Andrew J. Bierhals

A Pattern-based Approach to Assessment of Delayed Enhancement in Nonischemic Cardiomyopathy at MR Imaging

Although delayed contrast material-enhanced cardiac magnetic resonance (MR) imaging has traditionally been used to evaluate ischemic disease and myocardial viability, it is increasingly being used in the evaluation of nonischemic cardiomyopathies. Unlike myocardial infarction, which demonstrates subendocardial or transmural delayed contrast enhancement in a vascular distribution, nonischemic cardiomyopathies demonstrate enhancement that is not limited to a vascular territory. In combination with other cardiac MR imaging features, the location (subendocardial, transmural, subepicardial, or mesocardial) and pattern (patchy or diffuse) of abnormal delayed myocardial enhancement allow differentiation between ischemic (infarct-related) and nonischemic cardiomyopathies and, in cases of nonischemic cardiomyopathy, narrowing of the differential diagnosis. With use of a structured approach, delayed contrast-enhanced cardiac MR imaging can be helpful in the early detection and appropriate treatment of nonischemic cardiomyopathies.

MDCT of partial anomalous pulmonary venous return (PAPVR) in adults.

Purpose The purpose of this study was to determine the lobar distribution and associated radiologic/clinical findings of partial anomalous pulmonary venous return (PAPVR) in the adult population using multidetector computed tomography (MDCT). Materials and Methods The radiology information database was queried for patients with PAPVR diagnosed on chest computed tomography. Forty-seven cases of PAPVR were retrospectively identified from 45,538 contrast-enhanced chest computed tomography examinations performed over an 8-year period. Diagnostic findings were confirmed via consensus review by 2 cardiothoracic radiologists. Medical charts were evaluated for ancillary radiographic data, cardiopulmonary signs and symptoms, and subsequent surgical interventions. Results Calculated disease prevalence was 0.1%, with mean patient age of 58 years and a 58% female predominance. PAPVR was observed with 47% frequency in the left upper lobe, 38% right upper lobe (RUL), 13% right lower lobe, and 2% left lower lobe. Among cases of RUL PAPVR, 42% were associated with sinus venosus atrial septal defect (ASD). Other reported anomalies were right-sided volume overload (47%), isolated upper lobe PAPVR (29% left and 5% right), bilateral PAPVR (4%), scimitar syndrome (13%), persistent left superior vena cava (9%), and azygos continuation of the inferior vena cava (4%). Reported cardiopulmonary signs/symptoms and imaging modalities other than MDCT were neither sensitive nor specific for PAPVR. Surgical repair was performed in 21% of cases and included ASD patching, intracardiac baffle, anomalous vein anastomosis, systemic vein translocation, and Warden procedure. Conclusions This represents the largest and only consecutive retrospective study of PAPVR in adults to date. Left upper lobe PAPVR was the most frequent location detected on MDCT, whereas RUL PAPVR was slightly less common and moderately associated with sinus venosus ASD. Utilization of contrast-enhanced studies and MDCT technology has enabled improved detection and characterization of PAPVR for early diagnosis and/or intervention.

Effects of CT section thickness and reconstruction kernel on emphysema quantification relationship to the magnitude of the CT emphysema index.

RATIONALE AND OBJECTIVES Computed tomography (CT) section thickness and reconstruction kernel each influence CT measurements of emphysema. This study was performed to assess whether their effects are related to the magnitude of the measurement. MATERIALS AND METHODS Low-radiation-dose multidetector CT was performed in 21 subjects representing a wide range of emphysema severity. Images were reconstructed using 20 different combinations of section thickness and reconstruction kernel. Emphysema index values were determined as the percentage of lung pixels having attenuation lower than multiple thresholds ranging from -960 HU to -890 HU. The index values obtained from the different thickness-kernel combinations were compared by repeated measures analysis of variance and Bland-Altman plots of mean versus difference in all subjects, and correlated with quantitative histology (mean linear intercept, Lm) in a subset of resected lung specimens. RESULTS The effects of section thickness and reconstruction kernel on the emphysema index were significant (P < .001) and diminished as the index attenuation threshold was raised. The changes in index values from changing the thickness-kernel combination were largest for subjects with intermediate index values (10%-30%), and became progressively smaller for those with lower and higher index values. This pattern was consistent regardless of the thickness-kernel combinations compared and the HU threshold used. Correlations between the emphysema index values obtained with each thickness-kernel combination and Lm ranged from r = 0.55-0.68 (P = .007-.03). CONCLUSION The effects of CT section thickness and kernel on emphysema index values varied systematically with the magnitude of the emphysema index. All reconstruction techniques provided significant correlations with quantitative histology.

Comparison of standard- and low-radiation-dose CT for quantification of emphysema.

OBJECTIVE This study was performed to compare standard- and low-radiation-dose techniques in the CT quantification of emphysema. MATERIALS AND METHODS The study population consisted of 36 men and 20 women who were current or former heavy smokers and underwent standard-dose (effective tube current, 100-250 mAs) chest CT at our institution within 6 months of having undergone low-dose (effective tube current, 30-60 mAs) chest CT. All CT scans were reconstructed at 5-mm slice thickness with a smooth filter. CT-measured lung volume, mean and median lung attenuation, and percentage of lung volume with attenuation lower than multiple thresholds (emphysema index values) were compared by Pearson correlation, two-tailed and paired Students t tests, and regression analysis. RESULTS There were no significant differences in mean attenuation (-848 vs -846 H, p > 0.35) for the low dose and the standard dose or in median lung attenuation (-879 vs -878 H, p > 0.66). Low- and standard-dose emphysema indexes were correlated at all attenuation thresholds (r = 0.86-0.97). Mean emphysema indexes were higher on the low-dose scans, but the mean difference at all thresholds was less than 3%. The differences were significant (p < 0.05) only at the lower index thresholds, correlated with differences in lung volume (r < or = 0.86), and increased with greater differences in dose. CONCLUSION Low-dose technique has minimal effect on CT quantification of emphysema.

Brain neoplasms: epidemiology, diagnosis, and prospects for cost-effective imaging

Currently, the literature lacks a solid body of research on decision and cost-effectiveness analysis of imaging strategies for adults and children suspected of having a brain neoplasm. This article describes the epidemiology and clinical presentation of brain neoplasms, reviews current diagnostic strategies, highlights gaps in the literature on decision and cost-effectiveness analysis, and suggests directions for future research.

Original investigationEffects of CT Section Thickness and Reconstruction Kernel on Emphysema Quantification: Relationship to the Magnitude of the CT Emphysema Index

RATIONALE AND OBJECTIVES Computed tomography (CT) section thickness and reconstruction kernel each influence CT measurements of emphysema. This study was performed to assess whether their effects are related to the magnitude of the measurement. MATERIALS AND METHODS Low-radiation-dose multidetector CT was performed in 21 subjects representing a wide range of emphysema severity. Images were reconstructed using 20 different combinations of section thickness and reconstruction kernel. Emphysema index values were determined as the percentage of lung pixels having attenuation lower than multiple thresholds ranging from -960 HU to -890 HU. The index values obtained from the different thickness-kernel combinations were compared by repeated measures analysis of variance and Bland-Altman plots of mean versus difference in all subjects, and correlated with quantitative histology (mean linear intercept, Lm) in a subset of resected lung specimens. RESULTS The effects of section thickness and reconstruction kernel on the emphysema index were significant (P < .001) and diminished as the index attenuation threshold was raised. The changes in index values from changing the thickness-kernel combination were largest for subjects with intermediate index values (10%-30%), and became progressively smaller for those with lower and higher index values. This pattern was consistent regardless of the thickness-kernel combinations compared and the HU threshold used. Correlations between the emphysema index values obtained with each thickness-kernel combination and Lm ranged from r = 0.55-0.68 (P = .007-.03). CONCLUSION The effects of CT section thickness and kernel on emphysema index values varied systematically with the magnitude of the emphysema index. All reconstruction techniques provided significant correlations with quantitative histology.

Effects of Phosphate Binder Therapy on Vascular Stiffness in Early Stage Chronic Kidney Disease

Background/Aims: Cardiovascular disease (CVD) is increased in chronic kidney disease (CKD), and contributed to by the CKD-mineral bone disorder (CKD-MBD). CKD-MBD begins in early CKD and its vascular manifestations begin with vascular stiffness proceeding to increased carotid artery intima-media thickness (cIMT) and vascular calcification (VC). Phosphorus is associated with this progression and is considered a CVD risk factor in CKD. We hypothesized that modifying phosphorus balance with lanthanum carbonate (LaCO3) in early CKD would not produce hypophosphatemia and may affect vascular manifestations of CKD-MBD. Methods: We randomized 38 subjects with normophosphatemic stage 3 CKD to a fixed dose of LaCO3 or matching placebo without adjusting dietary phosphorus in a 12-month randomized, double-blind, pilot and feasibility study. The primary outcome was the change in serum phosphorus. Secondary outcomes were changes in measures of phosphate homeostasis and vascular stiffness assessed by carotid-femoral pulse wave velocity (PWV), cIMT and VC over 12 months. Results: There were no statistically significant differences between LaCO3 and placebo with respect to the change in serum phosphorus, urinary phosphorus, tubular reabsorption of phosphorus, PWV, cIMT, or VC. Biomarkers of the early CKD-MBD such as plasma fibroblast growth factor-23, Dickkopf-related protein 1 (DKK1), and sclerostin were increased 2- to 3-fold at baseline, but were not affected by LaCO3. Conclusion: Twelve months of LaCO3 had no effect on serum phosphorus and did not alter phosphate homeostasis, PWV, cIMT, VC, or biomarkers of CKD-MBD.

Effects of diffusion time on short‐range hyperpolarized 3He diffusivity measurements in emphysema

To characterize the effect of diffusion time on short‐range hyperpolarized 3He magnetic resonance imaging (MRI) diffusion measurements across a wide range of emphysema severity.

Loss of function mutation in LOX causes thoracic aortic aneurysm and dissection in humans

Significance The mechanical integrity of the arterial wall is dependent on a properly structured ECM. Elastin and collagen are key structural components of the ECM, contributing to the stability and elasticity of normal arteries. Lysyl oxidase (LOX) normally cross-links collagen and elastin molecules in the process of forming proper collagen fibers and elastic lamellae. Here, using whole-genome sequencing in humans and genome engineering in mice, we show that a missense mutation in LOX causes aortic aneurysm and dissection because of insufficient elastin and collagen cross-linking in the aortic wall. These findings confirm mutations in LOX as a cause of aortic disease in humans and identify LOX as a diagnostic and potentially therapeutic target. Thoracic aortic aneurysms and dissections (TAAD) represent a substantial cause of morbidity and mortality worldwide. Many individuals presenting with an inherited form of TAAD do not have causal mutations in the set of genes known to underlie disease. Using whole-genome sequencing in two first cousins with TAAD, we identified a missense mutation in the lysyl oxidase (LOX) gene (c.893T > G encoding p.Met298Arg) that cosegregated with disease in the family. Using clustered regularly interspaced short palindromic repeats (CRISPR)/clustered regularly interspaced short palindromic repeats-associated protein-9 nuclease (Cas9) genome engineering tools, we introduced the human mutation into the homologous position in the mouse genome, creating mice that were heterozygous and homozygous for the human allele. Mutant mice that were heterozygous for the human allele displayed disorganized ultrastructural properties of the aortic wall characterized by fragmented elastic lamellae, whereas mice homozygous for the human allele died shortly after parturition from ascending aortic aneurysm and spontaneous hemorrhage. These data suggest that a missense mutation in LOX is associated with aortic disease in humans, likely through insufficient cross-linking of elastin and collagen in the aortic wall. Mutation carriers may be predisposed to vascular diseases because of weakened vessel walls under stress conditions. LOX sequencing for clinical TAAD may identify additional mutation carriers in the future. Additional studies using our mouse model of LOX-associated TAAD have the potential to clarify the mechanism of disease and identify novel therapeutics specific to this genetic cause.

Effects of sodium thiosulfate on vascular calcification in end-stage renal disease: a pilot study of feasibility, safety and efficacy.

Background and Objectives: Vascular calcification is a major contributor to morbidity and mortality in hemodialysis. The objective of this pilot study was to determine the feasibility, safety and efficacy of sodium thiosulfate (STS) in the progression of vascular calcification in hemodialysis patients. Methods: Chronic hemodialysis patients underwent a battery of cardiovascular tests. Those with coronary artery calcium (Agatston scores >50) received intravenous STS after each dialysis for 5 months (n = 22) and the tests were repeated. Changes in MDCT-determined calcification were assessed as the mean annualized rate of change in 3 vascular beds (coronary, thoracic and carotid arteries) and in L1-L2 vertebral bone density. Results: Although individual analyses showed coronary artery calcification progression in 14/22 subjects, there was no progression in the mean annualized rate of change of vascular calcification in the entire group. The L1-L2 vertebral bone density showed no changes. There were no correlations between rates of progression of vascular calcification and phosphorus, fetuin or C-reactive protein levels. Changes in coronary artery calcification scores correlated with those of the thoracic aorta. Conclusion: STS treatment is feasible, appears safe and may decrease the rate of progression of vascular calcification in hemodialysis patients. A large, randomized, controlled trial is warranted.