Associate Professor
Research Kinesiologist, Rehabilitation Research and Training Center in Neuromuscular Disease
I graduated from Computer Science department at Stanford University in 1972 with PhD degree. Then I spent 30 years at the University of Pennsylvania as a professor in Computer and Information Science department. In 2001 I joined the EECS department at UC Berkeley,CA. Over 40 years I have pursued research in Computer Vision, Robotics and Medical Imaging. I am a member of the NAE and IOM of the National Academy of Sciences.
Introduction: One of the major challenges in the neuromuscular field has been lack of upper extremity outcome measures that can be useful for clinical therapeutic efficacy studies. Using vision-based sensor system and customized software, 3-dimensional (3D) upper extremity motion analysis can reconstruct a reachable workspace as a valid, reliable and sensitive outcome measure in various neuromuscular conditions where proximal upper extremity range of motion and function is impaired.
Methods: Using a stereo-camera sensor system, 3D reachable workspace envelope surface area normalized to an individual’s arm length (relative surface area: RSA) to allow comparison between subjects was determined for 20 healthy controls and 9 individuals with varying degrees of upper extremity dysfunction due to neuromuscular conditions. All study subjects were classified based on Brooke upper extremity function scale. Right and left upper extremity reachable workspaces were determined based on three repeated measures. The RSAs for each frontal hemi-sphere quadrant and total reachable workspaces were determined with and without loading condition (500 gram wrist weight). Data were analyzed for assessment of the developed system and validity, reliability, and sensitivity to change of the reachable workspace outcome.
Results: The mean total RSAs of the reachable workspace for the healthy controls and individuals with NMD were significantly different (0.586 ± 0.085 and 0.299 ± 0.198 respectively; p<0.001). All quadrant RSAs were reduced for individuals with NMDs compared to the healthy controls and these reductions correlated with reduced upper limb function as measured by Brooke grade. The upper quadrants of reachable workspace (above the shoulder level) demonstrated greatest reductions in RSA among subjects with progressive severity in upper extremity impairment. Evaluation of the developed outcomes system with the Bland-Altman method demonstrated narrow 95% limits of agreement (LOA) around zero indicating high reliability. In addition, the intraclass correlation coefficient (ICC) was 0.97. Comparison of the reachable workspace with and without loading condition (wrist weight) showed significantly greater RSA reduction in the NMD group than the control group (p<0.012), with most of the workspace reduction occurring in the ipsilateral upper quadrant relative to the tested arm (p<0.001). Reduction in reachable workspace due to wrist weight was most notable in those subjects with NMD with marginal strength reserve and moderate degree of impairment (Brooke = 2) rather than individuals with mild upper extremity impairment (Brooke = 1) or individuals who were more severely impaired (Brooke =3).
Discussion: The developed reachable workspace evaluation method using scalable 3D vision technology appears promising as an outcome measure system for clinical studies. A rationally-designed combination of upper extremity outcome measures including a region-specific global upper extremity outcome measure, such as the reachable workspace, complemented by targeted disease- or function-specific endpoints, may be optimal for future clinical efficacy trials.
Most efficacy clinical trials in neuromuscular diseases (NMDs) to date have focused on ambulatory outcome measures as the primary endpoints. However, focusing solely on the ambulatory outcome measures for clinical trials excludes a large portion of potential study populations (e.g. those who are non-ambulatory, older, or at various stages of disease progression not satisfying the mobility criteria). This becomes doubly critical in neuromuscular diseases where majority are also rare conditions with small pool of potential study participants. Thus, one of the major challenges in NMD research has been lack of upper extremity clinical endpoints that can be useful for clinical trials.
Several recent international workshops and studies have highlighted the need to identify and/or develop clinical outcome measures that can be used for efficacy studies in both ambulatory and non-ambulatory NMD populations.
Many traditional clinical evaluations of upper extremity function are available and include range of motion (ROM), manual and quantitative muscle strength test (MMT, QMT), standardized timed function tests (9-hole peg test, Jebsen-Taylor hand function test) and various motor function scales (Brooke).
A wide range of daily activities require unrestricted movement of the upper extremity, primarily in the shoulder, to extend the reachability of the hand which is used to grasp, position or otherwise interact with various objects and environment.
An in-depth characterization of the proximal upper extremity motion can be obtained using traditional motion analysis systems with active or passive markers (multiple cameras arrayed to provide 360° motion information).
Recently, an innovative method to measure and graphically reconstruct an individual’s upper extremity 3D reachable workspace using a low-cost single stereo camera sensor system was developed by the study investigators.
In this paper we assess the applicability of the developed 3D vision sensor-based upper extremity reachable workspace outcome measure by examining the test-retest reliability, validity, and sensitivity to change in neuromuscular disease patients. For validity testing, we assessed the outcome measure’s ability to differentiate individuals with and without functional impairments, and whether it can discriminate between individuals with mild to moderate impairments. To assess the reliability of the system, three repeated trials were performed on the same day for the dominant and the non-dominant arm. To initially assess the sensitivity of the system, we examined whether additional load to the upper extremity (500 gram wrist weight) can alter the total and quadrant 3D reachable workspace envelope surface area. Our hypothesis was that the relatively low weight would not affect the reachability in healthy controls while the patients with shoulder girdle weakness (individuals with neuromuscular conditions with marginal reserve function) would exhibit changes in ability to reach the utmost portions of the workspace envelope (observe most changes in the top quadrants) under the loading condition with a wrist weight. We also examined whether there were gender and hand-dominance differences in upper extremity 3D reachable workspace detectable by the developed stereo-camera sensor system.
Assessment of upper limb functional status was performed with all subjects using the Brooke upper extremity function scale. All control subjects were healthy and had a Brooke grade of 1. Brooke grades and demographic information (diagnosis, age, and sex) for the subjects with upper extremity impairments are shown in Table 1. For reference, grading of Brooke scale with respective functional descriptions is shown in Table 2.
Id
Age
Sex
Diagnosis
Brooke Grade
1
47
M
BMD
1
2
49
M
BMD
1
3
55
M
BMD
2
4
29
M
BMD
2
5
70
F
FSHD
2
6
29
M
Pompe
2
7
13
M
DMD
2
8
54
M
BMD
3
9
49
M
FSHD
3
Grade
Functional description
1
Starting with arms at the sides, the patient can abduct the arms in a full circle until they touch above the head.
2
Can raise arms above head only by flexing the elbow (shortening the circumference of the movement) or using accessory muscles.
3
Cannot raise hands above head, but can raise an 8-oz glass of water to the mouth.
4
Can raise hands to the mouth, but cannot raise an 8-oz glass of water to the mouth.
5
Cannot raise hands to the mouth, but can use hands to hold a pen or pick up pennies from the table.
6
Cannot raise hands to the mouth and has no useful function of hands.
We calculated the absolute reachable workspace surface envelope area (m2) for each of the quadrants and the summated total area (m2). Normalization of acquired reachable workspace surface areas to the surface area of the unit hemi-sphere allowed comparison between subjects. This relative surface area (RSA) represents the portion of the unit hemi-sphere that is covered by the hand movement. It is determined by dividing the area by the factor
Example graphical outputs of RSA for a healthy individual (control subject), an individual with Becker muscular dystrophy and mild phenotype (BMD, Brooke=1), an individual with Duchenne muscular dystrophy (DMD, Brooke=2), and an individual with Facioscapulohumeral dystrophy (FSHD, Brooke=3).
As shown in Table 3, the total mean relative surface area (RSA) of the subjects with NMD and the healthy controls are significantly different from each other. In addition, the RSA of each quadrant was significantly different between the subjects with NMD and the healthy controls. There was relatively greater loss of upper quadrant reachable workspace (above the shoulder quadrants 1 and 3) in subjects with NMDs as compared to controls, as can be expected.
Means ± SD and sample size (n) are presented as the average value over three repeated trials for dominant and non-dominant sides (there were no significant side to side difference). NMD vs Control by two-sample t-test. Ha: mean = 0
Quad 1
Quad 2
Quad 3
Quad 4
TOTAL
Subject samples (n)
Contralateral Quadrants Upper & Lower
Ipsilateral Quadrants Upper & Lower
NMD
0.014 ±0.019 (18)
0.012 ±0.019 (18)
0.122 ±0.107 (18)
0.151 ±0.072 (18)
0.299 ±0.198 (18)
CONTROL
0.070 ±0.031 (40)
0.035 ±0.016 (40)
0.248 ±0.054 (40)
0.234 ±0.031 (40)
0.586 ±0.085 (40)
NMD vs CONTROL
p<0.001
p<0.001
p<0.001
p<0.001
p<0.001
Further analysis was performed to assess the relative surface area (RSA) of the subjects with NMD by documented impairment as determined by the Brooke upper extremity functional grade. An analysis of variance revealed significant differences between the total RSA by Brooke grade of the subjects with NMD (p<0.05). The mean total RSA for subjects with NMD with a Brooke grades of 1, 2, and 3 were 0.493 ± 0.066, 0.294 ± 0.153, and 0.080 ± 0.023, respectively. As shown in Figure 3 with the radar plot, the NMD group with a Brooke grade of 1 had a slightly reduced reachable workspace area than healthy controls with the same Brooke grade of 1, with most appreciable losses in Quad 1 and Quad 3 (upper quadrants). Individuals with Brooke grade of 2 demonstrate reductions in RSA of both the ipsilateral upper and lower quadrants when compared to controls (48% in Quad 3 and 39% in Quad 4 respectively). Individuals who had a Brooke grade of 3 displayed minimal reachable workspace that was essentially limited to the lower ipsilateral quadrant (quadrant 4).
For additional validity testing, two-sample t-tests were used to assess whether gender and hand dominancy affects the total as well as quadrant RSAs; however, these did not have significant effects (data not shown). Briefly, the RSA of Quadrant 2 was statistically greater only for the healthy able-bodied female subjects than males, which may be indicative of their greater flexibility. However, no other significant gender or hand dominancy differences were observed either in the control or NMD groups in the total reachable workspace or in other quadrants.
Controls with Brooke grade 1 is shown in blue line, subjects with NMD with Brooke grade 1,2,3 are shown in red, green, and purple lines respectively (shown in right upper extremity orientation).
The Bland-Altman plot for the total reachable surface area (a). The mean difference for the groups was 0.014 and the upper lines and lower lines designate the 95% limits of agreement. Reproducibility of the total RSA at trial 2 and trial 3 versus trial 1 (b).
Means ± SD. One-sample t-test. p-value represents comparison between RSAs with and without loading condition. ns= not significant. Ha: mean > 0
Quad 1
Quad 2
Quad 3
Quad 4
TOTAL
Contralateral Quadrants Upper & Lower
Ipsilateral Quadrants Upper & Lower
CONTROL
0.011 ±0.026 (39) p<0.007
0.001 ±0.016 (39) ns
0.007 ±0.028 (39) ns
0.007 ±0.026 (39) ns
0.025 ±0.069 (39) p<0.016
NMD
0.004 ±0.007 (17) p<0.016
0.005 ±0.012 (17) ns
0.022 ±0.031 (17) p<0.005
0.018 ±0.030 (17) p<0.012
0.039 ±0.049 (17) p<0.002
The results of RSA reduction are shown for the following groups: controls (a), NMD subjects with Brooke grade 1 (b), with grade 2 (c), and with grade 3 (d). (Shown in right upper extremity orientation. Note: scale is different for better visualization).
Subjects who had a moderate degree of impairment (Brooke grade = 2) exhibited a greater percent reduction of their original reachable workspace with loading condition than individuals with mild upper extremity impairment (Brooke = 1) or individuals who were more severely impaired (Brooke =3). Analysis of which quadrant most significantly contributed to this reduction in overall RSA showed that quadrant 3 was most affected by the loading protocol (p<0.008). Although the sample sizes are small, the results suggest that reachable workspace measurement in combination with loading condition protocol may provide finer granularity in detection of marginal shoulder weakness and upper extremity impairments.
In our previously published paper, we demonstrated the feasibility of using a relatively inexpensive vision-based sensor system to acquire an upper extremity region-specific outcome measure (reachable workspace) capable of discerning changes in the upper extremity function for a clinical trial. In this paper, we follow up on the previously published work
Even though the sample sizes were relatively small, the data suggests that the developed system and methodology is not only capable of detecting differences in the total reachable workspace surface area, but also suggest that the system might be sensitive enough to differentiate the changes in reachable workspace of each quadrant between individuals with no documented impairment, mild impairment, and moderate impairment as categorized by Brooke scale. These results will need verification with a larger sample per subgroup. The continuous variable nature of the reachable workspace outcome measure as opposed to the ordinal nature of the Brooke scale will likely contribute to the sensitivity and utility of the developed outcome measure. In addition, through validity testing the methodology, the results reveal, as was suspected, that the individuals with NMD and mild phenotype begin to lose ROM in their upper quadrants first (with ipsilateral upper quadrant undergoing somewhat greater reduction in reachable workspace than the contralateral upper quadrant). The Bland-Altman methodology and the intraclass correlation coefficient indicates a high test-retest reliability.
The sensitivity of the developed measurement system was evaluated by addition of a very small load (500 gram wrist weight). The developed loading condition methodology in combination with the reachable workspace outcome measure was able to detect reduction in reachable workspace with loading conditions in both the healthy control and the subjects with NMD. As we hypothesized, even a relatively small additional wrist weight had a greater effect on the subjects with NMD than on the able-bodied control subjects, as observed by greater reduction of RSA in subjects with NMD. As expected, the upper quadrants’ reachable workspace was reduced to a greater degree than the lower quadrants’. Furthermore, the loading protocol had the most profound effect on individuals who had a Brooke grade of 2 (those individuals with marginal weakness who can raise arms above head only by flexing the elbow, by shortening the circumference of the movement or using accessory muscles). There was less degree of reduction in RSA for the subjects with NMD with Brooke grade 1 and 3, most likely due to presence of adequate reserve strength to overcome the small load in case with Brooke grade 1, and the underlying severity of weakness in those with Brooke grade 3 which suggests a floor effect of the method using the selected weight. Although this study has a very small sample size, it shows that the methodology might be capable of detecting small differences in reachable workspace.
Overall, the results suggest that reachable workspace measurement in combination with alternative loading condition protocols with weights gradually increasing from low to higher weights may further improve the sensitivity of the test, and provide additional granularity to detect subtle differences in upper extremity function found in individuals with various neuromuscular conditions. For this present study, an additional load of 500 g wrist weight was chosen as a standard weight for the protocol, but it was also chosen with consideration for clinical meaning because it is similar to the weight of a glass of water and various office-setting objects. The ability to maneuver this weight in space may have a profound effect on activities of daily living such as being able to handle and drink from a cup/mug, feed independently, or perform work-related duties. The results of the study encourage us to further investigate the effects of various load conditions (i.e., using set of lighter weights) on the reachable workspace envelope that can be used to further quantify the upper extremity function, provide finer granularity to the outcome measure, and assess fatigue effects.
Some of the limitations of this study were the small sample sizes and that the study did not examine individuals who had severe impairments in the arm function with Brooke grade >3. The study’s focus is the reachable workspace outcome measure and in fact, the developed method is most appropriate with individuals with mild to moderate proximal upper extremity impairments, with Brooke grade ≤3. In general with neuromuscular conditions (there are also exceptions), individuals with more profound impairment of their upper extremity function have very little movements at the shoulder. For these instances, other tests will need to be developed and may be more appropriate to assess range of motion and function for the distal upper extremity (forearm, wrist, hand, and fingers).
Future studies involving the developed 3D reachable workspace outcome include further correlation with other established upper extremity measures as well as person-reported outcome measures of function and correlation with clinically-meaningful milestone events such as loss of self-feeding ability. Building on the developed foundational methodology and the concept of reachable workspace outcome measure, the investigators are also developing a Kinect sensor-based system
This study has shown that the developed innovative approach to assessing upper extremity function by reachable workspace outcome measure, using a 3D vision-based sensor system is valid, reliable, and sensitive to small changes in upper extremity range of motion. The 3D reachable workspace surface envelope area as a continuous variable is a direct measurement of overall ROM in the upper extremity, and does alleviate some problems associated with other surrogate measures (e.g. ordinal scale, lack of granularity in data, task-oriented outcomes with limited generalizability, time variable as a sole outcome for performance of complicated tasks). In addition, the developed reachable workspace outcome measure provides an intuitive region-specific global metric for upper extremity that can be used across multiple neuromuscular conditions. Continued progress in development of innovative upper extremity outcome measures will facilitate the overall therapeutic discovery process.
The authors have declared that no competing interests exist.
We would like to thank the study participants for their time and effort, Craig McDonald for departmental support and encouragement of the research project, Sunny Kim for statistical advice, Evan deBie for manuscript figure preparation.