Developing fMRI protocol for clinical use Comparison of 6 Arabic paradigms for brain language mapping in native Arabic speakers

Objectives:To assess a baseline assessment using developed functional magnetic resonance imaging (fMRI) language paradigms for Arabic-speakers.Methods:24-healthy right-handed volunteers scanned on a 3.0 Tesla MRI machine. For fMRI, a BOLD-sensitive sequence used to measure signals over time across 6 language paradigms: rhyming (RH), semantic category generations (SCG), silent word generation (SWG), verb generation picture (VGp), verb generation word (VGw), and verb generation audio (VGa). fMRI data was analyzed using FMRIB Software Library (FSL).Results:We found that VGa, SWG, VGw and VGp robustly activated language-related regions in the dominant hemisphere. RH and SCG failed to adequately define these activation regions but this may be related to the study’s preliminary nature and limitations. After assessment of their validity, considerable activation of the inferior frontal gyrus during VGa, SWG, VGw and VGp suggests that these paradigms have the potential for localizing of Broca’s area in native Arabic speakers.Conclusion:Set of well adapted, and evidence-based, fMRI paradigms were established for Arabic-speakers to enable accurate and sufficient localization and lateralization of the language area. After validation, these paradigms may provide sequences for accurate localization of brain language areas, and could be used as a presurgical evaluation tool.

Functional magnetic resonance imaging (fMRI) allows precise, and non-invasive, localization and lateralization of brain functions. Clinically, these techniques have considerable success, and hold great potential in the management of a variety of neurological disorders. One of the most promising clinical applications of fMRI is presurgical linguistic mapping.1-5 The 3 classical language areas that are involved in language production and processing are Broca’s and Wernicke’s areas, and angular gyrus. Wernicke’s area can be described as a receptive region, for processing and integrating auditory sensory information, while Broca’s area can be described as a productive region, for making vocal signals, and meaningful words or sentences. The latter includes pars opercularis and triangularis. The angular gyrus area is particularly involved in reading and transitioning between written and spoken forms of language. Injury to language regions produces noticeable clinical deficits, and the location of these regions may become difficult to assess without advanced anatomical imaging such as fMRI. Internationally, fMRI replaces the more invasive Wada test (also known as the intracarotid sodium amobarbital procedure) in lateralizing language and memory at some centers.6,7Language is a highly complex system that markedly varies across individuals. Patients native language affects brain activation responses during fMRI scans.8-13 As such, language paradigms for presurgical fMRI mapping should be developed and validated using native language paradigms. Language dominance of the left cerebral hemisphere has been well researched and established, but native language and social factors were also reported to play a key role in cortical association of verbal processing.8,14-16Although language localization using fMRI has been routinely used in western countries, and more recently in an Arabic country,17 studies clearly demonstrated that different cultures may process language in different manners, using different brain mechanisms.8,14-16 Existing language paradigms, created for non-Arabic speaking patients, require major modifications before applying them in examining native Arabic speakers.17Language lateralization is another broadly used clinical application of fMRI. Concordance with Wada test has long been demonstrated and validated in the literature using paradigms with various tasks such as verbal fluency, comprehension, and semantic judgment .18-21 These have shown that concordance with Wada test can reach 90% in temporal lobe epilepsy, especially in left-dominant patients. A slightly lower concordance was achieved in right-dominant patients. Although fMRI language lateralization works well for patients with typical language dominance, clinicians need to be careful when interpreting results of patients with atypical language representation.22Semitic languages such as Arabic differ from other languages in many aspects, including orthography (including diacritics), phonology, and syntax. Therefore, significant research in developing and validating language paradigms for Arabic is required. To our knowledge, very few studies in this domain have been carried out.17,23 One developed several language and memory paradigms in neurological patients, while emphasizing consideration for educational and cultural adjustments,17 and the other examined neuronal correlates of diacritics (vs. lack of thereof) in 11 healthy men.23We aim to establish tasks adapted to the Arabic language, that also reliably activate Broca’s and Wernicke’s areas in a relatively short scanning time. This study is a baseline assessment using 6 developed fMRI language paradigms for Arabic-speaking presurgical candidates. The desired outcome of this work is to create a set of Arabic language localization protocols, along with standard operating procedures.     

Screening Diverse Rice (Oryza sativa L) Genotypes for Manganese Efficiency

Soil manganese (Mn) deficiency limits the growth and crop yield. Growing Mn efficient cultivars i.e. the cultivars with high yield at low Mn supply would represent a long term solution and sustainable approach to crop production. To evaluate Mn efficiency of 38 diverse rice genotypes, field experiment was conducted during kharif seasons using Mn deficient (2.20?mg?kg^?1) soil. Typic Ustrochrepts loamy sand soil, treated with 0?kg Mn?ha^?1 (no Mn, low level) and 20?kg Mn?ha^?1 supplemented with two foliar sprays@ 0.5?% MnSO₄ (high level). The relative grain yield i.e. Mn efficiency index varied from 100 to 84?% and relative grain Mn uptake i.e. Mn efficiency from 80 to 53?% among the genotypes and the cultivar PR116 was having highest Mn efficiency index as well as efficiency. On the basis of grain yield and Mn efficiency, genotypes were classified as efficient and responsive (PR116, 3047, PAU201, 3131, 3125, HKR127, 3106, 3129, 3128, 3100 and 3138), efficient and nonresponsive (PR120, PR113, 3126, 3033, 3132, 3056, 3130, 3036, 3109, 3124, 3101 and 3136), inefficient and responsive (3127, PR115, 3133, 3134 and 3142), and inefficient and nonresponsive (PR114, PR118, 3137, PR111, 3108, PUSA44, 3135, 3139, 3140 and 3141). From a practical point of view, genotypes that produce high grain yield at a low level of Mn and respond well to Mn additions are the most desirable because they are able to express their high yield potential in a wide range of Mn availability.     

Evolutionary design of magnetic soft continuum robots

Worldwide cardiovascular diseases such as stroke and heart disease are the leading cause of mortality. While guidewire/catheter-based minimally invasive surgery is used to treat a variety of cardiovascular disorders, existing passive guidewires and catheters suffer from several limitations such as low steerability and vessel access through complex geometry of vasculatures and imaging-related accumulation of radiation to both patients and operating surgeons. To address these limitations, magnetic soft continuum robots (MSCRs) in the form of magnetic field–controllable elastomeric fibers have recently demonstrated enhanced steerability under remotely applied magnetic fields. While the steerability of an MSCR largely relies on its workspace—the set of attainable points by its end effector—existing MSCRs based on embedding permanent magnets or uniformly dispersing magnetic particles in polymer matrices still cannot give optimal workspaces. The design and optimization of MSCRs have been challenging because of the lack of efficient tools. Here, we report a systematic set of model-based evolutionary design, fabrication, and experimental validation of an MSCR with a counterintuitive nonuniform distribution of magnetic particles to achieve an unprecedented workspace. The proposed MSCR design is enabled by integrating a theoretical model and the genetic algorithm. The current work not only achieves the optimal workspace for MSCRs but also provides a powerful tool for the efficient design and optimization of future magnetic soft robots and actuators.

Cardiovascular diseases such as stroke and heart disease are the leading cause of long-term disability and death worldwide, with an annual cost of over $300 billion in the United States alone (1, 2). Diverse cardiovascular diseases are treated with minimally invasive surgery (Fig. 1A), which is less traumatic and more effective than open surgery (3–6). The conventional minimally invasive treatments of cardiovascular diseases typically employ a passive guidewire and catheter with a preshaped tip that is manually operated under radioscopic imaging. For example, in mechanical thrombectomy, a surgeon usually inserts a guidewire/catheter combination from the patient’s femoral artery over the leg and navigates this combination using fluoroscopic imaging through the aorta into the target occluded artery (usually in the brain or lungs) for mechanical clot removal (7). As another example, in atrial fibrillation ablation, a surgeon usually threads a catheter into the patient’s heart, where the catheter’s tip applies high or low temperature to disrupt heart conduction that generates faulty electrical signals (8). This manual operation of passive guidewires and catheters, however, is often limited by low steerability through complex vasculatures, difficulty in accessing small branches, long operation times, and/or increased accumulated imaging-related radiation to both patients and operating surgeons (9). To overcome these challenges, immense efforts have been committed to exploring robotic-assisted minimally invasive treatments in a remotely operated manner. In particular, because of the untethered and biocompatible nature of magnetic fields, a promising robotic-assisted minimally invasive platform has recently emerged based on magnetic field–controllable elastomeric fibers—magnetic soft continuum robots (MSCRs) (10–13).Open in a separate windowFig. 1.MSCRs for minimally invasive treatments. (A) Cardiovascular diseases in hard-to-reach areas across the human body where MSCRs can find utility. (B) Schematic illustration of the active bending of the MSCR navigating in a complex blood vessel. The workspace is defined as the area of attainable locations by the MSCR’s end effector via tuning the actuation magnetic field. (C) Schematic illustration of operating the MSCR at lesion tissues in atrial fibrillation ablation. (D) Schematic illustration of the distal portion of an MSCR in which hard-magnetic particles (e.g., NdFeB) are dispersed in the polymer matrix (e.g., silicone).An MSCR typically consists of a magneto-active distal portion that can be actively bent by tuning the actuation magnetic field and a nonmagnetized body that can be advanced or retracted by controlling the motor connected to the MSCR’s proximal end. In a typical minimally invasive treatment, a surgeon remotely controls the motor to advance the MSCR up to locations that require active steering, such as in front of branches of blood vessels (Fig. 1B) or lesion tissues (Fig. 1C) (14, 15). At these locations, the surgeon needs to remotely apply a magnetic field to bend the distal portion of the MSCR so that the MSCR’s end effector reaches the desired location. Thereafter, the surgeon further advances or operates the MSCR actively steered by the actuation magnetic field. Evidently, the steerability of an MSCR is largely determined by the set of attainable locations by its end effector via tuning the actuation magnetic field named the workspace of the MSCR (16, 17). A larger workspace gives a higher steerability of the MSCR in minimally invasive treatments.Existing MSCRs are mostly fabricated by embedding one or more permanent magnets in the distal portion of the MSCR (18–25). More recently, a new type of MSCR has been developed by uniformly dispersing hard-magnetic particles in elastomeric fibers (16) (Fig. 1D). However, the workspaces of MSCRs with both embedded magnets and uniformly distributed hard-magnetic particles are still limited, mainly because of the lack of efficient design and optimization tools for MSCRs. Indeed, existing designs of MSCRs heavily rely on experimental trial and error or numerical simulations (26, 27) that are not ideal for design or optimization with a large number of design parameters. Hence, an efficient design strategy capable of maximizing the workspaces of MSCRs remains an important, yet unresolved, challenge in the field.Here, we report an evolutionary design strategy to maximize the workspaces of MSCRs by integrating theoretical modeling (17, 28) and the genetic algorithm (29) to identify the optimal magnetization and rigidity patterns within the MSCRs (Fig. 2A). We first develop a hard-magnetic elastica theory to calculate the deflections of an MSCR with a specific magnetization and rigidity pattern under uniform magnetic fields up to 40 mT applied along various directions in one plane (17) (SI Appendix, Fig. S1). Notably, 40 mT is a typical magnetic-field strength for operating MSCRs (16, 30). We then calculate the area of the workspace for this MSCR and repeat the calculations for MSCRs with various random magnetization and rigidity patterns. Thereafter, we only select the MSCRs with relatively large workspaces, mutate and cross over their magnetization and rigidity patterns to give a new generation of MSCRs, and then calculate the workspaces of the new generation of MSCRs (29). By repeating this evolutionary process over a few generations, we can achieve an optimal design of the MSCR with an unprecedented workspace. We further validate this evolutionary design of the MSCR by both finite element simulations and experiments.Open in a separate windowFig. 2.Designing MSCRs by programming their magnetization and rigidity pattern in the distal portion. (A) Each voxel is encoded with a specific remanent magnetization M by tuning its magnetic particle volume fraction ϕ. The direction of the remanent magnetization of all voxels is along the axial direction pointing to the distal tip. (B) The normalized magnetization strength M(ϕ)/M0 (Left, black) and shear modulus G(ϕ)/G0 (Right, red) of the MSCR as a function of particle volume fraction ϕ.