Amyloid-ß signals through tau to drive ectopic neuronal cell cycle re-entry in Alzheimer's disease.

Normally post-mitotic neurons that aberrantly re-enter the cell cycle without dividing account for a substantial fraction of the neurons that die in Alzheimer's disease (AD). We now report that this ectopic cell cycle re-entry (CCR) requires soluble amyloid-ß (Aß) and tau, the respective building blocks of the insoluble plaques and tangles that accumulate in AD brain. Exposure of cultured wild type (WT) neurons to Aß oligomers caused CCR and activation of the non-receptor tyrosine kinase, fyn, the cAMP-regulated protein kinase A and calcium-calmodulin kinase II, which respectively phosphorylated tau on Y18, S409 and S416. In tau knockout (KO) neurons, Aß oligomers activated all three kinases, but failed to induce CCR. Expression of WT, but not Y18F, S409A or S416A tau restored CCR in tau KO neurons. Tau-dependent CCR was also observed in vivo in an AD mouse model. CCR, a seminal step in AD pathogenesis, therefore requires signaling from Aß through tau independently of their incorporation into plaques and tangles.

Ubiquitin-derived artificial binding proteins targeting oncofetal fibronectin reveal scaffold plasticity by ß-strand slippage.

Affilin proteins, artificial binding proteins based on the ubiquitin scaffold, have been generated by directed protein evolution to yield de-novo variants that bind the extra-domain B (EDB) of oncofetal fibronectin, an established marker of tumor neovasculature. The crystal structures of two EDB-specific Affilin variants reveal a striking structural plasticity of the ubiquitin scaffold, characterised by ß-strand slippage, leading to different negative register shifts of the ß5 strands. This process recruits amino acid residues from ß5 towards the N-terminus to an adjacent loop region and subsequent residues into ß5, respectively, remodeling the binding interface and leading to target specificity and affinity. Protein backbone alterations resulting from ß-strand register shifts, as seen in the ubiquitin fold, can pose additional challenges to protein engineering as structural evidence of these events is still limited and they are difficult to predict. However, they can surface under the selection pressure of directed evolution and suggest that backbone plasticity allowing ß-strand slippages can increase structural diversity, enhancing the evolutionary potential of a protein scaffold.

Organ-based computed tomographic (CT) radiation dose reduction to the lenses: impact on image quality for CT of the head.

PURPOSE: Recently, a new specific organ dose adaption and reduction protocol, or SODAR tool (X-CARE, Siemens Healthcare), which reduces dose to the anterior aspect of the body of patients, was installed on our computed tomographic scanner. The purpose of this pilot project was to evaluate image quality and dose distribution in the acquired data with the new protocol. MATERIALS AND METHODS: Sixteen consecutive patients were scanned with the new SODAR head protocol. The findings were compared with 16 matched patients who were imaged with the standard computed tomographic head trauma protocol. Image quality was assessed qualitatively using a scale of 1 to 4 (1, excellent; 2, good; 3, fair; 4, nondiagnostic). Additionally, 1-cm regions of interest were placed in the white matter of the cerebral hemispheres, the cerebellar hemispheres, and the brain stem at the level of the pons for a quantitative analysis. The standard deviation of each measurement was recorded as an indicator for image noise. Dose measurement trials were performed using optically stimulated luminescence dosimeters on head phantoms and then on patients. RESULTS: Subjective image quality ranged between 1 and 3; no scan areas were considered nondiagnostic. Overall image quality of the posterior fossa averaged at 1.656 was slightly reduced compared to the cerebral hemispheres (mean, 1.141). The mean standard protocol brain stem image quality was 1.604, with only minimal deterioration to 1.708 in the SODAR group.No significant difference in image noise could be found between the SODAR group with a mean noise of 4.515 and standard images with a mean of 4.721 (P > 0.05).The dose to the anterior aspect of the patient was lowered to 3.2 mGy compared to 4.5 mGy on the lateral aspect of the scan (P > 0.05). To compensate for the photon loss in the posterior aspect, the dose has to be slightly increased to a mean of 6 mGy, but overall, a significant dose reduction with stable image quality could be achieved by reducing the dose length product from 1489 to 1347 mGy·cm using SODAR (P < 0.0001). CONCLUSION: Using the SODAR protocol resulted not only in an impressive 46% to 59% frontal dose reduction but also in the overall dose reduction. This dose reduction was obtained without sacrificing image quality, providing diagnostic images of the brain while protecting radiosensitive structures like the eye lenses in trauma brain imaging. Future applications will be reducing dose to other radiosensitive structures such as the thyroid gland and breast tissue from potentially harmful low-energy radiation without compromising image quality.

Dual-energy computed tomography: is there a penalty in image quality and radiation dose compared with single-energy computed tomography?

OBJECTIVE: To assess dose and image quality of dual-energy (DE) mixed images in comparison to single-energy (SE) images. METHODS: A phantom containing iodine contrast inserts was scanned using SE and DE protocols. Dual-energy mixed images were reconstructed with varying composition ratios (ratio describing the contribution of 80 and 140 data in the mixed images). Image noise, iodine contrast, and contrast-to-noise ratios (CNRs) were assessed inside and outside the central field of view (FoV). RESULTS: With the default composition ratio (0.3), noise and contrast were comparable between both protocols in the central FoV. Peripherally, DE image noise exceeded noise in SE images; CNR in the periphery was lower in the DE images. The highest CNR was found for a composition ratio of 0.5 to 0.9, exceeding the CNR of SE images. CONCLUSIONS: Dual-energy mixed images offer an image quality comparable to SE images within the central FoV at comparable dose levels. In the peripheral FoV, image quality is decreased. By optimizing the composition ratio in the DE mixed images, higher CNRs than in the SE images can be achieved, leading to a dose reduction potential.

Semi-automatic assessment of global left ventricular function and left ventricular parameters with dual-source computed tomography: comparison with invasive angiography.

This study assesses the global left ventricular function and volumes using dual-source computed tomography (DSCT) with improved temporal resolution (83 ms) by use of a semi-automatic software tool in comparison to invasive angiography (IVA). One hundred patients scheduled for invasive coronary angiography because of suspected or known coronary artery disease (80 men; 20 women, mean age 62 +/- 10 years) were additionally examined by DSCT. Global left ventricular function (LVF), left ventricular end-diastolic volume (LVEDV), end-systolic volume (LVESV), and stroke volume (SV) were calculated by the use of semi-automatic post-processing software and results compared with those of IVA. Bland-Altman analysis revealed a good concordance between DSCT and IVA in terms of LVF: Pearson's r 0.78, confidence interval [CI] 0.68-0.86, P < 0.0001, bias 7.1% +/- 9.1%. The same was true for LVESV (Pearson's r 0.78, CI 0.67-0.85, P < 0.0001, bias 15.0 +/- 21.0 ml), whereas the agreement for LVEDV and SV was only moderate (LVEDV: Pearson's r 0.59, CI 0.43-0.72, P < 0.0001, bias 13.0 +/- 18.1 ml; SV: Pearson's r 0.47, CI 0.28-0.62, P < 0.0001, bias -1.4 +/- 28.4 ml). Semi-automatic evaluation of left ventricular parameters with DSCT revealed good correlation for LVF and LVESV, whereas LVEDV and SV showed only a moderate correlation. Moreover, LVF is systematically underestimated by DSCT.

Quantitative parameters to compare image quality of non-invasive coronary angiography with 16-slice, 64-slice and dual-source computed tomography.

Multi-slice computed tomography (MSCT) is a non-invasive modality to visualize coronary arteries with an overall good image quality. Improved spatial and temporal resolution of 64-slice and dual-source computed tomography (DSCT) scanners are supposed to have a positive impact on diagnostic accuracy and image quality. However, quantitative parameters to compare image quality of 16-slice, 64-slice MSCT and DSCT are missing. A total of 256 CT examinations were evaluated (Siemens, Sensation 16: n = 90; Siemens Sensation 64: n = 91; Siemens Definition: n = 75). Mean Hounsfield units (HU) were measured in the cavum of the left ventricle (LV), the ascending aorta (Ao), the left ventricular myocardium (My) and the proximal part of the left main (LM), the left anterior descending artery (LAD), the right coronary artery (RCA) and the circumflex artery (CX). Moreover, the ratio of intraluminal attenuation (HU) to myocardial attenuation was assessed for all coronary arteries. Clinical data [body mass index (BMI), gender, heart rate] were accessible for all patients. Mean attenuation (CA) of the coronary arteries was significantly higher for DSCT in comparison to 64- and 16-slice MSCT within the RCA [347 +/- 13 vs. 254 +/- 14 (64-MSCT) vs. 233 +/- 11 (16-MSCT) HU], LM (362 +/- 11/275 +/- 12/262 +/- 9), LAD (332 +/- 17/248 +/- 19/219 +/- 14) and LCX (310 +/- 12/210 +/- 13/221 +/- 10, all p < 0.05), whereas there was no significant difference between DSCT and 64-MSCT for the LV, the Ao and My. Heart rate had a significant impact on CA ratio in 16-slice and 64-slice CT only (p < 0.05). BMI had no impact on the CA ratio in DSCT only (p < 0.001). Improved spatial and temporal resolution of dual-source CT is associated with better opacification of the coronary arteries and a better contrast with the myocardium, which is independent of heart rate. In comparison to MSCT, opacification of the coronary arteries at DSCT is not affected by BMI. The main advantage of DSCT lies with the heart rate independency, which might have a positive impact on the diagnostic accuracy.

Estimation of the radiation exposure of a chest pain protocol with ECG-gating in dual-source computed tomography.

The aim of the study was to evaluate radiation exposure of a chest pain protocol with ECG-gated dual-source computed tomography (DSCT). An Alderson Rando phantom equipped with thermoluminescent dosimeters was used for dose measurements. Exposure was performed on a dual-source computed tomography system with a standard protocol for chest pain evaluation (120 kV, 320 mAs/rot) with different simulated heart rates (HRs). The dose of a standard chest CT examination (120 kV, 160 mAs) was also measured. Effective dose of the chest pain protocol was 19.3/21.9 mSv (male/female, HR 60), 17.9/20.4 mSv (male/female, HR 80) and 14.7/16.7 mSv (male/female, HR 100). Effective dose of a standard chest examination was 6.3 mSv (males) and 7.2 mSv (females). Radiation dose of the chest pain protocol increases significantly with a lower heart rate for both males (p = 0.040) and females (p = 0.044). The average radiation dose of a standard chest CT examination is about 36.5% that of a CT examination performed for chest pain. Using DSCT, the evaluated chest pain protocol revealed a higher radiation exposure compared with standard chest CT. Furthermore, HRs markedly influenced the dose exposure when using the ECG-gated chest pain protocol.

Dual-source CT: effect of heart rate, heart rate variability, and calcification on image quality and diagnostic accuracy.

PURPOSE: To prospectively evaluate the effect of heart rate, heart rate variability, and calcification on dual-source computed tomography (CT) image quality and to prospectively assess diagnostic accuracy of dual-source CT for coronary artery stenosis, by using invasive coronary angiography as the reference standard. MATERIALS AND METHODS: This study had local Ethics Committee approval; all patients gave informed consent. Patients who underwent bypass surgery were excluded; patients with coronary artery stent-grafts were included. One hundred patients (20 women, 80 men; mean age, 62 years +/- 10 [standard deviation]) known to have or suspected of having coronary artery disease underwent dual-source CT and invasive coronary angiography. Image quality was assessed. Accuracy of dual-source CT in depiction or exclusion of significant stenosis (>or=50%) was evaluated on a per-segment and per-patient basis. Effects of heart rate, heart rate variability, and calcification on image quality and accuracy were analyzed by using multivariate regression and were analyzed between subgroups of predictor variables. Simple regression was performed to calculate thresholds for adequate image quality. RESULTS: Mean heart rate was 64.9 beats per minute +/- 13.2, mean variability was 23.6 beats per CT examination +/- 36.2, and mean Agatston score was 786.5 +/- 965.9. Diagnostic image quality was obtained in 90.2% of segments. Sensitivity, specificity, and positive and negative predictive values for the presence of significant stenosis were, respectively, 91.1%, 92.0%, 75.4%, and 97.5% by segment and 100%, 81.5%, 93.6%, and 100% by patient. Image quality was significantly related to heart rate variability (P = .015) and calcification (P < .001); the number of nondiagnostic segments was significantly affected by calcification only. Calcification was the single factor with significant impact on diagnostic accuracy (P = .001). CONCLUSION: While dual-source CT resulted in heart-rate independent image quality, image quality remained prone to heart rate variability and calcification.

Late enhancement using multidetector row computer tomography: a feasibility study with low dose 80 kV protocol.

AIMS: Detecting stenoses of coronary arteries with multidetector row computer tomography (MDCT) is a well feasible non-invasive method. However, there is still the problem of deciding whether a stenosis is hemodynamically relevant or not. Objective of the present study was to validate the feasibility of a low dose protocol for MDCT using 80 kV for detecting late enhancement. METHODS AND RESULTS: Using a Alderson-Rando Phantom evaluation of the effective dose of this LE protocol was performed. Ten patients (six male, four female, mean age 61) with known coronary artery disease and scheduled for a conventional coronary angiogram in our facility were subsequently recruited. All patients underwent CT-angiography (CTA) 1 day prior to magnetic resonance imaging. Five minutes after the application of 100ml contrast agent for the CTA scan, a low dose late enhancement scan (80 kV, 400 mA s maximum, ECG pulsed scan, 64 mm x 0.6mm collimation, 0.33 s tube rotation) was performed. Phantom dose measurements showed an effective dose for this protocol of 1.19 mSv (male) and 1.61 mSv (female). Fifty-six percent (5/9) of the patients showed a late enhancement on the MRI scan. Three transmural late enhancements and all four negative findings were correctly identified by CT. This represents a sensitivity of 78% (3/5), specificity of 100% (3/3), NPV of 100% (4/4) and a PPV of 97%. CONCLUSION: We were able to show that the low dose protocol is feasible and, furthermore, preliminary results look promising.

Usefulness of noninvasive cardiac imaging using dual-source computed tomography in an unselected population with high prevalence of coronary artery disease.

The aim of the present study was to evaluate the diagnostic accuracy of a new dual-source computed tomographic scanner generation with 83-ms temporal resolution in cardiac imaging. Fifty-one unselected consecutive patients (mean age 64 +/- 10 years) scheduled for invasive coronary angiography because of suspected or known coronary artery disease (CAD) were examined with dual-source computed tomography (DSCT). All coronary segments were analyzed regarding the presence of coronary artery lesions. The findings were compared with invasive coronary angiography. During computed tomographic examination, mean heart rate was 65 +/- 14 beats/min. Thirteen of 51 patients (25%) did not have sinus rhythm. Mean Agatston score equivalent was 779 (median 358, range 0 to 3,898). Prevalence of CAD was 75%. Based on a coronary segment model, sensitivity was 96%, specificity 87%, positive predictive value 61%, and negative predictive value 99% for the detection of significant lesions (> or =50% diameter stenosis). The main reason for false-positive results was an overestimation of mild lesions by DSCT. In conclusion, our initial data indicate that DSCT allows a high accuracy to exclude relevant coronary stenosis in unselected patients with a high prevalence of CAD and a relevant number with heart rhythm irregularities. However, overestimation of stenosis, especially in cases of calcifications, is still a limitation.

Influence of a lipid-lowering therapy on calcified and noncalcified coronary plaques monitored by multislice detector computed tomography: results of the New Age II Pilot Study.

PURPOSE: Multislice detector computed tomography (MSCT) is an accurate noninvasive modality to detect and classify different stages of atherosclerosis. The aim of the New Age II Study was to detect coronary lesions in men without established coronary artery disease (CAD) but with a distinct cardiovascular risk profile. We also sought to assess the effect after 1 year of a lipid-lowering therapy (LLT) using 20 mg of atorvastatin. METHODS: Forty-sixe male patients (mean, 61 +/- 10 years) with an elevated risk for CAD (PROCAM score >3 quintile) without LLT were included. Native and contrast-enhanced scans were performed in all patients. A total of 27 of 46 patients received a follow-up scan (after 488 +/- 138 days). Coronary plaque burden (CPB) was assessed volumetrically. RESULTS: The prevalence of CAD was 83% (38/46 patients), and 11% (5/46) without coronary calcifications still had noncalcified plaques. Total cholesterol and low-density lipoprotein cholesterol levels decreased significantly under LLT (225 +/- 41 mg/dL vs. 162 +/- 37 mg/dL, P < 0.0001 and 148 +/- 7 mg/dL vs. 88 +/- 5 mg/dL, P < 0.001, respectively). On follow-up, calcium score and CPB remained unchanged (Agatston score: 261 +/- 301 vs. 282 +/- 360; CPB: 0.149 +/- 0.108 vs. 0.128 +/- 0.075 mL, P > 0.05), whereas mean plaque volume of noncalcified plaques decreased significantly from 0.042 +/- 0.029 mL versus 0.030 +/- 0.014 mL (P < 0.05, mean reduction 0.012 +/- 0.017 mL or 24 +/- 13%). CONCLUSIONS: Statin therapy led to a significant reduction of noncalcified plaque burden that was not reflected in calcium scoring or total plaque burden. This finding might explain the risk reduction after the initiation of statin therapy. Using multislice detector computed tomography, physicians have the potential to monitor medical treatment in patients with coronary atherosclerosis.

Dual-source computed tomography: advances of improved temporal resolution in coronary plaque imaging.

OBJECTIVES: The aim of this study was to quantify image quality gains of a moving coronary plaque phantom using dual-source computed tomography (DSCT) providing 83 milliseconds temporal resolution in direct comparison to 64 slice single-source multidetector CT (MDCT) with a temporal resolution of 165 milliseconds. MATERIALS AND METHODS: Three cardiac vessel phantoms with fixed 50% stenosis and changing plaque configurations were mounted on a moving device simulating cardiac motion. Scans were performed at a simulated heart frequency of 60 to 120 bpm. Image quality assessment was performed in different anatomic orientations inside a thoracic phantom. RESULTS: A significant improvement of image quality using the DSCT could be found (P=0.0002). Relevant factors influencing image quality aside from frequency (P=0.0002) are plaque composition (P<0.0001), as well as orientation (P<0.0001). CONCLUSION: Scanning with 83 milliseconds temporal resolution improved image quality of coronary plaque at higher heart frequencies.

Dual-source CT with improved temporal resolution in assessment of left ventricular function: a pilot study.

OBJECTIVE: Functional analysis using MDCT has been limited by insufficient temporal resolution. The aim of this study was to assess the performance of a dual-source CT system with improved temporal resolution in the determination of both volume- or time-dependent functional parameters and regional wall motion in comparison with cine MRI. SUBJECTS AND METHODS: Twenty patients (15 of whom had previous myocardial infarction) were prospectively examined using dual-source CT. MRI was used as the standard of reference. Using the Simpson's method, ventricular volumes were determined for the whole of the cardiac cycle and results compared using Parson's correlation and Bland-Altman analysis. Regional wall motion was assessed on cine images and compared using weighted kappa statistics. RESULTS: Dual-source CT revealed a strong correlation with cine MRI regarding the quantification of end-diastolic volume (r = 0.98), end-systolic volume (r = 0.99), stroke volume (r = 0.96), and ejection fraction (r = 0.95). Good correlation was obtained for peak ejection rate (r = 0.79) and peak filling rate (r = 0.84), whereas agreement proved only moderate for time-to-peak ejection rate (r = 0.68) or time-to-peak filling rate from end-systole (r = 0.64). The mean difference for ejection fraction was negligible (bias, 0.72%). Good agreement between both techniques was likewise found for regional wall motion (kappa = 0.88). CONCLUSION: With the improvement of temporal resolution between 42 and 83 milliseconds, dual-source CT not only enables accurate assessment of global functional parameters, but it also allows for quantification of time-dependent variables and reliable evaluation of regional wall motion.

Diagnostic accuracy of multislice computed tomography for the detection of coronary artery disease in diabetic patients.

BACKGROUND: Diabetes mellitus is an important risk factor for coronary artery disease. Cardiac multislice computed tomography (MSCT) permits visualization of the coronary arteries with good sensitivity and specificity. However, at present, there are no data whether MSCT allows an accurate assessment of coronary arteries of diabetic patients, in comparison to nondiabetic patients. Thus, we compared the catheter-controlled MSCT results from diabetic and nondiabetic patients in a cohort of 116 patients with regard to sensitivity, specificity, positive predictive value, and negative predictive value, as well as image quality. METHODS AND MATERIALS: Twenty-two diabetic patients (age, 64.6+/-8.5 years; number of risk factors, 3.4+/-1.1) and 94 nondiabetic patients (age, 64.2+/-9.2 years; number of risk factors, 2.4+/-1.0) were examined by MSCT (Sensation 16 Speed 4 D, Siemens, Forchheim, Germany; gantry rotation time, 375 ms) and invasive coronary angiography. MSCT results were compared, blinded to the results of the coronary angiography with regard to the presence or absence of a significant stenosis (>50%) in a modified American Heart Association 13-segment model. Image quality was assessed on a qualitative scale between 1 (very good) and 5 (invisible) for each segment. RESULTS: Sensitivity, specificity, positive predictive value, and negative predictive value were statistically not different in diabetic and nondiabetic patients (0.85/0.98/0.92/0.96 vs. 0.84/0.97/0.91/0.95). One diabetic and three nondiabetic patients had to be excluded from analysis. Diabetic patients had relevantly more risk factors (P < .05), but calcium scoring was not different in both groups (Agatston score 1090+/-1278 vs. 798+/-1033). The image quality in both cohorts was comparable. CONCLUSIONS: MSCT allows the assessment of the coronary arteries noninvasively in diabetic patients with a good sensitivity and specificity, and diabetes does not have an impact on the number of evaluable segments. Thus, MSCT is a noninvasive tool in the care of these patients.

Technology insight: possible applications of multislice computed tomography in clinical cardiology.

With the introduction of four-slice scanners in 1999, multislice CT (MSCT) technology became available for investigative examination of the heart. Since then, MSCT technology has undergone rapid technical progress; temporal and spatial resolutions have been especially improved. The improved diagnostic image quality has led to more possible uses of MSCT being defined. At present, issues such as visualization of coronary artery bypass grafts, detection of stenoses of native coronary arteries, description of coronary anomalies, and calcium scoring, can be investigated reasonably well. Other features, such as plaque imaging and visualization of intracoronary stents, need further evaluation. A large number of factors, however, such as heart rate, atrial fibrillation, breathing artefacts and severe calcification, still influence image quality and reduce validity. In this article we provide a summary of current fields of application of cardiac MSCT. The word 'indication' is consciously avoided because official guidelines for the use of MSCT in heart examination have not yet been issued. Hopefully, prospective multicenter trials will be performed soon, providing more data with which to establish guidelines for both cardiologist and radiologist.

Clinical utility of ultra high pitch dual source thoracic CT imaging of acute pulmonary embolism in the emergency department: are we one step closer towards a non-gated triple rule out?

OBJECTIVES/PURPOSE: Aim of this study was to retrospectively compare the image quality and the radiation dose of an ultra high pitch CT scan for the evaluation of pulmonary embolism and visualization of cardiac structures in comparison to our institution's standard pulmonary embolism protocol. METHOD AND MATERIALS: The study cohort consisted of 115 consecutive patients, 57 underwent CT pulmonary angiography on a dual source 128 slice scanner (Siemens Somatom Definition FLASH) via an ultra high pitch mode (Pitch 2.8) while 58 were scanned on a dual source 64 slice scanner (Siemens Somatom Definition Dual Source) with standard pitch (Pitch 0.9). Qualitative image assessment was determined by two blinded radiologists with 3 and 15 years' experience in chest and cardiac CT. Quantitative image assessment was determined by the signal to noise ratio (SNR) and contrast to noise ratio (CNR). Effective radiation dose was calculated via the product of the dose length product. RESULTS: For the ultra high pitch protocol, 14% (8/57) were positive for pulmonary embolus compared to 13.7% (8/58) for the standard pitch group. 98.2% of the ultra high pitch scans were diagnostic for pulmonary embolus vs. 94.8% of the standard protocol. Visualization of cardiac structures was significantly improved with the ultra high pitch protocol (p<0.0001). Significantly more lung parenchymal motion was observed on the standard protocol (p<0.0001). The mean pulmonary vessel attenuation, SNR, and CNR were not significantly different. The mean effective dose was lower for the ultra high pitch studies (4.09mSv±0.78 vs. 7.72mSv±2.60, p<0.0001). CONCLUSION: Ultra high pitch CT imaging for pulmonary embolus is a technique which has potential to assess motion free evaluation of most cardiac structures and proximal coronary arteries at lower radiation doses.

Accuracy of automated attenuation-based 3-dimensional segmentation: in the analysis of left ventricular function compared with magnetic resonance imaging.

We evaluated attenuation-based 3-dimensional segmentation for the analysis of left ventricular function, using as our standard of reference magnetic resonance imaging and dual-source computed tomography with traditional short-axis planimetry.Twenty patients with known or suspected coronary artery disease were examined prospectively. In all magnetic resonance and computed tomographic datasets, global functional values were determined by 2-dimensional planimetry. Computed tomographic scans were further evaluated by automated 3-dimensional segmentation, and the results were compared by Pearson correlation and Bland-Altman analysis.Agreement between magnetic resonance imaging and dual-source computed tomographic 2-dimensional planimetry was good for all values (end-diastolic volume, bias= -4.2, r=0.99; end-systolic volume, bias= -1.7, r=0.99, stroke-volume, bias= -2.4, r=0.98; ejection fraction, bias=0.26, r=0.94; and myocardial mass, bias= 2.5, r=0.90). By contrast, dual-source computed tomographic 3-dimensional segmentation overestimated end-diastolic volume (bias= -19.1, P <0.001), stroke-volume (bias= -16.9, P <0.001), and myocardial mass (bias= -34.4, P <0.001). Moreover, correlation with magnetic resonance imaging proved disappointing for ejection fraction (r=0.72). Results were similar in a direct comparison between dual-source computed tomographic 2-dimensional planimetry and 3-dimensional segmentation (end-diastolic volume, bias= -14.9, r=0.94; end-systolic volume, bias= -0.5, r=0.90; stroke volume, bias= -14.5, r=0.83; ejection fraction, bias= -2.8, r=0.74; and myocardial mass, bias= -36.8, r=0.79).Due to significant overestimation of volumes and poor correlation of ejection fraction with cine magnetic resonance imaging results, attenuation-based 3-dimensional segmentation compares unfavorably with traditional planimetry. Hence this method should be used with caution, and its time benefits should be weighed against its imprecision of functional analysis.

Self-inflicted nail-gun injury with intracranial and intracardiac nails.

Nail-gun injury is commonly encountered in the emergency department. The severity of the injury depends on the specific injuries to organs and vascular structures. Computed tomography (CT) is the ideal imaging test of choice, as it can identify the more critical injuries that require immediate intervention. We present a case of self-inflicted nail-gun injury with intracranial and intracardiac nails that was optimally evaluated with CT. CT significantly changed the patient's management, giving priority to potentially life-threatening penetrating cardiac injuries.

Molecular control of systemic bile acid homeostasis by the liver glucocorticoid receptor.

Systemic bile acid (BA) homeostasis is a critical determinant of dietary fat digestion, enterohepatic function, and postprandial thermogenesis. However, major checkpoints for the dynamics and the molecular regulation of BA homeostasis remain unknown. Here we show that hypothalamic-pituitary-adrenal (HPA) axis impairment in humans and liver-specific deficiency of the glucocorticoid receptor (GR) in mice disrupts the normal changes in systemic BA distribution during the fasted-to-fed transition. Fasted mice with hepatocyte-specific GR knockdown had smaller gallbladder BA content and were more susceptible to developing cholesterol gallstones when fed a cholesterol-rich diet. Hepatic GR deficiency impaired liver BA uptake/transport via lower expression of the major hepatocyte basolateral BA transporter, Na(+)-taurocholate transport protein (Ntcp/Slc10a1), which affected dietary fat absorption and brown adipose tissue activation. Our results demonstrate a role of the HPA axis in the endocrine regulation of BA homeostasis through the liver GR control of enterohepatic BA recycling.

Hepatic deficiency in transcriptional cofactor TBL1 promotes liver steatosis and hypertriglyceridemia.

The aberrant accumulation of lipids in the liver ("fatty liver") is tightly associated with several components of the metabolic syndrome, including type 2 diabetes, coronary heart disease, and atherosclerosis. Here we show that the impaired hepatic expression of transcriptional cofactor transducin beta-like (TBL) 1 represents a common feature of mono- and multigenic fatty liver mouse models. Indeed, the liver-specific ablation of TBL1 gene expression in healthy mice promoted hypertriglyceridemia and hepatic steatosis under both normal and high-fat dietary conditions. TBL1 deficiency resulted in inhibition of fatty acid oxidation due to impaired functional cooperation with its heterodimerization partner TBL-related (TBLR) 1 and the nuclear receptor peroxisome proliferator-activated receptor (PPAR) α. As TBL1 expression levels were found to also inversely correlate with liver fat content in human patients, the lack of hepatic TBL1/TBLR1 cofactor activity may represent a molecular rationale for hepatic steatosis in subjects with obesity and the metabolic syndrome.