Dena R. Howland

Regularized positive-definite fourth order tensor field estimation from DW-MRI.

In Diffusion Weighted Magnetic Resonance Image (DW-MRI) processing, a 2nd order tensor has been commonly used to approximate the diffusivity function at each lattice point of the DW-MRI data. From this tensor approximation, one can compute useful scalar quantities (e.g. anisotropy, mean diffusivity) which have been clinically used for monitoring encephalopathy, sclerosis, ischemia and other brain disorders. It is now well known that this 2nd-order tensor approximation fails to capture complex local tissue structures, e.g. crossing fibers, and as a result, the scalar quantities derived from these tensors are grossly inaccurate at such locations. In this paper we employ a 4th order symmetric positive-definite (SPD) tensor approximation to represent the diffusivity function and present a novel technique to estimate these tensors from the DW-MRI data guaranteeing the SPD property. Several articles have been reported in literature on higher order tensor approximations of the diffusivity function but none of them guarantee the positivity of the estimates, which is a fundamental constraint since negative values of the diffusivity are not meaningful. In this paper we represent the 4th-order tensors as ternary quartics and then apply Hilberts theorem on ternary quartics along with the Iwasawa parametrization to guarantee an SPD 4th-order tensor approximation from the DW-MRI data. The performance of this model is depicted on synthetic data as well as real DW-MRIs from a set of excised control and injured rat spinal cords, showing accurate estimation of scalar quantities such as generalized anisotropy and trace as well as fiber orientations.

Locomotor Training Restores Walking in a Nonambulatory Child With Chronic, Severe, Incomplete Cervical Spinal Cord Injury

Background and Purpose: Locomotor training (LT) enhances walking in adult experimental animals and humans with mild-to-moderate spinal cord injuries (SCIs). The animal literature suggests that the effects of LT may be greater on an immature nervous system than on a mature nervous system. The purpose of this study was to evaluate the effects of LT in a child with chronic, incomplete SCI. Subject: The subject was a nonambulatory 4½-year-old boy with an American Spinal Injury Association Impairment Scale (AIS) C Lower Extremity Motor Score (LEMS) of 4/50 who was deemed permanently wheelchair-dependent and was enrolled in an LT program 16 months after a severe cervical SCI. Methods: A pretest-posttest design was used in the study. Over 16 weeks, the child received 76 LT sessions using both treadmill and over-ground settings in which graded sensory cues were provided. The outcome measures were ASIA Impairment Scale score, gait speed, walking independence, and number of steps. Result: One month into LT, voluntary stepping began, and the child progressed from having no ability to use his legs to community ambulation with a rolling walker. By the end of LT, his walking independence score had increased from 0 to 13/20, despite no change in LEMS. The childs final self-selected gait speed was 0.29 m/s, with an average of 2,488 community-based steps per day and a maximum speed of 0.48 m/s. He then attended kindergarten using a walker full-time. Discussion and Conclusion: A simple, context-dependent stepping pattern sufficient for community ambulation was recovered in the absence of substantial voluntary isolated lower-extremity movement in a child with chronic, severe SCI. These novel data suggest that some children with severe, incomplete SCI may recover community ambulation after undergoing LT and that the LEMS cannot identify this subpopulation.

Effects of trunk restraint combined with intensive task practice on poststroke upper extremity reach and function: a pilot study.

Background. Poststroke reaching is characterized by excessive trunk motion and abnormal shoulder—elbow coordination. Little attention is typically given to arm—trunk kinematics during task practice. Preventing compensatory trunk motion during short-term practice immediately improves kinematics, but effects of longer-term practice are unknown. Objective. This study compared the effects of intensive task practice with and without trunk restraint on poststroke reaching kinematics and function. Methods. A total of 11 individuals with chronic stroke, baseline Fugl-Meyer Upper Extremity Assessment scores 26 to 54, were randomized to 2 constraint-therapy intervention groups. All participants wore a mitt on the unaffected hand for 90% of waking hours over 14 days and participated in 10 days/6 hours/day of supervised progressive task practice. During supervised sessions, one group trained with a trunk restraint (preventing anterior trunk motion) and one group did not. Tasks for the trunk-restraint group were located to afford repeated use of a shoulder flexion—elbow extension reaching pattern. Outcome measures included kinematics of unrestrained targeted reaching and tests of functional arm ability. Results. Posttraining, the trunk-restraint group demonstrated straighter reach trajectories (P = .000) and less trunk displacement (P = .001). The trunk-restraint group gained shoulder flexion (P = .006) and elbow extension (P = .022) voluntary ranges of motion, the nonrestraint group did not. Posttraining angle—angle plots illustrated that individuals from the trunk-restraint group transitioned from elbow flexion to elbow extension during mid-reach; individuals in the nonrestraint group retained pretraining movement strategies. Both groups gained functional arm ability (P < .05 all tests). Conclusion. Intensive task practice structured to prevent compensatory trunk movements and promote shoulder flexion—elbow extension coordination may reinforce development of “normal” reaching kinematics.

Transplants Enhance Locomotion in Neonatal Kittens Whose Spinal Cords Are Transected: A Behavioral and Anatomical Study

We have studied the locomotor development of kittens that received complete low thoracic spinal cord transections and embryonic spinal cord transplants as newborns. Embryonic spinal cord (E21-E26) transplanted into the site of a transection integrated well with the host spinal cord and promoted the development of overground locomotion. Spinalized kittens with transplants were first distinguished from spinalized kittens during the 2nd and 3rd postnatal weeks when kittens with transplants positioned their hindlimbs underneath their bodies which promoted support of the hindquarters. By postnatal Week 6, kittens with transplants exhibited overground locomotion characterized by full weight support and moderate balance control. By 20 weeks of age, as many as 96% of the step cycles showed full weight support and as few as 2% of the step cycles were interrupted by a fall. Most kittens also showed coordination between the forelimbs and the hindlimbs. They differed from normal in the precocious onset of reflex stepping and in the less precise interlimb coordination and more precarious balance during overground locomotion. The overground locomotor performance of kittens with transplants greatly exceeded that of spinal kittens without transplants since few spinalized kittens showed any full-weight-supported step cycles and none showed coordination between the forelimbs and the hindlimbs. In the absence of a transplant, no fibers could grow across the lesion site. In the presence of a transplant, fibers grew across the lesion site and established anatomical connectivity with the host. Host segmental systems identified by the presence of calcitonin gene-related peptide- and substance P-immunoreactive fibers were found throughout the transplants. Descending host systems of supraspinal origin were identified by serotonin- and dopamine beta-hydroxylase-immunoreactive fibers throughout the transplants. The growth of supraspinal axons into the transplant, and in one case into the caudal host spinal cord, provided a possible anatomical basis for the development of coordinated overground locomotion.

Fetal Neural Grafts and Repair of the Injured Spinal Cord

Solid or suspension grafts of fetal spinal cord (FSC), caudal brainstem (FBSt), neocortex (FNCx) or a combination of either FSC/FNCx or FSC/FBSt were placed into cavities produced by static loading (i.e., compression) of the spinal cord of adult cats two to 30 weeks after injury. Extensively vascularized, viable graft tissue was found in all animals with the exception of two cats which showed active rejection of their transplants. Surviving grafts showed many immature characteristics 6–9 weeks after transplantation. However, by 20–30 weeks FSC and FBSt grafts were more mature. Grafts integrated with the host gray and white matter and neuritic processes from both host and graft were seen crossing the host‐graft interface. Host calcitonin gene related peptide (CGRP)‐like immunoreactive axons could be traced into FSC and FBSt grafts. A more restricted ingrowth of host serotonin (5‐HT)‐like immunoreactive fibers was seen in FSC grafts. Our results suggest that the capacity of homotypic transplants to promote recovery of function is greater than heterotypic transplants. Additionally, it appears that the functional capacity of the graft depends upon graft survival, the time interval between injury and transplantation, and whether or not the lesion cavity was debrided prior to grafting.

Intact aggrecan and chondroitin sulfate-depleted aggrecan core glycoprotein inhibit axon growth in the adult rat spinal cord

Aggrecan is a chondroitin sulfate (CS)/keratan sulfate (KS)-substituted proteoglycan (PG) abundant in cartilage which is also present within the mammalian embryonic, adult, and injured adult central nervous system (CNS). Although its role within the CNS is not clear, cell culture studies show that when substituted with CS, aggrecan inhibits neurite extension. To better understand the inhibitory effect of aggrecan on injured adult axons in vivo, we developed a model to independently test intact aggrecan and CS-depleted aggrecan core glycoprotein. Acute rat spinal cord hemisection cavities were filled with a growth-promoting matrix, Matrigel, and severed dorsal rootlets were placed into this matrix. This created an assay in which axons readily grew. The extent of ingrowth in this baseline assay was compared to the ingrowth in Matrigel loaded with intact aggrecan or the purified core glycoprotein of aggrecan. Our results show that both intact aggrecan and equivalent concentrations of the core glycoprotein component significantly inhibit axonal growth in this model system. These results confirm that aggrecan can inhibit the growth of adult axons in vivo and suggest that the inhibitory effects of aggrecan may be mediated, at least in part, by structures located on the core glycoprotein in the absence of the bulk of the CS chains.

Extracting Tractosemas from a Displacement Probability Field for Tractography in DW-MRI

In this paper we present a novel method for estimating a field of asymmetric spherical functions, dubbed tractosemas, given the intra-voxel displacement probability information. The peaks of tractosemas correspond to directions of distinct fibers, which can have either symmetric or asymmetric local fiber structure. This is in contrast to the existing methods that estimate fiber orientation distributions which are naturally symmetric and therefore cannot model asymmetries such as splaying fibers. We propose a method for extracting tractosemas from a given field of displacement probability iso-surfaces via a diffusion process. The diffusion is performed by minimizing a kernel convolution integral, which leads to an update formula expressed in the convenient form of a discrete kernel convolution. The kernel expresses the probability of diffusion between two neighboring spherical functions and we model it by the product of Gaussian and von Mises distributions. The model is validated via experiments on synthetic and real diffusion-weighted magnetic resonance (DW-MRI) datasets from a rat hippocampus and spinal cord.

Development of locomotor behavior in the spinal kitten

This study was undertaken to determine the locomotor capability of kittens whose spinal cords were transected at birth. The postnatal development of reflex and goal-directed locomotion was examined during the first 5 postnatal months in kittens that received low thoracic spinal cord transections as newborns. Some spinal kittens developed aberrant quadrupedal forms of locomotion. The onset of quadrupedal locomotion, however, was delayed by 2-3 months compared to the normal kitten (42) and deteriorated by 5 months of age. Qualitative and quantitative analyses demonstrated that the quadrupedal locomotion was abnormal. Although some step cycles were characterized by full weight support, the typical hindlimb step cycle of the best performing cat showed inadequate weight support and balance. No spinal cat was able to coordinate the hindlimbs with the forelimbs during overground locomotion on a runaway or during quadrupedal locomotion on a treadmill. Neuroanatomical tracing with WGA-HRP and immunocytochemical techniques showed no axonal regeneration or growth into or across the lesion sites. The aberrant form of quadrupedal locomotion developed without descending input to the caudal spinal cord. The variability in performance among animals suggested that compensatory strategies were important factors in the spinal kittens achievement of quadrupedal locomotion. Hindlimb weight-supported stepping during quadrupedal locomotion in some animals underscored the capacity of the isolated caudal spinal cord to generate both rhythmical stepping movements and weight support. The maintenance of developmentally immature, but functional, hindlimb postures suggested that the development of the isolated caudal spinal cord was arrested in the absence of descending input.

Ongoing Walking Recovery 2 Years After Locomotor Training in a Child With Severe Incomplete Spinal Cord Injury

Background and Purpose The authors previously reported on walking recovery in a nonambulatory child with chronic, severe, incomplete cervical spinal cord injury (SCI) after 76 sessions of locomotor training (LT). Although clinical measures did not predict his recovery, reciprocal patterned leg movements developed, affording recovery of independent walking with a reverse rolling walker. The long-term functional limitations and secondary complications often associated with pediatric-onset SCI necessitate continued follow-up of children with SCI. Therefore, the purpose of this case report is to describe this childs walking function and musculoskeletal growth and development during the 2 years since his participation in an LT program and subsequent walking recovery. Case Description Following LT, the child attended elementary school as a full-time ambulator. He was evaluated 1 month (baseline), 1 year, and 2 years after LT. Examination of walking function included measures of walking independence, gait speed and spatiotemporal parameters, gait kinematics, and daily step activity. Growth and development were assessed by tracking his height, weight, incidence of musculoskeletal complications, and gross motor task performance. Outcomes Over the 2 years, the child continued to ambulate independently with a reverse rolling walker, increasing his fastest gait speed. Spatiotemporal and kinematic features of his walking improved, and daily step activity increased. Height and weight remained on their preinjury trajectory and within age-appropriate norms. The child experienced only minor musculoskeletal complications. Additionally, he gained the ability to use reciprocal patterned leg movements during locomotor tasks such as assisted stair climbing and independent tricycle pedaling. Conclusions Two years after recovery of walking, this child with incomplete SCI had maintained and improved his walking function and experienced age-appropriate growth and development.

Arm and leg coordination during treadmill walking in individuals with motor incomplete spinal cord injury: A preliminary study

Arm and leg coordination naturally emerges during walking, but can be affected by stroke or Parkinsons disease. The purpose of this preliminary study was to characterize arm and leg coordination during treadmill walking at self-selected comfortable walking speeds (CWSs) in individuals using arm swing with motor incomplete spinal cord injury (iSCI). Hip and shoulder angle cycle durations and amplitudes, strength of peak correlations between contralateral hip and shoulder joint angle time series, the time shifts at which these peak correlations occur, and associated variability were quantified. Outcomes in individuals with iSCI selecting fast CWSs (range, 1.0-1.3m/s) and speed-matched individuals without neurological injuries are similar. Differences, however, are detected in individuals with iSCI selecting slow CWSs (range, 0.25-0.65 m/s) and may represent compensatory strategies to improve walking balance or forward propulsion. These individuals elicit a 1:1, arm:leg frequency ratio versus the 2:1 ratio observed in non-injured individuals. Shoulder and hip movement patterns, however, are highly reproducible (coordinated) in participants with iSCI, regardless of CWS. This high degree of inter-extremity coordination could reflect an inability to modify a single movement pattern post-iSCI. Combined, these data suggest inter-extremity walking coordination may be altered, but is present after iSCI, and therefore may be regulated, in part, by neural control.