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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

White matter and neurite morphology differ in psychogenic nonepileptic seizures.

OBJECTIVE: To further evaluate the relationship between the clinical profiles and limbic and motor brain regions and their connecting pathways in psychogenic nonepileptic seizures (PNES). Neurite Orientation Dispersion and Density Indices (NODDI) multicompartment modeling was used to test the relationships between tissue alterations in patients with traumatic brain injury (TBI) and multiple psychiatric symptoms. METHODS: The sample included participants with prior TBI (TBI; N = 37) but no PNES, and with TBI and PNES (TBI + PNES; N = 34). Participants completed 3T Siemens Prisma MRI high angular resolution imaging diffusion protocol. Statistical maps, including fractional anisotropy (FA), mean diffusivity (MD), neurite dispersion [orientation dispersion index (ODI)] and density [intracellular volume fraction (ICVF), and free water (i.e., isotropic) volume fraction (V-ISO)] signal intensity, were generated for each participant. Linear mixed-effects models identified clusters of between-group differences in indices of white matter changes. Pearson's r correlation tests assessed any relationship between signal intensity and psychiatric symptoms. RESULTS: Compared to TBI, TBI + PNES revealed decreases in FA, ICVF, and V-ISO and increases in MD for clusters within cingulum bundle, uncinate fasciculus, fornix/stria terminalis, and corticospinal tract pathways (cluster threshold α = 0.05). Indices of white matter changes for these clusters correlated with depressive, anxiety, PTSD, psychoticism, and somatization symptom severity (FDR threshold α = 0.05). A follow-up within-group analysis revealed that these correlations failed to reach the criteria for significance in the TBI + PNES group alone. INTERPRETATION: The results expand support for the hypothesis that alterations in pathways comprising the specific PNES network correspond to patient profiles. These findings implicate myelin-specific changes as possible contributors to PNES, thus introducing novel potential treatment targets.

A Benchtop Approach to the Location Specific Blood Brain Barrier Opening using Focused Ultrasound in a Rat Model.

Stereotaxic surgery is the gold standard for localized drug and gene delivery to the rodent brain. This technique has many advantages over systemic delivery including precise localization to a target brain region and reduction of off target side effects. However, stereotaxic surgery is highly invasive which limits its translational efficacy, requires long recovery times, and provides challenges when targeting multiple brain regions. Focused ultrasound (FUS) can be used in combination with circulating microbubbles to transiently open the blood brain barrier (BBB) in millimeter sized regions. This allows intracranial localization of systemically delivered agents that cannot normally cross the BBB. This technique provides a noninvasive alternative to stereotaxic surgery. However, to date this technique has yet to be widely adopted in neuroscience laboratories due to the limited access to equipment and standardized methods. The overall goal of this protocol is to provide a benchtop approach to FUS BBB opening (BBBO) that is affordable and reproducible and can therefore be easily adopted by any laboratory.

Focused ultrasound blood brain barrier opening mediated delivery of MRI-visible albumin nanoclusters to the rat brain for localized drug delivery with temporal control.

There is an ongoing need for noninvasive tools to manipulate brain activity with molecular, spatial and temporal specificity. Here we have investigated the use of MRI-visible, albumin-based nanoclusters for noninvasive, localized and temporally specific drug delivery to the rat brain. We demonstrated that IV injected nanoclusters could be deposited into target brain regions via focused ultrasound facilitated blood brain barrier opening. We showed that nanocluster location could be confirmed in vivo with MRI. Additionally, following confirmation of nanocluster delivery, release of the nanocluster payload into brain tissue can be triggered by a second focused ultrasound treatment performed without circulating microbubbles. Release of glutamate from nanoclusters in vivo caused enhanced c-Fos expression, indicating that the loading capacity of the nanoclusters is sufficient to induce neuronal activation. This novel technique for noninvasive stereotactic drug delivery to the brain with temporal specificity could provide a new way to study brain circuits in vivo preclinically with high relevance for clinical translation.

Effects of a carbohydrate-restricted diet on hepatic lipid content in adolescents with non-alcoholic fatty liver disease: A pilot, randomized trial.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) has emerged as the most common form of liver disease among adolescents in industrialized countries. While lifestyle intervention remains the hallmark treatment for NAFLD, the most effective dietary strategy to reverse NAFLD in children is unknown. OBJECTIVE: The objective of this study was to determine the effects of a moderately CHO-restricted diet (CRD) vs fat-restricted diet (FRD) in adolescents with NAFLD on reduction in liver fat and insulin resistance. METHODS: Thirty-two children/adolescents (age 9-17) with obesity and NAFLD were randomized to a CRD (<25:25:>50% energy from CHO:protein:fat) or FRD (55:25:20) for 8 weeks. Caloric intakes were calculated to be weight maintaining. Change in hepatic lipid content was measured via magnetic resonance imaging, body composition via dual energy X ray absorptiometry and insulin resistance via a fasting blood sample. RESULTS: Change in hepatic lipid did not differ with diet, but declined significantly (-6.0 ± 4.7%, P < .001 only within the CRD group. We found significantly greater decreases in insulin resistance (HOMA-IR, <.05), abdominal fat mass (P < .01) and body fat mass (P < .01) in response to the CRD vs FRD. CONCLUSION: These findings suggest that consumption of a moderately CHO-restricted diet may result in decreased hepatic lipid as well as improvements in body composition and insulin resistance in adolescents with NAFLD even in the absence of intentional caloric restriction. Larger studies are needed to determine whether a CHO-restricted diet induces change in hepatic lipid independent of change in body fat.

Somatotopic Arrangement of the Human Primary Somatosensory Cortex Derived From Functional Magnetic Resonance Imaging.

Functional magnetic resonance imaging (fMRI) was used to estimate neuronal activity in the primary somatosensory cortex of six participants undergoing cutaneous tactile stimulation on skin areas spread across the entire body. Differences between the accepted somatotopic maps derived from Penfield's work and those generated by this fMRI study were sought, including representational transpositions or replications across the cortex. MR-safe pneumatic devices mimicking the action of a Wartenberg wheel supplied touch stimuli in eight areas. Seven were on the left side of the body: foot, lower, and upper leg, trunk beneath ribcage, anterior forearm, middle fingertip, and neck above the collarbone. The eighth area was the glabella. Activation magnitude was estimated as the maximum cross-correlation coefficient at a certain phase shift between ideal time series and measured blood oxygen level dependent (BOLD) time courses on the cortical surface. Maximally correlated clusters associated with each cutaneous area were calculated, and cortical magnification factors were estimated. Activity correlated to lower limb stimulation was observed in the paracentral lobule and superomedial postcentral region. Correlations to upper extremity stimulation were observed in the postcentral area adjacent to the motor hand knob. Activity correlated to trunk, face and neck stimulation was localized in the superomedial one-third of the postcentral region, which differed from Penfield's cortical homunculus.

Role of Surface Chemistry in Mediating the Uptake of Ultrasmall Iron Oxide Nanoparticles by Cancer Cells.

Ultrasmall iron oxide nanoparticles (USIONPs) (<4 nm) have recently attracted significant attention because of their potential as positive T1 magnetic resonance imaging (MRI) contrast agent contrary to larger superparamagnetic iron oxide nanoparticles (>6 nm) which act as negative T2 MRI contrast agents. However, studies on the cellular uptake behavior of these nanoparticles are very limited compared to their counterpart, larger-sized superparamagnetic iron oxide nanoparticles. In particular, the effects of specific nanoparticle parameters on the cellular uptake behavior of USIONPs by various cancer cells are not available. Here, we specifically investigated the role of USIONPs' surface functionalities [tannic acid (TA) and quinic acid (QA)] in mediating cellular uptake behavior of cancer cells pertaining to primary (U87 cells) and metastatic (MDA-MB-231Br cells) brain malignancies. Here, we chose TA and QA as representative capping molecules, wherein TA coating provides a general negatively charged nontargeting surface while QA provides a tumor-targeting surface as QA and its derivatives are known to interact with selectin receptors expressed on tumor cells and tumor endothelium. We observed differential cellular uptake in the case of TA- and QA-coated USIONPs by cancer cells. Both the cell types showed significantly higher cellular uptake of QA-coated USIONPs compared to TA-coated USIONPs at 4, 24, and 72 h. Blocking studies indicated that P-selectin cell surface receptors, in part, mediated the cellular uptake of QA-coated USIONPs. Given that P-selectin is overexpressed in cancer cells, tumor microenvironment, and at the metastatic niche, QA-coated USIONPs hold potential to be utilized as a platform for tumor-targeted drug delivery and in imaging and detection of primary and metastatic tumors.

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.