Understanding and subsequently controlling the non-specific interactions between engineered nanomaterials and the biological environment have become increasingly important for further developing and advancing nanotechnology for biomedical applications. Such non-specific interactions, also known as the biofouling effect, mainly associate with the adsorption of biomolecules (such as proteins, DNAs, RNAs, and peptides) onto the surface of nanomaterials and the adhesion or uptake of nanomaterials by various cells. By altering the surface properties of nanomaterials, the biofouling effect can lead to in situ changes of physicochemical properties, pharmacokinetics, functions, and toxicity of nanomaterials. This review provides discussions on the current understanding of the biofouling effect, the factors that affect the non-specific interactions associated with biofouling, and the impact of the biofouling effect on the performance and functions of nanomaterials. An overview of the development and applications of various anti-biofouling coating materials to preserve and improve the properties and functions of engineered nanomaterials for intended biomedical applications is also provided.
Brain temperature is an understudied parameter relevant to brain injury and ischemia. To advance our understanding of thermal dynamics in the human brain, combined with the challenges of routine experimental measurements, a biophysical modeling framework was developed to facilitate individualized brain temperature predictions. Model-predicted brain temperatures using our fully conserved model were compared with whole brain chemical shift thermometry acquired in 30 healthy human subjects (15 male and 15 female, age range 18–36 years old). Magnetic resonance (MR) thermometry, as well as structural imaging, angiography, and venography, were acquired prospectively on a Siemens Prisma whole body 3 T MR scanner. Bland–Altman plots demonstrate agreement between model-predicted and MR-measured brain temperatures at the voxel-level. Regional variations were similar between predicted and measured temperatures (< 0.55 °C for all 10 cortical and 12 subcortical regions of interest), and subcortical white matter temperatures were higher than cortical regions. We anticipate the advancement of brain temperature as a marker of health and injury will be facilitated by a well-validated computational model which can enable predictions when experiments are not feasible.
Background: Molecular markers for classification of gliomas include isocitrate dehydrogenase (IDH) mutations and codeletion of chromosomal arms 1p and 19q (1p/19q). While mutations in IDH enzymes result in the well-characterized production of oncometabolite 2-hydroxyglutarate, dysregulation of other metabolites in IDH tumors is less characterized. Similarly, the effects of 1p/19q codeletion on cellular metabolism are also unclear. Aim: This study aimed to quantify changes in tumor metabolites in human glioma tissue as a function of both IDH mutation and 1p/19q codeletion. Methods and Results: Deidentified human glioma tissue and associated clinical data were obtained from the Emory University Winship Cancer Institute tissue biobank from 14 patients (WHO grades II, III, and IV; seven female and seven male). Proton (1H) high-resolution magic angle spinning (HR-MAS) nuclear magnetic resonance (NMR) spectroscopy data were acquired using a 600 MHz Bruker AVANCE III NMR spectrometer. Metabolite concentrations were calculated using LCModel. Differences in metabolite concentrations as a function of IDH mutation, 1p/19q codeletion, and survival status were determined using Mann–Whitney U tests. Concentrations of alanine, glutamine, and glutamate were significantly lower in glioma tissue with IDH mutations compared to tissue with IDH wildtype. Additionally, glutamate concentration was significantly lower in glioma tissue with 1p/19q codeletion compared to intact 1p/19q. Exploratory analysis revealed alanine concentration varied significantly as a function of survival status. Conclusions: Given the emerging landscape of glioma treatments that target metabolic dysregulation, an improved understanding of altered metabolism in molecular sub-types of gliomas, including those with IDH mutation and 1p/19q codeletion, is an important consideration for treatment stratification and personalized medicine.
Background and Purpose: Many patients with chronic pain report hypersensitivity not only to noxious stimuli, but also to other modalities including innocuous touch, sound, and light, possibly due to differences in the processing of these stimuli. The goal of this study was to characterize functional connectivity (FC) differences between subjects with temporomandibular disorders (TMD) and pain-free controls during a visual functional magnetic resonance imaging (fMRI) task that included an unpleasant, strobing visual stimulus. We hypothesized the TMD cohort would exhibit maladaptations in brain networks consistent with multisensory hypersensitivities observed in TMD patients. Methods: This pilot study included 16 subjects, 10 with TMD and 6 pain-free controls. Clinical pain was characterized using self-reported questionnaires. Visual task-based fMRI data were collected on a 3T MR scanner and used to determine differences in FC via group independent component analysis. Results: Compared to controls, subjects with TMD exhibited abnormally increased FC between the default mode network and lateral prefrontal areas involved in attention and executive function, and impaired FC between the frontoparietal network and higher order visual processing areas. Conclusions: The results indicate maladaptation of brain functional networks, likely due to deficits in multisensory integration, default mode network function, and visual attention and engendered by chronic pain mechanisms.
Temporomandibular disorders (TMD) involve chronic pain in the masticatory muscles and jaw joints, but the mechanisms underlying the pain are heterogenous and vary across individuals. In some cases, structural, functional, and metabolic changes in the brain may underlie the condition. In the present study, we evaluated the functional connectivity between 86 regions of interest (ROIs), which were chosen based on previously reported neuroimaging studies of pain and differences in brain morphology identified in an initial surface-based morphometry analysis. Our main objectives were to investigate the topology of the network formed by these ROIs and how it differs between individuals with TMD and chronic pain (n = 16) and pain-free control participants (n = 12). In addition to a true resting state functional connectivity scan, we also measured functional connectivity during a 6-min application of a noxious cuff stimulus applied to the left leg. Our principal finding is individuals with TMD exhibit more suprathreshold correlations (higher nodal degree) among all ROIs but fewer "hub" nodes (i.e., decreased betweenness centrality) across conditions and across all pain pathways. These results suggest is this pain-related network of nodes may be "over-wired" in individuals with TMD and chronic pain compared to controls, both at rest and during experimental pain.
Purpose: The presence of orientation-dependent susceptibility artifacts in magnetic resonance chemical shift thermometry (CST) can confound accurate temperature calculations. Here, we quantify the effect of white matter (WM) tract orientation on CST due to tissue-specific susceptibility. Methods: Twenty-nine healthy volunteers (27 ± 4 years old) were scanned on a 3 T MR scanner with a 32-channel head coil. Diffusion tensor imaging (DTI), T1-weighted imaging, and single voxel spectroscopy (SVS) for CST were acquired. Participants were then asked to rotate their head ∼3–5° (yaw or roll) to alter the orientation of WM tracts relative to the external magnetic field. After head rotation, a second SVS scan and T1-weighted imaging were acquired. The WM-fraction-normalized DTI principal eigenvector (V1) images were used to calculate the length of the x-y component of V1, which was used as a surrogate for WM tracts perpendicular to B0. A linear regression model was used to determine the relationship between the perpendicular WM tracts and brain temperature. Results: Significant temperature differences between post- and pre-head rotation scans were observed for brain (−0.72 °C ± 1.36 °C, p = 0.01) but not body (0.012 °C ± 0.07 °C, p = 0.37) temperatures. The difference in brain temperature was positively associated with the corresponding change in perpendicular WM tracts after head rotation (R2 = 0.26, p = 0.005). Conclusion: Our results indicate WM tract orientation affects temperature calculations, suggesting artifacts from orientation-dependent susceptibility may be present in CST.
The glutamine pathway is emerging as an important marker of cancer prognosis and a target for new treatments. In gliomas, the most common type of brain tumors, metabolic reprogramming leads to abnormal consumption of glutamine as an energy source, and increased glutamine concentrations are associated with treatment resistance and proliferation. A key challenge in the development of glutamine-based biomarkers and therapies is the limited number of in vivo tools to noninvasively assess local glutamine metabolism and monitor its changes. In this review, we describe the importance of glutamine metabolism in gliomas and review the current landscape of translational and emerging imaging techniques to measure glutamine in the brain. These techniques include MRS, PET, SPECT, and preclinical methods such as fluorescence and mass spectrometry imaging. Finally, we discuss the roadblocks that must be overcome before incorporating glutamine into a personalized approach for glioma management.
Elevated expression of β-amyloid (Aβ1-42) and tau are considered risk-factors for Alzheimer's disease in healthy older adults. We investigated the effect of aging and cerebrospinal fluid levels of Aβ1-42 and tau on 1) frontal metabolites measured with proton magnetic resonance spectroscopy (MRS) and 2) cognition in cognitively normal older adults (n = 144; age range 50-85). Levels of frontal gamma aminobutyric acid (GABA+) and myo-inositol relative to creatine (mI/tCr) were predicted by age. Levels of GABA+ predicted cognitive performance better than mI/tCr. Additionally, we found that frontal levels of n-acetylaspartate relative to creatine (tNAA/tCr) were predicted by levels of t-tau. In cognitively normal older adults, levels of frontal GABA+ and mI/tCr are predicted by aging, with levels of GABA+ decreasing with age and the opposite for mI/tCr. These results suggest that age- and biomarker-related changes in brain metabolites are not only located in the posterior cortex as suggested by previous studies and further demonstrate that MRS is a viable tool in the study of aging and biomarkers associated with pathological aging and Alzheimer's disease.
Diversity of participants in biomedical research with respect to race, ethnicity, and biological sex is crucial, particularly given differences in disease prevalence, recovery, and survival rates between demographic groups. The objective of this systematic review was to report on the demographics of neuroimaging studies using magnetic resonance imaging (MRI). The Web of Science database was used and data collection was performed between June 2021 to November 2021; all articles were reviewed independently by at least two researchers. Articles utilizing MR data acquired in the United States, with n ≥ 10 human subjects, and published between 2010–2020 were included. Non-primary research articles and those published in journals that did not meet a quality control check were excluded. Of the 408 studies meeting inclusion criteria, approximately 77% report sex, 10% report race, and 4% report ethnicity. Demographic reporting also varied as function of disease studied, participant age range, funding, and publisher. We anticipate quantitative data on the extent, or lack, of reporting will be necessary to ensure inclusion of diverse populations in biomedical research.
Background
Adiposity and mitochondrial dysfunction are related factors contributing to metabolic disease development. This pilot study examined whether in vivo and ex vivo indices of mitochondrial metabolism were differentially associated with body composition in males and females.
Methods
Thirty-four participants including 19 females (mean 27 yr) and 15 males (mean 29 yr) had body composition assessed by dual energy x-ray absorptiometry and magnetic resonance (MR) imaging. Monocyte reserve capacity and maximal oxygen consumption rate (OCR) were determined ex vivo using extracellular flux analysis. In vivo quadriceps mitochondrial function was measured using 31P-MR spectroscopy based on post-exercise recovery kinetics (τPCr). The homeostatic model assessment of insulin resistance (HOMA-IR) was calculated from fasting glucose and insulin levels. Variables were log-transformed, and Pearson correlations and partial correlations were used for analyses.
Results
Mitochondrial metabolism was similar between sexes (p > 0.05). In males only, higher fat mass percent (FM%) was correlated with lower reserve capacity (r = − 0.73; p = 0.002) and reduced muscle mitochondrial function (r = 0.58, p = 0.02). Thigh subcutaneous adipose tissue was inversely related to reserve capacity in males (r = − 0.75, p = 0.001), but in females was correlated to higher maximal OCR (r = 0.48, p = 0.046), independent of FM. In females, lean mass was related to greater reserve capacity (r = 0.47, p = 0.04). In all participants, insulin (r = 0.35; p = 0.04) and HOMA-IR (r = 0.34; p = 0.05) were associated with a higher τPCr.
Conclusions
These novel findings demonstrate distinct sex-dependent associations between monocyte and skeletal muscle mitochondrial metabolism with body composition. With further study, increased understanding of these relationships may inform sex-specific interventions to improve mitochondrial function and metabolic health.