Adipose tissue in the small airways: How much is enough to drive functional changes?

Obesity is a contributing factor to asthma severity; while it has long been understood that obesity is related to greater asthma burden, the mechanisms though which this occurs have not been fully elucidated. One common explanation is that obesity mechanically reduces lung volume through accumulation of adipose tissue external to the thoracic cavity. However, it has been recently demonstrated that there is substantial adipose tissue within the airway wall itself, and that the presence of adipose tissue within the airway wall is related to body mass index. This suggests the possibility of an additional mechanism by which obesity may worsen asthma, namely by altering the behaviour of the airways themselves. To this end, we modify Anafi & Wilson's classic model of the bistable terminal airway to incorporate adipose tissue within the airway wall in order to answer the question of how much adipose tissue would be required in order to drive substantive functional changes. This analysis suggests that adipose tissue within the airway wall on the order of 1%-2% of total airway cross-sectional area could be sufficient to drive meaningful changes, and further that these changes may interact with volume effects to magnify the overall burden.

Imaging of abdominopelvic oncologic emergencies.

With advancements in cancer treatment, the survival rates for many malignancies have increased. However, both the primary tumors and the treatments themselves can give rise to various complications. Acute symptoms in oncology patients require prompt attention. Abdominopelvic oncologic emergencies can be classified into four distinct categories: vascular, bowel, hepatopancreatobiliary, and bone-related complications. Radiologists need to be familiar with these complications to ensure timely diagnosis, which ultimately enhances patient outcomes.

Airway-associated adipose tissue accumulation is increased in a kisspeptin receptor knockout mouse model.

Airway-associated adipose tissue increases with body mass index and is a local source of pro-inflammatory adipokines that may contribute to airway pathology in asthma co-existing with obesity. Genetic susceptibility to airway adiposity was considered in the present study through kisspeptin/kisspeptin receptor signalling, known to modulate systemic adiposity and potentially drive airway remodelling. Therefore, the aim of the study was to determine the effects of kisspeptin/kisspeptin receptor signalling in the lung, focusing on airway-associated adipose tissue deposition and impact on airway structure-function. Wild-type, heterozygous and kisspeptin receptor knockout mice were studied at 6 or 8 weeks of age. Lung mechanics were assessed before and after methacholine challenge and were subsequently fixed for airway morphometry. A separate group of mice underwent glucose tolerance testing and bronchoalveolar lavage. At 6 weeks of age, kisspeptin/kisspeptin receptor signalling did not affect body adiposity, airway inflammation, wall structure or function. Despite no differences in body adiposity, there was a greater accumulation of airway-associated adipose tissue in knockout mice. By 8 weeks of age, female knockout mice displayed a non-diabetic phenotype with increased body adiposity but not males. Airway-associated adipose tissue area was also increased in both knockout females and males at 8 weeks of age, but again no other respiratory abnormality was apparent. In summary, airway-associated adipose tissue is decoupled from body adiposity in prepubescent mice which supports a genetic susceptibility to fatty deposits localised to the airway wall. There was no evidence that airway-associated adipose tissue drives pathology or respiratory impairment in the absence of other environmental exposures.

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.

From Beneath the Skin to the Airway Wall: Understanding the Pathological Role of Adipose Tissue in Comorbid Asthma-Obesity.

This article provides a contemporary report on the role of adipose tissue in respiratory dysfunction. Adipose tissue is distributed throughout the body, accumulating beneath the skin (subcutaneous), around organs (visceral), and importantly in the context of respiratory disease, has recently been shown to accumulate within the airway wall: "airway-associated adipose tissue." Excessive adipose tissue deposition compromises respiratory function and increases the severity of diseases such as asthma. The mechanisms of respiratory impairment are inflammatory, structural, and mechanical in nature, vary depending on the anatomical site of deposition and adipose tissue subtype, and likely contribute to different phenotypes of comorbid asthma-obesity. An understanding of adipose tissue-driven pathophysiology provides an opportunity for diagnostic advancement and patient-specific treatment. As an exemplar, the potential impact of airway-associated adipose tissue is highlighted, and how this may change the management of a patient with asthma who is also obese. © 2023 American Physiological Society. Compr Physiol 13:4321-4353, 2023.

Distribution, composition, and activity of airway-associated adipose tissue in the porcine lung.

Patients with comorbid asthma-obesity experience greater disease severity and are less responsive to therapy. We have previously reported adipose tissue within the airway wall that positively correlated with body mass index. Accumulation of biologically active adipose tissue may result in the local release of adipokines and disrupt large and small airway function depending on its anatomical distribution. This study therefore characterized airway-associated adipose tissue distribution, lipid composition, and adipokine activity in a porcine model. Airway segments were systematically dissected from different locations of the bronchial tree in inflation-fixed lungs. Cryosections were stained with hematoxylin and eosin (H&E) for airway morphology, oil red O to distinguish adipose tissue, and Nile blue A for lipid subtype delineation. Excised airway-associated adipose tissue was cultured for 72 h to quantify adipokine release using immunoassays. Results showed that airway-associated adipose tissue extended throughout the bronchial tree and occupied an area proportionally similar to airway smooth muscle within the wall area. Lipid composition consisted of pure neutral lipids (61.7 ± 3.5%), a mixture of neutral and acidic lipids (36.3 ± 3.4%), or pure acidic lipids (2.0 ± 0.8%). Following tissue culture, there was rapid release of IFN-γ, IL-1ß, and TNF-α at 12 h. Maximum IL-4 and IL-10 release was at 24 and 48 h, and peak leptin release occurred between 48 and 72 h. These data extend previous findings and demonstrate that airway-associated adipose tissue is prevalent and biologically active within the bronchial tree, providing a local source of adipokines that may be a contributing factor in airway disease.

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.

Determining risk factors for triple whammy acute kidney injury.

Concurrent use of a diuretic, a renin-angiotensin system (RAS) inhibitor, and a non-steroidal anti-inflammatory drug (NSAID) significantly increases the risk of acute kidney injury (AKI). This phenomenon is known as "triple whammy". Diuretics and RAS inhibitors, such as an angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker, are often prescribed in tandem for the treatment of hypertension, whereas some NSAIDs, such as ibuprofen, are available over the counter. As such, concurrent treatment with all three drugs is common. The goals of this study are to better understand the mechanisms underlying the development of triple whammy AKI and to identify physiological factors that may increase an individual's susceptibility. To accomplish these goals, we utilize sex-specific computational models of long-term blood pressure regulation. These models include variables describing the heart and circulation, kidney function, sodium and water reabsorption in the nephron and the RAS and are parameterized separately for men and women. Hypertension is modeled as overactive renal sympathetic nervous activity. Model simulations suggest that low water intake, the myogenic response, and drug sensitivity may predispose patients with hypertension to develop triple whammy-induced AKI. Triple treatment involving an ACE inhibitor, furosemide, and NSAID results in blood pressure levels similar to double treatment with ACEI and furosemide. Additionally, the male and female hypertensive models act similarly in most situations, except for the ACE inhibitor and NSAID double treatment.

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.

Intrauterine Growth Restriction Promotes Postnatal Airway Hyperresponsiveness Independent of Allergic Disease.

Introduction: Intrauterine growth restriction (IUGR) is associated with asthma. Murine models of IUGR have altered airway responsiveness in the absence of any inflammatory exposure. Given that a primary feature of asthma is airway inflammation, IUGR-affected individuals may develop more substantial respiratory impairment if subsequently exposed to an allergen. This study used a maternal hypoxia-induced mouse model of IUGR to determine the combined effects of IUGR and allergy on airway responsiveness. Methods: Pregnant BALB/c mice were housed under hypoxic conditions (10.5% O2) from gestational day (GD) 11-GD 17.5 (IUGR group; term = GD 21). Following hypoxic exposure, mice were returned to a normoxic environment (21% O2). A second group of pregnant mice were housed under normoxic conditions throughout pregnancy (Control). All offspring were sensitized to ovalbumin (OVA) and assigned to one of four treatment groups: Control - normoxic and saline challenge; IUGR - hypoxic and saline challenge; Allergy - normoxic and OVA challenge; and IUGR + Allergy - hypoxic and OVA challenge. At 8 weeks of age, and 24 h post-aerosol challenge, mice were tracheostomised for methacholine challenge and assessment of lung mechanics by the forced oscillation technique, and lungs subsequently fixed for morphometry. Results: IUGR offspring were lighter than Control at birth and in adulthood. Both Allergy and IUGR independently increased airway resistance after methacholine challenge. The IUGR group also exhibited an exaggerated increase in tissue damping and elastance after methacholine challenge compared with Control. However, there was no incremental effect on airway responsiveness in the combined IUGR + Allergy group. There was no impact of IUGR or Allergy on airway structure and no effect of sex on any outcome. Conclusion: IUGR and aeroallergen independently increased bronchoconstrictor response, but when combined the pathophysiology was not worsened. Findings suggest that an association between IUGR and asthma is mediated by baseline airway responsiveness rather than susceptibility to allergen.

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.

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.

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.

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.

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.