Millimeter-wave breast cancer imaging by means of a dual-step approach combining radar and tomographic techniques: preliminary results.

Breast cancer is one of the most diagnosed forms of cancer among women worldwide. However, the survival rate is very high when the tumor is diagnosed early. The search for diagnostic techniques increasingly able to detect lesions of the order of a few millimeters and to overcome the limitations of current diagnostic techniques (e.g., the X-ray mammography, currently used as standard for screening campaigns) is always active. Among the main emerging techniques, microwave and millimeter-wave imaging systems have been proposed, using either radar or tomographic approaches. In this paper, a novel dual-step millimeter-wave imaging which combines the advantages of tomographic and radar approaches is proposed. The goal of this work is to reconstruct the dielectric profile of suspicious regions by exploiting the morphological information from the radar maps as a priori information within quantitative tomographic techniques. Promising preliminary dielectric reconstruction results against simulated data are shown in both single- and dual-target scenarios, in which high-density healthy and tumor tissues are present. The reconstruction results were compared to the dielectric characteristics of human breast exvivo tissues used in the simulated models. The proposed dual-step approach allows to distinguish the nature of the targets also in the most challenging case represented by the co-presence of high-density healthy tissues and a malignant lesion, thus paving the way for a deeper investigation of this approach in experimental scenarios. Clinical Relevance-The proposed dual-step approach in the millimeter-wave regime allows to improve the reliability of the diagnostic technique, increasing its specificity.

Early-life perturbations in glucocorticoid activity impacts on the structure, function and molecular composition of the adult zebrafish (Danio rerio) heart.

BACKGROUND: Transient early-life perturbations in glucocorticoids (GC) are linked with cardiovascular disease risk in later life. Here the impact of early life manipulations of GC on adult heart structure, function and gene expression were assessed. METHODS AND RESULTS: Zebrafish embryos were incubated in dexamethasone (Dex) or injected with targeted glucocorticoid receptor (GR) morpholino knockdown (GR Mo) over the first 120 h post fertilisation (hpf); surviving embryos (>90%) were maintained until adulthood under normal conditions. Cardiac function, heart histology and cardiac genes were assessed in embryonic (120 hpf) and adult (120 days post fertilisation (dpf)) hearts. GR Mo embryos (120 hpf) had smaller hearts with fewer cardiomyocytes, less mature striation pattern, reduced cardiac function and reduced levels of vmhc and igf mRNA compared with controls. GR Mo adult hearts were smaller with diminished trabecular network pattern, reduced expression of vmhc and altered echocardiographic Doppler flow compared to controls. Dex embryos had larger hearts at 120 hpf (Dex 107.2 ± 3.1 vs. controls 90.2 ± 1.1 µm, p < 0.001) with a more mature trabecular network and larger cardiomyocytes (1.62 ± 0.13 cells/µm vs control 2.18 ± 0.13 cells/µm, p < 0.05) and enhanced cardiac performance compared to controls. Adult hearts were larger (1.02 ± 0.07 µg/mg vs controls 0.63 ± 0.06 µg/mg, p = 0.0007), had increased vmhc and gr mRNA levels. CONCLUSION: Perturbations in GR activity during embryonic development results in short and long-term alterations in the heart.

Physiological roles of glucocorticoids during early embryonic development of the zebrafish (Danio rerio).

While glucocorticoids (GCs) are known to be present in the zebrafish embryo, little is known about their physiological roles at this stage. We hypothesised that GCs play key roles in stress response, hatching and swim activity during early development. To test this, whole embryo cortisol (WEC) and corticosteroid-related genes were measured in embryos from 6 to 120 h post fertilisation (hpf) by enzyme linked immunosorbent assay (ELISA) and quantitative real-time polymerase chain reaction (qRT-PCR). Stress response was assessed by change in WEC following stirring, hypoxia or brief electrical impulses applied to the bathing water. The impact of pharmacological and molecular GC manipulation on the stress response, spontaneous hatching and swim activity at different stages of development was also assessed. WEC levels demonstrated a biphasic pattern during development with a decrease from 0 to 36 hpf followed by a progressive increase towards 120 hpf. This was accompanied by a significant and sustained increase in the expression of genes encoding cyp11b1 (GC biosynthesis), hsd11b2 (GC metabolism) and gr (GC receptor) from 48 to 120 hpf. Metyrapone (Met), an inhibitor of 11ß-hydroxylase (encoded by cyp11b1), and cyp11b1 morpholino (Mo) knockdown significantly reduced basal and stress-induced WEC levels at 72 and 120 hpf but not at 24 hpf. Spontaneous hatching and swim activity were significantly affected by manipulation of GC action from approximately 48 hpf onwards. We have identified a number of key roles of GCs in zebrafish embryos contributing to adaptive physiological responses under adverse conditions. The ability to alter GC action in the zebrafish embryo also highlights its potential value for GC research.

Modeling and simulation of ultrasound fields generated by 2D phased array transducers for medical applications.

Modern ultrasound imaging instrumentation for clinical applications allows real-time volumetric scanning of the patients' body. 4D imaging has been made possible thanks to the development of new echographic probes which consist in 2D phased arrays of piezoelectric transducers. In these new devices it is the system electronics which properly drives the matrix elements and focuses the beam in order to obtain a sequence of volumetric images. This paper introduces an ultrasound field simulator based on the Spatial Impulse Response method which is being properly developed to analyze the characteristics of the ultrasound field generated by a 2D phased array of transducers. Thanks to its high configurability by the user, it will represent a very useful tool for electronics designers in developing 4D ultrasound imaging systems components.

Bio-inspired controller for a dexterous prosthetic hand based on Principal Components Analysis.

Controlling a dexterous myoelectric prosthetic hand with many degrees of freedom (DoFs) could be a very demanding task, which requires the amputee for high concentration and ability in modulating many different muscular contraction signals. In this work a new approach to multi-DoF control is proposed, which makes use of Principal Component Analysis (PCA) to reduce the DoFs space dimensionality and allow to drive a 15 DoFs hand by means of a 2 DoFs signal. This approach has been tested and properly adapted to work onto the underactuated robotic hand named CyberHand, using mouse cursor coordinates as input signals and a principal components (PCs) matrix taken from the literature. First trials show the feasibility of performing grasps using this method. Further tests with real EMG signals are foreseen.

Why do normal weight young women look for diet-therapy? Findings from a pilot study in a clinical and non-clinical population.

The behavioural factors that drive a normal weight woman to embark on a diet and to look for nutritional support in weight loss clinics are still not completely understood. A pilot cross-sectional study was carried out in 70 young (age range: 18-35 yr), normal weight women attending a weight loss clinic in South of Italy (Naples). They were compared to a population of 94 normal weight students (age range:17-23 yr) who had never attended a weight loss clinic. Subjects with eating disorders have been excluded. Weight and height were measured and body mass index (BMI) was calculated. Eating behaviour was assessed using a validated Italian version of the Eating Disorders Inventory (EDI) questionnaire. The two groups were matched for BMI (22.4 vs 22.1 kg/m2), smoking and physical activity. Students were more educated and less likely to be on a diet at the time of the study. Students had statistically significant lower scores for drive for thinness, body dissatisfaction, inadequacy and interpersonal disrupt. The bulimia scale was the only significant predictor (p<0.05) of BMI in the patients' group; body dissatisfaction (p<0.05) predicted BMI in the control group. This study has shown that weight concern and health awareness are not the only factors that lead a normal weight woman to look for nutritional counselling but there is an underlying substrate of psychological and social distress behind the request, which should be properly assessed before starting any nutritional therapy in the clinical practice.

The impact of treatment complexity and computer-control delivery technology on treatment delivery errors.

PURPOSE: To analyze treatment delivery errors for three-dimensional (3D) conformal therapy performed at various levels of treatment delivery automation and complexity, ranging from manual field setup to virtually complete computer-controlled treatment delivery using a computer-controlled conformal radiotherapy system (CCRS). METHODS AND MATERIALS: All treatment delivery errors which occurred in our department during a 15-month period were analyzed. Approximately 34,000 treatment sessions (114,000 individual treatment segments [ports]) on four treatment machines were studied. All treatment delivery errors logged by treatment therapists or quality assurance reviews (152 in all) were analyzed. Machines "M1" and "M2" were operated in a standard manual setup mode, with no record and verify system (R/V). MLC machines "M3" and "M4" treated patients under the control of the CCRS system, which (1) downloads the treatment delivery plan from the planning system; (2) performs some (or all) of the machine set up and treatment delivery for each field; (3) monitors treatment delivery; (4) records all treatment parameters; and (5) notes exceptions to the electronically-prescribed plan. Complete external computer control is not available on M3; therefore, it uses as many CCRS features as possible, while M4 operates completely under CCRS control and performs semi-automated and automated multi-segment intensity modulated treatments. Analysis of treatment complexity was based on numbers of fields, individual segments, nonaxial and noncoplanar plans, multisegment intensity modulation, and pseudoisocentric treatments studied for a 6-month period (505 patients) concurrent with the period in which the delivery errors were obtained. Treatment delivery time was obtained from the computerized scheduling system (for manual treatments) or from CCRS system logs. Treatment therapists rotate among the machines; therefore, this analysis does not depend on fixed therapist staff on particular machines. RESULTS: The overall reported error rate (all treatments, machines) was 0.13% per segment, or 0.44% per treatment session. The rate (per machine) depended on automation and plan complexity. The error rates per segment for machines M1 through M4 were 0.16%, 0.27%, 0.12%, 0.05%, respectively, while plan complexity increased from M1 up to machine M4. Machine M4 (the most complex plans and automation) had the lowest error rate. The error rate decreased with increasing automation in spite of increasing plan complexity, while for the manual machines, the error rate increased with complexity. Note that the real error rates on the two manual machines are likely to be higher than shown here (due to unnoticed and/or unreported errors), while (particularly on M4) virtually all random treatment delivery errors were noted by the CCRS system and related QA checks (including routine checks of machine and table readouts for each treatment). Treatment delivery times averaged from 14 min to 23 min per plan, and depended on the number of segments/plan, although this analysis is complicated by other factors. CONCLUSION: Use of a sophisticated computer-controlled delivery system for routine patient treatments with complex 3D conformal plans has led to a decrease in treatment delivery errors, while at the same time allowing delivery of increasingly complex and sophisticated conformal plans with little increase in treatment time. With renewed vigilance for the possibility of systematic problems, it is clear that use of complete and integrated computer-controlled delivery systems can provide improvements in treatment delivery, since more complex plans can be delivered with fewer errors, and without increasing treatment time.

A computer-controlled conformal radiotherapy system. I: Overview.

PURPOSE: Equipment developed for use with computer-controlled conformal radiotherapy (CCRT) treatment techniques, including multileaf collimators and/or computer-control systems for treatment machines, are now available. The purpose of this work is to develop a system that will allow the safe, efficient, and accurate delivery of CCRT treatments as routine clinical treatments, and permit modifications of the system so that the delivery process can be optimized. METHODS AND MATERIALS: The needs and requirements for a system that can fully support modern computer-controlled treatment machines equipped with multileaf collimators and segmental or dynamic conformal therapy capabilities have been analyzed and evaluated. This analysis has been used to design and then implement a complete approach to the delivery of CCRT treatments. RESULTS: The computer-controlled conformal radiotherapy system (CCRS) described here consists of a process for the delivery of CCRT treatments, and a complex software system that implements the treatment process. The CCRS system described here includes systems for plan transfer, treatment delivery planning, sequencing of the actual treatment delivery process, graphical simulation and verification tools, as well as an electronic chart that is an integral part of the system. The CCRS system has been implemented for use with a number of different treatment machines. The system has been used clinically for more than 2 years to perform CCRT treatments for more than 200 patients. CONCLUSIONS: A comprehensive system for the implementation and delivery of computer-controlled conformal radiation therapy (CCRT) plans has been designed and implemented for routine clinical use with multisegment, computer-controlled, multileaf-collimated conformal therapy. The CCRS system has been successfully implemented to perform these complex treatments, and is considered quite important to the clinical use of modern computer-controlled treatment techniques.

A computer-controlled conformal radiotherapy system. II: Sequence processor.

PURPOSE: A sequence processor (SP) is described as part of a larger computer-controlled conformal radiotherapy system (CCRS). The SP provides the means to accept and then translate highly sophisticated radiation therapy treatment plans into vendor specific instructions to control treatment delivery on a computer-controlled treatment machine. METHODS AND MATERIALS: The sequence processor (SP) is a small workstation computer that interfaces to the control computer of computer-controlled treatment machines, and to other parts of the larger CCRS system. The system reported here has been interfaced to a computer-controlled racetrack microtron with two treatment gantries, and also to other linear accelerator treatment machines equipped with multileaf collimators. An extensive design process has been used in defining the role of the SP within the context of the larger CCRS project. Flexibility and integration with various components of the project, including databases, treatment planning system, graphical simulator, were key factors in the development. In conjunction with the planned set of treatment fields, a procedural scripting language is used to define the sequence of treatment events that are performed, including operator interactions, communications to other systems such as dosimetry and portal imaging devices, and database management. RESULTS: A flexible system has been developed to allow investigation into procedural steps required for simulating and delivering complex radiation treatments. The system has been used to automate portions of the acceptance testing for the control system of the microtron, and is used for routine daily quality assurance testing. The sequence processor system described here has been used to deliver all clinical treatments performed on the microtron system in 2 years of clinical treatment (more than 200 patients treated to a variety of treatment sites). CONCLUSIONS: The sequence processor system has enabled the delivery of complex treatment using computer-controlled treatment machines. The flexibility of the system allows integration with secondary devices and modification of procedural steps, making it possible to develop effective techniques for insuring safe and efficient computer-controlled conformal radiation therapy treatments.

A computer-controlled conformal radiotherapy system. IV: Electronic chart.

PURPOSE: The design and implementation of a system for electronically tracking relevant plan, prescription, and treatment data for computer-controlled conformal radiation therapy is described. METHODS AND MATERIALS: The electronic charting system is implemented on a computer cluster coupled by high-speed networks to computer-controlled therapy machines. A methodical approach to the specification and design of an integrated solution has been used in developing the system. The electronic chart system is designed to allow identification and access of patient-specific data including treatment-planning data, treatment prescription information, and charting of doses. An in-house developed database system is used to provide an integrated approach to the database requirements of the design. A hierarchy of databases is used for both centralization and distribution of the treatment data for specific treatment machines. RESULTS: The basic electronic database system has been implemented and has been in use since July 1993. The system has been used to download and manage treatment data on all patients treated on our first fully computer-controlled treatment machine. To date, electronic dose charting functions have not been fully implemented clinically, requiring the continued use of paper charting for dose tracking. CONCLUSIONS: The routine clinical application of complex computer-controlled conformal treatment procedures requires the management of large quantities of information for describing and tracking treatments. An integrated and comprehensive approach to this problem has led to a full electronic chart for conformal radiation therapy treatments.

A large screen digitizer system for radiation therapy treatment planning.

PURPOSE: This paper describes a new technique for manually drawing contours of anatomy over image data for the purposes of radiation therapy treatment planning. METHODS AND MATERIALS: A large area rear-projectible digitizer tablet is used together with a projection TV system to display computer graphics and image data. Large images of computed tomography or magnetic resonance cross-sections are displayed and the digitizer is used to directly trace outlines of important organs. Digitizer menus allow multiple functions for selecting images and structures, for changing the grayscale level and window, and for zooming and roaming the image. RESULTS: This device has been in clinical operation for many years and has proven to greatly increase the speed of entering cross-sectional outlines defined for serial computed tomography images sets. A small timing study of clinical usage demonstrates up to a factor of ten improvement in the speed of contour entry. CONCLUSION: For 3-dimensional radiation therapy, tumor, and target volumes, as well as important critical organs, must be delineated from serial sets of computed tomography or magnetic resonance images. Often 30 or more slices must be considered and the process of outlining structures on this number of slices can represent a significant fraction of the total treatment planning time. The device described in this paper greatly improve the ease and speed of manual contour entry for 3-dimensional radiation therapy planning.

Controlling factors in the development of ceruloplasmin in pigs during the neonatal growth period.

The sequence of ceruloplasmin development and limiting factors controlling this process in neonatal piglets was studied in a randomized block design. Guided by the change in serum ceruloplasmin levels, the liver copper concentrations of piglets fed copper-deficient and copper-supplemented diets were compared in three different periods. The plasma of piglets was devoid of both apo- and holo-ceruloplasmin at birth. The system responsible for the synthesis of apoceruloplasmin developed shortly after birth as indicated by a steady increase in serum ceruloplasmin activity during the first week without being affected by the diet. Copper apparently was not the limiting factor at this stage since very high concentrations of copper were found in the livers of newborn piglets. However, the liver copper was depleted quickly within 1 to 2 weeks and became the limiting factor if the diet was deficient in copper. The livers of these piglets were fractionated by differential centrifugation to compare the liver copper distribution in the two dietary groups with and without copper supplementation. The treatments did not affect the copper distribution on a percentage of total liver copper basis. However, fractionation study revealed that, unlike adult pig livers, about 70% to 80% of copper was present in the heavier particle fractions of piglet livers.

Effect of molybdate on sulfide production from methionine and sulfate by ruminal microorganisms of sheep.

Purified diets containing sodium sulfate and DL-methionine as sole dietary sources of sulfur were fed to fistulated sheep. The effect of dietary sodium molybdate (50 ppm Mo) on the capacity of the rumen microorganisms to produce sulfide from either sulfate or methionine was assayed in the two sulfur diets. Dietary molybdenum significantly inhibited the production of sulfide from sulfate but enhanced significantly the production of sulfide from methionine. The inhibitory effect of molybdenum on sulfide production in vitro and the number of sulfide-producing bacteria present in the rumen of these sheep are discussed in considering the mechanism of the molybdate effect on sulfide production.

Methodological studies on the uptake of zinc by 3T3 cells.

In the present work, experiments were conducted on the uptake of zinc by 3T3 cells. (1) The percent Zn uptake gradually decreased with addition of increasing amount of zinc (0.05-8.4 mug). (2) With the increase of the incubation period from 2 to 16 hr, Zn uptake by nearly confluent cells increases gradually; however, confluent cells which are newly replated show a distinct cyclic increase in the Zn uptake after 2, 6, and 10 hr. (3) The amino acids of DMM and serum decrease Zn uptake. (4) Histidine at a molar excess of 1:50, 1:500, and 1:5000 reduces Zn uptake in comparison to a treatment with 65Zn-Zn-L-hist2 at a molar ratio of 1:5. (5) When zinc is added in the form of different Zn compounds, at a molar ratio of 1:2 or 1:1 (Zn:ligand), EDTA decreases the Zn uptake markedly. A small influence was shown also by albumin and histidine; however, other amino and organic acids at a molar ratio of 1:2 did not alter Zn uptake significantly.

Development of ceruloplasmin in pigs during the neonatal period.

Colostrum-free newborn pigs were raised artificially to investigate the appearance of ceruloplasmin in the serum of piglets. The sensitivity of the p-phenylenediamine oxidase activity assay, commonly used as a measure of ceruloplasmin, has been increased 10-fold. Based on this activity, no evidence was found that this copper protein was present in the serum of baby pigs at birth, although some evidence was obtained that the protein moiety (apoceruloplasmin) was present. Holoceruloplasmin usually became detectable in the serum 10-15 hours after birth. Its concentration increased slowly at first and then at an accelerated rate. The ceruloplasmin in the sera of 2-3-day-old piglets was isolated and compared with that isolated from the serum of adults. Contrary to a previous report, the physical and chemical properties of ceruloplasmin synthesized during the first 3 days of life of the piglet showed no significant difference from that synthesized by the adult.

Sulfate reduction by a Desulfovibrio species isolated from sheep rumen.

Several dissimilatory, sulfate-reducing bacteria were isolated from the rumen fluid of sheep fed purified diets containing sulfate. One isolate, strain D, was selected for characterization. This organism is a nonsporeforming, obligately anaerobic, mesophilic, nonmotile, gram-negative, straight rod. Cell-free extracts show absorption maxima for cytochrome c(3) and desulfoviridin, characteristic of Desulfovibrio. Carbohydrates, as a sole carbon source, will support growth. Lactate supports growth in the presence of sulfate, not in its absence, whereas glucose or pyruvate support growth either in the presence or absence of sulfate. The isolate has a deoxyribonucleic acid base composition of 61.2% guanine plus cytosine, which is similar to that of several other species of Desulfovibrio; however, it differs from previously described species in morphology, motility, and carbon source utilization. Cell-free extracts of this bacterium exhibit adenosine 5'-triphosphate-sulfurylase, adenosine-5'-phosphosulfate-reductase, and hydrogenase activity. After incubation of cell-free extracts with adenine 5'-triphosphate and (35)SO(4) (2-), adenosine-5'-phosphosulfate rather than 3'-phosphoadenosine-5'-phosphosulfate was shown to be labeled, indicating that the pathway of sulfate reduction in this organism is similar to that of other dissimilatory sulfate reducers. This is the first report of a Desulfovibrio sp. isolated from the rumen.