Harmonized Multisite MRI-Based Quantification of Human Liver Fat and Stiffness: A Pilot Study.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a leading cause of end-stage liver disease. NAFLD diagnosis and follow-up relies on a combination of clinical data, liver imaging, and/or liver biopsy. However, intersite imaging differences impede diagnostic consistency and reduce the repeatability of the multisite clinical trials necessary to develop effective treatments. PURPOSE/HYPOTHESIS: The goal of this pilot study was to harmonize commercially available 3 T magnetic resonance imaging (MRI) measurements of liver fat and stiffness in human participants across academic sites and MRI vendors. STUDY TYPE: Cohort. SUBJECTS: Four community-dwelling adults with obesity. FIELD STRENGTH/SEQUENCE: 1.5 and 3 T, multiecho 3D imaging, PRESS, and GRE. ASSESSMENT: Harmonized proton density fat fraction (PDFF) and magnetic resonance spectroscopy (MRS) protocols were used to quantify the FF of synthetic phantoms and human participants with obesity using standard acquisition parameters at four sites that had four different 3 T MRI instruments. In addition, a harmonized magnetic resonance elastography (MRE) protocol was used to quantify liver stiffness among participants at two different sites at 1.5 and 3 T field strengths. Data were sent to a single data coordinating site for postprocessing. STATISTICAL TESTS: Linear regression in MATLAB, ICC analyses using SAS 9.4, one-sided 95% confidence intervals for the ICC. RESULTS: PDFF and MRS FF measurements were highly repeatable among sites in both humans and phantoms. MRE measurements of liver stiffness in three individuals at two sites using one 1.5 T and one 3 T instrument showed repeatability that was high although lower than that of MRS and PDFF. CONCLUSIONS: We demonstrated harmonization of PDFF, MRS, and MRE-based quantification of liver fat and stiffness through synthetic phantoms, traveling participants, and standardization of postprocessing analysis. Multisite MRI harmonization could contribute to multisite clinical trials assessing the efficacy of interventions and therapy for NAFLD. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 2.

Organic Fluorophore Coated Polycrystalline Ceramic LSO:Ce Scintillators for X-ray Bioimaging.

The current effort demonstrates that lutetium oxyorthosilicate doped with 1-10% cerium (Lu2SiO5:Ce, LSO:Ce) radioluminescent particles can be coated with a single dye or multiple dyes and generate an effective energy transfer between the core and dye(s) when excited via X-rays. LSO:Ce particles were surface modified with an alkyne modified naphthalimide (6-piperidin-1-yl-2-prop-2-yn-1-yl-1 H-benzo[ de]isoquinoline-1,3-(2 H)-dione, AlNap) and alkyne modified rhodamine B ( N-(6-diethylamino)-9-{2-[(prop-2-yn-1-yloxy)carbonyl]phenyl}-3 H-xanthen-3-ylidene)- N-ethylethanaminium, AlRhod) derivatives to tune the X-ray excited optical luminescence from blue to green to red using Förster Resonance Energy Transfer (FRET). As X-rays penetrate tissue much more effectively than UV/visible light, the fluorophore modified phosphors may have applications as bioimaging agents. To that end, the phosphors were incubated with rat cortical neurons and imaged after 24 h. The LSO:Ce surface modified with AlNap was able to be successfully imaged in vitro with a low-output X-ray tube. To use the LSO:Ce fluorophore modified particles as imaging agents, they must not induce cytotoxicity. Neither LSO:Ce nor LSO:Ce modified with AlNap showed any cytotoxicity toward normal human dermal fibroblast cells or mouse cortical neurons, respectively.

In vitro studies of heparin-coated magnetic nanoparticles for use in the treatment of neointimal hyperplasia.

Restenosis by neointimal hyperplasia is still an ongoing concern in endovascular surgery. Slowing vascular smooth muscle cell (VSMC) proliferation by reversing the phenotype change, would allow vessel healing and re-endotheliazation. To accomplish this, we have developed heparin-coated magnetic nanoparticles for targeted drug therapy of neointimal hyperplasia. Iron oxide nanoparticles were modified with a poly (ethylene oxide) based coating and then further functionalized with heparin. In vitro experiments were conducted to observe changes in phenotype, metabolic activity, and viability of three relevant cell lines including VSMC, endothelial cells and fibroblasts. Inhibition of proliferation of VSMCs was observed with doses as low as 1 µg/mL Fe of heparin loaded nanoparticle where endothelial cells showed an increase in proliferation in response to treatment. Fibroblasts showed relatively low response. Results suggest proliferation suppression of VSMCs due to phenotype coupled with the increase in endothelial cell proliferation at low doses of heparin coated nanoparticles.

Mapping the macaque superior temporal sulcus: functional delineation of vergence and version eye-movement-related activity.

It is currently thought that the primate oculomotor system has evolved distinct but interrelated subsystems to generate different types of visually guided eye movements (e.g., saccades/smooth pursuit/vergence). Although progress has been made in elucidating the neural basis of these movement types, no study to date has investigated all three movement types on a large scale and within the same animals. Here, we used fMRI in rhesus macaque monkeys to map the superior temporal sulcus (STS) for BOLD modulation associated with visually guided eye movements. Further, we ascertained whether modulation in a given area was movement type specific and, if not, the modulation each movement type elicited relative to the others (i.e., dominance). Our results show that multiple areas within STS modulate during all movement types studied, including the middle temporal, medial superior temporal, fundus of the superior temporal, lower superior temporal, and dorsal posterior inferotemporal areas. Our results also reveal an area in dorsomedial STS that is modulated almost exclusively by vergence movements. In contrast, we found that ventrolateral STS is driven preferentially during versional movements. These results illuminate an STS network involved in processes associated with multiple eye movement types, illustrate unique patterns of modulation within said network as a function of movement type, and provide evidence for a vergence-specific area within dorsomedial STS. We conclude that producing categorically different eye movement types requires access to a common STS network and that individual network nodes are recruited differentially based upon the type of movement generated.

Association Between Expiratory Central Airway Collapse and Respiratory Outcomes Among Smokers.

IMPORTANCE: Central airway collapse greater than 50% of luminal area during exhalation (expiratory central airway collapse [ECAC]) is associated with cigarette smoking and chronic obstructive pulmonary disease (COPD). However, its prevalence and clinical significance are unknown. OBJECTIVE: To determine whether ECAC is associated with respiratory morbidity in smokers independent of underlying lung disease. DESIGN, SETTING, AND PARTICIPANTS: Analysis of paired inspiratory-expiratory computed tomography images from a large multicenter study (COPDGene) of current and former smokers from 21 clinical centers across the United States. Participants were enrolled from January 2008 to June 2011 and followed up longitudinally until October 2014. Images were initially screened using a quantitative method to detect at least a 30% reduction in minor axis tracheal diameter from inspiration to end-expiration. From this sample of screen-positive scans, cross-sectional area of the trachea was measured manually at 3 predetermined levels (aortic arch, carina, and bronchus intermedius) to confirm ECAC (>50% reduction in cross-sectional area). EXPOSURES: Expiratory central airway collapse. MAIN OUTCOMES AND MEASURES: The primary outcome was baseline respiratory quality of life (St George's Respiratory Questionnaire [SGRQ] scale 0 to 100; 100 represents worst health status; minimum clinically important difference [MCID], 4 units). Secondary outcomes were baseline measures of dyspnea (modified Medical Research Council [mMRC] scale 0 to 4; 4 represents worse dyspnea; MCID, 0.7 units), baseline 6-minute walk distance (MCID, 30 m), and exacerbation frequency (events per 100 person-years) on longitudinal follow-up. RESULTS: The study included 8820 participants with and without COPD (mean age, 59.7 [SD, 6.9] years; 4667 [56.7%] men; 4559 [51.7%] active smokers). The prevalence of ECAC was 5% (443 cases). Patients with ECAC compared with those without ECAC had worse SGRQ scores (30.9 vs 26.5 units; P < .001; absolute difference, 4.4 [95% CI, 2.2-6.6]) and mMRC scale scores (median, 2 [interquartile range [IQR], 0-3]) vs 1 [IQR, 0-3]; P < .001]), but no significant difference in 6-minute walk distance (399 vs 417 m; absolute difference, 18 m [95% CI, 6-30]; P = .30), after adjustment for age, sex, race, body mass index, forced expiratory volume in the first second, pack-years of smoking, and emphysema. On follow-up (median, 4.3 [IQR, 3.2-4.9] years), participants with ECAC had increased frequency of total exacerbations (58 vs 35 events per 100 person-years; incidence rate ratio [IRR], 1.49 [95% CI, 1.29-1.72]; P < .001) and severe exacerbations requiring hospitalization (17 vs 10 events per 100 person-years; IRR, 1.83 [95% CI, 1.51-2.21]; P < .001). CONCLUSIONS AND RELEVANCE: In a cross-sectional analysis of current and former smokers, the presence of ECAC was associated with worse respiratory quality of life. Further studies are needed to assess long-term associations with clinical outcomes.

Prolonged treatment with bevacizumab is associated with brain atrophy: a pilot study in patients with high-grade gliomas.

Bevacizumab is widely used for treatment of high-grade gliomas and other malignancies. Because bevacizumab has been shown to be associated with neurocognitive decline, this study is designed to investigate whether prolonged treatment with bevacizumab is also associated with brain atrophy. We identified 12 high-grade glioma patients who received bevacizumab for 12 months at the first recurrence and 13 matched controls and blindly compared the volumes of the contralateral hemispheres and contralateral ventricle in these two groups at baseline and after 12 ± 2 months of the baseline scan by two independent analyses. The volumes of the contralateral hemispheres and ventricles did not differ significantly between the two groups at baseline. Whereas, in the control group the volumes of the contralateral hemisphere changed subtly from baseline to follow-up (p = 0.23), in the bevacizumab-treated group the volumes significantly decreased from baseline to follow-up (p = 0.03). There was significant increase in the contralateral ventricle volume from base line to follow-up scans in both the control group (p = 0.01) and in the bevacizumab group (p = 0.005). Both the absolute and the percentage changes of contralateral hemisphere volumes and contralateral ventricular volumes between the two patient groups were statistically significant (p < 0.05). Results of this study demonstrate prolonged treatment with bevacizumab is associated with atrophy of the contralateral brain hemisphere.

Compatibility of Standard Vagus Nerve Stimulation and Investigational Microburst Vagus Nerve Stimulation Therapy with fMRI.

Vagus nerve stimulation devices are conditionally approved for MR imaging with stimulation turned off, and the requirement to modify the stimulation settings may be a barrier to scanning in some radiology practices. There is increasing interest in studying the effects of stimulation during MR imaging/fMRI. This study evaluated the safety of standard and investigational microburst vagus nerve stimulation therapies during MR imaging/fMRI. A prospective, multicenter study was conducted in patients with an investigational vagus nerve stimulation device that delivered either standard or investigational microburst vagus nerve stimulation. Thirty participants underwent sequential MR imaging and fMRI scans, encompassing 188 total hours of scan time (62.7 hours with standard vagus nerve stimulation and 125.3 hours with investigational microburst vagus nerve stimulation). No adverse events were reported with active stimulation during MR imaging or during 12 months of follow-up. Our results support the safety of standard and investigational microburst vagus nerve stimulation therapy during MR imaging and fMRI scans.

Effects of a brief HIIT intervention on cognitive performance in older women.

Cardiorespiratory fitness (CRF) mitigates age-related decline in cognition and brain volume. Little is known, however, about the effects of high-intensity interval training (HIIT) on cognitive aging and the relationship between HIIT, cognition, hippocampal subfield volumes, and cerebral oxygen extraction fraction (OEF). Older sedentary women participated in an 8-week HIIT intervention. We conducted cognitive assessments, fitness assessments (VO2max), MRI scans: asymmetric spin echo oxygen extraction fraction (ASE-OEF), high-resolution multiple image co-registration and averaging (HR-MICRA) imaging, and transcranial Doppler ultrasonography before and after the intervention. VO2max increased from baseline (M = 19.36, SD = 2.84) to follow-up (M = 23.25, SD = 3.61), Z = - 2.93, p < .001, r = 0.63. Composite cognitive (Z = - 2.05, p = 0.041), language (Z = - 2.19, p = 0.028), and visuospatial memory (Z = - 2.22, p = 0.026), z-scores increased significantly. Hippocampal subfield volumes CA1 and CA3 dentate gyrus and subiculum decreased non-significantly (all p > 0.05); whereas a significant decrease in CA2 (Z = - 2.045, p = 0.041, r = 0.436) from baseline (M = 29.51; SD = 24.50) to follow-up (M = 24.50; SD = 13.38) was observed. Right hemisphere gray matter was correlated with language z-scores (p = 0.025; r = 0.679). The subiculum was correlated with attention (p = 0.047; r = 0.618) and verbal memory (p = 0.020; r = 0.700). The OEF and CBF were unchanged at follow-up (all p > .05). Although we observed cognitive improvements following 8 weeks of our HIIT intervention, they were not explained by hippocampal, OEF, or CBF changes.

Neuromorphometric associations with mood, cognition, and self-reported exercise levels in epilepsy and healthy individuals.

Regular physical activity may promote beneficial neuroplasticity, e.g., increased hippocampus volume. However, it is unclear whether self-reported physical exercise in leisure (PEL) levels are associated with the brain structure features demonstrated by exercise interventions. This pilot study investigated the relationship between PEL, mood, cognition, and neuromorphometry in patients with idiopathic generalized epilepsy (IGEs) compared to healthy controls (HCs). Seventeen IGEs and 19 age- and sex-matched HCs underwent magnetic resonance imaging (MRI) at 3T. The Baecke Questionnaire of Habitual Physical Activity, Profile of Mood States, and Montreal Cognitive Assessment (MoCA) assessed PEL, mood, and cognition, respectively. Structural MRI data were analyzed by voxel- and surface-based morphometry. IGEs had significantly lower PEL (p < 0.001), poorer mood (p = 0.029), and lower MoCA scores (p = 0.027) than HCs. These group differences were associated with reduced volume, decreased gyrification, and altered surface topology (IGEs < HCs) in frontal, temporal and cerebellar regions involved in executive function, memory retrieval, and emotional regulation, respectively. These preliminary results support the notion that increased PEL may promote neuroplasticity in IGEs, thus emphasizing the role of physical activity in promoting brain health in people with epilepsy.

Magnetic Resonance Imaging of Focused Ultrasound Radiation Force Strain Fields for Discrimination of Solid and Liquid Phases.

OBJECTIVE: Focused ultrasound (FUS) has become a non-invasive option for some surgical procedures, including tumor ablation and thalamotomy. Extension of magnetic resonance (MR) imaging-guided focused ultrasound for ablation of slowly perfused cerebrovascular lesions requires a novel treatment monitoring method that does not rely on thermometry or high-frequency Doppler methods. The goal of this study was to evaluate the sensitivity and specificity of strain estimates based on MR acoustic radiation force imaging (MR-ARFI) for differentiation of solids and liquids. METHODS: Strain fields were estimated in gelatin-based tissue-mimicking focused ultrasound phantoms on the basis of apparent displacement fields measured by MR-ARFI. MR-ARFI and diffusion-weighted imaging (DWI) measurements were made before and after FUS-induced heating to evaluate the performance of displacement, strain and apparent diffusion coefficient (ADC) measurements for the discrimination of solid and liquid phases. RESULTS: As revealed by receiver operating characteristic analyses, axial normal strain and shear strain components performed significantly better than axial displacement measurements alone when predicting whether a gelatin had melted. Additional measurements must be made to estimate certain strain components, so this trade-off must be considered when developing clinical strategies. ADC had the best overall performance, but DWI is vulnerable to signal dropouts and susceptibility artifacts near cerebrovascular lesions, so this metric may have limited clinical applicability. CONCLUSION: Strain components based on MR-ARFI apparent displacement measurements perform better than apparent displacement measurements alone at discriminating between solids and liquids. These methods are applicable to FUS treatment monitoring and evaluation of mechanical tissue properties in vivo.

LITE-1 mediates behavioral responses to X-rays in Caenorhabditis elegans.

Rapid sensory detection of X-ray stimulation has been documented across a wide variety of species, but few studies have explored the underlying molecular mechanisms. Here we report the discovery of an acute behavioral avoidance response in wild type Caenorhabditis elegans to X-ray stimulation. The endogenous C. elegans UV-photoreceptor protein LITE-1 was found to mediate the locomotory avoidance response. Transgenic expression of LITE-1 in C. elegans muscle cells resulted in paralysis and egg ejection responses to X-ray stimulation, demonstrating that ectopic expression of LITE-1 can confer X-ray sensitivity to otherwise X-ray insensitive cells. This work represents the first demonstration of rapid X-ray based genetically targeted (X-genetic) manipulation of cellular electrical activity in intact behaving animals. Our findings suggest that LITE-1 has strong potential for use in this minimally invasive form of neuromodulation to transduce transcranial X-ray signals for precise manipulation of neural activity in mammals, bypassing the need for invasive surgical implants to deliver stimulation.

Cortical Mechanisms Underlying Immersive Interactive Virtual Walking Treatment for Amelioration of Neuropathic Pain after Spinal Cord Injury: Findings from a Preliminary Investigation of Thalamic Inhibitory Function.

BACKGROUND: Neuropathic pain following spinal cord injury (SCI) affects approximately 60% of individuals with SCI. Effective pharmacological and non-pharmacological treatments remain elusive. We recently demonstrated that our immersive virtual reality walking intervention (VRWalk) may be effective for SCI NP. Additionally, we found that SCI NP may result from a decrease in thalamic γ-aminobutyric-acid (GABA), which disturbs central sensorimotor processing. OBJECTIVE: While we identified GABAergic changes associated with SCI NP, a critical outstanding question is whether a decrease in SCI NP generated by our VRWalk intervention causes GABA content to rise. METHOD: A subset of participants (n = 7) of our VRWalk trial underwent magnetic resonance spectroscopy pre- and post-VRWalk intervention to determine if the decrease in SCI NP is associated with an increase in thalamic GABA. RESULTS: The findings revealed a significant increase in thalamic GABA content from pre- to post-VRWalk treatment. CONCLUSION: While the current findings are preliminary and should be interpreted with caution, pre- to post-VRWalk reductions in SCI NP may be mediated by pre- to post-treatment increases in thalamic GABA by targeting and normalizing maladaptive sensorimotor cortex reorganization. Understanding the underlying mechanisms of pain recovery can serve to validate the efficacy of home-based VR walking treatment as a means of managing pain following SCI. Neuromodulatory interventions aimed at increasing thalamic inhibitory function may provide more effective pain relief than currently available treatments.

Potentiation of concentric force and acceleration only occurs early during the stretch-shortening cycle.

The purpose of this study was to determine where stretch-shortening cycle (SSC) potentiation of force, power, velocity, and acceleration occurs across the concentric phase of ballistic leg presses. Second, we examined the influence of late eccentric phase force and length of the amortization phase on potentiated concentric phase performance variables. Twenty-one male runners (age: 31.9 ± 4.7 years) performed SSC and concentric-only (CO) ballistic leg press throws. Potentiations of concentric actions were calculated as the difference between SSC and CO contractions. An analysis splitting the concentric range of motion (ROM) into 6 equal time intervals determined force and acceleration were potentiated (p < 0.05) only during the first one-sixth time interval of concentric motion, whereas velocity and power were potentiated (p < 0.05) at all time intervals over the entire concentric motion with the exception of power over the last one-sixth time interval. A more precise analysis examining 20-millisecond time intervals across the first 200 milliseconds of concentric motion determined force was potentiated only over the first 140 milliseconds and acceleration only over the first 160 milliseconds. Eccentric force measured during the last 100 milliseconds of eccentric motion was related to potentiated force during the initial 200 milliseconds of concentric motion (r = 0.44, p < 0.05) and potentiated mean power across the full concentric ROM (r = 0.62, p < 0.01). Results indicate that in contrast to power and velocity, potentiation of force and acceleration occurs only early during the concentric phase of SSC ballistic leg presses. Correlational findings imply late eccentric phase force is important for generating force and power during the concentric phase of the SSC and thus training focusing on enhancing late phase eccentric force appears important for developing explosive force and power during SSC movements.

X-ray perception: Animal studies of sensory and behavioral responses to X-rays.

Since their discovery in 1895, many studies have been conducted to understand the effect of X-rays on neural function and behavior in animals. These studies examined a range of acute and chronic effects, and a subset of studies has attempted to determine if X-rays can produce any sensory responses. Here we review literature on animal behavioral responses to X-rays from 1895 until 2021 to assess the evidence for detection of X-rays by sensory receptors in animals. We focus on the changes in appetitive and consummatory behavior, radiotaxis, behavioral arousal, and olfactory responses to X-rays that have been reported in the literature. Taken together, the reviewed literature provides a large body of evidence that X-rays can induce sensory responses in a wide variety of animals and also suggests that these responses are mediated by known sensory receptors. Furthermore, we postulate the role of reactive oxygen species (ROS), the most biologically active byproduct of X-rays, as a key mediator of sensory receptor responses to X-rays.

Somatotopic Mapping of the Fingers in the Somatosensory Cortex Using Functional Magnetic Resonance Imaging: A Review of Literature.

Multiple studies have demonstrated finger somatotopy in humans and other primates using a variety of brain mapping techniques including functional magnetic resonance imaging (fMRI). Here, we review the literature to better understand the reliability of fMRI for mapping the somatosensory cortex. We have chosen to focus on the hand and fingers as these areas have the largest representation and have been the subject of the largest number of somatotopic mapping experiments. Regardless of the methods used, individual finger somatosensory maps were found to be organized across Brodmann areas (BAs) 3b, 1, and 2 in lateral-to-medial and inferior-to-superior fashion moving from the thumb to the pinky. However, some consistent discrepancies are found that depend principally on the method used to stimulate the hand and fingers. Therefore, we suggest that a comparative analysis of different types of stimulation be performed to address the differences described in this review.

Aberrant visual circuitry associated with normal spatial match-to-sample accuracy in schizophrenia.

A goal of this study was to evaluate the function of the anterior cingulate cortex (ACC) and of the dorsolateral prefrontal cortex (DLPFC) in medicated patients with schizophrenia (SZ), a small group of first-degree relatives, and healthy controls using a visual delayed match-to-sample task in conjunction with functional magnetic resonance imaging (fMRI). To mitigate performance differences between SZ and healthy controls, we used a novel task that allows for individualized adjustment of task difficulty to match ability level. We also trained participants on the task prior to scanning. Using an event-related design, we modeled three components of the match-to-sample trial: visual encoding, delay, and discrimination. We did not find significant differences in ACC/medial frontal cortex activation between the groups. However, compared to healthy controls, SZ showed decreased activation in visual processing areas during the encoding and discrimination phases of the task and in the ventrolateral prefrontal cortex during the delay. These findings emphasize the tendency of schizophrenia subjects to solve perceptual memory problems by engaging diverse regions.

Focused Ultrasound Ablation of an Arteriovenous Malformation Model.

Brain AVMs are rare but serious vascular lesions that often pose a management dilemma between the risk of various treatment modalities and uncertain natural history during observation. We describe preliminary data on the use of focused ultrasound as a novel therapeutic strategy. In an AVM model, one session of ultrasound gradually reduced flow through the lesion without inducing rupture. Due to its non-invasive yet immediate ablative effects, focused ultrasound may allow safer treatment of AVMs. However, further studies are needed to clarify its efficacy and side effect profile.

X-ray excited luminescence spectroscopy and imaging with NaGdF4:Eu and Tb.

X-ray excited optical luminescence from nanophosphors can be used to selectively generate light in tissue for imaging and stimulating light-responsive materials and cells. Herein, we synthesized X-ray scintillating NaGdF4:Eu and Tb nanophosphors via co-precipitate and hydrothermal methods, encapsulated with silica, functionalized with biotin, and characterized by X-ray excited optical luminescence spectroscopy and imaging. The nanophosphors synthesized by co-precipitate method were ∼90 and ∼106 nm in diameter, respectively, with hydrothermally synthesized particles showing the highest luminescence intensity. More importantly, we investigated the effect of thermal annealing/calcination on the X-ray excited luminescence spectra and intensity. At above 1000 °C, the luminescence intensity increased, but particles fused together. Coating with a 15 nm thick silica shell prevented particle fusion and enabled silane-based chemical functionalization, although luminescence decreased largely due to the increased mass of non-luminescent material. We observed an increase in luminesce intensity with temperature until at 400 °C. At above 600 °C, NaGdF4:Eu@SiO2 converts to NaGd9Si6O26:Eu, an X-ray scintillator brighter than annealed NPs at 400 °C and dimmer than NPs synthesized using the hydrothermal method. The particles generate light through tissue and can be selectively excited using a focused X-ray source for imaging and light generation applications. The particles also act as MRI contrast agents for multi-modal localization.

Feasibility of cerium-doped LSO particles as a scintillator for x-ray induced optogenetics.

Objective.Non-invasive light delivery into the brain is needed forin vivooptogenetics to avoid physical damage. An innovative strategy could employ x-ray activation of radioluminescent particles (RLPs) to emit localized light. However, modulation of neuronal or synaptic function by x-ray induced radioluminescence from RLPs has not yet been demonstrated.Approach.Molecular and electrophysiological approaches were used to determine if x-ray dependent radioluminescence emitted from RLPs can activate light sensitive proteins. RLPs composed of cerium doped lutetium oxyorthosilicate (LSO:Ce), an inorganic scintillator that emits blue light, were used as they are biocompatible with neuronal function and synaptic transmission.Main results.We show that 30 min of x-ray exposure at a rate of 0.042 Gy s-1caused no change in the strength of basal glutamatergic transmission during extracellular field recordings in mouse hippocampal slices. Additionally, long-term potentiation, a robust measure of synaptic integrity, was induced after x-ray exposure and expressed at a magnitude not different from control conditions (absence of x-rays). We found that x-ray stimulation of RLPs elevated cAMP levels in HEK293T cells expressing OptoXR, a chimeric opsin receptor that combines the extracellular light-sensitive domain of rhodopsin with an intracellular second messenger signaling cascade. This demonstrates that x-ray radioluminescence from LSO:Ce particles can activate OptoXR. Next, we tested whether x-ray activation of the RLPs can enhance synaptic activity in whole-cell recordings from hippocampal neurons expressing channelrhodopsin-2, both in cell culture and acute hippocampal slices. Importantly, x-ray radioluminescence caused an increase in the frequency of spontaneous excitatory postsynaptic currents in both systems, indicating activation of channelrhodopsin-2 and excitation of neurons.Significance.Together, our results show that x-ray activation of LSO:Ce particles can heighten cellular and synaptic function. The combination of LSO:Ce inorganic scintillators and x-rays is therefore a viable method for optogenetics as an alternative to more invasive light delivery methods.

Age and gender differences in hip extension and flexion torque steadiness.

BACKGROUND: Lower extremity torque steadiness has been shown to be an independent predictor of functional performance in older women. Hip muscle function is crucial for many types of activities of daily living, yet existing studies investigating torque steadiness for lower extremities are limited to assessing steadiness at the knee and ankle. OBJECTIVE: The purpose of this study was to compare age and gender differences in hip extension (HE) and flexion (HF) strength, torque steadiness, and torque accuracy (TA). METHODS: Twenty young adults (10 men, 10 women; age 24.0 ± 2.2 years) and 21 older adults (11 men, 10 women; age 65.4 ± 4.5 years) matched across age for height and body mass participated. Dominant leg HE and HF isometric strength was assessed by maximal voluntary contractions (MVC); relative (5, 25 and 50% MVC) and absolute (25 Nm) torque steadiness were assessed as standard deviation and coefficient of variation of torque fluctuations, and TA was determined as the mean deviation from target torque levels. RESULTS: MVC was lower for HF than HE (p = 0.007), but HE had greater torque fluctuations (p < 0.05). For HE, the coefficient of variation of 5% MVC was greater for older than young adults (p < 0.05) and greater for women than men (p < 0.05). For HF torque steadiness there were no age or gender differences (p > 0.05). For both HE and HF, older adults were less accurate (higher TA) than their young counterparts at 25 Nm (p < 0.022). CONCLUSIONS: Our results indicate older as compared to young adults, and women as compared to men are less steady (greater torque fluctuations) in HE at 5% MVC target torque levels, but not at higher torque levels. For HF, torque steadiness is similar across low to high target torque levels in both genders and across younger and older adults. For both HE and HF, TA is impaired in older compared to young adults at absolute target torque levels, but not at relative torque levels.