Metastasis from the tumor interior and necrotic core formation are regulated by breast cancer-derived angiopoietin-like 7.

Necrosis in the tumor interior is a common feature of aggressive cancers that is associated with poor clinical prognosis and the development of metastasis. How the necrotic core promotes metastasis remains unclear. Here, we report that emergence of necrosis inside the tumor is correlated temporally with increased tumor dissemination in a rat breast cancer model and in human breast cancer patients. By performing spatially focused transcriptional profiling, we identified angiopoietin-like 7 (Angptl7) as a tumor-specific factor localized to the perinecrotic zone. Functional studies showed that Angptl7 loss normalizes central necrosis, perinecrotic dilated vessels, metastasis, and reduces circulating tumor cell counts to nearly zero. Mechanistically, Angptl7 promotes vascular permeability and supports vascular remodeling in the perinecrotic zone. Taken together, these findings show that breast tumors actively produce factors controlling central necrosis formation and metastatic dissemination from the tumor core.

CT perfusion as a potential biomarker for pancreatic ductal adenocarcinoma during routine staging and restaging.

PURPOSE: To evaluate the significance of CT perfusion parameters predicting response to neoadjuvant therapy in patients with pancreatic ductal adenocarcinoma (PDAC). MATERIALS AND METHODS: Seventy patients with PDAC prospectively had CT perfusion acquisition incorporated into baseline multiphase staging CT. Twenty-eight who were naïve to therapy were retained for further investigation. Perfusion was performed 5-42.5 s after contrast, followed by parenchymal and portal venous phases. Blood flow (BF), blood volume (BV), and permeability surface area product (PS) were calculated using deconvolution algorithms. Patients were categorized as responders or non-responders per RECIST 1.1. Perfusion variables with AUC ≥ 0.70 in differentiating responders from non-responders were retained. Logistic regression was used to assess associations between baseline perfusion variables and response. RESULTS: 18 of 28 patients showed favorable response to therapy. Baseline heterogeneity variables in tumor max ROI were higher in non-responders than responders [median BF coefficient of variation (CV) 0.91 vs. 0.51 respectively, odds ratio (OR) 6.8 per one standard deviation (1-SD) increase, P = 0.047; median PS CV 1.6 vs. 0.68, OR 3.9 per 1-SD increase, P = 0.047; and median BV CV 0.75 vs. 0.54, OR = 4.0 per 1-SD increase, P = 0.047]. Baseline BV mean in tumor center was lower in non-responders than responders (median BV mean: 0.74 vs. 2.9 ml/100 g respectively, OR 0.28 per 1-SD increase, P = 0.047). CONCLUSION: For patients with PDAC receiving neoadjuvant therapy, lower and more heterogeneous perfusion parameters correlated with an unfavorable response to therapy. Such quantitative information can be acquired utilizing a comprehensive protocol interleaving perfusion CT acquisition with standard of care multiphase CT scans using a single contrast injection, which could be used to identify surgical candidates and predict outcome.

A Method for Reducing Variability Across Dual-Energy CT Manufacturers in Quantification of Low Iodine Content Levels.

BACKGROUND. Clinical use of the dual-energy CT (DECT) iodine quantification technique is hindered by between-platform (i.e., across different manufacturers) variability in iodine concentration (IC) values, particularly at low iodine levels. OBJECTIVE. The purpose of this study was to develop in an anthropomorphic phantom a method for reducing between-platform variability in quantification of low iodine content levels using DECT and to evaluate the method's performance in patients undergoing serial clinical DECT examinations on different platforms. METHODS. An anthropomorphic phantom in three body sizes, incorporating varied lesion types and scanning conditions, was imaged with three distinct DECT implementations from different manufacturers at varying radiation exposures. A cross-platform iodine quantification model for correcting between-platform variability at low iodine content was developed using the phantom data. The model was tested in a retrospective series of 30 patients (20 men, 10 women; median age, 62 years) who each underwent three serial contrast-enhanced DECT examinations of the abdomen and pelvis (90 scans total) for routine oncology surveillance using the same three DECT platforms as in the phantom. Estimated accuracy of phantom IC values was summarized using root-mean-square error (RMSE) relative to known IC. Between-platform variability in patients was summarized using root-mean-square deviation (RMSD). RMSE and RMSD were compared between platform-based IC (ICPB) and cross-platform IC (ICCP). ICPB was normalized to aorta and portal vein. RESULTS. In the phantom study, mean RMSE of ICPB across platforms and other experimental conditions was 0.65 ± 0.18 mg I/mL compared with 0.40 ± 0.08 mg I/mL for ICCP (38% decrease in mean RMSE; p < .05). Intrapatient between-platform variability across serial DECT examinations was higher for ICPB than ICCP (RMSD, 97% vs 88%; p < .001). Between-platform variability was not reduced by normalization of ICPB to aorta (RMSD, 97% vs 101%; p = .12) or portal vein (RMSD, 97% vs 97%; p = .81). CONCLUSION. The developed cross-platform method significantly decreased between-platform variability occurring at low iodine content with platform-based DECT iodine quantification. CLINICAL IMPACT. With further validation, the cross-platform method, which has been implemented as a web-based app, may expand clinical use of DECT iodine quantification, yielding meaningful IC values that reflect tissue biologic viability or treatment response in patients who undergo serial examinations on different platforms.

Quantitative dual-energy CT techniques in the abdomen.

Advances in dual-energy CT (DECT) technology and spectral techniques are catalyzing the widespread implementation of this technology across multiple radiology subspecialties. The inclusion of energy- and material-specific datasets has ushered overall improvements in CT image contrast and noise as well as artifacts reduction, leading to considerable progress in radiologists' ability to detect and characterize pathologies in the abdomen. The scope of this article is to provide an overview of various quantitative clinical DECT applications in the abdomen and pelvis. Several of the reviewed applications have not reached mainstream clinical use and are considered investigational. Nonetheless awareness of such applications is critical to having a fully comprehensive knowledge base to DECT and fostering future clinical implementation.

Use of Intravenous Gadolinium-Based Contrast Media in Patients With Kidney Disease: Consensus Statements from the American College of Radiology and the National Kidney Foundation.

Inaugural consensus statements were developed and endorsed by the American College of Radiology (ACR) and National Kidney Foundation to improve and standardize the care of patients with kidney disease who have indication(s) to receive ACR-designated group II or group III intravenous gadolinium-based contrast media (GBCM). The risk of nephrogenic systemic fibrosis (NSF) from group II GBCM in patients with advanced kidney disease is thought to be very low (zero events following 4931 administrations to patients with estimated glomerular filtration rate [eGFR] <30 mL/min per 1.73 m2; upper bounds of the 95% confidence intervals: 0.07% overall, 0.2% for stage 5D chronic kidney disease [CKD], 0.5% for stage 5 CKD and no dialysis). No unconfounded cases of NSF have been reported for the only available group III GBCM (gadoxetate disodium). Depending on the clinical indication, the potential harms of delaying or withholding group II or group III GBCM for an MRI in a patient with acute kidney injury or eGFR less than 30 mL/min per 1.73 m2 should be balanced against and may outweigh the risk of NSF. Dialysis initiation or alteration is likely unnecessary based on group II or group III GBCM administration.

Virtual Unenhanced Dual-Energy CT Images Obtained with a Multimaterial Decomposition Algorithm: Diagnostic Value for Renal Mass and Urinary Stone Evaluation.

Background Virtual unenhanced (VUE) images obtained by using a dual-energy CT (DECT) multimaterial decomposition algorithm hold promise for diagnostic use in the abdomen in lieu of true unenhanced (TUE) images. Purpose To assess VUE images obtained from a DECT multimaterial decomposition algorithm in patients undergoing renal mass and urinary stone evaluation. Materials and Methods In this retrospective Health Insurance Portability and Accountability Act-compliant study, DECT was performed in patients undergoing evaluation for renal mass or urinary stone. VUE images were compared quantitatively to TUE images and qualitatively assessed by four independent radiologists. Differences in attenuation between VUE and TUE images were summarized by using 95% limits of agreement. Diagnostic performance in urinary stone detection was summarized by using area under the receiver operating characteristic curve, sensitivity, and specificity. Results A total of 221 patients (mean age ± standard deviation, 61 years ± 14; 129 men) with 273 renal masses were evaluated. Differences in renal mass attenuation between VUE and TUE images were within 3 HU for both enhancing masses (95% limits of agreement, -3.1 HU to 2.7 HU) and nonenhancing cysts (95% limits of agreement, -2.9 HU to 2.5 HU). Renal mass classification as enhancing mass versus nonenhancing cyst did not change (reclassification rate of enhancing masses, 0% [0 of 78]; 95% CI: 0, 5; reclassification rate of nonenhancing cysts, 0% [0 of 193]; 95% CI: 0, 2) with use of VUE in lieu of TUE images. Among 166 urinary stones evaluated, diagnostic performance of VUE images for stone detection was lower compared with that of TUE images (area under the receiver operating characteristic curve, 0.79 [95% CI: 0.73, 0.84] vs 0.93 [95% CI: 0.91, 0.95]; P < .001) due to reduced sensitivity of VUE for detection of stones 3 mm in diameter or less compared with those greater than 3 mm (sensitivity, 23% [25 of 108; 95% CI: 12, 40] vs 88% [126 of 144; 95% CI: 77, 94]; P < .001). Conclusion Compared with true unenhanced images, virtual unenhanced (VUE) images were unlikely to change renal mass classification as enhancing mass versus nonenhancing cyst. Diagnostic performance of VUE images remained suboptimal for urinary stone detection due to subtraction of stones 3 mm or less in diameter. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Sosna in this issue.

Feasibility of wide detector CT perfusion imaging performed during routine staging and restaging of pancreatic ductal adenocarcinoma.

PURPOSE: To evaluate the feasibility of CT perfusion performed during routine multiphase contrast-enhanced CT on a 160 mm wide-coverage 256-slice scanner in patients with pancreatic ductal adenocarcinoma (PDAC). METHODS: Fifty-seven patients had a CT perfusion acquisition during their routine multiphase CT. Perfusion was performed 5 to 42.5 s (15 passes at 2.5 s intervals) after intravenous contrast administration (4.2-5 ml/s), followed by pancreatic parenchymal and portal venous phases for clinical interpretation. Perfusion maps were generated and blood flow (BF), blood volume (BV), and permeability surface area product (PS) for tumor and uninvolved pancreas were calculated using deconvolution algorithms and compared to existing similar publications. Radiation dose information was recorded and size-specific dose estimate (SSDE) was calculated using body dimensions. RESULTS: Diagnostic quality of standard images was unaffected by performing the perfusion acquisition. Average tumor center BF was 20.8 ± 12.1 ml/100 g/min, BV 2.5 ± 2.1 ml/100 g and PS 15.5 ± 39.4 ml/100 g/min. Average pancreas BF was 90.8 ± 50.2 ml/100 g/min, BV 11.9 ± 4.3 ml/100 g and PS 33.6 ± 27.7 ml/100 g/min. For the perfusion acquisition, mean SSDE was 57 ± 11 mGy, CTDIvol 43 ± 6 mGy and DLP 685 ± 100 mGy-cm. CONCLUSION: Adding a perfusion CT acquisition to standard pancreatic CT protocol is feasible using a wide-detector 256-slice CT scanner and adds quantitative information while maintaining diagnostic quality of the standard of care examination. This novel protocol adds no time or cost to the examination and yields perfusion parameters that are comparable to existing literature using a separate dedicated perfusion protocol.

Use of Intravenous Gadolinium-based Contrast Media in Patients with Kidney Disease: Consensus Statements from the American College of Radiology and the National Kidney Foundation.

Inaugural consensus statements were developed and endorsed by the American College of Radiology (ACR) and the National Kidney Foundation to improve and standardize the care of patients with kidney disease who have indication(s) to receive ACR-designated group II or group III intravenous gadolinium-based contrast media (GBCM). The risk of nephrogenic systemic fibrosis (NSF) from group II GBCM in patients with advanced kidney disease is thought to be very low (zero events following 4931 administrations to patients with estimated glomerular filtration rate [eGFR] <30 mL/min per 1.73 m2; upper bounds of the 95% confidence intervals: 0.07% overall, 0.2% for stage 5D chronic kidney disease [CKD], 0.5% for stage 5 CKD and no dialysis). No unconfounded cases of NSF have been reported for the only available group III GBCM (gadoxetate disodium). Depending on the clinical indication, the potential harms of delaying or withholding group II or group III GBCM for an MRI in a patient with acute kidney injury or eGFR less than 30 mL/min per 1.73 m2 should be balanced against and may outweigh the risk of NSF. Dialysis initiation or alteration is likely unnecessary based on group II or group III GBCM administration. This article is a simultaneous joint publication in Radiology and Kidney Medicine. The articles are identical except for stylistic changes in keeping with each journal's style. Either version may be used in citing this article.

Diagnostic Yield of Computed Tomography for the Identification of Coronavirus Disease 2019 Using Repeated Reverse Transcriptase Polymerase Chain Reaction Testing or Confirmed True-Negative State as Reference Standard: Systematic Review and Meta-Analysis.

OBJECTIVE: The aim of this study was to perform a meta-analysis assessing the diagnostic yield of computed tomography (CT) for the identification of coronavirus disease 2019 (COVID-19) using repeated reverse transcriptase polymerase chain reaction testing or confirmed true-negative state as reference standard. METHODS: In May 2020, we interrogated the MEDLINE, Embase, and CENTRAL databases. Pooled sensitivity, specificity, and diagnostic odds ratios of CT for COVID-19 identification were computed. Cumulative positive predictive value (PPV) and negative predictive value, stratified by disease prevalence, were calculated. RESULTS: Ten articles were included (1332 patients). Pooled sensitivity, specificity, and summary diagnostic odds ratio of CT were 82% [95% confidence interval (CI), 79%-84%], 68% (95% CI, 65%-71%), and 18 (95% CI, 9.8-32.8). The PPV and negative predictive value were 54% (95% CI, 30%-77%) and 94% (95% CI, 88%-99%) at a COVID-19 prevalence lower than 40%, and 80% (95% CI, 62%-91%) and 77% (95% CI, 68%-85%) at a prevalence higher than 40%. CONCLUSION: CT yields higher specificity and PPV, albeit lower sensitivity, than previously reported for the identification of COVID-19.

Use of Intravenous Iodinated Contrast Media in Patients With Kidney Disease: Consensus Statements from the American College of Radiology and the National Kidney Foundation.

Intravenous iodinated contrast media are commonly used with CT to evaluate disease and to determine treatment response. The risk of acute kidney injury (AKI) developing in patients with reduced kidney function following exposure to intravenous iodinated contrast media has been overstated. This is due primarily to historic lack of control groups sufficient to separate contrast-induced AKI (CI-AKI; ie, AKI caused by contrast media administration) from contrast-associated AKI (CA-AKI; ie, AKI coincident to contrast media administration). Although the true risk of CI-AKI remains uncertain for patients with severe kidney disease, prophylaxis with intravenous normal saline is indicated for patients who have AKI or an estimated glomerular filtration rate less than 30 mL/min/1.73 m2 who are not undergoing maintenance dialysis. In individual high-risk circumstances, prophylaxis may be considered in patients with an estimated glomerular filtration rate of 30-44 mL/min/1.73 m2 at the discretion of the ordering clinician.

Contrast Reaction Readiness for Your Department or Facility.

Moderate and severe contrast reactions are rare but can be life threatening. Appropriate contrast reaction management is necessary for the best patient outcome. This review summarizes the types and incidences of adverse events to contrast media, treatment algorithms, and equipment needed to treat common contrast reactions, the current status of contrast reaction management training, and preventative strategies to help mitigate adverse contrast events.

Comparison of Histogram-Based Gaussian Analysis With and Without Noise Correction for the Characterization of Indeterminate Adrenal Nodules.

OBJECTIVE. The purpose of this study is to determine whether gaussian-based histogram analysis without and with noise correction can characterize indeterminate adrenal nodules (those with attenuation greater than 10 HU on unenhanced CT) as lipid-poor adenomas. MATERIALS AND METHODS. This retrospective study evaluated adrenal nodules larger than 1 cm on unenhanced CT using gaussian analysis without and with noise correction on intralesional ROIs. Two independent readers who were blinded to the final diagnoses evaluated the nodules. The final diagnosis for each nodule was determined on the basis of pathologic findings or accepted imaging criteria. Interreader agreement was assessed using the intraclass correlation coefficient. Algorithm performance was summarized using sensitivity, specificity, and the AUC. RESULTS. Ninety-four adrenal nodules in 85 patients were analyzed; 36 of these were metastases (34 of which were pathologically confirmed), and 58 were presumed adenomas. Interreader agreement was excellent for nodule size, mean attenuation, SD of attenuation, and the gaussian index. Noise-corrected gaussian analysis had significantly higher specificity (81.9% vs 55.6%; p < 0.001) and lower sensitivity (36.2% vs 56.9%; p < 0.001) for identifying adenomas than did the uncorrected gaussian analysis. The AUC of corrected gaussian analysis was 0.72, which is significantly greater than that of uncorrected gaussian analysis (0.51; p ≤ 0.001) and similar to that of mean attenuation (0.77). CONCLUSION. Noise correction is necessary when using a gaussian analysis characterization of indeterminate adrenal nodules on modern unenhanced CT examinations. This method may be able to discriminate between adenomas and nonadenomas.

Use of Intravenous Iodinated Contrast Media in Patients with Kidney Disease: Consensus Statements from the American College of Radiology and the National Kidney Foundation.

Intravenous iodinated contrast media are commonly used with CT to evaluate disease and to determine treatment response. The risk of acute kidney injury (AKI) developing in patients with reduced kidney function following exposure to intravenous iodinated contrast media has been overstated. This is due primarily to historic lack of control groups sufficient to separate contrast-induced AKI (CI-AKI; ie, AKI caused by contrast media administration) from contrast-associated AKI (CA-AKI; ie, AKI coincident to contrast media administration). Although the true risk of CI-AKI remains uncertain for patients with severe kidney disease, prophylaxis with intravenous normal saline is indicated for patients who have AKI or an estimated glomerular filtration rate less than 30 mL/min/1.73 m2 who are not undergoing maintenance dialysis. In individual high-risk circumstances, prophylaxis may be considered in patients with an estimated glomerular filtration rate of 30-44 mL/min/1.73 m2 at the discretion of the ordering clinician. This article is a simultaneous joint publication in Radiology and Kidney Medicine. The articles are identical except for stylistic changes in keeping with each journal's style. Either version may be used in citing this article.

Bridging the Radiation Oncology and Diagnostic Radiology Communication Gap: A Survey to Determine Usefulness and Optimal Presentation of Radiotherapy Treatment Plans for Radiologists.

RATIONALE AND OBJECTIVES: We hypothesized that providing visual-spatial information to radiologists on where radiation has been delivered in an easily accessible way may improve the accuracy of image interpretation and thereby improve quality of patient care. We present a national representation of radiologists' opinions regarding the usefulness and optimal approach for implementing a system to promote access to radiotherapy (RT) plans. METHODS: An anonymous survey was sent to the members of the Association of University Radiologists. Descriptive statistics were performed. RESULTS: Questionnaires were returned by 95 of 1383 members. Demographics comprised of 76% attendings with 94% practicing within an academic setting. Only 40% of radiologists reported that they knew most of the time whether a patient has received RT in the field scanned. A large majority of respondents (88%) felt that a history of prior radiation in a cancer patient was at least an occasional barrier that affected the ability to interpret imaging findings in a clinically useful way. The following types of information was considered helpful when interpreting a scan: screenshots of the radiation plan (85%), scrollable DICOM data on planning CT showing delivered RT dose lines (54%), and written text RT treatment summary (47%). Nearly all (89%) desired DICOM data within the clinical radiology Picture Archiving and Communication System system. Radiologists expected the ease of accessibility to RT plans to result in increased efficiency (76%) and accuracy (88%). CONCLUSION: Diagnostic radiologists desire improved access and integration of radiotherapy plans into the diagnostic radiology clinical workup in the form of visual-spatial data.

Patterns of distant metastases in 215 Merkel cell carcinoma patients: Implications for prognosis and surveillance.

Approximately one-third of Merkel cell carcinoma (MCC) patients eventually develop distant metastatic disease. Little is known about whether the location of the primary lesion is predictive of initial distant metastatic site, or if survival likelihood differs depending on the metastatic site. Such data could inform imaging/surveillance practices and improve prognostic accuracy. Multivariate and competing-risk analyses were performed on a cohort of 215 MCC patients with distant metastases, 31% of whom had two or more initial sites of distant metastasis. At time of initial distant metastasis in the 215 patients, metastatic sites (n = 305) included non-regional lymph nodes (present in 41% of patients), skin/body wall (25%), liver (23%), bone (21%), pancreas (8%), lung (7%), and brain (5%). Among the 194 patients who presented with MCC limited to local or regional sites (stage I-III) but who ultimately developed distant metastases, distant progression occurred in 49% by 1 year and in 80% by 2 years following initial diagnosis. Primary MCC locations differed in how likely they were to metastasize to specific organs/sites (P < .001). For example, liver metastases were far more likely from a head/neck primary (43% of 58 patients) versus a lower limb primary (5% of 39 patients; P < .0001). Skin-only distant metastasis was associated with lower MCC-specific mortality as compared to metastases in multiple organs/sites (HR 2.7; P = .003), in the liver (HR 2.1; P = .05), or in distant lymph nodes (HR 2.0; P = .045). These data reflect outcomes before PD1-pathway inhibitor availability, which may positively impact survival. In conclusion, primary MCC location is associated with a pattern of distant spread, which may assist in optimizing surveillance. Because it is linked to survival, the site of initial distant metastasis should be considered when assessing prognosis.

ACR Appropriateness Criteria® Lower Urinary Tract Symptoms-Suspicion of Benign Prostatic Hyperplasia.

Lower urinary tract symptoms due to benign prostatic enlargement have a high prevalence in men over 50 years of age. Diagnosis is made with a combination of focused history and physician examination and validated symptom questionnaires. Urodynamic studies can help to differentiate storage from voiding abnormalities. Pelvic ultrasound may be indicated to assess bladder volume and wall thickness. Other imaging modalities, including prostate MRI, are usually not indicated in the initial workup and evaluation of uncomplicated lower urinary tract symptoms from an enlarged prostate. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

ACR Appropriateness Criteria® Penetrating Trauma-Lower Abdomen and Pelvis.

Lower urinary tract injury is most commonly the result of blunt trauma but can also result from penetrating or iatrogenic trauma. Clinical findings in patients with a mechanism of penetrating trauma to the lower urinary tract include lacerations or puncture wounds of the pelvis, perineum, buttocks, or genitalia, as well as gross hematuria or inability to void. CT cystography or fluoroscopy retrograde cystography are usually the most appropriate initial imaging procedures in patients with a mechanism of penetrating trauma to the lower urinary tract. CT of the pelvis with intravenous contrast, pelvic radiography, fluoroscopic retrograde urethrography, and CT of the pelvis without intravenous contrast may be appropriate in some cases. Arteriography, radiographic intravenous urography, CT of the pelvis without and with intravenous contrast, ultrasound, MRI, and nuclear scintigraphy are usually not appropriate. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.