Contrast Media-driven Anthropogenic Gadolinium: Knowns and Unknowns.

Gadolinium-based contrast agents (GBCAs) have augmented the capabilities of MRI, which has led to their widespread and increasing use in radiology practice. GBCAs are introduced into the environment through disposal of unused product and elimination after intravenous injection, both primarily via liquid dispersion into the environment. This human introduction of gadolinium into the environment, referred to as anthropogenic gadolinium, is associated with the detection of gadolinium in water systems, raising concerns for potential adverse impact and prompting certain mitigation actions. This article summarizes the existing knowledge and problem scope, conveys the relevant underlying chemical principles of chelate dissociation, and offers an inferred perspective that the magnitude of the problem is most unlikely to cause human harm. The merits and limitations regarding possible mitigation tactics, such as collecting urine after GBCA administration, use of lower-dose high-relaxivity macrocyclic GBCAs, and the option for virtual contrast-enhanced examinations, will be discussed. Finally, the potential for monitoring gadolinium uptake in bone will be presented, and recommendations for future research will be offered. © RSNA, 2024 See also the article by Ibrahim et al in this issue. See also the article by McKee et al in this issue.

A Novel Modality Enables New Evidence-Based Individual Risk Stratification That Can Potentially Lead to Decisive Management and Treatment Decisions in Prostate Cancer.

A key step in providing management/treatment options to men with suspected prostate cancer (PCa) is categorizing the risk in terms of the presence of benign, low-risk, intermediate-risk, or high-risk disease. Our novel modality brings new evidence, based on the long-known hallmark characteristic of PCa-decreased zinc (Zn), which is the most direct metabolic sign of malignancy and its aggressiveness. To date, this approach has not been adopted for clinical use for a number of reasons that are described in this article, and which have been addressed by our approach. Zn has to be measured on fresh samples, prior to fixating in formalin; therefore, samples have to be scanned during the biopsy session. As Zn depletion occurs in the glands where the tumors develop, estimation of the glands' levels in the scanned tissue, along with their compactness, are essential for accurate diagnosis. Combined with the Zn depletion, this facilitates a reliable assessment of disease aggressiveness. Data gathered in the clinical study described here indicate that, in addition to improving the biopsy quality by real-time interactive guidance, a malignancy score can now be established for the entire prostate, allowing higher granularity personalized risk stratification and more decisive treatment decisions for all PCa patients.

Investigating new CT contrast agents: a phantom study exploring quantification and differentiation methods for high-Z elements using dual-energy CT.

OBJECTIVES: To develop a dual-energy CT method for differentiating and quantifying high-Z contrast elements and to evaluate the limitations based on element concentration and atomic number by using an anthropomorphic phantom study. METHODS: Mass spectrometry standards for iodine, barium, gadolinium, ytterbium, tantalum, gold, and bismuth were diluted from 10.0 to 0.3 mg/mL, placed inside 7-mL vials, and scanned with dual-energy CT using an abdominal phantom and cylindrical water-filled insert. This procedure was repeated with all seven high-Z elements at six isoattenuating values from 250 to 8 HU. Quantification accuracy was measured using a linear regression model and residual error analysis with 90% limits of agreement. The limit of detection for each element was evaluated using the limit of blank of water. Pairwise differentiation of isoattenuating vials was evaluated using AUC values and the difference in fit angles between the two elements. RESULTS: Each high-Z element had a unique concentration vector in a two-dimensional plot of Compton scattering versus photoelectric effect attenuations. Mean quantification values were within ± 0.1 mg/mL of the true values for each element with no proportional bias. Limits of detection ranged from 0.35 to 0.56 mg/mL. Pairwise differentiations were proportional to the isoattenuating HU and the angle between the linear fits with mean AUC values increasing from 0.61 to 0.98 at 8 to 250 HU, respectively. CONCLUSION: Dual-energy CT can differentiate and quantify isoattenuating high-Z elements. The high-attenuation characteristics and unique concentration vectors of ytterbium, tantalum, gold, and bismuth are well suited for new dual-energy CT contrast agents especially when simultaneously imaged with iodine, barium, or gadolinium. KEY POINTS: • Dual-energy CT can accurately quantify high-Z contrast elements and readily differentiate iodine, barium, and gadolinium from ytterbium, tantalum, gold, and bismuth. • The differentiation and quantification capabilities for high-Z contrast elements are largely unaffected by phantom size and transaxial location within the phantom. • Potential benefits of new CT contrast agents based on these high-Z elements include alternatives for patients with iodine sensitivity, high conspicuity at both 120 and 140 kVp, simultaneous imaging of two contrast agents, and reduced injection volume.

Combining inhomogeneous magnetization transfer and multipoint Dixon acquisition: Potential utility and evaluation.

PURPOSE: The recently introduced inhomogeneous magnetization transfer (ihMT) method has predominantly been applied for imaging the central nervous system. Future applications of ihMT, such as in peripheral nerves and muscles, will involve imaging in the vicinity of adipose tissues. This work aims to systematically investigate the partial volume effect of fat on the ihMT signal and to propose an efficient fat-separation method that does not interfere with ihMT measurements. METHODS: First, the influence of fat on ihMT signal was studied using simulations. Next, the ihMT sequence was combined with a multi-echo Dixon acquisition for fat separation. The sequence was tested in 9 healthy volunteers using a 3T human scanner. The ihMT ratio (ihMTR) values were calculated in regions of interest in the brain and the spinal cord using standard acquisition (no fat saturation), water-only, in-phase, and out-of-phase reconstructions. The values obtained were compared with a standard fat suppression method, spectral presaturation with inversion recovery. RESULTS: Simulations showed variations in the ihMTR values in the presence of fat, depending on the TEs used. The IhMTR values in the brain and spinal cord derived from the water-only ihMT multi-echo Dixon images were in good agreement with values from the unsuppressed sequence. The ihMT-spectral presaturation with inversion recovery combination resulted in 24%-35% lower ihMTR values compared with the standard non-fat-suppressed acquisition. CONCLUSION: The presence of fat within a voxel affects the ihMTR calculations. The IhMT multi-echo Dixon method does not compromise the observable ihMT effect and can potentially be used to remove fat influence in ihMT.

How the Chemical Properties of GBCAs Influence Their Safety Profiles In Vivo.

The extracellular class of gadolinium-based contrast agents (GBCAs) is an essential tool for clinical diagnosis and disease management. In order to better understand the issues associated with GBCA administration and gadolinium retention and deposition in the human brain, the chemical properties of GBCAs such as relative thermodynamic and kinetic stabilities and their likelihood of forming gadolinium deposits in vivo will be reviewed. The chemical form of gadolinium causing the hyperintensity is an open question. On the basis of estimates of total gadolinium concentration present, it is highly unlikely that the intact chelate is causing the T1 hyperintensities observed in the human brain. Although it is possible that there is a water-soluble form of gadolinium that has high relaxitvity present, our experience indicates that the insoluble gadolinium-based agents/salts could have high relaxivities on the surface of the solid due to higher water access. This review assesses the safety of GBCAs from a chemical point of view based on their thermodynamic and kinetic properties, discusses how these properties influence in vivo behavior, and highlights some clinical implications regarding the development of future imaging agents.

Concentration-dependent Early Antivascular and Antitumor Effects of Itraconazole in Non-Small Cell Lung Cancer.

PURPOSE: Itraconazole has been repurposed as an anticancer therapeutic agent for multiple malignancies. In preclinical models, itraconazole has antiangiogenic properties and inhibits Hedgehog pathway activity. We performed a window-of-opportunity trial to determine the biologic effects of itraconazole in human patients. EXPERIMENTAL DESIGN: Patients with non-small cell lung cancer (NSCLC) who had planned for surgical resection were administered with itraconazole 300 mg orally twice daily for 10-14 days. Patients underwent dynamic contrast-enhanced MRI and plasma collection for pharmacokinetic and pharmacodynamic analyses. Tissues from pretreatment biopsy, surgical resection, and skin biopsies were analyzed for itraconazole and hydroxyitraconazole concentration, and vascular and Hedgehog pathway biomarkers. RESULTS: Thirteen patients were enrolled in this study. Itraconazole was well-tolerated. Steady-state plasma concentrations of itraconazole and hydroxyitraconazole demonstrated a 6-fold difference across patients. Tumor itraconazole concentrations trended with and exceeded those of plasma. Greater itraconazole levels were significantly and meaningfully associated with reduction in tumor volume (Spearman correlation, -0.71; P = 0.05) and tumor perfusion (Ktrans; Spearman correlation, -0.71; P = 0.01), decrease in the proangiogenic cytokines IL1b (Spearman correlation, -0.73; P = 0.01) and GM-CSF (Spearman correlation, -1.00; P < 0.001), and reduction in tumor microvessel density (Spearman correlation, -0.69; P = 0.03). Itraconazole-treated tumors also demonstrated distinct metabolic profiles. Itraconazole treatment did not alter transcription of GLI1 and PTCH1 mRNA. Patient size, renal function, and hepatic function did not predict itraconazole concentrations. CONCLUSIONS: Itraconazole demonstrates concentration-dependent early antivascular, metabolic, and antitumor effects in patients with NSCLC. As the number of fixed dose cancer therapies increases, attention to interpatient pharmacokinetics and pharmacodynamics differences may be warranted.

MRI of the Placenta Accreta Spectrum (PAS) Disorder: Radiomics Analysis Correlates With Surgical and Pathological Outcome.

BACKGROUND: Placenta accreta spectrum (PAS) in women with previous cesarean delivery has become increasingly prevalent. Depending on the severity, patient management may involve cesarean hysterectomy. PURPOSE: To investigate textural analyses as the radiomics in MRI of the placenta in predicting the PAS requiring cesarean hysterectomy in a high-risk population. STUDY TYPE: Retrospective. POPULATION: Sixty-two women with prior cesarean delivery referred for MRI because of sonographic suspicion for PAS. FIELD STRENGTH/SEQUENCE: 1.5T with T1 W, T2 W, and diffusion-weighted imaging (DWI). ASSESSMENT: Two reviewers independently evaluated MR images based on five established PAS variables. Placental regions of interest (ROIs) were generated on T2 W, DWI, and an apparent diffusion coefficient (ADC) map, based on definitions of areas of placenta in proximity to and remote from previous surgical incision sites. STATISTICAL TESTS: Reader agreement was assessed by simple kappa and prevalence adjusted bias adjusted kappa (PABAK). T-tests and chi-square analyses between the primary outcome (hysterectomy vs. no hysterectomy) were performed. Thirteen Haralick texture features calculated from gray-level co-occurrence matrixes were extracted from manually drawn placental ROIs within each of three MR acquisitions. Univariate and multivariable logistic regression were used to assess the association with cesarean hysterectomy. RESULTS: Of 62 pregnancies at risk for PAS, 40 required cesarean hysterectomy (65%), with excellent correlation between need for hysterectomy and pathology confirmation of PAS in the hysterectomy specimen [κ = 0.82 (0.62, 1)]. Reader agreement was fair to moderate. Of the 13 Haralick variables within each of three acquisition groups, significant differences (P < 0.05) were seen in 22 of 39 parameters comparing placental ROIs in proximity to incision scar(s) to those ROIs remote from scar. A stepwise selection algorithm indicated that the combination of T2 W Fcm.sum.var , ADC Fcm.diff.entr , and DWI Fcm.energy gave the highest leave-one-out-AUC of 0.80 (0.68, 0.91). DATA CONCLUSION: Assessment of PAS severity is subjective and dependent on radiologist expertise. We identified textural features on placental MR images in the region of the prior uterine scar that differentiated pregnancies requiring cesarean hysterectomy based on clinical suspicion of PAS from those that did not, suggesting predictive capabilities of these objective radiomics features. LEVEL OF EVIDENCE: 3 Technical Efficacy Stage: 1 J. Magn. Reson. Imaging 2020;51:936-946.

Does Tumor FDG-PET Avidity Represent Enhanced Glycolytic Metabolism in Non-Small Cell Lung Cancer?

BACKGROUND: In non-small cell lung cancer (NSCLC), 18fluoro-2-deoxyglucose-positron emission tomography (FDG-PET) assists in diagnosis, staging, and evaluating treatment response. One variable of FDG-PET, the maximum standard uptake value (SUVm), is considered an objective measure of glucose uptake. However, little is known about the fate of glucose in FDG-avid lung tumors in vivo. This study used stable glucose isotope tracing to determine whether the SUVm predicts glycolytic metabolism or other glucose fates in tumors. METHODS: In this prospective Institutional Review Board-approved clinical trial, 52 untreated potentially resectable confirmed NSCLC patients underwent FDG-PET computed tomography. During the surgical procedure, the patients were infused with 13C-labeled glucose. Blood, tumor, and normal lung samples were analyzed by mass spectrometry to determine 13C enrichment in glycolytic intermediates. These values were compared with clinical variables, including SUVm, maximum tumor diameter, stage, grade, and MIB-1/Ki67 proliferation index. RESULTS: For each patient, 13C enrichment in each metabolite was compared between tumor and adjacent lung. Although all tumors metabolized glucose, SUVm did not correlate with glycolytic intermediate labeling. Rather, SUVm correlated with markers indicating the use of other respiratory substrates, including lactate, and with the proliferation index. CONCLUSIONS: SUVm does not correlate with glycolytic metabolism in human NSCLC but does correlate with the proliferation index, suggesting that SUVm predicts glucose use by pathways other than glycolysis. These pathways may offer alternative therapeutic targets, including biosynthetic pathways required for cell proliferation. The research techniques in this study offer the opportunity to understand the relationships between SUVm, tumor metabolism, and therapeutic vulnerabilities in human NSCLCs.

A Technique to Identify Isoattenuating Gallstones with Dual-Layer Spectral CT: An ex Vivo Phantom Study.

Background Previously reported dual-energy CT methods for detecting noncalcified gallstones have reduced accuracy for gallstones smaller than 9 mm. Purpose To develop a dual-energy CT method for differentiating isoattenuating gallstones from bile and compare it with previously reported dual-energy CT methods by using a prospective ex vivo phantom reader study. Materials and Methods From May 2017 to May 2018, gallstones were collected from 105 patients (34 men; mean age, 51 years; age range, 18-84 years) undergoing cholecystectomy and placed inside 120-mL vials containing ox bile. The vials were placed inside a water-filled phantom and were scanned with dual-layer dual-energy CT. Thirty isoattenuating gallstones (4.3-24.7 mm in diameter) were evaluated. Conventional CT images, virtual noncontrast images, and monoenergetic images at 200 and 40 keV were created. Segmented images were created by using a two-dimensional histogram of Compton and photoelectric attenuation. Six readers evaluated the presence of isoattenuating gallstones in each image. Intra- and interreader agreement was measured by using percentage agreement, diagnostic performance was evaluated by using mean area under the receiver operating characteristic curve (AUC) estimates and pairwise comparisons, and the agreement of gallstone sizes measured at pathologic examination with those measured on segmented images was compared by using Bland-Altman analysis. Results For all gallstones, segmented images provided the highest mean intrareader (88.1%) and interreader (88.2% and 93.6%) agreements for all readers and reading sessions and the highest overall AUC (0.99; 95% confidence interval [CI]: 0.97, 1.00; adjusted P < .02 for all). For gallstones larger than 9 mm, no significant difference was found between the segmented and monoenergetic AUCs (all P > .94, adjusted P > .05 for all). For gallstones measuring 9 mm or smaller, the segmented images had the highest overall AUC (0.99; 95% CI: 0.97, 1.00; adjusted P < .01 for all). The mean difference in stone sizes was -0.6 mm, with limits of agreement from 2.6 to -3.8 mm. Conclusion Segmented images from Compton and photoelectric attenuation coefficients improve detection of isoattenuating gallstones compared with previously reported dual-energy CT methods. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Matos in this issue.

Texture analysis of magnetic resonance images of the human placenta throughout gestation: A feasibility study.

As fetal gestational age increases, other modalities such as ultrasound have demonstrated increased levels of heterogeneity in the normal placenta. In this study, we introduce and apply ROI-based texture analysis to a retrospective fetal MRI database to characterize the second-order statistics of placenta and to evaluate the relationship between heterogeneity and gestational age. Positive correlations were observed for several Haralick texture metrics derived from fetal-brain specific T2-weighted and gravid uterus T1-weighted and T2-weighted images, confirming a quantitative increase in placental heterogeneity with gestational age. Our study shows the importance of identifying baseline MR textural changes at certain gestational ages from which placental diseased states may be compared. Specifically, when evaluating for placental invasion or insufficiency, findings should be evaluated in the context of the normal placental aging process, which occurs throughout gestation.

Separating High-Z Oral Contrast From Intravascular Iodine Contrast in an Animal Model Using Dual-Layer Spectral CT.

RATIONALE AND OBJECTIVES: To show that water and iodine two-material decomposition images from dual-layer dual-energy spectral X-ray computed tomography (DECT) can be used to separate intravascular iodine contrast from simultaneously administered oral tantalum, tungsten, or rhenium contrast in an animal model. MATERIALS AND METHODS: In this Institutional Animal Care and Use Committee approved study, four female Fischer rats were given simultaneous intravenous and oral X-ray computed tomography contrast. Intravenous iodine contrast was administered via tail vein injection. Oral barium, tantalum, tungsten, or rhenium contrast was administered via gavage. The animals were imaged on a dual-layer DECT system at 120 kVp. Water and iodine two-material decomposition images (water equivalent and iodine equivalent images) were used for qualitative analysis. Computer simulations were performed using a customized DECT simulator to better understand why certain high-Z elements disappear in the iodine equivalent images and what is the theoretical range of elements with this property. RESULTS: The iodine and barium contrast appeared only in the iodine equivalent images and could not be differentiated from each other. However, the tantalum, tungsten, and rhenium contrast only appeared in the water equivalent images. This allowed iodine contrast in the bowel wall to be easily segmented from tantalum, tungsten, and rhenium contrast in the bowel lumen. Simulations confirmed that certain high-Z elements will have pixel values of ≤0 mg iodine/mL in the iodine equivalent images due to a K-edge effect associated with DECT systems. CONCLUSIONS: Dual-layer DECT can separate iodine from certain high-Z elements using water equivalent and iodine equivalent images with an increased element range compared to other DECT systems. This K-edge effect could promote the development and approval of new high-Z contrast agents for DECT.

Accelerating chemical exchange saturation transfer MRI with parallel blind compressed sensing.

PURPOSE: Chemical exchange saturation transfer is a novel and promising MRI contrast method, but it can be time-consuming. Common parallel imaging methods, like SENSE, can lead to reduced quality of CEST. Here, parallel blind compressed sensing (PBCS), combining blind compressed sensing (BCS) and parallel imaging, is evaluated for the acceleration of CEST in brain and breast. METHODS: The CEST data were collected in phantoms, brain (N = 3), and breast (N = 2). Retrospective Cartesian undersampling was implemented and the reconstruction results of PBCS-CEST were compared with BCS-CEST and k-t sparse-SENSE CEST. The normalized RMSE and the high-frequency error norm were used for quantitative comparison. RESULTS: In phantom and in vivo brain experiments, the acceleration factor of R = 10 (24 k-space lines) was achieved and in breast R = 5 (30 k-space lines), without compromising the quality of the PBCS-reconstructed magnetization transfer rate asymmetry maps and Z-spectra. Parallel BCS provides better reconstruction quality when compared with BCS, k-t sparse-SENSE, and SENSE methods using the same number of samples. Parallel BCS overperforms BCS, indicating that the inclusion of coil sensitivity improves the reconstruction of the CEST data. CONCLUSION: The PBCS method accelerates CEST without compromising its quality. Compressed sensing in combination with parallel imaging can provide a valuable alternative to parallel imaging alone for accelerating CEST experiments.

Breast Tumor Microcalcification Induced by Bone Morphogenetic Protein-2: A New Murine Model for Human Breast Tumor Diagnosis.

Widespread use of screening mammography has recently increased the detection of breast microcalcifications. These nonpalpable microcalcifications with specific features in breast tissues are clinically considered an early indicator of breast carcinoma. Our goal in this study was to develop a murine breast microcalcification model for optimizing in vivo imaging. Recombinant human BMP-2 was expressed in E. coli, and the purified bioactive protein was used as inducing factor for the production of breast microcalcifications in a murine animal model. Syngeneic breast tumors were obtained by injection of MDA-MB-231 human breast cancer cells with Matrigel into the mammary fat pad of female nude mice. Different doses of bioactive rhBMP-2 were administered either as single or multiple intraperitoneal injections or directly into tumor on a weekly basis. Three weeks after the first injection of rhBMP-2, the microcalcification of breast tumor was detected by microcomputed tomography followed by intravenous injection of radiotracer [18F] Sodium fluoride for positron emission tomography imaging. Our findings indicate that rhBMP-2 induced microcalcifications of breast tumor by both systemic and direct injection of rhBMP-2 into tumors in a dose-dependent manner. Although little is known about the molecular mechanism of microcalcification, here we report a new murine model of human breast tumor induced microcalcification by rhBMP-2 to optimize in vivo imaging methods and to study the role of BMP-2 as a mediator of pathological mineralization and bone-like microcalcification formation in breast tumor. This BMP-2-induced microcalcification model may allow us to discriminate the type of microcalcification in tumors and to perform quantitative analysis on the calcification as a new detection strategy for early identification of pathological mineralization of breast tissues in women.

Gadolinium Retention: A Research Roadmap from the 2018 NIH/ACR/RSNA Workshop on Gadolinium Chelates.

Gadolinium-based contrast agents (GBCAs) have revolutionized MRI, enabling physicians to obtain crucial life-saving medical information that often cannot be obtained with other imaging modalities. Since initial approval in 1988, over 450 million intravenous GBCA doses have been administered worldwide, with an extremely favorable pharmacologic safety profile; however, recent information has raised new concerns over the safety of GBCAs. Mounting evidence has shown there is long-term retention of gadolinium in human tissues. Further, a small subset of patients have attributed a constellation of symptoms to GBCA exposure, although the association of these symptoms with GBCA administration or gadolinium retention has not been proven by scientific investigation. Despite evidence that macrocyclic GBCAs show less gadolinium retention than linear GBCAs, the safety implications of gadolinium retention are unknown. The mechanism and chemical forms of gadolinium retention, as well as the biologic activity and clinical importance of these retained gadolinium species, remain poorly understood and underscore the need for additional research. In February 2018, an international meeting was held in Bethesda, Md, at the National Institutes of Health to discuss the current literature and knowledge gaps about gadolinium retention, to prioritize future research initiatives to better understand this phenomenon, and to foster collaborative standardized studies. The greatest priorities are to determine (a) if gadolinium retention adversely affects the function of human tissues, (b) if retention is causally associated with short- or long-term clinical manifestations of disease, and (c) if vulnerable populations, such as children, are at greater risk for experiencing clinical disease. The purpose of the research roadmap is to highlight important information that is not known and to identify and prioritize needed research. ©RSNA, 2018 Online supplemental material is available for this article .

Low-to-high b value DWI ratio approaches in multiparametric MRI of the prostate: feasibility, optimal combination of b values, and comparison with ADC maps for the visual presentation of prostate cancer.

BACKGROUND: Diffusion-weighted imaging (DWI) is considered by experts as one of the key elements in multi-parametric magnetic resonance imaging (mpMRI) employed in oncological studies outside the brain. A low-to-high b value ratio DWI has been proposed as an approach to decrease acquisition time and simplify the analysis of DWI data without the need to use a mathematical model. METHODS: Forty-three men with biopsy-proven prostate cancer (PCa) who underwent mpMRI of the prostate were included. Apparent diffusion coefficient (ADC) maps were created in the MRI scanner using a mono-exponential algorithm [b value (× number of averages) =0 (×1), 10 (×1), 25 (×1), 50 (×1), 100 (×1), 250 (×1), 450 (×1), 1,000 (×2), 1,500 (×3), and 2,000 (×5) s/mm2]. DWI ratio images were calculated with three previously estimated optimal b value combinations: (I) b=100 and b=1,000 s/mm2 (R1); (II) b=100 and b=1,500 s/mm2 (R2); and (III) b=100 and b=2,000 s/mm2 (R3). For quantitative analysis, contrast-to-noise ratio (CNR) between normal and cancerous tissue was compared between the ADC maps and the DWI ratio images in terms of noninferiority. For qualitative analysis, two radiologists read all images in a randomized order without knowing whether the presented image was an ADC map or a DWI ratio image. All images were scored in terms of artifacts, cancer conspicuity and overall image quality with a 5-point scale. Agreement between the readers was assessed by weighted kappa statistics. Agreement was considered as poor when kappa <0.4, fair to good when kappa >0.4 and <0.75 and excellent when kappa >0.75. Mean scores were compared between ADC and each of the DWI ratio images. Agreement between ADC maps and DWI ratio based synthetic ADC were assessed by intraclass correlation (ICC). Values less than 0.5, between 0.5 and 0.75, between 0.75 and 0.9, and greater than 0.90 were indicative of poor, moderate, good, and excellent reliability, respectively. Median difference between low and intermediate/high risk were tested. RESULTS: Quantitative analysis shows DWI ratio images were not inferior to ADC maps quantitatively [P=0.0298 (ADC vs. R1), <0.0001 (ADC vs. R2) and <0.0001 (ADC vs. R3)]. Qualitatively, DWI ratio images were no more than 0.5 point on Likert scale lower than ADC in overall quality [P=0.0043 (ADC vs. R1), <0.0001 (ADC vs. R2), <0.0001 (ADC vs. R3)]. Reader agreement for the qualitative analysis was good to excellent (weighted kappa =0.4-0.7). Agreement between ADC maps and the synthetic ADC's were excellent. Significant difference between low and intermediate/high risk were found in all measurements on average (all P values <0.05). CONCLUSIONS: We presented an analytical method for searching for the optimal combination of high and low b values for DWI ratio images in terms of minimizing CNR between cancer and surrounding benign tissues. Optimized DWI ratio images are comparable both quantitatively and qualitatively to ADC maps for the interpretation of DWI data in the context of prostate mpMRI.

Pseudoenhancement effects on iodine quantification from dual-energy spectral CT systems: A multi-vendor phantom study regarding renal lesion characterization.

PURPOSE: To measure the effect of pseudoenhancement on spectral CT iodine quantification as a function of lesion size, lesion iodine level, background iodine level, helical versus axial scanning, and spectral CT scanner type in a phantom model. MATERIALS AND METHODS: A custom-built water-filled cylindrical phantom contained either six small vials (8 mm diameter) or six large vials (27 mm diameter) of aqueous iopamidol solutions (0, 0.5, 1.0, 2.0, 4.0 and 6.0 mg iodine/mL). The background iodine concentration was 0, 5, or 10 mg iodine/mL. Helical and axial scans were taken on three different dual-energy spectral CT scanners (two image-based and one projection-based) with the scan parameters consistent between the systems. ROIs were used to measure the average iodine concentration of the vials in the 36 individual scans. Linear fits of the true versus measured iodine values were used for pvalue statistical analysis. Having a y-intercept or slope p-value less than 0.05 implied statistically significant iodine quantification errors. RESULTS: Iodine quantification pseudoenhancement effects are inversely proportional to lesion size and lesion enhancement and are directly proportional to background attenuation level. No significant differences between helical and axial scans were observed. 100% and 88% of the slope and y-intercept p-values were below 0.05 for the two image-based systems, while 13% of the slope and y-intercept p-values were below 0.05 for the projection-based system. CONCLUSIONS: Pseudoenhancement can artificially increase spectral CT iodine quantification levels most notably for small low-enhancing lesions (<5.0 mg iodine/mL) surrounded by a high attenuating background (10 mg iodine/mL). In this study we found iodine quantification to be more accurate on projection-based spectral CT systems than image-based systems.

Phantom Validation of Spectral Detector Computed Tomography-Derived Virtual Monoenergetic, Virtual Noncontrast, and Iodine Quantification Images.

PURPOSE: Spectral detector computed tomography (SDCT) is a new CT technology that uses a dual-layer detector to perform energy separation. We aim to assess 3 clinical concepts using a phantom model: noise profile across the virtual monoenergetic (VME) spectrum, accuracy of iodine quantification, and virtual noncontrast (VNC) reconstructions' ability to remove iodine contribution to attenuation. METHODS: Six vials containing varying concentrations of iodinated contrast (0-6 mg/mL) diluted in water were placed in a water bath and scanned on an SDCT scanner. Virtual monoenergetic (40-200 keV at 10-keV increments), iodine-no-water, and VNC reconstructions were created. Attenuation (in Hounsfield units [HU]), VME noise at each energy level, CT-derived iodine concentration, and VNC attenuation were recorded. RESULTS: Virtual monoenergetic noise was improved at all energies compared with conventional images (conventional, 9.8-11.2; VME, 7.5-9.5). Noise profile showed a slightly higher image noise at 40 keV, but was otherwise relatively flat across the energy spectrum. On iodine-no-water reconstructions, measured varied from actual iodine concentration by ±0.1 mg/mL (SD, 0.16-0.36). Virtual noncontrast attenuation was within 5 HU of water attenuation at all iodine concentrations. CONCLUSION: Reconstructions of SDCT show lower VME image noise, accurate iodine quantification, and VNC attenuation values within 5 HU of expected in a phantom model.