GEANT4 Monte Carlo simulations for virtual clinical trials in breast X-ray imaging: Proof of concept

Virtual clinical trials (VCT) are in-silico reproductions of medical examinations, which adopt digital models of patients and simulated devices. They are intended to produce clinically equivalent outcome data avoiding long execution times, ethical issues related to radiation induced risks and huge costs related to real clinical trials with a patient population. In this work, we present a platform for VCT in 2D and 3D X-ray breast imaging. The VCT platform uses Monte Carlo simulations based on the Geant4 toolkit and patient breast models derived from a cohort of high resolution dedicated breast CT (BCT) volume data sets. Projection images of the breast and three-dimensional glandular dose maps are generated for a given breast model, by simulating both 2D full-field digital mammography (DM) and 3D BCT examinations. Uncompressed voxelized breast models were derived from segmented patient images. Compressed versions of the digital breast phantoms for DM were generated using a previously published digital compression algorithm. The Monte Carlo simulation framework has the capability of generating and tracking ~10⁵ photons/s using a server equipped with 16-cores and 3.0 GHz clock speed. The VCT platform will provide a framework for scanner design optimization, comparison between different scanner designs and between different modalities or protocols on computational breast models, without the need for scanning actual patients as in conventional clinical trials.     

Occupational exposures during abdominal fluoroscopically guided interventional procedures for different patient sizes — A Monte Carlo approach

In this study we evaluated the occupational exposures during an abdominal fluoroscopically guided interventional radiology procedure. We investigated the relation between the Body Mass Index (BMI), of the patient, and the conversion coefficient values (CC) for a set of dosimetric quantities, used to assess the exposure risks of medical radiation workers. The study was performed using a set of male and female virtual anthropomorphic phantoms, of different body weights and sizes. In addition to these phantoms, a female and a male phantom, named FASH3 and MASH3 (reference virtual anthropomorphic phantoms), were also used to represent the medical radiation workers. The CC values, obtained as a function of the dose area product, were calculated for 87 exposure scenarios. In each exposure scenario, three phantoms, implemented in the MCNPX 2.7.0 code, were simultaneously used. These phantoms were utilized to represent a patient and medical radiation workers. The results showed that increasing the BMI of the patient, adjusted for each patient protocol, the CC values for medical radiation workers decrease. It is important to note that these results were obtained with fixed exposure parameters.     

Monte Carlo simulation of the dose distribution of ICRP adult reference computational phantoms for acquisitions with a 320 detector-row cone-beam CT scanner

PurposeThe purpose of this study was to develop and validate a Monte Carlo (MC) simulation tool for patient dose assessment for a 320 detector-row CT scanner, based on the recommendations of International Commission on Radiological Protection (ICRP). Additionally, the simulation was applied on four clinical acquisition protocols, with and without automatic tube current modulation (TCM).MethodsThe MC simulation was based on EGS4 code and was developed specifically for a 320 detector-row cone-beam CT scanner. The ICRP adult reference phantoms were used as patient models. Dose measurements were performed free-in-air and also in four CTDI phantoms: 150 mm and 350 mm long CT head and CT body phantoms. The MC program was validated by comparing simulations results with these actual measurements acquired under the same conditions. The measurements agreed with the simulations across all conditions within 5%. Patient dose assessment was performed for four clinical axial acquisitions using the ICRP adult reference phantoms, one of them using TCM.ResultsThe results were nearly always lower than those obtained from other dose calculator tools or published in other studies, which were obtained using mathematical phantoms in different CT systems. For the protocol with TCM organ doses were reduced by between 28 and 36%, compared to the results obtained using a fixed mA value.ConclusionsThe developed simulation program provides a useful tool for assessing doses in a 320 detector-row cone-beam CT scanner using ICRP adult reference computational phantoms and is ready to be applied to more complex protocols.     

Monte Carlo evaluation of glandular dose in cone-beam X-ray computed tomography dedicated to the breast: Homogeneous and heterogeneous breast models

PurposeIn cone-beam computed tomography dedicated to the breast (BCT), the mean glandular dose (MGD) is the dose metric of reference, evaluated from the measured air kerma by means of normalized glandular dose coefficients (DgN_CT). This work aimed at computing, for a simple breast model, a set of DgN_CT values for monoenergetic and polyenergetic X-ray beams, and at validating the results vs. those for patient specific digital phantoms from BCT scans.MethodsWe developed a Monte Carlo code for calculation of monoenergetic DgN_CT coefficients (energy range 4.25–82.25 keV). The pendant breast was modelled as a cylinder of a homogeneous mixture of adipose and glandular tissue with glandular fractions by mass of 0.1%, 14.3%, 25%, 50% or 100%, enveloped by a 1.45 mm-thick skin layer. The breast diameter ranged between 8 cm and 18 cm. Then, polyenergetic DgN_CT coefficients were analytically derived for 49-kVp W-anode spectra (half value layer 1.25–1.50 mm Al), as in a commercial BCT scanner. We compared the homogeneous models to 20 digital phantoms produced from classified 3D breast images.ResultsPolyenergetic DgN_CT resulted 13% lower than most recent published data. The comparison vs. patient specific breast phantoms showed that the homogeneous cylindrical model leads to a DgN_CT percentage difference between −15% and +27%, with an average overestimation of 8%.ConclusionsA dataset of monoenergetic and polyenergetic DgN_CT coefficients for BCT was provided. Patient specific breast models showed a different volume distribution of glandular dose and determined a DgN_CT 8% lower, on average, than homogeneous breast model.     

Generating and using patient-specific whole-body models for organ dose estimates in CT with increased accuracy: Feasibility and validation

The estimation of patient dose using Monte Carlo (MC) simulations based on the available patient CT images is limited to the length of the scan. Software tools for dose estimation based on standard computational phantoms overcome this problem; however, they are limited with respect to taking individual patient anatomy into account. The purpose of this study was to generate whole-body patient models in order to take scattered radiation and over-scanning effects into account. Thorax examinations were performed on three physical anthropomorphic phantoms at tube voltages of 80 kV and 120 kV; absorbed dose was measured using thermoluminescence dosimeters (TLD). Whole-body voxel models were built as a combination of the acquired CT images appended by data taken from widely used anthropomorphic voxel phantoms. MC simulations were performed both for the CT image volumes alone and for the whole-body models. Measured and calculated dose distributions were compared for each TLD chip position; additionally, organ doses were determined.MC simulations based only on CT data underestimated dose by 8%–15% on average depending on patient size with highest underestimation values of 37% for the adult phantom at the caudal border of the image volume. The use of whole-body models substantially reduced these errors; measured and simulated results consistently agreed to better than 10%.This study demonstrates that combined whole-body models can provide three-dimensional dose distributions with improved accuracy. Using the presented concept should be of high interest for research studies which demand high accuracy, e.g. for dose optimization efforts.     

Radiomics software for breast imaging optimization and simulation studies

Background and ObjectiveThe development, control and optimisation of new x-ray breast imaging modalities could benefit from a quantitative assessment of the resulting image textures. The aim of this work was to develop a software tool for routine radiomics applications in breast imaging, which will also be available upon request.MethodsThe tool (developed in MATLAB) allows image reading, selection of Regions of Interest (ROI), analysis and comparison. Requirements towards the tool also included convenient handling of common medical and simulated images, building and providing a library of commonly applied algorithms and a friendly graphical user interface. Initial set of features and analyses have been selected after a literature search. Being open, the tool can be extended, if necessary.ResultsThe tool allows semi-automatic extracting of ROIs, calculating and processing a total of 23 different metrics or features in 2D images and/or in 3D image volumes. Computations of the features were verified against computations with other software packages performed with test images. Two case studies illustrate the applicability of the tool – (i) features on a series of 2D ‘left’ and ‘right’ CC mammograms acquired on a Siemens Inspiration system were computed and compared, and (ii) evaluation of the suitability of newly proposed and developed breast phantoms for x-ray-based imaging based on reference values from clinical mammography images. Obtained results could steer the further development of the physical breast phantoms.ConclusionsA new image analysis toolbox was realized and can now be used in a multitude of radiomics applications, on both clinical and test images.     

The construction of computer tomographic phantoms and their application in radiology and radiation protection

Summary In order to assess human organ doses for risk estimates under natural and man made radiation exposure conditions, human phantoms have to be used. As an improvement to the mathematical anthropomorphic phantoms, a new family of phantoms is proposed, constructed from computer tomographic (CT) data. A technique is developed which allows any physical phantom to be converted into computer files to be used for several applications. The new human phantoms present advantages towards the location and shape of the organs, in particular the hard bone and bone marrow. The CT phantoms were used to construct three dimensional images of high resolution; some examples are given and their potential is discussed. The use of CT phantoms is also demonstrated to assess accurately the proportion of bone marrow in the skeleton. Finally, the use of CT phantoms for Monte Carlo (MC) calculations of doses resulting from various photon exposures in radiology and radiation protection is discussed.Dedicated to Prof. W. Jacobi on the occasion of his 60th birthday     

Three-dimensional printer-generated patient-specific phantom for artificial in vivo dosimetry in radiotherapy quality assurance

Pretreatment intensity-modulated radiotherapy quality assurance is performed using simple rectangular or cylindrical phantoms; thus, the dosimetric errors caused by complex patient-specific anatomy are absent in the evaluation objects. In this study, we construct a system for generating patient-specific three-dimensional (3D)-printed phantoms for radiotherapy dosimetry. An anthropomorphic head phantom containing the bone and hollow of the paranasal sinus is scanned by computed tomography (CT). Based on surface rendering data, a patient-specific phantom is formed using a fused-deposition-modeling-based 3D printer, with a polylactic acid filament as the printing material. Radiophotoluminescence glass dosimeters can be inserted in the 3D-printed phantom. The phantom shape, CT value, and absorbed doses are compared between the actual and 3D-printed phantoms. The shape difference between the actual and printed phantoms is less than 1 mm except in the bottom surface region. The average CT value of the infill region in the 3D-printed phantom is −6 ± 18 Hounsfield units (HU) and that of the vertical shell region is 126 ± 18 HU. When the same plans were irradiated, the dose differences were generally less than 2%. These results demonstrate the feasibility of the 3D-printed phantom for artificial in vivo dosimetry in radiotherapy quality assurance.     

Automatic Synthesis of Anthropomorphic Pulmonary CT Phantoms

The great density and structural complexity of pulmonary vessels and airways impose limitations on the generation of accurate reference standards, which are critical in training and in the validation of image processing methods for features such as pulmonary vessel segmentation or artery–vein (AV) separations. The design of synthetic computed tomography (CT) images of the lung could overcome these difficulties by providing a database of pseudorealistic cases in a constrained and controlled scenario where each part of the image is differentiated unequivocally. This work demonstrates a complete framework to generate computational anthropomorphic CT phantoms of the human lung automatically. Starting from biological and image-based knowledge about the topology and relationships between structures, the system is able to generate synthetic pulmonary arteries, veins, and airways using iterative growth methods that can be merged into a final simulated lung with realistic features. A dataset of 24 labeled anthropomorphic pulmonary CT phantoms were synthesized with the proposed system. Visual examination and quantitative measurements of intensity distributions, dispersion of structures and relationships between pulmonary air and blood flow systems show good correspondence between real and synthetic lungs (p > 0.05 with low Cohen’s d effect size and AUC values), supporting the potentiality of the tool and the usefulness of the generated phantoms in the biomedical image processing field.     

Phantom evaluations of a dedicated dual-head scintimammography system

Results of aboratory evaluations are presented of the dual-head scintimammography system using two opposed and co-registered compact gamma heads. The system is intended for clinical studies imaging suspicious lesions in a compressed breast. The studies were performed using 5 cm and 6 cm compressed breast phantoms with lesion sizes from 6 to 10 mm and lesion to breast tissue activity ratios from 6 to 10. Two imagers with a field-of-view (FOV) of 15 cm×20 cm were placed on the opposite sides of the breast phartoms. In some studies anthropomorphic torso phantom was used to simulate realistic scatter gamma radiation field. Two types of parallel-hole lead collimators were employed. Combining the co-registered images from both detector heads resulted in an over two-fold increase in lesioin contrast in the central plane of the phantom and substantially increased detection sensitivity over the whole breast volume, especially of asymmetrically placed small lesions. The results confirm the important advantage of a co-registoed two-head scintimammography system over a single head system in lesion detection and localization.     

Structural and congenital heart disease interventions: the role of three-dimensional printing

Advances in catheter-based interventions in structural and congenital heart disease have mandated an increased demand for three-dimensional (3D) visualisation of complex cardiac anatomy. Despite progress in 3D imaging modalities, the pre- and periprocedural visualisation of spatial anatomy is relegated to two-dimensional flat screen representations. 3D printing is an evolving technology based on the concept of additive manufacturing, where computerised digital surface renders are converted into physical models. Printed models replicate complex structures in tangible forms that cardiovascular physicians and surgeons can use for education, preprocedural planning and device testing. In this review we discuss the different steps of the 3D printing process, which include image acquisition, segmentation, printing methods and materials. We also examine the expanded applications of 3D printing in the catheter-based treatment of adult patients with structural and congenital heart disease while highlighting the current limitations of this technology in terms of segmentation, model accuracy and dynamic capabilities. Furthermore, we provide information on the resources needed to establish a hospital-based 3D printing laboratory.     

Geometric inaccuracy and co-registration errors for CT,DynaCT and MRI images used in robotic stereotactic radiosurgery treatment planning

PurposeTo measure the combined errors due to geometric inaccuracy and image co-registration on secondary images (dynamic CT angiography (dCTA), 3D DynaCT angiography (DynaCTA), and magnetic resonance images (MRI)) that are routinely used to aid in target delineation and planning for stereotactic radiosurgery (SRS).MethodsThree phantoms (one commercial and two in-house built) and two different analysis approaches (commercial and MATLAB based) were used to quantify the magnitude of geometric image distortion and co-registration errors for different imaging modalities within CyberKnife’s MultiPlan treatment planning software. For each phantom, the combined errors were reported as a mean target registration error (TRE). The mean TRE’s for different intramodality imaging parameters (e.g., mAs, kVp, and phantom set-ups) and for dCTA, DynaCTA, and MRI systems were measured.ResultsOnly X-ray based imaging can be performed with the commercial phantom, and the mean TRE ± standard deviation values were large compared to the in-house analysis using MATLAB. With the 3D printed phantom, even drastic changes in treatment planning CT imaging protocols did not greatly influence the mean TRE (<0.5 mm for a 1 mm slice thickness CT). For all imaging modalities, the largest mean TRE was found on DynaCT, followed by T2-weighted MR images (albeit all <1 mm).ConclusionsThe user may overestimate the mean TRE if the commercial phantom and MultiPlan were used solely. The 3D printed phantom design is a sensitive and suitable quality assurance tool for measuring 3D geometric inaccuracy and co-registration errors across all imaging modalities.     

Development of a high resolution voxelised head phantom for medical physics applications

Computational anthropomorphic phantoms have become an important investigation tool for medical imaging and dosimetry for radiotherapy and radiation protection. The development of computational phantoms with realistic anatomical features contribute significantly to the development of novel methods in medical physics. For many applications, it is desirable that such computational phantoms have a real-world physical counterpart in order to verify the obtained results.In this work, we report the development of a voxelised phantom, the HIGH_RES_HEAD, modelling a paediatric head based on the commercial phantom 715-HN (CIRS). HIGH_RES_HEAD is unique for its anatomical details and high spatial resolution (0.18 × 0.18 mm² pixel size). The development of such a phantom was required to investigate the performance of a new proton computed tomography (pCT) system, in terms of detector technology and image reconstruction algorithms.The HIGH_RES_HEAD was used in an ad-hoc Geant4 simulation modelling the pCT system. The simulation application was previously validated with respect to experimental results. When compared to a standard spatial resolution voxelised phantom of the same paediatric head, it was shown that in pCT reconstruction studies, the use of the HIGH_RES_HEAD translates into a reduction from 2% to 0.7% of the average relative stopping power difference between experimental and simulated results thus improving the overall quality of the head phantom simulation.The HIGH_RES_HEAD can also be used for other medical physics applications such as treatment planning studies.A second version of the voxelised phantom was created that contains a prototypic base of skull tumour and surrounding organs at risk.     

Hybrid framework for feasible modeling of an edge illumination X-ray phase-contrast imaging system at a human scale

Here, we present a hybrid approach for simulating an edge illumination X-ray phase-contrast imaging (EIXPCi) set-up using graphics processor units (GPU) with a high degree of accuracy. In this study, the applicability of pixel, mesh and non-uniform rational B-splines (NURBS) objects to carry out realistic maps of X-ray phase-contrast distribution at a human scale is accounted for by using numerical anthropomorphic phantoms and a very fast and robust simulation framework which integrates total interaction probabilities along selected X-ray paths. We exploit the mathematical and algorithmic properties of NURBS and describe how to represent human scale phantoms in an edge illumination X-ray phase-contrast model. The presented implementation allows the modeling of a variety of physical interactions of x-rays with different mathematically described objects and the recording of quantities, e.g. path integrals, interaction sites and deposited energies. Furthermore, our efficient, scalable and optimized hybrid Monte Carlo and ray-tracing projector can be used in iterative reconstruction algorithms on multi GPU heterogeneous systems. The preliminary results of our innovative approach show the fine performance of an edge illumination X-ray phase-contrast medical imaging system on various human-like soft tissues with noticeably reduced computation time. Our approach to the EIXPCi modeling confirms that building a true imaging system at a human scale should be possible and the simulations presented here aim at its future development.     

What Is the Most Realistic Single-Compartment Model of Spike Initiation?

A large variety of neuron models are used in theoretical and computational neuroscience, and among these, single-compartment models are a popular kind. These models do not explicitly include the dendrites or the axon, and range from the Hodgkin-Huxley (HH) model to various flavors of integrate-and-fire (IF) models. The main classes of models differ in the way spikes are initiated. Which one is the most realistic? Starting with some general epistemological considerations, I show that the notion of realism comes in two dimensions: empirical content (the sort of predictions that a model can produce) and empirical accuracy (whether these predictions are correct). I then examine the realism of the main classes of single-compartment models along these two dimensions, in light of recent experimental evidence.     

Elastic phantoms generated by microfluidics technology: validation of an imaged-based approach for accurate measurement of the growth rate of lung nodules

This paper focuses on validating our approach for monitoring the development of lung nodules detected in successive chest low-dose computed tomography (LDCT) scans of a patient. Our methodology for monitoring detected lung nodules includes 3D LDCT data registration, which is a non-rigid technique and involves two steps: (i) global target-to-prototype alignment of one scan to another using the experience gained from a prior appearance model, followed by (ii) local alignment to correct for intricate relative deformations. We propose a new approach for validating the accuracy of our algorithm for elastic lung phantoms constructed with state-of-the-art microfluidics technology and in vivo data. Fabricated from a flexible transparent polymer, i.e. polydimethylsiloxane (PDMS), the phantoms mimic the contractions and expansions of the lung and nodules as seen during normal breathing. The in vivo data in our study had been collected from a small control group of four subjects and a larger test group of 27 subjects with known ground truth (biopsy diagnosis. The growth rate and diagnostic results for both phantoms and in vivo data confirm the high accuracy of our algorithm.     

Quantitative evaluation of transmission properties of breast tissue equivalent materials under Compton scatter imaging setup

To explore the potential of utilizing Compton scattered x-ray photons for imaging applications, it is critical to accurately evaluate scattered x-ray transmission properties of targeted tissue materials. In this study, scattered x-ray transmission of breast tissue equivalent phantoms was evaluated. Firstly, two validations were carried out using a primary x-ray beam at 80 kVp with both experimental measurement (ion chamber with narrow-beam setup) and analytical calculation (Spektr toolkit). The tungsten-anode x-ray spectrum model was thus validated by measuring and calculating the transmission through increasing thickness of 1100 Aluminum filters. Similarly, the composition models of breast tissue equivalent phantoms (CIRS, 012A) were validated by measuring and calculating x-ray transmission for three different breast compositions (BR30/70, BR50/50, and BR70/30). Following validation, transmission properties of Compton scattered x-ray photons were measured with a GOS based linear array detector at the 90° angle from the primary beam. The same study was performed through three independent approaches: experimental measurement, analytical calculation, and Monte Carlo simulation (GEANT4). For all three methods, the scattered x-ray photon transmission as functions of phantom thickness were determined and fit into exponential functions. The transmission curves from all three methods matched reasonably well, with a maximum difference of 6.3% for the estimated effective attenuation coefficients of the BR50/50 phantom. The relative difference among the three methods of estimated attenuation is under 3.5%. As an initial step to develop a novel Compton scatter-based breast imaging system, the quantitative results from this study paved a fundamental base for future work.     

Design of lymphedema ultrasound phantom with 3D-printed patient-specific subcutaneous anatomy: A-mode analysis approach for early diagnosis

The secondary lymphedema is mostly caused due to injury of lymphatic system during cancer treatment and its psychological and cosmetic issues are very critical for patients since it can cause severe thickening and swelling of lesions, mostly upper and lower limbs. Therefore, early diagnosis of the secondary lymphedema is more important to treat the symptoms in advance. The amplitude-mode (A-mode) ultrasound is suggested as an early diagnostic modality because it is relatively more cost-effective, portable, and easy to use than other previous diagnostic modalities. In order to see features of the A-mode ultrasound forearly diagnosis of lymphedema, ultrasound lymphedema phantoms were designed and fabricated with patient-specific subcutaneous honeycomb structures at the sub-stages of the international society of lymphedema (ISL) stage II and gelatin- or gelatin-salt based phantom materials. The patent-specific honeycomb structures were segmented from computed tomography (CT) venography images using various image process technologies and printed using a three dimensional (3D) printer for which its printing material shows similar acoustic impedance range with human subcutaneous tissues. The lymphedema phantoms showed similar subcutaneous anatomical features to those of patient's imagesin brightness mode (B-mode) ultrasound examination, and acoustic information originated from the stage-specific honeycomb structures was well represented in A-mode ultrasound examination. In particular, the A-mode wave form well represented stage-specific honeycomb information even with higher impedance value of fibrous fat region. Such stage-specific wave form information of A-mode ultrasound for the corresponding stage-specific lymphedema phantoms at the ISL stage II can be useful for further development of an A-mode ultrasound applications for early diagnosis of the secondary lymphedema.     

Tissue-simulating Phantoms for Assessing Potential Near-infrared Fluorescence Imaging Applications in Breast Cancer Surgery

Inaccuracies in intraoperative tumor localization and evaluation of surgical margin status result in suboptimal outcome of breast-conserving surgery (BCS). Optical imaging, in particular near-infrared fluorescence (NIRF) imaging, might reduce the frequency of positive surgical margins following BCS by providing the surgeon with a tool for pre- and intraoperative tumor localization in real-time. In the current study, the potential of NIRF-guided BCS is evaluated using tissue-simulating breast phantoms for reasons of standardization and training purposes.Breast phantoms with optical characteristics comparable to those of normal breast tissue were used to simulate breast conserving surgery. Tumor-simulating inclusions containing the fluorescent dye indocyanine green (ICG) were incorporated in the phantoms at predefined locations and imaged for pre- and intraoperative tumor localization, real-time NIRF-guided tumor resection, NIRF-guided evaluation on the extent of surgery, and postoperative assessment of surgical margins. A customized NIRF camera was used as a clinical prototype for imaging purposes.Breast phantoms containing tumor-simulating inclusions offer a simple, inexpensive, and versatile tool to simulate and evaluate intraoperative tumor imaging. The gelatinous phantoms have elastic properties similar to human tissue and can be cut using conventional surgical instruments. Moreover, the phantoms contain hemoglobin and intralipid for mimicking absorption and scattering of photons, respectively, creating uniform optical properties similar to human breast tissue. The main drawback of NIRF imaging is the limited penetration depth of photons when propagating through tissue, which hinders (noninvasive) imaging of deep-seated tumors with epi-illumination strategies.