Characterization of breast tissues in density and effective atomic number basis via spectral X-ray computed tomography.

Objective.Differentiation of breast tissues is challenging in X-ray imaging because tissues might share similar or even the same linear attenuation coefficientsµ. Spectral computed tomography (CT) allows for more quantitative characterization in terms of tissue density (ρ) and effective atomic number (Zeff) by exploiting the energy dependence ofµ. The objective of this study was to examine the potential ofρ/Zeffdecomposition in spectral breast CT so as to explore the benefits of tissue characterization and improve the diagnostic accuracy of this emerging 3D imaging technique.Approach.In this work, 5 mastectomy samples and a phantom with inserts mimicking breast soft tissues were evaluated in a retrospective study. The samples were imaged at three monochromatic energy levels in the range of 24-38 keV at 5 mGy per scan using a propagation-based phase-contrast setup at SYRMEP beamline at the Italian national synchrotron Elettra.Main results.A custom-made algorithm incorporating CT reconstructions of an arbitrary number of spectral energy channels was developed to extract the density and effective atomic number of adipose, fibro-glandular, pure glandular, tumor, and skin from regions selected by a radiologist.Significance.Preliminary results suggest that, via spectral CT, it is possible to enhance tissue differentiation. It was found that adipose, fibro-glandular and tumorous tissues have average effective atomic numbers (5.94 ± 0.09, 7.03 ± 0.012, and 7.40 ± 0.10) and densities (0.90 ± 0.02, 0.96 ± 0.02, and 1.07 ± 0.03 g cm-3) and can be better distinguished if both quantitative values are observed together.

First Results on Zinc Oxide Thick Film Deposition by Inverted Magnetron Sputtering for Cyclotron Solid Targets Production.

The magnetron sputtering technique has been investigated in recent years with ever-growing interest as a verifiable solid target manufacturing technology aimed at the production of medical radionuclides by using low-energy cyclotron accelerators. However, the possible loss of high-cost materials prevents access to work with isotopically enriched metals. The need for expensive materials for the supply of the growing demand for theranostic radionuclides makes the material-saving approach and recovery essential for the radiopharmaceutical field. To overcome the main magnetron sputtering drawback, an alternative configuration is proposed. In this work, an inverted magnetron prototype for the deposition of tens of µm film onto different substrates is developed. Such configuration for solid target manufacturing has been proposed for the first time. Two ZnO depositions (20-30 µm) onto Nb backing were carried out and analysed by SEM (Scanning Electron Microscopy) and XRD (X-ray Diffractogram). Their thermomechanical stability under the proton beam of a medical cyclotron was tested as well. A possible improvement of the prototype and the perspective of its utilisation were discussed.

The Effect of Submaximal Exercise on Jugular Venous Pulse Assessed by a Wearable Cervical Plethysmography System.

The jugular venous pulse (JVP) is a one of the crucial parameters of efficient cardiovascular function. Nowadays, limited data are available regarding the response of JVP to exercise because of its complex and/or invasive assessment procedure. The aim of the present work is to test the feasibility of a non-invasive JVP plethysmography system to monitor different submaximal exercise condition. Twenty (20) healthy subjects (13M/7F mean age 25 ± 3, BMI 21 ± 2) underwent cervical strain-gauge plethysmography, acquired synchronously with the electrocardiogram, while they were carrying out different activities: stand supine, upright, and during the execution of aerobic exercise (2 km walking test) and leg-press machine exercise (submaximal 6 RM test). Peaks a and x of the JVP waveform were investigated since they reflect the volume of cardiac filling. To this aim, the Δax parameter was introduced, representing the amplitude differences between a and x peaks. Significant differences in the values of a, x, and Δax were found between static and exercise conditions (p < 0.0001, p < 0.0001, p < 0.0001), respectively. Particularly, the Δax value for the leg press was approximately three times higher than the supine, and during walking was even nine times higher. The exercise monitoring by means of the novel JVP plethysmography system is feasible during submaximal exercise, and it provides additional parameters on cardiac filling and cerebral venous drainage to the widely used heartbeat rate value.

A Cationic Contrast Agent in X-ray Imaging of Articular Cartilage: Pre-Clinical Evaluation of Diffusion and Attenuation Properties.

The aim of this study was the preliminary assessment of a new cationic contrast agent, the CA4+, via the analysis of spatial distribution in cartilage of ex vivo bovine samples, at micrometer and millimeter scale. Osteochondral plugs (n = 18) extracted from bovine stifle joints (n = 2) were immersed in CA4+ solution up to 26 h. Planar images were acquired at different time points, using a microCT apparatus. The CA4+ distribution in cartilage and saturation time were evaluated. Tibial plates from bovine stifle joints (n = 3) were imaged with CT, before and after 24 h-CA4+ bath immersion, at different concentrations. Afterward, potential CA4+ washout from cartilage was investigated. From microCT acquisitions, the CA4+ distribution differentiated into three distinct layers inside the cartilage, reflecting the spatial distribution of proteoglycans. After 24 h of diffusion, the iodine concentration reached in cartilage was approximately seven times that of the CA4+ bath. The resulting saturation time was 1.9 ± 0.9 h and 2.6 ± 2.9 h for femoral and tibial samples, respectively. Analysis of clinical CT acquisitions confirmed overall contrast enhancement of cartilage after 24 h immersion, observed for each CA4+ concentration. Distinct contrast enhancement was reached in different cartilage regions, depending on tissue's local features. Incomplete but remarkable washout of cartilage was observed. CA4+ significantly improved cartilage visualization and its qualitative analysis.

Plethysmography System to Monitor the Jugular Venous Pulse: A Feasibility Study.

Cerebral venous outflow is investigated in the diagnosis of heart failure through the monitoring of jugular venous pulse, an indicator to assess cardiovascular diseases. The jugular venous pulse is a weak signal stemming from the lying internal jugular vein and often invasive methodologies requiring surgery are mandatory to detect it. Jugular venous pulse can also be extrapolated via the ultrasound technique, but it requires a qualified healthcare operator to perform the examination. In this work, a wireless, user-friendly, wearable device for plethysmography is developed to investigate the possibility of monitoring the jugular venous pulse non-invasively. The proposed device can monitor the jugular venous pulse and the electrocardiogram synchronously. To study the feasibility of using the proposed device to detect physiological variables, several measurements were carried out on healthy subjects by considering three different postures: supine, sitting, and upright. Data acquired in the experiment were properly filtered to highlight the cardiac oscillation and remove the breathing contribution, which causes a considerable shift in the amplitude of signals. To evaluate the proper functioning of the wearable device for plethysmography, a comparison with the ultrasound technique was carried out. As a satisfactory result, the acquired signals resemble the typical jugular venous pulse waveforms found in literature.

NO-HYPE: a novel hydrodynamic phantom for the evaluation of MRI flow measurements.

Accurate and reproducible measurement of blood flow profile is very important in many clinical investigations for diagnosing cardiovascular disorders. Given that many factors could affect human circulation, and several parameters must be set to properly evaluate blood flows with phase-contrast techniques, we developed an MRI-compatible hydrodynamic phantom to simulate different physiological blood flows. The phantom included a programmable hydraulic pump connected to a series of pipes immersed in a solution mimicking human soft tissues, with a blood-mimicking fluid flowing in the pipes. The pump is able to shape and control the flow by driving a piston through a dedicated software. Periodic waveforms are used as input to the pump to move the fluid into the pipes, with synchronization of the MRI sequences to the flow waveforms. A dedicated software is used to extract and analyze flow data from magnitude and phase images. The match between the nominal and the measured flows was assessed, and the scope of phantom variables useful for a reliable calibration of an MRI system was accordingly defined. Results showed that the NO-HYPE phantom is a valuable tool for the assessment of MRI scanners and sequence design for the MR evaluation of blood flows. Overview of the NOvel HYdrodynamic Phantom for the Evaluation of MRI flow measurements (NO-HYPE). Left: internal of the CompuFlow 1000 MR pump unit. Right: Setting of the NO-HYPE before a MRI acquisition session. Soft tissue mimicking material is hosted in the central part of the phantom (light blue chamber). Glass pipes pass through the chamber carrying the blood mimicking fluid.

Modelling physiology of haemodynamic adaptation in short-term microgravity exposure and orthostatic stress on Earth.

Cardiovascular haemodynamics alters during posture changes and exposure to microgravity. Vascular auto-remodelling observed in subjects living in space environment causes them orthostatic intolerance when they return on Earth. In this study we modelled the human haemodynamics with focus on head and neck exposed to different hydrostatic pressures in supine, upright (head-up tilt), head-down tilt position, and microgravity environment by using a well-developed 1D-0D haemodynamic model. The model consists of two parts that simulates the arterial (1D) and brain-venous (0D) vascular tree. The cardiovascular system is built as a network of hydraulic resistances and capacitances to properly model physiological parameters like total peripheral resistance, and to calculate vascular pressure and the related flow rate at any branch of the tree. The model calculated 30.0 mmHg (30%), 7.1 mmHg (78%), 1.7 mmHg (38%) reduction in mean blood pressure, intracranial pressure and central venous pressure after posture change from supine to upright, respectively. The modelled brain drainage outflow percentage from internal jugular veins is 67% and 26% for supine and upright posture, while for head-down tilt and microgravity is 65% and 72%, respectively. The model confirmed the role of peripheral veins in regional blood redistribution during posture change from supine to upright and microgravity environment as hypothesized in literature. The model is able to reproduce the known haemodynamic effects of hydraulic pressure change and weightlessness. It also provides a virtual laboratory to examine the consequence of a wide range of orthostatic stresses on human haemodynamics.

Experimental optimization of the energy for breast-CT with synchrotron radiation.

Breast Computed Tomography (bCT) is a three-dimensional imaging technique that is raising interest among radiologists as a viable alternative to mammographic planar imaging. In X-rays imaging it would be desirable to maximize the capability of discriminating different tissues, described by the Contrast to Noise Ratio (CNR), while minimizing the dose (i.e. the radiological risk). Both dose and CNR are functions of the X-ray energy. This work aims at experimentally investigating the optimal energy that, at fixed dose, maximizes the CNR between glandular and adipose tissues. Acquisitions of both tissue-equivalent phantoms and actual breast specimens have been performed with the bCT system implemented within the Syrma-3D collaboration at the Syrmep beamline of the Elettra synchrotron (Trieste). The experimental data have been also compared with analytical simulations and the results are in agreement. The CNR is maximized at energies around 26-28 keV. These results are in line with the outcomes of a previously presented simulation study which determined an optimal energy of 28 keV for a large set of breast phantoms with different diameters and glandular fractions. Finally, a study on photon starvation has been carried out to investigate how far the dose can be reduced still having suitable images for diagnostics.

Radiochromic film dosimetry in synchrotron radiation breast computed tomography: a phantom study.

This study relates to the INFN project SYRMA-3D for in vivo phase-contrast breast computed tomography using the SYRMEP synchrotron radiation beamline at the ELETTRA facility in Trieste, Italy. This peculiar imaging technique uses a novel dosimetric approach with respect to the standard clinical procedure. In this study, optimization of the acquisition procedure was evaluated in terms of dose delivered to the breast. An offline dose monitoring method was also investigated using radiochromic film dosimetry. Various irradiation geometries have been investigated for scanning the prone patient's pendant breast, simulated by a 14 cm-diameter polymethylmethacrylate cylindrical phantom containing pieces of calibrated radiochromic film type XR-QA2. Films were inserted mid-plane in the phantom, as well as wrapped around its external surface, and irradiated at 38 keV, with an air kerma value that would produce an estimated mean glandular dose of 5 mGy for a 14 cm-diameter 50% glandular breast. Axial scans were performed over a full rotation or over 180°. The results point out that a scheme adopting a stepped rotation irradiation represents the best geometry to optimize the dose distribution to the breast. The feasibility of using a piece of calibrated radiochromic film wrapped around a suitable holder around the breast to monitor the scan dose offline is demonstrated.

Paediatric haemodynamic modelling: development and experimental validation using quantitative flow MRI.

BACKGROUND: Congenital vascular disease is one of the leading causes of death in paediatric age. Despite the importance of paediatric haemodynamics, large investigations have been devoted to the evaluation of circulation in adults. The novelty of this study consists in the development of a well calibrated mathematical model of cardiovascular circulation in paediatric subjects. To reach the purpose, a model for adult circulation was modified and recalibrated with experimental data and literature from children to be able to calculate the flow rates and pressures in the brain and neck. METHODS: The haemodynamic model simulates the 76 main arteries, together with the main veins in brain and neck. A proper magnetic resonance imaging (MRI) dataset of 29 volunteers aged 12 ± 5 years (mean ± standard deviation) was used to extract age-dependent physiological and clinical parameters such as heart rate, flow rate, vessel cross section area, and blood pressure. The computational model was calibrated using such experimental data. The paediatric and adult model results were compared. RESULTS: Increase of the vessels stiffness due to aging contributes to a flow rate decrease while blood pressure increases. In accordance, our simulation results show about 16% decrease in mean pressure of internal jugular vein in paediatric rather than adult subjects. The model outcomes indicated about 88% correlation with MRI data. CONCLUSIONS: The mathematical model simulates the paediatric head and neck blood circulation. The model provides detailed information of human haemodynamics including arterial and venous network to study both paediatric and adult blood circulation.

Image quality comparison between a phase-contrast synchrotron radiation breast CT and a clinical breast CT: a phantom based study.

In this study we compared the image quality of a synchrotron radiation (SR) breast computed tomography (BCT) system with a clinical BCT in terms of contrast-to-noise ratio (CNR), signal-to-noise ratio (SNR), noise power spectrum (NPS), spatial resolution and detail visibility. A breast phantom consisting of several slabs of breast-adipose equivalent material with different embedded targets (i.e., masses, fibers and calcifications) was used. Phantom images were acquired using a dedicated BCT system installed at the Radboud University Medical Center (Nijmegen, The Netherlands) and the SR BCT system at the SYRMEP beamline of Elettra SR facility (Trieste, Italy) based on a photon-counting detector. Images with the SR setup were acquired mimicking the clinical BCT conditions (i.e., energy of 30 keV and radiation dose of 6.5 mGy). Images were reconstructed with an isotropic cubic voxel of 273 µm for the clinical BCT, while for the SR setup two phase-retrieval (PhR) kernels (referred to as "smooth" and "sharp") were alternatively applied to each projection before tomographic reconstruction, with voxel size of 57 × 57 × 50 µm3. The CNR for the clinical BCT system can be up to 2-times higher than SR system, while the SNR can be 3-times lower than SR system, when the smooth PhR is used. The peak frequency of the NPS for the SR BCT is 2 to 4-times higher (0.9 mm-1 and 1.4 mm-1 with smooth and sharp PhR, respectively) than the clinical BCT (0.4 mm-1). The spatial resolution (MTF10%) was estimated to be 1.3 lp/mm for the clinical BCT, and 5.0 lp/mm and 6.7 lp/mm for the SR BCT with the smooth and sharp PhR, respectively. The smallest fiber visible in the SR BCT has a diameter of 0.15 mm, while for the clinical BCT is 0.41 mm. Calcification clusters with diameter of 0.13 mm are visible in the SR BCT, while the smallest diameter for the clinical BCT is 0.29 mm. As expected, the image quality of the SR BCT outperforms the clinical BCT system, providing images with higher spatial resolution and SNR, and with finer granularity. Nevertheless, this study assesses the image quality gap quantitatively, giving indications on the benefits associated with SR BCT and providing a benchmarking basis for its clinical implementation. In addition, SR-based studies can provide a gold-standard in terms of achievable image quality, constituting an upper-limit to the potential clinical development of a given technique.

Optimization of the energy for Breast monochromatic absorption X-ray Computed Tomography.

The limits of mammography have led to an increasing interest on possible alternatives such as the breast Computed Tomography (bCT). The common goal of all X-ray imaging techniques is to achieve the optimal contrast resolution, measured through the Contrast to Noise Ratio (CNR), while minimizing the radiological risks, quantified by the dose. Both dose and CNR depend on the energy and the intensity of the X-rays employed for the specific imaging technique. Some attempts to determine an optimal energy for bCT have suggested the range 22 keV-34 keV, some others instead suggested the range 50 keV-60 keV depending on the parameters considered in the study. Recent experimental works, based on the use of monochromatic radiation and breast specimens, show that energies around 32 keV give better image quality respect to setups based on higher energies. In this paper we report a systematic study aiming at defining the range of energies that maximizes the CNR at fixed dose in bCT. The study evaluates several compositions and diameters of the breast and includes various reconstruction algorithms as well as different dose levels. The results show that a good compromise between CNR and dose is obtained using energies around 28 keV.

Advancements towards the implementation of clinical phase-contrast breast computed tomography at Elettra.

Breast computed tomography (BCT) is an emerging application of X-ray tomography in radiological practice. A few clinical prototypes are under evaluation in hospitals and new systems are under development aiming at improving spatial and contrast resolution and reducing delivered dose. At the same time, synchrotron-radiation phase-contrast mammography has been demonstrated to offer substantial advantages when compared with conventional mammography. At Elettra, the Italian synchrotron radiation facility, a clinical program of phase-contrast BCT based on the free-space propagation approach is under development. In this paper, full-volume breast samples imaged with a beam energy of 32 keV delivering a mean glandular dose of 5 mGy are presented. The whole acquisition setup mimics a clinical study in order to evaluate its feasibility in terms of acquisition time and image quality. Acquisitions are performed using a high-resolution CdTe photon-counting detector and the projection data are processed via a phase-retrieval algorithm. Tomographic reconstructions are compared with conventional mammographic images acquired prior to surgery and with histologic examinations. Results indicate that BCT with monochromatic beam and free-space propagation phase-contrast imaging provide relevant three-dimensional insights of breast morphology at clinically acceptable doses and scan times.

Quantitative characterization of breast tissues with dedicated CT imaging.

A quantitative characterization of the soft tissues composing the human breast is achieved by means of a monochromatic CT phase-contrast imaging system, through accurate measurements of their attenuation coefficients within the energy range of interest for breast CT clinical examinations. Quantitative measurements of linear attenuation coefficients are performed on tomographic reconstructions of surgical samples, using monochromatic x-ray beams from a synchrotron source and a free space propagation setup. An online calibration is performed on the obtained reconstructions, in order to reassess the validity of the standard calibration procedure of the CT scanner. Three types of healthy tissues (adipose, glandular, and skin) and malignant tumors, when present, are considered from each sample. The measured attenuation coefficients are in very good agreement with the outcomes of similar studies available in the literature, although they span an energy range that was mostly neglected in the previous studies. No globally significant differences are observed between healthy and malignant dense tissues, although the number of considered samples does not appear sufficient to address the issue of a quantitative differentiation of tumors. The study assesses the viability of the proposed methodology for the measurement of linear attenuation coefficients, and provides a denser sampling of attenuation data in the energy range useful to breast CT.

Monochromatic breast computed tomography with synchrotron radiation: phase-contrast and phase-retrieved image comparison and full-volume reconstruction.

A program devoted to performing the first in vivo synchrotron radiation (SR) breast computed tomography (BCT) is ongoing at the Elettra facility. Using the high spatial coherence of SR, phase-contrast (PhC) imaging techniques can be used. The latest high-resolution BCT acquisitions of breast specimens, obtained with the propagation-based PhC approach, are herein presented as part of the SYRMA-3D collaboration effort toward the clinical exam. Images are acquired with a 60 - µ m pixel dead-time-free single-photon-counting CdTe detector. The samples are imaged at 32 and 38 keV in a continuous rotating mode, delivering 5 to 20 mGy of mean glandular dose. Contrast-to-noise ratio (CNR) and spatial resolution performances are evaluated for both PhC and phase-retrieved images, showing that by applying the phase-retrieval algorithm a five-time CNR increase can be obtained with a minor loss in spatial resolution across soft tissue interfaces. It is shown that, despite having a poorer CNR, PhC images can provide a sharper visualization of microcalcifications, thus being complementary to phase-retrieved images. Furthermore, the first full-volume scan of a mastectomy sample ( 9 × 9 × 3 cm 3 ) is reported. This investigation into surgical specimens indicates that SR BCT in terms of CNR, spatial resolution, scan duration, and scan volume is feasible.

Phase-contrast breast CT: the effect of propagation distance.

X-ray phase imaging has the potential to dramatically improve soft tissue contrast sensitivity, which is a crucial requirement in many diagnostic applications such as breast imaging. In this context, a program devoted to perform in vivo phase-contrast synchrotron radiation breast computed tomography is ongoing at the Elettra facility (Trieste, Italy). The used phase-contrast technique is the propagation-based configuration, which requires a spatially coherent source and a sufficient object-to-detector distance. In this work the effect of this distance on image quality is quantitatively investigated scanning a large breast surgical specimen at three object-to-detector distances (1.6, 3, 9 m) and comparing the images both before and after applying the phase-retrieval procedure. The sample is imaged at 30 keV with a [Formula: see text] pixel pitch CdTe single-photon-counting detector, positioned at a fixed distance of 31.6 m from the source. The detector fluence is kept constant for all acquisitions. The study shows that, at the largest distance, a 20-fold SNR increase can be obtained by applying the phase-retrieval procedure. Moreover, it is shown that, for phase-retrieved images, changing the object-to-detector distance does not affect spatial resolution while boosting SNR (four-fold increase going from the shortest to the largest distance). The experimental results are supported by a theoretical model proposed by other authors, whose salient results are presented in this paper.

A multiscale model for the simulation of cerebral and extracerebral blood flows and pressures in humans.

PURPOSE: Brain hemodynamics is fundamental for the functioning of the human being. Many biophysical factors affect brain circulation, so that a satisfactory understanding of its behavior is challenging. We developed a mathematical model to simulate cerebral and extracerebral flows and pressures in humans. METHODS: The model is composed of an anatomically informed 1-D arterial network, and two 0-D networks of the cerebral circulation and brain drainage, respectively. It takes into account the pulse-wave transmission properties of the 55 main arteries and the main hydraulic and autoregulation mechanisms ensuring blood supply and drainage to the brain. Proper pressure outputs from the arterial 1-D model are used as input to the 0-D models, together with the contribution to venous pressure due to breathing that simulates the drainage effect of the thoracic pump. RESULTS: The model we developed is able to link the arterial tree with the venous pathways devoted to the brain drainage, and to simulate important factors affecting cerebral circulation both for physiological and pathological conditions, such as breathing and hypo/hypercapnia. Finally, the average value of simulated flows and pressures is in agreement with the available experimental data. CONCLUSIONS: The model has the potential to predict important clinical parameters before and after physiological and/or pathological changes.

A proposal for a quality control protocol in breast CT with synchrotron radiation.

Background The SYRMA-3D collaboration is setting up the first clinical trial of phase-contrast breast CT with synchrotron radiation at the Elettra synchrotron facility in Trieste, Italy. In this communication, a quality control protocol for breast CT is proposed, and a first test of image quality measurements is performed by means of a custom-made radiographic phantom. Materials and methods A set of projections is acquired and used to perform a CT reconstruction of two selected portions of the phantom. Such portions contain a uniform layer of water and a set of radiographic inserts, respectively. Together, they allow to perform several image quality measurements, namely CT number linearity, reconstruction accuracy, uniformity, noise, and low contrast resolution. All measurements are repeated at different beam energies in the range of interest, and at two different dose values. Results Measurements show a good linearity in the soft tissue range, paired to a high accuracy of the CT number reconstruction. Uniformity and noise measurements show that reconstruction inhomogeneities are bound to a few percent of the average pixel values. However, low contrast detectability is limited to the higher portion of the explored energy range. Conclusions The results of the measurements are satisfactory in terms of their quality, feasibility and reproducibility. With minimal modifications, the phantom is promising to allow a set of image quality measurements to be used in the upcoming clinical trial.

A comparative study of physical image quality in digital and synthetic mammography from commercially available mammography systems.

We present a comparison between full field digital mammography and synthetic mammography, performed on several mammography systems from four different manufacturers. The analysis is carried out on both the digital and synthetic images of two commercially available mammography phantoms, and focuses on a set of objective metrics that encode the geometrical appearance of imaging features of diagnostic interest. In particular, we measured sizes and contrasts of several clusters of microcalcification specks, shapes and contrasts of circular masses, and the power spectrum of background regions mimicking the heterogeneous texture of the breast parenchyma. Despite the potential issues of tomosynthesis in terms of image blurring, the synthetic images do not highlight any globally significant differences in the rendering of the details of interest, when compared to the original digital mammograms: relative contrasts are generally preserved, as well as the geometry of broad structures. We conclude that, as far as the considered objective metrics are concerned, the image quality of synthetic mammography does not exhibit significant differences with respect to the one of full field digital mammography, for all the considered systems.