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Open Access Publications from the University of California

This series is automatically populated with publications deposited by UC Riverside Bourns College of Engineering Bioengineering Department researchers in accordance with the University of California’s open access policies. For more information see Open Access Policy Deposits and the UC Publication Management System.

Cover page of Reference-Superimposed Reconstruction (RS-Recon) for Arterial Spin Labeling.

Reference-Superimposed Reconstruction (RS-Recon) for Arterial Spin Labeling.

(2026)

PURPOSE: Conventional arterial spin labeling (ASL) reconstruction suffers from sign-flipping errors and/or noise bias under strong background suppression (BS), limiting SNR optimization. We propose reference-superimposed reconstruction (RS-recon) to enable ideal BS and robust signal recovery. METHODS: RS-recon superimposes high-SNR M0 k-space data onto ASL k-space before reconstruction, with subsequent reference subtraction. Four volunteers underwent 3T scanning with pulsed ASL, pseudo-continuous ASL, and dual-module velocity-selective ASL across varying BS levels. RS-recon integrated reconstruction pipelines were compared to standard magnitude (Mag), complex subtraction (ComplexSub), and complex (Complex) reconstruction pipelines. The performance was evaluated by metrics including ASL signal, temporal SNR (tSNR), artifacts, misalignment robustness, and generalized auto-calibrating partially parallel acquisitions (GRAPPA) compatibility. RESULTS: RS-recon eliminated subtraction artifacts due to signal sign-flipping, recovered negative ASL signals, and enabled ideal BS for maximizing SNR. It significantly improved ASL signal and tSNR in gray/white matter across all labeling methods and different BS conditions. RS-recon corrected phase errors under low-SNR conditions, preserved signal signs, maintained Gaussian noise distribution, remained robust against misalignments between the reference and the ASL images, and integrated well with GRAPPA. Mag + RS performance matched complex-based (ComplexSub and Complex) RS pipelines and is recommended for its simplicity, compatibility, and robustness overall. CONCLUSION: RS-recon offers a simple, robust strategy for ASL image reconstruction, resolving subtraction errors even with magnitude output and enabling optimal background suppression. It enhances signal fidelity, SNR, and phase accuracy while integrating seamlessly with existing reconstruction pipelines and parallel imaging.

  • 1 supplemental PDF
Cover page of Associations between iron and mean kurtosis in iron-rich grey matter nuclei in aging.

Associations between iron and mean kurtosis in iron-rich grey matter nuclei in aging.

(2026)

OBJECTIVE: Elevated kurtosis values have been observed in subcortical grey matter structures of patients with neurodegenerative diseases. Here, we examined relationships between iron measures and kurtosis in iron-rich subcortical grey matter structures.Please check and confirm the affiliation 4 for the author "Xiaoping P. Hu".Affiliation 4 for Xiaoping P. Hu was incorrect since he is not associated with that department. We have removed this affiliation. Thanks!  MATERIALS AND METHODS: Multi-shell diffusion and multi-echo gradient echo acquisitions were used to derive mean kurtosis and iron measures (R2* and magnetic susceptibility), respectively, in subcortical grey matter nuclei and white matter tracts in a discovery cohort (110 healthy older and 63 younger adults) and replication cohort (72 healthy older adults).Please confirm if the author names are presented accurately and in the correct sequence (Ilana J. Bennett and Xiaoping P. Hu). Also, kindly confirm the details in the metadata are correct.Thanks for asking. We've checked and the names are presented accurately and in the correct sequence. We have corrected some details in the metadata - adding an affiliation to Murphy Shao (Department of Physics) and removing the Materials Science and Engineering affiliation for Xiaoping P. Hu. Is it possible to add an orcid id for Vala Masjedizadeh? His Orcid ID is  0009-0009-3692-2553 Everything else looks okay RESULTS: Iron-rich grey matter regions exhibited higher mean kurtosis, R2*, and magnetic susceptibility and white matter regions had lower mean kurtosis in the older adult group from the discovery cohort. In both cohorts, mean kurtosis was significantly correlated with R2* and magnetic susceptibility in iron-rich grey matter nuclei. No association was seen between signal-to-noise ratio and mean kurtosis in any grey matter region, indicating that the increase in mean kurtosis was not due to reduced signal-to-noise. As keywords are mandatory for this journal, please provide 3-6 keywords.I'm not sure where to put the keywords so I'll reply to the query with the keywords. Our keywords are: kurtosis, iron, grey matter, aging CONCLUSION: Our findings indicate that kurtosis is associated with iron-sensitive metrics in iron-rich grey matter structures, suggesting that iron deposits may be contributing to kurtosis.

Cover page of Investigating the correlation between force output, strains, and pressure for active skeletal muscle contractions.

Investigating the correlation between force output, strains, and pressure for active skeletal muscle contractions.

(2026)

Measuring the forces of individual muscles in a muscle group around a joint is non-trivial, and researchers have suggested using surrogates for individual muscle forces instead. Traditionally, experimentalists have shown that the force output of the skeletal muscle tissue can be correlated to the intra-muscular pressure (IMP) generated by the muscle belly. However, IMP proves difficult to measure in vivo, due to variations from sensor placement and invasiveness of the procedure. Numerical biomechanical simulations offer a tool to analyze muscle contractions, enabling new insights into the correlations among non-invasive experimentally measurable quantities, such as strains and the force output. In this work, we investigate the correlations between the muscle force output, the principal, shear and volumetric strains experienced by the muscle, as well as the pressure developed within the muscle belly as the tissue undergoes isometric contractions with varying activation profiles and magnitudes. It is observed that pressure does not correlate well with force output under higher sub-maximal and maximal activation levels, especially at locations away from the center of the muscle belly due to pressure relaxation effects. This study reveals strong correlations between force output and the strains at all locations of the belly, irrespective of the type of activation considered. This observation offers evidence for further in vivo studies using experimentally measurable principal and volumetric strains in the muscle belly as proxies for the force generation by the individual muscle and consequently enables the estimation on the contribution of various muscle groups to the total force.

The regenerative role of neural crest stem cells in physical stimuli-enhanced peripheral nerve repair

(2026)

Neural crest stem cells (NCSCs), capable of differentiating into neurons and Schwann cells, are essential for peripheral nerve regeneration. This study investigates the role of endogenous NCSC-like cells in mechano-electrical stimulation (MES)-enhanced peripheral nerve repair. In a critical-sized nerve injury model, MES leads to complete nerve reconnection, accompanied by a significant increase in NCSC-like cells at the injury sites. In vitro, MES promotes the simultaneous differentiation of NCSC-like cells into neurons and Schwann cells, with elevated neuregulin 1 (NRG1) expression, a key factor in Schwann cell development. Mechanistically, MES activates BMP/Smad signaling, driving neuronal differentiation and subsequent NRG1 secretion, which in turn promotes Schwann cell maturation through the ErBB/NFAT pathway. These findings demonstrate that MES enhances peripheral nerve regeneration by activating and directing stem cell differentiation, supporting a novel therapeutic approach that utilizes physical stimulation for stem cell modulation for nerve repair.

Comparative Evaluation of R134a and HFO‐1234ze Cryogen Spray Cooling Using a Mouse Model With Controllable Epidermal Pigmentation

(2026)

OBJECTIVES: Cryogen spray cooling (CSC) is critical for protecting the epidermis during laser dermatologic procedures. The widely used cryogen, R134a, has a high global warming potential (GWP), motivating interest in environmentally favorable alternatives such as HFO-1234ze. This study evaluated whether HFO-1234ze provides epidermal protection comparable to R134a during laser exposure and investigated the mechanistic basis underlying any differences in cooling performance. METHODS: Laser-induced epidermal injury in conjunction with two cryogens was assessed in K14-SCF Mc1re/e mice with pharmacologically controllable interfollicular epidermal pigmentation. Laser treatment sites were assigned fluences relative to baseline skin lightness (L*) to span subthreshold to suprathreshold injury conditions, with cryogen assignment randomized. Hypopigmentation at Day 7 served as the primary injury endpoint and was scored independently by three blinded raters. Surface cooling induced by each cryogen was measured separately using thin-film thermocouples on a skin phantom, and subsurface temperature distributions were estimated using one-dimensional transient heat-transfer modeling. RESULTS: Mean hypopigmentation scores did not differ significantly between R134a- and HFO-1234ze-cooled sites across the full range of pigmentation and fluence studied (p = 0.46). Heat-map analysis and regression modeling confirmed that hypopigmentation increased with fluence and darker pigmentation but was independent of cryogen type. Surface temperature measurements using skin phantom revealed that R134a produced more aggressive transient cooling than HFO-1234ze, reaching approximately 10°C lower minimum temperatures. However, numerical modeling of skin cooling using heat flux inferred from phantom measurement showed that this surface advantage decayed rapidly with depth, resulting in ≤ 2°C-3°C differences within the viable epidermis. CONCLUSIONS: Despite differences in surface cooling magnitude, R134a and HFO-1234ze provided equivalent epidermal protection under clinically relevant conditions. These findings support HFO-1234ze as an effective, lower-GWP alternative to R134a for CSC in laser dermatologic applications.

Effects of O+ and a Non‑O+ Blood Type, Number Concentration, and Membrane Phosphatidylserine Flipping on the Circulation Dynamics and Biodistribution of Microsized Erythrocyte-Derived Optical Particles in Mice

(2025)

Erythrocyte-derived microparticles containing near-infrared (NIR) dyes such as indocyanine green present a promising cell-based platform for optical imaging and phototherapeutics. Using real-time intravital NIR fluorescence imaging of mice vasculature, we investigated the effects of blood type, specifically O+ and B+, used in fabricating these particles, the number concentration (Nv) of the particles, and the relocalization of phosphatidylserine (PS) to the outer leaflet of the particles' membrane on the resulting circulation dynamics following a single retro-orbital injection. Additionally, we quantified the biodistribution of particles in various organs. We found that the fluorescence emission half-life for particles engineered from O+ blood type extended from 11.4 ± 3.0 to 43.1 ± 9.6 min with increased Nv from a low range of 0.4-0.6 to high range of 1.4-1.6 million particles/per μL, when only 30-55% of the particles demonstrated externalized PS. For these particles, the liver and gallbladder, lungs, and spleen showed similar levels of accumulation at 60 min post administration. When >90% of O+-particles showed PS externalization, or when the particles were fabricated from B+ blood type despite PS externalization in 30-55% of the particles, the emission half-life was reduced to 15.8 ± 5.9 and 18.1 ± 4.6 min, respectively. There was lower accumulation of these particles in the spleen as compared to the liver and gallbladder and the lungs. In vitro experiments demonstrated increased PS externalization correlated to a more efficient uptake of the particles by macrophages. These findings emphasize the importance of blood type, Nv, and PS in engineering erythrocyte-derived particles for future clinical applications.

Cover page of Optimization of deep learning–based denoising for arterial spin labeling: Effects of averaging and training strategies

Optimization of deep learning–based denoising for arterial spin labeling: Effects of averaging and training strategies

(2025)

PURPOSE: Systematic study of the effects of averaging and other relevant training strategies in deep learning (DL)-based denoising is required to optimize such processing pipelines for improving the quality of arterial spin labeling (ASL) images. METHODS: Different averaging strategies, including windowed and interleaved averaging methods, and different levels of averaging before and after convolutional neural network-based and transformer-based denoising were studied. The experiments were performed on 152 single-delay ASL scans from 152 subjects, including pulsed and pseudo-continuous ASL acquisitions. Four-fold cross-validation was implemented in all experiments. The effect of including calibration scans (M0) was studied and compared across images of different levels of signal-to-noise ratio (SNR). The generalizability of DL denoising was examined in experiments using low-SNR ground truth in training. The results were assessed using image-quality metrics including structural similarity, peak SNR, and normalized mean absolute error. RESULTS: Including M0 was almost always beneficial, with a dependence on the SNR of the input ASL images. Windowed averaging outperformed interleaved averaging, supporting the practice of reducing scan time. Averaging of ASL images before DL denoising was more advantageous than averaging after. Matching the SNR levels of the images in training and inferencing was important for optimal performance. These findings were consistent across convolutional neural network-based and transformer-based models. The generalizability of DL-based denoising was confirmed, and its capability to reduce artifacts was observed. CONCLUSION: This study supports the use of DL-based denoising in improving the image quality of ASL and reducing scan time and provides insights to help optimize DL-denoising pipelines.

  • 1 supplemental ZIP

Identifying indicators of consciousness in AI systems

(2025)

Rapid progress in artificial intelligence (AI) capabilities has drawn fresh attention to the prospect of consciousness in AI. There is an urgent need for rigorous methods to assess AI systems for consciousness, but significant uncertainty about relevant issues in consciousness science. We present a method for assessing AI systems for consciousness that involves exploring what follows from existing or future neuroscientific theories of consciousness. Indicators derived from such theories can be used to inform credences about whether particular AI systems are conscious. This method allows us to make meaningful progress because some influential theories of consciousness, notably including computational functionalist theories, have implications for AI that can be investigated empirically.

Cover page of Fuel-driven filamentous phage nanomotors

Fuel-driven filamentous phage nanomotors

(2025)

Virus-based nanocarriers have shown great potential for noninvasive delivery of drugs, diagnostics, and imaging agents to hard-to-reach anatomical locations. Yet, they largely depend on diffusion for transport, often lacking the force to actively penetrate biological barriers, and navigation to guide therapeutic agents. In these studies, the M13 bacteriophage, a linearly shaped virus, was converted from passive nanocarrier to actively propelled, fuel-driven nanomotor. Using the distinctive low symmetry of its capsid, a single Pt nanoparticle was added to one end of the M13 virus to form a tadpole-like structure. The Pt/M13 head/tail nanomotors exhibited notably enhanced diffusion in the presence of hydrogen peroxide fuel, and significantly improved uptake by SVOK3 ovarian cancer cells in vitro. Given the successes of the M13 bacteriophage as a nanocarrier, the demonstration of this simple, but comparatively mobile M13-based nanomotor platform represents an important step in advancing the potential therapeutic efficacy of viral nanocarriers.