Open AccessArticle Design of a Novel DXA Scanner with a CdTe Photon-Counting Timepix4 Detector for Peripheral Bone Densitometry 1 Scuola Superiore Meridionale, I-80138 Napoli, Italy 2 Dipartimento di Fisica “Ettore Pancini”, Università di Napoli Federico II, I-80126 Napoli, Italy 3 Istituto Nazionale di Fisica Nucleare (INFN), Sezione di Napoli, I-80126 Napoli, Italy 4 Institute of Experimental and Applied Physics, Czech Technical University in Prague, 110 00 Prague, Czech Republic 5 Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University, Baltimore, MD 21287, USA 6 McCaig Institute for Bone and Joint Health, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4Z6, Canada 7 Department of Radiology, University of Calgary, Calgary, AB T2N 4Z6, Canada * Author to whom correspondence should be addressed. Appl. Sci. 2026, 16(12), 5745; https://doi.org/10.3390/app16125745 (registering DOI) Submission received: 21 March 2026 / Revised: 9 May 2026 / Accepted: 3 June 2026 / Published: 7 June 2026 Featured Application The authors designed and are in the course of assembling a prototype scanner for in vivo bone mineral density assessment in the ankle and wrist via photon-counting dual-energy X-ray absorptiometry (DXA). The novel device has potential for clinical use in osteoporosis research, as well as for research on in-flight assessment of astronauts’ bone loss with a compact unit during long missions. Abstract 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/cm 2), in agreement with the clinical DXA value (0.571 g/cm 2 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. 1. Introduction This study presents the design of a novel compact bone densitometry scanner (called DXA4A) for the distal tibia and radius, based on a photon-counting, energy-sensitive hybrid pixel Timepix4 detector equipped with a 1 mm thick CdTe semiconductor sensor. The virtual twin of the scanner was prepared using Monte Carlo (MC) simulations. In this framework, we set up an MC tool (called VIT-OSTEO), for virtual imaging and dosimetry trials for bone densitometry studies. Laboratory tests of the new generation Timepix4-CdTe assembly were performed. We investigated various technical and conceptual solutions for the novel scanner, presenting them for illustration of the authors’ investigative approaches for technology understanding and for critical design parameter solutions. 1.1. Background Assessment of bone strength is an important aspect of human healthcare in the diagnosis and treatment of diseases related to reduced bone mineral density and reduced bone mass. Specifically, this is the condition of patients with osteoporosis, who are increasingly susceptible to bone fractures [ 1], with a risk of 40–50% of lifetime fracture due to osteoporosis [ 2]. Clinical assessment of low levels of bone mineral density (volumetric BMD, g/cm 3, bone mineral mass/bone volume) is commonly performed by dual-energy X-ray absorptiometry (DXA) non-invasive examinations of femoral neck, total hip, distal radius or lumbar vertebrae—expressed in terms of areal BMD (aBMD, g/cm 2), representing bone mineral mass measured on the projected area of the bone, either at specific skeletal sites or the entire skeleton. Low aBMD values can be diagnostically indicative of possible bone mechanical fragility, with a strong correlation to fracture risk [ 3]. DXA is a non-invasive, reliable, accurate (1–2.5%), precise (0.5–1%), promptly interpretable, low-dose, low-cost, and fast X-ray imaging examination, adopted in screening patients for osteoporosis, as well as for management and follow-up of related treatments and for assessment of possible vertebral fractures via lateral view of the thoracic/lumbar spine [ 4]. The measurement principle is based on the determination of the (logarithmic) attenuation of a collimated X-ray beam in soft tissue and bone components of body tissues. Acquisitions allow the extraction of aBMD from the derivation of beam attenuation for two separate X-ray energy spectra in a tissue of thickness t (cm), assuming known energy dependent mass attenuation coefficients, μ/ ρ (cm 2/g), of soft tissue and bone components, and unknown areal density, σ = ρ· t (g/cm 2), of each tissue component (with density ρ, g/cm 3) along the direction of propagation of the X-ray beam. Determinations of beam attenuation at two separate photon energy intervals permit the derivation of the unknown areal density σ for the two model tissue components of the body [ 5]. The 3D trabecular bone microarchitecture (at the level of 2) are used to acquire n images using a continuous (unfiltered) X-ray spectrum. This will enable the solution of a system of n equations, to either improve the determination of bone and soft-tissue areal density or to perform multi-material decomposition, possibly leading to a more accurate estimation of aBMD and to a simultaneous areal density determination of soft tissue components. Future work dedicated to investigating the novel MXA technique will highlight the compared simulated performance of DXA and MXA bone density scans. We point out that while the stationary DXA4A scanner here described is intended for distal tibia and radius scanning, in the future it will be possible to extend the proposed setup to scanning other anatomical sites (e.g., femur head, lumbar vertebrae), by designing a scanning detector geometry, with the detector/tube assembly translating across the region of interest, for any wider clinical application of the proposed techniques. 6. Conclusions We presented the design of a compact device for bone densitometry, which is potentially useful in the clinic and for monitoring astronauts’ bone density during a flight mission: the DXA4A scanner. In devising a novel platform for virtual imaging and dosimetry in osteoporosis research (VIT-OSTEO), an MC simulation tool (developed by the team at JHU, USA) was implemented to optimize the device’s design and to prove the feasibility of aBMD computation with an unfiltered X-ray spectrum combined with a photon-counting detector. As a byproduct of our feasibility study via MC simulation, we designed a digital twin of the scanner which can be easily adapted to commercially available DXA scanners, therefore providing a general platform for digital twinning of bone densitometers. We developed a virtual calibration phantom based on the design of the physical European Forearm Phantom for quality assurance and calibration of the digital scanner. With the virtual DXA4A scanner, in a virtual imaging study, we obtained a bone density assessment of a virtual female patient, which was in realistic agreement with the values obtained with a clinical DXA scanner on the physical patient. Laboratory tests have been presented of the photon-counting and energy-sensitive Timepix4 CdTe detector to be used in DXA4A, showing its potential in this X-ray imaging application and the efforts to improve its spectral performance with fluorescence photon detection. Author Contributions Conceptualization, L.A.C. and P.R.; methodology, L.A.C. and P.R.; software, L.A.C., Y.L., X.J., P.S., P.M. and B.B.; validation, L.A.C.; formal analysis, L.A.C. and P.R.; investigation, L.A.C., J.Ž., B.B., P.S., L.C. and P.R.; resources, P.R., L.C. and G.M.; data curation, L.A.C.; writing—original draft preparation, L.A.C. and P.R.; writing—review and editing, L.A.C., G.M., P.R., B.B., P.S., P.M., J.Ž., S.K.B. and Y.L.; supervision P.R., B.B., P.S. and J.Ž.; funding acquisition, L.A.C., L.C., P.R. and G.M. All authors have read and agreed to the published version of the manuscript. Funding This research was supported financially by the Università di Napoli Federico II (DXA4A project), within the framework of its International Collaboration Agreement with the Institute of Experimental and Applied Physics, Czech Technical University in Prague, and its STAR (Sostegno Territoriale alle Attività di Ricerca) program, which funded the mobility of L.A.C.; by the Istituto Nazionale di Fisica Nucleare (INFN), Italy (project: Medipix4), for the development of Timepix4 detectors; and by the Scuola Superiore Meridionale, Italy (PhD School in Cosmology, Space Science and Space Technology). Institutional Review Board Statement The study adopted a digital representation of the human anatomy of the wrist derived from clinical examinations (HR-pQCT and DXA) of a volunteer originally acquired for the Calgary Bone Health Study (CaBHS), a study conducted in accordance with the Declaration of Helsinki, and approved by the University of Calgary Conjoint Health Research Ethics Board (code REB21-1976). Informed Consent Statement Written informed consent was obtained from the subject involved in the Calgary Bone Health Study (CaBHS) from which computational phantoms were derived and used in this work. Data Availability Statement The original contributions presented in this study are included in the article. Further inquiries can be directed to the corresponding author. Clinical patient data access is restricted by ethical reasons. Acknowledgments The Timepix4 photon-counting detectors have been developed within the Medipix4 Collaboration based at CERN ( https://medipix.web.cern.ch/medipix4) (accessed on 3 May 2026). Conflicts of Interest The authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results. Abbreviations The following abbreviations are used in this manuscript: DXA Dual-Energy X-Ray Absorptiometry aBMD Areal Bone Mineral Density BMD Bone Mineral Density EFP European Forearm Phantom GPU Graphics Processing Unit HR-pQCT High-Resolution Peripheral Quantitative Computed Tomography IAEA International Atomic Energy Agency IEAP Institute of Experimental and Applied Physics INFN Istituto Nazionale di Fisica Nucleare LE Low Energy MC Monte Carlo NIST National Institute of Standards and Technology 3D Three-Dimensional QCT Quantitative Computed Tomography SSM Scuola Superiore Meridionale UD Ultradistal UNINA Università degli studi di Napoli Federico II UWB University of West Bohemia References Morin, S.N.; Leslie, W.D.; Schousboe, J.T. Osteoporosis: A Review. JAMA 2025, 334, 894–907. [ Google Scholar] [ CrossRef] Chen, M.; Gerges, M.; Raynor, W.Y.; Park, P.S.U.; Nguyen, E.; Chan, D.H.; Ali Gholamrezanezhad, A. State of the Art Imaging of Osteoporosis. Semin. Nucl. 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Design of a Novel DXA Scanner with a CdTe Photon-Counting Timepix4 Detector for Peripheral Bone Densitometry
