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Objectives: Various imaging methods have been evaluated regarding non-invasive differentiation of renal cell carcinoma (RCC) subtypes. Dual-energy computed tomography (DECT) allows iodine concentration (IC) analysis as a correlate of tissue perfusion. Microvascular density (MVD) in histopathology specimens is evaluated to determine intratumoral vascularization. The objective of this study was to assess the potential of IC and MVD regarding the differentiation between papillary and clear cell RCC and between well- and dedifferentiated tumors. Further, we aimed to investigate a possible correlation between these parameters., Methods: DECT imaging series of 53 patients with clear cell RCC (ccRCC) and 15 with papillary RCC (pRCC) were analyzed regarding IC. Histology samples were stained using CD31/CD34 monoclonal antibodies; MVD was evaluated digitally. Statistical analysis included performance of Mann-Whitney U test, ROC analysis, and Spearman rank correlation., Results: Analysis of IC demonstrated significant differences between ccRCC and pRCC (p < 0.001). A cutoff value of ≤ 3.1 mg/ml at IC analysis allowed identification of pRCC with an accuracy of 86.8%. Within the ccRCC subgroup, G1/G2 tumors could significantly be differentiated from G3/G4 carcinomas (p = 0.045). A significant positive correlation between IC and MVD could be determined for the entire RCC cohort and the ccRCC subgroup. Limitations include the small percentage of pRCCs., Conclusions: IC analysis is a useful method to differentiate pRCC from ccRCC. The significant positive correlation between IC and MVD indicates valid representation of tumor perfusion by DECT., Key Points: • Analysis of iodine concentration using DECT imaging could reliably distinguish papillary from clear cell subtypes of renal cell cancer (RCC). • A cutoff value of 3.1 mg/ml allowed a distinction between papillary and clear cell RCCs with an accuracy of 86.8%. • The positive correlation with microvascular density in tumor specimens indicates correct display of perfusion by iodine concentration analysis.

Objectives: The objective of this study was to evaluate the intra-individual, longitudinal consistency of iodine measurements regarding the vascular and renal blood pool in patients that underwent repetitive spectral detector computed tomography (SDCT) examinations to evaluate their utility for oncologic imaging., Methods: Seventy-nine patients with two (n = 53) or three (n = 26) clinically indicated biphasic SDCT scans of the abdomen were retrospectively included. ROI-based measurements of Hounsfield unit (HU) attenuation in conventional images and iodine concentration were performed by an experienced radiologist in the following regions (two ROIs each): abdominal aorta, vena cava inferior, portal vein, and renal cortices. Modified variation coefficients (MVCs) were computed to assess intra-individual longitudinal between the different time points., Results: Variation of HU attenuation and iodine concentration measurements was significantly lower in the venous than in the arterial phase images (attenuation/iodine concentration: arterial - 4.2/- 3.9, venous 0.4/1.0; p ≤ 0.05). Regarding attenuation in conventional images of the arterial phase, the median MVC was - 1.8 (- 20.5-21.3) % within the aorta and - 6.5 (- 44.0-25.0) % within the renal cortex while in the portal venous phase, it was 0.62 (- 11.1-11.7) % and - 1.6 (- 16.2-10.6) %, respectively. Regarding iodine concentration, MVC for arterial phase was - 2.5 (- 22.9-28.4) % within the aorta and - 5.8 (- 55.9-29.6) % within the renal cortex. The referring MVCs of the portal venous phase were - 0.7 (- 17.9-16.9) % and - 2.6 (- 17.6-12.5) %., Conclusions: Intra-individual iodine quantification of the vascular and cortical renal blood pool at different time points works most accurately in venous phase images whereas measurements conducted in arterial phase images underlay greater variability., Key Points: • There is an intra-individual, physiological variation in iodine map measurements from dual-energy computed tomography. • This variation is smaller in venous phase examinations compared with arterial phase and therefore venous phase images should be preferred to minimize this intra-individual variation. • Care has to be taken, when considering iodine measurements for clinical decision-making, particularly in the context of oncologic initial or follow-up imaging.

Objectives: To determine the correlation between iodine concentrations derived from dual-energy CT (DECT) and perfusion CT (PCT) parameters in patients with pathologically proven colorectal cancers (CRC) and to evaluate their reproducibility and respective radiation exposures., Methods: Institutional review board approval and written informed consents were obtained for this study. Forty-one patients with CRCs who underwent same-day DECT and PCT were prospectively enrolled. Three radiologists independently analyzed the iodine concentration of the tumors and iodine ratios [ratio of lesion to aorta (IRa) or to infrarenal IVC (IRv)] from DECT as well as blood flow (BF), blood volume (BV), permeability (PMB), and mean transit time (MTT) from PCT. Pearson R and linear correlation, paired t-test, and intraclass correlation coefficients (ICCs) were used., Results: Significant correlations were found between iodine parameters from DECT and PCT parameters: iodine concentration of tumors and BV (r = 0.32, p = 0.04), PMB (r = 0.34, p = 0.03), and MTT (r = -0.38, p = 0.02); iodine ratio (IRa) and MTT (r = -0.32, p = 0.04); iodine ratio (IRv) and BF (r = 0.32, p = 0.04) and PMB (r = 0.44, p = <0.01). DECT showed better intra- and interobserver agreements (ICC = 0.98, 0.90 in iodine concentration; 0.98, 0.91 in IRa; and 0.91, 0.93 in IRv, respectively) than PCT (ICC = 0.90, 0.78 in BF; 0.82, 0.76 in BV; 0.75, 0.75 in PMB; 0.64, 0.79 in MTT, respectively). As for radiation dosage, CTDIvol and DLP in DECT (10.48 ± 1.84 mGy and 519.7 ± 116.7 mGy·cm) were significantly lower than those of PCT (75.76 mGy and 911 mGy·cm) (p < 0.01)., Conclusion: Iodine parameters from DECT are significantly correlated with PCT parameters, but have higher intra- and interobserver agreements and lower radiation exposure., Key Points: • Quantitative iodine concentrations from DECT are significantly correlated with perfusion CT parameters. • Intra- and interobserver agreements of DECT are better than those of perfusion CT. • Effective radiation doses of DECT are significantly lower than those of perfusion CT. • DECT can be used as an alternative to perfusion CT with lower radiation doses.

Objectives: To investigate the minimum iodine delivery rate (IDR) required to achieve diagnostic coronary attenuation (300 HU) with dual-energy coronary CTA., Methods: Acquisitions were performed on a circulation phantom with a third- generation dual-source CT scanner. Contrast media was injected for a fixed time whilst IDRs varied from 1.0 to 0.3 gI/s in 0.1-gI/s intervals. Noise-optimized virtual monoenergetic imaging (VMI+) reconstructions from 40 to 90 keV in 5 keV increments were generated. Contrast-to-noise ratio (CNR) and coronary HU were measured for each injection., Results: VMI+ from 40-70 keV reached diagnostic attenuation with at least one IDR. The minimum IDR achieving a diagnostic attenuation ranged from 0.4 gI/s at 40 keV (312.8 HU) to 1.0 gI/s at 70 keV (334.1 HU). Attenuation values reached with IDR of 1.0 gI/s were significantly higher at each keV level (p<0.001). CNR showed a near perfect correlation with the IDR (ρ≥0.962; p<0.001), the IDR of 1.0 gI/s provided the highest CNR at each keV level, achieving the highest overall value at 40 keV (54.0±3.1)., Conclusions: IDRs from 0.4-1.0 gI/s associated with VMI+ from 40-70 keV provide diagnostic coronary attenuation with dual-energy coronary CTA., Key Points: • Iodine delivery rate (IDR) is a major determinant of contrast enhancement. • Low-keV noise-optimized monoenergetic images (VMI+) maximize iodine attenuation. • Low-keV VMI+ allows for lower IDRs while maintaining adequate coronary attenuation. • Lowest IDR to reach 300 HU was 0.4 gI/s, 40 keV VMI+.

Objectives: To quantify iodine uptake in articular cartilage as a marker of glycosaminoglycan (GAG) content using multi-energy spectral CT., Methods: We incubated a 25-mm strip of excised osteoarthritic human tibial plateau in 50 % ionic iodine contrast and imaged it using a small-animal spectral scanner with a cadmium telluride photon-processing detector to quantify the iodine through the thickness of the articular cartilage. We imaged both spectroscopic phantoms and osteoarthritic tibial plateau samples. The iodine distribution as an inverse marker of GAG content was presented in the form of 2D and 3D images after applying a basis material decomposition technique to separate iodine in cartilage from bone. We compared this result with a histological section stained for GAG., Results: The iodine in cartilage could be distinguished from subchondral bone and quantified using multi-energy CT. The articular cartilage showed variation in iodine concentration throughout its thickness which appeared to be inversely related to GAG distribution observed in histological sections., Conclusions: Multi-energy CT can quantify ionic iodine contrast (as a marker of GAG content) within articular cartilage and distinguish it from bone by exploiting the energy-specific attenuation profiles of the associated materials., Key Points: • Contrast-enhanced articular cartilage and subchondral bone can be distinguished using multi-energy CT. • Iodine as a marker of glycosaminoglycan content is quantifiable with multi-energy CT. • Multi-energy CT could track alterations in GAG content occurring in osteoarthritis.

Objectives: To assess the value of iodine concentration (IC) in computed tomography data acquired with 80 kVp, as a surrogate for perfusion imaging in hepatocellular carcinoma (HCC) and lymphoma by comparing iodine related attenuation (IRA) with quantitative Volume Perfusion CT (VPCT)-parameters., Methods: VPCT-parameters were compared with intra-tumoral IC at 5 time points after the aortic peak enhancement (APE) with a temporal resolution of 3.5 sec in untreated 30 HCC and 30 lymphoma patients., Results: Intra-tumoral perfusion parameters for HCC showed a blood flow (BF) of 52.7 ± 17.0 mL/100 mL/min, blood volume (BV) 12.6 ± 4.3 mL/100 mL, arterial liver perfusion (ALP) 44.4 ± 12.8 mL/100 mL/min. Lesion IC 7 sec after APE was 133.4 ± 57.3 mg/100 mL. Lymphoma showed a BF of 36.8 ± 13.4 mL/100 mL/min, BV of 8.8 ± 2.8 mL/100 mL and IC of 118.2 ± 64.5 mg/100 mL 3.5 sec after APE. Strongest correlations exist for VPCT-derived BF and ALP with IC in HCC 7 sec after APE (r = 0.71 and r = 0.84) and 3.5 sec after APE in lymphoma lesions (r = 0.77). Significant correlations are also present for BV (r = 0.60 and r = 0.65 for HCC and lymphoma, respectively)., Conclusions: We identified a good, time-dependent agreement between VPCT-derived flow values and IC in HCC and lymphoma. Thus, CT-derived ICs 7 sec after APE in HCC and 3.5 sec in lymphoma may be used as surrogate imaging biomarkers for tumor perfusion with 80 kVp., Key Points: • Iodine concentration derived from low kVp CT is regarded as perfusion surrogate • Correlation with Perfusion CT was performed to elucidate timing and histology dependencies • Highest correlation was present 7 sec after aortic peak enhancement in hepatocellular carcinoma • In lymphoma, highest correlation was calculated 3.5 sec after aortic peak enhancement • With these results, further optimization of Dual energy CT protocols is possible.

Objectives: To determine whether the quantification of iodine with stress dual-energy computed tomography (DECT-S) allows for the discrimination between a normal and an ischemic or necrotic myocardium using magnetic resonance (MR) as a reference., Methods: This retrospective study was approved by the institutional review board, with waiver of informed consent. Thirty-six cardiac MR and DECT-S images from patients with suspected coronary artery disease were evaluated. Perfusion defects were visually determined, and myocardial iodine concentration was calculated by two observers using DECT colour-coded iodine maps. Iodine concentration differences were calculated using parametric tests. Receiver operating characteristic (ROC) curve analysis was conducted to estimate the optimal iodine concentration threshold for discriminating pathologic myocardium., Results: In total, 576 cardiac segments were evaluated. There were differences in mean iodine concentration (p < 0.001) between normal (2.56 ± 0.66 mg/mL), ischemic (1.98 ± 0.36 mg/dL) and infarcted segments (1.35 ± 0.57 mg/mL). A myocardium iodine concentration of 2.1 mg/mL represented the optimal threshold to discriminate between normal and pathologic myocardium (sensitivity 75 %, specificity 73.6 %, area under the curve 0.806). Excellent agreement was found in measured myocardium iodine concentration (intraclass correlation coefficient 0.814)., Conclusion: Cardiac DECT-S with iodine quantification may be useful to differentiate healthy and ischemic or necrotic myocardium., Key Points: • DECT-S allows for determination of myocardial iodine concentration as a quantitative perfusion parameter. • A high interobserver correlation exists in measuring myocardial iodine concentration with DECT-S. • Myocardial iodine concentration may be useful in the assessment of patients with CAD.

Objectives: To investigate the potential contribution of iodine uptake calculation from dual-phase dual-energy CT (DE-CT) for lymph node staging and therapy response monitoring in lung cancer patients., Methods: Retrospective analysis of 27 patients with non-small cell lung carcinoma (NSCLC), who underwent dual-phase DE-CT before and after chemotherapy, was performed. Iodine uptake (mg/mL) and total iodine uptake (mg) were calculated using prototype software in the early (arterial) and late (venous) post-contrast circulatory phase in 110 mediastinal lymph nodes. The arterial enhancement fraction (AEF) was calculated and compared with lymph node size and response to chemotherapy., Results: A significant difference of AEF was observed between enlarged (90.4%; 32.3-238.5%) and non-enlarged (72.7%; -37.5-237.5%) lymph nodes (p = 0.044) before treatment onset. A significantly different change of AEF in responding (decrease of 26.3%; p = 0.022) and non-responding (increase of 43.0%; p = 0.031) lymph nodes was demonstrated. A higher value of AEF before treatment was observed in lymph nodes with subsequent favourable response (88.6% vs. 77.7%; p = 0.122), but this difference did not reach statistical significance., Conclusions: The dual-phase DE-CT examination with quantification of ratio of early and late post-contrast iodine uptake is a feasible and promising method for the functional evaluation of mediastinal lymph nodes including therapy response assessment., Key Points: • Dual-phase DE-CT is beneficial for mediastinal lymph node assessment in NSCLC. • Arterial to venous iodine uptake ratio was higher in enlarged lymph nodes. • Change of arterial enhancement fraction correlated to therapy response.

Purpose: To assess the accuracy of dual-energy CT (DECT) for the quantification of iodine concentrations in a thoracic phantom across various cardiac DECT protocols and simulated patient sizes., Materials and Methods: Experiments were performed on first- and second-generation dual-source CT (DSCT) systems in DECT mode using various cardiac DECT protocols. An anthropomorphic thoracic phantom was equipped with tubular inserts containing known iodine concentrations (0-20 mg/mL) in the cardiac chamber and up to two fat-equivalent rings to simulate different patient sizes. DECT-derived iodine concentrations were measured using dedicated software and compared to true concentrations. General linear regression models were used to identify predictors of measurement accuracy, Results: Correlation between measured and true iodine concentrations (n = 72) across CT systems and protocols was excellent (R = 0.994-0.997, P < 0.0001). Mean measurement errors were 3.0 ± 7.0% and -2.9 ± 3.8% for first- and second-generation DSCT, respectively. This error increased with simulated patient size. The second-generation DSCT showed the most stable measurements across a wide range of iodine concentrations and simulated patient sizes., Conclusion: Overall, DECT provides accurate measurements of iodine concentrations across cardiac CT protocols, strengthening the case for DECT-derived blood volume estimates as a surrogate of myocardial blood supply., Key Points: • Dual-energy CT provides new opportunities for quantitative assessment in cardiac imaging. • DECT can quantify myocardial iodine as a surrogate for myocardial perfusion. • DECT measurements of iodine concentrations are overall very accurate. • The accuracy of such measurements decreases as patient size increases.

Adverse reactions to iodinated contrast media (ICM) are more likely to develop in patients with asthma, a history of allergy or contrast reaction and in those who are debilitated or medically unstable. These reactions can be divided into renal and general, and the latter are subdivided into acute and delayed. Acute general reactions can be minor, intermediate or severe. Fatal reactions are rare. The introduction of low-osmolality agents has caused an overall reduction in the number of non-fatal contrast reactions. Prompt recognition and treatment of acute adverse side effects to ICM is invaluable and may prevent a reaction from becoming severe. Familiarity with cardiopulmonary resuscitation is essential for successful management of life-threatening reactions. Contrast-media-induced renal impairment can be reduced with the use of low-osmolality contrast media and extracellular volume expansion. The use of ICM in diabetic patients receiving metformin should be carried out with care to avoid metformin-induced lactic acidosis. However, this problem is mainly observed in patients with diabetic nephropathy.