Harmonized Multisite MRI-Based Quantification of Human Liver Fat and Stiffness: A Pilot Study.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a leading cause of end-stage liver disease. NAFLD diagnosis and follow-up relies on a combination of clinical data, liver imaging, and/or liver biopsy. However, intersite imaging differences impede diagnostic consistency and reduce the repeatability of the multisite clinical trials necessary to develop effective treatments. PURPOSE/HYPOTHESIS: The goal of this pilot study was to harmonize commercially available 3 T magnetic resonance imaging (MRI) measurements of liver fat and stiffness in human participants across academic sites and MRI vendors. STUDY TYPE: Cohort. SUBJECTS: Four community-dwelling adults with obesity. FIELD STRENGTH/SEQUENCE: 1.5 and 3 T, multiecho 3D imaging, PRESS, and GRE. ASSESSMENT: Harmonized proton density fat fraction (PDFF) and magnetic resonance spectroscopy (MRS) protocols were used to quantify the FF of synthetic phantoms and human participants with obesity using standard acquisition parameters at four sites that had four different 3 T MRI instruments. In addition, a harmonized magnetic resonance elastography (MRE) protocol was used to quantify liver stiffness among participants at two different sites at 1.5 and 3 T field strengths. Data were sent to a single data coordinating site for postprocessing. STATISTICAL TESTS: Linear regression in MATLAB, ICC analyses using SAS 9.4, one-sided 95% confidence intervals for the ICC. RESULTS: PDFF and MRS FF measurements were highly repeatable among sites in both humans and phantoms. MRE measurements of liver stiffness in three individuals at two sites using one 1.5 T and one 3 T instrument showed repeatability that was high although lower than that of MRS and PDFF. CONCLUSIONS: We demonstrated harmonization of PDFF, MRS, and MRE-based quantification of liver fat and stiffness through synthetic phantoms, traveling participants, and standardization of postprocessing analysis. Multisite MRI harmonization could contribute to multisite clinical trials assessing the efficacy of interventions and therapy for NAFLD. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 2.

Coronary Artery Calcium Scores in Older Adults With Diabetes and Their Association With Diabetes-Specific Risk Enhancers (from the Atherosclerosis Risk in Communities Study).

Coronary artery calcium (CAC) is a validated marker of atherosclerotic cardiovascular disease (ASCVD) risk; however, it is not routinely incorporated in ASCVD risk prediction in older adults with diabetes. We sought to assess the CAC distribution among this demographic and its association with "diabetes-specific risk enhancers," which are known to be associated with increased ASCVD risk. We used the ARIC (Atherosclerosis Risk in Communities) study data, including adults aged >75 years with diabetes, who had their CAC measured at ARIC visit 7 (2018 to 2019). The demographic characteristics of participants and their CAC distribution were analyzed using descriptive statistics. Multivariable-adjusted logistic regression models were used to estimate the association between diabetes-specific risk enhancers (duration of diabetes, albuminuria, chronic kidney disease, retinopathy, neuropathy, and ankle-brachial index) and elevated CAC, adjusting for age, gender, race, education level, dyslipidemia, hypertension, physical activity, smoking status, and family history of coronary heart disease. The mean age in our sample was 79.9 (SD 3.97) years, with 56.6% women and 62.1% White. The CAC scores were heterogenous, and the median CAC score was higher in participants with a greater number of diabetes risk enhancers, regardless of gender. In the multivariable-adjusted logistic regression models, participants with ≥2 diabetes-specific risk enhancers had greater odds of elevated CAC than those with <2 (odds ratio 2.31, 95% confidence interval 1.34 to 3.98). In conclusion, the distribution of CAC was heterogeneous among older adults with diabetes, with the CAC burden associated with the number of diabetes risk-enhancing factors present. These data may have implications for prognostication in older patients with diabetes and supports the possible incorporation of CAC in the assessment of cardiovascular disease risk in this population.

Lipoprotein(a) and Subclinical Vascular and Valvular Calcification on Cardiac Computed Tomography: The Atherosclerosis Risk in Communities Study.

Background Lipoprotein(a) (Lp(a)) is a potent causal risk factor for cardiovascular events and mortality. However, its relationship with subclinical atherosclerosis, as defined by arterial calcification, remains unclear. This study uses the ARIC (Atherosclerosis Risk in Communities Study) to evaluate the relationship between Lp(a) in middle age and measures of vascular and valvular calcification in older age. Methods and Results Lp(a) was measured at ARIC visit 4 (1996-1998), and coronary artery calcium (CAC), together with extracoronary calcification (including aortic valve calcium, aortic valve ring calcium, mitral valve calcification, and thoracic aortic calcification), was measured at visit 7 (2018-2019). Lp(a) was defined as elevated if >50 mg/dL and CAC/extracoronary calcification were defined as elevated if >100. Logistic and linear regression models were used to evaluate the association between Lp(a) and CAC/extracoronary calcification, with further stratification by race. The mean age of participants at visit 4 was 59.2 (SD 4.3) years, with 62.2% women. In multivariable adjusted analyses, elevated Lp(a) was associated with higher odds of elevated aortic valve calcium (adjusted odds ratio [aOR], 1.82; 95% CI, 1.34-2.47), CAC (aOR, 1.40; 95% CI, 1.08-1.81), aortic valve ring calcium (aOR, 1.36; 95% CI, 1.07-1.73), mitral valve calcification (aOR, 1.37; 95% CI, 1.06-1.78), and thoracic aortic calcification (aOR, 1.36; 95% CI, 1.05-1.77). Similar results were obtained when Lp(a) and CAC/extracoronary calcification were examined on continuous logarithmic scales. There was no significant difference in the association between Lp(a) and each measure of calcification by race or sex. Conclusions Elevated Lp(a) at middle age is significantly associated with vascular and valvular calcification in older age, represented by elevated CAC, aortic valve calcium, aortic valve ring calcium, mitral valve calcification, thoracic aortic calcification. Our findings encourage assessing Lp(a) levels in individuals with increased cardiovascular disease risk, with subsequent comprehensive vascular and valvular assessment where elevated.

Sex-and race-specific burden of aortic valve calcification among older adults without overt coronary heart disease: The Atherosclerosis Risk in Communities Study.

BACKGROUND AND AIMS: The prevalence of aortic valve calcification (AVC) increases with age. However, the sex-and race-specific burden of AVC and associated cardiovascular risk factors among adults ≥75 years are not well studied. METHODS: We calculated the sex-and race-specific burden of AVC among 2283 older Black and White adults (mean age:80.5 [SD:4.3] years) without overt coronary heart disease from the Atherosclerosis Risk in Communities Study who underwent non-contrast cardiac-gated CT-imaging at visit 7 (2018-2019). Using Poisson regression with robust variance, we calculated the adjusted prevalence ratios (aPR) of the association of AVC with cardiovascular risk factors. RESULTS: The overall AVC prevalence was 44.8%, with White males having the highest prevalence at 58.2%. The prevalence was similar for Black males (40.5%), White females (38.9%), and Black females (36.8%). AVC prevalence increased significantly with age among all race-sex groups. The probability of any AVC at age 80 years was 55.4%, 40.0%, 37.3%, and 36.2% for White males, Black males, White females, and Black females, respectively. Among persons with prevalent AVC, White males had the highest median AVC score (100.9 Agatston Units [AU]), followed by Black males (68.5AU), White females (52.3AU), and Black females (46.5AU). After adjusting for cardiovascular risk factors, Black males (aPR:0.53; 95%CI:0.33-0.83), White females (aPR:0.68; 95%CI:0.61-0.77), and Black females (aPR:0.49; 95%CI:0.31-0.77) had lower AVC prevalence compared to White males. In addition, systolic blood pressure, non-HDL-cholesterol, and lipoprotein (a) were independently associated with AVC, with no significant race/sex interactions. CONCLUSIONS: AVC, although highly prevalent, was not universally present in this cohort of older adults. White males had ∼50-60% higher prevalence than other race-sex groups. Moreover, cardiovascular risk factors measured in older age showed significant association with AVC.

Prospective validation of a rapid CT-based bone mineral density screening method using colored spinal images.

PURPOSE: To prospectively validate a method to accurately and rapidly differentiate normal from abnormal spinal bone mineral density (BMD) using colored abdominal CT images. METHODS: For this prospective observational study, 196 asymptomatic women ≥ 50 years of age presenting for screening mammograms underwent routine nonenhanced CT imaging of the abdomen. The CT images were processed with software designed to generate sagittal colored images with green vertebral trabecular bone indicating normal BMD and red indicating abnormal BMD (low BMD or osteoporosis). Four radiologists evaluated L1/L2 BMD on sagittal images using visual assessment of grayscale images, quantitative measurements of mean vertebral attenuation, and visual assessment of colored images. Mean BMD values at L1/L2 using quantitative CT with a phantom served as the reference standard. The average accuracy and time of interpretation were calculated. Inter-observer agreement was assessed using intraclass correlation coefficient (ICC). RESULTS: Mean attenuation at L1/L2 was highly correlated with mean BMD (r = 0.96/0.91, p < 0.001 for both). The average accuracy and mean time to assess BMD among four readers for differentiating normal from abnormal BMD was 66% and 6.0 s using visual assessment of grayscale images, 88% and 15.2 s using quantitative measurements of mean vertebral attenuation, and 92% and 2.1 s using visual assessment of colored images (p < 0.001 and p < 0.001, respectively). Inter-observer agreement was poor using visual assessment of grayscale images (ICC:0.31), good using quantitative measurements of mean vertebral attenuation (ICC:0.73), and excellent using visual assessment of colored images (ICC:0.90). CONCLUSION: Detection of abnormal BMD using colored abdominal CT images was highly accurate, rapid, and had excellent inter-observer agreement.

Comparative Effectiveness of Tumor Response Assessment Methods: Standard of Care Versus Computer-Assisted Response Evaluation.

PURPOSE: To compare the effectiveness of metastatic tumor response evaluation with computed tomography using computer-assisted versus manual methods. MATERIALS AND METHODS: In this institutional review board-approved, Health Insurance Portability and Accountability Act-compliant retrospective study, 11 readers from 10 different institutions independently categorized tumor response according to three different therapeutic response criteria by using paired baseline and initial post-therapy computed tomography studies from 20 randomly selected patients with metastatic renal cell carcinoma who were treated with sunitinib as part of a completed phase III multi-institutional study. Images were evaluated with a manual tumor response evaluation method (standard of care) and with computer-assisted response evaluation (CARE) that included stepwise guidance, interactive error identification and correction methods, automated tumor metric extraction, calculations, response categorization, and data and image archiving. A crossover design, patient randomization, and 2-week washout period were used to reduce recall bias. Comparative effectiveness metrics included error rate and mean patient evaluation time. RESULTS: The standard-of-care method, on average, was associated with one or more errors in 30.5% (6.1 of 20) of patients, whereas CARE had a 0.0% (0.0 of 20) error rate ( P < .001). The most common errors were related to data transfer and arithmetic calculation. In patients with errors, the median number of error types was 1 (range, 1 to 3). Mean patient evaluation time with CARE was twice as fast as the standard-of-care method (6.4 minutes v 13.1 minutes; P < .001). CONCLUSION: CARE reduced errors and time of evaluation, which indicated better overall effectiveness than manual tumor response evaluation methods that are the current standard of care.