Association of antimullerian hormone with the size of the appendix testis, the androgen and estrogen receptors and their expression in the appendix testis, in congenital cryptorchidism.

OBJECTIVES: Antimullerian hormone (AMH) causes regression of the mullerian ducts in the male fetus. The appendix testis (AT) is a vestigial remnant of mullerian duct origin, containing both androgen (AR) and estrogen (ER) receptors. The role of both AMH and AT in testicular descent is yet to be studied. We investigated the possible association of AMH with AT size, the AR and ER, and their expression in the AT, in congenital cryptorchidism. METHODS: A total of 26 patients with congenital unilateral cryptorchidism and 26 controls with orthotopic testes were investigated, and 21 ATs were identified in each group. AMH and insulin-like three hormone (INSL3) concentrations were measured with spectrophotometry. AR and ER receptor expression was assessed with immunohistochemistry using monoclonal antibodies R441 for AR and MAB463 for ER. For the estimation of receptor expression, the Allred Score method was used. RESULTS: AMH concentrations did not present significant differences between patients with congenital cryptorchidism and the controls. Also, no correlation was found between AMH, INSL3, and AT length. Allred scores did not present significant differences. However, expression percentiles and intensity for both receptors presented significant differences. Three children with cryptorchidism and the highest AMH levels also had the highest estrogen receptor scores in the AT. CONCLUSIONS: No association was found between AMH and the studied major parameters. However, higher AMH concentrations, in combination with higher estrogen receptor scores in the AT, may play a role in cryptorchidism in some children. Larger population samples are needed to verify this observation.

Seasonal variation and epidemiological parameters in children from Greece with type 1 diabetes mellitus (T1DM).

BACKGROUND: A positive correlation between T1DM onset and winter has been suggested by several studies. We investigated the seasonal variation of T1DM diagnosis and epidemiological parameters in children from Western Greece with T1DM. METHODS: One hundred and five patients, 44 males, aged 1-16 years were studied. The month of the diagnosis, the order of birth, gestational age, birth weight, the mode of delivery, parental age and pubertal status were recorded from the patients' files. RESULTS: The mean age at diagnosis was 8.1 ± 4.0 years. The majority of the studied patients were diagnosed during the period of October-March. The majority were born at full term, 11.7% were preterm babies and 52.3% were first born. The mean birth weight was 3266 ± 596 g. 60% were born by vaginal delivery. The majority of the patients were prepubertal at diagnosis. CONCLUSIONS: Our results are in agreement with the reported seasonal variation of T1DM onset in other regions of Greece and Europe. The positive correlation between T1DM presentation and colder temperatures may be explained by factors such as viral infections. This is the first report on epidemiological parameters that may be related to T1DM presentation in Western Greece. The study of such parameters extends the understanding on the disease as a whole. IMPACT: A seasonality of the T1DM diagnosis is shown, with a predominance of the colder months of the year. This is in agreement with previous reports from other countries. Our findings confirm previously reported data and add to the existing knowledge on T1DM in general. Additionally, this is one of the few reports on the incidence and epidemiology of T1DM in Greece and the first in the region of Western Greece. Safer and more accurate conclusions can be drawn with regards to the possible causes and predisposing factors of T1DM by the assessment of statistical data from different populations throughout the world. This offers a better understanding of T1DM and may also contribute to the identification of factors that may reduce the incidence of the disease in the future.

Correlation between insulin-like peptide 3 and appendix testis length in congenital cryptorchidism.

AIM: The appendix testis (AT) is a vestigial remnant of Müller's paramesonephric duct. Insulin-like 3 hormone (INSL3) is produced in the Leydig cells of the testis. We investigated the possible correlation between AT length and plasma INSL3 concentrations in patients with congenital cryptorchidism (CCO) and patients with hydrocele, who served as controls. METHODS: A total of 40 patients with CCO and 34 patients with hydrocele and orthotopic testes were investigated. Sixteen patients presented high cryptorchidism and 24 low cryptorchidism. During surgery, AT was identified in 34 patients with CCO (high cryptorchidism:15, low cryptorchidism:19) and 28 controls. Plasma INSL3 levels were measured with a spectrophotometry enzyme immunoassay Elisa sandwich technique. RESULTS: AT was present in 85.0% of the boys with CCO and 82.4% of the controls. A significant positive correlation was found between the AT length and INSL3 concentrations in CCO patients. CONCLUSIONS: A longer AT may reflect better testicular function in boys with CCO, since it is correlated with higher INSL3 concentrations.

The role of carbohydrate counting in glycemic control and oxidative stress in patients with type 1 diabetes mellitus (T1DM).

PURPOSE: Oxidative stress is closely related to type 1 diabetes mellitus (T1DM), playing a key role in the pathogenesis of the disease and progression of complications. It is characterized by loss of equilibrium between oxidative factors and antioxidant protective mechanisms. Several markers have been used to assess both components of oxidative status; two of which are malondialdehyde (MDA) and ferric reducing antioxidant power (FRAP). METHODS: We investigated glycated hemoglobin (HbA1c), lipid profile, MDA, and FRAP in 35 patients with T1DM, aged 2-23 years, at the end of two 4-month observational periods: period A: standard insulin dosing per meal, and period B: proper prandial insulin dosing based on the amount of carbohydrates contained in each meal. RESULTS: At the end of period B, (i) glucose control (HbA1c) was improved; (ii) oxidative stress, estimated by MDA, showed a tendency to decrease; and (iii) antioxidant capacity, estimated by FRAP, was significantly increased compared with that of period A. No significant differences were observed in the lipid profile of the patients between the two periods. CONCLUSION: Proper insulin dosing based on carbohydrate counting (CC) may have an impact on the antioxidant defensive mechanisms of patients with T1DM through the attainment of a better glycemic profile. There are also indications that it may reduce MDA, an important biomarker of oxidative stress and a significant mediator of complications in T1DM. Therefore, prompt dietetic intervention using CC as early as possible after the diagnosis of T1DM is important for achieving optimal glycemic control and improved oxidative status.

New insights into the expression of androgen and estrogen receptors of the appendix testis in congenital cryptorchidism.

Background The appendix testis (AT) is the most common vestigial remnant of the human testis. Variations in the presence and expression of AT androgen receptor (AR) and estrogen receptor (ER) have been reported in cryptorchidism. We studied the possible association of AR and ER expression of the AT with cryptorchidism. Methods ATs were resected from 40 boys who underwent inguinoscrotal surgery, (20 patients with congenital unilateral cryptorchidism [UC] and 20 controls with orthotopic testes and hydrocele). AR and ER expression was evaluated with immunohistochemistry, and the percentage and intensity of AR and ER expression were evaluated by the Allred scoring method. AT length was compared between the two groups. Correlation of AR and ER expression was evaluated independently in patients and controls. Results The Allred score for AR trended toward lower values in UC compared to controls (p = 0.193), while ER scores presented statistically significant lower values in UC compared to controls (p = 0.017). No significant difference or trend was found in the expression of both receptors between high and low cryptorchidism (p = 0.981 for AR, p = 0.824 for ER) and for the appendiceal length between UC and controls (p = 0.369). Conclusions The findings of a trend for lower AR expression and a statistically significant lower expression of ER in UC may suggest an association of AR and ER with cryptorchidism and may provide an insight into the process of testicular descent.

Quantitative assessment of microcalcification cluster image quality in digital breast tomosynthesis, 2-dimensional and synthetic mammography.

Quantitative assessment of microcalcification (MC) cluster image quality is presented, in terms of cluster signal-difference-to-noise ratio (SDNR) intercomparison among digital breast tomosynthesis (DBT) and 2-dimensional (2D) and synthetic-2-dimensional (s2D) mammography. A phantom that provides realistic appearance of MC clusters located in uniform and nonuniform background was imaged in 2D and DBT, considering various scattering conditions. MC cluster SDNR differentiation is investigated with respect to MC particle size (uniform background) and surrounding parenchyma density (nonuniform background). An accurate MC cluster segmentation method was used to delineate individual MC particles and estimate MC cluster SDNR. Analysis of the uniform part of the phantom indicated higher performance of DBT and 2D over s2D for the smallest cluster size (106-177 µm), no difference among mammographic modes for the largest MC cluster (224-354 µm), and enhanced role of 2D for decreasing cluster size and increasing scattering. Analysis of the nonuniform part of the phantom indicated DBT performed better than 2D and s2D in case of dense parenchyma pattern, while 2D and s2D did not differ across parenchyma density patterns and scattering conditions. The presented MC cluster SDNR analysis was capable of revealing subtle differences among mammographic modes and suggests a methodology for clinical image quality assessment. Graphical abstract.

The effect of increased body mass index on patient dose in paediatric radiography.

Radiation protection is of particular importance in paediatric radiology. In this study, the influence of increased body mass index (BMI) in radiation dose and associated risk was investigated for paediatric patients aged 5-6.5 years, undergoing chest (64 patients) or abdomen (64 patients) radiography. Patients were categorized into normal and overweight, according to the BMI classification scheme. Entrance surface dose (ESD), organ dose, effective dose (ED) and risk of exposure induced cancer death (REID) were calculated using the Monte Carlo based code PCXMC 2.0. Statistically significant increase in patient radiation dose and REID was obtained for overweight patients as compared to normal ones, in both chest and abdomen examinations (Wilcoxon singed-rank test for paired data, p<0.001). The percentage increase in overweight as compared to normal patients of ESD, organ dose (maximum value), ED and REID was 13.6%, 24.4%, 18.9% and 20.6%, respectively, in case of chest radiographs. Corresponding values in case of abdomen radiographs were 15.0%, 24.7%, 21.8% and 19.8%, respectively. An increased BMI results in increased patient radiation dose in chest and abdomen paediatric radiography.

Selecting registration schemes in case of interstitial lung disease follow-up in CT.

PURPOSE: Primary goal of this study is to select optimal registration schemes in the framework of interstitial lung disease (ILD) follow-up analysis in CT. METHODS: A set of 128 multiresolution schemes composed of multiresolution nonrigid and combinations of rigid and nonrigid registration schemes are evaluated, utilizing ten artificially warped ILD follow-up volumes, originating from ten clinical volumetric CT scans of ILD affected patients, to select candidate optimal schemes. Specifically, all combinations of four transformation models (three rigid: rigid, similarity, affine and one nonrigid: third order B-spline), four cost functions (sum-of-square distances, normalized correlation coefficient, mutual information, and normalized mutual information), four gradient descent optimizers (standard, regular step, adaptive stochastic, and finite difference), and two types of pyramids (recursive and Gaussian-smoothing) were considered. The selection process involves two stages. The first stage involves identification of schemes with deformation field singularities, according to the determinant of the Jacobian matrix. In the second stage, evaluation methodology is based on distance between corresponding landmark points in both normal lung parenchyma (NLP) and ILD affected regions. Statistical analysis was performed in order to select near optimal registration schemes per evaluation metric. Performance of the candidate registration schemes was verified on a case sample of ten clinical follow-up CT scans to obtain the selected registration schemes. RESULTS: By considering near optimal schemes common to all ranking lists, 16 out of 128 registration schemes were initially selected. These schemes obtained submillimeter registration accuracies in terms of average distance errors 0.18 ± 0.01 mm for NLP and 0.20 ± 0.01 mm for ILD, in case of artificially generated follow-up data. Registration accuracy in terms of average distance error in clinical follow-up data was in the range of 1.985-2.156 mm and 1.966-2.234 mm, for NLP and ILD affected regions, respectively, excluding schemes with statistically significant lower performance (Wilcoxon signed-ranks test, p < 0.05), resulting in 13 finally selected registration schemes. CONCLUSIONS: Selected registration schemes in case of ILD CT follow-up analysis indicate the significance of adaptive stochastic gradient descent optimizer, as well as the importance of combined rigid and nonrigid schemes providing high accuracy and time efficiency. The selected optimal deformable registration schemes are equivalent in terms of their accuracy and thus compatible in terms of their clinical outcome.

Automated 3D ιnterstitial lung disease εxtent quantification: performance evaluation and correlation to PFTs.

In this study, the performance of a recently proposed computer-aided diagnosis (CAD) scheme in detection and 3D quantification of reticular and ground glass pattern extent in chest computed tomography of interstitial lung disease (ILD) patients is evaluated. CAD scheme performance was evaluated on a dataset of 37 volumetric chest scans, considering five representative axial anatomical levels per scan. CAD scheme reliability analysis was performed by estimating agreement (intraclass correlation coefficient, ICC) of automatically derived ILD pattern extent to semi-quantitative disease extent assessment in terms of 29-point rating scale provided by two expert radiologists. Receiver operating characteristic (ROC) analysis was employed to assess CAD scheme accuracy in ILD pattern detection in terms of area under ROC curve (A z ). Correlation of reticular and ground glass volumetric pattern extent to pulmonary function tests (PFTs) was also investigated. CAD scheme reliability was substantial for ILD extent (ICC = 0.809) and distinct reticular pattern extent (0.806) and moderate for distinct ground glass pattern extent (0.543), performing within inter-observer agreement. CAD scheme demonstrated high accuracy in detecting total ILD (A z = 0.950 ± 0.018), while accuracy in detecting distinct reticular and ground glass patterns was 0.920 ± 0.023 and 0.883 ± 0.024, respectively. Moderate and statistically significant negative correlation was found between reticular volumetric pattern extent and diffusing capacity, forced expiratory volume in 1 s, forced vital capacity, and total lung capacity (R = -0.581, -0.513, -0.494, and -0.446, respectively), similar to correlations found between radiologists' semi-quantitative ratings with PFTs. CAD-based quantification of disease extent is in agreement with radiologists' semi-quantitative assessment and correlates to specific PFTs, suggesting a potential imaging biomarker for ILD staging and management.

Quantitative visually lossless compression ratio determination of JPEG2000 in digitized mammograms.

The current study presents a quantitative approach towards visually lossless compression ratio (CR) threshold determination of JPEG2000 in digitized mammograms. This is achieved by identifying quantitative image quality metrics that reflect radiologists' visual perception in distinguishing between original and wavelet-compressed mammographic regions of interest containing microcalcification clusters (MCs) and normal parenchyma, originating from 68 images from the Digital Database for Screening Mammography. Specifically, image quality of wavelet-compressed mammograms (CRs, 10:1, 25:1, 40:1, 70:1, 100:1) is evaluated quantitatively by means of eight image quality metrics of different computational principles and qualitatively by three radiologists employing a five-point rating scale. The accuracy of the objective metrics is investigated in terms of (1) their correlation (r) with qualitative assessment and (2) ROC analysis (A z index), employing pooled radiologists' rating scores as ground truth. The quantitative metrics mean square error, mean absolute error, peak signal-to-noise ratio, and structural similarity demonstrated strong correlation with pooled radiologists' ratings (r, 0.825, 0.823, -0.825, and -0.826, respectively) and the highest area under ROC curve (A z , 0.922, 0.920, 0.922, and 0.922, respectively). For each quantitative metric, the highest accuracy values of corresponding ROC curves were used to define metric cut-off values. The metrics cut-off values were subsequently used to suggest a visually lossless CR threshold, estimated to be between 25:1 and 40:1 for the dataset analyzed. Results indicate the potential of the quantitative metrics approach in predicting visually lossless CRs in case of MCs in mammography.

Size-adapted microcalcification segmentation in mammography utilizing scale-space signatures.

The purpose of this study is size-adapted segmentation of individual microcalcifications in mammography, based on microcalcification scale-space signature estimation, enabling robust scale selection for initialization of multiscale active contours. Segmentation accuracy was evaluated by the area overlap measure, by comparing the proposed method and two recently proposed ones to expert manual delineations. The method achieved area overlap of 0.61+/-0.15 outperforming statistically (p<0.001) the other two methods (0.53+/-0.18, 0.42+/-0.16). Only the proposed method performed equally for both small (< 460 microm) and large (>/= 460 microm) microcalcifications. Results indicate an accurate method, which could be utilized in computer-aided diagnosis schemes of microcalcification clusters.

B-spline active rays segmentation of microcalcifications in mammography.

Accurate segmentation of microcalcifications in mammography is crucial for the quantification of morphologic properties by features incorporated in computer-aided diagnosis schemes. A novel segmentation method is proposed implementing active rays (polar-transformed active contours) on B-spline wavelet representation to identify microcalcification contour point estimates in a coarse-to-fine strategy at two levels of analysis. An iterative region growing method is used to delineate the final microcalcification contour curve, with pixel aggregation constrained by the microcalcification contour point estimates. A radial gradient-based method was also implemented for comparative purposes. The methods were tested on a dataset consisting of 149 mainly pleomorphic microcalcification clusters originating from 130 mammograms of the DDSM database. Segmentation accuracy of both methods was evaluated by three radiologists, based on a five-point rating scale. The radiologists' average accuracy ratings were 3.96 +/- 0.77, 3.97 +/- 0.80, and 3.83 +/- 0.89 for the proposed method, and 2.91 +/- 0.86, 2.10 +/- 0.94, and 2.56 +/- 0.76 for the radial gradient-based method, respectively, while the differences in accuracy ratings between the two segmentation methods were statistically significant (Wilcoxon signed-ranks test, p < 0.05). The effect of the two segmentation methods in the classification of benign from malignant microcalcification clusters was also investigated. A least square minimum distance classifier was employed based on cluster features reflecting three morphological properties of individual microcalcifications (area, length, and relative contrast). Classification performance was evaluated by means of the area under ROC curve (Az). The area and length morphologic features demonstrated a statistically significant (Mann-Whitney U-test, p < 0.05) higher patient-based classification performance when extracted from microcalcifications segmented by the proposed method (0.82 +/- 0.06 and 0.86 +/- .05, respectively), as compared to segmentation by the radial gradient-based method (0.71 +/- 0.08 and 0.75 +/- 0.08). The proposed method demonstrates improved segmentation accuracy, fulfilling human visual criteria, and enhances the ability of morphologic features to characterize microcalcification clusters.

Breast cancer diagnosis: analyzing texture of tissue surrounding microcalcifications.

The current study investigates texture properties of the tissue surrounding microcalcification (MC) clusters on mammograms for breast cancer diagnosis. The case sample analyzed consists of 85 dense mammographic images, originating from the Digital Database for Screening Mammography. Mammograms analyzed contain 100 subtle MC clusters (46 benign and 54 malignant). The tissue surrounding MCs is defined on original and wavelet decomposed images, based on a redundant discrete wavelet transform. Gray-level texture and wavelet coefficient texture features at three decomposition levels are extracted from surrounding tissue regions of interest (ST-ROIs). Specifically, gray-level first-order statistics, gray-level cooccurrence matrices features, and Laws' texture energy measures are extracted from original image ST-ROIs. Wavelet coefficient first-order statistics and wavelet coefficient cooccurrence matrices features are extracted from subimages ST-ROIs. The ability of each feature set in differentiating malignant from benign tissue is investigated using a probabilistic neural network. Classification outputs of most discriminating feature sets are combined using a majority voting rule. The proposed combined scheme achieved an area under receiver operating characteristic curve ( A(z)) of 0.989. Results suggest that MCs' ST texture analysis can contribute to computer-aided diagnosis of breast cancer.

Texture classification-based segmentation of lung affected by interstitial pneumonia in high-resolution CT.

Accurate and automated lung field (LF) segmentation in high-resolution computed tomography (HRCT) is highly challenged by the presence of pathologies affecting lung borders, also affecting the performance of computer-aided diagnosis (CAD) schemes. In this work, a two-dimensional LF segmentation algorithm adapted to interstitial pneumonia (IP) patterns is presented. The algorithm employs k-means clustering followed by a filling operation to obtain an initial LF order estimate. The final LF border is obtained by an iterative support vector machine neighborhood labeling of border pixels based on gray level and wavelet coefficient statistics features. A second feature set based on gray level averaging and gradient features was also investigated to evaluate its effect on segmentation performance of the proposed method. The proposed method is evaluated on a dataset of 22 HRCT cases spanning a range of IP patterns such as ground glass, reticular, and honeycombing. The accuracy of the method is assessed using area overlap and shape differentiation metrics (d(mean), d(rms), and d(max)), by comparing automatically derived lung borders to manually traced ones, and further compared to a gray level thresholding-based (GLT-based) method. Accuracy of the methods evaluated is also compared to interobserver variability. The proposed method incorporating gray level and wavelet coefficient statistics demonstrated the highest segmentation accuracy, averaged over left and right LFs (overlap=0.954, d(mean)=1.080 mm, d(rms)=1.407 mm, and d(max)=4.944 mm), which is statistically significant (two-tailed student's t test for paired data, p<0.0083) with respect to all metrics considered as compared to the proposed method incorporating gray level averaging and gradient features (overlap=0.918, d(mean)=2.354 mm, d(rms)=3.711 mm, and d(max)=14.412 mm) and the GLT-based method (overlap=0.897, d(mean)=3.618 mm, d(rms)=5.007 mm, and d(max)=16.893 mm). The performance of the three segmentation methods, although decreased as IP pattern severity level (mild, moderate, and severe) was increased, did not demonstrate statistically significant difference (two-tailed student's t test for unpaired data, p>0.0167 for all metrics considered). Finally, the accuracy of the proposed method, based on gray level and wavelet coefficient statistics ranges within interobserver variability. The proposed segmentation method could be used as an initial stage of a CAD scheme for IP patterns.

A digital equalisation technique improving visualisation of dense mammary gland and breast periphery in mammography.

INTRODUCTION: In mammographic imaging, use of high contrast screen-film combinations results in under-exposed and over-exposed film areas corresponding to dense mammary gland and breast periphery (BP), respectively, characterised by degraded image contrast. A digital equalisation technique was designed and developed in order to deal with the problem of poor visualisation of these regions. METHODS AND MATERIAL: The technique is based on the film-digitiser characteristic curve and a layer model of the breast region, as depicted on a mammogram. It remaps each layer grey level (GL) values by a correction factor that accounts for thickness variation in BP and the presence of dense fibroglandular tissues at the mammary gland. The major steps of the technique are segmentation, to isolate the breast region from mammogram background, and adaptive layer GL remapping. RESULTS: The performance of the technique was initially evaluated on a sample of 60 mammograms. Comparative evaluation between the initial and processed images was performed on the basis of nine anatomical features situated at dense mammary gland and BP. The mammographic images resulting from application of the proposed technique are GL equalised and the visualisation improvement of all anatomical features was found to be statistically significant (P<0.05) or highly significant (P<0.0001). The proposed technique was also compared with contrast-limited adaptive histogram equalisation (CLAHE) and found to be more effective in the visualisation of all anatomical features examined, for both dense breast (DB) and BP. DISCUSSION AND CONCLUSION: Application of the proposed technique results in improved visualisation of both dense mammary gland and BP regions. The proposed technique is independent of breast size, breast symmetry and mammographic view. The technique contributes to breast dose minimisation by eliminating the need for a second acquisition.