Paolo Russo

Bone densitometry in osteoporosis diagnosis via dual-energy X-ray absorptiometry (DXA) can benefit from advances in imaging detector technology. We devised a compact imaging scanner—DXA4A—using a photon-counting and energy-sensitive Timepix4 hybrid pixel detector (512 × 448 pixels, 55 µm pitch), for areal bone mineral density (aBMD) assessments in the distal radius and tibia in the clinic and for future in-flight astronauts’ bone health assessment. We present the design and Monte Carlo simulations of the scanner. A Timepix4 detector with a 1 mm thick CdTe sensor was tested in the laboratory with X-ray tube sources, acquiring first images of test samples. Monte Carlo simulations were implemented for scanner design and performance prediction, using 50 kVp unfiltered and 100 kVp Sm K-edge filtered spectra. With a digital twin of the scanner and patient wrist, we set up a virtual imaging study and determined the aBMD in the forearm of a patient (0.515 ± 0.048 g/cm²), in agreement with the clinical DXA value (0.571 g/cm² for the total forearm). This study highlights the feasibility of realizing a compact DXA scanner for the distal tibia and radius with spectral capabilities, exploiting Timepix4 hybrid detectors for its peculiar energy sensitivity and photon event timing properties for tissue identification.

Spatially fractionated radiotherapy with X-ray minibeams (x-MBRT) aims to increase normal-tissue tolerance by delivering alternating high- and low-dose regions. We provide a Monte Carlo-based framework to design and optimize multi-slit collimators, quantifying how geometry and material govern peak–valley modulation. A validated digital twin of the SmART X-RAD225Cx irradiator was implemented in TOPAS/Geant4. Various x-MBRT collimators were simulated with parallel or divergent slits. The parameter space covered a slit width w (0.1–0.9 mm), center-to-center spacing CTC (1–3 mm), thickness T (1–5 mm), and acceptance angle θ. Dose was scored in a 2 × 2 × 2 cm³ water phantom at a 1 cm depth. For fixed w/CTC, peak-valley dose ratio PVDR increases with larger CTC via an increase in peak dose, with the valley dose nearly constant. Peak transmission saturated at θ ≈ 3°, indicating minimal benefit from larger acceptance. Divergent slits yielded flatter lateral profiles but higher valley doses than parallel slits, reducing PVDR around the central axis. This Monte Carlo study provides insights for optimizing collimator geometries in x-MBRT using small-animal irradiators, informing the design of more effective collimation systems to enhance treatment precision and normal-tissue sparing.

Spatially fractionated radiotherapy with X ray minibeams (x MBRT) aims to increase normal tissue tolerance by delivering alternating high and low dose regions. We provide a Monte Carlo–based framework to design and optimize multislit collimators, quantifying how geometry and material govern peak–valley modulation. A validated digital twin of the SmART X RAD225Cx irradiator was implemented in TOPAS/Geant4. Various x-MBRT collimators were simulated with parallel or divergent slits. The parameter space covered slit width w (0.1–0.9 mm), center to center spacing CTC (1–3 mm), thickness T (1–5 mm), and acceptance angle θ. Dose was scored in a 2 × 2 × 2 cm³ water phantom at 1 cm depth. The valley dose increased linearly with the filling factor (w/CTC) and as ~T². For fixed w/CTC, PVDR increases with larger CTC via an increase of peak dose, with valley dose nearly constant. Peak transmission saturated at θ ≈ 3°, indicating minimal benefit from larger acceptance. Divergent slits yielded flatter lateral profiles but higher valley doses than parallel slits, reducing PVDR around the central axis. This Monte Carlo study provides insights for optimizing collimator geometries in x-MBRT using small-animal irradiators, informing the design of more effective collimation systems to enhance treatment precision and normal tissue sparing.

Objective. To obtain maps of absorbed dose and an estimate of the effective dose to an adult patient for a high resolution peripheral quantitative computed tomography (HR-pQCT) (XtremeCT II) examination of the distal tibia and radius, using a graphical processing unit (GPU)-based Monte Carlo (MC) code. Approach. We adapted the validated code gCTD (GPU-based CT Dose calculator), to replicate the HR-pQCT configuration. MC simulations were performed on digital phantoms of the tibia and radius obtained from bilateral scans of the ankle and wrist of a 25 year-old female volunteer. Scans were segmented using an ad hoc algorithm in Fiji. Simulations run on an NVIDIA GeForce RTX 3090 GPU board. MC dose estimates were validated via computed tomography dose index measurements. Main Results. We obtained the absorbed dose distribution in the skin, bone, bone marrow, fat, and muscle tissues. The effective dose for the HR-pQCT examination were 2.05 μSv and 2.13 μSv for the right and left tibia, and 1.48 μSv and 1.49 μSv for the right and left radius, respectively, with a Type A statistical uncertainty of 0.06% (k = 3) with 4.66 × 10¹¹ photon histories. Corresponding effective dose conversion coefficients (k-factors) were 0.185 μSv ∙ mGy⁻¹ · cm⁻¹ (tibia), and 0.133 μSv mGy⁻¹ · cm⁻¹ (radius). Significance. We reported the first independent estimate of the effective dose for standard HR-pQCT clinical scans of the distal tibia and radius with the XtremeCT II scanner. Effective dose estimates (considering a total relative uncertainty of less than 40%) were lower than those indicated by the manufacturer and commonly reported for these scans. With 4.66 × 10⁹ photon histories, the gCTD MC code can produce 3D dose maps from segmented HR-pQCT images in less than 12 s (GPU time), with 0.9% (k = 3) statistical uncertainty, making real-time personalized dose estimate feasible.

Towards new and improved techniques in liquid biopsy for the diagnosis of diseases, this study reports experimental evidence of a rapid and reliable method based on terahertz (THz) time-domain spectroscopic ellipsometry (TDSE) for the early diagnosis of kidney-related diseases, using the detection of uric acid (UA) content in urine. Employing a custom-built THz-TDSE system, we analyzed the absorption and dispersion response of synthetic urine samples with varying concentrations of UA. The technique provides a prompt indication of UA presence and concentration, thanks to the sensitivity of THz waves to intermolecular interactions such as hydrogen bonding. The results clearly show a linear correlation between the UA concentration and changes in the absorption spectra of urine in the frequency window 0.2–1.2 THz, with the minimum detectable UA concentration being approximately close to the upper limit of normal UA levels in urine. The increase in the absorption coefficient as a function of the UA concentration provides a means for a quantifiable measure of the UA biomarker in urine for assessing disease stage. This study proves that THz-TDSE is capable of detecting UA at concentrations relevant for early-stage diagnosis of renal diseases, with an estimated sensitivity of 0.2 g/L in the region where the material response is linear.

In recent years, material extrusion-based additive manufacturing, particularly fused filament fabrication (FFF), has gained significant attention due to its versatility and cost-effectiveness in producing complex geometries. This paper presents the characterization of seven novel materials for FFF and twenty-two commercially available filaments in terms of X-ray computed tomography (CT) numbers, as tissue mimicking materials for the realization of 3D printed radiological phantoms. Two technical approaches, by 3D printing of cube samples and by producing cylinders of melted materials, are used for achieving this goal. Results showed that the CT numbers, given in Hounsfield unit (HU), of all the samples depended on the beam kilovoltage (kV). The CT numbers ranged from +411 HU to +3071 HU (at 80 kV), from −422 HU to +3071 HU (at 100 kV), and from −442 HU to +3070 HU (at 120 kV). Several commercial and custom-made filaments demonstrated suitability for substituting soft and hard human tissues, for realization of 3D printed phantoms with FFF in CT imaging. For breast imaging, an anthropomorphic phantom with two filaments could be fabricated using ABS-C (conductive acrylonitrile butadiene styrene) as a substitute for breast adipose tissue, and ASA-A (acrylic styrene acrylonitrile) for glandular breast tissue.

Objective. 3D-localization of gamma sources has the potential to improve the outcome of radio-guided surgery. The goal of this paper is to analyze the localization accuracy for point-like sources with a single coded aperture camera. Approach. We both simulated and measured a point-like 241 Am source at 17 positions distributed within the field of view of an experimental gamma camera. The setup includes a 0.11 mm thick Tungsten sheet with a MURA mask of rank 31 and pinholes of 0.08 mm in diameter and a detector based on the photon counting readout circuit Timepix3. Two methods, namely an iterative search including either a symmetric Gaussian fitting or an exponentially modified Gaussian fitting (EMG) and a center of mass method were compared to estimate the 3D source position. Main results. Considering the decreasing axial resolution with source-to-mask distance, the EMG improved the results by a factor of 4 compared to the Gaussian fitting based on the simulated data. Overall, we obtained a mean localization error of 0.77 mm on the simulated and 2.64 mm on the experimental data in the imaging range of 20 − 100 mm . Significance. This paper shows that despite the low axial resolution, point-like sources in the nearfield can be localized as well as with more sophisticated imaging devices such as stereo cameras. The influence of the source size and the photon count on the imaging and localization accuracy remains an important issue for further research.

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 replicating in silico the 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 10 ¹¹ –10 ¹² per 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 10 ⁹ primary 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.