Gd/kg body weight gadobutrol (group IV) or gadodiamide (group V). T1- and T2-weighted scans, as well as relaxation maps, were acquired at 1 week (all groups); 5, 12, 20, and 26 weeks (saline II, gadobutrol, gadodiamide); and at 35, 44, and 52 weeks (saline III, gadobutrol, gadodiamide) after the last administration. Saline I was euthanized after 1 week, saline II after 26 weeks, and the remaining groups after 52 weeks. Signal intensities (SIs) were evaluated for the DCN/pons (P) and the GP/piriform cortex (PC) ratios, and relaxation times for the DCN and the GP. Brain tissue was extracted, and the gadolinium, iron, and manganese contents were quantified with inductively coupled plasma mass spectrometry (ICP-MS) and laser ablation-ICP-MS imaging. RESULTS: T1-weighted SI ratios did not show any significant trend with age in any region. The between-group analysis at 52 weeks resulted in a significant difference for the DCN/P and GP/PC region ratio between gadodiamide and its comparators. T1 relaxation times dropped with increasing age in the GP with a 10% to 20% difference between first and last measurement for all groups, and in the DCN <10% with a significant decrease for the gadodiamide group only (DCN: P = 0.0158). Group-related differences were observed at the last measurement time point for T1 values between gadodiamide and saline III in the DCN (P = 0.0153) and gadodiamide and gadobutrol in the GP (P = 0.0287). Analysis of the SI ratios of the T2-weighted images revealed a significant increase for the DCN/P and a decrease for the GP/PC with increasing age for all groups and no differences at 52 weeks after the last injection between groups. T2 values of the GP showed a significant linear decrease over time for all groups (saline I-III: P = 0.0101; gadobutrol: P = 0.0001; gadodiamide: P = 0.0142) in the aging rat brain. Quantitative imaging of manganese and iron by laser ablation-ICP-MS showed a linear increase for the saline groups in the GP for both metals (Fe: P < 0.0001; Mn: P = 0.0306) and in the DCN for manganese only (P = 0.0187), but no differences between groups at 52 weeks. CONCLUSIONS: Extensive MRI evaluation did not reveal an indication of SI or relaxation time changes associated with multiple exposure to the macrocyclic-chelated GBCA gadobutrol in the DCN and the GP. With increasing age, a T1 and T2 shortening in the GP and an increase in T2-weighted SI ratio in the DCN/P, as well as a decrease in the GP/PC, were observed for all groups. Such age-related changes can potentially bias MRI results as an indicator for gadolinium presence in the brain.

Individualized Scan Protocols in Abdominal Computed Tomography: Radiation Versus Contrast Media Dose Optimization.

BACKGROUND: In contrast-enhanced abdominal computed tomography (CT), radiation and contrast media (CM) injection protocols are closely linked to each other, and therefore a combination is the basis for achieving optimal image quality. However, most studies focus on optimizing one or the other parameter separately. PURPOSE: Reducing radiation dose may be most important for a young patient or a population in need of repetitive scanning, whereas CM reduction might be key in a population with insufficient renal function. The recently introduced technical solution, in the form of an automated tube voltage selection (ATVS) slider, might be helpful in this respect. The aim of the current study was to systematically evaluate feasibility of optimizing either radiation or CM dose in abdominal imaging compared with a combined approach. METHODS: Six Göttingen minipigs (mean weight, 38.9 ± 4.8 kg) were scanned on a third-generation dual-source CT. Automated tube voltage selection and automated tube current modulation techniques were used, with quality reference values of 120 kVref and 210 mAsref. Automated tube voltage selection was set at 90 kV semimode. Three different abdominal scan and CM protocols were compared intraindividually: (1) the standard "combined" protocol, with the ATVS slider position set at 7 and a body weight-adapted CM injection protocol of 350 mg I/kg body weight, iodine delivery rate (IDR) of 1.1 g I/s; (2) the CM dose-saving protocol, with the ATVS slider set at 3 and CM dose lowered to 294 mg I/kg, resulting in a lower IDR of 0.9 g I/s; (3) the radiation dose-saving protocol, with the ATVS slider position set at 11 and a CM dose of 441 mg I/kg and an IDR 1.3 g I/s, respectively. Scans were performed with each protocol in arterial, portal venous, and delayed phase. Objective image quality was evaluated by measuring the attenuation in Hounsfield units, signal-to-noise ratio, and contrast-to-noise ratio of the liver parenchyma. The overall image quality, contrast quality, noise, and lesion detection capability were rated on a 5-point Likert scale (1 = excellent, 5 = very poor). Protocols were compared for objective image quality parameters using 1-way analysis of variance and for subjective image quality parameters using Friedman test. RESULTS: The mean radiation doses were 5.2 ± 1.7 mGy for the standard protocol, 7.1 ± 2.0 mGy for the CM dose-saving protocol, and 3.8 ± 0.4 mGy for the radiation dose-saving protocol. The mean total iodine load in these groups was 13.7 ± 1.7, 11.4 ± 1.4, and 17.2 ± 2.1 g, respectively. No significant differences in subjective overall image or contrast quality were found. Signal-to-noise ratio and contrast-to-noise ratio were not significantly different between protocols in any scan phase. Significantly more noise was seen when using the radiation dose-saving protocol (P < 0.01). In portal venous and delayed phases, the mean attenuation of the liver parenchyma significantly differed between protocols (P < 0.001). Lesion detection was significantly better in portal venous phase using the CM dose-saving protocol compared with the radiation dose-saving protocol (P = 0.037). CONCLUSIONS: In this experimental setup, optimizing either radiation (-26%) or CM dose (-16%) is feasible in abdominal CT imaging. Individualizing either radiation or CM dose leads to comparable objective and subjective image quality. Personalized abdominal CT examination protocols can thus be tailored to individual risk assessment and might offer additional degrees of freedom.

Low kV Computed Tomography of Parenchymal Abdominal Organs-A Systematic Animal Study of Different Contrast Media Injection Protocols.

OBJECTIVES: To evaluate multiphase low kV computed tomography (CT) imaging of the abdomen with reduced contrast media (CM) dose using different injection protocols. METHODS: Two injection protocols were evaluated for use with low kV (80 kV) multiphase abdominal imaging in comparison to the standard procedure acquired at 120 kV (500 mgI/kg; 5 mL/s). This evaluation was conducted in a highly standardized animal study (5 Goettingen minipigs). The low kV protocols consisted of (a) a single-flow (SF) injection with 40% reduced CM dose and injection rate (300 mgI/kg; 3 mL/s) and (b) a DualFlow (DF) injection protocol consisting of 60%/40% contrast to saline ratio administered at 5 mL/s. Dynamic CT was first performed within representative liver regions to determine optimal contrast phases, followed by evaluation of the three protocols in multiphase abdominal CT imaging. The evaluation criteria included contrast enhancement (CE) of abdominal organs and vasculature. RESULTS: The 80 kV DF injection protocol showed similar CE of the abdominal parenchymatous organs and vessels to the 120 kV reference and the 80 kV SF protocol. Hepatic parenchyma showed comparable CT values for all contrast phases. In particular, in the portal venous parenchymal phase, the 80 kV DF protocol demonstrated higher hepatic parenchymal enhancement; however, results were statistically non-significant. Similarly, CE of the kidney, pancreas, and abdominal arterial/venous vessels showed no significant differences between injection protocols. CONCLUSIONS: Adapted SF and DF injection protocols with reduced IDR/iodine load offer the potential to calibrate optimal CM doses to the tube voltage in abdominal multiphase low kV CT imaging. The data suggest that the DF approach allows the use of predefined injection protocols and adaption of the contrast to saline ratio to an individualized kV setting and yields the potential for patient-individualized CM adaption.

Intraindividual Comparison of Compressed Sensing-Accelerated Cartesian and Radial Arterial Phase Imaging of the Liver in an Experimental Tumor Model.

OBJECTIVES: The aim of this study was to intraindividually compare the performance of 2 compressed sensing (CS)-accelerated magnetic resonance imaging (MRI) sequences, 1 featuring Cartesian (compressed sensing volumetric interpolated breath-hold examination [CS-VIBE]) and the other radial (golden-angle radial sparse parallel [GRASP]) k-space sampling in continuous dynamic imaging during hepatic vascular phases, using extracellular and hepatocyte-specific contrast agents. MATERIALS AND METHODS: Seven New Zealand white rabbits, with induced VX2 liver tumors (median number of lesions, 2 ± 0.83; range, 1-3), received 2 continuously acquired T1-weighted prototype CS-accelerated MRI sequences (CS-VIBE and GRASP) with high spatial (0.8 × 0.8 × 1.5 mm) and temporal resolution (3.5 seconds) in randomized order on 2 separate days using a 1.5-T scanner. In all animals, imaging was performed using first gadobutrol at a dose of 0.1 mmol/kg and, then 45 minutes later, gadoxetic acid at a dose of 0.025 mmol/kg.The following qualitative parameters were assessed using 3- and 5-point Likert scales (3 and 5 being the highest scores respectively): image quality (IQ), arterial and venous vessel delineation, tumor enhancement, motion artifacts, and sequence-specific artifacts. Furthermore, the following quantitative parameters were obtained: relative peak signal enhancement, time to peak, mean transit time, and plasma flow ratios. Paired sampled t tests and Wilcoxon signed rank tests were used for intraindividual comparison. Image analysis was performed by 2 radiologists. RESULTS: Six of 7 animals underwent the full imaging protocol and obtained data were analyzed statistically. Overall IQ was rated moderate to excellent, not differing significantly between the 2 sequences.Gadobutrol-enhanced CS-VIBE examinations revealed the highest mean Likert scale values in terms of vessel delineation and tumor enhancement (arterial 4.4 [4-5], venous 4.3 [3-5], and tumor 2.9 [2-3]). Significantly, more sequence-specific artifacts were seen in GRASP examinations (P = 0.008-0.031). However, these artifacts did not impair IQ. Excellent Likert scale ratings were found for motion artifacts in both sequences. In both sequences, a maximum of 4 hepatic arterial dominant phases were obtained. Regarding the relative peak signal enhancement, CS-VIBE and GRASP showed similar results. The relative peak signal enhancement values did not differ significantly between the 2 sequences in the aorta, the hepatic artery, or the inferior vena cava (P = 0.063-0.536). However, significantly higher values were noted for CS-VIBE in gadoxetic acid-enhanced examinations in the portal vein (P = 0.031) and regarding the tumor enhancement (P = 0.005). Time to peak and mean transit time or plasma flow ratios did not differ significantly between the sequences. CONCLUSIONS: Both CS-VIBE and GRASP provide excellent results in dynamic liver MRI using extracellular and hepatocyte-specific contrast agents, in terms of IQ, peak signal intensity, and presence of artifacts.

Photon-Counting Multienergy Computed Tomography With Spectrally Optimized Contrast Media for Plaque Removal and Stenosis Assessment.

PURPOSE: The aim of this study was to systematically evaluate the potential to combine investigational contrast media with spectrally optimized energy-thresholding of photon-counting detector computed tomography (PCCT) for subtraction of calcified plaques in a coronary artery stenosis phantom. METHODS: A small vessel phantom containing 3 fillable tubes (diameter, 3 mm each) with calcified plaques was placed into an anthropomorphic chest phantom. The plaques had incremental thicknesses ranging from 0.3 to 2.7 mm, simulating vessel stenoses ranging from 10% to 90% of the lumen diameter. The phantom was filled with 5 different investigational contrast media (iodine, bismuth, hafnium, holmium, and tungsten) at equal mass concentrations (15 mg/mL) and was imaged on a prototype PCCT at 140 kVp using optimized, contrast media-dependent energy thresholds. Contrast maps (CMs) were reconstructed for each contrast medium by applying a linear 2-material decomposition algorithm. Image noise magnitude and noise texture of CM were compared among the contrast media using the noise power spectrum. Two blinded readers independently rated the vessel lumen visualization on short-axis and the overall subjective image quality on long-axis CM relative to iodine as the reference standard. Four readers determined the highest degree of stenosis that could be assessed with high diagnostic confidence on long-axis CM. RESULTS: Average image noise on CM was lower for tungsten (49 HU) and hafnium (62 HU) and higher for bismuth (81 HU) and holmium (165 HU) compared with iodine (78 HU). Noise texture of CM was similar among the contrast media. Interreader agreement for vessel lumen visualization on short-axis CM ranged from moderate to excellent (k = 0.567-0.814). Compared with iodine, lumen visualization of each reader was improved using tungsten (P < 0.001 for both readers), similar to improved using hafnium (P = 0.008, P = 0.29), similar using bismuth (P = 0.38, P = 0.69), and decreased using holmium (both, P < 0.001). Overall subjective image quality was similar for holmium and superior for tungsten, hafnium, and bismuth as compared with iodine. Higher-degree stenoses were evaluable with high confidence using tungsten (mean, 70%; interquartile range, 70%-70%), bismuth (70%; 60%-70%), and hafnium (75%; 70%-80%) compared with iodine (50%; 50%-60%) and holmium (50%; 50%-60%). CONCLUSIONS: Spectral optimization in PCCT combined with investigational contrast media can improve calcium subtraction and stenosis assessment in small vessels. Contrast maps of tungsten and, to a lesser extent, hafnium as contrast media yielded superior image noise properties and improved vessel lumen visualization, along with a higher subjective image quality compared with the reference standard iodine.

Impact of concentration and dilution of three macrocyclic gadolinium-based contrast agents on MRI signal intensity at 1.5T and 3T and different pulse sequences: results of a phantom study in human plasma.

BACKGROUND: Many factors influence the increase in signal intensity (SI) provided by magnetic resonance imaging (MRI) contrast media. PURPOSE: To assess the impact of different gadolinium concentrations and dilutions of three macrocyclic gadolinium-based contrast agents (GBCA) on SI. MATERIAL AND METHODS: This phantom study investigated gadobutrol, gadoteridol, and gadoterate in human plasma of a healthy donor pool at 37 °C. Different molar concentrations served to mimic conditions typically relevant for steady-state imaging; different dilutions served to mimic influence on first-pass bolus imaging. For SI measurement at 1.5T and 3T, we used two Magnetom Scanners (Siemens), applying the T1-weighted sequences Flash 2D/3D and VIBE. Regions of interest were placed on the central slice of the test vials. RESULTS: In the concentration series, gadobutrol showed the highest SI of all three GBCAs up to 2 mM, followed by gadoteridol and gadoterate. No major differences were seen between 1.5T and 3T. In the dilution series, gadobutrol showed the highest SI of all three GBCAs up to 10 mL/L. The highest effect was recorded with Flash 3D and VIBE at 3T. CONCLUSION: SIs measured in phantoms using three macrocyclic GBCAs strongly depend on their relaxivity and on the local concentration. The latter can be influenced-when comparing dilutions-by their initial concentration in their formulation. Furthermore, the pulse sequences and the chosen parameters have essential influence. At steady-state concentrations (≤2 mM) and first-pass bolus dilutions (up to 10 ml/L), gadobutrol showed highest SIs, followed by gadoterate and gadoteridol.

The Macrocyclic Gadolinium-Based Contrast Agents Gadobutrol and Gadoteridol Show Similar Elimination Kinetics From the Brain After Repeated Intravenous Injections in Rabbits.

MATERIALS AND METHODS: Male white New Zealand rabbits (2.4-3.1 kg) in 2 study groups (n = 21 each) received 3 injections of either gadobutrol or gadoteridol at 0.9 mmol Gd/kg within 5 days (total dose, 2.7 mmol Gd/kg). Animals in one control group (n = 9) received 3 injections of saline (1.8 mL/kg). After 2, 6, and 12 weeks, 7 animals from each study group and 3 from the control group were killed and the Gd concentrations in the cerebellum, cerebrum, in blood and in urine were determined by inductively coupled plasma mass spectrometry. The chemical species of excreted Gd in urine were determined by high pressure liquid chromatography. RESULTS: No significant (P > 0.05) differences in the Gd concentrations in the brain of rabbits were observed between the 2 macrocyclic GBCAs gadoteridol and gadobutrol at all time points. In the gadobutrol group, the mean Gd concentrations in the cerebellum and cerebrum decreased from 0.26 and 0.21 nmol Gd/g after 2 weeks, to 0.040 and 0.027 nmol Gd/g after 12 weeks, respectively, and in the gadoteridol group, from 0.25 and 0.21, to 0.037 and 0.023 nmol Gd/g, respectively. The plasma levels decreased from 0.11 and 0.13 nmol Gd/mL at 2 weeks for gadobutrol and gadoteridol to below the limit of quantification (<0.005 nmol Gd/mL) at 12 weeks. The urine concentration dropped in a biphasic course from 2 to 6 and from 6 to 12 weeks for both agents. The Gd excreted after 12 weeks was still present in the urine in the chemical form of the intact Gd complex for both agents. CONCLUSIONS: Contrary to what had been reported in rats, no significant differences in the elimination kinetics from brain tissue in rabbits were observed after intravenous injection of multiple doses of the macrocyclic GBCAs gadobutrol and gadoteridol.

Microdistribution of Magnetic Resonance Imaging Contrast Agents in Atherosclerotic Plaques Determined by LA-ICP-MS and SR-µXRF Imaging.

PURPOSE: Contrast-enhanced magnetic resonance imaging (MRI) has the potential to replace angiographic evaluation of atherosclerosis. While studies have investigated contrast agent (CA) uptake in atherosclerotic plaques, exact CA spatial distribution on a microscale is elusive. The purpose of this study was to investigate the microdistribution of gadolinium (Gd)- and iron (Fe) oxide-based CA in atherosclerotic plaques of New Zealand White rabbits. PROCEDURES: The study was performed as a post hoc analysis of archived tissue specimens obtained in a previous in vivo MRI study conducted to investigate signal changes induced by very small superparamagnetic iron oxide nanoparticles (VSOP) and Gd-BOPTA. For analytical discrimination from endogenous Fe, VSOP were doped with europium (Eu) resulting in Eu-VSOP. Formalin-fixed arterial specimens were cut into 5-µm serial sections and analyzed by immunohistochemistry (IHC: Movat's pentachrome, von Kossa, and Alcian blue (pH 1.0) staining, anti-smooth muscle cell actin (anti-SMA), and anti-rabbit macrophage (anti-RAM-11) immunostaining) and elemental microscopy with laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) and synchrotron radiation µX-ray fluorescence (SR-µXRF) spectroscopy. Elemental distribution maps of Fe, Eu, Gd, sulfur (S), phosphorus (P), and calcium (Ca) were investigated. RESULTS: IHC characterized atherosclerotic plaque pathomorphology. Elemental microscopy showed S distribution to match the anatomy of arterial vessel wall layers, while P distribution corresponded well with cellular areas. LA-ICP-MS revealed Gd and Fe with a limit of detection of ~ 0.1 nmol/g and ~ 100 nmol/g, respectively. Eu-positive signal identified VSOP presence in the vessel wall and allowed the comparison of Eu-VSOP and endogenous Fe distribution in tissue sections. Extracellular matrix material correlated with Eu signal intensity, Fe concentration, and maximum Gd concentration. Eu-VSOP were confined to endothelium in early lesions but accumulated in cellular areas in advanced plaques. Gd distribution was homogeneous in healthy arteries but inhomogeneous in early and advanced plaques. SR-µXRF scans at 0.5 µm resolution revealed Gd hotspots with increased P and Ca concentrations at the intimomedial interface, and a size distribution ranging from a few micrometers to submicrometers. CONCLUSIONS: Eu-VSOP and Gd have distinct spatial distributions in atherosclerotic plaques. While Eu-VSOP distribution is more cell-associated and might be used to monitor atherosclerotic plaque progression, Gd distribution indicates arterial calcification and might help in characterizing plaque vulnerability.