The Potential Role of PET in the Management of Peripheral Artery Disease.

PURPOSE OF REVIEW: Current non-invasive tests for evaluating patients with peripheral artery disease (PAD) have significant limitations for early detection and management of patients with PAD and are generally focused on the evaluation of large vessel disease. PAD often involves disease of microcirculation and altered metabolism. Therefore, there is a critical need for reliable quantitative non-invasive tools that can assess limb microvascular perfusion and function in the setting of PAD. RECENT FINDINGS: Recent developments in positron emission tomography (PET) imaging have enabled the quantification of blood flow to the lower extremities, the assessment of the viability of skeletal muscles, and the evaluation of vascular inflammation and microcalcification and angiogenesis in the lower extremities. These unique capabilities differentiate PET imaging from current routine screening and imaging methods. The purpose of this review is to highlight the promising role of PET in the early detection and management of PAD providing a summary of the current preclinical and clinical research related to PET imaging in patients with PAD and related advancement of PET scanner technology.

Proximal arm kinematics affect grip force-load force coordination.

During object manipulation, grip force is coordinated with load force, which is primarily determined by object kinematics. Proximal arm kinematics may affect grip force control, as proximal segment motion could affect control of distal hand muscles via biomechanical and/or neural pathways. The aim of this study was to investigate the impact of proximal kinematics on grip force modulation during object manipulation. Fifteen subjects performed three vertical lifting tasks that involved distinct proximal kinematics (elbow/shoulder), but resulted in similar end-point (hand) trajectories. While temporal coordination of grip and load forces remained similar across the tasks, proximal kinematics significantly affected the grip force-to-load force ratio (P = 0.042), intrinsic finger muscle activation (P = 0.045), and flexor-extensor ratio (P < 0.001). Biomechanical coupling between extrinsic hand muscles and the elbow joint cannot fully explain the observed changes, as task-related changes in intrinsic hand muscle activation were greater than in extrinsic hand muscles. Rather, between-task variation in grip force (highest during task 3) appears to contrast to that in shoulder joint velocity/acceleration (lowest during task 3). These results suggest that complex neural coupling between the distal and proximal upper extremity musculature may affect grip force control during movements, also indicated by task-related changes in intermuscular coherence of muscle pairs, including intrinsic finger muscles. Furthermore, examination of the fingertip force showed that the human motor system may attempt to reduce variability in task-relevant motor output (grip force-to-load force ratio), while allowing larger fluctuations in output less relevant to task goal (shear force-to-grip force ratio).

Abnormal proximal-distal interactions in upper-limb of stroke survivors during object manipulation: A pilot study.

Despite its importance, abnormal interactions between the proximal and distal upper extremity muscles of stroke survivors and their impact on functional task performance has not been well described, due in part to the complexity of upper extremity tasks. In this pilot study, we elucidated proximal-distal interactions and their functional impact on stroke survivors by quantitatively delineating how hand and arm movements affect each other across different phases of functional task performance, and how these interactions are influenced by stroke. Fourteen subjects, including nine chronic stroke survivors and five neurologically-intact subjects participated in an experiment involving transport and release of cylindrical objects between locations requiring distinct proximal kinematics. Distal kinematics of stroke survivors, particularly hand opening, were significantly affected by the proximal kinematics, as the hand aperture decreased and the duration of hand opening increased at the locations that requires shoulder abduction and elbow extension. Cocontraction of the extrinsic hand muscles of stroke survivors significantly increased at these locations, where an increase in the intermuscular coherence between distal and proximal muscles was observed. Proximal kinematics of stroke survivors was also affected by the finger extension, but the cocontraction of their proximal muscles did not significantly increase, suggesting the changes in the proximal kinematics were made voluntarily. Our results showed significant proximal-to-distal interactions between finger extension and elbow extension/shoulder abduction of stroke survivors exist during their functional movements. Increased cocontraction of the hand muscles due to increased neural couplings between the distal and proximal muscles appears to be the underlying mechanism.

Development of Self-Adaptable Mechanism to Compensate Angle-Dependent Flexor Tone of the Elbow Joint Post-stroke: A Pilot Study.

Upper extremity impairments are common among stroke survivors. Robotic devices enable a high-dose of repetitive training for patients, but most systems are confined to the laboratory settings due to their complexity and power requirements. Previously we developed a passive elbow device that can counteract the angle-dependent tone of flexor muscles with hypertonia, but its efficacy was found limited as the increase in passive assistance during elbow extension was found not sufficient to provide assistance to those with more severe impairments. Therefore, in this study, we developed a 'self-adaptable' passive device that adjusts its assistance level based on the movements of patients. In addition to the morphological design to adjust moment arms of the elastic components, we incorporated a self-adaptation mechanism, in which the lengths of the elastic bands were adjusted by a pair of miniature linear motors based on the joint position feedback signals. The capacity of the device was then tested in a pilot testing with two healthy subjects, for whom angle-dependent flexion torque was implemented to simulate flexor hypertonia. The additional adjustment of passive component lengths was found to further increase the elbow extension assistance as the elbow joint extended. The proposed self-adapting mechanism, which does not require any complex control input from the experimenters, can be incorporated with the existing passive device to improve its functional efficacy in home-based training.

Subject-specific, Impairment-based Robotic Training of Functional Upper Limb Movements.

Significant hand and upper-limb impairment is common post-stroke. Robotic training can administer a high-dose of repetitive movement training to stroke survivors, but its efficacy can be further improved by targeting specific impairments of individual patients. In this study, we developed a new robotic training protocol that identifies specific impairment patterns that degrade functional performance of individual patients and provide joint-specific assistance to counteract subject-specific impairments. The target tasks were also adjusted based on their task performance during training. Two chronic stroke survivors participated in a pilot training study to demonstrate the efficacy of the proposed impairment-based robotic training. Upper limb function of the participants was improved by the proposed training as shown in the clinical tests (6.5 ± 4.5 increase in Fugl-Meyer; 10 ± 6.9 increase in Action Research Arm Test), and the laboratory tests also showed improvement in their range of motion (hand) and voluntary reaching distance (arm). The impairment-based robotic training targeted (and improved) specific deficits of individual patients that hampered their task performance, which could have contributed to the observed functional improvement. The proposed training can enhance the rehabilitative outcome of robotic training by emphasizing the key components of effective rehabilitation, i.e., subject-specific, impairment-based training.Clinical Relevance- This study shows that impairment-based, 'subject-specific' robotic trainings can improve upper extremity function of stroke survivors.

Effects of task dynamics on coordination of the hand muscles and their adaptation to targeted muscle assistance.

Dynamic characteristics of a manual task can affect the control of hand muscles due to the difference in biomechanical/physiological characteristics of the muscles and sensory afferents in the hand. We aimed to examine the effects of task dynamics on the coordination of hand muscles, and on the motor adaptation to external assistance. Twenty-four healthy subjects performed one of the two types of a finger extension task, isometric dorsal fingertip force production (static) or isokinetic finger extension (dynamic). Subjects performed the tasks voluntarily without assistance, or with a biomimetic exotendon providing targeted assistance to their extrinsic muscles. In unassisted conditions, significant between-task differences were found in the coordination of the extrinsic and intrinsic hand muscles, while the extrinsic muscle activities were similar between the tasks. Under assistance, while the muscle coordination remained relatively unaffected during the dynamic task, significant changes in the coordination between the extrinsic and intrinsic muscles were observed during the static task. Intermuscular coherence values generally decreased during the static task under assistance, but increased during the dynamic task (all p-values < 0.01). Additionally, a significant change in the task dynamics was induced by assistance only during static task. Our study showed that task type significantly affect coordination between the extrinsic and intrinsic hand muscles. During the static task, a lack of sensory information from musculotendons and joint receptors (more sensitive to changes in length/force) is postulated to have resulted in a neural decoupling between muscles and a consequent isolated modulation of the intrinsic muscle activity.

Toward Restoration of Normal Mechanics of Functional Hand Tasks Post-Stroke: Subject-Specific Approach to Reinforce Impaired Muscle Function.

Robotic therapy enables mass practice of complex hand movements after stroke, but current devices generally enforce patients to reproduce prescribed kinematic patterns using rigid actuators, without considering individuals' unique impairment characteristics, thereby reducing their efficacy. In this paper, we tested the feasibility of a novel, theory-based "biomimetic" approach to restoring mechanics of complex hand tasks with subject-specific assistance patterns. Twelve chronic stroke survivors performed two simulated functional tasks: hand open and simulated pinch task (distal pad press). Assistance was provided by non-restraining actuators (exotendons) that counteracted 'subject-specific' impairments, identified during unassisted task performance. There was no constraint of movement to predefined patterns. Assistance patterns required to complete tasks were significantly different across subjects, reflecting high variability in impairment and required assistance patterns. For hand open, range of motion and interjoint coordination were significantly improved for severely impaired patients, while movement quality was enhanced (reduction in jerk) for those less impaired. For simulated pinch, subject-specific assistance restored task mechanics before injury, as patients were able to direct fingertip force toward the direction normal to surface; angular deviation reduced from 16.8°±10.4° to 3.7°±2.6°. Notably, electromyography data confirmed that subjects maintained an effort level under assistance comparable to unassisted conditions. The proposed method could lead to a novel paradigm for hand rehabilitation that restores complex task mechanics with a subject-specific assistance reflecting individual impairment characteristics while promoting subjects' participation.

Impact of Targeted Assistance of Multiarticular Finger Musculotendons on the Coordination of Finger Muscles During Isometric Force Production.

Neurological injuries often cause degraded motor control. While rehabilitation efforts typically focus on movement kinematics, abnormal muscle activation patterns are often the primary source of impairment. Muscle-based therapies are likely more effective than joint-based therapy. In this paper, we examined the feasibility of biomimetic input mimicking the action of human musculotendons in altering hand muscle coordination. Twelve healthy subjects produced a submaximal isometric dorsal fingertip force, while a custom actuator provided assistance mirroring the actions of either the extrinsic extensor or the intrinsic muscles of the index finger. The biomimetic inputs reduced the activation level of all task-related muscles, but the degree of change was different across the muscles, resulting in significant changes in their coordination (co-contraction ratios) and force-electromyography correlations. Each biomimetic assistance particularly increased the neural coupling between its targeted muscle and the antagonist muscle. Subjects appeared to fully take advantage of the assistance, as they provided minimal level of effort to achieve the task goal. The targeted biomimetic assistance may be used to retrain activation patterns post-stroke by effectively modulating connectivity between the muscles in the functional context and could be beneficial to restore hand function and reduce disability.

Restoring proper task mechanics of the hand post-stroke by targeted assistance of hand muscles.

Significant impairment in hand function is found prevalent among stroke survivors, but its effective restoration is challenging due to the complexity of the functional tasks of the hand. In this study, we proposed a novel approach to improve functionality of the hand post-stroke by providing `subject-specific' patterns of targeted assistance to impaired musculotendon of the hand during functional task performance. Eleven chronic stroke survivors participated in the experiment in which a biomimetic device provided targeted assistance to the impaired hand musculotendons. The proposed subject-specific approach was found to restore proper mechanics of two functional tasks, hand open and palmar pinch, as quantified by the joint kinematics and fingertip force direction. The range of motion and joint coordination was improved for the hand open task, and the fingertip force was directed towards normal direction by the targeted assistance of impaired muscles. The assistance pattern was significantly different across subjects, indicating significant between-subject variability in the impairment characteristics that affect task performance. The proposed method could enable an effective `subject-specific' training method that restores proper mechanics of functional hand tasks for stroke survivors.

Impact of actuator impedance characteristics on motor control of assisted hand movements.

Robotic devices hold potential to improve hand rehabilitation outcome by providing consistent sensorimotor training. However, most robotic devices focus on simply reproducing `predefined' kinematics of manual tasks without properly considering how human adapts to external assistance, while inherent impedance of the actuator could have a significant impact on the neural adaptation of human subjects. We thus examined the effects of the impedance characteristics of the actuators on human motor adaptation under external assistance. Four male subjects with no known impairment of hand function participated in an experiment, in which subjects performed hand open tasks (against resistance) while actuators of different impedance characteristics (pneumatic vs. motor) were used to provide assistance. It was found that the joint coordination pattern under pneumatic assistance was more similar to that of voluntary movements. More importantly, the pneumatic actuators improved agonist-antagonist ratio during movements. They also induced sustained contraction of task-related muscles during hold phase, while the activation of all muscles during hold phase decreased under motor assistance, possibly due to its poor backdrivability. Our results suggest that pneumatic-type actuators with low inherent impedance could provide many benefits compared to conventional electric motors, as it could reduce cocontraction of antagonist muscles of patients while effectively promoting active participation during training.