Ultrastable 3D Heterogeneous Integration via N-Heterocyclic Carbene Self-Assembled Nanolayers.

The commercialization of 3D heterogeneous integration through hybrid bonding has accelerated, and accordingly, Cu-polymer bonding has gained significant attention as a means of overcoming the limitations of conventional Cu-SiO2 hybrid bonding, offering high compatibility with other fabrication processes. Polymers offer robust bonding strength and a low dielectric constant, enabling high-speed signal transmission with high reliability, but suffer from low thermomechanical stability. Thermomechanical stability of polymers was not achieved previously because of thermal degradation and unstable anchoring. To overcome these limitations, wafer-scale Cu-polymer bonding via N-heterocyclic carbene (NHC) nanolayers was presented for 3D heterogeneous integration, affording ultrastable packing density, crystallinity, and thermal properties. NHC nanolayers were deposited on copper electrodes via electrochemical deposition, and wafer-scale 3D heterogeneous integration was achieved by adhesive bonding at 170 °C for 1 min. Ultrastable conductivity and thermomechanical properties were observed by the spatial mapping of conductivity, work function, and force-distance curves. With regard to the characterization of NHC nanolayers, low-temperature bonding, robust corrosion inhibition, enhanced electrical conductivity, back-end-of-line process compatibility, and fabrication process reduction, NHC Cu/polymer bonding provides versatile advances in 3D heterogeneous integration, indicating that NHC Cu/polymer bonding can be utilized as a platform for future 3D vertical chip architectures.

How good are collimated Gaussian beams produced with engineered diffusers?

Collimating a Gaussian beam from an uncollimated laser source has been achieved via the deployment of engineered diffusers (EDs)-also referred to as light shaping diffusers. When compared to conventional pinhole-based optical collimation systems, this method of beam collimation ensures high optical transmission efficiency at the expense of the introduction of additional speckle and a resulting reduction in spatial coherence. Despite a lower collimation quality, these ED-produced collimated beams are attractive and promising in terms of their deployment in various benchtop or tabletop systems that involve shorter beam propagation distances of up to a few meters while requiring a high optical power throughput. This paper aims to further the understanding of collimation quality and propagation properties of ED-produced Gaussian collimated beams via carefully designed experiments and accompanying analysis. We measure and document the beam divergence, Rayleigh distance, and M 2 factor, as well as evolution of the wavefront radius of curvature (RoC), of these ED-generated beams over a few meters of propagation-a propagation distance which encapsulates a vast majority of optical systems. We further investigate the changes in the beam profile with the addition of a laser speckle reducer (SR) and compare the ED-produced beams with a near-ideal collimated beam produced with spatial filtering systems.

Measuring the radius of curvature of spherical surfaces with actively tunable Fizeau and Twyman-Green interferometers.

Accurate and repeatable measurement of the radius of curvature (RoC) of spherical sample surfaces is of great importance in optics. This importance lies in the ubiquitous use of spherical optical elements such as curved mirrors and lenses. Due to a high measurement sensitivity, interferometric techniques are often deployed for accurate characterization of the sample surface RoC. One method by which a typical commercial Fizeau or Twyman-Green (TG) interferometer measures surface RoC is via scanning between two principal retroreflective optical configurations-namely, the confocal and catseye configurations. Switching between these two configurations is typically achieved by moving an optical head along the axis of the propagating laser beam and the RoC is estimated by measuring the magnitude of mechanical motion to switch between the two principal configurations. In this paper, we propose a motion-free catseye/confocal-imaging-based sample RoC measurement system. The necessity of bulk motion to switch between the two configurations is circumvented via the use of an actively controlled varifocal lens. We demonstrate the usefulness of the proposed innovation in RoC measurements with either the TG or the Fizeau interferometer. Furthermore, we convert a commercial motion-based Zygo RoC measurement system into a motion-free one by introducing a tunable lens inside the apparatus and using it to accurately characterize the RoC of different test samples. We also compute the wavefront aberrations for all spherical sample surfaces from the recorded measurement data.

Free-standing two-dimensional ferro-ionic memristor.

Two-dimensional (2D) ferroelectric materials have emerged as significant platforms for multi-functional three-dimensional (3D) integrated electronic devices. Among 2D ferroelectric materials, ferro-ionic CuInP2S6 has the potential to achieve the versatile advances in neuromorphic computing systems due to its phase tunability and ferro-ionic characteristics. As CuInP2S6 exhibits a ferroelectric phase with insulating properties at room temperature, the external temperature and electrical field should be required to activate the ferro-ionic conduction. Nevertheless, such external conditions inevitably facilitate stochastic ionic conduction, which completely limits the practical applications of 2D ferro-ionic materials. Herein, free-standing 2D ferroelectric heterostructure is mechanically manipulated for nano-confined conductive filaments growth in free-standing 2D ferro-ionic memristor. The ultra-high mechanical bending is selectively facilitated at the free-standing area to spatially activate the ferro-ionic conduction, which allows the deterministic local positioning of Cu+ ion transport. According to the local flexoelectric engineering, 5.76×102-fold increased maximum current is observed within vertical shear strain 720 nN, which is theoretically supported by the 3D flexoelectric simulation. In conclusion, we envision that our universal free-standing platform can provide the extendable geometric solution for ultra-efficient self-powered system and reliable neuromorphic device.

The dispensability of VH-VL pairing and the indispensability of VL domain integrity in the IgG1 secretion process.

Introduction: The CH1 domain of IgG antibodies controls assembly and secretion, mediated by the molecular chaperone BiP via the endoplasmic reticulum protein quality control (ERQC) mechanism. However, it is not clear whether the variable domains are necessary for this process. Methods: Here, we generated IgG1 antibodies in which the V domain (VH and/or VL) was either removed or replaced, and then assessed expression, assembly, and secretion in HEK293 cells. Results: All Ig variants formed a covalent linkage between the Cγ1 and Cκ, were successfully secreted in an assembled form. Replacement of the cognate Vκ with a non-secretory pseudo Vκ (ψVκ) hindered secretion of individual or assembled secretion of neither heavy chains (HCs) nor light chains (LCs). The ψLC (ψVκ-Cκ) exhibited a less folded structure compared to the wild type (wt) LC, as evidenced by enhanced stable binding to the molecular chaperone BiP and susceptibility to proteolytic degradation. Molecular dynamics simulation demonstrated dramatic alterations in overall structure of ψFab (Fd-ψLC) from wt Fab. Discussion: These findings suggest that V domains do not initiate HC:LC assembly and secretion; instead, the critical factor governing IgG assembly and secretion is the CH-CL pairing. Additionally, the structural integrity of the VL domain is crucial for IgG secretion. These data offer valuable insight into the design of bioactive molecules based on an IgG backbone.

Numerical investigation of the effect of air layer on drag reduction in channel flow over a superhydrophobic surface.

This study investigates the effects of an air layer on drag reduction and turbulence dynamics in channel flow over a superhydrophobic surface (SHS). Employing the OpenFOAM platform, direct numerical simulation was conducted to investigate turbulent channel flow with an air layer over an SHS. The simulations, which take into account the interaction between water and air, analyze various parameters such as velocity distribution, drag reduction (DR), Reynolds stress, turbulent kinetic energy (TKE), and coherent structures near the water-air interface. The presence of an air layer significantly alters the velocity distribution, leading to higher velocities at the interface compared to simulations without the air layer. Notably, the thickness of the air layer emerges as an important factor, with larger thicknesses resulting in increased velocities and drag reduction. This study underscores the substantial impact of the air layer on TKE near the superhydrophobic surface, emphasizing its role in understanding and optimizing drag reduction. Furthermore, the nonlinear relationship between slip velocity, Q contours, and coherent structures near the SHS are investigated.

High-Throughput Roll-to-Roll Processed Large-Area Perovskite Solar Cells Using Rapid Radiation Annealing Technique.

The development of a stable roll-to-roll (R2R) process for flexible large-area perovskite solar cells (PSCs) and modules is a pressing challenge. In this study, we introduced a new R2R PSC manufacturing system that employs a two-step deposition method for coating perovskite and uses intensive pulsed light (IPL) for annealing. This system has successfully fabricated small-sized cells and the first-ever large-sized, R2R-processed flexible modules. A key focus of our work was to accelerate the conversion of PbI2 to perovskite. To this end, we utilized IPL annealing and incorporated additives into the PbI2 layer. With these modifications, the R2R-processed perovskite films achieved a power conversion efficiency (PCE) of 16.87%, representing the highest reported value for R2R two-step processed PSCs. However, these cells exhibited hysteresis in reverse and forward PCE measurements. To address this, we introduced a dual-annealing process consisting of IPL followed by a 2-min thermal heating step. This approach successfully reduced hysteresis, resulting in low-hysteresis, R2R-processed flexible PSCs. Moreover, we fabricated large-scale flexible modules (10 × 10 cm2) with a PCE of 11.25% using the dual-annealing system, marking a significant milestone in this field.

Diagnosis of Unruptured Intracranial Aneurysms Using Proton-Density Magnetic Resonance Angiography: A Comparison With High-Resolution Time-of-Flight Magnetic Resonance Angiography.

OBJECTIVE: Differentiating intracranial aneurysms from normal variants using CT angiography (CTA) or MR angiography (MRA) poses significant challenges. This study aimed to evaluate the efficacy of proton-density MRA (PD-MRA) compared to high-resolution time-of-flight MRA (HR-MRA) in diagnosing aneurysms among patients with indeterminate findings on conventional CTA or MRA. MATERIALS AND METHODS: In this retrospective analysis, we included patients who underwent both PD-MRA and HR-MRA from August 2020 to July 2022 to assess lesions deemed indeterminate on prior conventional CTA or MRA examinations. Three experienced neuroradiologists independently reviewed the lesions using HR-MRA and PD-MRA with reconstructed voxel sizes of 0.253 mm3 or 0.23 mm3, respectively. A neurointerventionist established the gold standard with digital subtraction angiography. We compared the performance of HR-MRA, PD-MRA (0.253-mm3 voxel), and PD-MRA (0.23-mm3 voxel) in diagnosing aneurysms, both per lesion and per patient. The Fleiss kappa statistic was used to calculate inter-reader agreement. RESULTS: The study involved 109 patients (average age 57.4 ± 11.0 years; male:female ratio, 11:98) with 141 indeterminate lesions. Of these, 78 lesions (55.3%) in 69 patients were confirmed as aneurysms by the reference standard. PD-MRA (0.253-mm3 voxel) exhibited significantly higher per-lesion diagnostic performance compared to HR-MRA across all three readers: sensitivity ranged from 87.2%-91.0% versus 66.7%-70.5%; specificity from 93.7%-96.8% versus 58.7%-68.3%; and accuracy from 90.8%-92.9% versus 63.8%-69.5% (P ≤ 0.003). Furthermore, PD-MRA (0.253-mm3 voxel) demonstrated significantly superior per-patient specificity and accuracy compared to HR-MRA across all evaluators (P ≤ 0.013). The diagnostic accuracy of PD-MRA (0.23-mm3 voxel) surpassed that of HR-MRA and was comparable to PD-MRA (0.253-mm3 voxel). The kappa values for inter-reader agreements were significantly higher in PD-MRA (0.820-0.938) than in HR-MRA (0.447-0.510). CONCLUSION: PD-MRA outperformed HR-MRA in diagnostic accuracy and demonstrated almost perfect inter-reader consistency in identifying intracranial aneurysms among patients with lesions initially indeterminate on CTA or MRA.

Magnetite particles accelerate methanogenic degradation of highly concentrated acetic acid in anaerobic digestion process.

The anaerobic digestion (AD) process has become significant for its capability to convert organic wastewater into biogas, a valuable energy source. Excessive acetic acid accumulation in the anaerobic digester can inhibit methanogens, ultimately leading to the deterioration of process performance. Herein, the effect of magnetite particles (MP) as an enhancer on the methanogenic degradation of highly-concentrated acetate (6 g COD/L) was examined through long-term sequential AD batch tests. Bioreactors with (AM) and without (AO) MP were compared. AO experienced inhibition and its methane production rate (qm) converged to 0.45 L CH4/g VSS/d after 10 sequential batches (AO10, the 10th batch in a series of the sequential batch tests conducted using bioreactors without MP addition). In contrast, AM achieved 3-425% higher qm through the sequential batches, indicating that MP could counteract the inhibition caused by the highly-concentrated acetate. MP addition to inhibited bioreactors (AO10) successfully restored them, achieving qm of 1.53 L CH4/g VSS/d, 3.4 times increase from AO10 after 8 days lag time, validating its potential as a recovery strategy for inhibited digesters with acetate accumulation. AM exhibited higher microbial populations (1.8-3.8 times) and intracellular activity (9.3 times) compared to AO. MP enriched Methanosaeta, Peptoclostridium, Paraclostridium, OPB41, and genes related to direct interspecies electron transfer and acetate oxidation, potentially driving the improvement of qm through MP-mediated methanogenesis. These findings demonstrated the potential of MP supplementation as an effective strategy to accelerate acetate-utilizing methanogenesis and restore an inhibited anaerobic digester with high acetate accumulation.

Orbital-Selective Mott Transition Effects and Nontrivial Topology of Iron Chalcogenide.

The iron-based superconductor FeSe_{1-x}Te_{x} has recently gained significant attention as a host of two distinct physical phenomena: (i) Majorana zero modes that can serve as potential topologically protected qubits, and (ii) a realization of the orbital-selective Mott transition. In this Letter, we connect these two phenomena and provide new insights into the interplay between strong electronic correlations and nontrivial topology in FeSe_{1-x}Te_{x}. Using linearized quasiparticle self-consistent GW plus dynamical mean-field theory, we show that the topologically protected Dirac surface state has substantial Fe(d_{xy}) character. The proximity to the orbital-selective Mott transition plays a dual role: it facilitates the appearance of the topological surface state by bringing the Dirac cone close to the chemical potential but destroys the Z_{2} topological superconductivity when the system is too close to the orbital-selective Mott phase. We derive a reduced effective Hamiltonian that describes the topological band. Its parameters capture all the chemical trends found in the first principles calculation. Our findings provide a framework for further study of the interplay between strong electronic correlations and nontrivial topology in other iron-based superconductors.

Identification of differentially expressed mRNA/lncRNA modules in acutely regorafenib-treated sorafenib-resistant Huh7 hepatocellular carcinoma cells.

The multikinase inhibitor sorafenib is the standard first-line treatment for advanced hepatocellular carcinoma (HCC), but many patients become sorafenib-resistant (SR). This study investigated the efficacy of another kinase inhibitor, regorafenib (Rego), as a second-line treatment. We produced SR HCC cells, wherein the PI3K-Akt, TNF, cAMP, and TGF-beta signaling pathways were affected. Acute Rego treatment of these cells reversed the expression of genes involved in TGF-beta signaling but further increased the expression of genes involved in PI3K-Akt signaling. Additionally, Rego reversed the expression of genes involved in nucleosome assembly and epigenetic gene expression. Weighted gene co-expression network analysis (WGCNA) revealed four differentially expressed long non-coding RNA (DElncRNA) modules that were associated with the effectiveness of Rego on SR cells. Eleven putative DElncRNAs with distinct expression patterns were identified. We associated each module with DEmRNAs of the same pattern, thus obtaining DElncRNA/DEmRNA co-expression modules. We discuss the potential significance of each module. These findings provide insights and resources for further investigation into the potential mechanisms underlying the response of SR HCC cells to Rego.

Expression of Immunoglobulin G4 in Eosinophilic Esophagitis.

Background: Eosinophilic esophagitis (EoE) is a disease that has been subcategorized into two endoscopic phenotypes: inflammatory and fibrostenotic. Moreover, studies have shown a link between EoE and immunoglobulin G4 (IgG4), a subclass of the immunoglobulin G (IgG) antibody. In this study, we aimed to evaluate the relationship between histologic IgG4 expression and endoscopic phenotypes in patients with EoE. Methods: This case-control study included patients diagnosed with EoE (n = 19) and patients with non-obstructive dysphagia without abnormal findings as controls (NOD; n = 12). The EoE group was further divided into three subgroups based on endoscopic phenotype: inflammatory, fibrostenotic, or combined. Retrospective examination of endoscopic findings and pathological slides was performed to analyze IgG4 staining. Results: Histological analysis revealed a significant difference in IgG4 cell count (15.00 vs. 0.58, p = 0.003) and eosinophil cell count (84.67 vs. 0.08, p < 0.001) between the EoE and NOD groups. Symptom manifestation and blood test results were similar across all three endoscopic EoE phenotypes. However, histological analysis revealed a significant difference in IgG4 cell count between the inflammatory, fibrostenotic, and combined phenotypes (4.13 vs. 17.6 vs. 59.7, p = 0.030). Conclusions: IgG4 expression was higher in EoE patients than in those with NOD, the highest being in the combined phenotype subgroup. These findings emphasize the important role of endoscopic and histological examination in diagnosing EoE and the need for further research in this area.

Impaired Glymphatic Flow on Diffusion Tensor MRI as a Marker of Neurodegeneration in Alzheimer's Disease: Correlation with Gray Matter Volume Loss and Cognitive Decline Independent of Cerebral Amyloid Deposition.

Background: Impaired glymphatic flow on the Alzheimer's disease (AD) spectrum may be evaluated using diffusion tensor image analysis along the perivascular space (DTI-ALPS). Objective: We aimed to validate impaired glymphatic flow and explore its association with gray matter volume, cognitive status, and cerebral amyloid deposition on the AD spectrum. Methods: 80 participants (mean age, 76.9±8.5 years; 57 women) with AD (n = 65) and cognitively normal (CN) (n = 15) who underwent 3T brain MRI including DTI and/or amyloid PET were included. After adjusting for age, sex, apolipoprotein E status, and burden of white matter hyperintensities, the ALPS-index was compared according to the AD spectrum. The association between the ALPS-index and gray matter volume, cognitive status, and quantitative amyloid from PET was assessed. Results: The ALPS-index in the AD was significantly lower (mean, 1.476; 95% CI, 1.395-1.556) than in the CN (1.784;1.615-1.952; p = 0.026). Volumes of the entorhinal cortex, hippocampus, temporal pole, and primary motor cortex showed significant associations with the ALPS-index (all, p < 0.05). There was a positive correlation between the ALPS-index and MMSE score (partial r = 0.435; p < 0.001), but there was no significant correlation between the ALPS-index and amyloid SUVRs (all, p > 0.05). Conclusions: Decreased glymphatic flow measured by DTI-ALPS in AD may serve as a marker of neurodegeneration correlating with structural atrophy and cognitive decline.

Advances in algal lipid metabolism and their use to improve oil content.

Microalgae are eukaryotic photosynthetic micro-organisms that convert CO2 into carbohydrates, lipids, and other valuable metabolites. They are considered promising chassis for the production of various bioproducts, including fatty acid-derived biofuels. However, algae-based biofuels are not yet commercially available, mainly because of their low yields and high production cost. Optimizing strains to improve lipid productivity using the principles of synthetic biology should help move forward. This necessitates developments in the following areas: (1) identification of molecular bricks (enzymes, transcription factors, regulatory proteins etc.); (2) development of genetic tools; and (3) availability of high-throughput phenotyping methods. Here, we highlight the most recent developments in some of these areas and provide examples of the use of genome editing tools to improve oil content.

Photoautotrophic cultivation of a Chlamydomonas reinhardtii mutant with zeaxanthin as the sole xanthophyll.

BACKGROUND: Photosynthetic microalgae are known for their sustainable and eco-friendly potential to convert carbon dioxide into valuable products. Nevertheless, the challenge of self-shading due to high cell density has been identified as a drawback, hampering productivity in sustainable photoautotrophic mass cultivation. To address this issue, mutants with altered pigment composition have been proposed to allow a more efficient light diffusion but further study on the role of the different pigments is still needed to correctly engineer this process. RESULTS: We here investigated the Chlamydomonas reinhardtii Δzl mutant with zeaxanthin as the sole xanthophyll. The Δzl mutant displayed altered pigment composition, characterized by lower chlorophyll content, higher chlorophyll a/b ratio, and lower chlorophyll/carotenoid ratio compared to the wild type (Wt). The Δzl mutant also exhibited a significant decrease in the light-harvesting complex II/Photosystem II ratio (LHCII/PSII) and the absence of trimeric LHCIIs. This significantly affects the organization and stability of PSII supercomplexes. Consequently, the estimated functional antenna size of PSII in the Δzl mutant was approximately 60% smaller compared to that of Wt, and reduced PSII activity was evident in this mutant. Notably, the Δzl mutant showed impaired non-photochemical quenching. However, the Δzl mutant compensated by exhibiting enhanced cyclic electron flow compared to Wt, seemingly offsetting the impaired PSII functionality. Consequently, the Δzl mutant achieved significantly higher cell densities than Wt under high-light conditions. CONCLUSIONS: Our findings highlight significant changes in pigment content and pigment-protein complexes in the Δzl mutant compared to Wt, resulting in an advantage for high-density photoautotrophic cultivation. This advantage is attributed to the decreased chlorophyll content of the Δzl mutant, allowing better light penetration. In addition, the accumulated zeaxanthin in the mutant could serve as an antioxidant, offering protection against reactive oxygen species generated by chlorophylls.

Tracing the dynamics of superconducting order via transient terahertz third-harmonic generation.

Ultrafast optical control of quantum systems is an emerging field of physics. In particular, the possibility of light-driven superconductivity has attracted much of attention. To identify nonequilibrium superconductivity, it is necessary to measure fingerprints of superconductivity on ultrafast timescales. Recently, nonlinear THz third-harmonic generation (THG) was shown to directly probe the collective degrees of freedoms of the superconducting condensate, including the Higgs mode. Here, we extend this idea to light-driven nonequilibrium states in superconducting La2-xSrxCuO4, establishing an optical pump-THz-THG drive protocol to access the transient superconducting order-parameter quench and recovering on few-picosecond timescales. We show in particular the ability of two-dimensional TH spectroscopy to disentangle the effects of optically excited quasiparticles from the pure order-parameter dynamics, which are unavoidably mixed in the pump-driven linear THz response. Benchmarking the gap dynamics to existing experiments shows the ability of driven THG spectroscopy to overcome these limitations in ordinary pump-probe protocols.

Study on the Sodium-Doped Titania Interface-Type Memristor.

Memristors integrated into a crossbar-array architecture (CAA) are promising candidates for analog in-memory computing accelerators. However, the relatively low reliability of the memristor device and sneak current issues in CAA remain the main obstacles. Alkali ion-based interface-type memristors are promising solutions for implementing highly reliable memristor devices and neuromorphic hardware. This interface-type device benefits from self-rectifying and forming-free resistive switching (RS), and exhibits relatively low variation from device to device and cycle to cycle. In a previous report, we introduced an in situ grown Na/TiO2 memristor using atomic layer deposition (ALD) and proposed a RS mechanism from experimentally measured Schottky barrier modulation. Self-rectifying RS characteristics were observed by the asymmetric distribution of Na dopants and oxygen vacancies as the Ti metal used as the adhesion layer for the bottom electrode diffuses over the Pt electrode at 250 °C during the ALD process and is doped into the TiO2 layer. Here, we theoretically verify the modulation of the Schottky barrier at the TiO2/Pt electrode interface by Na ions. This study fabricated a Pt/Na/TiO2/Pt memristor device and confirmed its self-rectifying RS characteristics and stable retention characteristics for 24 h at 85 °C. Additionally, this device exhibited relative standard deviations of 27 and 7% in the high and low resistance states, respectively, in terms of cycle-to-cycle variation. To verify the RS mechanism, we conducted density functional theory simulations to analyze the impact of Na cations at interstitial sites on the Schottky barrier. Our findings can contribute to both fundamental understanding and the design of high-performance memristor devices for neuromorphic computing.

Recent Progress of Advanced Functional Separators in Lithium Metal Batteries.

As a representative in the post-lithium-ion batteries (LIBs) landscape, lithium metal batteries (LMBs) exhibit high-energy densities but suffer from low coulombic efficiencies and short cycling lifetimes due to dendrite formation and complex side reactions. Separator modification holds the most promise in overcoming these challenges because it utilizes the original elements of LMBs. In this review, separators designed to address critical issues in LMBs that are fatal to their destiny according to the target electrodes are focused on. On the lithium anode side, functional separators reduce dendrite propagation with a conductive lithiophilic layer and a uniform Li-ion channel or form a stable solid electrolyte interphase layer through the continuous release of active agents. The classification of functional separators solving the degradation stemming from the cathodes, which has often been overlooked, is summarized. Structural deterioration and the resulting leakage from cathode materials are suppressed by acidic impurity scavenging, transition metal ion capture, and polysulfide shuttle effect inhibition from functional separators. Furthermore, flame-retardant separators for preventing LMB safety issues and multifunctional separators are discussed. Further expansion of functional separators can be effectively utilized in other types of batteries, indicating that intensive and extensive research on functional separators is expected to continue in LIBs.

Imaging Genomics of Glioma Revisited: Analytic Methods to Understand Spatial and Temporal Heterogeneity.

An improved understanding of the cellular and molecular biologic processes responsible for brain tumor development, growth, and resistance to therapy is fundamental to improving clinical outcomes. Imaging genomics is the study of the relationships between microscopic, genetic, and molecular biologic features and macroscopic imaging features. Imaging genomics is beginning to shift clinical paradigms for diagnosing and treating brain tumors. This article provides an overview of imaging genomics in gliomas, in which imaging data including hallmarks such as IDH-mutation, MGMT methylation, and EGFR-mutation status can provide critical insights into the pretreatment and posttreatment stages. This article will accomplish the following: 1) review the methods used in imaging genomics, including visual analysis, quantitative analysis, and radiomics analysis; 2) recommend suitable analytic methods for imaging genomics according to biologic characteristics; 3) discuss the clinical applicability of imaging genomics; and 4) introduce subregional tumor habitat analysis with the goal of guiding future radiogenetics research endeavors toward translation into critically needed clinical applications.