Lucy Whitmore

All Publications

• Volumetric FLASH dosimetryin vivousing real-time radiacoustic imaging. Physics in medicine and biology Bjegovic, K., Whitmore, L., Pandey, P. K., Sun, L., Connell, L., Xu, Y., Aguilar, E. A., Velasquez, B. D., Schüler, E., Xiang, S. L. 2026; 71 (13)

  Abstract

  Objective.The main goal of this research is to verify the spatial fidelity of radiacoustic imaging (RAI) as a quantitative dosimetric monitoring tool for FLASH radiotherapy (FLASH-RT)in vivo. FLASH-RT delivers therapeutic radiation at ultra-high instantaneous dose rates (>106Gy s-1), offering substantial reductions in normal tissue toxicity while maintaining tumor control. However, clinical translation remains limited by the absence of real-time,in vivodosimetry systems capable of resolving dose delivery at microsecond timescales.Approach.Here, we present an RAI platform that enables volumetric, single-pulse mapping of radiation dose deposition during FLASH-RTin vivo. The system utilizes a 16 × 16 ultrasound transducer matrix array with a model-based reconstruction algorithm to generate quantitative, three-dimensional dose maps with single pulse-level temporal resolution.Main results.In both water phantoms andin vivomurine models, RAI demonstrates high concordance with film dosimetry and TOPAS Monte Carlo simulations (3%/3 mm gamma index pass rates greater than 90% for small fields).Significance.This work establishes RAI as a viable technology for real-time, quantitative electron FLASH dosimetryin vivofor the first time, with the potential to support adaptive delivery, improve treatment safety, and facilitate the clinical translation of FLASH-RT.

  View details for DOI 10.1088/1361-6560/ae7e38

  View details for PubMedID 42302829

• FLASH reduces radiation-induced oral mucositis in a mouse model of Fanconi anemia. bioRxiv : the preprint server for biology Loo, P., Pan, M., Zhao, M., Melemenidis, S., Chen, D., Whitmore, L., Richter, S., Dirbas, F. M., Casey, K. M., Graves, E. E., Epperly, M. W., Greenberger, J., Loo, B. W., Rankin, E. B. 2026

  Abstract

  Patients with Fanconi anemia (FA) are particularly susceptible to developing squamous cell carcinoma of the head and neck due to impaired DNA repair pathways. However, their hypersensitivity to DNA damaging agents can limit effective treatment with standard radiotherapy due to severe side effects and complications. In pre-clinical models, ultra-rapid FLASH radiotherapy (FLASH) reduces radiation-induced toxicity in normal tissues while maintaining similar tumor control compared to conventional dose rate radiotherapy (CONV). Here, we investigated the safety of FLASH for treatment of the head and neck in a mouse model of FA. 129/Sv wild-type (WT) and Fanca-deficient (Fanca -/-) mice received single-dose oral cavity irradiation with electron beam FLASH or CONV to evaluate radiation-induced toxicity in non-tumor-bearing mice. Fanca WT and Fanca -/- mice were irradiated with 25 and 18 Gy, respectively, of FLASH (190 Gy/sec) or CONV (0.2 Gy/sec), with tongues harvested at 12 hours (hpi) and 10 days (dpi) post-irradiation. At 10 dpi, FLASH-irradiated tongues in both genetic backgrounds demonstrated reduced ulceration at the dorsal tongue surface compared to CONV-irradiated counterparts. Histopathological analysis of the tongue revealed lower mucositis severity scores with decreased epithelial thinning and ulceration in FLASH-irradiated tongues compared to CONV-irradiated ones. Analysis of γ-H2AX foci formation at 12 hpi demonstrated fewer foci in WT mice treated with FLASH compared to CONV, with a similar trend observed in Fanca -/- mice. These findings suggest a potential normal tissue-sparing effect with FLASH and hold important clinical implications for the treatment of patients with Fanconi anemia and head and neck cancers.

  View details for DOI 10.64898/2026.05.25.727748

  View details for PubMedID 42244584

  View details for PubMedCentralID PMC13232302

• A Physics-Informed Neural Network for In Vivo Dosimetry Using Quantitative Radiacoustic Imaging. Research square Sun, L., Bjegovic, K., Rodriguez-Gonzalez, L., Xu, Y., Yan, Y., Gonzalez, G., Whitmore, L., Connell, L., Lang, Y., Pandey, P., Ren, L., Sch Ler, E., Chen, Y., Xiang, S. 2026

  Abstract

  Accurate dosimetry is critical for safe and effective radiotherapy, yet no clinical method currently measures dose directly within the patient in vivo. Radiacoustic imaging (RAI), which detects acoustic waves generated by thermoelastic expansion during radiation delivery, offers a promising solution but has been limited to qualitative output. We present a quantitative RAI (qRAI) framework powered by a physics-informed neural network (PINN) that reconstructs quantitative dose maps in vivo. The PINN incorporates the physics of acoustic wave generation and propagation, along with a digital twin of the radiation delivery and radiacoustic detection systems, enabling accurate reconstruction from limited-view data. Reconstructed pressure maps are calibrated against experimental and simulated dose references. We validate the method across diverse clinical scenarios, including water tank dosimetry, human torso phantoms, and FLASH electron therapy. Compared to purely data-driven models, our PINN approach offers superior robustness and generalizability, especially in clinical settings lacking experimental ground truth. These results establish PINN-based qRAI as a powerful tool for real-time, adaptive, and quantitative in vivo dosimetry.

  View details for DOI 10.21203/rs.3.rs-8503498/v1

  View details for PubMedID 41646377

  View details for PubMedCentralID PMC12869649

• Very high-energy electrons as radiotherapy opportunity EUROPEAN PHYSICAL JOURNAL PLUS Fischer, J., Whitmore, L., Desrosiers, C., Sheehy, S., Bazalova-Carter, M. 2024; 139 (8)

  View details for DOI 10.1140/epjp/s13360-024-05455-x

  View details for Web of Science ID 001290255200006

• CERN-based experiments and Monte-Carlo studies on focused dose delivery with very high energy electron (VHEE) beams for radiotherapy applications. Scientific reports Whitmore, L., Mackay, R. I., van Herk, M., Korysko, P., Farabolini, W., Malyzhenkov, A., Corsini, R., Jones, R. M. 2024; 14 (1): 11120

  Abstract

  Very High Energy Electron (VHEE) beams are a promising alternative to conventional radiotherapy due to their highly penetrating nature and their applicability as a modality for FLASH (ultra-high dose-rate) radiotherapy. The dose distributions due to VHEE need to be optimised; one option is through the use of quadrupole magnets to focus the beam, reducing the dose to healthy tissue and allowing for targeted dose delivery at conventional or FLASH dose-rates. This paper presents an in depth exploration of the focusing achievable at the current CLEAR (CERN Linear Electron Accelerator for Research) facility, for beam energies >200 MeV. A shorter, more optimal quadrupole setup was also investigated using the TOPAS code in Monte Carlo simulations, with dimensions and beam parameters more appropriate to a clinical situation. This work provides insight into how a focused VHEE radiotherapy beam delivery system might be achieved.

  View details for DOI 10.1038/s41598-024-60997-5

  View details for PubMedID 38750131

  View details for PubMedCentralID PMC11096185

• Focused VHEE (very high energy electron) beams and dose delivery for radiotherapy applications. Scientific reports Whitmore, L., Mackay, R. I., van Herk, M., Jones, J. K., Jones, R. M. 2021; 11 (1): 14013

  Abstract

  This paper presents the first demonstration of deeply penetrating dose delivery using focused very high energy electron (VHEE) beams using quadrupole magnets in Monte Carlo simulations. We show that the focal point is readily modified by linearly changing the quadrupole magnet strength only. We also present a weighted sum of focused electron beams to form a spread-out electron peak (SOEP) over a target region. This has a significantly reduced entrance dose compared to a proton-based spread-out Bragg peak (SOBP). Very high energy electron (VHEE) beams are an exciting prospect in external beam radiotherapy. VHEEs are less sensitive to inhomogeneities than proton and photon beams, have a deep dose reach and could potentially be used to deliver FLASH radiotherapy. The dose distributions of unfocused VHEE produce high entrance and exit doses compared to other radiotherapy modalities unless focusing is employed, and in this case the entrance dose is considerably improved over existing radiations. We have investigated both symmetric and asymmetric focusing as well as focusing with a range of beam energies.

  View details for DOI 10.1038/s41598-021-93276-8

  View details for PubMedID 34234203

  View details for PubMedCentralID PMC8263594