Dr. Weber's research seeks to develop markers of pain and sensorimotor function using machine-learning and advanced brain, spinal cord, and musculoskeletal magnetic resonance imaging. Dr. Weber aims to use these techniques to better understand the neuropathology of pain and neurological conditions and discover more effective treatments and preventative strategies.

Honors & Awards

  • Dermatomal Mapping with Spinal Cord Functional Magnetic Resonance Imaging (R01NS133305), National Institute of Neurological Disorders and Stroke (2023-2028)
  • Neuromuscular Signatures to Predict Surgical Response in Cervical Myelopathy (R01NS128478), National Institute of Neurological Disorders and Stroke (2023-2028)
  • NIH Clinical Research Extramural Loan Repayment Program Award (L30NS108301), National Institute of Neurological Disorders and Stroke (2022 - 2024)
  • George B. McClelland Researcher of the Year Award, American Chiropractic Association (2021)
  • Mentored Patient-Oriented Research Career Development Award (K23NS104211), National Institute of Neurological Disorders and Stroke (2018 - 2023)
  • NIH Clinical Research Extramural Loan Repayment Program Award (L30NS108301), National Institute of Neurological Disorders and Stroke (2020 - 2022)
  • MRI and Machine Learning to Improve Early Prognosis and Clinical Management after SCI (R03HD094577), Eunice Kennedy Shriver National Institute of Child Health and Human Development (2019 - 2021)
  • NIH Clinical Research Extramural Loan Repayment Program Award (L30NS108301), National Institute of Neurological Disorders and Stroke (2018 - 2020)
  • Ruth L. Kirschstein National Research Service Award Individual Fellowship (F32AT007800), National Center for Complementary and Integrative Health (2012 - 2015)

Education & Certifications

  • Postdoctoral Fellowship, Stanford University, Clinical Pain Research (2018)
  • PhD, Northwestern University, Neuroscience (2016)
  • DC, Palmer College of Chiropractic, Chiropractic (2009)
  • BS, Saginaw Valley State University, Biology (2006)


  • Neuroimaging-Based Brain and Spinal Cord Biomarkers for Cervical Radiculopathy


    Palo Alto, CA

Professional Affiliations and Activities

  • Staff Chiropractor, Palo Alto Veterans Affairs Health Care System (2024 - Present)
  • Co-Section Editor — Psychology, Psychiatry & Brain Neuroscience, Pain Medicine (2022 - Present)
  • Associate Editor, Pain Medicine (2020 - 2022)
  • Fellow, Chiropractic Academy for Research Leadership (2020 - Present)
  • Ambassador, NIH Loan Repayment Program (2019 - Present)

All Publications

  • Investigating the Associations between Lumbar Paraspinal Muscle Health and Age, BMI, Sex, Physical Activity and Back Pain using an Automated Computer-Vision Model: A UK Biobank Study. The spine journal : official journal of the North American Spine Society Wesselink, E. O., Pool-Goudzwaard, A., De Leener, B., Law, C., Fenyo, M. B., Ello, G. M., Coppieters, M. W., Elliott, J. M., Mackey, S., Weber, K. A. 2024


    BACKGROUND CONTEXT: The role of lumbar paraspinal muscle health in back pain (BP) is not straightforward. Challenges in this field have included the lack of tools and large, heterogenous datasets to interrogate the association between muscle health and BP. Computer-vision models have been transformative in this space, enabling the automated quantification of muscle health and the processing of large datasets.PURPOSE: To investigate the associations between lumbar paraspinal muscle health and age, sex, BMI, physical activity, and BP in a large, heterogenous dataset using an automated computer-vision model.DESIGN: Cross-sectional Study PATIENT SAMPLE: Participants from the UK Biobank with abdominal Dixon fat-water MRI (N=9,564) were included (41.8% women; mean (SD) 63.5 (7.6) years; BMI: 26.4 (4.1) kg/m2) of whom 6,953 reported no pain, 930 acute BP, and 1,681 chronic BP.OUTCOME MEASURES: Intramuscular fat (IMF) and average cross-sectional area (aCSA) were automatically derived using a computer-vision model for the left and right lumbar multifidus (LM), erector spinae (ES), and psoas major (PM) from the L1 to L5 vertebral levels.METHODS: Two-tailed partial Pearson correlations were generated for each muscle to assess the relationships between the muscle measures (IMF and aCSA) and age (controlling for BMI, sex, and physical activity), BMI (controlling for age, sex, and physical activity), and physical activity (controlling for age, sex, and BMI). One-way ANCOVA was used to identify sex differences in IMF and aCSA for each muscle while controlling for age, BMI, and physical activity. Similarly, one-way ANCOVA was used to identify between-group differences (no pain, acute BP, and chronic BP) for each muscle and along the superior-inferior expanse of the lumbar spine while controlling for age, BMI, sex, and physical activity (alpha=0.05).RESULTS: Females had higher IMF (LM mean difference (MD)=11.1%, ES MD=10.2%, PM MD=0.3%, p<0.001) and lower aCSA (LM MD=47.6 mm2, ES MD=350.0 mm2, PM MD=321.5 mm2, p<0.001) for all muscles. Higher age was associated with higher IMF and lower aCSA for all muscles (r≥0.232, p<0.001) except for LM and aCSA (r≤0.013, p≥0.267). Higher BMI was associated with higher IMF and aCSA for all muscles (r≥0.174, p<0.001). Higher physical activity was associated with lower IMF and higher aCSA for all muscles (r≥0.036, p≤0.002) except for LM and aCSA (r≤0.010, p≥0.405). People with chronic BP had higher IMF and lower aCSA than people with no pain (IMF MD≤1.6%, aCSA MD≤27.4 mm2, p<0.001) and higher IMF compared to acute BP (IMF MD≤1.1%, p<0.001). The differences between people with BP and people with no pain were not spatially localized to the inferior lumbar levels but broadly distributed across the lumbar spine.CONCLUSIONS: Paraspinal muscle health is associated with age, BMI, sex, and physical activity with the exception of the association between LM aCSA and age and physical activity. People with BP (chronic > acute) have higher IMF and lower aCSA than people reporting no pain. The differences were not localized but broadly distributed across the lumbar spine. When interpreting measures of paraspinal muscle health in the research or clinical setting, the associations with age, BMI, sex, and physical activity should be considered.

    View details for DOI 10.1016/j.spinee.2024.02.013

    View details for PubMedID 38417587

  • A single dermatome clinical prediction rule for independent walking one year after spinal cord injury. Archives of physical medicine and rehabilitation Smith, A. C., Draganich, C., Thornton, W. A., Berliner, J. C., Lennarson, P. J., Rejc, E., Sevigny, M., Charlifue, S., Tefertiller, C., Weber, K. A. 2023


    OBJECTIVE: To derive and validate a simple, accurate CPR to predict future independent walking ability after SCI at the bedside that does not rely on motor scores and is predictive for those initially classified in the middle of the SCI severity spectrum.DESIGN: Retrospective cohort study. Binary variables were derived, indicating degrees of sensation to evaluate predictive value of pinprick and light touch variables across dermatomes. The optimal single sensory modality and dermatome was used to derive our CPR, which was validated on an independent dataset.SETTING: Analysis of SCI Model Systems dataset.PARTICIPANTS: Individuals with traumatic SCI. 3,721 participants' data were included with 623 participants comprising the derivation dataset and 3,056 comprising the validation dataset.INTERVENTIONS: Not applicable.MAIN OUTCOME MEASURES: Self-reported ability to walk both indoors and outdoors.RESULTS: Pinprick testing at S1 over lateral heels, within 31 days of SCI, accurately identified future independent walkers one year after SCI. Normal pinprick in both lateral heels provided good prognosis, any pinprick sensation in either lateral heel provided fair prognosis, and no sensation provided poor prognosis. This CPR performed satisfactorily in the middle SCI severity subgroup.CONCLUSIONS: In this large multi-site study, we derived and validated a simple, accurate CPR using only pinprick sensory testing at lateral heels that predicts future independent walking after SCI.

    View details for DOI 10.1016/j.apmr.2023.06.015

    View details for PubMedID 37414239

  • Lateral corticospinal tract and dorsal column damage: predictive relationships with motor and sensory scores at discharge from acute rehabilitation after spinal cord injury. Archives of physical medicine and rehabilitation Smith, A. C., O'Dell, D. R., Albin, S. R., Berliner, J. C., Dungan, D., Robinson, E., Elliott, J. M., Carballido-Gamio, J., Stevens-Lapsley, J., Weber, K. A. 2021


    OBJECTIVE: to determine if lateral corticospinal tract (LCST) integrity demonstrates a significant predictive relationship with future ipsilateral lower extremity motor function (LEMS), and if dorsal column (DC) integrity demonstrates a significant predictive relationship with future light touch (LT) sensory function post SCI at time of discharge from inpatient rehabilitation.DESIGN: retrospective analyses of imaging and clinical outcomes.SETTING: University and academic hospital.PARTICIPANTS: 151 participants with SCI.INTERVENTIONS: Inpatient rehabilitation.MAIN OUTCOME MEASURES: LEMS and LT scores at discharge from inpatient rehabilitation.RESULTS: In 151 participants, right LCST spared tissue demonstrated a significant predictive relationship with right LEMS percent recovered (beta = 0.56, 95% CI: 0.37, 0.73, R = 0.43, p < 0.001). Left LCST spared tissue demonstrated a significant predictive relationship with left LEMS percent recovered (beta = 0.66, 95% CI: 0.50, 0.82, R = 0.51, p < 0.001). DC spared tissue demonstrated a significant predictive relationship with LT percent recovered (beta = 0.69, 95% CI: 0.52, 0.87, R = 0.55, p < 0.001). When subgrouping the participants into motor complete versus incomplete SCI, motor relationships were no longer significant but the sensory relationship remained significant. Those who had no voluntary motor function but recovered some also had significantly greater LCST spared tissue compared to those who did not recover motor function.CONCLUSIONS: LCST demonstrated significant moderate predictive relationships with lower extremity motor function at the time of discharge from inpatient rehabilitation, in an ipsilesional manner. DC integrity demonstrated a significant moderate predictive relationship with recovered function of LT. With further development, these neuroimaging methods might be used to predict potential deficits following SCI and to provide corresponding targeted interventions.

    View details for DOI 10.1016/j.apmr.2021.07.792

    View details for PubMedID 34371017

  • Assessing the Spatial Distribution of Cervical Spinal Cord Activity during Tactile Stimulation of the Upper Extremity in Humans with Functional Magnetic Resonance Imaging. NeuroImage Weber, K. A., Chen, Y., Paliwal, M., Law, C. S., Hopkins, B. S., Mackey, S., Dhaher, Y., Parrish, T. B., Smith, Z. A. 2020: 116905


    Dermatomal maps are a mainstay of clinical practice and provide information on the spatial distribution of the cutaneous innervation of spinal nerves. Dermatomal deficits can help isolate the level of spinal nerve root involvement in spinal conditions and guide clinicians in diagnosis and treatment. Dermatomal maps, however, have limitations, and the spatial distribution of spinal cord sensory activity in humans remains to be quantitatively assessed. Here we used spinal cord functional MRI to map and quantitatively compare the spatial distribution of sensory spinal cord activity during tactile stimulation of the left and right lateral shoulders (i.e. C5 dermatome) and dorsal third digits of the hands (i.e., C7 dermatome) in healthy humans (n = 24, age = 36.0 ± 11.8 years). Based on the central sites for processing of innocuous tactile sensory information, we hypothesized that the activity would be localized more to the ipsilateral dorsal spinal cord with the lateral shoulder stimulation activity being localized more superiorly than the dorsal third digit. The findings demonstrate lateralization of the activity with the left- and right-sided stimuli having more activation in the ipsilateral hemicord. Contradictory to our hypotheses, the activity for both stimulation sites was spread across the dorsal and ventral hemicords and did not demonstrate a clear superior-inferior localization. Instead, the activity for both stimuli had a broader than expected distribution, extending across the C5, C6, and C7 spinal cord segments. We highlight the complexity of the human spinal cord neuroanatomy and several sources of variability that may explain the observed patterns of activity. While the findings were not completely consistent with our a priori hypotheses, this study provides a foundation for continued work and is an important step towards developing normative quantitative spinal cord measures of sensory function, which may become useful objective MRI-based biomarkers of neurological injury and improve the management of spinal disorders.

    View details for DOI 10.1016/j.neuroimage.2020.116905

    View details for PubMedID 32387628

  • Lateralization of cervical spinal cord activity during an isometric upper extremity motor task with functional magnetic resonance imaging. NeuroImage Weber, K. A., Chen, Y., Wang, X., Kahnt, T., Parrish, T. B. 2016; 125: 233-243


    The purpose of this study was to use an isometric upper extremity motor task to detect activity induced blood oxygen level dependent signal changes in the cervical spinal cord with functional magnetic resonance imaging. Eleven healthy volunteers performed six 5minute runs of an alternating left- and right-sided isometric wrist flexion task, during which images of the cervical spinal cord were acquired with a reduced field-of-view T2*-weighted gradient-echo echo-planar-imaging sequence. Spatial normalization to a standard spinal cord template was performed, and group average activation maps were generated in a mixed-effects analysis. The task activity significantly exceeded that of the control analyses. The activity was lateralized to the hemicord ipsilateral to the task and reliable across the runs at the group and subject level. Finally, a multi-voxel pattern analysis was able to successfully decode the left and right tasks at the C6 and C7 vertebral levels.

    View details for DOI 10.1016/j.neuroimage.2015.10.014

    View details for PubMedID 26488256

  • Spinal cord lesion MRI and behavioral outcomes in a miniature pig model of spinal cord injury: exploring preclinical potential through an ad hoc comparison with human SCI. Spinal cord series and cases Smith, A. C., Ahmed, R. U., Weber, K. A., Negahdar, M., Gibson, D., Boakye, M., Rejc, E. 2024; 10 (1): 44


    prospective case series of Yucatan miniature pig spinal cord contusion injury model with comparison to human cases of spinal cord injury (SCI).to describe magnetic resonance imaging (MRI) measures of spinal cord lesion severity along with estimates of lateral corticospinal tracts spared neural tissue in both a less severe and more severe contusion SCI model, as well as to describe their corresponding behavioral outcome changes.University laboratory setting.Following a more severe and less severe SCI, each pig underwent spinal cord MRI to measure lesion characteristics, along with locomotor and urodynamics outcomes testing.In the pig with more severe SCI, locomotor and urodynamic outcomes were poor, and both the spinal cord lesion volume and damage estimates to the lateral corticospinal tracts were large. Conversely, in the pig with less severe SCI, locomotor and urodynamic outcomes were favorable, with the spinal cord lesion volume and damage estimates to the lateral corticospinal tracts being less pronounced. For two human cases matched on estimates of damage to the lateral corticospinal tract regions, the clinical presentations were similar to the pig outcomes, with more limited mobility and more limited bladder functional independence in the more severe case.Our initial findings contribute valuable insights to the emergent field of MRI-based evaluation of spinal cord lesions in pig models, offering a promising avenue for understanding and potentially improving outcomes in spinal cord injuries.

    View details for DOI 10.1038/s41394-024-00658-x

    View details for PubMedID 38977671

    View details for PubMedCentralID 6129752

  • Lesion characteristics are associated with bowel, bladder, and overall independence following cervical spinal cord injury. The journal of spinal cord medicine Thornton, W. A., Smulligan, K., Weber, K. A., Tefertiller, C., Manago, M., Sevigny, M., Wiley, L., Stevens-Lapsley, J., Smith, A. C. 2024: 1-9


    CONTEXT/OBJECTIVE: There is a growing global interest in quantifying spinal cord lesions and spared neural tissue using magnetic resonance imaging (MRI) in individuals with spinal cord injury (SCI). The primary objective of this study was to assess the relationships between spinal cord lesion characteristics assessed on MRI and bowel, bladder, and overall independence following SCI.DESIGN: Retrospective, exploratory study.PARTICIPANTS: 93 individuals with cervical SCI who were enrolled in a local United States Model Systems SCI database from 2010 to 2017.METHODS: Clinical and MRI data were obtained for potential participants, and MRIs of eligible participants were analyzed. Explanatory variables, captured on MRIs, included intramedullary lesion length (IMLL), midsagittal ventral tissue bridge width (VTBW), midsagittal dorsal tissue bridge width (DTBW), and axial damage ratio (ADR).OUTCOME MEASURES: Bowel and bladder management scale of the Functional Independence Measure (FIM) and FIM total motor score.RESULTS: When accounting for all four variables, only ADR was significantly associated with bowel independence (OR=0.970, 95% CI: 0.942-0.997, P=0.030), and both ADR and IMLL were strongly associated with bladder independence (OR=0.967, 95% CI: 0.936-0.999, P=0.046 and OR=0.948, 95% CI: 0.919-0.978, P=0.0007, respectively). 32% of the variation in overall independence scores were explained by all four predictive variables, but only ADR was significantly associated with overall independence after accounting for all other predictive variables (beta=-0.469, 95% CI: -0.719, -0.218, P=0.0004).CONCLUSIONS: Our results suggest that the MRI-measured extent of spinal cord lesion may be predictive of bowel, bladder, and overall independence following cervical SCI.

    View details for DOI 10.1080/10790268.2024.2363005

    View details for PubMedID 38958637

  • Prognostic value of tissue bridges in cervical spinal cord injury: a longitudinal, multicentre, retrospective cohort study. The Lancet. Neurology Pfyffer, D., Smith, A. C., Weber, K. A., Grillhoesl, A., Mach, O., Draganich, C., Berliner, J. C., Tefertiller, C., Leister, I., Maier, D., Schwab, J. M., Thompson, A., Curt, A., Freund, P. 2024


    The accuracy of prognostication in patients with cervical spinal cord injury (SCI) needs to be improved. We aimed to explore the prognostic value of preserved spinal tissue bridges-injury-spared neural tissue adjacent to the lesion-for prediction of sensorimotor recovery in a large, multicentre cohort of people with SCI.For this longitudinal study, we included patients with acute cervical SCI (vertebrae C1-C7) admitted to one of three trauma or rehabilitation centres: Murnau, Germany (March 18, 2010-March 1, 2021); Zurich, Switzerland (May 12, 2002-March 2, 2019); and Denver, CO, USA (Jan 12, 2010-Feb 16, 2017). Patients were clinically assessed at admission (baseline), at discharge (3 months), and at 12 months post SCI. Midsagittal tissue bridges were quantified from T2-weighted images assessed at 3-4 weeks post SCI. Fractional regression and unbiased recursive partitioning models, adjusted for age, sex, centre, and neurological level of injury, were used to assess associations between tissue bridge width and baseline-adjusted total motor score, pinprick score, and light touch scores at 3 months and 12 months. Patients were stratified into subgroups according to whether they showed better or worse predicted recovery.The cohort included 227 patients: 93 patients from Murnau (22 [24%] female); 43 patients from Zurich (four [9%] female); and 91 patients from Denver (14 [15%] female). 136 of these participants (from Murnau and Zurich) were followed up for up to 12 months. At 3 months, per preserved 1 mm of tissue bridge at baseline, patients recovered a mean of 9·3% (SD 0·9) of maximal total motor score (95% CI 7·5-11.2), 8·6% (0·8) of maximal pinprick score (7·0-10·1), and 10·9% (0·8) of maximal light touch score (9·4-12·5). At 12 months post SCI, per preserved 1 mm of tissue bridge at baseline, patients recovered a mean of 10·9% (1·3) of maximal total motor score (8·4-13·4), 5·7% (1·3) of maximal pinprick score (3·3-8·2), and 6·9% (1·4) of maximal light touch score (4·1-9·7). Partitioning models identified a tissue bridge cutoff width of 2·0 mm to be indicative of higher or lower 3-month total motor, pinprick, and light touch scores, and a cutoff of 4·0 mm to be indicative of higher and lower 12-month scores. Compared with models that contained clinical predictors only, models additionally including tissue bridges had significantly improved prediction accuracy across all three centres.Tissue bridges, measured in the first few weeks after SCI, are associated with short-term and long-term clinical improvement. Thus, tissue bridges could potentially be used to guide rehabilitation decision making and to stratify patients into more homogeneous subgroups of recovery in regenerative and neuroprotective clinical trials.Wings for Life, International Foundation for Research in Paraplegia, EU project Horizon 2020 (NISCI grant), and ERA-NET NEURON.

    View details for DOI 10.1016/S1474-4422(24)00173-X

    View details for PubMedID 38945142

  • Sagittal balance parameters measurement on cervical spine MR images based on superpixel segmentation. Frontiers in bioengineering and biotechnology Zhong, Y. F., Dai, Y. X., Li, S. P., Zhu, K. J., Lin, Y. P., Ran, Y., Chen, L., Ruan, Y., Yu, P. F., Li, L., Li, W. X., Xu, C. L., Sun, Z. T., Weber, K. A., Kong, D. W., Yang, F., Lin, W. P., Chen, J., Chen, B. L., Jiang, H., Zhou, Y. J., Sheng, B., Wang, Y. J., Tian, Y. Z., Sun, Y. L. 2024; 12: 1337808


    Introduction: Magnetic Resonance Imaging (MRI) is essential in diagnosing cervical spondylosis, providing detailed visualization of osseous and soft tissue structures in the cervical spine. However, manual measurements hinder the assessment of cervical spine sagittal balance, leading to time-consuming and error-prone processes. This study presents the Pyramid DBSCAN Simple Linear Iterative Cluster (PDB-SLIC), an automated segmentation algorithm for vertebral bodies in T2-weighted MR images, aiming to streamline sagittal balance assessment for spinal surgeons. Method: PDB-SLIC combines the SLIC superpixel segmentation algorithm with DBSCAN clustering and underwent rigorous testing using an extensive dataset of T2-weighted mid-sagittal MR images from 4,258 patients across ten hospitals in China. The efficacy of PDB-SLIC was compared against other algorithms and networks in terms of superpixel segmentation quality and vertebral body segmentation accuracy. Validation included a comparative analysis of manual and automated measurements of cervical sagittal parameters and scrutiny of PDB-SLIC's measurement stability across diverse hospital settings and MR scanning machines. Result: PDB-SLIC outperforms other algorithms in vertebral body segmentation quality, with high accuracy, recall, and Jaccard index. Minimal error deviation was observed compared to manual measurements, with correlation coefficients exceeding 95%. PDB-SLIC demonstrated commendable performance in processing cervical spine T2-weighted MR images from various hospital settings, MRI machines, and patient demographics. Discussion: The PDB-SLIC algorithm emerges as an accurate, objective, and efficient tool for evaluating cervical spine sagittal balance, providing valuable assistance to spinal surgeons in preoperative assessment, surgical strategy formulation, and prognostic inference. Additionally, it facilitates comprehensive measurement of sagittal balance parameters across diverse patient cohorts, contributing to the establishment of normative standards for cervical spine MR imaging.

    View details for DOI 10.3389/fbioe.2024.1337808

    View details for PubMedID 38681963

    View details for PubMedCentralID PMC11048045

  • Response to Letter to the Editor on "A single dermatome clinical prediction rule for independent walking one year after spinal cord injury.". Archives of physical medicine and rehabilitation Smith, A. C., Draganich, C., Thornton, W. A., Berliner, J. C., Lennarson, P. J., Rejc, E., Sevigny, M., Charlifue, S., Tefertiller, C., Weber, K. A. 2024

    View details for DOI 10.1016/j.apmr.2024.04.002

    View details for PubMedID 38582334

  • Peak Slope Ratio of the Recruitment Curves Compared to Muscle Evoked Potentials to Optimize Standing Configurations with Percutaneous Epidural Stimulation after Spinal Cord Injury JOURNAL OF CLINICAL MEDICINE Alazzam, A. M., Ballance, W. B., Smith, A. C., Rejc, E., Weber, K. A., Trainer, R., Gorgey, A. S. 2024; 13 (5)
  • Quantifying lumbar paraspinal intramuscular fat: Accuracy and reliability of automated thresholding models. North American Spine Society journal Wesselink, E. O., Elliott, J. M., Pool-Goudzwaard, A., Coppieters, M. W., Pevenage, P. P., Di Ieva, A., Weber Ii, K. A. 2024; 17: 100313


    The reported level of lumbar paraspinal intramuscular fat (IMF) in people with low back pain (LBP) varies considerably across studies using conventional T1- and T2-weighted magnetic resonance imaging (MRI) sequences. This may be due to the different thresholding models employed to quantify IMF. In this study we investigated the accuracy and reliability of established (two-component) and novel (three-component) thresholding models to measure lumbar paraspinal IMF from T2-weighted MRI.In this cross-sectional study, we included MRI scans from 30 people with LBP (50% female; mean (SD) age: 46.3 (15.0) years). Gaussian mixture modelling (GMM) and K-means clustering were used to quantify IMF bilaterally from the lumbar multifidus, erector spinae, and psoas major using two and three-component thresholding approaches (GMM2C; K-means2C; GMM3C; and K-means3C). Dixon fat-water MRI was used as the reference for IMF. Accuracy was measured using Bland-Altman analyses, and reliability was measured using ICC3,1. The mean absolute error between thresholding models was compared using repeated-measures ANOVA and post-hoc paired sample t-tests (α = 0.05).We found poor reliability for K-means2C (ICC3,1 ≤ 0.38), moderate to good reliability for K-means3C (ICC3,1 ≥ 0.68), moderate reliability for GMM2C (ICC3,1 ≥ 0.63) and good reliability for GMM3C (ICC3,1 ≥ 0.77). The GMM (p < .001) and three-component models (p < .001) had smaller mean absolute errors than K-means and two-component models, respectively. None of the investigated models adequately quantified IMF for psoas major (ICC3,1 ≤ 0.01).The performance of automated thresholding models is strongly dependent on the choice of algorithms, number of components, and muscle assessed. Compared to Dixon MRI, the GMM performed better than K-means and three-component performed better than two-component models for quantifying lumbar multifidus and erector spinae IMF. None of the investigated models accurately quantified IMF for psoas major. Future research is needed to investigate the performance of thresholding models in a more heterogeneous clinical dataset and across different sites and vendors.

    View details for DOI 10.1016/j.xnsj.2024.100313

    View details for PubMedID 38370337

    View details for PubMedCentralID PMC10869289

  • Recent developments and future avenues for human corticospinal neuroimaging. Frontiers in human neuroscience Kaptan, M., Pfyffer, D., Konstantopoulos, C. G., Law, C. S., Weber Ii, K. A., Glover, G. H., Mackey, S. 2024; 18: 1339881


    Non-invasive neuroimaging serves as a valuable tool for investigating the mechanisms within the central nervous system (CNS) related to somatosensory and motor processing, emotions, memory, cognition, and other functions. Despite the extensive use of brain imaging, spinal cord imaging has received relatively less attention, regardless of its potential to study peripheral communications with the brain and the descending corticospinal systems. To comprehensively understand the neural mechanisms underlying human sensory and motor functions, particularly in pathological conditions, simultaneous examination of neuronal activity in both the brain and spinal cord becomes imperative. Although technically demanding in terms of data acquisition and analysis, a growing but limited number of studies have successfully utilized specialized acquisition protocols for corticospinal imaging. These studies have effectively assessed sensorimotor, autonomic, and interneuronal signaling within the spinal cord, revealing interactions with cortical processes in the brain. In this mini-review, we aim to examine the expanding body of literature that employs cutting-edge corticospinal imaging to investigate the flow of sensorimotor information between the brain and spinal cord. Additionally, we will provide a concise overview of recent advancements in functional magnetic resonance imaging (fMRI) techniques. Furthermore, we will discuss potential future perspectives aimed at enhancing our comprehension of large-scale neuronal networks in the CNS and their disruptions in clinical disorders. This collective knowledge will aid in refining combined corticospinal fMRI methodologies, leading to the development of clinically relevant biomarkers for conditions affecting sensorimotor processing in the CNS.

    View details for DOI 10.3389/fnhum.2024.1339881

    View details for PubMedID 38332933

    View details for PubMedCentralID PMC10850311

  • The association between lateral hip muscle size/intramuscular fat infiltration and hip strength in active young adults with long standing hip/groin pain. Physical therapy in sport : official journal of the Association of Chartered Physiotherapists in Sports Medicine Perraton, Z., Mosler, A. B., Lawrenson, P. R., Weber Ii, K., Elliott, J. M., Wesselink, E. O., Crossley, K. M., Kemp, J. L., Stewart, C., Girdwood, M., King, M. G., Heerey, J. J., Scholes, M. J., Mentiplay, B. F., Semciw, A. I. 2023; 65: 95-101


    To investigate associations between lateral hip muscle size/intramuscular fat infiltration (MFI) and hip strength in active young adults with longstanding hip/groin pain.Cross-sectional study.University/Clinical.Sub-elite soccer and Australian Football players (n = 180; 37 female) with long standing hip/groin pain.Muscle size (volume) and MFI of gluteus maximus, medius, and minimis, and tensor fascia latae (TFL) were assessed using magnetic resonance imaging. Isometric hip strength was measured with handheld dynamometry. Associations between muscle size/MFI were assessed using linear regression models, adjusted for body mass index and age, with sex-specific interactions.Positive associations were identified between lateral hip muscle volume and hip muscle strength, particularly for gluteus maximus and gluteus minimus volume. For all muscles, hip abduction was associated with an increase in strength by up to 0.69 N (R2 ranging from 0.29 to 0.39). These relationships were consistent across sexes with no sex interactions observed. No associations were found between MFI and strength measures.Greater lateral hip muscle volumes are associated with greater hip strength in active young adults with long standing hip/groin pain, irrespective of sex. Gluteus maximus and minimus volume showed the most consistent relationships with hip strength across multiple directions.

    View details for DOI 10.1016/j.ptsp.2023.11.007

    View details for PubMedID 38101293

  • Evaluating tissue injury in cervical spondylotic myelopathy with spinal cord MRI: a systematic review. European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society Khan, A. F., Mohammadi, E., Haynes, G., Hameed, S., Rohan, M., Anderson, D. B., Weber, K. A., Muhammad, F., Smith, Z. A. 2023


    Cervical Spondylotic Myelopathy (CSM) is a degenerative condition that leads to loss of cervical spinal cord (CSC) integrity. Various spinal cord Magnetic Resonance Imaging (MRI) methods can identify and characterize the extent of this damage. This systematic review aimed to evaluate the diagnostic, biomarker, and predictive utilities of different spinal cord MRI methods in clinical research studies of CSM. The aim was to provide a comprehensive understanding of the progress in this direction for future studies and effective diagnosis and management of CSM.A comprehensive literature search was conducted on PubMed and EMBASE from 2010 to 2022 according to PRISMA guidelines. Studies with non-human subjects, less than 3T magnetic field strength, non-clinical design, or not quantitatively focusing on the structural integrity of CSC were excluded. The extracted data from each study included demographics, disease severity, MRI machine characteristics, quantitative metrics, and key findings in terms of diagnostic, biomarker, and predictive utilities of each MRI method. The risk of bias was performed using the guide from AHRQ. The quality of evidence was assessed separately for each type of utility for different MRI methods using GRADE.Forty-seven studies met the inclusion criteria, utilizing diffusion-weighted imaging (DTI) (n = 39), magnetization transfer (MT) (n = 6), MR spectroscopy (n = 3), and myelin water imaging (n = 1), as well as a combination of MRI methods (n = 12). The metric fractional anisotropy (FA) showed the highest potential in all facets of utilities, followed by mean diffusivity. Other promising metrics included MT ratio and intracellular volume fraction, especially in multimodal studies. However, the level of evidence for these promising metrics was low due to a small number of studies. Some studies, mainly DTI, also reported the usefulness of spinal cord MRI in mild CSM.Spinal cord MRI methods can potentially facilitate the diagnosis and management of CSM by quantitatively interrogating the structural integrity of CSC. DTI is the most promising MRI method, and other techniques have also shown promise, especially in multimodal configurations. However, this field is in its early stages, and more studies are needed to establish the usefulness of spinal cord MRI in CSM.

    View details for DOI 10.1007/s00586-023-07990-0

    View details for PubMedID 37926719

    View details for PubMedCentralID 10400518

  • Isolating Neurologic Deficits in Cervical Spondylotic Myelopathy: A Case-Controlled Study, Using the NIH Toolbox Motor Battery. Neurology. Clinical practice Muhammad, F., Baha, A., Haynes, G., Shakir, H., Omini, M., Martin, M., Weber, K. A., Paliwal, M., Van Hal, M., Dickson, D., Dhaher, Y., Zhao, Y. D., Smith, Z. A. 2023; 13 (2): e200126


    Patients with cervical spondylotic myelopathy (CSM) have motor impairments, including weakness, imbalance, and loss of dexterity. The reliable assessment of these symptoms is critical for treatment decisions. This study aimed to determine, for the first time, the use of the NIH Toolbox motor battery (NIHTBm) in the objective assessment of motor deficits in patients with CSM.Patients with symptoms and MRI evidence of CSM and age-matched healthy controls (HC), with no evidence of spinal disorder or surgery were included in this case-control study based on our inclusion and exclusion criteria. We performed motor tests, dexterity, gait speed, grip strength, and balance tests, using the NIHTBm in patients with CSM and HCs. Motor impairment rates were determined in patients with CSM based on the NIHTBm scores. We determined the association between NIHTBm scores and patient-reported outcome scores; patient-reported outcome measures (the modified Japanese Orthopedic Association [mJOA] and Nurick grade) to determine the association. One-way analysis of variance was used to analyze group differences and the Spearman rank correlation to determine the relationship between assessment scores.We enrolled 24 patients with CSM with a mean age (SD) of 57.96 (10.61) years and 24 age-matched HCs with a mean age (SD) of 53.17 (6.04) years in this study. Overall, we observed a significant decrease in the motor function T-scores mean (SD): dexterity 31.54 (14.82) vs 51.54 (9.72), grip strength 32.00 (17.47) vs 56.79 (8.46), balance 27.58 (16.65) vs 40.21 (6.35), and gait speed 0.64 (0.18) vs 0.99 (0.17) m/s, in patients with CSM compared with that in HCs. The lower extremity dysfunction scores on the NIHTBm, balance (ρ = -0.67) and gait speed (ρ = -0.62), were associated with higher Nurick grades. We observed a similar but weaker association with the Nurick grades and NIHTBm tests: dexterity (ρ = -0.49) and grip strength (ρ = -0.31) scores. The total motor mJOA showed a positive but weak association with NIHTBm scores, gait speed (ρ = 0.38), balance (ρ = 0.49), grip strength (ρ = 0.41), and dexterity (ρ = 0.45).Patients with CSM had significantly lower NIHTBm scores compared with HCs. The results from the NIHTBm are consistent with the clinical presentation of CSM showing patients have motor impairments in both upper and lower extremities. As a neurologic-specific scale, NIHTBm should be used in the evaluation and clinical management of patients with CSM.

    View details for DOI 10.1212/CPJ.0000000000200126

    View details for PubMedID 37064579

    View details for PubMedCentralID PMC10101713

  • The Problem of Pain in the United States: A Population-Based Characterization of Biopsychosocial Correlates of High Impact Chronic Pain using the National Health Interview Survey. The journal of pain Falasinnu, T., Hossain, M. B., Weber, K. A., Helmick, C. G., Karim, M. E., Mackey, S. 2023


    Over 20 million adults in the United States live with High Impact Chronic Pain (HICP), or chronic pain that limits life or work activities for ≥3 months. It is critically important to differentiate people with HICP from those who sustain normal activities although experiencing chronic pain. Therefore, we aim to help clinicians and researchers identify those with HICP by: (1) developing models that identify factors associated with HICP using the 2016 National Health Interview Survey (NHIS) and (2) evaluating the performances of those models overall and by sociodemographic subgroups (sex, age, and race/ethnicity). Our analysis included 32,980 respondents. We fitted logistic regression models with LASSO (a parametric model) and random forest (a nonparametric model) for predicting HICP using the whole sample. Both models performed well. The most important factors associated with HICP were those related to underlying ill-health (arthritis and rheumatism, hospitalizations, and emergency department visits) and poor psychological well-being. These factors can be used for identifying higher-risk sub-groups for screening for HICP. We will externally validate these findings in future work. We need future studies that longitudinally predict the initiation and maintenance of HICP, then use this information to prevent HICP and direct patients to optimal treatments. PERSPECTIVE: Our study developed models to identify factors associated with high-impact chronic pain (HICP) using the 2016 National Health Interview Survey. There was homogeneity in the factors associated with HICP by gender, age and race/ethnicity. Understanding these risk factors is crucial to support the identification of populations and individuals at highest risk for developing HICP and improve access to interventions that target these high-risk subgroups.

    View details for DOI 10.1016/j.jpain.2023.03.008

    View details for PubMedID 36965649

  • Biopsychosocial Sequelae and Recovery Trajectories From Whiplash Injury Following a Motor Vehicle Collision. The spine journal : official journal of the North American Spine Society Elliott, J. M., Walton, D. M., Albin, S. R., Courtney, D. M., Siegmund, G. P., Carroll, L. J., Weber, K. A., Smith, A. C. 2023


    Five out of ten injured in a motor vehicle collision (MVC) will develop persistent pain and disability. It is unclear if prolonged symptoms are related to peritraumatic pain/disability, psychological distress, muscle fat, lower extremity weakness.To test if widespread muscle fat infiltration (MFI) was i) unique to those with poor recovery, ii) present in the peri-traumatic stage, iii) related to known risk factors.A cohort study, single-center Academic Hospital.97 men and women (age 18-65) presenting to an urban academic emergency medicine department following MVC, but not requiring inpatient hospitalization.Neck disability at 12-months.Participants underwent magnetic resonance imaging (MRI) to quantify neck and lower extremity MFI, completed questionnaires on pain/disability and psychological distress (< 1-week, 2-weeks, 3-, and 12-months) and underwent maximum volitional torque testing of their lower extremities (2-weeks, 3-, and 12-months). Percentage score on the Neck Disability Index at 12-months was used for a model of a) Recovered (0-8%), b) Mild (10-28%), and 3) Moderate/Severe (≥ 30%). This model was adjusted for BMI and age.Significant differences for neck MFI were revealed, with the Recovered group having significantly lower neck MFI than the Mild and Moderate/Severe groups at all time points. The Mild group had significantly more leg MFI at 12-months (p=0.02) than the Recovered group. There were no other significant differences at any other time point. Lower extremity torques revealed no group differences. The Traumatic Injury Distress Scale (TIDS) and MFI of the neck at 1-week post injury significantly predicted NDI score at 12-months.Higher neck MFI and distress may represent a risk factor though it is unclear whether this is a pre-existing phenotype or result of the Identifier: XXXX.

    View details for DOI 10.1016/j.spinee.2023.03.005

    View details for PubMedID 36958668

  • Predicting Outdoor Walking 1 Year After Spinal Cord Injury: A Retrospective, Multisite External Validation Study. Journal of neurologic physical therapy : JNPT Draganich, C., Weber, K. A., Thornton, W. A., Berliner, J. C., Sevigny, M., Charlifue, S., Tefertiller, C., Smith, A. C. 2023


    BACKGROUND AND PURPOSE: Predicting future outdoor walking ability after spinal cord injury (SCI) is important, as this is associated with community engagement and social participation. A clinical prediction rule (CPR) was derived for predicting outdoor walking 1 year after SCI. While promising, this CPR has not been validated, which is necessary to establish its clinical value. The objective of this study was to externally validate the CPR using a multisite dataset.METHODS: This was a retrospective analysis of US SCI Model Systems data from 12 centers. L3 motor score, L5 motor score, and S1 sensory score were used as predictor variables. The dataset was split into testing and training datasets. The testing dataset was used as a holdout dataset to provide an unbiased estimate of prediction performance. The training dataset was used to determine the optimal CPR threshold through a "leave-one-site-out" cross-validation framework. The primary outcome was self-reported outdoor walking ability 1 year after SCI.RESULTS: A total of 3721 participants' data were included. Using the optimal CPR threshold (CPR ≥ 33 threshold value), we were able to predict outdoor walking 1 year with high cross-validated accuracy and prediction performance. For the entire dataset, area under receiver operator characteristic curve was 0.900 (95% confidence interval: 0.890-0.910; P < 0.0001).DISCUSSION AND CONCLUSIONS: The outdoor walking CPR has been externally validated. Future research should conduct a clinical outcomes and cost-benefit impact analysis for implementing this CPR. Our results support that clinicians may use this 3-variable CPR for prediction of future outdoor walking ability.Video Abstract available for more insights from the authors (see the Video, Supplemental Digital Content 1, available at:

    View details for DOI 10.1097/NPT.0000000000000428

    View details for PubMedID 36630206

  • Confounds in neuroimaging: A clear case of sex as a confound in brain-based prediction. Frontiers in neurology Weber, K. A., Teplin, Z. M., Wager, T. D., Law, C. S., Prabhakar, N. K., Ashar, Y. K., Gilam, G., Banerjee, S., Delp, S. L., Glover, G. H., Hastie, T. J., Mackey, S. 2022; 13: 960760


    Muscle weakness is common in many neurological, neuromuscular, and musculoskeletal conditions. Muscle size only partially explains muscle strength as adaptions within the nervous system also contribute to strength. Brain-based biomarkers of neuromuscular function could provide diagnostic, prognostic, and predictive value in treating these disorders. Therefore, we sought to characterize and quantify the brain's contribution to strength by developing multimodal MRI pipelines to predict grip strength. However, the prediction of strength was not straightforward, and we present a case of sex being a clear confound in brain decoding analyses. While each MRI modality-structural MRI (i.e., gray matter morphometry), diffusion MRI (i.e., white matter fractional anisotropy), resting state functional MRI (i.e., functional connectivity), and task-evoked functional MRI (i.e., left or right hand motor task activation)-and a multimodal prediction pipeline demonstrated significant predictive power for strength (R 2 = 0.108-0.536, p ≤ 0.001), after correcting for sex, the predictive power was substantially reduced (R 2 = -0.038-0.075). Next, we flipped the analysis and demonstrated that each MRI modality and a multimodal prediction pipeline could significantly predict sex (accuracy = 68.0%-93.3%, AUC = 0.780-0.982, p < 0.001). However, correcting the brain features for strength reduced the accuracy for predicting sex (accuracy = 57.3%-69.3%, AUC = 0.615-0.780). Here we demonstrate the effects of sex-correlated confounds in brain-based predictive models across multiple brain MRI modalities for both regression and classification models. We discuss implications of confounds in predictive modeling and the development of brain-based MRI biomarkers, as well as possible strategies to overcome these barriers.

    View details for DOI 10.3389/fneur.2022.960760

    View details for PubMedID 36601297

    View details for PubMedCentralID PMC9806266

  • Is fatty infiltration in paraspinal muscles reversible with exercise in people with low back pain? A systematic review. European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society Wesselink, E. O., Pool, J. J., Mollema, J., Weber, K. A., Elliott, J. M., Coppieters, M. W., Pool-Goudzwaard, A. L. 2022


    Increased fatty infiltration in paraspinal muscles has been recognized as a feature of muscle quality loss in people with Low Back Pain (LBP) and is highly associated with the severity of LBP and dysfunction. Reducing fatty infiltration has been recognized as a rehabilitation aim. An earlier systematic review published in 2014 revealed conflicting evidence for the reversibility of paraspinal muscle quality by means of exercise and no updates have been published since. A new systematic literature search is warranted.Pubmed, CINAHL and Embase were searched from inception to July 2022. Randomized, non-randomized controlled trials (RCT and non-RCT) and single-arm trials were included if they reported the effect of exercise on paraspinal fatty infiltration in people with LBP. Effect sizes and statistical power were calculated for (1) exercise versus control, and (2) pre-post exercise changes. Available data from the RCTs were pooled via meta-analysis when appropriate. Otherwise, data were synthesized qualitatively.Two RCTs, one non-RCT and three single-arm trials met the selection criteria. Data were not pooled due to substantial clinical heterogeneity. Effect sizes from the RCTs revealed no significant difference for exercise versus control. One single-arm trial with high risk of bias demonstrated a significant pre-post difference with moderate effect size, but only at one (T12-L1) of the investigated levels.Moderate quality evidence is available that paraspinal fatty infiltration is not reversible with exercise in people with LBP. More larger RCT's are needed to draw firmer conclusions.

    View details for DOI 10.1007/s00586-022-07471-w

    View details for PubMedID 36459201

    View details for PubMedCentralID 3784852

  • Greater muscle volume and muscle fat infiltrate in the deep cervical spine extensor muscles (multifidus with semispinalis cervicis) in individuals with chronic idiopathic neck pain compared to age and sex-matched asymptomatic controls: a cross-sectional study. BMC musculoskeletal disorders Snodgrass, S. J., Stanwell, P., Weber, K. A., Shepherd, S., Kennedy, O., Thompson, H. J., Elliott, J. M. 2022; 23 (1): 973


    Muscle size and composition (muscle volume and muscle fat infiltrate [MFI]) may provide insight into possible mechanisms underpinning chronic idiopathic neck pain, a common condition with no definitive underlying pathology. In individuals with chronic idiopathic neck pain > 3 months and age- and sex-matched asymptomatic controls, muscle volumes of levator scapulae, multifidus including semispinalis cervicis (MFSS), semispinalis capitis, splenius capitis including splenius cervicis (SCSC), sternocleidomastoid and longus colli from C3 through T1 were quantified from magnetic resonance imaging. Between-group differences were determined using linear mixed models, accounting for side (left or right), muscle, spinal level, sex, age, and body mass index (BMI). Individuals with pain had greater muscle volume (mean difference 76.8mm3; 95% CI 26.6-127.0; p = .003) and MFI (2.3%; 0.2-4.5; p = .034) of the MFSS compared to matched controls with no differences in relative volume, accounting for factors associated with the outcomes: muscle, spinal level, side (left had smaller volume, relative volume and MFI than right), sex (females had less volume and relative volume than males), age (older age associated with less relative volume and greater MFI), and BMI (higher BMI associated with greater muscle volume and MFI). Greater MFI in individuals with chronic idiopathic neck pain suggests a possible underlying mechanism contributing to neck pain. Perspective: These findings suggest MFI in the MFSS may be radiologic sign, potentially identifying patients with a less favourable prognosis. Future studies are needed to confirm this finding and determine if MFI is a contributor to the development or persistence of neck pain, or consequence of neck pain.

    View details for DOI 10.1186/s12891-022-05924-3

    View details for PubMedID 36357864

  • Effects of variability in manually contoured spinal cord masks on fMRI co-registration and interpretation. Frontiers in neurology Hoggarth, M. A., Wang, M. C., Hemmerling, K. J., Vigotsky, A. D., Smith, Z. A., Parrish, T. B., Weber, K. A., Bright, M. G. 2022; 13: 907581


    Functional magnetic resonance imaging (fMRI) of the human spinal cord (SC) is a unique non-invasive method for characterizing neurovascular responses to stimuli. Group-analysis of SC fMRI data involves co-registration of subject-level data to standard space, which requires manual masking of the cord and may result in bias of group-level SC fMRI results. To test this, we examined variability in SC masks drawn in fMRI data from 21 healthy participants from a completed study mapping responses to sensory stimuli of the C7 dermatome. Masks were drawn on temporal mean functional image by eight raters with varying levels of neuroimaging experience, and the rater from the original study acted as a reference. Spatial agreement between rater and reference masks was measured using the Dice Similarity Coefficient, and the influence of rater and dataset was examined using ANOVA. Each rater's masks were used to register functional data to the PAM50 template. Gray matter-white matter signal contrast of registered functional data was used to evaluate the spatial normalization accuracy across raters. Subject- and group-level analyses of activation during left- and right-sided sensory stimuli were performed for each rater's co-registered data. Agreement with the reference SC mask was associated with both rater (F(7, 140) = 32.12, P < 2 × 10-16, η2 = 0.29) and dataset (F(20, 140) = 20.58, P < 2 × 10-16, η2 = 0.53). Dataset variations may reflect image quality metrics: the ratio between the signal intensity of spinal cord voxels and surrounding cerebrospinal fluid was correlated with DSC results (p < 0.001). As predicted, variability in the manually-drawn masks influenced spatial normalization, and GM:WM contrast in the registered data showed significant effects of rater and dataset (rater: F(8, 160) = 23.57, P < 2 × 10-16, η2 = 0.24; dataset: F(20, 160) = 22.00, P < 2 × 10-16, η2 = 0.56). Registration differences propagated into subject-level activation maps which showed rater-dependent agreement with the reference. Although group-level activation maps differed between raters, no systematic bias was identified. Increasing consistency in manual contouring of spinal cord fMRI data improved co-registration and inter-rater agreement in activation mapping, however our results suggest that improvements in image acquisition and post-processing are also critical to address.

    View details for DOI 10.3389/fneur.2022.907581

    View details for PubMedID 36341092

    View details for PubMedCentralID PMC9630922

  • Editorial: Mechanisms and models of musculoskeletal pain and nonpharmacological treatment. Frontiers in integrative neuroscience Reed, W. R., Weber, K. A., Martins, D. F. 2022; 16: 998413

    View details for DOI 10.3389/fnint.2022.998413

    View details for PubMedID 36035442

    View details for PubMedCentralID PMC9402260

  • Convolutional neural networks for the automatic segmentation of lumbar paraspinal muscles in people with low back pain. Scientific reports Wesselink, E. O., Elliott, J. M., Coppieters, M. W., Hancock, M. J., Cronin, B., Pool-Goudzwaard, A., Weber Ii, K. A. 2022; 12 (1): 13485


    The size, shape, and composition of paraspinal muscles have been widely reported in disorders of the cervical and lumbar spine. Measures of size, shape, and composition haverequiredtime-consuming and rater-dependent manual segmentation techniques. Convolutional neural networks (CNNs) provide alternate timesaving, state-of-the-art performance measures, which could realise clinical translation. Here wetrained a CNN for the automatic segmentation of lumbar paraspinal muscles and determined the impact of CNN architecture and training choices on segmentation performance. T2-weighted MRI axial images from 76 participants (46 female; age (SD): 45.6 (12.8) years) with low back pain were used to train CNN models to segment the multifidus, erector spinae, and psoas major muscles (left and right segmented separately). Using cross-validation, we compared 2D and 3D CNNs with and without data augmentation. Segmentation accuracy was compared between the models using the Sorensen-Dice index as theprimary outcome measure. The effect of increasing network depth on segmentation accuracy was also investigated. Each model showed high segmentation accuracy (Sorensen-Diceindex≥0.885) and excellent reliability (ICC2,1≥0.941). Overall, across all muscles, 2D models performed better than 3D models (p=0.012), and training without data augmentation outperformed training with data augmentation (p<0.001). The 2D model trained without data augmentation demonstrated the highest average segmentation accuracy. Increasing network depth did not improve accuracy (p=0.771). All trained CNN models demonstrated high accuracy and excellent reliability for segmenting lumbar paraspinal muscles. CNNs can be used to efficiently and accurately extract measures of paraspinal muscle health from MRI.

    View details for DOI 10.1038/s41598-022-16710-5

    View details for PubMedID 35931772

  • Towards defining muscular regions of interest from axial magnetic resonance imaging with anatomical cross-reference: a scoping review of lateral hip musculature. BMC musculoskeletal disorders Perraton, Z., Lawrenson, P., Mosler, A. B., Elliott, J. M., Weber, K. A., Flack, N. A., Cornwall, J., Crawford, R. J., Stewart, C., Semciw, A. I. 2022; 23 (1): 533


    Measures of hip muscle morphology and composition (e.g., muscle size and fatty infiltration) are possible with magnetic resonance imaging (MRI). Standardised protocols or guidelines do not exist for evaluation of hip muscle characteristics, hindering reliable and valid inter-study analysis. This scoping review aimed to collate and synthesise MRI methods for measuring lateral hip muscle size and fatty infiltration to inform the future development of standardised protocols.Five electronic databases (Medline, CINAHL, Embase, SportsDISCUS and AMED) were searched. Healthy or musculoskeletal pain populations that used MRI to assess lateral hip muscle size and fatty infiltration were included. Lateral hip muscles of interest included tensor fascia late (TFL), gluteus maximus, gluteus medius, and gluteus minimus. Data on MRI parameters, axial slice location, muscle size and fatty infiltrate measures were collected and analysed. Cross referencing for anatomical locations were made between MRI axial slice and E-12 anatomical plastinate sections.From 2684 identified publications, 78 studies contributed data on volume (n = 31), cross sectional area (CSA) (n = 24), and fatty infiltration (n = 40). Heterogeneity was observed for MRI parameters and anatomical boundaries scrutinizing hip muscle size and fatty infiltration. Seven single level axial slices were identified that provided consistent CSA measurement, including three for both gluteus maximus and TFL, and four for both gluteus medius and minimus. For assessment of fatty infiltration, six axial slice locations were identified including two for TFL, and four for each of the gluteal muscles.Several consistent anatomical levels were identified for single axial MR slice to facilitate muscle size and fatty infiltration muscle measures at the hip, providing the basis for reliable and accurate data synthesis and improvements in the validity of future between studies analyses. This work establishes the platform for standardised methods for the MRI assessment of lateral hip musculature and will aid in the examination of musculoskeletal conditions around the hip joint. Further studies into whole muscle measures are required to further optimise methodological parameters for hip muscle assessment.

    View details for DOI 10.1186/s12891-022-05439-x

    View details for PubMedID 35658932

  • Improving the measurement of intrinsic foot muscle morphology and composition from high-field (7T) magnetic resonance imaging. Journal of biomechanics Franettovich Smith, M. M., Mendis, M. D., Weber, K. A., Elliott, J. M., Ho, R., Wilkes, M. J., Collins, N. J. 2022; 140: 111164


    Magnetic resonance imaging (MRI) can be used to quantify intrinsic foot muscle morphology and composition. Due to the high spatial resolution required to adequately capture the architecturally complex anatomy, manual segmentation is time consuming and not clinically feasible. The aim of this study was to evaluate if a reduced number of MRI slices can be used to accurately estimate intrinsic foot muscle volume and composition. A three-dimensional 2-point Dixon sequence of the whole foot was acquired at 7-Tesla for thirteen asymptomatic individuals and twenty individuals with plantar heel pain. Slice intervals of 2, 3, 5, 10, 15 and 30 were used to calculate alternative muscle volume and composition, and were compared to reference values calculated from every available slice. Agreement between methods was assessed by calculating mean differences and 95% limits of agreement, and inspection of Bland -Altman plots. In both groups, slice intervals of 2, 3 and 5 provided excellent precision for all muscles (measurement error < 1%). Larger slice intervals of 10, 15 and 30 provided excellent precision for some muscles, but for other muscles (e.g. small forefoot muscles), error was up to 7.3%. Bland-Altman plots showed no systematic measurement bias. This study provides a quantitative basis for selecting a reduced number of slices to measure intrinsic foot muscle volume and composition from MRI. A slice interval of 10 may provide a balance between efficiency (36 mins vs. 6 h) and accuracy (error < 2.4%) across all intrinsic foot muscles in asymptomatic individuals and those with plantar heel pain.

    View details for DOI 10.1016/j.jbiomech.2022.111164

    View details for PubMedID 35661535

  • Preventive Supplementation of Omega-3 Reduces Pain and Pro-inflammatory Cytokines in a Mouse Model of Complex Regional Pain Syndrome Type I. Frontiers in integrative neuroscience de Oliveira Galassi, T., Fernandes, P. F., Salgado, A. S., Cidral-Filho, F. J., Piovezan, A. P., Lüdtke, D. D., Mack, J. M., Weber, K. A., Reed, W. R., Bobinski, F., Martins, D. F. 2022; 16: 840249


    Complex regional pain syndrome type I (CRPS-I) is a condition that responds poorly to treatments. The role of omega-3 fatty acids in the treatment of inflammatory disorders is well described in the literature; however, few studies have evaluated its therapeutic benefits in different types of pain. We evaluated the potential antihyperalgesic and anti-inflammatory effects of preventive omega-3 supplementation in an animal model of CRPS-I. In experiment 1, Swiss female mice were supplemented for 30 days with omega-3 before the induction of the CRPS-I model and 14 days after. Mechanical hyperalgesia was evaluated at baseline and from the 4th to the 14th day after CPRS-I induction along with open field locomotor activity after 30 days of supplementation. In experiment 2, Swiss female mice were supplemented for 30 days with omega-3 and then subjected to the CRPS-I model. Twenty-four hours later the animals were euthanized, and tissue samples of the spinal cord and right posterior paw muscle were taken to measure pro-inflammatory cytokine TNF and IL-1β concentrations. Omega-3 supplementation produced antihyperalgesic and anti-inflammatory effects, as well as reducing pro-inflammatory cytokine concentrations, without altering the animals' locomotion. No open field locomotor changes were found. The 30-day supplementation at the tested dose was effective in the CRPS-I model.

    View details for DOI 10.3389/fnint.2022.840249

    View details for PubMedID 35431823

    View details for PubMedCentralID PMC9005766

  • Differences in Structural Brain Characteristics Between Individuals with Chronic Nonspecific Neck Pain and Asymptomatic Controls: A Case-Control Study. Journal of pain research de Zoete, R. M., Stanwell, P., Weber, K. A., Snodgrass, S. J. 2022; 15: 521-531


    Neck pain is a prevalent and costly problem, but its underlying mechanisms are poorly understood. Neuroimaging studies show alterations in brain morphometry in chronic musculoskeletal pain, but reports on neck pain are scarce.This study investigates (1) differences in brain morphometry between individuals with chronic nonspecific neck pain and asymptomatic individuals and (2) associations between brain morphometry and patient-reported outcomes.Sixty-three participants (33 pain, 11 female, mean [SD] age 35 [10] years; 30 control, 12 female, age 35 [11] years) underwent magnetic resonance imaging. Brain regions of interest (ROIs) were determined a priori, outcomes included cortical thickness and volume. Between-group differences were determined using cluster-wise correction for multiple comparisons and analyses of pain-related ROIs.Between-group differences in volume were identified in the precentral, frontal, occipital, parietal, temporal, and paracentral cortices. ROI analyses showed that parahippocampal cortical thickness was larger in the neck pain group (p=0.015, 95% CI: -0.27 to -0.03). Moderate to strong associations between volume and thickness of the cingulate cortex, prefrontal cortex, and temporal lobe and neck pain duration, pain intensity, and neck disability were identified (p-values 0.006 to 0.048).Alterations in brain morphology that are associated with clinical characteristics inform the mechanisms underlying chronic nonspecific neck pain and may guide the development of more effective treatment approaches.

    View details for DOI 10.2147/JPR.S345365

    View details for PubMedID 35210851

    View details for PubMedCentralID PMC8863323

  • Utilization of Mid-Thigh Magnetic Resonance Imaging to Predict Lean Body Mass and Knee Extensor Strength in Obese Adults. Frontiers in rehabilitation sciences Bodkin, S. G., Smith, A. C., Bergman, B. C., Huo, D., Weber, K. A., Zarini, S., Kahn, D., Garfield, A., Macias, E., Harris-Love, M. O. 2022; 3


    Purpose: To train and test a machine learning model to automatically measure mid-thigh muscle cross-sectional area (CSA) to provide rapid estimation of appendicular lean mass (ALM) and predict knee extensor torque of obese adults.Methods: Obese adults [body mass index (BMI) = 30-40 kg/m2, age = 30-50 years] were enrolled for this study. Participants received full-body dual-energy X-ray absorptiometry (DXA), mid-thigh MRI, and completed knee extensor and flexor torque assessments via isokinetic dynamometer. Manual segmentation of mid-thigh CSA was completed for all MRI scans. A convolutional neural network (CNN) was created based on the manual segmentation to develop automated quantification of mid-thigh CSA. Relationships were established between the automated CNN values to the manual CSA segmentation, ALM via DXA, knee extensor, and flexor torque.Results: A total of 47 obese patients were enrolled in this study. Agreement between the CNN-automated measures and manual segmentation of mid-thigh CSA was high (>0.90). Automated measures of mid-thigh CSA were strongly related to the leg lean mass (r = 0.86, p < 0.001) and ALM (r = 0.87, p < 0.001). Additionally, mid-thigh CSA was strongly related to knee extensor strength (r = 0.76, p < 0.001) and moderately related to knee flexor strength (r = 0.48, p = 0.002).Conclusion: CNN-measured mid-thigh CSA was accurate compared to the manual segmented values from the mid-thigh. These values were strongly predictive of clinical measures of ALM and knee extensor torque. Mid-thigh MRI may be utilized to accurately estimate clinical measures of lean mass and function in obese adults.

    View details for DOI 10.3389/fresc.2022.808538

    View details for PubMedID 35419566

  • Spinal Cord Tissue Bridges Validation Study: Predictive Relationships With Sensory Scores Following Cervical Spinal Cord Injury. Topics in spinal cord injury rehabilitation Smith, A. C., O'Dell, D. R., Thornton, W. A., Dungan, D., Robinson, E., Thaker, A., Gisbert, R., Weber, K. A., Berliner, J. C., Albin, S. R. 2022; 28 (2): 111-115


    Background: Using magnetic resonance imaging (MRI), widths of ventral tissue bridges demonstrated significant predictive relationships with future pinprick sensory scores, and widths of dorsal tissue bridges demonstrated significant predictive relationships with future light touch sensory scores, following spinal cord injury (SCI). These studies involved smaller participant numbers, and external validation of their findings is warranted.Objectives: The purpose of this study was to validate these previous findings using a larger independent data set.Methods: Widths of ventral and dorsal tissue bridges were quantified using MRI in persons post cervical level SCI (average 3.7 weeks post injury), and pinprick and light touch sensory scores were acquired at discharge from inpatient rehabilitation (average 14.3 weeks post injury). Pearson product-moments were calculated and linear regression models were created from these data.Results: Wider ventral tissue bridges were significantly correlated with pinprick scores (r = 0.31, p < 0.001, N = 136) and wider dorsal tissue bridges were significantly correlated with light touch scores (r = 0.31, p < 0.001, N = 136) at discharge from inpatient rehabilitation.Conclusion: This retrospective study's results provide external validation of previous findings, using a larger sample size. Following SCI, ventral tissue bridges hold significant predictive relationships with future pinprick sensory scores and dorsal tissue bridges hold significant predictive relationships with future light touch sensory scores.

    View details for DOI 10.46292/sci21-00018

    View details for PubMedID 35521064

  • Response to Lawrence DJ: the global summit on the efficacy and effectiveness of spinal manipulative therapy for the prevention and treatment of non-musculoskeletal disorders: a systematic review of the literature. Chiropractic & manual therapies Cote, P., Hartvigsen, J., Axen, I., Leboeuf-Yde, C., Corso, M., Shearer, H., Wong, J., Marchand, A., Cassidy, J. D., French, S., Kawchuk, G. N., Mior, S., Poulsen, E., Srbely, J., Ammendolia, C., Blanchette, M., Busse, J. W., Bussieres, A., Cancelliere, C., Christensen, H. W., De Carvalho, D., De Luca, K., Rose, A. D., Eklund, A., Engel, R., Goncalves, G., Hebert, J., Hincapie, C. A., Hondras, M., Kimpton, A., Lauridsen, H. H., Innes, S., Meyer, A., Newell, D., O'Neill, S., Page, I., Passmore, S., Perle, S. M., Quon, J., Rezai, M., Stupar, M., Swain, M., Vitiello, A., Weber, K., Young, K. J., Yu, H. 2021; 29 (1): 26

    View details for DOI 10.1186/s12998-021-00380-7

    View details for PubMedID 34284791

  • Classifying chronic pain using multidimensional pain-agnostic symptom assessments and clustering analysis. Science advances Gilam, G., Cramer, E. M., Webber, K. A., Ziadni, M. S., Kao, M. C., Mackey, S. C. 2021; 7 (37): eabj0320


    [Figure: see text].

    View details for DOI 10.1126/sciadv.abj0320

    View details for PubMedID 34516888

  • Fatty infiltration in cervical flexors and extensors in patients with degenerative cervical myelopathy using a multi-muscle segmentation model. PloS one Paliwal, M., Weber, K. A., Smith, A. C., Elliott, J. M., Muhammad, F., Dahdaleh, N. S., Bodurka, J., Dhaher, Y., Parrish, T. B., Mackey, S., Smith, Z. A. 2021; 16 (6): e0253863


    BACKGROUND: In patients with degenerative cervical myelopathy (DCM) that have spinal cord compression and sensorimotor deficits, surgical decompression is often performed. However, there is heterogeneity in clinical presentation and post-surgical functional recovery.OBJECTIVES: Primary: a) to assess differences in muscle fat infiltration (MFI) in patients with DCM versus controls, b) to assess association between MFI and clinical disability. Secondary: to assess association between MFI pre-surgery and post-surgical functional recovery.STUDY DESIGN: Cross-sectional case control study.METHODS: Eighteen patients with DCM (58.6 ± 14.2 years, 10 M/8F) and 25 controls (52.6 ± 11.8 years, 13M/12 F) underwent 3D Dixon fat-water imaging. A convolutional neural network (CNN) was used to segment cervical muscles (MFSS- multifidus and semispinalis cervicis, LC- longus capitis/colli) and quantify MFI. Modified Japanese Orthopedic Association (mJOA) and Nurick were collected.RESULTS: Patients with DCM had significantly higher MFI in MFSS (20.63 ± 5.43 vs 17.04 ± 5.24, p = 0.043) and LC (18.74 ± 6.7 vs 13.66 ± 4.91, p = 0.021) than controls. Patients with increased MFI in LC and MFSS had higher disability (LC: Nurick (Spearman's rho = 0.436, p = 0.003) and mJOA (rho = -0.399, p = 0.008)). Increased MFI in LC pre-surgery was associated with post-surgical improvement in Nurick (rho = -0.664, p = 0.026) and mJOA (rho = -0.603, p = 0.049).CONCLUSION: In DCM, increased muscle adiposity is significantly associated with sensorimotor deficits, clinical disability, and functional recovery after surgery. Accurate and time efficient evaluation of fat infiltration in cervical muscles may be conducted through implementation of CNN models.

    View details for DOI 10.1371/journal.pone.0253863

    View details for PubMedID 34170961

  • Spinal cord imaging markers and recovery of standing with epidural stimulation in individuals with clinically motor complete spinal cord injury. Experimental brain research Smith, A. C., Angeli, C. A., Ugiliweneza, B., Weber, K. A., Bert, R. J., Negahdar, M., Mesbah, S., Boakye, M., Harkema, S. J., Rejc, E. 2021


    Spinal cord epidural stimulation (scES) is an intervention to restore motor function in those with severe spinal cord injury (SCI). Spinal cord lesion characteristics assessed via magnetic resonance imaging (MRI) may contribute to understand motor recovery. This study assessed relationships between standing ability with scES and spared spinal cord tissue characteristics at the lesion site. We hypothesized that the amount of lateral spared cord tissue would be related to independent extension in the ipsilateral lower limb. Eleven individuals with chronic, clinically motor complete SCI underwent spinal cord MRI, and were subsequently implanted with scES. Standing ability and lower limb activation patterns were assessed during an overground standing experiment with scES. This assessment occurred prior to any activity-based intervention with scES. Lesion hyperintensity was segmented from T2 axial images, and template-based analysis was used to estimate spared tissue in anterior, posterior, right, and left spinal cord regions. Regression analysis was used to assess relationships between imaging and standing outcomes. Total volume of spared tissue was related to left (p = 0.007), right (p = 0.005), and bilateral (p = 0.011) lower limb extension. Spared tissue in the left cord region was related to left lower limb extension (p = 0.019). A positive trend (p = 0.138) was also observed between right spared cord tissue and right lower limb extension. In this study, MRI measures of spared spinal cord tissue were significantly related to standing outcomes with scES. These preliminary results warrant future investigation of roles of supraspinal input and MRI-detected spared spinal cord tissue on lower limb motor responsiveness to scES.

    View details for DOI 10.1007/s00221-021-06272-9

    View details for PubMedID 34854934

  • Generic acquisition protocol for quantitative MRI of the spinal cord. Nature protocols Cohen-Adad, J., Alonso-Ortiz, E., Abramovic, M., Arneitz, C., Atcheson, N., Barlow, L., Barry, R. L., Barth, M., Battiston, M., Büchel, C., Budde, M., Callot, V., Combes, A. J., De Leener, B., Descoteaux, M., de Sousa, P. L., Dostál, M., Doyon, J., Dvorak, A., Eippert, F., Epperson, K. R., Epperson, K. S., Freund, P., Finsterbusch, J., Foias, A., Fratini, M., Fukunaga, I., Wheeler-Kingshott, C. A., Germani, G., Gilbert, G., Giove, F., Gros, C., Grussu, F., Hagiwara, A., Henry, P. G., Horák, T., Hori, M., Joers, J., Kamiya, K., Karbasforoushan, H., Keřkovský, M., Khatibi, A., Kim, J. W., Kinany, N., Kitzler, H., Kolind, S., Kong, Y., Kudlička, P., Kuntke, P., Kurniawan, N. D., Kusmia, S., Labounek, R., Laganà, M. M., Laule, C., Law, C. S., Lenglet, C., Leutritz, T., Liu, Y., Llufriu, S., Mackey, S., Martinez-Heras, E., Mattera, L., Nestrasil, I., O'Grady, K. P., Papinutto, N., Papp, D., Pareto, D., Parrish, T. B., Pichiecchio, A., Prados, F., Rovira, À., Ruitenberg, M. J., Samson, R. S., Savini, G., Seif, M., Seifert, A. C., Smith, A. K., Smith, S. A., Smith, Z. A., Solana, E., Suzuki, Y., Tackley, G., Tinnermann, A., Valošek, J., Van De Ville, D., Yiannakas, M. C., Weber, K. A., Weiskopf, N., Wise, R. G., Wyss, P. O., Xu, J. 2021


    Quantitative spinal cord (SC) magnetic resonance imaging (MRI) presents many challenges, including a lack of standardized imaging protocols. Here we present a prospectively harmonized quantitative MRI protocol, which we refer to as the spine generic protocol, for users of 3T MRI systems from the three main manufacturers: GE, Philips and Siemens. The protocol provides guidance for assessing SC macrostructural and microstructural integrity: T1-weighted and T2-weighted imaging for SC cross-sectional area computation, multi-echo gradient echo for gray matter cross-sectional area, and magnetization transfer and diffusion weighted imaging for assessing white matter microstructure. In a companion paper from the same authors, the spine generic protocol was used to acquire data across 42 centers in 260 healthy subjects. The key details of the spine generic protocol are also available in an open-access document that can be found at . The protocol will serve as a starting point for researchers and clinicians implementing new SC imaging initiatives so that, in the future, inclusion of the SC in neuroimaging protocols will be more common. The protocol could be implemented by any trained MR technician or by a researcher/clinician familiar with MRI acquisition.

    View details for DOI 10.1038/s41596-021-00588-0

    View details for PubMedID 34400839

  • Open-access quantitative MRI data of the spinal cord and reproducibility across participants, sites and manufacturers. Scientific data Cohen-Adad, J., Alonso-Ortiz, E., Abramovic, M., Arneitz, C., Atcheson, N., Barlow, L., Barry, R. L., Barth, M., Battiston, M., Büchel, C., Budde, M., Callot, V., Combes, A. J., De Leener, B., Descoteaux, M., de Sousa, P. L., Dostál, M., Doyon, J., Dvorak, A., Eippert, F., Epperson, K. R., Epperson, K. S., Freund, P., Finsterbusch, J., Foias, A., Fratini, M., Fukunaga, I., Gandini Wheeler-Kingshott, C. A., Germani, G., Gilbert, G., Giove, F., Gros, C., Grussu, F., Hagiwara, A., Henry, P. G., Horák, T., Hori, M., Joers, J., Kamiya, K., Karbasforoushan, H., Keřkovský, M., Khatibi, A., Kim, J. W., Kinany, N., Kitzler, H. H., Kolind, S., Kong, Y., Kudlička, P., Kuntke, P., Kurniawan, N. D., Kusmia, S., Labounek, R., Laganà, M. M., Laule, C., Law, C. S., Lenglet, C., Leutritz, T., Liu, Y., Llufriu, S., Mackey, S., Martinez-Heras, E., Mattera, L., Nestrasil, I., O'Grady, K. P., Papinutto, N., Papp, D., Pareto, D., Parrish, T. B., Pichiecchio, A., Prados, F., Rovira, À., Ruitenberg, M. J., Samson, R. S., Savini, G., Seif, M., Seifert, A. C., Smith, A. K., Smith, S. A., Smith, Z. A., Solana, E., Suzuki, Y., Tackley, G., Tinnermann, A., Valošek, J., Van De Ville, D., Yiannakas, M. C., Weber Ii, K. A., Weiskopf, N., Wise, R. G., Wyss, P. O., Xu, J. 2021; 8 (1): 219


    In a companion paper by Cohen-Adad et al. we introduce the spine generic quantitative MRI protocol that provides valuable metrics for assessing spinal cord macrostructural and microstructural integrity. This protocol was used to acquire a single subject dataset across 19 centers and a multi-subject dataset across 42 centers (for a total of 260 participants), spanning the three main MRI manufacturers: GE, Philips and Siemens. Both datasets are publicly available via git-annex. Data were analysed using the Spinal Cord Toolbox to produce normative values as well as inter/intra-site and inter/intra-manufacturer statistics. Reproducibility for the spine generic protocol was high across sites and manufacturers, with an average inter-site coefficient of variation of less than 5% for all the metrics. Full documentation and results can be found at . The datasets and analysis pipeline will help pave the way towards accessible and reproducible quantitative MRI in the spinal cord.

    View details for DOI 10.1038/s41597-021-00941-8

    View details for PubMedID 34400655

  • Multi-muscle deep learning segmentation to automate the quantification of muscle fat infiltration in cervical spine conditions. Scientific reports Weber, K. A., Abbott, R., Bojilov, V., Smith, A. C., Wasielewski, M., Hastie, T. J., Parrish, T. B., Mackey, S., Elliott, J. M. 2021; 11 (1): 16567


    Muscle fat infiltration (MFI) has been widely reported across cervical spine disorders. The quantification of MFI requires time-consuming and rater-dependent manual segmentation techniques. A convolutional neural network (CNN) model was trained to segment seven cervical spine muscle groups (left and right muscles segmented separately, 14 muscles total) from Dixon MRI scans (n = 17, 17 scans < 2 weeks post motor vehicle collision (MVC), and 17 scans 12 months post MVC). The CNN MFI measures demonstrated high test reliability and accuracy in an independent testing dataset (n = 18, 9 scans < 2 weeks post MVC, and 9 scans 12 months post MVC). Using the CNN in 84 participants with scans < 2 weeks post MVC (61 females, 23 males, age = 34.2 ± 10.7 years) differences in MFI between the muscle groups and relationships between MFI and sex, age, and body mass index (BMI) were explored. Averaging across all muscles, females had significantly higher MFI than males (p = 0.026). The deep cervical muscles demonstrated significantly greater MFI than the more superficial muscles (p < 0.001), and only MFI within the deep cervical muscles was moderately correlated to age (r > 0.300, p ≤ 0.001). CNN's allow for the accurate and rapid, quantitative assessment of the composition of the architecturally complex muscles traversing the cervical spine. Acknowledging the wider reports of MFI in cervical spine disorders and the time required to manually segment the individual muscles, this CNN may have diagnostic, prognostic, and predictive value in disorders of the cervical spine.

    View details for DOI 10.1038/s41598-021-95972-x

    View details for PubMedID 34400672

  • Spinal Cord Resting State Activity in Individuals With Fibromyalgia Who Take Opioids. Frontiers in neurology Martucci, K. T., Weber, K. A., Mackey, S. C. 2021; 12: 694271


    Chronic pain coincides with myriad functional alterations throughout the brain and spinal cord. While spinal cord mechanisms of chronic pain have been extensively characterized in animal models and in vitro, to date, research in patients with chronic pain has focused only very minimally on the spinal cord. Previously, spinal cord functional magnetic resonance imaging (fMRI) identified regional alterations in spinal cord activity in patients (who were not taking opioids) with fibromyalgia, a chronic pain condition. Here, in patients with fibromyalgia who take opioids (N = 15), we compared spinal cord resting-state fMRI data vs. patients with fibromyalgia not taking opioids (N = 15) and healthy controls (N = 14). We hypothesized that the opioid (vs. non-opioid) patient group would show greater regional alterations in spinal cord activity (i.e., the amplitude of low frequency fluctuations or ALFF, a measure of regional spinal cord activity). However, we found that regional spinal cord activity in the opioid group was more similar to healthy controls, while regional spinal cord activity in the non-opioid group showed more pronounced differences (i.e., ventral increases and dorsal decreases in regional ALFF) vs. healthy controls. Across patient groups, self-reported fatigue correlated with regional differences in spinal cord activity. Additionally, spinal cord functional connectivity and graph metrics did not differ among groups. Our findings suggest that, contrary to our main hypothesis, patients with fibromyalgia who take opioids do not have greater alterations in regional spinal cord activity. Thus, regional spinal cord activity may be less imbalanced in patients taking opioids compared to patients not taking opioids.

    View details for DOI 10.3389/fneur.2021.694271

    View details for PubMedID 34421798

    View details for PubMedCentralID PMC8371264

  • The influence of conventional T2 MRI indices in predicting who will walk outside one year after spinal cord injury. The journal of spinal cord medicine Berliner, J. C., O'Dell, D. R., Albin, S. R., Dungan, D. n., Sevigny, M. n., Elliott, J. M., Weber, K. A., Abdie, D. R., Anderson, J. S., Rich, A. A., Seib, C. A., Sagan, H. G., Smith, A. C. 2021: 1–7


    Magnetic resonance imaging (MRI) indices of spinal cord damage are predictive of future motor function after spinal cord injury (SCI): hyperintensity length, midsagittal tissue bridges, and Brain and Spinal Injury Center (BASIC) scores. Whether these indices are predictive of outdoor walking after SCI is unknown. The primary purpose was to see if these MRI indices predict the ability to walk outdoors one-year after SCI. The secondary purpose was to determine if MRI indices provide additional predictive value if initial lower extremity motor scores are available.Retrospective. Clinical T2-weighted MRIs were used to quantify spinal cord damage. Three MRI indices were calculated: midsagittal ventral tissue bridges, hyperintensity length, BASIC scores.Academic hospital.129 participants with cervical SCI.Inpatient rehabilitation.One year after SCI, participants self-reported their outdoor walking ability.Midsagittal ventral tissue bridges, hyperintensity length, and BASIC scores significantly correlated with outdoor walking ability (R = 0.34, P < 0.001; R = -0.25, P < 0.01; Rs = -0.35, P < 001, respectively). Using midsagittal ventral tissue bridges and hyperintensity length, the final adjusted R2 for model 1 = 0.19. For model 2, the adjusted R2 using motor scores alone = 0.81 and MRI variables were non-significant. All five participants with observable intramedullary hemorrhage reported they were unable to walk one block outdoors.The MRI indices were significant predictors of outdoor walking ability, but when motor scores were available, this was the strongest predictor and neither midsagittal tissue bridges nor hyperintensity length contributed additional value. MRI indices may be a quick and convenient supplement to physical examination when motor testing is unavailable.

    View details for DOI 10.1080/10790268.2021.1907676

    View details for PubMedID 33798025

  • The global summit on the efficacy and effectiveness of spinal manipulative therapy for the prevention and treatment of non-musculoskeletal disorders: a systematic review of the literature. Chiropractic & manual therapies Côté, P. n., Hartvigsen, J. n., Axén, I. n., Leboeuf-Yde, C. n., Corso, M. n., Shearer, H. n., Wong, J. n., Marchand, A. A., Cassidy, J. D., French, S. n., Kawchuk, G. N., Mior, S. n., Poulsen, E. n., Srbely, J. n., Ammendolia, C. n., Blanchette, M. A., Busse, J. W., Bussières, A. n., Cancelliere, C. n., Christensen, H. W., De Carvalho, D. n., De Luca, K. n., Du Rose, A. n., Eklund, A. n., Engel, R. n., Goncalves, G. n., Hebert, J. n., Hincapié, C. A., Hondras, M. n., Kimpton, A. n., Lauridsen, H. H., Innes, S. n., Meyer, A. L., Newell, D. n., O'Neill, S. n., Pagé, I. n., Passmore, S. n., Perle, S. M., Quon, J. n., Rezai, M. n., Stupar, M. n., Swain, M. n., Vitello, A. n., Weber, K. n., Young, K. J., Yu, H. n. 2021; 29 (1): 8


    A small proportion of chiropractors, osteopaths, and other manual medicine providers use spinal manipulative therapy (SMT) to manage non-musculoskeletal disorders. However, the efficacy and effectiveness of these interventions to prevent or treat non-musculoskeletal disorders remain controversial.We convened a Global Summit of international scientists to conduct a systematic review of the literature to determine the efficacy and effectiveness of SMT for the primary, secondary and tertiary prevention of non-musculoskeletal disorders.The Global Summit took place on September 14-15, 2019 in Toronto, Canada. It was attended by 50 researchers from 8 countries and 28 observers from 18 chiropractic organizations. At the summit, participants critically appraised the literature and synthesized the evidence.We searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, the Cumulative Index to Nursing and Allied Health, and the Index to Chiropractic Literature from inception to May 15, 2019 using subject headings specific to each database and free text words relevant to manipulation/manual therapy, effectiveness, prevention, treatment, and non-musculoskeletal disorders. Eligible for review were randomized controlled trials published in English. The methodological quality of eligible studies was assessed independently by reviewers using the Scottish Intercollegiate Guidelines Network (SIGN) criteria for randomized controlled trials. We synthesized the evidence from articles with high or acceptable methodological quality according to the Synthesis without Meta-Analysis (SWiM) Guideline. The final risk of bias and evidence tables were reviewed by researchers who attended the Global Summit and 75% (38/50) had to approve the content to reach consensus.We retrieved 4997 citations, removed 1123 duplicates and screened 3874 citations. Of those, the eligibility of 32 articles was evaluated at the Global Summit and 16 articles were included in our systematic review. Our synthesis included six randomized controlled trials with acceptable or high methodological quality (reported in seven articles). These trials investigated the efficacy or effectiveness of SMT for the management of infantile colic, childhood asthma, hypertension, primary dysmenorrhea, and migraine. None of the trials evaluated the effectiveness of SMT in preventing the occurrence of non-musculoskeletal disorders. Consensus was reached on the content of all risk of bias and evidence tables. All randomized controlled trials with high or acceptable quality found that SMT was not superior to sham interventions for the treatment of these non-musculoskeletal disorders. Six of 50 participants (12%) in the Global Summit did not approve the final report.Our systematic review included six randomized clinical trials (534 participants) of acceptable or high quality investigating the efficacy or effectiveness of SMT for the treatment of non-musculoskeletal disorders. We found no evidence of an effect of SMT for the management of non-musculoskeletal disorders including infantile colic, childhood asthma, hypertension, primary dysmenorrhea, and migraine. This finding challenges the validity of the theory that treating spinal dysfunctions with SMT has a physiological effect on organs and their function. Governments, payers, regulators, educators, and clinicians should consider this evidence when developing policies about the use and reimbursement of SMT for non-musculoskeletal disorders.

    View details for DOI 10.1186/s12998-021-00362-9

    View details for PubMedID 33596925

  • New insights into intrinsic foot muscle morphology and composition using ultra-high-field (7-Tesla) magnetic resonance imaging. BMC musculoskeletal disorders Franettovich Smith, M. M., Elliott, J. M., Al-Najjar, A. n., Weber, K. A., Hoggarth, M. A., Vicenzino, B. n., Hodges, P. W., Collins, N. J. 2021; 22 (1): 97


    The intrinsic muscles of the foot are key contributors to foot function and are important to evaluate in lower limb disorders. Magnetic resonance imaging (MRI), provides a non-invasive option to measure muscle morphology and composition, which are primary determinants of muscle function. Ultra-high-field (7-T) magnetic resonance imaging provides sufficient signal to evaluate the morphology of the intrinsic foot muscles, and, when combined with chemical-shift sequences, measures of muscle composition can be obtained. Here we aim to provide a proof-of-concept method for measuring intrinsic foot muscle morphology and composition with high-field MRI.One healthy female (age 39 years, mass 65 kg, height 1.73 m) underwent MRI. A T1-weighted VIBE - radio-frequency spoiled 3D steady state GRE - sequence of the whole foot was acquired on a Siemens 7T MAGNETOM scanner, as well as a 3T MAGNETOM Prisma scanner for comparison. A high-resolution fat/water separation image was also acquired using a 3D 2-point DIXON sequence at 7T. Coronal plane images from 3T and 7T scanners were compared. Using 3D Slicer software, regions of interest were manually contoured for each muscle on 7T images. Muscle volumes and percentage of muscle fat infiltration were calculated (muscle fat infiltration % = Fat/(Fat + Water) x100) for each muscle.Compared to the 3T images, the 7T images provided superior resolution, particularly at the forefoot, to facilitate segmentation of individual muscles. Muscle volumes ranged from 1.5 cm3 and 19.8 cm3, and percentage muscle fat infiltration ranged from 9.2-15.0%.This proof-of-concept study demonstrates a feasible method of quantifying muscle morphology and composition for individual intrinsic foot muscles using advanced high-field MRI techniques. This method can be used in future studies to better understand intrinsic foot muscle morphology and composition in healthy individuals, as well as those with lower disorders.

    View details for DOI 10.1186/s12891-020-03926-7

    View details for PubMedID 33478467

    View details for PubMedCentralID PMC7818930

  • Spinal manipulation and modulation of pain sensitivity in persistent low back pain: a secondary cluster analysis of a randomized trial. Chiropractic & manual therapies Nim, C. G., Weber, K. A., Kawchuk, G. N., O'Neill, S. n. 2021; 29 (1): 10


    Pain hypersensitivity can be assessed using Quantitative Sensory Testing (QST) and is associated with persistent low back pain. Spinal manipulation appears to modify pain hypersensitivity, and this could function as one mechanism leading to clinical improvements. In the current study, we applied a comprehensive QST battery to assess pain sensitivity in a cohort of low back pain patients before and after spinal manipulation to improve our understanding of the association between QST and clinical improvements. This study addresses two questions: Are clinical improvements following spinal manipulation in low back pain patients contingent on pain hypersensitivity, and does pain sensitivity change following spinal manipulation?We performed a secondary analysis of data from a randomized clinical trial. One hundred and thirty-two participants with persistent LBP were treated with spinal manipulation four times over two weeks. Patient-reported outcomes and QST were assessed at baseline, after the fourth spinal manipulation session, and 14-days later. The clinical outcomes were changes in low back pain intensity and disability. Using latent profile analysis, we categorized the participants into clusters depending on their baseline QST scores. We used linear mixed models to examine the association between clusters and changes in patient-reported outcomes and QST.Two clusters emerged: a Sensitized and a Not sensitized. The former had significantly lower regional pressure and thermal pain thresholds, remote pressure pain tolerance, and lower inhibitory conditioned pain modulation than the Not sensitized group. However, we only found between-cluster differences for regional pressure pain threshold following spinal manipulation. Thus, the clusters were not associated with patient-reported pain and disability changes or the remaining QST outcomes.We report that the baseline QST profile was not associated with clinical improvements following spinal manipulation. We did observe a substantial change for regional pressure pain threshold, which suggests that any effect of spinal manipulation on pain sensitivity is most likely to be observed as changes in regional, mechanical pain threshold. However, the mechanism that invokes clinical improvement and pain sensitivity changes appear distinct. Due to methodological caveats, we advise caution when interpreting the identifier: NCT04086667 , registered 11 September 2019 - Retrospectively registered,

    View details for DOI 10.1186/s12998-021-00367-4

    View details for PubMedID 33627163

    View details for PubMedCentralID PMC7903787

  • Misinformation, chiropractic, and the COVID-19 pandemic. Chiropractic & manual therapies Axen, I., Bergstrom, C., Bronson, M., Cote, P., Nim, C. G., Goncalves, G., Hebert, J. J., Hertel, J. A., Innes, S., Larsen, O. K., Meyer, A., O'Neill, S., Perle, S. M., Weber, K. A., Young, K. J., Leboeuf-Yde, C. 2020; 28 (1): 65


    BACKGROUND: In March 2020, the World Health Organization elevated the coronavirus disease (COVID-19) epidemic to a pandemic and called for urgent and aggressive action worldwide. Public health experts have communicated clear and emphatic strategies to prevent the spread of COVID-19. Hygiene rules and social distancing practices have been implemented by entire populations, including 'stay-at-home' orders in many countries. The long-term health and economic consequences of the COVID-19 pandemic are not yet known.MAIN TEXT: During this time of crisis, some chiropractors made claims on social media that chiropractic treatment can prevent or impact COVID-19. The rationale for these claims is that spinal manipulation can impact the nervous system and thus improve immunity. These beliefs often stem from nineteenth-century chiropractic concepts. We are aware of no clinically relevant scientific evidence to support such statements. We explored the internet and social media to collect examples of misinformation from Europe, North America, Australia and New Zealand regarding the impact of chiropractic treatment on immune function. We discuss the potential harm resulting from these claims and explore the role of chiropractors, teaching institutions, accrediting agencies, and legislative bodies.CONCLUSIONS: Members of the chiropractic profession share a collective responsibility to act in the best interests of patients and public health. We hope that all chiropractic stakeholders will view the COVID-19 pandemic as a call to action to eliminate the unethical and potentially dangerous claims made by chiropractors who practise outside the boundaries of scientific evidence.

    View details for DOI 10.1186/s12998-020-00353-2

    View details for PubMedID 33208144

  • Axial MRI biomarkers of spinal cord damage to predict future walking and motor function: a retrospective study. Spinal cord Smith, A. C., Albin, S. R., O'Dell, D. R., Berliner, J. C., Dungan, D., Sevigny, M., Draganich, C., Elliott, J. M., Weber Ii, K. A. 2020


    STUDY DESIGN: Retrospective.OBJECTIVES: Primary: to assess if axial damage ratios are predictors of future walking after spinal cord injury (SCI), and if they add any predictive value if initial neurological impairment grades are available. Secondary: to determine if lateral spinal cord regions are predictors of future lower extremity motor scores (LEMS).SETTING: University/hospital.METHODS: Axial T2-weighted MRIs were used. Axial damage ratios and non-damaged lateral cord volumes were calculated. Each participant answered at 1 year after SCI, "Are you able to walk for 150 feet? (45.72 meters)" For the secondary aim, right and left LEMS were used.RESULTS: In total, 145 participants were selected. Individuals that could walk had smaller ratios than those that were unable. Walking and axial damage ratios were negatively correlated. A 0.374 ratio cut-off showed optimal sensitivity/specificity. When initial neurological grades were used, axial damage ratios did not add predictive value. Forty-two participants had LEMS available and were included for the secondary aim. Right cord regions and right LEMS were positively correlated and left regions and left LEMS, but these variables were also correlated with each other.CONCLUSIONS: Axial damage ratios were significant predictors of walking ability 1 year after SCI. However, this measure did not add predictive value over initial neurological grades. Lateral cord regions correlated with same-side LEMS, but the opposite was also found, calling this biomarker's specificity into question. Axial damage ratios may be useful in predicting walking after SCI if initial neurological grades are unavailable.SPONSORSHIP: This research was funded by a National Institutes of Health award, National Institute of Child Health and Development-NIH R03HD094577.

    View details for DOI 10.1038/s41393-020-00561-w

    View details for PubMedID 33024298

  • Association of State Policies Allowing Medical Cannabis for Opioid Use Disorder With Dispensary Marketing for This Indication. JAMA network open Shover, C. L., Vest, N. A., Chen, D., Stueber, A., Falasinnu, T. O., Hah, J. M., Kim, J., Mackey, I., Weber, K. A., Ziadni, M., Humphreys, K. 2020; 3 (7): e2010001


    Importance: Misinformation about cannabis and opioid use disorder (OUD) may increase morbidity and mortality if it leads individuals with OUD to forego evidence-based treatment. It has not been systematically evaluated whether officially designating OUD as a qualifying condition for medical cannabis is associated with cannabis dispensaries suggesting cannabis as a treatment for OUD.Objective: To examine whether state-level policies designating OUD a qualifying condition for medical cannabis are associated with more dispensaries claiming cannabis can treat OUD.Design, Setting, and Participants: This cross-sectional, mixed-methods study of 208 medical dispensary brands was conducted in 2019 using the brands' online content. The study included dispensaries operating in New Jersey, New York, and Pennsylvania, where OUD is a qualifying condition for medical cannabis, and in Connecticut, Delaware, Maryland, Ohio, and West Virginia, where this policy does not exist.Exposures: Presence of OUD on the list of qualifying conditions for a state's medical cannabis program.Main Outcomes and Measures: Binary indicators of whether online content from the brand said cannabis can treat OUD, can replace US Food and Drug Administration-approved medications for OUD, can be an adjunctive therapy to Food and Drug Administration-approved medications for OUD, or can be used as a substitute for opioids to treat other conditions (eg, chronic pain).Results: After excluding duplicates, listings for nonexistent dispensaries, and those without online content, 167 brands across 7 states were included in the analysis (44 [26.3%] in states where OUD was a qualifying condition and 123 [73.7%] in adjacent states). A dispensary listed in a directory for West Virginia was not operational; therefore, comparison states were Connecticut, Delaware, Maryland, and Ohio. In policy-exposed states, 39% (95% CI, 23%-55%) more dispensaries claimed cannabis could treat OUD compared with unexposed states (P<.001). For replacing medications for OUD and being an adjunctive therapy, the differences were 14% (95% CI, 2%-26%; P=.002) and 28% (95% CI, 14%-42%; P<.001), respectively. The suggestion that cannabis could substitute for opioids (eg, to treat chronic pain) was made by 25% (95% CI, 9%-41%) more brands in policy-exposed states than adjacent states (P=.002).Conclusions and Relevance: In this study, state-level policies designating OUD as a qualifying condition for medical cannabis were associated with more dispensaries claiming cannabis can treat OUD. In the current policy environment, in which medical claims by cannabis dispensaries are largely unregulated, these advertisements could harm patients. Future research linking these policies to patient outcomes is warranted.

    View details for DOI 10.1001/jamanetworkopen.2020.10001

    View details for PubMedID 32662844

  • Midsagittal tissue bridges are associated with walking ability in incomplete spinal cord injury: A magnetic resonance imaging case series JOURNAL OF SPINAL CORD MEDICINE O'Dell, D. R., Weber, K. A., Berliner, J. C., Elliott, J. M., Connor, J. R., Cummins, D. P., Heller, K. A., Hubert, J. S., Kates, M. J., Mendoza, K. R., Smith, A. C. 2020; 43 (2): 268–71
  • Muscle fat infiltration following whiplash: A computed tomography and magnetic resonance imaging comparison. PloS one Elliott, J. M., Smith, A. C., Hoggarth, M. A., Albin, S. R., Weber, K. A., Haager, M. n., Fundaun, J. n., Wasielewski, M. n., Courtney, D. M., Parrish, T. B. 2020; 15 (6): e0234061


    Here we present a secondary analysis from a parent database of 97 acutely injured participants enrolled in a prospective inception cohort study of whiplash recovery after motor vehicle collision (MVC). The purpose was to investigate the deep and superficial neck extensor muscles with peri-traumatic computed tomography (CT) and longitudinal measures of magnetic resonance imaging (MRI) in participants with varying levels of whiplash-related disability. Thirty-six underwent standard care imaging of the cervical spine with CT at a level-1 trauma designated emergency department. All 36 participants were assessed with MRI of the cervical spine at <1-week, 2-weeks, 3-, and 12-months post-injury and classified into three groups using initial pain severity and percentage scores on the Neck Disability Index (recovered (NDI of 0-8%), mild (NDI of 10-28%), or severe (NDI ≥ 30%)) at 3-months post MVC. CT muscle attenuation values were significantly correlated to muscle fat infiltration (MFI) on MRI at one-week post MVC. There was no significant difference in muscle attenuation across groups at the time of enrollment. A trend of lower muscle attenuation in the deep compared to the superficial extensors was observed in the severe group. MFI values in the deep muscles on MRI were significantly higher in the severe group when compared to the mild group at 1-year post MVC. This study provides further evidence that the magnitude of 1) deep MFI appears unique to those at risk of and eventually transitioning to chronic WAD and that 2) pre- or peri-traumatic muscular health, determined by CT muscle attenuation, may be contribute to our understanding of long-term recovery.

    View details for DOI 10.1371/journal.pone.0234061

    View details for PubMedID 32484835

  • Macromolecular changes in spinal cord white matter characterize whiplash outcome at 1-year post motor vehicle collision. Scientific reports Hoggarth, M. A., Elliott, J. M., Smith, Z. A., Paliwal, M. n., Kwasny, M. J., Wasielewski, M. n., Weber, K. A., Parrish, T. B. 2020; 10 (1): 22221


    Each year, whiplash injuries from motor vehicle collisions (MVC) affect millions worldwide, with no strong evidence of pathology. While the majority recover soon after the injury, the same is not true for roughly 20% reporting higher levels of pain and distress, without diagnostic options. This study used magnetization transfer (MT) imaging to quantify white matter integrity in 78 subjects with varying levels of pain, 1 year after MVC. MT images of the cervical spinal cord were collected parallel to the intervertebral disks. MT ratios (MTR) were calculated in select white matter tracts along with MTR homogeneity (MTRh) at each level. Significant differences were observed between clinical outcome groups in the left and right spinothalamic tracts (p = 0.003 and 0.020) and MTRh (p = 0.009). MTRh was elevated in females with poor recovery versus females reporting recovery (p < 0.001) or milder symptoms (p < 0.001), and in males reporting recovery (p = 0.007) or no recovery (p < 0.001). There was a significant interaction between recovery status and sex (p = 0.015). MT imaging identified tract specific and regional changes in white matter integrity suggesting potential insults to the cord. Additionally, significant MTRh differences between sexes were observed, characterizing the heterogeneity of whiplash recovery and worse outcomes in females.

    View details for DOI 10.1038/s41598-020-79190-5

    View details for PubMedID 33335188

    View details for PubMedCentralID PMC7747591

  • Foot exercise plus education versus wait and see for the treatment of plantar heel pain (FEET trial): a protocol for a feasibility study. Journal of foot and ankle research Franettovich Smith, M. M., Collins, N. J., Mellor, R. n., Grimaldi, A. n., Elliott, J. n., Hoggarth, M. n., Weber Ii, K. A., Vicenzino, B. n. 2020; 13 (1): 20


    Plantar heel pain (PHP) is present in a wide range of individuals and creates significant burden to quality of life and participation in physical activity. The high recurrence rates and persistence of PHP suggests current management options may not address all potentially modifiable factors associated with the condition. Reports of intrinsic foot muscle (IFM) atrophy in individuals with PHP, together with biomechanical evidence of their important contribution to optimal foot function, suggests that an intervention focused on IFM training may be beneficial in managing PHP. We will test the feasibility of a prospective, assessor-blinded, parallel-group, randomised clinical trial that compares foot exercise plus education to brief advice in individuals with PHP.Twenty participants with PHP will be randomly allocated to one of two groups for a 12-week intervention period: (i) foot exercise plus education, or (ii) brief advice. The foot exercise plus education group will attend eight sessions with a physiotherapist and receive detailed education on self-management strategies as well as a progressive exercise program for the IFMs. The brief advice group will attend one session with a physiotherapist and receive brief information about self-management strategies and reassurance. Outcome measures will be obtained at baseline and the primary end-point of 12 weeks. Primary outcomes will be the feasibility of conducting a full-scale randomised clinical trial (RCT), and the credibility and acceptability of the foot exercise plus education intervention. Secondary outcomes will explore treatment effects, which will consist of pain, physical function, physical activity level, pain self-efficacy, perceived treatment effect, magnetic resonance and ultrasound image measurement of IFM morphology, ultrasound imaging measurement of plantar fascia thickness, IFM motor performance, foot posture, foot mobility, ankle dorsiflexion range of motion, toe flexor and plantar flexor strength/endurance.To reduce the burden of PHP on individuals and society, there is a need to establish effective treatments that are feasible and accepted by patients and health professionals. This trial will be the first to evaluate the feasibility of conducting a full-scale RCT, as well as the credibility, acceptability, and treatment effects, of education and foot exercise for PHP. The findings of this study will inform the development of a full-scale RCT.The trial protocol was prospectively registered with the Australia and New Zealand Clinical Trial Registry (ACTRN12619000987167) on 11th July 2019.

    View details for DOI 10.1186/s13047-020-00384-1

    View details for PubMedID 32384905

    View details for PubMedCentralID PMC7206811

  • Spinal Cord Imaging Markers and Recovery of Volitional Leg Movement With Spinal Cord Epidural Stimulation in Individuals With Clinically Motor Complete Spinal Cord Injury. Frontiers in systems neuroscience Rejc, E. n., Smith, A. C., Weber, K. A., Ugiliweneza, B. n., Bert, R. J., Negahdar, M. n., Boakye, M. n., Harkema, S. J., Angeli, C. A. 2020; 14: 559313


    Previous studies have shown that epidural stimulation of the lumbosacral spinal cord (scES) can re-enable lower limb volitional motor control in individuals with chronic, clinically motor complete spinal cord injury (SCI). This observation entails that residual supraspinal connectivity to the lumbosacral spinal circuitry still persisted after SCI, although it was non-detectable when scES was not provided. In the present study, we aimed at exploring further the mechanisms underlying scES-promoted recovery of volitional lower limb motor control by investigating neuroimaging markers at the spinal cord lesion site via magnetic resonance imaging (MRI). Spinal cord MRI was collected prior to epidural stimulator implantation in 13 individuals with chronic, clinically motor complete SCI, and the spared tissue of specific regions of the spinal cord (anterior, posterior, right, left, and total cord) was assessed. After epidural stimulator implantation, and prior to any training, volitional motor control was evaluated during left and right lower limb flexion and ankle dorsiflexion attempts. The ability to generate force exertion and movement was not correlated to any neuroimaging marker. On the other hand, spared tissue of specific cord regions significantly and importantly correlated with some aspects of motor control that include activation amplitude of antagonist (negative correlation) muscles during left ankle dorsiflexion, and electromyographic coordination patterns during right lower limb flexion. The fact that amount and location of spared spinal cord tissue at the lesion site were not related to the ability to generate volitional lower limb movements may suggest that supraspinal inputs through spared spinal cord regions that differ across individuals can result in the generation of lower limb volitional motor output prior to any training when epidural stimulation is provided.

    View details for DOI 10.3389/fnsys.2020.559313

    View details for PubMedID 33192348

    View details for PubMedCentralID PMC7654217

  • Magnetization Transfer Ratio and Morphometrics Of the Spinal Cord Associates with Surgical Recovery in Patients with Degenerative Cervical Myelopathy. World neurosurgery Paliwal, M. n., Weber, K. A., Hopkins, B. S., Cantrell, D. R., Hoggarth, M. A., Elliott, J. M., Dahdaleh, N. S., Mackey, S. n., Parrish, T. D., Dhaher, Y. n., Smith, Z. A. 2020


    Longitudinal Cohort Study OBJECTIVES: To assess prognostic value of pre-surgical Magnetization Transfer Ratio (MTR) and morphometrics of the spinal cord in patients with Degenerative Cervical Myelopathy (DCM).Thirteen subjects with DCM underwent 3T magnetization transfer imaging. MTR was calculated for spinal cord regions and specific white matter tracts. Morphometric measures were extracted. Clinical (modified Japanese orthopedics Association (mJOA) and Nurick) and health related quality of life scores were assessed before and after cervical decompression surgery. Association between MRI metrics and post- surgical recovery was assessed (Spearman's correlation). Receiver operator characteristics (ROC) assessed the accuracy of MRI metrics in identifying at least 50% recovery in function.Preoperative anterior cord MTR were associated with recovery in mJOA scores (ρ =0.608, p=0.036 and AUC =0.66). Preoperative lateral cord MTR was correlated with neck disability index (ρ =0.699, p=0.011) and pain interference (ρ =0.732, p=0.007). Preoperative rubrospinal tract MTR was associated mJOA score recovery (ρ =0.573, p=0.041, AUC= 0.86). Preoperative corticospinal tract and reticulospinal MTR were related to recovery in pain interference scores (ρ =0.591, p=0.033 and ρ =0.583, p=0.035). Eccentricity of the cord was associated with Nurick scores (ρ = 0.606, p=0.028) and mJOA (ρ =0.651, p=0.025, AUC=0.92).Preoperative MTR and eccentricity measurements of the spinal cord have prognostic value in assessing response to surgery and recovery in patient with DCM. Advanced MRI and atlas-based post processing techniques can inform interventions and advance healthcare received by patients with DCM.

    View details for DOI 10.1016/j.wneu.2020.09.148

    View details for PubMedID 33010502

  • Machine Learning for the Prediction of Cervical Spondylotic Myelopathy: A Post Hoc Pilot Study of 28 Participants WORLD NEUROSURGERY Hopkins, B. S., Weber, K. A., Kesavabhotla, K., Paliwal, M., Cantrell, D. R., Smith, Z. A. 2019; 127: E436–E442
  • Dynamic per slice shimming for simultaneous brain and spinal cord fMRI MAGNETIC RESONANCE IN MEDICINE Islam, H., Law, C. W., Weber, K. A., Mackey, S. C., Glover, G. H. 2019; 81 (2): 825–38

    View details for DOI 10.1002/mrm.27388

    View details for Web of Science ID 000462086300010

  • Evidence for decreased Neurologic Pain Signature activation following thoracic spinal manipulation in healthy volunteers and participants with neck pain. NeuroImage. Clinical Weber Ii, K. A., Wager, T. D., Mackey, S. n., Elliott, J. M., Liu, W. C., Sparks, C. L. 2019; 24: 102042


    Spinal manipulation (SM) is a common treatment for neck and back pain, theorized to mechanically affect the spine leading to therapeutic mechanical changes. The link between specific mechanical effects and clinical improvement is not well supported. SM's therapeutic action may instead be partially mediated within the central nervous system.To introduce brain-based models of pain for spinal pain and manual therapy research, characterize the distributed central mechanisms of SM, and advance the preliminary validation of brain-based models as potential clinical biomarkers of pain.Secondary analysis of two functional magnetic resonance imaging studies investigating the effect of thoracic SM on pain-related brain activity: A non-controlled, non-blinded study in healthy volunteers (Study 1, n = 10, 5 females, and mean age = 31.2 ± 10.0 years) and a randomized controlled study in participants with acute to subacute neck pain (Study 2, n = 24, 16 females, mean age = 38.0 ± 15.1 years).Functional magnetic resonance imaging was performed during noxious mechanical stimulation of the right index finger cuticle pre- and post-intervention. The effect of SM on pain-related activity was studied within brain regions defined by the Neurologic Pain Signature (NPS) that are predictive of physical pain.In Study 1, evoked mechanical pain (p < 0.001) and NPS activation (p = 0.010) decreased following SM, and the changes in evoked pain and NPS activation were correlated (rRM2 = 0.418, p = 0.016). Activation within the NPS subregions of the dorsal anterior cingulate cortex (dACC, p = 0.012) and right secondary somatosensory cortex/operculum (rS2_Op, p = 0.045) also decreased following SM, and evoked pain was correlated with dACC activity (rRM2 = 0.477, p = 0.019). In Study 2, neck pain (p = 0.046) and NPS (p = 0.033) activation decreased following verum but not sham SM. Associations between evoked pain, neck pain, and NPS activation, were not significant and less clear, possibly due to inadequate power, methodological limitations, or other confounding factors.The findings provide preliminary evidence that SM may alter the processing of pain-related brain activity within specific pain-related brain regions and support the use of brain-based models as clinical biomarkers of pain.

    View details for DOI 10.1016/j.nicl.2019.102042

    View details for PubMedID 31670070

  • MRI atlas-based volumetric mapping of the cervical cord gray matter in cervical canal stenosis. World neurosurgery Smith, Z. A., Weber, K. A., Paliwal, M. n., Hopkins, B. S., Barry, A. J., Cantrell, D. n., Ganju, A. n., Koski, T. R., Parrish, T. B., Dhaher, Y. n. 2019

    View details for DOI 10.1016/j.wneu.2019.10.109

    View details for PubMedID 31669690

  • Are Magnetic Resonance Imaging Technologies Crucial to Our Understanding of Spinal Conditions? The Journal of orthopaedic and sports physical therapy Crawford, R. J., Fortin, M. n., Weber, K. A., Smith, A. n., Elliott, J. M. 2019: 1–32


    The development of persistent spinal (traumatic and non-traumatic) pain is common and contributes to high societal and personal costs, globally. There is an acknowledged urgency for new and interdisciplinary approaches to the problem, and soft tissues including skeletal muscles, the spinal cord, and brain are rightly receiving increased attention as important biological contributors. In reaction to recent suspicion of and questioned value for imaging-based findings, this paper serves to recognize the promise that the technological evolution of imaging techniques, and particularly magnetic resonance imaging (MRI), is allowing in characterizing previously less visible morphology. We emphasize the value for quantification and data analysis of several contributors in the biopsychosocial model for understanding spinal pain. Further, we highlight emerging evidence regarding the pathobiology of changes to muscle composition (eg, atrophy, fatty infiltration) as well as advancements in neuro- and musculoskeletal imaging techniques (eg, fat/water imaging, functional MRI, diffusion imaging, magnetization transfer imaging) of these important soft tissues. These non-invasive and objective data sources may complement known prognostic factors of poor recovery, patient self-report, diagnostic tests, and the -omics fields. When combined, advanced 'big-data' analyses may assist in identifying associations previously not considered. Our clinical commentary is supported by empirical findings that may orient future efforts towards collaborative conversation and hypotheses-generation, interdisciplinary research, translating across a number of health fields. Our emphasis is that MRI technologies and research are crucial to the advancement of our understanding of the complexities of spinal conditions. J Orthop Sports Phys Ther, Epub 26 Mar 2019. doi:10.2519/jospt.2019.8793.

    View details for DOI 10.2519/jospt.2019.8793

    View details for PubMedID 30913967

  • Deep Learning Convolutional Neural Networks for the Automatic Quantification of Muscle Fat Infiltration Following Whiplash Injury. Scientific reports Weber, K. A., Smith, A. C., Wasielewski, M. n., Eghtesad, K. n., Upadhyayula, P. A., Wintermark, M. n., Hastie, T. J., Parrish, T. B., Mackey, S. n., Elliott, J. M. 2019; 9 (1): 7973


    Muscle fat infiltration (MFI) of the deep cervical spine extensors has been observed in cervical spine conditions using time-consuming and rater-dependent manual techniques. Deep learning convolutional neural network (CNN) models have demonstrated state-of-the-art performance in segmentation tasks. Here, we train and test a CNN for muscle segmentation and automatic MFI calculation using high-resolution fat-water images from 39 participants (26 female, average = 31.7 ± 9.3 years) 3 months post whiplash injury. First, we demonstrate high test reliability and accuracy of the CNN compared to manual segmentation. Then we explore the relationships between CNN muscle volume, CNN MFI, and clinical measures of pain and neck-related disability. Across all participants, we demonstrate that CNN muscle volume was negatively correlated to pain (R = -0.415, p = 0.006) and disability (R = -0.286, p = 0.045), while CNN MFI tended to be positively correlated to disability (R = 0.214, p = 0.105). Additionally, CNN MFI was higher in participants with persisting pain and disability (p = 0.049). Overall, CNN's may improve the efficiency and objectivity of muscle measures allowing for the quantitative monitoring of muscle properties in disorders of and beyond the cervical spine.

    View details for DOI 10.1038/s41598-019-44416-8

    View details for PubMedID 31138878

  • Establishing the inter-rater reliability of spinal cord damage manual measurement using magnetic resonance imaging. Spinal cord series and cases Cummins, D. P., Connor, J. R., Heller, K. A., Hubert, J. S., Kates, M. J., Wisniewski, K. R., Berliner, J. C., O'Dell, D. R., Elliott, J. M., Weber, K. A., Smith, A. C. 2019; 5: 20


    Study design: Retrospective study.Objectives: To establish the inter-rater reliability in the quantitative evaluation of spinal cord damage following cervical incomplete spinal cord injury (SCI) utilizing magnetic resonance imaging (MRI). MRI was used to perform manual measurements of the cranial and caudal boundaries of edema, edema length, midsagittal tissue bridge ratio, axial damage ratio, and edema volume in 10 participants with cervical incomplete SCI.Setting: Academic university setting.Methods: Structural MRIs of 10 participants with SCI were collected from Northwestern University's Neuromuscular Imaging and Research Lab. All manual measures were performed using OsiriX (Pixmeo Sarl, Geneva, Switzerland). Intraclass correlation coefficients (ICC) were used to determine inter-rater reliability across seven raters of varying experience.Results: High-to-excellent inter-rater reliability was found for all measures. ICC values for cranial/caudal levels of involvement, edema length, midsagittal tissue bridge ratio, axial damage ratio, and edema volume were 0.99, 0.98, 0.90, 0.84, and 0.93, respectively.Conclusions: Manual MRI measures of spinal cord damage are reliable between raters. Researchers and clinicians may confidently utilize manual MRI measures to quantify cord damage. Future research to predict functional recovery following SCI and better inform clinical management is warranted.

    View details for DOI 10.1038/s41394-019-0164-1

    View details for PubMedID 31240117

  • Altered Cervical Spinal Cord Resting State Activity in Fibromyalgia. Arthritis & rheumatology (Hoboken, N.J.) Martucci, K. T., Weber, K. A., Mackey, S. C. 2018


    OBJECTIVE: Altered afferent input and central neural modulation are thought to contribute to fibromyalgia symptoms, and these processes converge within the spinal cord. We hypothesized that, using resting state functional magnetic resonance imaging (rs-fMRI) of the cervical spinal cord, we would observe altered frequency dependent activity in fibromyalgia.METHODS: Cervical spinal cord rs-fMRI was performed in fibromyalgia patients and healthy controls. We analyzed a measure of low frequency oscillatory power, the amplitude of low frequency fluctuations (ALFF), for frequencies 0.01 - 0.198 Hz and frequency sub-bands, to determine regional and frequency-specific alterations in fibromyalgia. Functional connectivity and graph metrics were also analyzed.RESULTS: As compared to controls, greater ventral and lesser dorsal Mean ALFF of the cervical spinal cord was observed in fibromyalgia (p < 0.05, uncorrected) for frequencies 0.01 - 0.198 Hz and all sub-bands. Additionally, lesser Mean ALFF within the right dorsal quadrant (p < 0.05, corrected) for frequencies 0.01 - 0.198 Hz and sub-band frequencies 0.073 - 0.198 Hz was observed in fibromyalgia. Regional Mean ALFF was not correlated with pain, however, regional lesser Mean ALFF was correlated with fatigue in patients (r = 0.763, p = 0.001). Functional connectivity and graph metrics were similar between groups.CONCLUSION: Our results indicate unbalanced activity between the ventral and dorsal cervical spinal cord in fibromyalgia. Increased ventral neural processes and decreased dorsal neural processes may reflect the presence of central sensitization and contribute to fatigue and other bodily symptoms in fibromyalgia. This article is protected by copyright. All rights reserved.

    View details for PubMedID 30281205

  • Tract-Specific Volume Loss on 3T MRI in Patients with Cervical Spondylotic Myelopathy. Spine Hopkins, B. S., Weber, K. A., Cloney, M. B., Paliwal, M. n., Parrish, T. B., Smith, Z. A. 2018


    Case-control.The aim of this study was to understand the role of high-resolution magnetic resonance (MR) in identifying regional cord volume loss in cervical spondylotic myelopathy (CSM).Preliminary studies suggest that compression of the ventral region of the cord may contribute disproportionately to CSM symptomology; however, tract-specific data are lacking in the CSM population. The current study is the first to use 3T MR imaging (MRI) images of CSM patients to determine specific volume loss at the level of detail of individual descending white matter tracts.Twelve patients with CSM and 14 age-matched were enrolled prospectively and underwent 3-Tesla MRI of the cervical spine. Using the high-resolution images of the spinal cord, straightening and alignment with a template was performed and specific spinal cord tract volumes were measured using Spinal Cord Tool-box version 3.0.7. Modified Japanese orthopedic association (mJOA) and Nurick disability scores were collected in a prospective manner and were analyzed in relation to descending spinal tract volumes.Having CSM was predicted by anterior/posterior diameter, eccentricity of the cord [odds ratio (OR) 0.000000621, P = 0.004], ventral reticulospinal tract volume (OR 1.167, P = 0.063), lateral corticospinal tract volume (OR 1.034, P = 0.046), rubrospinal tract volume (OR 1.072, P = 0.011), and ventrolateral reticulospinal tract volume (OR 1.474, P = 0.005) on single variable logistic regression. Single variable linear regression showed decreases in anterior/posterior spinal cord diameter (P = 0.022), ventral reticulospinal tract volumes (P = 0.007), and ventrolateral reticulospinal tract volumes (P = 0.017) to significantly predict worsening mJOA scores. Similarly, decreases in ventral reticulospinal tract volumes significantly predicted increasing Nurick scores (P = 0.039).High-resolution 3T MRI can detect tract-specific volume loss in descending spinal cord tracts in CSM patients. Anterior/posterior spinal cord diameter, ventral reticulospinal tract, ventrolateral reticulospinal tract, lateral corticospinal tract, and rubrospinal tract volume loss are associated with CSM symptoms.2.

    View details for PubMedID 29649085

  • High-resolution magnetization transfer MRI in patients with cervical spondylotic myelopathy. Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia Suleiman, L. I., Weber, K. A., Rosenthal, B. D., Bhatt, S. A., Savage, J. W., Hsu, W. K., Patel, A. A., Parrish, T. B. 2018


    Magnetization transfer (MT) contrast has been established as a marker of myelin integrity, and cervical spondylotic myelopathy is known to cause demyelination. Ten patients with clinical and magnetic resonance imaging (MRI) manifestations of cervical spondylotic myelopathy (CSM) were compared to the MRIs of seven historic healthy controls, using the magnetization transfer ratio (MTR) and Nurick scores as the primary metrics. Transverse slices through the intervertebral discs of the cervical spine were acquired using a gradient echo sequence (MEDIC) with and without an MT saturation pulse on a 3 Tesla Siemens Prisma scanner (TR = 300 ms, TEeff = 17 ms, flip angle = 30°, in-plane resolution = 0.47 × 0.47 mm2). The CSM patients tended to have a lower mean MTR (30.4 ± 6.5) than the controls (34.8 ± 3.8), but the difference was not significant (independent samples t-test, p = 0.110, Cohen's d = 0.80). The mean MTR across all intervertebral disc levels was not significantly correlated to the Nurick score (Spearman's ρ = -0.489, p = 0.151). The intervertebral level with the lowest MTR in each cohort was not significantly different between groups (equal variances not assumed, t = 1.965, dof = 14.8, p = 0.068, Cohen's d = 0.88), but the CSM patients tended to have a lower MTR. The mean MTR at this level was negatively correlated to the Nurick score among CSM patients (Spearman's ρ = -0.725, p = 0.018). CSM patients tended to have decreased MTR indicating myelin degradation compared to our healthy subjects, and MTR was negatively correlated with the severity of CSM.

    View details for PubMedID 29530383

  • Ambulatory function in motor incomplete spinal cord injury: a magnetic resonance imaging study of spinal cord edema and lower extremity muscle morphometry. Spinal cord Smith, A. C., Weber, K. A., Parrish, T. B., Hornby, T. G., Tysseling, V. M., McPherson, J. G., Wasielewski, M., Elliott, J. M. 2017


    This research utilized a cross-sectional design.Spinal cord edema length has been measured with T2-weighted sagittal MRI to predict motor recovery following spinal cord injury. The purpose of our study was to establish the correlational value of axial spinal cord edema using T2-weighted MRI. We hypothesized a direct relationship between the size of damage on axial MRI and walking ability, motor function and distal muscle changes seen in motor incomplete spinal cord injury (iSCI).University-based laboratory in Chicago, IL, USA.Fourteen participants with iSCI took part in the study. Spinal cord axial damage ratios were assessed using axial T2-weighted MRI. Walking ability was investigated using the 6-min walk test and daily stride counts. Maximum plantarflexion torque was quantified using isometric dynomometry. Muscle fat infiltration (MFI) and relative muscle cross-sectional area (rmCSA) were quantified using fat/water separation magnetic resonance imaging.Damage ratios were negatively correlated with distance walked in 6 min, average daily strides and maximum plantarflexion torque, and a negative linear trend was found between damage ratios and lower leg rmCSA. While damage ratios were not significantly correlated with MFI, we found significantly higher MFI in the wheelchair user participant group compared to community walkers.Damage ratios may be useful in prognosis of motor recovery in spinal cord injury. The results warrant a large multi-site research study to investigate the value of high-resolution axial T2-weighted imaging to predict walking recovery following motor incomplete spinal cord injury.Spinal Cord advance online publication, 28 February 2017; doi:10.1038/sc.2017.18.

    View details for DOI 10.1038/sc.2017.18

    View details for PubMedID 28244504

  • Thermal Stimulation Alters Cervical Spinal Cord Functional Connectivity in Humans. Neuroscience Weber, K. A., Sentis, A. I., Bernadel-Huey, O. N., Chen, Y. n., Wang, X. n., Parrish, T. B., Mackey, S. n. 2017


    The spinal cord has an active role in the modulation and transmission of the neural signals traveling between the body and the brain. Recent advancements in functional magnetic resonance imaging (fMRI) have made the in vivo examination of spinal cord function in humans now possible. This technology has been recently extended to the investigation of resting state functional networks in the spinal cord, leading to the identification of distinct patterns of spinal cord functional connectivity. In this study, we expand on the previous work and further investigate resting state cervical spinal cord functional connectivity in healthy participants (n = 15) using high resolution imaging coupled with both seed-based functional connectivity analyses and graph theory-based metrics. Within spinal cord segment functional connectivity was present between the left and right ventral horns (bilateral motor network), left and right dorsal horns (bilateral sensory network), and the ipsilateral ventral and dorsal horns (unilateral sensory-motor network). Functional connectivity between the spinal cord segments was less apparent with the connectivity centered at the region of interest and spanning < 20 mm along the superior-inferior axis. In a subset of participants (n = 10), the cervical spinal cord functional network was demonstrated to be state-dependent as thermal stimulation of the right ventrolateral forearm resulted in significant disruption of the bilateral sensory network, increased network global efficiency, and decreased network modularity.

    View details for PubMedID 29101078

  • Quantitative Magnetization Transfer MRI Measurements of the Anterior Spinal cord Region are Associated with Clinical Outcomes in Cervical Spondylotic Myelopathy. Spine Cloney, M. B., Smith, Z. A., Weber, K. A., Parrish, T. B. 2017


    case-control.To understand the role of magnetization transfer ratio in identifying patients with clinically significant myelopathy and disability.Magnetization transfer ratio (MTR) is a quantitative measure that correlates with myelin loss and neural tissue destruction in a variety of neurological diseases. However, the usefulness of MTR in patients with cervical spondylotic myelopathy (CSM) has not been examined.We prospectively enrolled seven CSM patients and seven age-matched controls to undergo MRI imaging of the cervical spine. Nurick, Neck Disability Index (NDI), and modified Japanese Orthopedic Association (mJOA) scores were collected for all patients. Clinical hyperreflexia was tested at the MCP joint, using a 6-axis load cell. Reflex was simulated by quickly moving the joint from maximum flexion to maximum extension (300 °/sec). Anterior, lateral, and posterior cord MTR measurements were compared to clinical outcomes.Compared to controls, CSM patients had lower anterior cord MTR (38.29 v. 29.97, Δ = -8.314, p = 0.0022), and equivalent posterior cord (p = 0.2896) and lateral cord (p = 0.3062) MTR. Higher Nurick scores were associated with lower anterior cord MTR (p = 0.0205), but not lateral cord (p = 0.5446) or posterior cord MTR (p = 0.1222). Lower mJOA was associated with lower anterior cord MTR (p = 0.0090), but not lateral cord (p = 0.4864) or posterior cord MTR (p = 0.4819). There was no association between NDI and MTR of the anterior (p = 0.4351), lateral (p = 0.7557), or posterior cord (p = 0.9171). There was a linear relationship between hyperreflexia and anterior cord MTR (slope = -117.3, R = 0.6598, p = 0.0379), but not lateral cord (p = 0.1906, R = 0.4511) or posterior cord (p = 0.2577, R = 0.3957) MTR.Anterior cord MTR correlates with clinical outcomes as measured by mJOA index, Nurick score, and quantitative hyperreflexia, and could play a role in the preoperative assessment of CSM.2.

    View details for PubMedID 29068880

  • Lateral corticospinal tract damage correlates with motor output in incomplete spinal cord injury. Archives of physical medicine and rehabilitation Smith, A. C., Weber, K. A., O'Dell, D. R., Parrish, T. B., Wasielewski, M. n., Elliott, J. M. 2017


    To investigate the relationship between spinal cord damage and specific motor function in participants with incomplete spinal cord injury (iSCI).single-blinded cross-sectional study design SETTING: University setting research laboratory.Fourteen individuals with chronic cervical iSCI (1 female and 13 males, average age = 43 ± 12 years old).Not applicable.Axial T2 MRI of spinal cord damage was performed in 14 participants with iSCI. Each participants' damage was processed for total damage quantification, lateral corticospinal tract (LCST) and gracilis fasciculus (GF) analysis. Plantarflexion and knee extension were quantified using an isokinetic dynamometer. Walking ability was assessed using a 6-minute walk test.Total damage was correlated with plantarflexion, knee extension, and distance walked in 6 minutes. Right LCST damage was correlated with right plantarflexion and right knee extension, while left LCST damage was correlated with left sided measures. Right and left GF damage were not correlated with the motor output measures.MRI measures of spinal cord damage were correlated to motor function, and this measure appears to have spatial specificity to descending tracts, which may offer prognostic value following spinal cord injury.

    View details for PubMedID 29107041

  • Advancements in Imaging Technology: Do They (or Will They) Equate to Advancements in Our Knowledge of Recovery in Whiplash? JOURNAL OF ORTHOPAEDIC & SPORTS PHYSICAL THERAPY Elliott, J. M., Dayanidhi, S., Hazle, C., Hoggarth, M. A., Mcpherson, J., Sparks, C. L., Weber, K. A. 2016; 46 (10): 862-873


    Synopsis It is generally accepted that up to 50% of those with a whiplash injury following a motor vehicle collision will fail to fully recover. Twenty-five percent of these patients will demonstrate a markedly complex clinical picture that includes severe pain-related disability, sensory and motor disturbances, and psychological distress. A number of psychosocial factors have shown prognostic value for recovery following whiplash from a motor vehicle collision. To date, no management approach (eg, physical therapies, education, psychological interventions, or interdisciplinary strategies) for acute whiplash has positively influenced recovery rates. For many of the probable pathoanatomical lesions (eg, fracture, ligamentous rupture, disc injury), there remains a lack of available clinical tests for identifying their presence. Fractures, particularly at the craniovertebral and cervicothoracic junctions, may be radiographically occult. While high-resolution computed tomography scans can detect fractures, there remains a lack of prevalence data for fractures in this population. Conventional magnetic resonance imaging has not consistently revealed lesions in patients with acute or chronic whiplash, a "failure" that may be due to limitations in the resolution of available devices and the use of standard sequences. The technological evolution of imaging techniques and sequences eventually might provide greater resolution to reveal currently elusive anatomical lesions (or, perhaps more importantly, temporal changes in physiological responses to assumed lesions) in those patients at risk of poor recovery. Preliminary findings from 2 prospective cohort studies in 2 different countries suggest that this is so, as evidenced by changes to the structure of skeletal muscles in those who do not fully recover. In this clinical commentary, we will briefly introduce the available imaging decision rules and the current knowledge underlying the pathomechanics and pathophysiology of whiplash. We will then acknowledge known prognostic factors underlying functional recovery. Last, we will highlight emerging evidence regarding the pathobiology of muscle degeneration/regeneration, as well as advancements in neuroimaging and musculoskeletal imaging techniques (eg, functional magnetic resonance imaging, magnetization transfer imaging, spectroscopy, diffusion-weighted imaging) that may be used as noninvasive and objective complements to known prognostic factors associated with whiplash recovery, in particular, poor functional recovery. J Orthop Sports Phys Ther 2016;46(10):861-872. doi:10.2519/jospt.2016.6735.

    View details for DOI 10.2519/jospt.2016.6735

    View details for Web of Science ID 000384398400008

    View details for PubMedID 27690836

  • Functional Magnetic Resonance Imaging of the Cervical Spinal Cord During Thermal Stimulation Across Consecutive Runs. NeuroImage Weber, K. A., Chen, Y., Wang, X., Kahnt, T., Parrish, T. B. 2016


    The spinal cord is the first site of nociceptive processing in the central nervous system and has a role in the development and perpetuation of clinical pain states. Advancements in functional magnetic resonance imaging are providing a means to non-invasively measure spinal cord function, and functional magnetic resonance imaging may provide an objective method to study spinal cord nociceptive processing in humans. In this study, we tested the validity and reliability of functional magnetic resonance imaging using a selective field-of-view gradient-echo echo-planar-imaging sequence to detect activity induced blood oxygenation level-dependent signal changes in the cervical spinal cord of healthy volunteers during warm and painful thermal stimulation across consecutive runs. At the group and subject level, the activity was localized more to the dorsal hemicord, the spatial extent and magnitude of the activity was greater for the painful stimulus than the warm stimulus, and the spatial extent and magnitude of the activity exceeded that of a control analysis. Furthermore, the spatial extent of the activity for the painful stimuli increased across the runs likely reflecting sensitization. Overall, the spatial localization of the activity varied considerably across the runs, but despite this variability, a machine-learning algorithm was able to successfully decode the stimuli in the spinal cord based on the distributed pattern of the activity. In conclusion, we were able to successfully detect and characterize cervical spinal cord activity during thermal stimulation at the group and subject level.

    View details for DOI 10.1016/j.neuroimage.2016.09.015

    View details for PubMedID 27616641

  • Measuring Pain for Patients Seeking Physical Therapy: Can Functional Magnetic Resonance Imaging (fMRI) Help? Physical therapy Elliott, J. M., Owen, M. n., Bishop, M. D., Sparks, C. n., Tsao, H. n., Walton, D. M., Weber, K. A., Wideman, T. H. 2016


    In the multidisciplinary fields of pain medicine and rehabilitation, advancing techniques such as functional magnetic resonance imaging (fMRI) are used to enhance our understanding of the pain experience. Given that such measures, in some circles, are expected to help us understand the brain in pain, future research in pain measurement is undeniably rich with possibility. However, pain remains intensely personal and represents a multifaceted experience, unique to each individual; no single measure in isolation, fMRI included, can prove or quantify its magnitude beyond the patient self-report. Physical therapists should be aware of cutting-edge advances in measuring the patient's pain experience, and they should work closely with professionals in other disciplines (eg, magnetic resonance physicists, biomedical engineers, radiologists, psychologists) to guide the exploration and development of multimodal pain measurement and management on a patient-by-patient basis. The primary purpose of this perspective article is to provide a brief overview of fMRI and inform physical therapist clinicians of the pros and cons when utilized as a measure of the patient's perception of pain. A secondary purpose is to describe current known factors that influence the quality of fMRI data and its analyses, as well as the potential for future clinical applications relevant to physical therapist practice. Lastly, the interested reader is introduced and referred to existing guidelines and recommendations for reporting fMRI research.

    View details for DOI 10.2522/ptj.20160089

    View details for PubMedID 27470977

  • White matter microstructure changes induced by motor skill learning utilizing a body machine interface. NeuroImage Wang, X., Casadio, M., Weber, K. A., Mussa-Ivaldi, F. A., Parrish, T. B. 2013; 88C: 32-40


    The purpose of this study is to identify white matter microstructure changes following bilateral upper extremity motor skill training to increase our understanding of learning-induced structural plasticity and enhance clinical strategies in physical rehabilitation. Eleven healthy subjects performed two visuo-spatial motor training tasks over 9 sessions (2-3 sessions per week). Subjects controlled a cursor with bilateral simultaneous movements of the shoulders and upper arms using a body machine interface. Before the start and within 2days of the completion of training, whole brain diffusion tensor MR imaging data were acquired. Motor training increased fractional anisotropy (FA) values in the posterior and anterior limbs of the internal capsule, the corona radiata, and the body of the corpus callosum by 4.19% on average indicating white matter microstructure changes induced by activity-dependent modulation of axon number, axon diameter, or myelin thickness. These changes may underlie the functional reorganization associated with motor skill learning.

    View details for DOI 10.1016/j.neuroimage.2013.10.066

    View details for PubMedID 24220038

    View details for PubMedCentralID PMC4016193

  • Understanding inhibitory mechanisms of lumbar spinal manipulation using H-reflex and F-wave responses: A methodological approach JOURNAL OF NEUROSCIENCE METHODS Dishman, J. D., Weber, K. A., Corbin, R. L., Burke, J. R. 2012; 210 (2): 169-177


    The purpose of this research was to characterize unique neurophysiologic events following a high velocity, low amplitude (HVLA) spinal manipulation (SM) procedure. Descriptive time series analysis techniques of time plots, outlier detection and autocorrelation functions were applied to time series of tibial nerve H-reflexes that were evoked at 10-s intervals from 100 s before the event until 100 s after three distinct events L5-S1 HVLA SM, or a L5-S1 joint pre-loading procedure, or the control condition. Sixty-six subjects were randomly assigned to three procedures, i.e., 22 time series per group. If the detection of outliers and correlograms revealed a pattern of non-randomness that was only time-locked to a single, specific event in the normalized time series, then an experimental effect would be inferred beyond the inherent variability of H-reflex responses. Tibial nerve F-wave responses were included to determine if any new information about central nervous function following a HVLA SM procedure could be ascertained. Time series analyses of H(max)/M(max) ratios, pre-post L5-S1 HVLA SM, substantiated the hypothesis that the specific aspects of the manipulative thrust lead to a greater attenuation of the H(max)/M(max) ratio as compared to the non-specific aspects related to the postural perturbation and joint pre-loading. The attenuation of the H(max)/M(max) ratio following the HVLA SM procedure was reliable and may hold promise as a translational tool to measure the consistency and accuracy of protocol implementation involving SM in clinical trials research. F-wave responses were not sensitive to mechanical perturbations of the lumbar spine.

    View details for DOI 10.1016/j.jneumeth.2012.07.014

    View details for Web of Science ID 000309376900006

    View details for PubMedID 22878176

  • Non-invasive brain stimulation enhances fine motor control of the hemiparetic ankle: implications for rehabilitation EXPERIMENTAL BRAIN RESEARCH Madhavan, S., Weber, K. A., Stinear, J. W. 2011; 209 (1): 9-17


    We set out to answer two questions with this study: 1. Can stroke patients improve voluntary control of their paretic ankle by practising a visuo-motor ankle-tracking task? 2. Are practice effects enhanced with non-invasive brain stimulation? A carefully selected sample of chronic stroke patients able to perform the experimental task attended three data collection sessions. Facilitatory transcranial direct current stimulation (tDCS) was applied in a random order over the lower limb primary motor cortex of the lesioned hemisphere or the non-lesioned hemisphere or sham stimulation was delivered over the lesioned hemisphere. In each session, tDCS was applied as patients practiced tracking a sinusoidal waveform for 15 min using dorsiflexion-plantarflexion movements of their paretic ankle. The difference in tracking error prior to, and after, the 15 min of practice was calculated. A practice effect was revealed following sham stimulation, and this effect was enhanced with tDCS applied over the lesioned hemisphere. The practice effect observed following sham stimulation was eliminated by tDCS applied over the non-lesioned hemisphere. The study provides the first evidence that non-invasive brain stimulation applied to the lesioned motor cortex of moderate- to well-recovered stroke patients enhances voluntary control of the paretic ankle. The results provide a basis for examining whether this enhanced ankle control can be induced in patients with greater impairments and whether enhanced control of a single or multiple lower limb joints improves hemiparetic gait patterns.

    View details for DOI 10.1007/s00221-010-2511-0

    View details for Web of Science ID 000287147500002

    View details for PubMedID 21170708

  • Chiropractic students and research: assessing the research culture at a north american chiropractic college. The Journal of chiropractic education Weber Ii, K. A., He, X. 2010; 24 (1): 35-45


    To continue positive professional growth and boost research endeavors, chiropractic institutions need to develop a research-oriented foundation and produce a larger body of researchers. The purpose of this study was to provide a current analysis of the research culture among students at Palmer College of Chiropractic Florida. This study will gain insight toward the research contributions of the next generation of chiropractors and identify the difficulties toward participation. This will help modify current academic programs to better foster research and ensure a promising, credible future for the chiropractic profession.Participants were students at Palmer College of Chiropractic Florida enrolled in quarters 1 through 12 during the 2008 summer term. To evaluate the research culture, participants were asked to complete a 33-item web-based survey.A total of 303 students completed the survey. Forty-four percent were female, and the mean age was 26 (SD = 4.2). Ninety-nine percent of respondents agreed that research was necessary for positive growth within the chiropractic profession. A majority of students reported having research experience, and 58% planned to participate in research activities prior to graduation. Technical writing was reported as the most challenging aspect of research, and heavy academic workload was reported as the greatest deterrent to participation.This study expresses possibilities for building a strong research culture at the college. Students were aware of the necessity for research and were openly interested in conducting research. Modification of current academic policies will allow for greater student research opportunities and the development of tomorrow's researchers.

    View details for PubMedID 20480013