Resting State Functional Networks in Gliomas: Validation With Direct Electric Stimulation of a New Tool for Planning Brain Resections.

BACKGROUND AND OBJECTIVES: Precise mapping of functional networks in patients with brain tumor is essential for tailoring personalized treatment strategies. Resting-state functional MRI (rs-fMRI) offers an alternative to task-based fMRI, capable of capturing multiple networks within a single acquisition, without necessitating task engagement. This study demonstrates a strong concordance between preoperative rs-fMRI maps and the gold standard intraoperative direct electric stimulation (DES) mapping during awake surgery. METHODS: We conducted an analysis involving 28 patients with glioma who underwent awake surgery with DES mapping. A total of 100 DES recordings were collected to map sensorimotor (SMN), language (LANG), visual (VIS), and speech articulation cognitive domains. Preoperative rs-fMRI maps were generated using an updated version of the ReStNeuMap software, specifically designed for rs-fMRI data preprocessing and automatic detection of 7 resting-state networks (SMN, LANG, VIS, speech articulation, default mode, frontoparietal, and visuospatial). To evaluate the agreement between these networks and those mapped with invasive cortical mapping, we computed patient-specific distances between them and intraoperative DES recordings. RESULTS: Automatically detected preoperative functional networks exhibited excellent agreement with intraoperative DES recordings. When we spatially compared DES points with their corresponding networks, we found that SMN, VIS, and speech articulatory DES points fell within the corresponding network (median distance = 0 mm), whereas for LANG a median distance of 1.6 mm was reported. CONCLUSION: Our findings show the remarkable consistency between key functional networks mapped noninvasively using presurgical rs-fMRI and invasive cortical mapping. This evidence highlights the utility of rs-fMRI for personalized presurgical planning, particularly in scenarios where awake surgery with DES is not feasible to protect eloquent areas during tumor resection. We have made the updated tool for automated functional network estimation publicly available, facilitating broader utilization of rs-fMRI mapping in various clinical contexts, including presurgical planning, functional reorganization over follow-up periods, and informing future treatments such as radiotherapy.

Instrumented Upper Limb Functional Assessment Using a Robotic Exoskeleton: Normative References Intervals.

Upper-limb rehabilitation exoskeletons offer a valuable solution to support and enhance the rehabilitation path of neural-injured patients. Such devices are usually equipped with a network of sensors that can be exploited to evaluate and monitor the performances of the users. In this work, we assess the normality ranges of different motor-performance indicators on a group of 15 healthy participants, computed with the benchmark toolbox of AGREE, an upper limb motorized exoskeleton. The toolbox implements a benchmarking scheme for the evaluation of the upper limb, used to test anterior reaching at rest position height and hand-to-mouth motor skills. We selected kinematic and electromyography performance indicators to assess the different motor abilities. We performed a pilot evaluation on three neurological patients, to verify if the AGREE benchmark toolbox was able to distinguish patients from healthy subjects on the basis of the selected performance indicators. Through a comparison between results obtained by the healthy and the small group of motor-impaired users, we successfully calculated the normality ranges for the selected performance indicators, and we pilot-showed how data gathered from AGREE can be used to evaluate the current status of the patients.

Technology Acceptance Model for Exoskeletons for Rehabilitation of the Upper Limbs from Therapists' Perspectives.

Over the last few years, exoskeletons have been demonstrated to be useful tools for supporting the execution of neuromotor rehabilitation sessions. However, they are still not very present in hospitals. Therapists tend to be wary of this type of technology, thus reducing its acceptability and, therefore, its everyday use in clinical practice. The work presented in this paper investigates a novel point of view that is different from that of patients, which is normally what is considered for similar analyses. Through the realization of a technology acceptance model, we investigate the factors that influence the acceptability level of exoskeletons for rehabilitation of the upper limbs from therapists' perspectives. We analyzed the data collected from a pool of 55 physiotherapists and physiatrists through the distribution of a questionnaire. Pearson's correlation and multiple linear regression were used for the analysis. The relations between the variables of interest were also investigated depending on participants' age and experience with technology. The model built from these data demonstrated that the perceived usefulness of a robotic system, in terms of time and effort savings, was the first factor influencing therapists' willingness to use it. Physiotherapists' perception of the importance of interacting with an exoskeleton when carrying out an enhanced therapy session increased if survey participants already had experience with this type of rehabilitation technology, while their distrust and the consideration of others' opinions decreased. The conclusions drawn from our analyses show that we need to invest in making this technology better known to the public-in terms of education and training-if we aim to make exoskeletons genuinely accepted and usable by therapists. In addition, integrating exoskeletons with multi-sensor feedback systems would help provide comprehensive information about the patients' condition and progress. This can help overcome the gap that a robot creates between a therapist and the patient's human body, reducing the fear that specialists have of this technology, and this can demonstrate exoskeletons' utility, thus increasing their perceived level of usefulness.

AGREE: an upper-limb robotic platform for personalized rehabilitation, concept and clinical study design.

Rehabilitation exoskeletons can supplement therapist-based training allowing post-stroke patients to perform functional, high-dosage, repetitive exercises. The use of robotic devices allows providing intense rehabilitation sessions and permits clinicians to personalize the therapy according to the patient's need. In this work, we propose an upper-limb rehabilitation system developed within the AGREE project. The platform relies on a four degrees-of-freedom arm exoskeleton, capable of assisting state-of-the-art rehabilitation exercises under different training modalities while behaving transparently to user-generated and therapist-applied forces. The system is provided with a LEDs-matrix mat to guide patients during reaching tasks with visual feedback, an EMG reader to evaluate the patient's involvement during the therapy, and several software tools to help clinicians customize the treatment and monitor the patient's progress. A randomized controlled pilot study aimed at evaluating the usability and the effectiveness of the AGREE rehabilitation platform to improve arm impairment after stroke is currently ongoing.

In vivo immunomanipulation of V gamma 9V delta 2 T cells with a synthetic phosphoantigen in a preclinical nonhuman primate model.

Vgamma9Vdelta2(+) cells represent the major population of gammadelta T cells in primate blood and react in an MHC-unrestricted fashion to a set of low m.w. nonpeptide phosphoantigens. Two types of structurally related agonists have been discovered so far: the natural phosphoantigens (hydroxydimethyl allyl-pyrophosphate or isopentenyl-pyrophosphate (IPP)) acting directly on Vgamma9Vdelta2(+) TCR and aminobisphosphonates, which block the mevalonate pathway in target cells, leading to accumulation of natural phosphoantigens that in turn activate Vgamma9Vdelta2(+) cells. We demonstrate in the cynomolgus monkey that Vgamma9Vdelta2 can be manipulated in vivo with bromohydrin pyrophosphate (BrHPP)/Phosphostim, a potent synthetic agonist for which the mechanism of action is similar to natural phosphoantigens. Although of very short half-life, injection of BrHPP leads to strong activation of Vgamma9Vdelta2, inducing production of a high level of Th1 cytokines. Combination of BrHPP with low-dose rhIL-2 induces specific amplification of effector-memory peripheral Vgamma9Vdelta2 in blood in a dose-dependant manner. This transient response returns to baseline within 10-15 days. Successive infusions of BrHPP and rhIL-2 induce less vigorous expansions, suggesting a progressive exhaustion of the response. As no toxicity is detected with or without IL-2, this scheme represents a promising immunotherapeutic strategy for induction of systemic Th1 cytokines and massive expansion of gammadelta T cell subset with antitumor and anti-infectious properties.