X-ray Vision Research Articles

Enabling three-dimensional real-space analysis of ionic colloidal crystallization.

Structures of molecular crystals are identified using scattering techniques because we cannot see inside them. Micrometre-sized colloidal particles enable the real-time observation of crystallization with optical microscopy, but in practice this is still hampered by a lack of 'X-ray vision'. Here we introduce a system of index-matched fluorescently labelled colloidal particles and demonstrate the robust formation of ionic crystals in aqueous solution, with structures that can be controlled by size ratio and salt concentration. Full three-dimensional coordinates of particles are distinguished through in situ confocal microscopy, and the crystal structures are identified via comparison of their simulated scattering pattern with known atomic arrangements. Finally, we leverage our ability to look inside colloidal crystals to observe the motion of defects and crystal melting in time and space and to reveal the origin of crystal twinning. Using this platform, the path to real-time analysis of ionic colloidal crystallization is now 'crystal clear'.

Abstract CT140: A phase 1 study of the IAP inhibitor xevinapant (Debio 1143) to evaluate food effect and drug-drug interactions with a proton pump inhibitor in healthy volunteers

Abstract INTRODUCTION: Xevinapant is an oral IAP (inhibitor of apoptosis protein) inhibitor designed to restore cancer cell sensitivity to apoptosis, thereby enhancing the efficacy of chemoradiotherapy (CRT) and radiotherapy (RT). Xevinapant 200 mg/d (d1-14, Q3W) + CRT showed clinical benefit vs placebo + CRT in a phase 2 study of patients with locally advanced squamous cell carcinoma of the head and neck (LA SCCHN; NCT02022098). Two phase 3 studies are currently ongoing evaluating xevinapant in combination with CRT (TrilynX; NCT04459715) or RT (XRay Vision; NCT05386550) in patients with LA SCCHN, with dosing under fasting conditions or without regard to food, respectively. METHODS: A 2-stage study (Debio 1143-107) was conducted to assess the effect of food on 2 different formulations of xevinapant and the effect of co-administration with the proton pump inhibitor pantoprazole to evaluate the effect of high gastric pH on bioavailability of xevinapant. Stage 1 was an open-label, randomized, 4-arm, crossover study with 26 healthy volunteers (HV) treated with a single oral dose of xevinapant 200 mg in fasted or fed (high-fat diet) conditions with 2 different formulations. Stage 2 was a randomized, 2-way crossover study with 12 HV treated with a single oral dose of xevinapant 200 mg with or without pantoprazole. Pharmacokinetics (PK) and pharmacodynamics (PD) samples (Ciap1 levels in peripheral blood mononuclear cells [PBMCs]) were collected over 72 h post dose. The utilization of HV to address clinical pharmacology aspects of xevinapant was justified by holistic assessment of the toxicology, safety, and pharmacology profiles. RESULTS: Following a single dose of xevinapant 200 mg, exposures in HV under fasted conditions were consistent with those observed previously in cancer patients. Xevinapant formulations were bioequivalent and were considered safe and well tolerated in both fasted and fed conditions. Food delayed Tmax and decreased xevinapant Cmax by 39% but did not meaningfully alter the extent of absorption of xevinapant, as evidenced by no change in AUC, which is the most relevant exposure metric for efficacy based on xevinapant’s mechanism of action. Stage 2 data indicated that the PK of xevinapant was not affected by treatment with pantoprazole. Ciap1 levels in PBMCs decreased at least 4-fold compared to the baseline for all treatments and were reduced up to 72 h post single dose. No relevant differences in PD were observed across treatments. PK simulations indicated no relevant change in AUC and no impact on target engagement at steady state with food. CONCLUSION: These data indicate that xevinapant can be administered without regard to food or gastric acid reducing agents, which would be advantageous for patient convenience and compliance. Citation Format: Valérie Nicolas-Métral, Elisabeth Rouits, Camille Riff, Dany Spaggiari, Norbert Wiedemann, Pierre Colin, Eleanor Harrison-Moench, Rafael Crabbé, Heidi Nauwelaerts, Andreas Schroeder, Carolina Haefliger, Yulia Vugmeyster. A phase 1 study of the IAP inhibitor xevinapant (Debio 1143) to evaluate food effect and drug-drug interactions with a proton pump inhibitor in healthy volunteers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT140.

NeXtFusion: Attention-Based Camera-Radar Fusion Network for Improved Three-Dimensional Object Detection and Tracking

Accurate perception is crucial for autonomous vehicles (AVs) to navigate safely, especially in adverse weather and lighting conditions where single-sensor networks (e.g., cameras or radar) struggle with reduced maneuverability and unrecognizable targets. Deep Camera-Radar fusion neural networks offer a promising solution for reliable AV perception under any weather and lighting conditions. Cameras provide rich semantic information, while radars act like an X-ray vision, piercing through fog and darkness. This work proposes a novel, efficient Camera-Radar fusion network called NeXtFusion for robust AV perception with an improvement in object detection accuracy and tracking. Our proposed approach of utilizing an attention module enhances crucial feature representation for object detection while minimizing information loss from multi-modal data. Extensive experiments on the challenging nuScenes dataset demonstrate NeXtFusion’s superior performance in detecting small and distant objects compared to other methods. Notably, NeXtFusion achieves the highest mAP score (0.473) on the nuScenes validation set, outperforming competitors like OFT (35.1% improvement) and MonoDIS (9.5% improvement). Additionally, NeXtFusion demonstrates strong performance in other metrics like mATE (0.449) and mAOE (0.534), highlighting its overall effectiveness in 3D object detection. Furthermore, visualizations of nuScenes data processed by NeXtFusion further demonstrate its capability to handle diverse real-world scenarios. These results suggest that NeXtFusion is a promising deep fusion network for improving AV perception and safety for autonomous driving.

XRay Vision: A Phase 3 Study of Xevinapant Plus Radiotherapy (RT) for High-risk, Cisplatin-ineligible Patients with Resected, Locally Advanced Squamous Cell Carcinoma of the Head and Neck (LA SCCHN)

XRay Vision: A Phase 3 Study of Xevinapant Plus Radiotherapy (RT) for High-risk, Cisplatin-ineligible Patients with Resected, Locally Advanced Squamous Cell Carcinoma of the Head and Neck (LA SCCHN)

Xevinapant plus radiotherapy in resected, high-risk, cisplatin-ineligible LA SCCHN: the phase III XRay Vision study design.

There is a significant unmet need and lack of treatment options for patients with resected, high-risk, cisplatin-ineligible locally advanced squamous cell carcinoma of the head and neck (LA SCCHN). Xevinapant, a first-in-class, potent, oral, small-molecule IAP inhibitor, is thought to restore cancer cell sensitivity to chemotherapy and radiotherapy in clinical and preclinical studies. We describe the design of XRay Vision (NCT05386550), an international, randomized, double-blind, phase III study. Approximately 700 patients with resected, high-risk, cisplatin-ineligible LA SCCHN will be randomized 1:1 to receive 6 cycles of xevinapant or placebo, in combination with radiotherapy for the first 3 cycles. The primary end point is disease-free survival, and secondary end points include overall survival, health-related quality of life, and safety.

Visualizing indoor layout for spatial learning using Mixed Reality-based X-ray vision

Visualizing indoor layout for spatial learning using Mixed Reality-based X-ray vision

XRay Vision: A phase 3 study of xevinapant plus radiotherapy (RT) for high-risk, cisplatin-ineligible patients with resected, locally advanced squamous cell carcinoma of the head and neck (LA SCCHN).

TPS6101 Background: The current standard of care for patients with resected LA SCCHN who are at high-risk of disease recurrence and are cisplatin eligible is chemoradiotherapy (CRT; cisplatin + RT). For patients at high risk of disease recurrence who cannot receive cisplatin, treatment options are limited, and there is currently no treatment specifically recommended by international guidelines. Xevinapant is a first-in-class, small-molecule IAP (inhibitor of apoptosis protein) inhibitor that has been shown to restore cancer cell sensitivity to apoptosis, thereby enhancing the effects of chemotherapy and RT. In a randomized phase 2 study in patients with unresected LA SCCHN, treatment with xevinapant + CRT was associated with a 53% lower risk of death after 5 years of follow-up and reduced the risk of death or disease progression by 67% after 3 years of follow-up vs placebo + CRT. In preclinical SCCHN models, xevinapant + RT alone also demonstrated antitumor activity. These promising clinical and preclinical data provide a strong rationale for combining xevinapant and RT in cisplatin-ineligible patients with LA SCCHN. Methods: XRay Vision (NCT05386550) is a randomized, double-blind, placebo-controlled, phase 3 study comparing xevinapant or placebo in combination with intensity-modulated RT (IMRT) in patients with resected LA SCCHN who are ineligible for cisplatin and have a high risk of relapse. Eligible patients must have histologically confirmed cancer of the oral cavity, oropharynx, hypopharynx, or larynx; undergone surgery with curative intent 4 to 8 weeks before the start of treatment; high risk of relapse; no residual disease by computed tomography scan; and ineligible for cisplatin (meeting ≥1 of the following criteria: estimated glomerular filtration rate <60 mL/min/1.73 m2; hearing loss [grade ≥2 audiometric hearing loss or grade ≥2 tinnitus]; grade ≥2 peripheral neuropathy; and if aged ≥70 years old, unfit according to the G8 questionnaire [score ≤14]). Other eligibility criteria include ECOG performance status of 0 or 1 and adequate hematologic and hepatic function. Approximately 700 eligible patients will be randomized to oral xevinapant (200 mg/day on days 1-14 of a 3-week cycle) or placebo for 3 cycles + standard fractionation IMRT (66 Gy in 33 fractions, 2 Gy per fraction, 5 days per week) followed by 3 cycles of xevinapant or placebo. The primary endpoint is disease-free survival. Secondary endpoints include overall survival, time to subsequent cancer treatments, safety, and health-related quality of life. Patients will be followed up for a minimum of 60 months. Enrollment is planned in 27 countries, including the US, and countries in South America, Europe, and Asia. The study started in October 2022, and recruitment is ongoing. Clinical trial information: NCT05386550 .

Leveraging the mechanism of action (MOA) of xevinapant, an IAP inhibitor, for phase 3 dosing (RP3D) strategies in combination with radiation (RT) and chemoradiotherapy (CRT) in patients with locally advanced squamous cell carcinoma of the head and neck (LA SCCHN).

e18001 Background: Xevinapant is a first-in-class, oral IAP (inhibitor of apoptosis protein) inhibitor designed to restore cancer cell sensitivity to apoptosis, thereby enhancing the efficacy of RT and CRT. Xevinapant 200 mg/d (d1-14, Q3W) + CRT showed clinical benefit vs placebo + CRT in a phase (ph) 2 study of patients (pts) with LA SCCHN (NCT02022098). Exposure-response (E-R) relationships for efficacy and the composite safety endpoint of “mucositis and/or dysphagia” (AE_MD, a known RT-associated toxicity) were also identified. Two ph 3 studies of 200 mg/d xevinapant (d1-14, Q3W) + RT (XRay Vision; NCT05386550) or CRT (TrilynX; NCT04459715) followed by xevinapant monotherapy (MT) in pts with LA SCCHN are ongoing. We leverage the MOA of xevinapant to confirm RP3D strategy. Methods: Results from clinical and preclinical studies and quantitative pharmacology modeling were integrated. Results: Updated analyses of NCT02022098 data show an association between complete response (CR) and AE_MD in both treatment arms; AE_MD was the only AE with identified E-R relationship out of 13 AEs tested. In the xevinapant arm, the CR+AE_MD+ group had the highest median AUC but it overlapped with other groups (CR-AE_MD+, CR+AE_MD-, CR-AE_MD-) which all had similar AUCs. These data suggest that AE_MD is related to the RT-enhancing MOA of xevinapant and that decoupling efficacy from AE_MD incidence by exposure modulation is not feasible. Intermittent dosing for xevinapant was designed for recovery from epithelial toxicities considering the turnover of mucosal cells. In a human breast cancer mouse model, cIAP1 degradation with the intermittent regimen (100 mg/kg Q3D) at the end of the dosing interval was ~50% compared with the continuous one (30 mg/kg QD) expected to maintain maximal (max) cIAP1 degradation, but showed similar efficacy. This suggests continuous max cIAP1 degradation may not be required for efficacy, consistent with RT-enhancing MOA. Based on population PKPD modeling, at the RP3D for xevinapant max cIAP1 degradation was achieved during the dosing period; 91% of pts had at least 50% suppression at the end of the cycle. Xevinapant MT cycles are supported by enhanced anti-tumor activity with extended MT dosing following xevinapant/ RT cycles in MC38 syngeneic mouse model. Food-agnostic dosing is supported by similar AUCs observed in fed and fasted conditions. A human ADME study showed that urinary excretion is a minor elimination pathway, supporting no dose adjustment for pts with moderate renal impairment. Conclusions: Integrated assessment of all available clinical and nonclinical data supports the proposed RP3D strategy for xevinapant combined with RT or CRT, selected to maximize efficacy while minimizing potential adverse events and cumulative toxicity. Clinical trial information: NCT02022098 .

Effect of extended treatment with IAP inhibitor xevinapant post radiotherapy (RT) on efficacy and the tumor microenvironment (TME) in preclinical models.

6027 Background: Xevinapant is a first-in-class, oral IAP (inhibitor of apoptosis protein) inhibitor designed to restore cancer cell sensitivity to apoptosis, induced by RT and chemotherapy, and enhance antitumor immunity. In a randomized phase 2 study of patients with unresected locally advanced squamous cell carcinoma of the head and neck, xevinapant + chemoradiotherapy (CRT) significantly improved 18-month locoregional control and improved 3-year progression-free survival and 5-year overall survival vs placebo + CRT. A phase 3 confirmatory study (TrilynX NCT04459715) and a phase 3 study to evaluate xevinapant + RT in post-operative, high-risk, cisplatin-ineligible patients (XRay Vision NCT05386550) are ongoing. In these studies, we investigate 3 additional cycles of xevinapant or placebo monotherapy after completing combination treatment. Based on the role of IAPs in apoptosis, immunity, and stromal activation, continual dosing of xevinapant post RT may have additional therapeutic benefits. Methods: MC38 syngeneic tumor-bearing mice were treated with vehicle control, RT alone (3.6Gy once daily [QD], 5 days), or RT + xevinapant (100 mg/kg QD, 1, 2, or 4 weeks). To assess treatment-mediated TME modulation, immune cells in tumors were evaluated by fluorescence-activated cell sorting (FACS)–based immunophenotyping, and tumor-specific T cell responses were investigated by enzyme-linked immunosorbent spot (ELISpot) assays. To understand the effect of xevinapant on RT-induced cancer associated fibroblast (CAF) activation, CAF gene expression was profiled on cell lines and patient-derived primary cultures. Results: Xevinapant + RT increased antitumor efficacy compared with vehicle control or RT alone. Moreover, RT in combination with extended dosing of xevinapant for 4 weeks significantly improved therapeutic efficacy and prolonged survival compared with RT + shorter xevinapant dosing durations. FACS analysis demonstrated trends of increased numbers of CD8+ T cells, natural killer cells, and dendritic cells and decreased numbers of regulatory T cells in mice treated with xevinapant + RT. FACS and ELISpot further suggested an increase in antigen-specific T cell counts from baseline with combination therapy arm vs vehicle control or RT alone. Xevinapant may also suppress RT-mediated CAF activation, as indicated by downregulation of activation markers and CAF-derived secretory proteins. Conclusions: In preclinical models, extended dosing of xevinapant for 4 weeks post RT improved antitumor efficacy. Our data suggest that the effect may be, in part, modulated by TME responses, including enhanced antitumor immunity and suppressed pro-tumorigenic phenotype of CAFs. Based on these results, further evaluation is warranted to determine the mechanisms that underscore the therapeutic benefit offered by extended dosing of xevinapant.

CONCEPTUAL METAPHORS IN AUGMENTED REALITY PROJECTS

Purpose. The objective of this study is to conduct a semiotic analysis of augmented reality projects, with the aim of establishing patterns and identifying the most common conceptual metaphors. The study seeks to determine the impact of these metaphors on functional and symbolic form.
 Methodology. To achieve the research goal, the visual materials were subjected to visual-analytical, formal, functional, and semiotic analysis methods.
 Results. The present study identified the eight most common metaphors used in AR project design, namely the magic mirror, false window, active print, X-ray vision, geo-layer, aquarium, visor, and flashlight. The impact of these metaphors on the functional-figurative form can vary depending on the metaphor chosen, and may set more blurred or specific boundaries. It was found that metaphors differ not only in their figurative-semantic differences, but also in the viewer’s position regarding representation, the type of first or third-person view, the impact on the imagery of the content, and the nature of interaction with space. While most metaphors benefit from the use of three-dimensional graphics, some, such as mirrors, active print, and sights, can use two-dimensional graphics without depriving AR of the feeling of naturalness. One technique for playing with metaphors is to go beyond conventional boundaries and manipulate space. The study also revealed that AR based on video mixing more frequently uses metaphors than optical mixing, which can directly merge with the environment. It was demonstrated that using the same metaphor does not limit the creative potential in solving tasks, and leaves the designer sufficient space for maneuvering and the possibility of both literal and formal following of the metaphor. Overall, the findings of this study contribute to a better understanding of the role of metaphors in AR project design and provide insights for designers to effectively use metaphors to enhance user experience.
 Scientific novelty. An analysis of augmented reality (AR) projects was conducted with the aim of identifying conceptual metaphors. A synthesis of these conceptual metaphors was performed, followed by a typology-based classification of the AR projects grounded in the identified metaphors.
 Practical significance. The findings of this research contribute to the theoretical foundation of designing AR products by providing a framework for representing AR design concepts. The identified metaphors can be utilized as a guide for designers to develop effective AR interfaces.

An empirical evaluation of enhanced teleportation for navigating large urban immersive virtual environments

Navigation is the most prevalent interaction in large urban virtual environments (VEs). Any Metaverse application that foresees navigating or exploring virtual cities requires an effective and efficient navigation technique. These environments, however, have distinct characteristics that make the navigation more challenging and the design of the interactions more critical. We have conducted an empirical study to assess how enhancing the teleportation technique with additional capabilities affects the performance of navigating large urban VEs. For this purpose, three interactions have been developed that extend the conventional point-and-click teleportation. The first one is named Mini-Map and provides a top-down view of the user’s surroundings. Portal Preview provides a preview of the selected target location and allows users to choose their desired orientation at that location. The last technique, called X-Ray Vision, makes the buildings around the user translucent and allows teleporting to locations that would otherwise be obscured. A within-subject controlled lab study with twenty five participants has been conducted, where each extension is evaluated individually as well as in combination with others. Our results show that extending the teleportation can significantly improve its performance when navigating large urban VEs. Overall, the X-Ray Vision was the most successful extension with respect to both task metrics and usability measures. Mini-Map was able to improve some of the task metrics, but did not have a significant effect on most self-reported measures. Portal Preview was the least effective extension, however, multiple participants liked the fact that they could define their desired orientation with the controller. Combining all interactions together performed well with respect to the task metrics, but this option was not favored by the participants. Extending the teleportation with X-Ray Vision and Mini-Map was by far the most favored option.

Gravitational Waves—A New Window on the Universe

Imagine you could choose a new set of eyes that would help you see things you have never been able to see before. Maybe you would choose Superman’s X-ray vision, or maybe you would prefer to zoom into tiny things and see the wonders of the microscopic world. Science has recently gained a new set of eyes—a new way to look into the mysteries of the universe—using gravitational waves, which are waves produced by gravity itself. In this article, I will take you on a journey that begins with an explanation of gravity—from the classical perspective of Isaac Newton to the modern and more complex view of Albert Einstein. I will then explain how movements of massive objects create gravitational waves, which are ripples in space and time, and how they might be used to explain some mysteries of the universe, and even help us to understand the origins of our planet Earth.

X-ray vision of Cu(In,Ga)Se2: from the Ga/In ratio to solar-cell performance

Cost efficiency and defect passivation are the two major challenges that thin-film solar cells have to overcome for economic competitiveness. For Cu(In,Ga)Se solar cells, the first is addressed by an increase of the Ga/In ratio, which widens the bandgap favorably for tandem applications and reduces the requirement of costly, rare In. The second is addressed by heavy alkali post-deposition treatments. However, the maximum device efficiency is typically achieved with a comparably low Ga/In ratio, which is in contrast to the economic interest of a higher Ga/In ratio and makes it paramount to identify, understand and mitigate the sources of local underperformance in Ga-rich cells. In this work, we investigate a series of Cu(In,Ga)Se cells with varying Ga/In concentration in the absorber, using multi-modal scanning x-ray microscopy. In particular, we analyze differences in chemical composition and electrical performance on the nanoscale, with a focus on the effect of Rb. We find that In-rich cells show, along with a greater overall performance, a more homogeneous distribution of the nanoscale performance compared to the Ga-rich cells. Our analysis on Rb suggests that this effect is due to a more effective passivation of structural defects in the absorbers, i.e. voids and grain boundaries. These results shine light on the causes of the superiority of Ga-poor/In-rich absorbers and substantiate the trend to higher defect density for Ga-rich absorbers.

Transmission Mysteries: Art and Technophilia

Transmission Mysteries: Art and Technophilia

Rapture

Rapture

X-Ray Vision during Iodine-125 Plaque Radiation Treatment of a Choroidal Melanoma

X-Ray Vision during Iodine-125 Plaque Radiation Treatment of a Choroidal Melanoma

Hilma af Klint and the Need for Historical Revision

Hilma af Klint and the Need for Historical Revision

Augmented Reality for Head and Neck Carcinoma Imaging: Description and Feasibility of an Instant Calibration, Markerless Approach

Background and Objective: Augmented reality (AR) can help to overcome current limitations in computer assisted head and neck surgery by granting “X-ray vision” to physicians. Still, the acceptance of AR in clinical applications is limited by technical and clinical challenges. We aim to demonstrate the benefit of a marker-free, instant calibration AR system for head and neck cancer imaging, which we hypothesize to be acceptable and practical for clinical use.Methods: We implemented a novel AR system for visualization of medical image data registered with the head or face of the patient prior to intervention. Our system allows the localization of head and neck carcinoma in relation to the outer anatomy. Our system does not require markers or stationary infrastructure, provides instant calibration and allows 2D and 3D multi-modal visualization for head and neck surgery planning via an AR head-mounted display. We evaluated our system in a pre-clinical user study with eleven medical experts.Results: Medical experts rated our application with a system usability scale score of 74.8 ± 15.9, which signifies above average, good usability and clinical acceptance. An average of 12.7 ± 6.6 minutes of training time was needed by physicians, before they were able to navigate the application without assistance.Conclusions: Our AR system is characterized by a slim and easy setup, short training time and high usability and acceptance. Therefore, it presents a promising, novel tool for visualizing head and neck cancer imaging and pre-surgical localization of target structures.

Photoacoustic imaging for surgical guidance: Principles, applications, and outlook.

Minimally invasive surgeries often require complicated maneuvers and delicate hand–eye coordination and ideally would incorporate “x-ray vision” to see beyond tool tips and underneath tissues prior to making incisions. Photoacoustic imaging has the potential to offer this feature but not with ionizing x-rays. Instead, optical fibers and acoustic receivers enable photoacoustic sensing of major structures—such as blood vessels and nerves—that are otherwise hidden from view. This imaging process is initiated by transmitting laser pulses that illuminate regions of interest, causing thermal expansion and the generation of sound waves that are detectable with conventional ultrasound transducers. The recorded signals are then converted to images through the beamforming process. Photoacoustic imaging may be implemented to both target and avoid blood-rich surgical contents (and in some cases simultaneously or independently visualize optical fiber tips or metallic surgical tool tips) in order to prevent accidental injury and assist device operators during minimally invasive surgeries and interventional procedures. Novel light delivery systems, counterintuitive findings, and robotic integration methods introduced by the Photoacoustic & Ultrasonic Systems Engineering Lab are summarized in this invited Perspective, setting the foundation and rationale for the subsequent discussion of the author’s views on possible future directions for this exciting frontier known as photoacoustic-guided surgery.

The all-seeing baggage scanner

SOME YEARS AGO, the three of us found ourselves together in a very long security line at Reagan National Airport in Washington, D.C. Maybe, we joked, Superman could use his X-ray vision to help out the beleaguered Transportation Security Administration (TSA) employees and the traveling masses.