Long-Horizon Associative Learning Explains Human Sensitivity to Statistical and Network Structures in Auditory Sequences.

Networks are a useful mathematical tool for capturing the complexity of the world. In a previous behavioral study, we showed that human adults were sensitive to the high-level network structure underlying auditory sequences, even when presented with incomplete information. Their performance was best explained by a mathematical model compatible with associative learning principles, based on the integration of the transition probabilities between adjacent and nonadjacent elements with a memory decay. In the present study, we explored the neural correlates of this hypothesis via magnetoencephalography (MEG). Participants (N = 23, 16 females) passively listened to sequences of tones organized in a sparse community network structure comprising two communities. An early difference (∼150 ms) was observed in the brain responses to tone transitions with similar transition probability but occurring either within or between communities. This result implies a rapid and automatic encoding of the sequence structure. Using time-resolved decoding, we estimated the duration and overlap of the representation of each tone. The decoding performance exhibited exponential decay, resulting in a significant overlap between the representations of successive tones. Based on this extended decay profile, we estimated a long-horizon associative learning novelty index for each transition and found a correlation of this measure with the MEG signal. Overall, our study sheds light on the neural mechanisms underlying human sensitivity to network structures and highlights the potential role of Hebbian-like mechanisms in supporting learning at various temporal scales.

Sex-specific ventricular morphology, function, and tissue characteristics in arterial hypertension: a magnetic resonance study of the Hamburg city health cohort.

OBJECTIVE: To determine the influence of arterial hypertension (AHT), sex, and the interaction between both left- and right ventricular (LV, RV) morphology, function, and tissue characteristics. METHODS: The Hamburg City Health Study (HCHS) is a population-based, prospective, monocentric study. 1972 individuals without a history of cardiac diseases/ interventions underwent 3 T cardiac MR imaging (CMR). Generalized linear models were conducted, including AHT, sex (and the interaction if significant), age, body mass index, place of birth, diabetes mellitus, smoking, hyperlipoproteinemia, atrial fibrillation, and medication. RESULTS: Of 1972 subjects, 68% suffered from AHT. 42% with AHT and 49% controls were female. Females overall showed a higher ejection fraction (EF) (LV: regression coefficient +2.4% [95% confidence interval: 1.7; 3.1]), lower volumes and LV mass (-19.8% [-21.3; -18.5]), and prolonged native septal T1 (+22.1 ms [18.3; 25.9])/T2 relaxation times (+1.1 ms [0.9; 1.3]) (all p < 0.001) compared to males. Subjects with AHT showed a higher EF (LV: +1.2% [0.3; 2.0], p = 0.009) and LV mass (+6.6% [4.3; 9.0], p < 0.001) than controls. The interaction between sex and AHT influenced mapping. After excluding segments with LGE, males (-0.7 ms [-1.0; -0.3 | ) and females with AHT (-1.1 ms [-1.6; -0.6]) showed shorter T2 relaxation times than the sex-respective controls (p < 0.001), but the effect was stronger in females. CONCLUSION: In the HCHS, female and male subjects with AHT likewise showed a higher EF and LV mass than controls, independent of sex. However, differences in tissue characteristics between subjects with AHT and controls appeared to be sex-specific. CLINICAL RELEVANCE STATEMENT: The interaction between sex and cardiac risk factors is an underestimated factor that should be considered when comparing tissue characteristics between hypertensive subjects and controls, and when establishing cut-off values for normal and pathological relaxation times. KEY POINTS: There are sex-dependent differences in arterial hypertension, but it is unclear if cardiac MR parameters are sex-specific. Differences in cardiac MR parameters between hypertensive subjects and healthy controls appeared to be sex-specific for tissue characteristics. Sex needs to be considered when comparing tissue characteristics in patients with arterial hypertension to healthy controls.

Sensitivity to geometric shape regularity in humans and baboons: A putative signature of human singularity.

Among primates, humans are special in their ability to create and manipulate highly elaborate structures of language, mathematics, and music. Here we show that this sensitivity to abstract structure is already present in a much simpler domain: the visual perception of regular geometric shapes such as squares, rectangles, and parallelograms. We asked human subjects to detect an intruder shape among six quadrilaterals. Although the intruder was always defined by an identical amount of displacement of a single vertex, the results revealed a geometric regularity effect: detection was considerably easier when either the base shape or the intruder was a regular figure comprising right angles, parallelism, or symmetry rather than a more irregular shape. This effect was replicated in several tasks and in all human populations tested, including uneducated Himba adults and French kindergartners. Baboons, however, showed no such geometric regularity effect, even after extensive training. Baboon behavior was captured by convolutional neural networks (CNNs), but neither CNNs nor a variational autoencoder captured the human geometric regularity effect. However, a symbolic model, based on exact properties of Euclidean geometry, closely fitted human behavior. Our results indicate that the human propensity for symbolic abstraction permeates even elementary shape perception. They suggest a putative signature of human singularity and provide a challenge for nonsymbolic models of human shape perception.

Differentiation of acute non-ST elevation myocardial infarction and acute infarct-like myocarditis by visual pattern analysis: a head-to-head comparison of different cardiac MR techniques.

OBJECTIVES: Parametric cardiac magnetic resonance (CMR) techniques have improved the diagnosis of pathologies. However, the primary tool for differentiating non-ST elevation myocardial infarction (NSTEMI) from myocarditis is still a visual assessment of conventional signal-intensity-based images. This study aimed at analyzing the ability of parametric compared to conventional techniques to visually differentiate ischemic from non-ischemic myocardial injury patterns. METHODS: Twenty NSTEMI patients, twenty infarct-like myocarditis patients, and twenty controls were examined using cine, T2-weighted CMR (T2w) and late gadolinium enhancement (LGE) imaging and T1/T2 mapping on a 1.5 T scanner. CMR images were presented in random order to two experienced fully blinded observers, who had to assign them to three categories by a visual analysis: NSTEMI, myocarditis, or healthy. RESULTS: The conventional approach (cine, T2w and LGE combined) had the best diagnostic accuracy with 92% (95%CI: 81-97) for NSTEMI and 86% (95%CI: 71-94) for myocarditis. The diagnostic accuracies using T1 maps were 88% (95%CI: 74-95) and 80% (95%CI: 62-91), 84% (95%CI: 67-93) and 74% (95%CI: 54-87) for LGE, and 83% (95%CI: 66-92) and 73% (95%CI: 53-87) for T2w. The accuracies for cine (72% (95%CI: 52-86) and 60% (95%CI: 38-78)) and T2 maps (62% (95%CI: 40-79) and 47% (95%CI: 28-68)) were significantly lower compared to the conventional approach (p < 0.001 and p < 0.0001). CONCLUSIONS: The conventional approach provided a reliable visual discrimination between NSTEMI, myocarditis, and controls. The diagnostic accuracy of a visual pattern analysis of T1 maps was not significantly inferior, whereas the diagnostic accuracy of T2 maps was not sufficient in this context. CLINICAL RELEVANCE STATEMENT: The ability of parametric compared to conventional CMR techniques to visually differentiate ischemic from non-ischemic myocardial injury patterns can avoid potentially unnecessary invasive coronary angiography and help to shorten CMR protocols and to reduce the need of gadolinium contrast agents. KEY POINTS: • A visual differentiation of ischemic from non-ischemic patterns of myocardial injury is reliably achieved by a combination of conventional CMR techniques (cine, T2-weighted and LGE imaging). • There is no significant difference in accuracies between visual pattern analysis on native T1 maps without providing quantitative values and a conventional combined approach for differentiating non-ST elevation myocardial infarction, infarct-like myocarditis, and controls. • T2 maps do not provide a sufficient diagnostic accuracy for visual pattern analysis for differentiating non-ST elevation myocardial infarction, infarct-like myocarditis, and controls.

DreamCoder: growing generalizable, interpretable knowledge with wake-sleep Bayesian program learning.

Expert problem-solving is driven by powerful languages for thinking about problems and their solutions. Acquiring expertise means learning these languages-systems of concepts, alongside the skills to use them. We present DreamCoder, a system that learns to solve problems by writing programs. It builds expertise by creating domain-specific programming languages for expressing domain concepts, together with neural networks to guide the search for programs within these languages. A 'wake-sleep' learning algorithm alternately extends the language with new symbolic abstractions and trains the neural network on imagined and replayed problems. DreamCoder solves both classic inductive programming tasks and creative tasks such as drawing pictures and building scenes. It rediscovers the basics of modern functional programming, vector algebra and classical physics, including Newton's and Coulomb's laws. Concepts are built compositionally from those learned earlier, yielding multilayered symbolic representations that are interpretable and transferrable to new tasks, while still growing scalably and flexibly with experience. This article is part of a discussion meeting issue 'Cognitive artificial intelligence'.

A language of thought for the mental representation of geometric shapes.

In various cultures and at all spatial scales, humans produce a rich complexity of geometric shapes such as lines, circles or spirals. Here, we propose that humans possess a language of thought for geometric shapes that can produce line drawings as recursive combinations of a minimal set of geometric primitives. We present a programming language, similar to Logo, that combines discrete numbers and continuous integration to form higher-level structures based on repetition, concatenation and embedding, and we show that the simplest programs in this language generate the fundamental geometric shapes observed in human cultures. On the perceptual side, we propose that shape perception in humans involves searching for the shortest program that correctly draws the image (program induction). A consequence of this framework is that the mental difficulty of remembering a shape should depend on its minimum description length (MDL) in the proposed language. In two experiments, we show that encoding and processing of geometric shapes is well predicted by MDL. Furthermore, our hypotheses predict additive laws for the psychological complexity of repeated, concatenated or embedded shapes, which we confirm experimentally.

Dual-Energy CT Vital Iodine Tumor Burden for Response Assessment in Patients With Metastatic GIST Undergoing TKI Therapy: Comparison With Standard CT and FDG PET/CT Criteria.

BACKGROUND. CT-based criteria for assessing the gastrointestinal stromal tumor (GIST) response to tyrosine kinase inhibitor (TKI) therapy are limited in part because tumor attenuation is influenced by treatment-related changes including hemorrhage and calcification. The iodine concentration may be less impacted by such changes. OBJECTIVE. The purpose of this study was to determine whether the dual-energy CT (DECT) vital iodine tumor burden (TB) allows improved differentiation between treatment responders and nonresponders among patients with metastatic GIST who are undergoing TKI therapy compared with established CT and PET/CT criteria. METHODS. An anthropomorphic phantom with spherical inserts mimicking GIST lesions of varying iodine concentrations and having nonenhancing central necrotic cores underwent DECT to determine a threshold iodine concentration. Forty patients (25 women and 15 men; median age, 57 years) who were treated with TKI for metastatic GIST were retrospectively evaluated. Patients underwent baseline and follow-up DECT and FDG PET/CT. Response assessment was performed using RECIST 1.1, modified Choi (mChoi) criteria, vascular tumor burden (VTB) criteria, DECT vital iodine TB criteria, and European Organization for Research and Treatment of Cancer (EORTC) PET criteria. DECT vital iodine TB criteria used the same percentage changes as RECIST 1.1 response categories. Progression-free survival was compared between responders and nonresponders for each response criterion by use of Cox proportional hazard ratios and Harrell C-indexes (i.e., concordance indexes). RESULTS. The phantom experiment identified a threshold of 0.5 mg/mL to differentiate vital from nonvital tissue. With use of the DECT vital iodine TB, median progression-free survival was significantly different between responders and nonresponders (623 vs 104 days; p < .001).. For nonresponders versus responders, the hazard ratio for disease progression for DECT vital iodine TB was 6.9 versus 7.6 for EORTC PET criteria, 3.3 for VTB criteria, 2.3 for RECIST 1.1, and 2.1 for mChoi criteria. The C-index was 0.74 for EORTC PET criteria, 0.73 for DECT vital iodine TB criteria, 0.67 for VTB criteria, 0.61 for RECIST 1.1, and 0.58 for mChoi criteria. The C-index was significantly greater for DECT vital iodine TB criteria than for RECIST 1.1 (p = .02) and mChoi criteria (p = .002), but it was not different from that for VTB and EORTC PET criteria (p > .05). CONCLUSION. DECT vital iodine TB criteria showed performance comparable to that of EORTC PET criteria and outperformed RECIST 1.1 and mChoi criteria for response assessment of metastatic GIST treated with TKI therapy. CLINICAL IMPACT. DECT vital iodine TB could help guide early management decisions in patients receiving TKI therapy.

Can radiomic analysis of a single-phase dual-energy CT improve the diagnostic accuracy of differentiating enhancing from non-enhancing small renal lesions?

BACKGROUND: The value of dual-energy computed tomography (DECT)-based radiomics in renal lesions is unknown. PURPOSE: To develop DECT-based radiomic models and assess their incremental values in comparison to conventional measurements for differentiating enhancing from non-enhancing small renal lesions. MATERIAL AND METHODS: A total of 349 patients with 519 small renal lesions (390 non-enhancing, 129 enhancing) who underwent contrast-enhanced nephrographic phase DECT examinations between June 2013 and January 2020 on multiple DECT platforms were retrospectively recruited. Cohort A included all lesions, while cohort B included Bosniak II-IV and solid enhancing renal lesions. Radiomic models were built with features selected by the least absolute shrinkage and selection operator regression (LASSO). ROC analyses were performed to compare the diagnostic accuracy among conventional and radiomic models for predicting enhancing renal lesions. RESULTS: The individual iodine concentration (IC), normalized IC, mean attenuation on 75-keV images, radiomic model of iodine images, 75-keV images and a combined model integrating all the above-mentioned features all demonstrated high AUCs for predicting renal lesion enhancement in cohort A (AUCs = 0.934-0.979) as well as in the test dataset (AUCs = 0.892-0.962) of cohort B (P values with Bonferroni correction >0.003). The AUC (0.864) of mean attenuation on 75-keV images was significantly lower than those of other models (all P values ≤0.001) except the radiomic model of 75-keV images (P = 0.038) in the training dataset of cohort B. CONCLUSION: No incremental value was found by adding radiomic and machine learning analyses to iodine images for differentiating enhancing from non-enhancing renal lesions.

CT Radiomic Features of Superior Mesenteric Artery Involvement in Pancreatic Ductal Adenocarcinoma: A Pilot Study.

Background Current imaging methods for prediction of complete margin resection (R0) in patients with pancreatic ductal adenocarcinoma (PDAC) are not reliable. Purpose To investigate whether tumor-related and perivascular CT radiomic features improve preoperative assessment of arterial involvement in patients with surgically proven PDAC. Materials and Methods This retrospective study included consecutive patients with PDAC who underwent surgery after preoperative CT between 2012 and 2019. A three-dimensional segmentation of PDAC and perivascular tissue surrounding the superior mesenteric artery (SMA) was performed on preoperative CT images with radiomic features extracted to characterize morphology, intensity, texture, and task-based spatial information. The reference standard was the pathologic SMA margin status of the surgical sample: SMA involved (tumor cells ≤1 mm from margin) versus SMA not involved (tumor cells >1 mm from margin). The preoperative assessment of SMA involvement by a fellowship-trained radiologist in multidisciplinary consensus was the comparison. High reproducibility (intraclass correlation coefficient, 0.7) and the Kolmogorov-Smirnov test were used to select features included in the logistic regression model. Results A total of 194 patients (median age, 66 years; interquartile range, 60-71 years; age range, 36-85 years; 99 men) were evaluated. Aside from surgery, 148 patients underwent neoadjuvant therapy. A total of 141 patients' samples did not involve SMA, whereas 53 involved SMA. A total of 1695 CT radiomic features were extracted. The model with five features (maximum hugging angle, maximum diameter, logarithm robust mean absolute deviation, minimum distance, square gray level co-occurrence matrix correlation) showed a better performance compared with the radiologist assessment (model vs radiologist area under the curve, 0.71 [95% CI: 0.62, 0.79] vs 0.54 [95% CI: 0.50, 0.59]; P < .001). The model showed a sensitivity of 62% (33 of 53 patients) (95% CI: 51, 77) and a specificity of 77% (108 of 141 patients) (95% CI: 60, 84). Conclusion A model based on tumor-related and perivascular CT radiomic features improved the detection of superior mesenteric artery involvement in patients with pancreatic ductal adenocarcinoma. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Do and Kambadakone in this issue.

Reproducibility of CT Radiomic Features within the Same Patient: Influence of Radiation Dose and CT Reconstruction Settings.

Background Results of recent phantom studies show that variation in CT acquisition parameters and reconstruction techniques may make radiomic features largely nonreproduceable and of limited use for prognostic clinical studies. Purpose To investigate the effect of CT radiation dose and reconstruction settings on the reproducibility of radiomic features, as well as to identify correction factors for mitigating these sources of variability. Materials and Methods This was a secondary analysis of a prospective study of metastatic liver lesions in patients who underwent staging with single-energy dual-source contrast material-enhanced staging CT between September 2011 and April 2012. Technique parameters were altered, resulting in 28 CT data sets per patient that included different dose levels, section thicknesses, kernels, and reconstruction algorithm settings. By using a training data set (n = 76), reproducible intensity, shape, and texture radiomic features (reproducibility threshold, R2 ≥ 0.95) were selected and correction factors were calculated by using a linear model to convert each radiomic feature to its estimated value in a reference technique. By using a test data set (n = 75), the reproducibility of hierarchical clustering based on 106 radiomic features measured with different CT techniques was assessed. Results Data in 78 patients (mean age, 60 years ± 10; 33 women) with 151 liver lesions were included. The percentage of radiomic features deemed reproducible for any variation of the different technical parameters was 11% (12 of 106). Of all technical parameters, reconstructed section thickness had the largest impact on the reproducibility of radiomic features (12.3% [13 of 106]) if only one technical parameter was changed while all other technical parameters were kept constant. The results of the hierarchical cluster analysis showed improved clustering reproducibility when reproducible radiomic features with dedicated correction factors were used (ρ = 0.39-0.71 vs ρ = 0.14-0.47). Conclusion Most radiomic features are highly affected by CT acquisition and reconstruction settings, to the point of being nonreproducible. Selecting reproducible radiomic features along with study-specific correction factors offers improved clustering reproducibility. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Sosna in this issue.

Virtual Unenhanced Images at Dual-Energy CT: Influence on Renal Lesion Characterization.

Background Dual-energy (DE) CT allows reconstruction of virtual noncontrast (VNC) images from a single-phase contrast agent-enhanced examination, potentially reducing the need for multiphasic CT to characterize renal lesions. However, data regarding diagnostic performance of VNC images for the characterization of renal lesions are limited. Purpose To determine whether renal mass CT performed by using VNC images allows for reliable identification of renal lesions and differentiation of contrast-enhanced from unenhanced lesions, compared with unenhanced images. Materials and Methods This is a retrospective study of 293 patients (105 women [mean age, 65 years; age range, 18-91 years] and 188 men [mean age, 66 years; age range, 23-90 years] with 379 renal lesions [craniocaudal diameter, 1.0-4.0 cm]) who underwent a single-energy unenhanced CT examination followed by a nephrographic-phase DE CT between June 2013 and October 2017 by using one of four different DE CT platforms from two vendors. VNC images were calculated by using vendor-specific algorithms. Each lesion was classified in a blinded and independent fashion by using the VNC or unenhanced image in combination with the nephrographic images. Attenuation measurements were obtained on the VNC, unenhanced, and nephrographic images. Unenhanced images and pathologic or imaging follow-up for more than 24 months served as reference standard. Results There was strong overall agreement between VNC and unenhanced images for renal lesion characterization (Cramer V = 0.85). VNC images yielded a high diagnostic performance (area under the receiver operating characteristic curve, 0.91; 95% confidence interval: 0.86, 0.95) for facilitation of differentiation of contrast-enhanced from unenhanced renal lesions. However, there was a reduction in diagnostic performance for depicting contrast-enhanced renal lesions by using VNC compared with unenhanced images (area under the receiver operating characteristic curve, 0.91 [95% confidence interval: 0.86, 0.95] vs 0.96 [95% confidence interval: 0.93, 0.99]; P < .001). Mean absolute difference between the VNC and unenhanced attenuation was 9.2 HU ± 8.7. Conclusion Virtual noncontrast images enabled accurate renal lesion characterization, albeit with a reduction in diagnostic performance for contrast-enhanced lesion characterization. © RSNA, 2019 Online supplemental material is available for this article.

Angiocrine Bmp2 signaling in murine liver controls normal iron homeostasis.

Microvascular endothelial cells (ECs) display a high degree of phenotypic and functional heterogeneity among different organs. Organ-specific ECs control their tissue microenvironment by angiocrine factors in health and disease. Liver sinusoidal endothelial cells (LSECs) are uniquely differentiated to fulfill important organ-specific functions in development, under homeostatic conditions, and in regeneration and liver pathology. Recently, Bmp2 has been identified by us as an organ-specific angiokine derived from LSECs. To study angiocrine Bmp2 signaling in the liver, we conditionally deleted Bmp2 in LSECs using EC subtype-specific Stab2-Cre mice. Genetic inactivation of hepatic angiocrine Bmp2 signaling in Stab2-Cre;Bmp2fl/fl (Bmp2LSECKO) mice caused massive iron overload in the liver and increased serum iron levels and iron deposition in several organs similar to classic hereditary hemochromatosis. Iron overload was mediated by decreased hepatic expression of hepcidin, a key regulator of iron homeostasis. Thus, angiocrine Bmp2 signaling within the hepatic vascular niche represents a constitutive pathway indispensable for iron homeostasis in vivo that is nonredundant with Bmp6. Notably, we demonstrate that organ-specific angiocrine signaling is essential not only for the homeostasis of the respective organ but also for the homeostasis of the whole organism.

Cerebral sodium (23Na) magnetic resonance imaging in patients with migraine - a case-control study.

OBJECTIVE: Evaluation of MRI-derived cerebral 23Na concentrations in patients with migraine in comparison with healthy controls. MATERIALS AND METHODS: In this case-control study, 24 female migraine patients (mean age, 34 ± 11 years) were enrolled after evaluation of standardized questionnaires. Half (n = 12) of the cohort suffered from migraine, the other half was impaired by both migraine and tension-type headaches (TTH). The combined patient cohort was matched to 12 healthy female controls (mean age, 34 ± 11 years). All participants underwent a cerebral 23Na-magnetic resonance imaging examination at 3.0 T, which included a T1w MP-RAGE sequence and a 3D density-adapted, radial gradient echo sequence for 23Na imaging. Circular regions of interests were placed in predetermined anatomic regions: cerebrospinal fluid (CSF), gray and white matter, brain stem, and cerebellum. External 23Na reference phantoms were used to calculate the total 23Na tissue concentrations. Pearson's correlation, Kendall Tau, and Wilcoxon rank sum test were used for statistical analysis. RESULTS: 23Na concentrations of all patients in the CSF were significantly higher than in healthy controls (p < 0.001). The CSF of both the migraine and mixed migraine/TTH group showed significantly increased sodium concentrations compared to the control group (p = 0.007 and p < 0.001). Within the patient cohort, a positive correlation between pain level and TSC in the CSF (r = 0.62) could be observed. CONCLUSION: MRI-derived cerebral 23Na concentrations in the CSF of migraine patients were found to be statistically significantly higher than in healthy controls. KEY POINTS: • Cerebral sodium MRI supports the theory of ionic imbalances and may aid in the challenging pathophysiologic understanding of migraine. • Case-control study shows significantly higher sodium concentrations in cerebrospinal fluid of migraineurs. • Cerebral sodium MRI may become a non-invasive imaging tool for drugs to modulate sodium, and hence migraine, on a molecular level, and influence patient management.

Negative Biopsy of Focal Hepatic Lesions: Decision Tree Model for Patient Management.

OBJECTIVE: The purpose of this study was to investigate patient- and procedure-related variables affecting the false-negative rate of ultrasound (US)-guided liver biopsy and to develop a standardized patient-tailored predictive model for the management of negative biopsy results. MATERIALS AND METHODS: We retrospectively included 389 patients (mean age ± SD, 62 ± 12 years old) who had undergone US-guided liver biopsy of 405 liver lesions between January 1, 2013, and June 30, 2015. We collected multiple patient- and procedure-related variables. By comparing pathology reports of biopsy and the reference standard (further histology or imaging follow-up), we were able to categorize the biopsy results as true-positive, true-negative, and false-negative. Diagnostic accuracy and diagnostic yield were measured. Univariate and multivariate analyses were performed to identify variables predicting false-negative results. A standardized patient-tailored predictive model of false-negative results based on a decision tree was fitted. RESULTS: Diagnostic accuracy and diagnostic yield were 93.8% (380/405) and 89.4% (362/405), respectively. The false-negative rate was 6.5% (25/387). Predictive variables of false-negative results at univariate analysis included body mass index, lesion size, sample acquisition techniques, and immediate specimen adequacy. The only independent predictors at multivariate analysis were patient age and Charlson comorbidity index. By combining lesion size and location with patient age and history of malignancy, we developed a decision tree model that predicts false-negative results with high confidence (up to 100%). CONCLUSION: False-negative results are not negligible at US-guided liver biopsy. The combination of selected lesion- and patient-specific variables may help predict when aggressive management is warranted in patients with likely false-negative results.

Comparison of Iodine Quantification and Conventional Attenuation Measurements for Differentiating Small, Truly Enhancing Renal Masses From High-Attenuation Nonenhancing Renal Lesions With Dual-Energy CT.

OBJECTIVE. The purpose of this study is to determine whether iodine quantification techniques from contrast-enhanced dual-energy CT (DECT) data allow equal differentiation of small enhancing renal masses from high-attenuation (> 20 HU of unenhanced attenuation) nonenhancing lesions, compared with conventional attenuation measurements. MATERIALS AND METHODS. A total of 220 nonconsecutive patients (mean [± SD] age, 66 ± 13 years; 130 men and 90 women) with 265 high-attenuation renal lesions (mean attenuation, 54 ± 33 HU; 91 enhancing lesions) were included. Each patient underwent single-energy unenhanced CT followed by DECT during the nephrographic phase using one of four different high-end DECT platforms (first- and second-generation rapid-kilovoltage-switching DECT platforms and second- and third-generation dual-source DECT platforms). Iodine quantification measurements and conventional attenuation change measurements were calculated for each lesion. Diagnostic accuracy was determined by pathologic analysis, confirmation with another imaging modality, or greater than 24 months of imaging follow-up as the reference standard. RESULTS. The diagnostic accuracy for differentiating enhancing from nonenhancing renal lesions was significantly higher for conventional attenuation change measurements, compared with iodine quantification measurements (AUC values, 0.973 vs 0.875; p < 0.0001). The diagnostic performance of iodine quantification measurements improved only marginally with the utilization of DECT platform-specific optimized iodine quantification thresholds, yielding AUC values of 0.907 and 0.893 for the rapid-kilovoltage-switching DECT and dual-source DECT platforms, respectively. Unenhanced lesion attenuation (p = 0.0010) and intraparenchymal location (p = 0.0249) significantly influenced the diagnostic accuracy of the iodine quantification techniques. CONCLUSION. Iodine quantification from DECT data yields inferior diagnostic accuracy when compared with conventional attenuation change measurements for differentiating small, truly enhancing renal masses and high-attenuation renal lesions.

Local Tumor Control and Patient Outcome Using Stereotactic Body Radiation Therapy for Hepatocellular Carcinoma: iRECIST as a Potential Substitute for Traditional Criteria.

OBJECTIVE. The purpose of this study was to investigate whether, compared with traditional criteria, the modified Response Evaluation Criteria in Solid Tumors version 1.1 for immune-based therapeutics (iRECIST) improves prediction of local tumor control and survival in patients with hepatocellular carcinoma (HCC) treated with stereotactic body radiotherapy (SBRT). MATERIALS AND METHODS. Fifty-one HCC lesions (mean size, 3.1 cm) treated with SBRT in 41 patients (mean age, 67 years) were retrospectively included. Each patient underwent CT or MRI before SBRT and at least once after SBRT. Best overall response was categorized using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1), iRECIST, World Health Organization (WHO) criteria, modified Response Evaluation Criteria in Solid Tumors (mRECIST), and European Association for the Study of the Liver (EASL) criteria. Lesions were then classified as local tumor control (i.e., stable disease, partial response, or complete response) or local treatment failure (i.e., progressive disease) by each tumor response criteria. Proportions of local tumor control were compared using the McNemar exact test. The 1-year overall survival was estimated using the Kaplan-Meier method. RESULTS. The median follow-up after SBRT was 21.0 months. The local tumor control rate was 94.1% (48/51) by iRECIST, 88.2% (45/51) by RECIST 1.1, 72.5% (37/51) by WHO criteria, 80.4% (41/51) by mRECIST, and 72.5% (37/51) by EASL criteria. The local tumor control rate was significantly higher according to iRECIST compared with WHO (p = 0.0010) and EASL (p = 0.0225) criteria. The 1-year survival rate for patients with local tumor control according to iRECIST (86.4%) was higher (although not statistically significant) compared with the 1-year survival rate for patients with local tumor control according to the other response criteria. CONCLUSION. iRECIST may provide more robust interpretation of HCC response after SBRT, yielding improved prediction of local tumor control and 1-year survival rates compared with traditional criteria.

LI-RADS: Diagnostic Performance of Hepatobiliary Phase Hypointensity and Major Imaging Features of LR-3 and LR-4 Lesions Measuring 10-19 mm With Arterial Phase Hyperenhancement.

OBJECTIVE. The purpose of this study was to determine the diagnostic performance of hepatobiliary phase hypointensity and Liver Imaging Reporting and Data System (LI-RADS) major imaging features in the diagnosis of hepatocellular carcinoma (HCC) in hepatic lesions with arterial phase hyperenhancement (APHE) measuring 10-19 mm in patients at high risk of HCC. MATERIALS AND METHODS. A composite reference standard of pathologic analysis and imaging follow-up was used. The diagnostic performance (sensitivity and specificity) of hepatobiliary phase hypointensity and LI-RADS major imaging features other than APHE for the diagnosis of HCC was assessed and compared by means of a logistic regression model. RESULTS. This retrospective dual-institution study included 189 LI-RADS LR-3 and LR-4 lesions measuring 10-19 mm and having APHE in 144 consecutively registered patients (96 men, 48 women; mean age, 58 years). Hepatobiliary phase hypointensity had significantly higher sensitivity (84% [92/109], p < 0.00001) than major imaging features in the diagnosis of HCC but lower specificity (84% [67/80]; p = 0.01). However, hepatobiliary phase hypointensity in LR-3 observations measuring 10-19 mm and having APHE had moderately elevated sensitivity (73% [44/60]) and specificity (85%, 64/75). All three major imaging features had high specificity for the diagnosis of HCC, including 95% (76/80) for washout, 100% (80/80) for enhancing capsule, and 99% (79/80) for threshold growth. CONCLUSION. Major imaging features have high specificity for the diagnosis of HCC in lesions measuring 10-19 mm that have APHE. The finding of hepatobiliary phase hypointensity significantly improves sensitivity while moderately high specificity is maintained for the diagnosis of HCC in LR-3 lesions measuring 10-19 mm that exhibit APHE.

Dual-Energy CT Material Density Iodine Quantification for Distinguishing Vascular From Nonvascular Renal Lesions: Normalization Reduces Intermanufacturer Threshold Variability.

OBJECTIVE: The purpose of this study was to determine whether a single, uniform normalized iodine threshold reduces variability and enables reliable differentiation between vascular and nonvascular renal lesions independent of the dual-energy CT (DECT) platform used. MATERIALS AND METHODS: In this retrospective, HIPAA-compliant, institutional review board-approved study, 247 patients (156 men, 91 women; mean age ± SD, 67 ± 12 years old) with 263 renal lesions (193 nonvascular, 70 vascular) underwent unenhanced single-energy and contrast-enhanced DECT scans. One hundred and six nonvascular and 38 vascular lesions were scanned on two dual-source DECT (dsDECT) scanners, and 87 nonvascular and 32 vascular lesions were scanned on two rapid-kilovoltage-switching single-source DECT (rsDECT) scanners. Optimal absolute and normalized (to aorta) lesion iodine thresholds were determined for each platform type and for the entire cohort combined. RESULTS: Mean optimal absolute discriminant thresholds were 1.3 mg I/mL (95% CI, 1.2-1.9 mg I/mL), 1.6 mg I/mL (95% CI, 0.9-1.5 mg I/mL), and 1.5 mg I/mL (95% CI, 1.4-1.7 mg I/mL) for dsDECT, rsDECT, and combined cohorts, respectively. Optimal normalized discriminant thresholds were 0.3 mg I/mL (95% CI, 0.2-0.4 mg I/mL) for both the dsDECT and rsDECT cohorts, and 0.3 mg I/mL (0.3-0.4 mg I/mL) for the combined cohort. The AUC, sensitivity, and specificity for the combined optimal normalized discriminant threshold of 0.3 mg I/mL was 0.96 (95% CI, 0.92-1.00), 0.93 (0.84-0.97), and 0.95 (0.91-0.98), respectively. Normalization resulted in decreased variability and better lesion separation (effect size, 1.77 vs 1.69, p < 0.0001). CONCLUSION: The optimal absolute discriminant threshold for evaluating renal lesions varies depending on the type of DECT platform, though this difference is not statistically significant. Variation can be reduced with a better separation of vascular and nonvascular lesions by normalizing iodine quantification to the aorta.

Feasibility of spectral shaping for detection and quantification of coronary calcifications in ultra-low dose CT.

OBJECTIVES: To evaluate detectability and quantification of coronary calcifications for CT with a tin filter for spectral shaping. METHODS: Phantom inserts with 100 small and 9 large calcifications, and a moving artificial artery with 3 calcifications (speed 0-30 mm/s) were placed in a thorax phantom simulating different patient sizes. The phantom was scanned in high-pitch spiral mode at 100 kVp with tin filter (Sn100 kVp), and at a reference of 120 kVp, with electrocardiographic (ECG) gating. Detectability and quantification of calcifications were analyzed for standard (130 HU) and adapted thresholds. RESULTS: Sn100 kVp yielded lower detectability of calcifications (9 % versus 12 %, p = 0.027) and lower Agatston scores (p < 0.008), irrespective of calcification, patient size and speed. Volume scores of the moving calcifications for Sn100 kVp at speed 10-30 mm/s were lower (p < 0.001), while mass scores were similar (p = 0.131). For Sn100 kVp with adapted threshold of 117 HU, detectability (p = 1.000) and Agatston score (p > 0.206) were similar to 120 kVp. Spectral shaping resulted in median dose reduction of 62.3 % (range 59.0-73.4 %). CONCLUSIONS: Coronary calcium scanning with spectral shaping yields lower detectability of calcifications and lower Agatston scores compared to 120 kVp scanning, for which a HU threshold correction should be developed. KEY POINTS: • Sn100kVp yields lower detectability and lower Agatston scores compared to 120kVp • Adapted HU threshold for Sn100kVp provides Agatston scores comparable to 120kVp • Sn100 kVp considerably reduces dose in calcium scoring versus 120 kVp.

Low-tube-voltage selection for triple-rule-out CTA: relation to patient size.

OBJECTIVES: To investigate the relationship between image quality and patient size at 100 kilovoltage (kV) compared to 120 kV ECG-gated Triple-Rule-Out CT angiography (TRO-CTA). METHODS: We retrospectively included 73 patients (age 64 ± 14 years) who underwent retrospective ECG-gated chest CTA. 40 patients were scanned with 100 kV while 33 patients with 120 kV. Body mass index (BMI), patients' chest circumference (PC) and thoracic surface area (TSA) were recorded. Quantitative image quality was assessed as vascular attenuation in the ascending aorta (AA), pulmonary trunk (PA) and left coronary artery (LCA) and the signal-to-noise ratio (SNR) in the AA. RESULTS: There was no significant difference in BMI (26.0 ± 4.6 vs. 28.0 ± 6.7 kg/m2), PC (103 ± 7 vs. 104 ± 10 cm2) and TSA (92 ± 15 vs. 91 ± 19 cm2) between 100 kV and 120 kV group. Mean vascular attenuation was significantly higher in the 100 kV compared to the 120 kV group (AA 438 vs. 354 HU, PA 460 vs. 349 HU, LCA 370 vs. 299 HU all p < 0.001). SNR was not significantly different, even after adjusting for patient size. Radiation dose was significantly lower in the 100 kV group (10.7 ± 4.1 vs. 20.7 ± 10.7 mSv; p < 0.001). CONCLUSIONS: 100 kV TRO-CTA is feasible in normal-to-overweight patients while maintaining image quality and achieving substantial dose reduction. KEY POINTS: • 100 kV protocols result in a significantly lower radiation dose. • Mean vascular attenuation is significantly higher using 100 kV. • SNR and CNR are not significantly different between 100 kV and 120 kV. • 100 kV CTA is feasible regardless of patient size while maintaining image quality.