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.

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.

Synchrotron radiation external beam rotational radiotherapy of breast cancer: proof of principle.

The principle of rotational summation of the absorbed dose for breast cancer treatment with orthovoltage X-ray beams was proposed by J. Boone in 2012. Here, use of X-ray synchrotron radiation for image guided external beam rotational radiotherapy treatment of breast cancer is proposed. Tumor irradiation occurs with the patient in the prone position hosted on a rotating bed, with her breast hanging from a hole in the bed, which rotates around a vertical axis passing through the tumor site. Horizontal collimation of the X-ray beam provides for whole breast or partial breast irradiation, while vertical translation of the bed and successive rotations allow for irradiation of the full tumor volume, with dose rates which permit also hypofractionated treatments. In this work, which follows a previous preliminary report, results are shown of a full series of measurements on polyethylene and acrylic cylindrical phantoms carried out at the Australian Synchrotron, confirmed by Geant4 Monte Carlo simulations, intended to demonstrate the proof of principle of the technique. Dose measurements were carried out with calibrated ion chambers, radiochromic films and thermoluminescence dosimeters. The photon energy investigated was 60 keV. Image guidance may occur with the transmitted beam for contrast-enhanced breast computed tomography. For a horizontal beam collimation of 1.5 cm and rotation around the central axis of a 14 cm-diameter polyethylene phantom, a periphery-to-center dose ratio of 14% was measured. The simulations showed that under the same conditions the dose ratio decreases with increasing photon energy down to 10% at 175 keV. These values are comparable with those achievable with conventional megavoltage radiotherapy of breast cancer with a medical linear accelerator. Dose painting was demonstrated with two off-center `cancer foci' with 1.3 Gy and 0.6 Gy target doses. The use of a radiosensitizing agent for dose enhancement is foreseen.

Survival fraction and phenotype alterations of Xenopus laevis embryos at 3 Gy, 150 kV X-ray irradiation.

To determine the radiosensitivity of Xenopus laevis embryos, aquatic organism model, for toxicity studies utilizing X-rays at acute high dose levels, by analysing its survival fraction and phenotype alterations under one-exposure integral dose. We used the standard Frog Embryo Teratogenesis Assay Xenopus test during the early stages of X. laevis development. The embryos were harvested until st. 46 when they were irradiated. The radiation effects were checked daily for a week and the survival, malformations and growth inhibition were assessed. Sibling tadpoles as control organisms were used. Statistical analysis was performed to assess the extent of any damage. Irradiation was performed with an X-ray tube operated at 150 kV. The tube containing the tadpoles was exposed to an air kerma of 3 Gy as measured in air with an in-beam ionization chamber. After one week, survival fraction of irradiated embryos was 58%, while for control embryos it was 81%. Hence, irradiation with 150 kV, 3 Gy X-rays produced a 23% decrease of survival in regard to unirradiated embryos. The 70% of the irradiated embryos showed an altered distribution of the skin pigmentation, in particular on the dorsal area and in the olfactory pits, where the pigment concentration increased by a factor 2. In conclusion exposure of X. laevis to 3 Gy, 150 kV X-rays induced a reduction of embryos survival and a significant modification of pigmentation. The authors think that X. laevis embryos, at st 46, is a suitable biological model for large scale investigations on the effects of ionizing radiation.

Virtual dosimetry study with three cone-beam breast computed tomography scanners using a fast GPU-based Monte Carlo code.

Objective. To compare the dosimetric performance of three cone-beam breast computed tomography (BCT) scanners, using real-time Monte Carlo-based dose estimates obtained with the virtual clinical trials (VCT)-BREAST graphical processing unit (GPU)-accelerated platform dedicated to VCT in breast imaging. Approach. A GPU-based Monte Carlo (MC) code was developed for replicatingin silicothe geometric, x-ray spectra and detector setups adopted, respectively, in two research scanners and one commercial BCT scanner, adopting 80 kV, 60 kV and 49 kV tube voltage, respectively. Our cohort of virtual breasts included 16 anthropomorphic voxelized breast phantoms from a publicly available dataset. For each virtual patient, we simulated exams on the three scanners, up to a nominal simulated mean glandular dose of 5 mGy (primary photons launched, in the order of 1011-1012per scan). Simulated 3D dose maps (recorded for skin, adipose and glandular tissues) were compared for the same phantom, on the three scanners. MC simulations were implemented on a single NVIDIA GeForce RTX 3090 graphics card.Main results.Using the spread of the dose distribution as a figure of merit, we showed that, in the investigated phantoms, the glandular dose is more uniform within less dense breasts, and it is more uniformly distributed for scans at 80 kV and 60 kV, than at 49 kV. A realistic virtual study of each breast phantom was completed in about 3.0 h with less than 1% statistical uncertainty, with 109primary photons processed in 3.6 s computing time.Significance. We reported the first dosimetric study of the VCT-BREAST platform, a fast MC simulation tool for real-time virtual dosimetry and imaging trials in BCT, investigating the dose delivery performance of three clinical BCT scanners. This tool can be adopted to investigate also the effects on the 3D dose distribution produced by changes in the geometrical and spectrum characteristics of a cone-beam BCT scanner.

Monte Carlo and experimental evaluation of a Timepix4 compact gamma camera for coded aperture nuclear medicine imaging with depth resolution.

PURPOSE: We designed a prototype compact gamma camera (MediPROBE4) for nuclear medicine tasks, including radio-guided surgery and sentinel lymph node imaging with a 99mTc radiotracer. We performed Monte Carlo (MC) simulations for image performance assessment, and first spectroscopic imaging tests with a 300 µm thick silicon detector. METHODS: The hand-held camera (1 kg weight) is based on a Timepix4 readout circuit for photon-counting, energy-sensitive, hybrid pixel detectors (24.6 × 28.2 mm2 sensitive area, 55 µm pixel pitch), developed by the Medipix4 Collaboration. The camera design adopts a CdTe detector (1 or 2 mm thick) bump-bonded to a Timepix4 readout chip and a coded aperture collimator with 0.25 mm diameter round holes made of 3D printed 1-mm thick tungsten. Image reconstruction is performed via autocorrelation deconvolution. RESULTS: Geant4 MC simulations showed that, for a 99mTc source in air, at 50 mm source-collimator distance, the estimated collimator sensitivity (4 × 10-4) is 292 times larger than that of a single hole in the mask; the system sensitivity is 0.22 cps/kBq (2 mm CdTe); the lateral spatial resolution is 1.7 mm FWHM. The estimated axial longitudinal resolution is 8.2 mm FWHM at 40 mm distance. First experimental tests with a 300 µm thick Silicon pixel detector bump-bonded to a Timepix4 chip and a high-resolution coded aperture collimator showed time-over-threshold and time-of-arrival capabilities with 241Am and 133Ba gamma-ray sources. CONCLUSIONS: MC simulations and validation lab tests showed the expected performance of the MediPROBE4 compact gamma camera for gamma-ray 3D imaging.

Patient-specific Monte Carlo-based organ dose estimates in spiral CT via optical 3D body scanning and adaptation of a voxelized phantom dataset: proof-of-principle.

Objective. We present a method for personalized organ dose estimates obtained before the computed tomography (CT) exam, via 3D optical body scanning and Monte Carlo (MC) simulations.Approach. A voxelized phantom is derived by adapting a reference phantom to the body size and shape measured with a portable 3D optical scanner, which returns the 3D silhouette of the patient. This was used as an external rigid envelope for incorporating a tailored version of the internal body anatomy derived from a phantom dataset (National Cancer Institute, NIH, USA) matched for gender, age, weight, and height. The proof-of-principle was conducted on adult head phantoms. The Geant4 MC code provided estimates of the organ doses from 3D absorbed dose maps in the voxelized body phantom.Main results. We applied this approach for head CT scanning using an anthropomorphic voxelized head phantom derived from 3D optical scans of manikins. We compared the estimates of head organ doses with those provided by the NCICT 3.0 software (NCI, NIH, USA). Head organ doses differed up to 38% using the proposed personalized estimate and MC code, with respect to corresponding estimates calculated for the standard (non-personalized) reference head phantom. Preliminary application of the MC code to chest CT scans is shown. Real-time pre-exam personalized CT dosimetry is envisaged with adoption of a Graphics Processing Unit-based fast MC code.Significance. The developed procedure for personalized organ dose estimates before the CT exam, introduces a new approach for realistic description of size and shape of patients via voxelized phantoms specific for each patient.

Cone-beam breast computed tomography with a displaced flat panel detector array.

PURPOSE: In cone-beam computed tomography (CBCT), and in particular in cone-beam breast computed tomography (CBBCT), an important issue is the reduction of the image artifacts produced by photon scatter and the reduction of patient dose. In this work, the authors propose to apply the detector displacement technique (also known as asymmetric detector or "extended view" geometry) to approach this goal. Potentially, this type of geometry, and the accompanying use of a beam collimator to mask the unirradiated half-object in each projection, permits some reduction of radiation dose with respect to conventional CBBCT and a sizeable reduction of the overall amount of scatter in the object, for a fixed contrast-to-noise ratio (CNR). METHODS: The authors consider a scan configuration in which the projection data are acquired from an asymmetrically positioned detector that covers only one half of the scan field of view. Monte Carlo simulations and measurements, with their CBBCT laboratory scanner, were performed using PMMA phantoms of cylindrical (70-mm diameter) and hemiellipsoidal (140-mm diameter) shape simulating the average pendant breast, at 80 kVp. Image quality was evaluated in terms of contrast, noise, CNR, contrast-to-noise ratio per unit of dose (CNRD), and spatial resolution as width of line spread function for high contrast details. RESULTS: Reconstructed images with the asymmetric detector technique deviate less than 1% from reconstruction with a conventional symmetric detector (detector view) and indicate a reduction of the cupping artifact in CT slices. The maximum scatter-to-primary ratio at the center of the phantom decreases by about 50% for both small and large diameter phantoms (e.g., from 0.75 in detector view to 0.40 in extended view geometry at the central axis of the 140-mm diameter PMMA phantom). Less cupping produces an increase of the CT number accuracy and an improved image detail contrast, but the associated increase of noise observed may produce a decrease of detail CNR. By simulating the energy deposited inside the phantoms, the authors evaluated a maximum 50% reduction of the absorbed dose at the expense of a decrease of CNR, for the half beam irradiation of the object performed with the displaced detector technique with respect to full beam irradiation. The decrease in CNR, and in absorbed dose as well, translates into a detail CNRD showing values comparable to or higher than the ones obtained for a conventional symmetric detector technique, attributed to the effect of decreased scatter in particular at the axis of the irradiated object. An estimate is provided (about 12%) for the average dose reduction possible in CBBCT at constant CNR for the average uncompressed breast (14 cm diameter, 50% glandularity), in case of minimum image overlapping in extended view. CONCLUSIONS: Simulations and experiments show that CBCT reconstructions with the displaced detector technique and with a half beam collimator are less affected by scatter artifacts, which could lead to some decrease of the radiation dose to the irradiated object with respect to a conventional reconstruction. This dose reduction is associated with increase of noise, decrease of CNR, but equal or improved CNRD values. The use of a small area detector would allow also to reduce the apparatus cost and to improve the data transfer speed with a corresponding increment of frame rate.

Attenuation coefficient in the energy range 14-36 keV of 3D printing materials for physical breast phantoms.

Objective.To measure the monoenergetic x-ray linear attenuation coefficient,µ, of fused deposition modeling (FDM) colored 3D printing materials (ABS, PLAwhite, PLAorange, PET and NYLON), used as adipose, glandular or skin tissue substitutes for manufacturing physical breast phantoms.Approach. Attenuation data (at 14, 18, 20, 24, 28, 30 and 36 keV) were acquired at Elettra synchrotron radiation facility, with step-wedge objects, using the Lambert-Beer law and a CCD imaging detector. Test objects were 3D printed using the Ultimaker 3 FDM printer. PMMA, Nylon-6 and high-density polyethylene step objects were also investigated for the validation of the proposed methodology. Printing uniformity was assessed via monoenergetic and polyenergetic imaging (32 kV, W/Rh).Main results. Maximum absolute deviation ofµfor PMMA, Nylon-6 and HD-PE was 5.0%, with reference to literature data. For ABS and NYLON,µdiffered by less than 6.1% and 7.1% from that of adipose tissue, respectively; for PET and PLAorangethe difference was less than 11.3% and 6.3% from glandular tissue, respectively. PLAorangeis a good substitute of skin (differences from -9.4% to +1.2%). Hence, ABS and NYLON filaments are suitable adipose tissue substitutes, while PET and PLAorangemimick the glandular tissue. PLAwhitecould be printed at less than 100% infill density for matching the attenuation of glandular tissue, using the measured density calibration curve. The printing mesh was observed for sample thicknesses less than 60 mm, imaged in the direction normal to the printing layers. Printing dimensional repeatability and reproducibility was less 1%.Significance. For the first time an experimental determination was provided of the linear attenuation coefficient of common 3D printing filament materials with estimates ofµat all energies in the range 14-36 keV, for their use in mammography, breast tomosynthesis and breast computed tomography investigations.

Comparisons of glandular breast dose between digital mammography, tomosynthesis and breast CT based on anthropomorphic patient-derived breast phantoms.

PURPOSE: To evaluate the bias to the mean glandular dose (MGD) estimates introduced by the homogeneous breast models in digital breast tomosynthesis (DBT) and to have an insight into the glandular dose distributions in 2D (digital mammography, DM) and 3D (DBT and breast dedicated CT, BCT) x-ray breast imaging by employing breast models with realistic glandular tissue distribution and organ silhouette. METHODS: A Monte Carlo software for DM, DBT and BCT simulations was adopted for the evaluation of glandular dose distribution in 60 computational anthropomorphic phantoms. These computational phantoms were derived from 3D breast images acquired via a clinical BCT scanner. RESULTS: g·c·s·T conversion coefficients based on homogeneous breast model led to a MGD overestimate of 18% in DBT when compared to MGD estimated via anthropomorphic phantoms; this overestimate increased up to 21% for recently computed DgNDBT conversion coefficients. The standard deviation of the glandular dose distribution in BCT resulted 60% lower than in DM and 55% lower than in DBT. The glandular dose peak - evaluated as the average value over the 5% of the gland receiving the highest dose - is 2.8 times the MGD in DM, this factor reducing to 2.6 and 1.6 in DBT and BCT, respectively. CONCLUSIONS: Conventional conversion coefficients for MGD estimates based on homogeneous breast models overestimate MGD by 18%, when compared to MGD estimated via anthropomorphic phantoms. The ratio between the peak glandular dose and the MGD is 2.8 in DM. This ratio is 8% and 75% higher than in DBT and BCT, respectively.

Virtual Clinical Trials in 2D and 3D X-ray Breast Imaging and Dosimetry: Comparison of CPU-Based and GPU-Based Monte Carlo Codes.

Computational reproductions of medical imaging tests, a form of virtual clinical trials (VCTs), are increasingly being used, particularly in breast imaging research. The accuracy of the computational platform that is used for the imaging and dosimetry simulation processes is a fundamental requirement. Moreover, for practical usage, the imaging simulation computation time should be compatible with the clinical workflow. We compared three different platforms for in-silico X-ray 3D breast imaging: the Agata (University & INFN Napoli) that was based on the Geant4 toolkit and running on a CPU-based server architecture; the XRMC Monte Carlo (University of Cagliari) that was based on the use of variance reduction techniques, running on a CPU hardware; and the Monte Carlo code gCTD (University of Texas Southwestern Medical Center) running on a single GPU platform with CUDA environment. The tests simulated the irradiation of cylindrical objects as well as anthropomorphic breast phantoms and produced 2D and 3D images and 3D maps of absorbed dose. All the codes showed compatible results in terms of simulated dose maps and imaging values within a maximum discrepancy of 3%. The GPU-based code produced a reduction of the computation time up to factor 104, and so permits real-time VCT studies for X-ray breast imaging.

Fabrication of 3D printed patient-derived anthropomorphic breast phantoms for mammography and digital breast tomosynthesis: Imaging assessment with clinical X-ray spectra.

PURPOSE: To design, fabricate and characterize 3D printed, anatomically realistic, compressed breast phantoms for digital mammography (DM) and digital breast tomosynthesis (DBT) x-ray imaging. MATERIALS: We realized 3D printed phantoms simulating healthy breasts, via fused deposition modeling (FDM), with a layer resolution of 0.1 mm and 100% infill density, using a dual extruder printer. The digital models were derived from a public dataset of segmented clinical breast computed tomography scans. Three physical phantoms were printed in polyethylene terephthalate (PET), acrylonitrile-butadiene-styrene (ABS), or in polylactic-acid (PLA) materials, using ABS as a substitute for adipose tissue, and PLA or PET filaments for replicating glandular and skin tissues. 3D printed phantoms were imaged at three clinical centers with DM and DBT scanners, using typical spectra. Anatomical noise of the manufactured phantoms was evaluated via the estimates of the ß parameter both in DM images and in images acquired via a clinical computed tomography (CT) scanner. RESULTS: DM and DBT phantom images showed an inner texture qualitatively similar to the images of a clinical DM or DBT exam, suitably reproducing the glandular structure of their computational phantoms. ß parameters evaluated in DM images of the manufactured phantoms ranged between 2.84 and 3.79; a lower ß was calculated from the CT scan. CONCLUSIONS: FDM 3D printed compressed breast phantoms have been fabricated using ABS, PLA and PET filaments. DM and DBT images with clinical x-ray spectra showed realistic textures. These phantoms appear promising for clinical applications in quality assurance, image quality and dosimetry assessments.

Breast radiotherapy with kilovoltage photons and gold nanoparticles as radiosensitizer: An in vitro study.

PURPOSE: We investigated the dose enhancement and internalization of gold nanoparticles (AuNPs) used as a radiosensitizer agent for rotational radiotherapy of breast cancer using a kilovoltage (kV) X-ray beam. METHODS: Human breast cancer cells MDA-MB-231 were incubated with or without 100 µg/mL (4.87 nM) or 200 µg/mL (9.74 nM) 15 nm AuNPs and irradiated with 100 kV, 190 kV, or 6 MV X-rays. To assess the toxicity of the AuNPs, we performed a Sulforhodamine B assay. Using atomic absorption spectroscopy, scanning electron microscopy, transmission electron microscopy, and time-lapse optical microscopy (rate of 2 frames per minute), we carried out a quantitative assessment of the amount of gold internalized by MDA-MB-231 cells and a characterization of the static and dynamical aspects of this internalization process. RESULTS: No effect of AuNPs alone was shown on cell viability. Time-lapse optical microscopy showed for the first time AuNPs cellular uptake and the dynamics of AuNPs internalization. Electron microscopy demonstrated AuNPs localization in endosomal vesicles, preferentially in the perinuclear region. After irradiation at doses up to 2 Gy, cell survival fraction curves showed increased mortality with AuNPs, with respect to irradiation without AuNPs. The highest effect of radioenhancement by AuNPs (at 9.74 nM AuNPs concentration) was observed at 190 kV showing a dose enhancement factor of 1.33 ± 0.06 (1.34 ± 0.02 at 100 kV), while at 6 MV it was 1.14 ± 0.06. CONCLUSIONS: The observed radio-sensitization effect is promising for future radio-enhanced kV radiotherapy of breast cancer and quantitatively in the order of previous observations for 15 nm AuNPs. These results of a significant dose enhancement were obtained at 15 nm AuNPs concentration as low as several nanomolar units, at dose levels typical of a single dose fraction in a radiotherapy session. Dynamical behavior of the 3D spatial distribution of 15 nm AuNPs outside the nucleus of single breast cancer cell was observed, with possible implications for future models of AuNPs sensitization.

Method for measuring the focal spot size of an x-ray tube using a coded aperture mask and a digital detector.

PURPOSE: The goal of this study is to evaluate a new method based on a coded aperture mask combined with a digital x-ray imaging detector for measurements of the focal spot sizes of diagnostic x-ray tubes. Common techniques for focal spot size measurements employ a pinhole camera, a slit camera, or a star resolution pattern. The coded aperture mask is a radiation collimator consisting of a large number of apertures disposed on a predetermined grid in an array, through which the radiation source is imaged onto a digital x-ray detector. The method of the coded mask camera allows one to obtain a one-shot accurate and direct measurement of the two dimensions of the focal spot (like that for a pinhole camera) but at a low tube loading (like that for a slit camera). A large number of small apertures in the coded mask operate as a "multipinhole" with greater efficiency than a single pinhole, but keeping the resolution of a single pinhole. METHODS: X-ray images result from the multiplexed output on the detector image plane of such a multiple aperture array, and the image of the source is digitally reconstructed with a deconvolution algorithm. Images of the focal spot of a laboratory x-ray tube (W anode: 35-80 kVp; focal spot size of 0.04 mm) were acquired at different geometrical magnifications with two different types of digital detector (a photon counting hybrid silicon pixel detector with 0.055 mm pitch and a flat panel CMOS digital detector with 0.05 mm pitch) using a high resolution coded mask (type no-two-holes-touching modified uniformly redundant array) with 480 0.07 mm apertures, designed for imaging at energies below 35 keV. Measurements with a slit camera were performed for comparison. A test with a pinhole camera and with the coded mask on a computed radiography mammography unit with 0.3 mm focal spot was also carried out. RESULTS: The full width at half maximum focal spot sizes were obtained from the line profiles of the decoded images, showing a focal spot of 0.120 mm x 0.105 mm at 35 kVp and M = 6.1, with a detector entrance exposure as low as 1.82 mR (0.125 mA s tube load). The slit camera indicated a focal spot of 0.112 mm x 0.104 mm at 35 kVp and M = 3.15, with an exposure at the detector of 72 mR. Focal spot measurements with the coded mask could be performed up to 80 kVp. Tolerance to angular misalignment with the reference beam up to 7 degrees in in-plane rotations and 1 degrees deg in out-of-plane rotations was observed. The axial distance of the focal spot from the coded mask could also be determined. It is possible to determine the beam intensity via measurement of the intensity of the decoded image of the focal spot and via a calibration procedure. CONCLUSIONS: Coded aperture masks coupled to a digital area detector produce precise determinations of the focal spot of an x-ray tube with reduced tube loading and measurement time, coupled to a large tolerance in the alignment of the mask.

Evaluation of a CdTe semiconductor based compact γ camera for sentinel lymph node imaging.

PURPOSE: The authors assembled a prototype compact gamma-ray imaging probe (MediPROBE) for sentinel lymph node (SLN) localization. This probe is based on a semiconductor pixel detector. Its basic performance was assessed in the laboratory and clinically in comparison with a conventional gamma camera. METHODS: The room-temperature CdTe pixel detector (1 mm thick) has 256 x 256 square pixels arranged with a 55 microm pitch (sensitive area 14.08 x 14.08 mm2), coupled pixel-by-pixel via bump-bonding to the Medipix2 photon-counting readout CMOS integrated circuit. The imaging probe is equipped with a set of three interchangeable knife-edge pinhole collimators (0.94, 1.2, or 2.1 mm effective diameter at 140 keV) and its focal distance can be regulated in order to set a given field of view (FOV). A typical FOV of 70 mm at 50 mm skin-to-collimator distance corresponds to a minification factor 1:5. The detector is operated at a single low-energy threshold of about 20 keV. RESULTS: For 99 mTc, at 50 mm distance, a background-subtracted sensitivity of 6.5 x 10(-3) cps/kBq and a system spatial resolution of 5.5 mm FWHM were obtained for the 0.94 mm pinhole; corresponding values for the 2.1 mm pinhole were 3.3 x 10(-2) cps/kBq and 12.6 mm. The dark count rate was 0.71 cps. Clinical images in three patients with melanoma indicate detection of the SLNs with acquisition times between 60 and 410 s with an injected activity of 26 MBq 99 mTc and prior localization with standard gamma camera lymphoscintigraphy. CONCLUSIONS: The laboratory performance of this imaging probe is limited by the pinhole collimator performance and the necessity of working in minification due to the limited detector size. However, in clinical operative conditions, the CdTe imaging probe was effective in detecting SLNs with adequate resolution and an acceptable sensitivity. Sensitivity is expected to improve with the future availability of a larger CdTe detector permitting operation at shorter distances from the patient skin.

Normalized glandular dose coefficients for digital breast tomosynthesis systems with a homogeneous breast model.

This work aims at calculating and releasing tabulated values of dose conversion coefficients, DgNDBT, for mean glandular dose (MGD) estimates in digital breast tomosynthesis (DBT). The DgNDBT coefficients are proposed as unique conversion coefficients for MGD estimates, in place of dose conversion coefficients in mammography (DgNDM or c, g, s triad as proposed in worldwide quality assurance protocols) used together with the T correction factor. DgNDBT is the MGD per unit incident air kerma measured at the breast surface for a 0° projection and the entire tube load used for the scan. The dataset of polyenergetic DgNDBT coefficients was derived via a Monte Carlo software based on the Geant4 toolkit. Dose coefficients were calculated for a grid of values of breast characteristics (breast thickness in the range 20-90 mm and glandular fraction by mass of 1%, 25%, 50%, 75%, 100%) and the simulated geometries, scan protocols, irradiation geometries and typical spectral qualities replicated those of six commercial DBT systems (GE SenoClaire, Hologic Selenia Dimensions, GE Senographe Pristina, Fujifilm Amulet Innovality, Siemens Mammomat Inspiration and IMS Giotto Class). For given breast characteristics, target/filter combination, tube voltage and half value layer (HVL), two spectra with two HVL values have been simulated in order to permit MGD estimates from experimental HVL values via mathematical interpolation from tabulated values. The adopted breast model assumes homogenous composition of glandular and adipose tissues; it includes a 1.45 mm thick skin envelope in place of the 4-5 mm envelope commonly adopted in dosimetry protocols. The simulation code was validated versus AAPM Task group 195 Monte Carlo reference data sets (absolute differences not higher than 1.1%) and by comparison to relative dosimetry measurements with radiochromic film in a PMMA test object (differences within the maximum experimental uncertainty of 11%). The calculated coefficients show maximum relative deviations of -17.6% and +6.1% from those provided by the DBT dose coefficients adopted in the EUREF protocol and of 1.5%, on average, from data in the AAPM TG223 report. A spreadsheet is provided for interpolating the tabulated DgNDBT coefficients for arbitrary values of HVL, compressed breast thickness and glandular fraction, in the corresponding investigated ranges, for each DBT unit modeled in this work.

Radiomics software for breast imaging optimization and simulation studies.

BACKGROUND AND OBJECTIVE: The 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. METHODS: The 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. RESULTS: The 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. CONCLUSIONS: A new image analysis toolbox was realized and can now be used in a multitude of radiomics applications, on both clinical and test images.

Dataset of patient-derived digital breast phantoms for in silico studies in breast computed tomography, digital breast tomosynthesis, and digital mammography.

PURPOSE: To present a dataset of computational digital breast phantoms derived from high-resolution three-dimensional (3D) clinical breast images for the use in virtual clinical trials in two-dimensional (2D) and 3D x-ray breast imaging. ACQUISITION AND VALIDATION METHODS: Uncompressed computational breast phantoms for investigations in dedicated breast CT (BCT) were derived from 150 clinical 3D breast images acquired via a BCT scanner at UC Davis (California, USA). Each image voxel was classified in one out of the four main materials presented in the field of view: fibroglandular tissue, adipose tissue, skin tissue, and air. For the image classification, a semi-automatic software was developed. The semi-automatic classification was compared via manual glandular classification performed by two researchers. A total of 60 compressed computational phantoms for virtual clinical trials in digital mammography (DM) and digital breast tomosynthesis (DBT) were obtained from the corresponding uncompressed phantoms via a software algorithm simulating the compression and the elastic deformation of the breast, using the tissue's elastic coefficient. This process was evaluated in terms of glandular fraction modification introduced by the compression procedure. The generated cohort of 150 uncompressed computational breast phantoms presented a mean value of the glandular fraction by mass of 12.3%; the average diameter of the breast evaluated at the center of mass was 105 mm. Despite the slight differences between the two manual segmentations, the resulting glandular tissue segmentation did not consistently differ from that obtained via the semi-automatic classification. The difference between the glandular fraction by mass before and after the compression was 2.1% on average. The 60 compressed phantoms presented an average glandular fraction by mass of 12.1% and an average compressed thickness of 61 mm. DATA FORMAT AND ACCESS: The generated digital breast phantoms are stored in DICOM files. Image voxels can present one out of four values representing the different classified materials: 0 for the air, 1 for the adipose tissue, 2 for the glandular tissue, and 3 for the skin tissue. The generated computational phantoms datasets were stored in the Zenodo public repository for research purposes (http://doi.org/10.5281/zenodo.4529852, http://doi.org/10.5281/zenodo.4515360). POTENTIAL APPLICATIONS: The dataset developed within the INFN AGATA project will be used for developing a platform for virtual clinical trials in x-ray breast imaging and dosimetry. In addition, they will represent a valid support for introducing new breast models for dose estimates in 2D and 3D x-ray breast imaging and as models for manufacturing anthropomorphic physical phantoms.

Artificial intelligence applications in medical imaging: A review of the medical physics research in Italy.

PURPOSE: To perform a systematic review on the research on the application of artificial intelligence (AI) to imaging published in Italy and identify its fields of application, methods and results. MATERIALS AND METHODS: A Pubmed search was conducted using terms Artificial Intelligence, Machine Learning, Deep learning, imaging, and Italy as affiliation, excluding reviews and papers outside time interval 2015-2020. In a second phase, participants of the working group AI4MP on Artificial Intelligence of the Italian Association of Physics in Medicine (AIFM) searched for papers on AI in imaging. RESULTS: The Pubmed search produced 794 results. 168 studies were selected, of which 122 were from Pubmed search and 46 from the working group. The most used imaging modality was MRI (44%) followed by CT(12%) ad radiography/mammography (11%). The most common clinical indication were neurological diseases (29%) and diagnosis of cancer (25%). Classification was the most common task for AI (57%) followed by segmentation (16%). 65% of studies used machine learning and 35% used deep learning. We observed a rapid increase of research in Italy on artificial intelligence in the last 5 years, peaking at 155% from 2018 to 2019. CONCLUSIONS: We are witnessing an unprecedented interest in AI applied to imaging in Italy, in a diversity of fields and imaging techniques. Further initiatives are needed to build common frameworks and databases, collaborations among different types of institutions, and guidelines for research on AI.

CdTe compact gamma camera for coded aperture imaging in radioguided surgery.

The aim of this work was to assess the performance of a prototype compact gamma camera (MediPROBE) based on a CdTe semiconductor hybrid pixel detector, for coded aperture imaging. This probe can be adopted for various tasks in nuclear medicine such as preoperative sentinel lymph node localization, breast imaging with 99mTc radiotracers and thyroid imaging, and in general in radioguided surgery tasks. The hybrid detector is an assembly of a 1-mm thick CdTe semiconductor detector bump-bonded to a photon-counting CMOS readout circuit of the Medipix2 series or energy-sensitive Timepix detector. MediPROBE was equipped with a set of two coded aperture masks with 0.07-mm or 0.08-mm diameter holes. We performed laboratory measurements of field of view, system spatial resolution, and signal-difference-to-noise ratio, by using gamma-emitting radioactive sources (109Cd, 125I, 241Am, 99mTc). The system spatial resolution in the lateral direction was 0.56 mm FWHM (coded aperture mask with holes of 0.08 mm and a 60 keV source) at a source-collimator distance of 50 mm and a field of view of 40 mm by side. Correspondingly, the longitudinal resolution in 3D source localization tasks was about 3 mm. MediPROBE showed a significant improvement in terms of spatial resolution when equipped with the high-resolution coded apertures, with respect to the performance previously reported with 1-2 mm pinhole apertures as well as with respect to adopting a 0.35 mm pinhole aperture.