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.

An ultrasound model to calculate the brain blood outflow through collateral vessels: a pilot study.

BACKGROUND: The quantification of the flow returning from the head through the cervical veins and the collaterals of the internal jugular vein (IJV), is becoming of prominent interest in clinical practice. We developed a novel model to calculate the cerebral venous return, normalized to the arterial inflow, in the different segments of the IJV. METHODS: We assessed, by established Echo Colour Doppler (ECD) methodology, the head inflow (HBinF) defined as the sum of common carotids and vertebral arteries, as well as the cerebral flow (CBF) defined as the sum of internal carotid and vertebral arteries. We also assessed the head outflow (HBoutF) defined as the sum of the measurements at the junction of the IJV and the vertebral veins. In addition, we also calculated the collateral flow index (CFI) by estimating the flow which re-enters directly into the superior vena cava as the amount of blood extrapolated by the difference between the HBinF and the HBoutF. We preliminarily tested the model by comparing ten healthy controls (HC) with ten patients affected by chronic cerebral spinal venous insufficiency (CCSVI), a condition characterized by some blockages in the IJV which are bypassed by collateral circulation. RESULTS: In HC the HBinF was 956+-105ml/min, whereas the HBoutF was > 90% of the HBinF, leading to a final CFI value of 1%. The last result shows that a very small amount of blood is drained by the collaterals. In upright we confirmed a reduction of the outflow through the IJV which increased CFI to 9%. When we applied the model to CCSVI, the HBinF was not significantly different from controls. In supine, the flow of CCSVI patients in the IJV junction was significantly lower (p < 0.001) while the correspondent CFI value significantly increased (61%, p < 0.0002). CONCLUSIONS: Our preliminary application of the novel model in the clinical setting suggests the pivotal role of the collateral network in draining the blood into the superior vena cava under CCSVI condition.

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.

Mechanical Function of Internal Jugular Vein Valve: Post-analysis of M-Mode Imaging under Cardiac Monitoring.

Because the internal jugular vein (IJV) valve is the only protective valve between the brain and heart, recent studies have focused on the dynamic behaviour of the valve and its importance in regulating the cerebral blood outflow pathway. However, the mechanism underlying valve opening and closure, as well as the normal opening time, has not been investigated before. The aim of the study described here was to investigate IJV physiology in healthy young adults by means of ultrasound imaging. Twenty-four normal young adults (16 male, 8 female, 21.79 ± 0.79 y of age) were enrolled in this study. Each participant underwent IJV B- and M-mode ultrasound scans of the neck veins in supine position. Data on IJV leaflet movement and IJV blood velocity were extracted from images with the associated electrocardiogram traces to analyze the opening and closure cycles of IJV leaflets. The normal opening time calculated in this study includes 70% of the dynamic valve cycle. The normal opening time of the IJV valve could be a new physiologic metric and serves as a premise for further studies in the field of cerebral venous return.

Altered velocity gradient in lower limb chronic venous disease.

BACKGROUND: In physiology, velocity of the deep venous compartment is higher than the one in the saphenous compartment which is higher than the one in the tributaries. Considering that velocity variation is associated with changes in the pressure gradient, aim of the present study is to assess changes in venous kinetics in case of superficial chronic venous disease, so to provide further clues in venous drainage direction determination. METHODS: Venous ultrasound scanning was performed on 40 lower limbs of 28 chronic venous disease patients (C2-6Ep,As,Pr). Velocities were measured in three different venous segments: great saphenous vein at 2 cm above the origin of the incompetent tributary (Group-A). great saphenous vein at 2 cm below the origin of tributary (Group-B). tributary at 2 cm from its origin from the great saphenous vein (Group-C.). RESULTS: Diastolic time average velocity was higher in group-C (-21.3 ± 8.5 cm/s) than in group-A (-15.7 ± 5.2 cm/s; p = .0001) and group-B (-11.1 ± 2.9 cm/s; p = .0001), thus indicating an inversion of the physiological velocity gradient in chronic venous disease patients. DISCUSSION: Chronic venous disease presents a subverted velocity gradient. These data introduce objective hemodynamics data, paving the way for further investigation in venous drainage direction determination.

Abstract ID: 176 Geant4 implementation of inter-atomic interference effect in small-angle coherent X-ray scattering for materials of medical interest.

Advanced applications of digital mammography such as dual-energy and tomosynthesis require multiple exposures and thus deliver higher dose compared to standard mammograms. A straightforward manner to reduce patient dose without affecting image quality would be removal of the anti-scatter grid, provided that the involved reconstruction algorithms are able to take the scatter figure into account [1]. Monte Carlo simulations are very well suited for the calculation of X-ray scatter distribution and can be used to integrate such information within the reconstruction software. Geant4 is an open source C++ particle tracking code widely used in several physical fields, including medical physics [2,3]. However, the coherent scattering cross section used by the standard Geant4 code does not take into account the influence of molecular interference. According to the independent atomic scattering approximation (the so-called free-atom model), coherent radiation is indistinguishable from primary radiation because its angular distribution is peaked in the forward direction. Since interference effects occur between x-rays scattered by neighbouring atoms in matter, it was shown experimentally that the scatter distribution is affected by the molecular structure of the target, even in amorphous materials. The most important consequence is that the coherent scatter distribution is not peaked in the forward direction, and the position of the maximum is strongly material-dependent [4]. In this contribution, we present the implementation of a method to take into account inter-atomic interference in small-angle coherent scattering in Geant4, including a dedicated data set of suitable molecular form factor values for several materials of clinical interest. Furthermore, we present scatter images of simple geometric phantoms in which the Rayleigh contribution is rigorously evaluated.

Lower limbs venous kinetics and consequent impact on drainage direction.

Background Literature concerning the lower limbs physiological venous haemodynamics is still lacking of reference velocity values and consequent impact on drainage direction. Aim of the present study is to assess the flow velocities in the different venous compartments, evaluating the possible Venturi effect role, thus finding clues for the identification of the physical model governing the flow direction. Methods Thirty-six lower limbs underwent a velocity and diameters echo-color-Doppler assessment in several anatomical point of analysis along both the deep and superficial venous systems. The investigation protocol included and compared two different manoeuvres to elicit the flow: manual calf compression/relaxation (CR) and active foot dorsiflexion (AFD). Both peak systolic (PSV) and time average velocities (TAV) were measured. Results The different venous segments demonstrated an overlap among the velocity values and the anatomical subdivision of the deep and superficial compartments. At the CR, TAV was 34 ± 12 cm/s in the deep venous system (N1), 15 ± 7 cm/s in the saphenous system (N2), 5 ± 2 cm/s in the saphenous tributaries (N3); PSV was 89 ± 35 cm/s in N1, 34 ± 16 cm/s in N2, 11 ± 4 cm/s in N3, p < 0.05. At the AFD, TAV was 33 ± 13 cm/s in N1, 15 ± 7 in N2, 9 ± 5 in N3; PSV was 83 ± 35 in N1, 32 ± 17 in N2, 15 ± 4 in N3, p < 0.05. A diameter decrease was reported from N1 to N3 ( p < 0.05). Conclusion This investigation provides evidences of the velocity decrease from the deepest to the most superficial compartments. These data introduce the Venturi effect as potential factor in the flow aspiration from the tributary to the deeper veins. The reported data represent a first step towards an objective evaluation of the physic laws governing the drainage. These values can constitute the basis for further investigations in pathological and post-procedural scenarios.

Ultrasound Monitoring of Jugular Venous Pulse during Space Missions: Proof of Concept.

The jugular venous pulse (JVP) is one of the main parameters of cardiac function and is used by cardiologists in diagnosing heart failure. Its waveform comprises three positive waves (a, c and v) and two negative waves (x and y). Recently, it was found that JVP can be extrapolated from an ultrasound (US) video recording of the internal jugular vein (IJV), suggesting its application in space missions, on which US scanners are already widely used. To date, the feasibility of assessing JVP in microgravity (microG) has not been investigated. To verify the feasibility of JVP assessment in microG, we tested a protocol of self-performed B-mode ultrasound on the International Space Station (ISS). The protocol consisted of a video recording of IJV synchronized with electrocardiogram that produces a cross-sectional area time trace (JVP trace) (in cm2). The scans were acquired in six experimental sessions; two pre-flight (BDC1 and -2), two in space (ISS1 and -2) and two post-flight (Houston PF1, Cologne PF2). We measured the mean and standard deviation of the JVP waves and the phase relationship between such waves and P and T waves on the electrocardiogram. We verified that such parameters had the same accuracy on Earth as they did under microG, and we compared their values. The sensitivity, specificity and accuracy of JVP trace in microgravity are higher than those on Earth. The sequence of (a, c, and v) ascents and (x and y) descents along the cardiac cycle in microG is the same as that on Earth. The cause-and-effect relationship between the P and T waves on the electrocardiogram and a and v waves, respectively, of JVP is also confirmed in microG. Our experiment indicated the feasibility of deriving a JVP trace from a B-mode US examination self-performed by an astronaut in microG.

A novel approach to background subtraction in contrast-enhanced dual-energy digital mammography with commercially available mammography devices: Noise minimization.

PURPOSE: Dual-energy image subtraction represents a useful tool to improve the detectability of small lesions, especially in dense breasts. A feature it shares with all x-ray imaging techniques is the appearance of fluctuations in the texture of the background, which can obscure the visibility of interesting details. The aim of the work is to investigate the main noise sources, in order to create a better performing subtraction mechanism. In particular, the structural noise cancellation was achieved by means of a suitable extension of the dual-energy algorithm. METHODS: The effect of the cancellation procedure was tested on an analytical simulation of a target with varying structural composition. Subsequently, the subtraction algorithm was also applied to a set of actual radiographs of a breast phantom exhibiting a nonuniform background pattern. The background power spectra of the outcomes were computed and compared to the ones obtained from a standard subtraction algorithm. RESULTS: The comparison between the standard and the proposed cancellations showed an overall suppression of the magnitudes of the spectra, as well as a flattening of the frequency dependence of the structural component of the noise. CONCLUSIONS: The proposed subtraction procedure provides an effective cancellation of the residual background fluctuations. When combined with the polychromatic correction already described in a companion publication, it results in a high performing dual-energy subtraction scheme for commercial mammography units.

X-ray focal spot reconstruction by circular penumbra analysis-Application to digital radiography systems.

PURPOSE: The quality of a radiography system is affected by several factors, a major one being the focal spot size of the x-ray tube. In fact, the measurement of such size is recognized to be of primary importance during acceptance tests and image quality evaluations of clinical radiography systems. The most common device providing an image of the focal spot emission distribution is a pin-hole camera, which requires a high tube loading in order to produce a measurable signal. This work introduces an alternative technique to obtain an image of the focal spot, through the processing of a single radiograph of a simple test object, acquired with a suitable magnification. METHODS: The radiograph of a magnified sharp edge is a well-established method to evaluate the extension of the focal spot profile along the direction perpendicular to the edge. From a single radiograph of a circular x-ray absorber, it is possible to extract simultaneously the radial profiles of several sharp edges with different orientations. The authors propose a technique that allows to obtain an image of the focal spot through the processing of these radial profiles by means of a pseudo-CT reconstruction technique. In order to validate this technique, the reconstruction has been applied to the simulated radiographs of an ideal disk-shaped absorber, generated by various simulated focal spot distributions. Furthermore, the method has been applied to the focal spot of a commercially available mammography unit. RESULTS: In the case of simulated radiographs, the results of the reconstructions have been compared to the original distributions, showing an excellent agreement for what regards both the overall distribution and the full width at half maximum measurements. In the case of the experimental test, the method allowed to obtain images of the focal spot that have been compared with the results obtained through standard techniques, namely, pin-hole camera and slit camera. CONCLUSIONS: The method was proven to be effective for simulated images and the results of the experimental test suggest that it could be considered as an alternative technique for focal spot distribution evaluation. The method offers the possibility to measure the actual focal spot size and emission distribution at the same exposure conditions as clinical routine, avoiding high tube loading as in the case of the pin-hole imaging technique.

Clinical Applicability of Assessment of Jugular Flow over the Individual Cardiac Cycle Compared with Current Ultrasound Methodology.

There is growing interest in measuring cerebral venous outflow with ultrasound (US). However, results obtained with the current US Doppler methodology, which uses just a single value of cross-sectional area (CSA) of the vessel, are highly variable and inconclusive. The product of CSA and time-averaged velocity in the case of pulsatile vessels may be a possible source of error, particularly for a pulsatile vein like the internal jugular vein (IJV), where the cardiac pump transmits a sequence of well-established waves along the conduit. We herein propose a novel technique for US IJV flow assessment that accurately accounts for IJV CSA variations during the cardiac cycle. Five subjects were investigated with a high-resolution real-time B-mode video, synchronized with an electrocardiography trace. In this approach, CSA variations representing the pulsatility of the IJV are overlapped with the velocity curve obtained by the usual spectral Doppler trace. The overlap is then phased point by point using the electrocardiography pacemaker. This allows us to experimentally measure the velocity variation in relation to the change in CSA precisely, ultimately enabling calculation of IJV flow. (i) The sequence of CSA variation with respect to the electrocardiography waves corresponds exactly to the jugular venous pulse as measured in physiology. (ii) The methodology permits us to phase the velocity and CSA, which is ultimately what is currently lacking to precisely calculate the flow in the IJV with US. (iii) The time-averaged flow, calculated with the described technique, is very close to that calculated assuming a constant IJV CSA, whereas the time-dependent flow shows differs as much as 40%. (iv) Finally, we tested the accuracy of the technique with a methodology that may allow for universal assessment of the accuracy of each personal US-based evaluation of flow rate.

The Oscillating Component of the Internal Jugular Vein Flow: The Overlooked Element of Cerebral Circulation.

The jugular venous pulse (JVP) provides valuable information about cardiac haemodynamics and filling pressures and is an indirect estimate of the central venous pressure (CVP). Recently it has been proven that JVP can be obtained by measuring the cross-sectional area (CSA) of the IJV on each sonogram of an ultrasound B-mode sonogram sequence. It has also been proven that during its pulsation the IJV is distended and hence that the pressure gradient drives the IJV haemodynamics. If this is true, then it will imply the following: (i) the blood velocity in the IJV is a periodic function of the time with period equal to the cardiac period and (ii) the instantaneous blood velocity is given by a time function that can be derived from a flow-dynamics theory that uses the instantaneous pressure gradient as a parameter. The aim of the present study is to confirm the hypothesis that JVP regulates the IJV blood flow and that pressure waves are transmitted from the heart toward the brain through the IJV wall.

A novel approach to background subtraction in contrast-enhanced dual-energy digital mammography with commercially available mammography devices: Polychromaticity correction.

PURPOSE: Contrast-enhanced digital mammography is an image subtraction technique that is able to improve the detectability of lesions in dense breasts. One of the main sources of error, when the technique is performed by means of commercial mammography devices, is represented by the intrinsic polychromaticity of the x-ray beams. The aim of the work is to propose an iterative procedure, which only assumes the knowledge of a small set of universal quantities, to take into account the polychromaticity and correct the subtraction results accordingly. METHODS: In order to verify the procedure, it has been applied to an analytical simulation of a target containing a contrast medium and to actual radiographs of a breast phantom containing cavities filled with a solution of the same medium. RESULTS: The reconstructed densities of contrast medium were compared, showing very good agreement between the theoretical predictions and the experimental results already after the first iteration. Furthermore, the convergence of the iterative procedure was studied, showing that only a small number of iterations is necessary to reach limiting values. CONCLUSIONS: The proposed procedure represents an efficient solution to the polychromaticity issue, qualifying therefore as a viable alternative to inverse-map functions.

An ultrasonographic technique to assess the jugular venous pulse: a proof of concept.

The purpose of the work described here was to investigate the feasibility of assessing the jugular venous pulse (JVP) using ultrasound (US) equipment. Three young healthy subjects underwent a B-mode US scan of the internal jugular vein (IJV) to acquire a sonogram sequence in the transverse plane. On each acquired sonogram, the IJV contour was manually traced, and both the cross-sectional area (CSA) and the perimeter were measured. The CSA data set represents the US jugular diagram (USJD). The arterial distension waveform of the subjects was compared with its USJD. The correlation between the CSA and the perimeter was assessed during the cardiac cycle to verify IJV distension. For each subject, a short sonogram sequence of a few seconds was recorded, and the USJD obtained exhibited periodic behavior. Furthermore, for all subjects, the CSA was found to be correlated with the perimeter (Pearson coefficient, R > 0.9), indicating that the IJV in supine position is distended. We compared 390 manually traced contours of the IJV cross-sectional area with corresponding values semi-automatically calculated by an algorithm developed in-house. For all subjects, the sensitivity, specificity and accuracy were around 95%, 85% and 90% respectively. We found that a diagram reflecting the JVP can be obtained by analyzing a B-mode sonogram sequence of the IJV; such a diagram can result in a new methodology to assess the IJV functionality.

Does thoracic pump influence the cerebral venous return?

We assessed the hemodynamic effects induced by the thoracic pump in the intra- and extracranial veins of the cerebral venous system on healthy volunteers. Activation of the thoracic pump was standardized among subjects by setting the deep inspiration at 70% of individual vital capacity. Peak velocity (PV), time average velocity (TAV), vein area (VA), and flow quantification (Q) were assessed by means of echo color Doppler in supine posture. Deep respiration significantly increases PV, TAV, and Q, but it is limited to the extracranial veins. To the contrary, no significant hemodynamic changes were recorded at the level of the intracranial venous network. Moreover, at rest TAV in the jugular veins was significantly correlated with Q of the intracranial veins. We conclude that the modulation of the atmospheric pressure operated by the thoracic pump significantly modifies the hemodynamics of the jugular veins and of the reservoir of the neck and facial veins, with no effect on the vein network of the intracranial compartment.

Digital mammography: physical principles and future applications.

Mammography is currently considered the best tool for the detection of breast cancer, pathology with a rate of incidence in constant increase. To produce the radiological picture a screen film combination is conventionally used. One of the inherent limitations of screen- film combination is the fact that the detection, display and storage processes are one and the same, making it impossible to separately optimize each stage. These limitations can be overcome with digital systems. In this work we evaluate the main characteristics of digital detectors available on the market and we compare the performance of digital and conventional systems. Digital mammography, due to the possibility to process images, offers many potential advantages, among these the possibility to introduce the dual-energy technique which employs the composition of two digital images obtained with two different energies to enhance the inherent contrast of pathologies by removing the uniform background. This technique was previously tested by using synchrotron monochromatic beam and a digital detector, and then the Senographe 2000D full-field digital system manufactured by GE Medical Systems. In this work we present preliminary results and the future applications of this technique.

Patient dose in full-field digital mammography: an Italian survey.

The aim of this study was to compare performance and patient dose of full-field digital mammography units for clinical use. Measurements of linearity and automatic exposure control stability were performed on four units installed in as many Italian sites. The tube output was also obtained by the same ionization chamber, permitting to evaluate ratios mGy/mAs for each available spectrum. The entrance air-kerma was calculated over a sample of 800 cranio-caudal mammograms and the average glandular dose obtained, assuming two mean glandular compositions of 50 and 30%, respectively. Digital systems showed very good linearity and comparable responses. The stability of the automatic exposure control was better than 5% for all systems. Regarding doses, the two mammography units that work mainly in contrast mode deliver, respectively, 17 and 28% more dose compared with those working in standard mode. For the latter mode, the mean average glandular dose was in the range 1.25-1.37 mGy and 1.37-1.49 mGy for the 50 and 30% glandular composition, respectively. Results of this study were compared with those of other surveys, showing that full-field digital mammography allows a significant clinical dose reduction compared with screen/film mammography.

Digital mammography: quality and dose control.

PURPOSE: For almost 3 years, Radiologists and Physicists from Padova and Ferrara Universities have collaborated together, with the aim of collecting and comparing experimental data useful to define the most significant parameters for quality controls in digital mammography. Successively, radiologists and physicists working in other sites where a digital mammography unit was installed joined the work-group. MATERIALS AND METHODS: In this study we report the results obtained from measurements of linearity, uniformity, short- and long-term reproducibility, AEC stability performed on 5 digital equipment by using a simple test object. X-ray beam quality and tube yield were preliminarily checked in such a way that possible uncertainties of digital system responses could be separated from those due to differences among X-ray tubes. RESULTS: Results showed that the equipment considered, comparable in terms of both beam quality (HVL) and tube yield, always displayed linear response and reproducibility errors lower than 5%. Uniformity was very good and the grey level compensation as a function of exposure parameters remained within 5%. Differences in choice of parameters by exposure control system (AOP) were emphasised, especially for crossing between track/filter combinations (from Mo/Mo to Mo/Rh and from Mo/Rh to Rh/Rh); those differences were attributed to the +/-2 mm tolerance of breast thickness measurement (mechanically obtained) greater than the AOP tolerance (+/-1 mm). DISCUSSION AND CONCLUSIONS: Obtained results can be useful, as comparison and reference values, for users employing a digital mammography unit of the same kind reported in this paper. Moreover, the same results could be used as "orientation" also by other users having different digital mammography technologies, whose operation should be nevertheless specifically studied and understood in order to find the most useful parameters for quality controls. The acquired experience clearly showed us that years of investigations will be necessary in order to be able to write reliable protocols. This should induce people to contemplate the necessity of not improvising "theoretical" protocols, that are unreliable and dangerous for their negative clinical implications.