Liver Attenuation Research Articles

Diagnostic Accuracy of CT for the Detection of Hepatic Steatosis: A Systematic Review and Meta-Analysis.

Background CT plays an important role in the opportunistic identification of hepatic steatosis. CT performance for steatosis detection has been inconsistent across various studies, and no clear guidelines on optimum thresholds have been established. Purpose To conduct a systematic review and meta-analysis to assess CT diagnostic accuracy in hepatic steatosis detection and to determine reliable cutoffs for the commonly mentioned measures in the literature. Materials and Methods A systematic search of the PubMed, Embase, and Scopus databases (English-language studies published from September 1977 to January 2024) was performed. Studies evaluating the diagnostic accuracy of noncontrast CT (NCCT), contrast-enhanced (CECT), and dual-energy CT (DECT) for hepatic steatosis detection were included. Reference standards included biopsy, MRI proton density fat fraction (PDFF), or NCCT. In several CECT and DECT studies, NCCT was used as the reference standard, necessitating subgroup analysis. Statistical analysis included a random-effects meta-analysis, assessment of heterogeneity with use of the I2 statistic, and meta-regression to explore potential sources of heterogeneity. When available, mean liver attenuation, liver-spleen attenuation difference, liver to spleen attenuation ratio, and the DECT-derived fat fraction for hepatic steatosis diagnosis were assessed. Results Forty-two studies (14 186 participants) were included. NCCT had a sensitivity and specificity of 72% and 88%, respectively, for steatosis (>5% fat at biopsy) detection and 82% and 94% for at least moderate steatosis (over 20%-33% fat at biopsy) detection. CECT had a sensitivity and specificity of 66% and 90% for steatosis detection and 68% and 93% for at least moderate steatosis detection. DECT had a sensitivity and specificity of 85% and 88% for steatosis detection. In the subgroup analysis, the sensitivity and specificity for detecting steatosis were 80% and 99% for CECT and 84% and 93% for DECT. There was heterogeneity among studies focusing on CECT and DECT. Liver attenuation less than 40-45 HU, liver-spleen attenuation difference less than -5 to 0 HU, and liver to spleen attenuation ratio less than 0.9-1 achieved high specificity for detection of at least moderate steatosis. Conclusion NCCT showed high performance for detection of at least moderate steatosis. © RSNA, 2024 Supplemental material is available for this article.

Multi-Protective Effects of Petunidin-3-O-(trans-p-coumaroylrutinoside)-5-O-glucoside on D-Gal-Induced Aging Mice

Petunidin-3-O-(trans-p-coumaroylrutinoside)-5-O-glucoside (PtCG), the primary anthocyanin ingredient in Lycium ruthenicum Murr., possesses a range of biological activities, including antioxidative properties and melanin inhibition. This study aimed to investigate the protective effect of PtCG on D-galactose (D-gal)-induced aging in female mice and elucidate the underlying molecular pathways. Behavioral experiments, including the MWW and Y-maze tests, revealed that PtCG significantly ameliorated cognitive decline and enhanced learning and memory abilities in aging mice. Regarding biochemical indicators, PtCG considerably improved superoxide dismutase (SOD) and glutathione (GSH) activity while reducing malondialdehyde (MDA) and acetylcholinesterase (AChE) levels in the hippocampus and serum. Furthermore, PtCG ingestion alleviated liver injury by decreasing alanine transaminase (ALT), aspartate transaminase (AST), and alkaline phosphatase (AKP) levels, and attenuated renal damage by reducing blood urea nitrogen (BUN) and uric acid (UA) levels. Transmission electron microscopy (TEM) results demonstrated that PtCG restored the function and quantity of synapses in the hippocampus. Hematoxylin and eosin (H&E), Masson’s trichrome, and Nissl staining revealed that PtCG significantly improved the relevant pathological characteristics of liver and hippocampal tissues in aging mice. The molecular mechanism investigation showed that PtCG downregulated the protein expression of microglial marker ionized calcium-binding adapter molecule 1 (Iba1), astrocytic marker glial fibrillary acidic protein (GFAP), β-secretase 1 (BACE-1), and amyloid-beta1–42 (Aβ1–42) in the hippocampus of aging mice. The protein expression of inflammatory pathway components, including nuclear factor-kappa B (NF-κB), cyclooxygenase-2 (COX2), inducible nitric oxide synthase (iNOS), and interleukin-1 beta (IL-1β), was also suppressed. These findings suggest that PtCG may possess anti-aging properties, with its mechanism of action potentially linked to the attenuation of neuroinflammation, oxidative stress, and liver and kidney damage. PtCG may have future applications as a functional food for the treatment of aging-related disorders.

Can Cardiovascular Risk Be Simply Estimated in Nonalcoholic Fatty Liver Disease Patients?

Backgrounds and Aims: In the pathogenesis of nonalcoholic fatty liver disease (NAFLD), inflammation plays a pivotal role. The presence of inflammatory cells is closely linked with epicardial adipose tissue (EAT). A recently identified prognostic indicator for cardiovascular disease (CVD) is the ratio of monocyte count to HDL-cholesterol (MHR). Our primary aim was to investigate the relationship between EAT and markers of inflammation in individuals with NAFLD, and to evaluate its predictability using straightforward diagnostic measures. Material-Method: This retrospective study included two hundred eighteen patients who underwent thoracic computed tomography angiography between 2014 and 2021. The patients were divided into the NAFLD group (HU48 IU) according to the liver attenuation ratio. 136 patients in the NAFLD group and 82 in the non-NAFLD group. Results: The body mass index (BMI), triglyceride levels, notably the EAT volume and MHR in the NAFLD group, exhibited higher values than non-NAFLD group. Among participants in the NAFLD group, a positive correlation was observed between EAT volume and factors such as age, MHR, c-reactive protein, BMI, urea, glucose, and alanine aminotransferase. Through linear regression analysis, it was determined that MHR stood as the sole independent predictor of EAT volume in patients with NAFLD. Conclusion: EAT volume, a risk marker for CVD, can be predicted in NAFLD patients by MHR without radiological methods. Thus, easier and earlier detection of NAFLD patients in the high-risk group for CVD will be possible.

Can Opportunistic Use of Computed Tomography Help Reveal the Association Between Hepatic Steatosis and Disease Severity in Hospitalized COVID-19 Patients?

To measure hepatic steatosis (HS) in hospitalized COVID-19 patients using unenhanced chest computed tomography (CT) imaging and to evaluate the relationship between disease severity and prognosis in adult patients.This retrospective study included 152 consecutive hospitalized COVID-19 patients with a positive reverse transcriptase polymerase chain reaction (RT-PCR) test. The COVID-19 Reporting and Data System (CO-RADS) and the chest CT score were evaluated. HS measurements were performed based on CT images using a single region of interest placed on the right liver lobe (segments V-VII). HS was defined as a liver attenuation value <40 Hounsfield units. Data were collected and compared with the patients' prognostic parameters.Of the 152 inpatients, 137 patients (90.1%) had a CT score ≥3 and 109 patients (71.7%) had a CO-RADS score ≥4, 43 (28.2%) had HS. All patients with HS (100%) and 94/109 (86.2%) patients without HS had a CT score ≥3. There was a statistically significant difference between the two groups in terms of chest CT score (p=0.006). There was no statistically significant difference between the two groups in terms of CO-RADS score (p=0.291). The median CRP levels were significantly increased in patients with HS compared to patients without HS (p=0.023). There was no significant difference in ICU hospitalization and mortality due to the presence of HS (p>0.05).The current study revealed significantly higher chest CT scores in COVID-19 patients with HS measured on CT compared to those without HS. Opportunistic use of CT images for the detection of HS can be considered as an adjunctive tool in the risk analysis of COVID-19 patients hospitalized due to COVID-19 pneumonia.The severity of COVID-19 disease is increased in hospitalized patients with hepatosteatosis compared to patients with a normal liver. Density measurements for the evaluation of HS using opportunistic CT applications can be considered as an adjunctive tool in the prognostic evaluation of hospitalized patients with COVID-19 pneumonia. · Parlak AE, Erdem Toslak İ, Turkoglu Selcuk N. Can Opportunistic Use of Computed Tomography Help Reveal the Association Between Hepatic Steatosis and Disease Severity in Hospitalized COVID-19 Patients?. Fortschr Röntgenstr 2024; DOI 10.1055/a-2369-8377.

Feasibility of a single-phase portal venous CT protocol using bolus tracking technique and lean body weight-based contrast media dose.

To evaluate the impact of the use of lean body weight (LBW)-based contrast material (CM) dose and bolus tracking technique on portal venous phase abdominal CT image quality. IRB-approved prospective study; informed consent was acquired. In the period July-November 2023, we randomly selected 105 oncologic patients scheduled for a portal venous phase abdominal CT to undergo our experimental protocol (i.e., 0.7 gI/Kg of LBW CM administration and bolus tracking on the liver). Included patients had performed a "standard" portal venous phase abdominal CT (i.e., 0.6 gI/Kg of total body weight (TBW) contrast material administration and 70 s fixed delay) on the same scanner within the previous 12 months. One reader evaluated CT images measuring liver, portal vein, kidney cortex, and spleen attenuation; values were normalized to paraspinal muscles. Median administered contrast dose (350 mgI/mL CM) was 99 mL (IQR: 81-115 mL) using the experimental protocol and 110 mL (IQR: 100-120 mL) using the standard one (p < 0.0001). Median acquisition delay using the experimental protocol was 65" (IQR 59-73"). Median normalized hepatic enhancement was significantly higher using the experimental protocol (1.97, IQR: 1.83-2.47 vs. 1.86, IQR: 1.58-2.11; p < 0.0001). Median normalized portal vein enhancement was significantly higher using the experimental protocol (3.43, IQR: 2.73-4.04 vs. 2.91, IQR: 2.58-3.41; p < 0.0001). No statistically significant differences were found in the kidneys' cortex and aorta normalized enhancement (p > 0.05). The combination of LBW-based CM dose administration and bolus tracking allows a significant CM dose reduction and a significant liver and portal vein enhancement increase. Lean body weight-based contrast material (CM) dose administration and bolus tracking technique in portal venous phase CT scans overcome differences in body composition and hemodynamics, improving reproducibility. It allows a significant CM dose reduction with increased liver and portal vein enhancement. Lean body weight (LBW)-based contrast material (CM) dosing could be superior to total body weight dosing. Portal venous phase CT with a liver bolus tracking technique improved liver and spleen enhancement with a reduced contrast dose. The combination of LBW-based CM dosing and liver bolus tracking technique enables more "customized" CT examinations.

Detecting Hepatic Steatosis Among Potential Liver Donors by Using Non-Invasive Methods

Objective: To evaluate the effectiveness of non-invasive methods in detecting hepatic steatosis among potential liver donors. Methodology: This cross-sectional descriptive study included 67 potential liver donors, recruited via consecutive non-probability sampling over a two-year period (2021-2023). Data collection involved a semi-structured questionnaire covering demographics and biochemical indicators like serum bilirubin, cholesterol levels, ALT, AST, platelets, INR, and GGT. Hepatic steatosis was assessed using Fasting Lipid Profile, Fibroscan/Shearwave ultrasonography, and Liver Attenuation Index (LAI) from CT scans. Descriptive statistics were applied, and gender-based variations in biochemical markers, CAP, and LSM were analyzed using independent t-tests. Chi-square tests evaluated gender differences in steatosis identified by pathology and CAP. A significance level of P &lt; 0.05 was used. Results: Of the 67 donors, 49 were males, with a mean age of 30.1 ± 8.8 years. Pathology revealed mild steatosis in 35 and moderate steatosis in 5 donors. Ultrasound showed normal liver echotexture in 47 subjects, while 18 had fatty liver. CAP findings indicated mild steatosis in both genders, with females showing higher values (P = 0.02) and more advanced steatosis (P &lt; 0.01). Mean LSM was 4.6 ± 1.53 kPa, indicating normal liver stiffness. LAI findings suggested 37 donors required further evaluation. Among overweight donors, 22% had advanced steatosis compared to 14% in the healthy-weight group. Conclusion: Ultrasound-directed CAP, LSM, and BMI are effective non-invasive tools for diagnosing hepatic steatosis in potential liver donors.

AI-based abdominal CT measurements of orthotopic and ectopic fat predict mortality and cardiometabolic disease risk in adults.

To evaluate the utility of CT-based abdominal fat measures for predicting the risk of death and cardiometabolic disease in an asymptomatic adult screening population. Fully automated AI tools quantifying abdominal adipose tissue (L3 level visceral [VAT] and subcutaneous [SAT] fat area, visceral-to-subcutaneous fat ratio [VSR], VAT attenuation), muscle attenuation (L3 level), andliver attenuation were applied to non-contrast CT scans in asymptomatic adults undergoing CT colonography (CTC). Longitudinal follow-up documented subsequent deaths, cardiovascular events, and diabetes. ROC andtime-to-event analyses were performed to generate AUCs andhazard ratios (HR) binned by octile. A total of 9223 adults (mean age, 57 years; 4071:5152 M:F) underwent screening CTC from April 2004 to December 2016. 549 patients died on follow-up (median, nine years). Fat measures outperformed BMI for predicting mortality risk-5-year AUCs for muscle attenuation, VSR, and BMI were 0.721, 0.661, and 0.499, respectively. Higher visceral, muscle, and liver fat were associated with increased mortality risk-VSR > 1.53, HR = 3.1; muscle attenuation < 15 HU, HR = 5.4; liver attenuation < 45 HU, HR = 2.3. Higher VAT area and VSR were associated with increased cardiovascular event and diabetes risk-VSR > 1.59, HR = 2.6 for cardiovascular event; VAT area > 291 cm2, HR = 6.3 for diabetes (p < 0.001). A U-shaped association was observed for SAT with a higher risk of death for very low and very high SAT. Fully automated CT-based measures of abdominal fat are predictive of mortality and cardiometabolic disease risk in asymptomatic adults and uncover trends that are not reflected in anthropomorphic measures. Fully automated CT-based measures of abdominal fat soundly outperform anthropometric measures for mortality and cardiometabolic risk prediction in asymptomatic patients. Abdominal fat depots associated with metabolic dysregulation and cardiovascular disease can be derived from abdominal CT. Fully automated AI body composition tools can measure factors associated with increased mortality and cardiometabolic risk. CT-based abdominal fat measuresuncover trends in mortality and cardiometabolic risk not captured by BMI in asymptomatic outpatients.

Predicting of Hepatic Steatosis in Living Liver Donor via CT Liver Attenuation Index (LAI) and Fibroscan Controlled Attenuation Parameter (CAP) Correlation with Biopsy Result

Abstract Background The most prevalent persistent parenchymatous liver alterations in healthy individuals are thought to be hepatic steatosis. The liver biopsy is the most crucial procedure for the identification and measurement of hepatic steatosis. By identifying the liver attenuation index (LAI) at an unenhanced CT image, hepatic steatosis can be evaluated without the risk of liver resection. Objective Using liver biopsy histological analysis as a reference standard, to examine the precision of the CT liver attenuation index (LAI) and fibroscan controlled attenuation parameter (CAP) for quantitative evaluation of macro vesicular steatosis in living related liver donors. Methods In this study comparing CT liver attenuation index &amp; fibroscan controlled attenuation parameter with liver pathology of steatosis in subject's candidate for liver living donors 50 subjects in each two study's correlation with biopsy results, conducted at Ain Shams Shams Specialized hospital and other Private hospitals over about 2 years. Results Our study reported that liver – spleen attenuation index of 9 is the cutoff value with sensitivity 100% and specificity 80% that make it a very good method to exclude donor to have steatosis ≥15%, which mean if donor had LS index &amp;lt; 9 we can safely do proceed do liver biopsy. Our study reported that CAP measurement had an AUROC OF 0.780, for detecting steatosis ≥ 15 %, with sensitivity is only 60% with specificity as CT LAI of 80%, which consider low compared to other study, that could be due to small number of donors in out study with steatosis ≥ 15 % (5 case from 50 donors) unlike the other studies. Conclusion When used to estimate the amount of liver fat in liver donors, the examined CAP and CT indices worked equally. But according to multivariate analysis, the only factor strongly linked with hepatic steatosis in alive donors was the CT L-S attenuation index. We contend that the combination of CT L-S attenuation index and CAP allows for the detection of the degree of hepatic steatosis and can be used as an option to liver biopsy, reserving liver biopsy for those with positive steatosis donors.

Automated hepatic steatosis assessment on dual-energy CT-derived virtual non-contrast images through fully-automated 3D organ segmentation

PurposeTo evaluate the efficacy of volumetric CT attenuation-based parameters obtained through automated 3D organ segmentation on virtual non-contrast (VNC) images from dual-energy CT (DECT) for assessing hepatic steatosis.Materials and methodsThis retrospective study included living liver donor candidates having liver DECT and MRI-determined proton density fat fraction (PDFF) assessments. Employing a 3D deep learning algorithm, the liver and spleen were automatically segmented from VNC images (derived from contrast-enhanced DECT scans) and true non-contrast (TNC) images, respectively. Mean volumetric CT attenuation values of each segmented liver (L) and spleen (S) were measured, allowing for liver attenuation index (LAI) calculation, defined as L minus S. Agreements of VNC and TNC parameters for hepatic steatosis, i.e., L and LAI, were assessed using intraclass correlation coefficients (ICC). Correlations between VNC parameters and MRI-PDFF values were assessed using the Pearson’s correlation coefficient. Their performance to identify MRI-PDFF ≥ 5% and ≥ 10% was evaluated using receiver operating characteristic (ROC) curve analysis.ResultsOf 252 participants, 56 (22.2%) and 16 (6.3%) had hepatic steatosis with MRI-PDFF ≥ 5% and ≥ 10%, respectively. LVNC and LAIVNC showed excellent agreement with LTNC and LAITNC (ICC = 0.957 and 0.968) and significant correlations with MRI-PDFF values (r = − 0.585 and − 0.588, Ps < 0.001). LVNC and LAIVNC exhibited areas under the ROC curve of 0.795 and 0.806 for MRI-PDFF ≥ 5%; and 0.916 and 0.932, for MRI-PDFF ≥ 10%, respectively.ConclusionVolumetric CT attenuation-based parameters from VNC images generated by DECT, via automated 3D segmentation of the liver and spleen, have potential for opportunistic hepatic steatosis screening, as an alternative to TNC images.

Post-contrast CT liver attenuation alone is superior to the liver-spleen difference for identifying moderate hepatic steatosis.

To assess the diagnostic performance of post-contrast CT for predicting moderate hepatic steatosis in an older adult cohort undergoing a uniform CT protocol, utilizing hepatic and splenic attenuation values. A total of 1676 adults (mean age, 68.4 ± 10.2 years; 1045M/631F) underwent a CT urothelial protocol that included unenhanced, portal venous, and 10-min delayed phases through the liver and spleen. Automated hepatosplenic segmentation for attenuation values (in HU) was performed using a validated deep-learning tool. Unenhanced liver attenuation < 40.0 HU, corresponding to > 15% MRI-based proton density fat, served as the reference standard for moderate steatosis. The prevalence of moderate or severe steatosis was 12.9% (216/1676). The diagnostic performance of portal venous liver HU in predicting moderate hepatic steatosis (AUROC = 0.943) was significantly better than the liver-spleen HU difference (AUROC = 0.814) (p < 0.001). Portal venous phase liver thresholds of 80 and 90 HU had a sensitivity/specificity for moderate steatosis of 85.6%/89.6%, and 94.9%/74.7%, respectively, whereas a liver-spleen difference of -40 HU and -10 HU had a sensitivity/specificity of 43.5%/90.0% and 92.1%/52.5%, respectively. Furthermore, livers with moderate-severe steatosis demonstrated significantly less post-contrast enhancement (mean, 35.7 HU vs 47.3 HU; p < 0.001). Moderate steatosis can be reliably diagnosed on standard portal venous phase CT using liver attenuation values alone. Consideration of splenic attenuation appears to add little value. Moderate steatosis not only has intrinsically lower pre-contrast liver attenuation values (< 40 HU), but also enhances less, typically resulting in post-contrast liver attenuation values of 80 HU or less. Moderate steatosis can be reliably diagnosed on post-contrast CT using liver attenuation values alone. Livers with at least moderate steatosis enhance less than those with mild or no steatosis, which combines with the lower intrinsic attenuation to improve detection. The liver-spleen attenuation difference is frequently utilized in routine practice but appears to have performance limitations. The liver-spleen attenuation difference is less effective than liver attenuation for moderate steatosis. Moderate and severe steatosis can be identified on standard portal venous phase CT using liver attenuation alone.

Deep-learning segmentation to select liver parenchyma for categorizing hepatic steatosis on multinational chest CT

Unenhanced CT scans exhibit high specificity in detecting moderate-to-severe hepatic steatosis. Even though many CTs are scanned from health screening and various diagnostic contexts, their potential for hepatic steatosis detection has largely remained unexplored. The accuracy of previous methodologies has been limited by the inclusion of non-parenchymal liver regions. To overcome this limitation, we present a novel deep-learning (DL) based method tailored for the automatic selection of parenchymal portions in CT images. This innovative method automatically delineates circular regions for effectively detecting hepatic steatosis. We use 1,014 multinational CT images to develop a DL model for segmenting liver and selecting the parenchymal regions. The results demonstrate outstanding performance in both tasks. By excluding non-parenchymal portions, our DL-based method surpasses previous limitations, achieving radiologist-level accuracy in liver attenuation measurements and hepatic steatosis detection. To ensure the reproducibility, we have openly shared 1014 annotated CT images and the DL system codes. Our novel research contributes to the refinement the automated detection methodologies of hepatic steatosis on CT images, enhancing the accuracy and efficiency of healthcare screening processes.

Comparation between Fibroscan and Hepatus for detecting NAFLD in patients with metabolic dysregulation

Background The clinical application of the innovative instantaneous elasticity and fat attenuation measurement technology, Hepatus, is currently in the evaluation stage. This study aimed to compare the detection performance of Fibroscan and Hepatus in patients with metabolic dysregulation who are "at-risk" for non-alcoholic fatty liver disease (NAFLD).Methods Between January 2021 and April 2021, 149 patients were enrolled in this study. Clinical data were collected, and all patients underwent both Fibroscan and Hepatus assessments to determine liver stiffness measurement (LSM) and attenuation parameters. The correlation between the results obtained from the two transient elastography (TE) devices was analyzed. Receiver operating characteristic curves (ROC) were constructed to compare the diagnostic value of Fibroscan and Hepatus for Hepatic Steatosis Index (HSI)-based NAFLD.Results The detection success rate of Hepatus (100.0%) was higher than that of Fibroscan (96.0%). LSM (r = 0.663, P0.05) and attenuation parameters (r = 0.778, P0.05) obtained by Fibroscan and Hepatus were significantly correlated. Hepatus tended to produce a higher LSM (Hepatus vs. Fibroscan: 6.04 vs. 5.66 kPa, P=0.016) but a lower attenuation parameter than Fibroscan (Hepatus vs. Fibroscan: 264 vs. 277 dB/m, P0.001). The area under the ROC curve for detecting HSI-based NAFLD was 0.811 for Fibroscan and 0.832 for Hepatus.Conclusion Measurements obtained by Fibroscan and Hepatus are strongly correlated, and the diagnostic value of the two TE devices is comparable in detecting HSI-based NAFLD. Hepatus offer a potential TE alternative in NAFLD examination.

Deep learning imaging phenotype can classify metabolic syndrome and is predictive of cardiometabolic disorders

BackgroundCardiometabolic disorders pose significant health risks globally. Metabolic syndrome, characterized by a cluster of potentially reversible metabolic abnormalities, is a known risk factor for these disorders. Early detection and intervention for individuals with metabolic abnormalities can help mitigate the risk of developing more serious cardiometabolic conditions. This study aimed to develop an image-derived phenotype (IDP) for metabolic abnormality from unenhanced abdominal computed tomography (CT) scans using deep learning. We used this IDP to classify individuals with metabolic syndrome and predict future occurrence of cardiometabolic disorders.MethodsA multi-stage deep learning approach was used to extract the IDP from the liver region of unenhanced abdominal CT scans. In a cohort of over 2,000 individuals the IDP was used to classify individuals with metabolic syndrome. In a subset of over 1,300 individuals, the IDP was used to predict future occurrence of hypertension, type II diabetes, and fatty liver disease.ResultsFor metabolic syndrome (MetS) classification, we compared the performance of the proposed IDP to liver attenuation and visceral adipose tissue area (VAT). The proposed IDP showed the strongest performance (AUC 0.82) compared to attenuation (AUC 0.70) and VAT (AUC 0.80). For disease prediction, we compared the performance of the IDP to baseline MetS diagnosis. The models including the IDP outperformed MetS for type II diabetes (AUCs 0.91 and 0.90) and fatty liver disease (AUCs 0.67 and 0.62) prediction and performed comparably for hypertension prediction (AUCs of 0.77).ConclusionsThis study demonstrated the superior performance of a deep learning IDP compared to traditional radiomic features to classify individuals with metabolic syndrome. Additionally, the IDP outperformed the clinical definition of metabolic syndrome in predicting future morbidities. Our findings underscore the utility of data-driven imaging phenotypes as valuable tools in the assessment and management of metabolic syndrome and cardiometabolic disorders.

Abstract PO4-04-09: Incidence, prevalence, risk factors, and impact of fatty liver disease in metastatic HR+/HER2− breast cancer patients treated with Endocrine Therapy and CDK 4/6 Inhibitor

Abstract Background: In patients with early-stage breast cancer (BC), non-alcoholic fatty liver disease (NAFLD) is associated with increased recurrence, cardiovascular events, and non-cancer death. Endocrine therapy increases the risk of NAFLD. The impact of cyclin-dependent kinases 4/6 inhibitors (CDKi) combined with endocrine therapy on NAFLD and prognostic association in metastatic breast canceris unknown. Here, we characterize the incidence, prevalence, risk factors, and treatment outcomes of NAFLD in women with metastatic HR+/HER2- BC. Methods: We conducted a retrospective cohort study of patients with advanced HR+/HER2- BC receiving first line endocrine and CDKi at Princess Margaret Cancer Centre, Toronto, Canada between January 2018 – June 2022. Patients were excluded if they had liver disease, prior chemotherapy, or no access to CT scans. Demographic, treatment, toxicity, and survival data were extracted. Liver Attenuation Index (LAI) on contrast-enhanced portal venous phase CT scan was utilized.NAFLD was defined as LAI &amp;gt;25 HU. Univariable binary-logistic regression analysis wasused to assess independent predictive factors of NAFLD. Statistical significance was defined as p&amp;lt; 0.05. Quantitative significance was defined by the Burnand criteria. Time to treatment failure (TTF) was assessed using Cox proportional hazards modeling. Results: Of approximately 90 eligible patients, 40 are included in this analysis. Baseline demographics included median age 61 years, 72% post-menopausal, 58% de-novo metastatic disease, and 27% visceral disease. Of 40 patients, 28 (70%) had NAFLD at anytime (12 at baseline and 16 incident). Associations with NAFLD are shown in Table 1. Presence of NAFLD was associated quantitatively but not statistically with age &amp;gt; 65 (OR 2.6), post-menopausal status (OR 2.6), and inversely associated with prior chemotherapy (OR 0.27) and visceral disease (OR 0.38). Lack of NAFLD at any time was significantly associated with worse TTF (mean TTF 497 versus 1228 days, HR=4.28, 95% CI: 1.89-9.68, p&amp;lt; 0.001). Patients without NAFLD at baseline also had a worse TTF (mean 903 vs 1186 days) compared to those with it at baseline, but this difference was not statistically significance (HR=1.93, 95%CI: 0.77-4.83, p= 0.163). No significant differences were found in grade 3/4 adverse events. Patients who have presented NAFLD at any time received an average of 1.36 subsequent lines of therapy compared to 2.08 in those without. Discussion &amp; Conclusion: This analysis demonstrated an association between presence of NAFLD and longer TTF. This may reflect reverse causation whereby longer exposure to ET and CDKi increases the observation of NAFLD or that these are distinct populations with different molecular pathways leading to differences in response to treatment and prognosis. It is noteworthy that the median time to develop NAFLD in the incident group was 339 days, and the group that never developed NAFLD was on treatment longer than this. Overexpression of CDK 4/6 pathway, could increase sensitivity and duration to treatment with CDKi but produce adverse metabolic changes of increased lipid synthesis, as described in pre-clinical models. If this hypothesis is confirmed, synergistically addressing these metabolic changes with physical exercise, dietary, or pharmacological interventions may improve these patients’ fitness for subsequent lines of therapy. Table 1 Citation Format: Diego Malon Gimenez, Consolacion Molto Valiente, Shopnil Prasla, Danielle Cuthbert, Abhenil Mittal, Faris Tamimi, Massimo Di Iorio, Meredith Li, Neha Pathak, Eitan Amir, Kartik Jhaveri, Michelle Nadler. Incidence, prevalence, risk factors, and impact of fatty liver disease in metastatic HR+/HER2− breast cancer patients treated with Endocrine Therapy and CDK 4/6 Inhibitor [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-04-09.

Decreased portal vein attenuation and liver enhancement with reduced intravenous contrast dosage during the national iodinated contrast shortage of 2022.

The worldwide shortage of intravenous (IV) Omnipaque iodinated contrast (Iohexol, GE Healthcare; Milwaukee, WI, USA) forced institutions to adopt various policies regarding contrast allocation. We sought to evaluate the impact of our hospital's response to the shortage, which was to decrease the dose of IV contrast from 100 mL to 75 mL for patients weighing between 45.4 and 136 kg (100-300 lbs) undergoing abdominal computed tomography (CT) examinations. The main objective was to assess for any differences in liver attenuation and enhancement between contrast dosages. Secondary outcomes included assessing differences in aortic and portal vein attenuation, the variance in attenuation measurements, and whether radiology reports included the correct IV contrast dose. Consecutive CT abdomen or CT abdomen and pelvis examinations without and with contrast were analyzed for the 3 months before the contrast shortage and for 3 months during the contrast shortage. Attenuation in Hounsfield units (HUs) was measured in the liver on pre-contrast and portal venous phase images. Vessel attenuation was measured in the aorta (arterial phase) and main portal vein (portal venous phase). Standard deviation of liver attenuation measurements was recorded as an indicator of signal-to-noise. Liver enhancement was calculated as the difference between liver portal venous phase attenuation and pre-contrast attenuations. Thirty-nine fixed dose (100 mL) and 36 reduced dose (75 mL) consecutive CT studies were included in the study. There were no significant differences between the two groups with respect to baseline characteristics such as age, weight, body mass index, and gender. There was no significant difference in pre-contrast liver attenuation between groups, but there was statistically significant greater liver attenuation (99.6 vs. 91.2 HU, P = 0.04) and liver enhancement (51.5 vs. 39.1 HU, P < 0.0001) during the portal venous phase for the fixed-dose group compared to the reduced dose group. There was significantly greater main portal vein opacification during the portal venous phase for the fixed dose group (146.6 vs. 122.2 HU, P < 0.0001). No significant difference was found in aortic opacification during the arterial phase (245 vs. 254 HU, P = 0.52). There was no difference in the standard deviation of liver attenuation measurements on the portal venous phase between the groups. The dose was reported correctly in all the patients receiving the fixed dose and in 92% of patients receiving the reduced dose, which was not statistically significant (P = 0.11). Reducing the IV contrast dose from 100 mL to 75 mL Omnipaque 350 in patients weighing 45.4-136 kg (100-300 lbs) undergoing an abdominal CT examination resulted in significantly decreased portal vein opacification and liver enhancement. In particular, liver enhancement and calculated iodine concentrations fell below suggested thresholds for adequate conspicuity of liver lesions. The change in contrast administration protocol also led to more errors in contrast dose reporting in the radiologist's report. These findings are broadly applicable to many practice settings and can help inform strategies in response to any potential future-iodinated contrast shortage.

Hepatic steatosis: Qualitative and quantitative sonographic assessment in comparison to histology.

Globally, B-mode ultrasound is the most common modality used for the diagnosis of hepatic steatosis. We aimed to assess the correlation between qualitative liver ultrasound parameters, attenuation imaging (ATI) and histopathology-diagnosed steatosis grade obtained from liver biopsy. Our secondary aim was to examine the interobserver variability of qualitative ultrasound features. A retrospective cohort study was performed which included adult patients (age ≥ 18 years) who had same-day liver ultrasound, ATI and liver biopsy for grading hepatic steatosis severity between 2018 and 2022. The qualitative US features for hepatic steatosis were independently scored by three radiologists and interobserver variability was examined. Histologic steatosis grade, ATI and qualitative ultrasound parameters were compared. Ninety patients were included; 67% female with a median age of 54 (IQR 39-65) years. The radiologist's overall impression had the highest correlation (very strongly correlated) with histologic steatosis grade (r = 0.82, P < 0.001). ATI coefficient and all qualitative ultrasound B-mode features except for liver echotexture and focal fat sparing were strongly correlated with histologic steatosis grade (r ≥ 0.70, P < 0.001). Most qualitative ultrasound features had good agreement between observers (Kappa statistic 0.61-1.0, P < 0.001), (Kendall coefficient 0.92, P < 0.001). The examined qualitative ultrasound parameters and ATI had good-excellent performance for diagnosing clinically significant hepatic steatosis; however, the radiologist's overall impression had the best correlation with histologic steatosis grade. Our findings suggest an ongoing role for qualitative liver ultrasound assessment of hepatic steatosis despite the emergence of newer quantitative measures.

Associations of Fecal Microbiota with Ectopic Fat in African Caribbean Men.

The gut microbiome has been associated with visceral fat (VAT) in European and Asian populations; however, associations with VAT and with ectopic fats among African-ancestry individuals are not known. Our objective was to investigate cross-sectional associations of fecal microbiota diversity and composition with VAT and ectopic fat, as well as body mass index (BMI), among middle-aged and older African Caribbean men. We included in our analysis n = 193 men (mean age = 62.2 ± 7.6 years; mean BMI = 28.3 ± 4.9 kg/m2) from the Tobago Health Study. We assessed fecal microbiota using V4 16s rRNA gene sequencing. We evaluated multivariable-adjusted associations of microbiota features (alpha diversity, beta diversity, microbiota differential abundance) with BMI and with computed tomography-measured VAT and ectopic fats (pericardial and intermuscular fat; muscle and liver attenuation). Lower alpha diversity was associated with higher VAT and BMI, and somewhat with higher pericardial and liver fat. VAT, BMI, and pericardial fat each explained similar levels of variance in beta diversity. Gram-negative Prevotellaceae and Negativicutes microbiota showed positive associations, while gram-positive Ruminococcaceae microbiota showed inverse associations, with ectopic fats. Fecal microbiota features associated with measures of general adiposity also extend to metabolically pernicious VAT and ectopic fat accumulation in older African-ancestry men.

Hepatic lipid accumulation is associated with multiple metabolic pathway alterations but not dyslipidemia and insulin resistance in central bearded dragons (Pogona vitticeps).

To investigate associations between hepatic fat accumulation, fibrosis, and plasma values of primary metabolites, biochemical measurands, insulin, and lipoproteins in bearded dragons. 48 adult central bearded dragons (Pogona vitticeps). Dragons were sedated with alfaxalone, and a blood sample was collected. Plasma was submitted for untargeted primary metabolomics using gas chromatography time-of-flight mass spectrometry, a biochemistry panel, and a lipoprotein panel determined by PAGE. Hepatic lipid content was quantified by liver attenuation measurements from CT images and digital image analysis of standardized histologic sections of the liver. Fibrosis was quantified by digital image analysis on Masson's trichrome-stained histologic sections. Severity was determined from pathologic review of liver sections according to a standardized grading system. Statistical associations were investigated using serial linear models adjusted for false discovery rate and multivariate statistics. Both hepatic fat and fibrosis had a significant effect on CT liver attenuation values. Several oligosaccharides (maltotriose, maltose, ribose, trehalose) and alkaline phosphatase were significantly and linearly increased with hepatic lipid content (all q < .05). On partial least square-discriminant analysis, β-hydroxybutyric acid was the most important discriminatory variable between fatty liver severity grades on histology. No significant associations were found with insulin, lipoproteins, and succinic acid. Bearded dragons with hepatic lipid accumulation experienced multiple metabolic pathway disruptions, some being compatible with mitochondrial dysfunction. No evidence of insulin resistance or dyslipidemia was found. Hepatic biopsy and histopathology remain recommended for reliably diagnosing and staging fatty liver disease in bearded dragons.

Point-of-care β-hydroxybutyrate measurement predicts adequate glucose metabolism suppression in cardiac FDG-PET/CT.

The aims of our study were to evaluate whether point-of-care β-hydroxybutyrate (BHB) measurement can be used to identify patients with adequate cardiac glucose metabolism suppression for cardiac[18F]-fluoro-2-deoxy-d-glucose-positron emission tomography with computerized tomography(FDG-PET/CT) and to develop a pretest probability calculator of myocardial suppression using other metabolic factors attainable before imaging. We recruited 193 patients with any clinical indication for whole body [18F]-FDG-PET/CT. BHB level was measured with a point-of-care device. Maximal myocardial standardized uptake value using lean body mass (SULmax) was measured from eight circular regions of interest with 1 cm circumference and background from left ventricular blood pool. Correlations SULmax and point-of-care measured BHB were analysed. The ability of BHB test to predict adequate suppression was evaluated with receiver operating characteristic analysis. Liver and spleen attenuation in computed tomography weremeasured to assess the presence of fatty liver. BHB level correlated with myocardial uptake and, using a cut-off value of 0.35 mmol/L to predict adequate myocardial suppression, we reached specificity of 90% and sensitivity of 56%. Other variables to predict adequate suppression were diabetes, obesity, ketogenic diet and fatty liver. Using information attainable before imaging, we created a pretest probability calculator of inadequate myocardial glucose metabolism suppression. The area under the curve for BHB test alone was 0.802 and was 0.857 for the pretest calculator (p = 0.319). BHB level measured with a point-of-care device is useful in predicting adequate myocardial glucose metabolism suppression. More detailed assessment of other factors potentially contributing to cardiac metabolism is needed.

Assessment of the functional state of gut microbiota in patients with metabolic-associated fatty liver disease in combination with type 2 diabetes mellitus

Background. The purpose of the study was to assess the functional state of gut microbiota in patients with metabolic-associated fatty liver disease (MAFLD) combined with type 2 diabetes mellitus (T2DM). Materials and methods. The prospective interventional randomized study included 71 patients with MAFLD in combination with T2DM, who were examined and divided into the 2 groups. The first group included 39 people with MAFLD and T2DM without small intestinal bacterial overgrowth (SIBO). The second group consisted of 32 patients with MAFLD in combination with T2DM and SIBO. The control group included 25 practically healthy patients. The content of serum zonulin was determined by enzyme-linked immunosorbent assay (ELISA) using test systems IDK Zonulin ELISA, KR5601. Serum concentration of interleukin (IL) 6 and IL-10 was assessed by the ELISA method using the Human Interleukin 6 and 10 ELISA Kit test systems. The content of short-chain fatty acids in feces was determined by gas chromatography with mass spectrometry in the PerkinElmer Clarus 680 GC Gas Chromatograph. Results. Patients of the first and second groups had an increase in hepatic aminotransferases, total cholesterol, triglycerides, fasting blood glucose, insulin, HOMA-IR, glycosylated hemoglobin, serum zonulin, leptin, IL-6 and liver attenuation coefficient and a decrease in high-density lipoprotein. The results of steatometry revealed a severe degree of hepatic steatosis (S3) in patients with MAFLD combined with T2DM and SIBO and without SIBO. During the quantitative study of the level of butyric acid in feces, it was found to be significantly reduced, by 2.3 times in the first group and by 3.4 times in the second one, compared to the controls (p &lt; 0.001). The content of butyric acid was decreased by 1.4 times in the second group compared to the first one (p &lt; 0.001). When evaluating the level of acetic acid, it was found to be significantly increased compared to the controls, by 1.2 times in the first group and by 1.3 times in the second one (p &lt; 0.001). The concentration of propionic acid was increased by 1.3 times in the first group and by 1.5 times in the second one compared the control group (p &lt; 0.05). When comparing the level of acetic acid, a significant increase by 1.3 times was observed in patients of the first and second groups compared to patients of the control group (p &lt; 0.001). The content of propionic and acetic acids was increased by 1.1 times in the second group compared to patients of the first group (p &lt; 0.05). When analyzing the correlation coefficients in patients with MAFLD combined with T2DM and SIBO and without SIBO, a direct proportional strong correlation was revealed between the levels of butyric, acetic and propionic acids and serum zonulin, IL-6, IL-10. A direct moderate correlation was found between the content of short-chain fatty acids and leptin, indicators of lipid metabolism (total cholesterol, triglycerides), carbohydrate metabolism (fasting blood glucose, HOMA-IR, HbA1c) and inverse weak correlation with high-density lipoprotein. A direct moderate correlation was revealed between levels of short-chain fatty acids and indicators of functional activity of the liver (alanine aminotransferase, aspartate aminotransferase), liver attenuation coefficient in patients with MAFLD combined with T2DM and SIBO and without SIBO. Conclusions. Increased intestinal permeability and hyperleptinemia have been found in patients with МAFLD combined with T2DM and SIBO and without SIBO. When studying the functional state of the gut microbiota, an increase was found in propionic and acetic acids and a decrease in butyric acid, which indicates an increase in the number of Bacteroidetes in the intestine and a decrease in Firmicutes. Patients with MAFLD combined with Т2DM and SIBO and without SIBO had a direct proportional strong correlation between the levels of butyric, acetic and propionic acids and serum zonulin, IL-6, IL-10, which is associated with pro-inflammatory and anti-inflammatory processes in the intestinal mucosa and a violation of the permeability of the intestinal barrier. It was found that concentrations of short-chain fatty acids correlate with indicators of functional activity of the liver (alanine aminotransferase, aspartate aminotransferase), leptin, indicators of carbohydrate and lipid metabolism, degree of hepatic steatosis.