Kenneth Weber

All Publications

• 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

  Abstract

  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

• 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., Elliott, J. M., Liu, W. C., Sparks, C. L. 2019; 24: 102042

  Abstract

  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

• 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., Eghtesad, K., Upadhyayula, P. A., Wintermark, M., Hastie, T. J., Parrish, T. B., Mackey, S., Elliott, J. M. 2019; 9 (1): 7973

  Abstract

  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

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

  Abstract

  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

• 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

  Abstract

  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

• 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

  Abstract

  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

• 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

  Abstract

  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

  Abstract

  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

  View details for DOI 10.1080/10790268.2018.1527079

  View details for Web of Science ID 000518604700013

• 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., Fundaun, J., Wasielewski, M., Courtney, D. M., Parrish, T. B. 2020; 15 (6): e0234061

  Abstract

  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

• 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., Grimaldi, A., Elliott, J., Hoggarth, M., Weber Ii, K. A., Vicenzino, B. 2020; 13 (1): 20

  Abstract

  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

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

  Abstract

  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 (? =0.608, p=0.036 and AUC =0.66). Preoperative lateral cord MTR was correlated with neck disability index (? =0.699, p=0.011) and pain interference (? =0.732, p=0.007). Preoperative rubrospinal tract MTR was associated mJOA score recovery (? =0.573, p=0.041, AUC= 0.86). Preoperative corticospinal tract and reticulospinal MTR were related to recovery in pain interference scores (? =0.591, p=0.033 and ? =0.583, p=0.035). Eccentricity of the cord was associated with Nurick scores (? = 0.606, p=0.028) and mJOA (? =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

  View details for DOI 10.1016/j.wneu.2019.03.165

  View details for Web of Science ID 000473128300054

• 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

• 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

  Abstract

  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

• 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., Hopkins, B. S., Barry, A. J., Cantrell, D., Ganju, A., Koski, T. R., Parrish, T. B., Dhaher, Y. 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., Weber, K. A., Smith, A., Elliott, J. M. 2019: 1?32

  Abstract

  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

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

  Abstract

  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., Parrish, T. B., Smith, Z. A. 2018

  Abstract

  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

  Abstract

  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 ??=?-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 ??=?-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

  Abstract

  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

• 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

  Abstract

  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, ? = -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., Elliott, J. M. 2017

  Abstract

  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

  Abstract

  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

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

  Abstract

  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

  Abstract

  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

  Abstract

  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

  Abstract

  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

  Abstract

  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