Gert Weijers

Noninvasive detection of hepatic lipidosis in dairy cows with calibrated ultrasonographic image analysis.

The aim was to test the accuracy of calibrated digital analysis of ultrasonographic hepatic images for diagnosing fatty liver in dairy cows. Digital analysis was performed by means of a novel method, computer-aided ultrasound diagnosis (CAUS), previously published by the authors. This method implies a set of pre- and postprocessing steps to normalize and correct the transcutaneous ultrasonographic images. Transcutaneous hepatic ultrasonography was performed before surgical correction on 151 German Holstein dairy cows (mean +/- standard error of the means; body weight: 571+/-7 kg; age: 4.9+/-0.2 yr; DIM: 35+/-5) with left-sided abomasal displacement. Concentration of triacylglycerol (TAG) was biochemically determined in liver samples collected via biopsy and values were considered the gold standard to which ultrasound estimates were compared. According to histopathologic examination of biopsies, none of the cows suffered from hepatic disorders other than hepatic lipidosis. Hepatic TAG concentrations ranged from 4.6 to 292.4 mg/g of liver fresh weight (FW). High correlations were found between the hepatic TAG and mean echo level (r=0.59) and residual attenuation (ResAtt; r=0.80) obtained in ultrasonographic imaging. High correlation existed between ResAtt and mean echo level (r=0.76). The 151 studied cows were split randomly into a training set of 76 cows and a test set of 75 cows. Based on the data from the training set, ResAtt was statistically selected by means of stepwise multiple regression analysis for hepatic TAG prediction (R(2)=0.69). Then, using the predicted TAG data of the test set, receiver operating characteristic analysis was performed to summarize the accuracy and predictive potential of the differentiation between various measured hepatic TAG values, based on TAG predicted from the regression formula. The area under the curve values of the receiver operating characteristic based on the regression equation were 0.94 (<50 vs. >or=50mg of TAG/g of FW), 0.83 (<100 vs. >or=100mg of TAG/g of FW), and 0.97 (<50 vs. >or=100mg of TAG/g of FW). The CAUS methodology and software for digitally analyzing liver ultrasonographic images is considered feasible for noninvasive screening of fatty liver in dairy herd health programs. Using the single parameter linear regression equation might be ideal for practical applications.

Quantitative Ultrasound Imaging of Healthy and Reconstructed Cleft Lip: A Feasibility Study:

Objective: To investigate the feasibility of echographic imaging of healthy and reconstructed cleft lip and to estimate tissue dimensions and normalized echo level. Methods: Echographic images of the upper lip were made on three healthy subjects and two patients using a linear array transducer (7 to 11 MHz bandwidth) and a noncontact gel coupling. Tissue dimensions were measured using calipers. Echo levels were calibrated and were corrected for beam characteristics, gel path, and tissue attenuation using a tissue-mimicking phantom. Results: At the central position of the philtrum, mean thickness (SD) of lip loose connective tissue layer, orbicularis oris muscle, and dense connective layer was 4.0 (0.1) mm, 2.3 (0.7) mm, and 2.2 (0.7) mm, respectively, in healthy lip at rest; and 4.1 (0.9) mm, 3.8 (1.7) mm, and 2.6 (0.6) mm, respectively, in contracted lip. Mean (SD) echo level of muscle and dense connective tissue layer with respect to echo level of lip loose connective tissue layer was −19.3 (0.6) dB and −10.7 (4.0) dB, respectively, in relaxed condition and −20.7 (1.5) dB and −7.7 (2.3) dB, respectively, in contracted state. Color mode echo images were calculated, showing lip tissues in separate colors and highlighting details like discontinuity of the orbicularis oris muscle and presence of scar tissue. Conclusions: Quantitative assessment of thickness and echo level of various lip tissues is feasible after proper echographic equipment calibration. Diagnostic potentials of this method for noninvasive evaluation of cleft lip reconstruction outcome are promising.

Serum GDF15 Levels Correlate to Mitochondrial Disease Severity and Myocardial Strain, but Not to Disease Progression in Adult m.3243A>G Carriers

In this observational cohort study, we examined the prognostic value of growth and differentiation factor 15 (GDF15) in indicating and monitoring general mitochondrial disease severity and progression in adult carriers of the m.3243A>G mutation.Ninety-seven adult carriers of the m.3243A>G mutation were included in this study. The Newcastle mitochondrial disease adult scale was used for rating mitochondrial disease severity. In parallel, blood was drawn for GDF15 analysis by ELISA. Forty-nine carriers were included in a follow-up study. In a small subset of subjects of whom an echocardiogram was available from general patient care, myocardial deformation was assessed using two-dimensional speckle-tracking strain analysis.A moderate positive correlation was found between the concentration of GDF15 and disease severity (r = 0.59; p < 0.001). The concentration of serum GDF15 was higher in m.3243A>G carriers with diabetes mellitus, cardiomyopathy, and renal abnormalities. After a 2-year follow-up, no significant correlation was found between the change in disease severity and the change in the concentration of GDF15 or between the GDF15 level at the first assessment and the change in disease severity. In the subcohort of patients of whom an echocardiogram was available, the concentration of GDF15 correlated moderately to longitudinal global strain (r = 0.55; p = 0.006; n = 23) but not to circumferential or radial strain.Our results indicate that serum GDF15 is not a strong surrogate marker for general mitochondrial disease severity. Its value in indicating myocardial deformation should be confirmed in a prospective longitudinal study.

Synchronicity of systolic deformation in healthy pediatric and young adult subjects: a two-dimensional strain echocardiography study.

Two-dimensional speckle tracking echocardiography (2DSTE) offers valuable information in the echocardiographic assessment of ventricular myocardial function. It enables the quantification and timing of systolic ventricular myocardial deformation. In addition, 2DSTE can be used to identify mechanical dyssynchrony, which is an important parameter in predicting the response to cardiac resynchronization therapy for heart failure. Detailed knowledge of normal timing of systolic deformation and its degree of synchronicity in children is lacking. We aimed to establish the normal timing of left ventricular myocardial systolic deformation using 2DSTE in a large cohort of healthy children and young adults. Transthoracic echocardiograms were acquired in 195 healthy subjects (139 children and 56 young adult <40 yr of age) and were retrospectively analyzed. Time to peak systolic longitudinal, circumferential, and radial strain was determined by means of speckle tracking. Strong, statistically significant relations between age as well as various anthropometric variables (e.g., heart rate) and timing of systolic deformation (P < 0.0001) were present. The extent of dyssynchronous deformation increased with age. This is the first report that establishes reference values per cardiac segment for time to peak systolic myocardial strain values in all three directions assessed with 2DSTE in a large pediatric and young adult cohort. We emphasize the need for using age-specific reference values as well as heart rate correction for the adequate interpretation of 2DSTE measurements.

Interactive vs. automatic ultrasound image segmentation methods for staging hepatic lipidosis.

The aim of this study was to test the hypothesis that automatic segmentation of vessels in ultrasound (US) images can produce similar or better results in grading fatty livers than interactive segmentation. A study was performed in postpartum dairy cows (N= 151), as an animal model of human fatty liver disease, to test this hypothesis. Five transcutaneous and five intraoperative US liver images were acquired in each animal and a liver biopsy was taken. In liver tissue samples, triacylglycerol (TAG) was measured by biochemical analysis and hepatic diseases other than hepatic lipidosis were excluded by histopathologic examination. Ultrasonic tissue characterization (UTC) parameters — Mean echo level, standard deviation (SD) of echo level, signal-to-noise ratio (SNR), residual attenuation coefficient (ResAtt) and axial and lateral speckle size—were derived using a computer-aided US (CAUS) protocol and software package. First, the liver tissue was interactively segmented by two observers. With increasing fat content, fewer hepatic vessels were visible in the ultrasound images and, therefore, a smaller proportion of the liver needed to be excluded from these images. Automatic-segmentation algorithms were implemented and it was investigated whether better results could be achieved than with the subjective and time-consuming interactive-segmentation procedure. The automatic-segmentation algorithms were based on both fixed and adaptive thresholding techniques in combination with a ‘speckle’-shaped moving-window exclusion technique. All data were analyzed with and without postprocessing as contained in CAUS and with different automated-segmentation techniques. This enabled us to study the effect of the applied postprocessing steps on single and multiple linear regressions of the various UTC parameters with TAG. Improved correlations for all US parameters were found by using automatic-segmentation techniques. Stepwise multiple linear-regression formulas where derived and used to predict TAG level in the liver. Receiver-operating-characteristics (ROC) analysis was applied to assess the performance and area under the curve (AUC) of predicting TAG and to compare the sensitivity and specificity of the methods. Best speckle-size estimates and overall performance (R 2 = 0.71, AUC = 0.94) were achieved by using an SNR-based adaptive automatic-segmentation method (used TAG threshold: 50 mg/g liver wet weight). Automatic segmentation is thus feasible and profitable.

Transcutaneous versus intraoperative quantitative ultrasound for staging bovine hepatic steatosis

The aim of this study was to test the hypothesis that the Computer Aided UltraSound (CAUS) method developed by the authors [1-4] for the estimation of UltraSound Tissue Characteristics (UTC) parameters on transcutaneous (Transc) ultrasound (US) images can predict the liver fat content with similar accuracy and precision as with intraoperative (Intraop) US. A large animal study in post partum dairy cows (N=151) was performed to test these hypotheses. Five Transc B-Mode US liver image were acquired before surgery. During abomasal displacement surgery five Intraop US B-Mode liver images and a liver biopsy was taken. In liver tissue samples, triacylglycerol (TAG) content was measured by biochemical analysis. Firstly the equipment preset, which was kept fixed during whole study time, was carefully calibrated[5]. For the echo level calibration a TMP was used, and all UTC parameters were expressed relatively to those of the phantom. Prior to UTC parameters estimation several pre-processing steps were performed: Back-Scan Conversion (BSC); Look Up Table (LUT) correction; superficial tissue layers (Fat layer) attenuation correction and Automatic Gain Correction (AGC) were performed. Also several postprocessing steps were incorporated like: Automatic segmentation and residual attenuation correction were performed. Stepwise multiple linear regression analysis on a training set (N=76) was performed. In all cases the Residual Attenuation coefficient (ResAtt, R=0.81) was the only selected parameter. The results were tested on the residual cows (test set N=75) to predict the TAG content in the liver. Receiver Operating Characteristics (ROC) analysis then was applied to estimate the Area Under the Curve (AUC) and the sensitivity and specificity of the CAUS method. Equivalent high predictive values for AUC (95%), sensitivity(87%) and specificity (83%) for Intraop and Transc applications were found. Consequently, it can be concluded, applied Fat layer attenuation correction to Transc US images was performed adequately.

Ultrasound strain imaging: From nano-scale motion detection to macro-scale functional imaging

With ultrasound strain imaging, the function of tissue and organs can be identified. The technique uses multiple images, acquired from tissue under different degrees of deformation. We recently applied this technique on hearts and skeletal muscles. Cardiac data was acquired in dogs with a valvar aorta stenosis. Muscle data was acquired from the orbicular oral muscle in the upper lip. For accurate assessment of deformation, the displacement of tissue can be determined at nanometer scale. Raw ultrasound data, containing the amplitude as well as the phase information is required for this analysis. A 2D coarse-to-fine strain estimation strategy is proposed to calculate the minute differential displacements in tissue, while the tissue itself is moving on a macro scale. The technique was validated using phantom experiments. These experiments demonstrated that accurate strain images can be determined using the proposed technique. Cardiac evaluation in dogs showed that the strain can be determined in three dimensions. The strain curves over the cardiac cycle are in correspondence with the severity of the stenosis of the aortic valve. In patients with a reconstructed cleft lip, the orbicular oral muscle in the reconstructed region showed decreased strain values. In normal individuals, similar strain values were found for all regions of the muscle. Ultrasound strain imaging is a promising technique enabling the addition of functional information to the geometrical information that is already provided by the conventional ultrasound imaging technique.

Cardiac function in paediatric patients with congenital adrenal hyperplasia due to 21 hydroxylase deficiency

Hyperandrogenism and exogenous glucocorticoid excess may cause unfavourable changes in the cardiovascular risk profile of patients with congenital adrenal hyperplasia (CAH).

Staging hepatic steatosis in nonalcoholic fatty liver disease by quantitative conventional ultrasound imaging, validated with histopathology

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disorder in developed countries with a global prevalence of approximately 25%. NAFLD represents a spectrum of disorders and starts with benign steatosis (NAFL, ≥5% hepatic steatosis (HS)), but may lead to nonalcoholic steatohepatitis (NASH), inflammation with hepatocyte injury with or without fibrosis, which may lead to cirrhosis. Qualitative scoring of liver biopsies still is the gold standard for staging steatosis however, they are invasive and complications such as bleeding and infection may occur. For this reason we developed and tested a computer aided ultrasound (CAUS) protocol for the non-invasive assessment of liver HS using quantitative ultrasound (QUS) B-mode images. CAUS showed to have high predictive values (area under the curve (AUC) up to 0.95) in cows and similar correlations value with HS in a human pilot study. The current study was conducted in order to assess the predictive values of CAUS in staging hepatic steatosis in-vivo.

Predicting treatment response in invasive ductal breast carcinoma using three-dimensional quantitative ultrasound analysis

About 1 in 8 women will develop breast cancer. Histological tumor grade and biological markers such as oestrogen receptors (ER), progesterone receptors (PR), and human epidermal growth factor receptor 2 (HER2) are prognostic indicators for the clinical response to medical treatment and patient prognosis. Breast ultrasound (US) is mainly used to diagnose breast cancer or guide breast biopsies. However, quantitative analysis of US could also be of clinical value by giving additional information on tissue type. The automated breast volume scanner (ABUS) allows an automated assessment of a complete 3D US breast volume. By analyzing the texture of the B-mode images of the ABUS we have already shown that 3D quantitative breast ultrasound (3DQBUS) provides good discrimination between fibroadenomas (benign lesions) and invasive ductal carcinomas (IDC)(AUC=0.89). In this study we investigated whether 3DQBUS can be used to predict grade and receptor status.