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Magnetic Resonance Imaging (MRI) to Assess Changes to Trabecular Microarchitecture (Trb µArch) of the Hip

BACKGROUND . Calculated loss rates in trabecular (Trb) volumetric bone mineral density (vBMD), in astronauts after return from 6-month long-duration (LD) spaceflight, are rapid relative to menopause-induced loss rates and could contribute to the observed lack of recovery. Perforations in the Trb bony struts, skeletal fragility and fractures [5] have been associated with the rapid rate of bone loss in women due to menopause. The more rapid loss rate observed in astronauts could be inducing similar, irreversible losses of trabecular connectivity as seen in cadaver studies of female skeletons. These changes are not detectable by DXA technology and would not be discovered in astronauts during scheduled, triennial DXA testing for primary osteoporosis. High-resolution-peripheral quantitative computed tomography (HR-pQCT) of the lower leg have detected losses in Trb vBMD (vBMD) and changes in Trb microarchitecture (µArch) in astronauts immediately following routine 6-month spaceflights and continuing in some individuals for 1 or more years postflight with no signs of recovery. Resolution of these microarchitectural changes by whole body QCT, especially in the deeply embedded hip bone, is prohibitive due to excessive and unsafe radiation exposures. While HR-pQCT has sufficient resolution to study Trb µArch at safe and lower radiation exposure testing is restricted only to the lower leg and wrist. Hence, a technology to detect detrimental changes to Trb µArch in astronauts, especially of the hip, is needed to inform type and timing of countermeasures to irreversible deficits (preflight, inflight and postflight). METHODS . This HRP-funded study (2023-2027) will verify the sensitivity of a protocol for MRI scanning (on a 3T Siemens Vida) to detect changes to hip Trb µArch in persons following spinal cord injury (SCI); skeletal immobilization below the spinal lesion will serve as an analog for non-weight-bearing during spaceflight. The study period has been extended by 1 yr due to delayed Richmond IRB approval in Y1. A 3T MRI protocol will characterize serial changes in hip Trb µArch in SCI patients from time of admission at the Richmond VA Medical Center to their scheduled annual exam 12-months later. SCI patients with age, sex, and physical characteristics like ISS astronauts will be consented. The ability of 3T MRI hip scan to discriminate loss of trabecular connectivity subjects with SCI will be compared to age- and sex-matched ambulatory controls. A comparison between HR-pQCT and MRI measurements at the ankle (distal tibia) of study subjects will also be performed. A modified DXA scan analysis (3D-Shaper) will also be verified as a potential method for monitoring concurrent changes in hip Trb bone over 12-month. SIGNIFICANCE . Deliverables: a surveillance method for assessing for irreversible losses of connectivity and how skeletal changes after LD spaceflight(s) would modify the terrestrial risk of primary osteoporosis.

Risk Surveillance↗

Development and validation of a 30-day mortality index based on pre-existing medical administrative data from 13,323 COVID-19 patients: The Veterans Health Administration COVID-19 (VACO) Index

Background Available COVID-19 mortality indices are limited to acute inpatient data. Using nationwide medical administrative data available prior to SARS-CoV-2 infection from the US Veterans Health Administration (VA), we developed the VA COVID-19 (VACO) 30-day mortality index and validated the index in two independent, prospective samples. Methods and findings We reviewed SARS-CoV-2 testing results within the VA between February 8 and August 18, 2020. The sample was split into a development cohort (test positive between March 2 and April 15, 2020), an early validation cohort (test positive between April 16 and May 18, 2020), and a late validation cohort (test positive between May 19 and July 19, 2020). Our logistic regression model in the development cohort considered demographics (age, sex, race/ethnicity), and pre-existing medical conditions and the Charlson Comorbidity Index (CCI) derived from ICD-10 diagnosis codes. Weights were fixed to create the VACO Index that was then validated by comparing area under receiver operating characteristic curves (AUC) in the early and late validation cohorts and among important validation cohort subgroups defined by sex, race/ethnicity, and geographic region. We also evaluated calibration curves and the range of predictions generated within age categories. 13,323 individuals tested positive for SARS-CoV-2 (median age: 63 years; 91% male; 42% non-Hispanic Black). We observed 480/3,681 (13%) deaths in development, 253/2,151 (12%) deaths in the early validation cohort, and 403/7,491 (5%) deaths in the late validation cohort. Age, multimorbidity described with CCI, and a history of myocardial infarction or peripheral vascular disease were independently associated with mortality–no other individual comorbid diagnosis provided additional information. The VACO Index discriminated mortality in development (AUC = 0.79, 95% CI: 0.77–0.81), and in early (AUC = 0.81 95% CI: 0.78–0.83) and late (AUC = 0.84, 95% CI: 0.78–0.86) validation. The VACO Index allows personalized estimates of 30-day mortality after COVID-19 infection. For example, among those aged 60–64 years, overall mortality was estimated at 9% (95% CI: 6–11%). The Index further discriminated risk in this age stratum from 4% (95% CI: 3–7%) to 21% (95% CI: 12–31%), depending on sex and comorbid disease. Conclusion Prior to infection, demographics and comorbid conditions can discriminate COVID-19 mortality risk overall and within age strata. The VACO Index reproducibly identified individuals at substantial risk of COVID-19 mortality who might consider continuing social distancing, despite relaxed state and local guidelines.

60 APPLIED LIFE SCIENCES↗

Video-Camera-Based Position-Measuring System

A prototype optoelectronic system measures the three-dimensional relative coordinates of objects of interest or of targets affixed to objects of interest in a workspace. The system includes a charge-coupled-device video camera mounted in a known position and orientation in the workspace, a frame grabber, and a personal computer running image-data-processing software. Relative to conventional optical surveying equipment, this system can be built and operated at much lower cost; however, it is less accurate. It is also much easier to operate than are conventional instrumentation systems. In addition, there is no need to establish a coordinate system through cooperative action by a team of surveyors. The system operates in real time at around 30 frames per second (limited mostly by the frame rate of the camera). It continuously tracks targets as long as they remain in the field of the camera. In this respect, it emulates more expensive, elaborate laser tracking equipment that costs of the order of 100 times as much. Unlike laser tracking equipment, this system does not pose a hazard of laser exposure. Images acquired by the camera are digitized and processed to extract all valid targets in the field of view. The three-dimensional coordinates (x, y, and z) of each target are computed from the pixel coordinates of the targets in the images to accuracy of the order of millimeters over distances of the orders of meters. The system was originally intended specifically for real-time position measurement of payload transfers from payload canisters into the payload bay of the Space Shuttle Orbiters (see Figure 1). The system may be easily adapted to other applications that involve similar coordinate-measuring requirements. Examples of such applications include manufacturing, construction, preliminary approximate land surveying, and aerial surveying. For some applications with rectangular symmetry, it is feasible and desirable to attach a target composed of black and white squares to an object of interest (see Figure 2). For other situations, where circular symmetry is more desirable, circular targets also can be created. Such a target can readily be generated and modified by use of commercially available software and printed by use of a standard office printer. All three relative coordinates (x, y, and z) of each target can be determined by processing the video image of the target. Because of the unique design of corresponding image-processing filters and targets, the vision-based position- measurement system is extremely robust and tolerant of widely varying fields of view, lighting conditions, and varying background imagery.

Lane, John↗

Stellar Occultation Observations to Constrain the Stratosphere of Uranus for Aerocapture

Background on Uranus: Voyager 2 (V2) UV stellar and solar occultations at Uranus detected a warm stratosphere and extremely hot thermosphere [1, 2], far in excess of solar irradiance [3, 4] and internal heating [5, 6]. New theories to explain similar heating at Jupiter [7] and Saturn [8] cannot be tested at Uranus due to a dearth of reliable measurements. In [9, 10], we reprocessed 26 archival Earth-based stellar occultations by Uranus (1977-1996), finding stratospheric temperatures (~200 K) warmer than the original (~100 K), but in stark tension with V2 (~300-500 K). In [10], we built a physics-based, 1-D atmospheric model (see Fig 1) that finds a nearly isothermal stratosphere and a dynamic heat sink in the lower thermosphere. Aerocapture: Aerocapture is spacecraft maneuver that uses a single deep dip to enter orbit. It could decrease cruise time and launch mass for a Uranus mission, but the greatest impediment is uncertain stratospheric densities of Uranus [11]. Aims: 1) Observe and process many high S/N Uranus stellar occultations in the next decade; 2) constrain stratospheric densities for aerocapture; 3) better understand the energy balance; 4) determine stratospheric changes since 1996. Upcoming Occultations: We will present our observing plan for the 2025 April Uranus occultation (K mag 8) and discuss the best-in-a-century 2031 event (K mag 4). We will discuss other events in the early 2030s [12] [13], predicted constraints on density, and simulations of aerocapture for UOP. We will discuss the Shadow Chaser, a small satellite concept for observing occultations from Earth orbit [12]. Conclusions: New stellar occultations can vastly improve profiles of the stratosphere of Uranus; this is critical for understanding energy circulation and constraining densities for using aerocapture on UOP. References: [1] Herbert, F. et al. (1987). JGR. [2] Stevens, M. et al. (1993). Icarus. [3] Marley, M. & McKay, C. (1999). Icarus, [4] Li, C. et al. (2018). JQRST. [5] Pearl, J. et al. (1990). Icarus. [6] Melin, H (2020). Nat Astron. [7] O’Donoghue, J. et al. (2021) Nature. [8] Mueller-Wodarg, I. et al. (2019) GRL. [9] Saunders, W. et al. (2023). PSJ. [10] Saunders, W. et al. (2024). PSJ. [11] Report of the Aerocapture Demonstration Relevance Assessment Team (2023). [12] Saunders, W. et al. (2022). P&SS. [13] French, R. & Souami, D. (2023) PSJ.

William Saunders↗