Ralf W. Bauer

Dual-energy CT of head and neck cancer: average weighting of low- and high-voltage acquisitions to improve lesion delineation and image quality-initial clinical experience.

Objectives:Mixing low- and high-voltage acquisitions of dual-energy CT (DECT) scan using different weighting factors leads to differences in attenuation values and image quality. The aim of this work was to evaluate whether average weighting of DECT acquisitions could improve delineation of head and neck cancer and image quality. Materials and Methods:Among 60 consecutive patients who underwent DECT scan of the head and neck, 35 patients had positive findings and were included in the study. Images were reconstructed as pure 80 kVp, pure Sn140 kVp, and weighted-average (WA) image datasets from low- and high-voltage acquisitions using 3 different weighting factors (0.3, 0.6, 0.8) incorporating 30%, 60%, 80% from the 80 kVp data, respectively. Lesion contrast-to-noise ratio (CNR), attenuation measurements, and objective noise were compared between different image datasets. Two independent blinded radiologists subjectively rated the overall image quality of each image dataset on a 5-point grading scale comprising lesion delineation, image sharpness, and subjective noise. Results:Mean venous and tumor enhancement and muscle attenuation increased stepwise with decreasing tube voltage from Sn140 kVp through 80 kVp. CNR increased significantly from Sn140 kVp to weighting factor 0.3 then to weighting factor 0.6 (P < 0.0001). The increase in CNR from weighting factor 0.6 to 0.8 then to 80 kVp was nonsignificant (P = 1.00). The 0.6 weighted-average image dataset received the best image quality score by the 2 readers. Conclusion:Mixing the DE data from the 80 kVp and Sn140 kVp tubes using weighting factor 0.6 (60% from 80 kVp data) could improve lesion CNR and subjective overall image quality (including lesion delineation). This weighting factor was significantly superior to the 0.3 weighting factor which simulates standard 120 kVp acquisition.

Virtual monoenergetic dual-energy computed tomography: optimization of kiloelectron volt settings in head and neck cancer.

ObjectivesThe aim of this study was to evaluate the effects on objective and subjective image quality of virtual monoenergetic reconstructions at various energy levels of dual-energy computed tomography (DECT) in patients with head and neck cancer. Materials and MethodsWe included 71 (53 men, 18 women; age, 59.3 ± 12.0 years; range, 33–90 years) patients with biopsy-proven untreated primary (n = 55) or recurrent (n = 16) squamous cell carcinoma who underwent head and neck DECT. Images were reconstructed with a linear blending setting emulating 120 kV acquisition (M_0.3; 30% of 80 kV, 70% of 140 kV spectrum) and as virtual monoenergetic images with photon energies of 40, 60, 80, and 100 keV. Attenuation of lesion, various anatomic landmarks, and image noise were objectively measured, and lesion contrast-to-noise ratio (CNR) was calculated. Two independent blinded radiologists subjectively rated each image series using a 5-point grading scale regarding overall image quality, lesion delineation, image sharpness, and image noise. ResultsTumor attenuation peaked at 40 keV (140.2 ± 42.6 HU) followed by the 60 keV (121.7 ± 25.5 HU) and M_0.3 series (102.7 ± 22.3; all P < 0.001). However, the calculated lesion CNR was highest in the 60 keV reconstructions (12.45 ± 7.17), 80 keV reconstructions (8.66 ± 6.58), and M_0.3 series (5.21 ± 3.15; all P < 0.001) and superior to the other monoenergetic series (all P < 0.001). Subjective image analysis was highest for the 60 keV series regarding overall image quality (4.22; &kgr; = 0.411) and lesion delineation (4.35; &kgr; = 0.459) followed by the M_0.3 series (3.81; &kgr; = 0.394; 3.77; &kgr; = 0.451; all P < 0.001). Image sharpness showed no significant difference between both series (3.81 vs 3.79; P = 0.78). Image noise was rated superior in the 80 and 100 keV series (4.31 vs 4.34; P = 0.522). ConclusionsCompared with linearly blended images, virtual monoenergetic reconstructions of DECT data at 60 keV significantly improve lesion enhancement and CNR, subjective overall image quality, and tumor delineation of head and neck squamous cell carcinoma.

Contrasting effects of steroids and angiotensin-converting-enzyme inhibitors in a mouse model of dystrophin-deficient cardiomyopathy

Duchenne muscular dystrophy (DMD) is associated with progressive cardiomyopathy. Oral corticosteroids are the gold standard for the treatment of skeletal muscle weakness; however, the effects of steroids on cardiac function have not been prospectively studied. In addition, the early role of ACE‐inhibitors (ACE‐I) is controversial. We aimed to determine the effects of steroids and ACE‐I on development of left ventricular dysfunction in the mdx mouse, a model for dystrophin‐deficient cardiomyopathy.

Prevention of cardiomyopathy in δ-sarcoglycan knockout mice after systemic transfer of targeted adeno-associated viral vectors

AIMS Delta-sarcoglycan is a member of the dystrophin-associated glycoprotein complex linking the cytoskeleton to the extracellular matrix. Similar to patients with defects in the gene encoding delta-sarcoglycan (Sgcd), knockout mice develop cardiomyopathy and muscular dystrophy. The aim of our study was to develop an approach for preventing cardiomyopathy in Sgcd-deficient mice by cardiac expression of the intact cDNA upon systemic delivery of adeno-associated viral (AAV) vectors. METHODS AND RESULTS We packaged the Sgcd cDNA under transcriptional control of a myosin light chain-promoter fused with a cytomegalovirus enhancer into AAV-9 capsids. Vectors carrying either the Sgcd cDNA or an enhanced green fluorescent protein (EGFP) reporter gene were intravenously injected into adult Sgcd knockout mice. After 6 months, immunohistochemistry revealed almost complete reconstitution of the sarcoglycan subcomplex in heart but not skeletal muscle of mice with the Sgcd vector. Furthermore, Sgcd gene transfer resulted in prevention of cardiac fibrosis and significantly increased running distance measured by voluntary wheel running. Left ventricular function remained stable in mice expressing Sgcd while it deteriorated in EGFP controls within 6 months, paralleled by increased expression of brain natriuretic peptide, a molecular marker of heart failure. CONCLUSION Our study establishes an approach to specifically treat hereditary cardiomyopathies by targeting gene expression into the myocardium upon systemic application of AAV vectors.

Dual-Energy CT Applications in Head and Neck Imaging

OBJECTIVE Dual-energy scanning is a breakthrough in CT technology that has several applications in chest and abdominal imaging. Dual-energy CT also has potential for head and neck imaging. This review describes the role of dual-energy CT in head and neck imaging. CONCLUSION As with other body regions, both image fusion and material characterization dual-energy applications can be used for head and neck imaging. Early results are promising, and further research is encouraged.

Dual-energy computed tomography for the detection of late enhancement in reperfused chronic infarction: a comparison to magnetic resonance imaging and histopathology in a porcine model.

Objectives:To evaluate the performance of late enhancement dual-energy CT (LE-DECT) for the detection of infarcted myocardium as compared with 1.5-T late enhancement magnetic resonance imaging (LE-MRI) in a porcine model of reperfused chronic myocardial infarction (MI), using histopathology as standard of reference. Materials and Methods:In 8 healthy minipigs, MI was induced by 30-minute balloon occlusion of the left anterior descending coronary artery. Sixty-one ± 4 days after left anterior descending coronary artery occlusion, LE-DECT was performed 5, 10, and 15 minutes subsequent to contrast material injection. Therefore, a dual-source CT scanner (Somatom Definition, Siemens Healthcare, Forchheim, Germany) was used in dual-energy mode with the following protocol: tube potential/current 140 kV/95 mAs on tube A and 100 kV/165 mAs on tube B, collimation 2 × 32 × 0.6 mm, 1.5 mL/kg contrast material injected at 3 to 4 mL/s. Myocardial iodine distribution was calculated from the dual-energy data and superimposed on the gray scale multiplanar reformats of the heart in short-axis view. Fifty ± 12 minutes after LE-DECT imaging, 1.5-T LE-MRI (Magnetom Avanto, Siemens Healthcare, Forchheim, Germany) was performed 10 minutes successive to injection of contrast material using phase-sensitive inversion recovery sequences. For all pigs investigated, 2,3,5-triphenyltetrazolium chloride staining and histopathology of stained-tissue samples were acquired. Two experienced radiologists assessed all imaging studies in a random manner and were blinded to the results of the other techniques for the presence of late enhancement (LE). The American Heart Association 17-segment model was used to compare the results of LE-DECT, 100 kV grayscale LE images, LE-MRI, and histopathology. Size of MI was calculated for histopathological findings, LE-MRI, LE-DECT, and 100 kV grayscale LE images 10 minutes after contrast agent injection. Agreement between infarct size assessed with imaging modalities and histopathology was evaluated with Bland-Altman analysis. Results:Of the 136 myocardial segments in 8 minipigs, histopathology found MI in 27 segments. Diagnostic per-segment sensitivities and specificities for 100 kV grayscale LE images, LE-DECT images, and MR images obtained 10 minutes after contrast agent injection for both the readers were 0.62, 0.77, 0.79 and 0.97, 0.92, 0.94, respectively. Although sensitivities were higher for LE-DECT and LE-MRI than for 100 kV grayscale images, no statistically significant difference for the diagnostic accuracies of 100 kV grayscale LE images, LE-DECT images, and MR images (0.9, 0.89, 0.9) existed 10 minutes successive to contrast agent injection (all P > 0.05). Infarct size for LE-MRI, LE-DECT, and 100 kV grayscale LE images correlated well with histopathological findings (r2 = 0.97, 0.96, and 0.94; all P < 0.01). Conclusions:This feasibility study shows a high accuracy and a good correlation of LE-DECT and LE-MRI to histopathology for the detection of LE in a porcine model of reperfused chronic MI.

The NF-κB Subunit c-Rel Stimulates Cardiac Hypertrophy and Fibrosis

Cardiac remodeling and hypertrophy are the pathological consequences of cardiovascular disease and are correlated with its associated mortality. Activity of the transcription factor NF-κB is increased in the diseased heart; however, our present understanding of how the individual subunits contribute to cardiovascular disease is limited. We assign a new role for the c-Rel subunit as a stimulator of cardiac hypertrophy and fibrosis. We discovered that c-Rel-deficient mice have smaller hearts at birth, as well as during adulthood, and are protected from developing cardiac hypertrophy and fibrosis after chronic angiotensin infusion. Results of both gene expression and cross-linked chromatin immunoprecipitation assay analyses identified transcriptional activators of hypertrophy, myocyte enhancer family, Gata4, and Tbx proteins as Rel gene targets. We suggest that the p50 subunit could limit the prohypertrophic actions of c-Rel in the normal heart, because p50 overexpression in H9c2 cells repressed c-Rel levels and the absence of cardiac p50 was associated with increases in both c-Rel levels and cardiac hypertrophy. We report for the first time that c-Rel is highly expressed and confined to the nuclei of diseased adult human hearts but is restricted to the cytoplasm of normal cardiac tissues. We conclude that c-Rel-dependent signaling is critical for both cardiac remodeling and hypertrophy. Targeting its activities could offer a novel therapeutic strategy to limit the effects of cardiac disease.

Steroid treatment causes deterioration of myocardial function in the δ-sarcoglycan-deficient mouse model for dilated cardiomyopathy

AIMS As oral corticosteroids have a beneficial effect on muscle strength in Duchenne muscular dystrophy, it has been suggested that they may also be a useful treatment in the pathologically related sarcoglycanopathies. The delta-sarcoglycan-deficient mouse (Sgcd-null) is a model for both limb girdle muscular dystrophy 2F (LGMD2F) and dilated cardiomyopathy. METHODS AND RESULTS To study the effect of oral corticosteroids on cardiac function, we treated 8-week-old Sgcd-null mice with prednisolone (1.5 mg/kg body weight/day orally) for 8 weeks. In vivo cardiac function was assessed by pressure-volume loops using a conductance catheter. We found a well-compensated cardiomyopathy at baseline in Sgcd-null mice with decreased myocardial contractility, increased preload, and decreased afterload, maintaining a high cardiac output. Cardiac haemodynamics, surprisingly, did not improve in prednisolone-treated mice, but instead deteriorated with evidence of ventricular stiffening. On histology, after steroid treatment there was increased myocardial cell damage and increased myocardial fibrosis. CONCLUSION Prednisolone led to a decompensation of cardiac haemodynamics in Sgcd-null mice and induced additional cardiac damage. On the basis of these findings, although mouse models may not completely replicate the human situation for LGMD2F, we conclude that careful cardiac monitoring is clearly indicated in patients on long-term corticosteroids.

Dual-Energy CT–based Display of Bone Marrow Edema in Osteoporotic Vertebral Compression Fractures: Impact on Diagnostic Accuracy of Radiologists with Varying Levels of Experience in Correlation to MR Imaging

Purpose To evaluate whether a dual-energy (DE) computed tomographic (CT) virtual noncalcium technique can improve the detection rate of acute thoracolumbar vertebral compression fractures in patients with osteoporosis compared with that at magnetic resonance (MR) imaging depending on the level of experience of the reading radiologist. Materials and Methods This retrospective study was approved by the institutional ethics committee. Informed consent was obtained from all patients. Forty-nine patients with osteoporosis who were suspected of having acute vertebral fracture underwent DE CT and MR imaging. Conventional linear-blended CT scans and corresponding virtual noncalcium reconstructions were obtained. Five radiologists with varying levels of experience evaluated gray-scale CT scans for the presence of fractures and their suspected age. Then, virtual noncalcium images were evaluated to detect bone marrow edema. Findings were compared with those from MR imaging (the standard of reference). Sensitivity and specificity analyses for diagnostic performance and matched pair analyses were performed on vertebral fracture and patient levels. Results Sixty-two fractures were classified as fresh and 52 as old at MR imaging. The diagnostic performance of all readers in the detection of fresh fractures improved with the addition of virtual noncalcium reconstructions compared with that with conventional CT alone. Although the diagnostic accuracy of the least experienced reader with virtual noncalcium CT (accuracy with CT alone, 61%; accuracy with virtual noncalcium technique, 83%) was within the range of that of the most experienced reader with CT alone, the latter improved his accuracy with the noncalcium technique (from 81% to 95%), coming close to that with MR imaging. The number of vertebrae rated as unclear decreased by 59%-90% or from 15-53 to 2-13 in absolute numbers across readers. The number of patients potentially referred to MR imaging decreased by 36%-87% (from 11-23 to 2-10 patients). Considering the gain in true decisions with the virtual noncalcium technique on a patient level, between 12 (most experienced reader) and 17 (least experienced reader) MR examinations could have been avoided. Conclusion The DE CT-based virtual noncalcium technique may enable depiction of bone marrow edema in thoracolumbar vertebral compression fractures in patients with osteoporosis, with good accordance with MR imaging when images are read by experienced radiologists. Although less experienced readers improved their diagnostic performance to some degree, the experienced readers diagnostic performance approached that with MR imaging. (©) RSNA, 2016.

Diagnostic accuracy of late iodine-enhancement dual-energy computed tomography for the detection of chronic myocardial infarction compared with late gadolinium-enhancement 3-T magnetic resonance imaging.

ObjectivesThe purpose of the study was to compare the performance of late iodine–enhancement (LIE) dual-energy computed tomography (DECT) linear blending and selective myocardial iodine mapping for the detection of chronic myocardial infarction (CMI) with late gadolinium–enhancement (LGE) 3-T magnetic resonance imaging. Materials and MethodsThis study was approved by the institutional review board, and the patients gave informed consent. A total of 20 patients with a history of CMI underwent cardiac LIE-DECT and LGE-MRI. Images of the LIE-DECT were reconstructed as 100 kilovolt (peak) (kV[p]), 140 kV(p), and weighted-average (WA; linear blending) images from low– and high–kilovoltage peak data using 3 different weighting factors (0.8, 0.6, 0.3). Additional color-coded myocardial iodine distribution maps were calculated. The images were reviewed for the presence of late enhancement, transmural extent, signal characteristics, infarct volume, and subjective image quality. ResultsSegmental analysis of LIE-DECT data from 100 kV(p), WA of 0.8, and WA of 0.6 showed identical results for the identification of CMI (89% sensitivity, 98% specificity, 96% accuracy) and correctly identified all segments with transmural scarring detected through LGE-MRI. Weighted average of 0.6 received the best subjective image quality rating (15/20 votes) and average measured infarct size correlated best with LGE-MRI (5.7% difference). In comparison with LGE-MRI, iodine distribution maps were susceptible to false-positive and false-negative findings (52% sensitivity, 88% specificity, 81% accuracy), overestimating quantity of transmural scars by 78% while underestimating infarct volume by 55%. ConclusionsLate iodine enhancement cardiac dual-energy computed tomography correlates well with LGE-MRI for detecting CMI, whereas iodine distribution analysis provides inferior accuracy. Linear blending further improves image quality and enables more precise estimation of scar volume.