Mindfulness-Based Stress Reduction, Cognitive Behavioral Therapy, and Acupuncture in Chronic Low Back Pain: Protocol for Two Linked Randomized Controlled Trials.
JMIR research protocols
2022; 11 (9): e37823
BACKGROUND: Nonpharmacologic mind-body therapies have demonstrated efficacy in low back pain. However, the mechanisms underlying these therapies remain to be fully elucidated.OBJECTIVE: In response to these knowledge gaps, the Stanford Center for Low Back Pain-a collaborative, National Institutes of Health P01-funded, multidisciplinary research center-was established to investigate the common and distinct biobehavioral mechanisms of three mind-body therapies for chronic low back pain: cognitive behavioral therapy (CBT) that is used to treat pain, mindfulness-based stress reduction (MBSR), and electroacupuncture. Here, we describe the design and implementation of the center structure and the associated randomized controlled trials for characterizing the mechanisms of chronic low back pain treatments.METHODS: The multidisciplinary center is running two randomized controlled trials that share common resources for recruitment, enrollment, study execution, and data acquisition. We expect to recruit over 300 chronic low back pain participants across two projects and across different treatment arms within each project. The first project will examine pain-CBT compared with MBSR and a wait-list control group. The second project will examine real versus sham electroacupuncture. We will use behavioral, psychophysical, physical measure, and neuroimaging techniques to characterize the central pain modulatory and emotion regulatory systems in chronic low back pain at baseline and longitudinally. We will characterize how these interventions impact these systems, characterize the longitudinal treatment effects, and identify predictors of treatment efficacy.RESULTS: Participant recruitment began on March 17, 2015, and will end in March 2023. Recruitment was halted in March 2020 due to COVID-19 and resumed in December 2021.CONCLUSIONS: This center uses a comprehensive approach to study chronic low back pain. Findings are expected to significantly advance our understanding in (1) the baseline and longitudinal mechanisms of chronic low back pain, (2) the common and distinctive mechanisms of three mind-body therapies, and (3) predictors of treatment response, thereby informing future delivery of nonpharmacologic chronic low back pain treatments.TRIAL REGISTRATION: ClinicalTrials.gov NCT02503475; https://clinicaltrials.gov/ct2/show/NCT02503475.INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/37823.
View details for DOI 10.2196/37823
View details for PubMedID 36166279
- Response to Scholkmann Commentary: "Effect of Wearing a Face Mask on fMRI BOLD Contrast". NeuroImage 2021: 118773
Prediction of Cognitive Function with Multimodal Brain MRI
WILEY. 2021: S42
View details for Web of Science ID 000704705300063
- Author Correction: Open-access quantitative MRI data of the spinal cord and reproducibility across participants, sites and manufacturers. Scientific data 2021; 8 (1): 242
THE TEMPORAL RELATIONSHIP BETWEEN NEGATIVE AFFECT AND SLEEP BRUXISM IN PATIENTS WITH CHRONIC BACK PAIN
OXFORD UNIV PRESS INC. 2021: S478
View details for Web of Science ID 000648922701161
Effect of Wearing a Face Mask on fMRI BOLD Contrast.
International spread of the coronavirus SARS-CoV-2 has prompted many MRI scanning facilities to require scan subjects to wear a facial covering ("mask") during scanning as a precaution against transmission of the virus. Because wearing a mask mixes expired air with the subject's inspired air stream, the concentration of inspired carbon dioxide [CO2] is elevated, resulting in mild hypercapnia. Changes in the inspired gas mixture have been demonstrated to alter R2*-weighted Blood Oxygen Dependent (BOLD) contrast. In this study, we investigate a potential for face masking to alter BOLD contrast during a sensory-motor task designed to activate visual, auditory, and sensorimotor cortices in 8 subjects. We utilize a nasal cannula to supply air to the subject wearing a surgical mask in on-off blocks of 90s to displace expired CO2, while the subject performs the sensory-motor task. While only a small fraction (2.5%) of the sensory-motor task activation is related to nasal air modulation, a 30.0% change in gray matter BOLD signal baseline is found due to air modulation. Repeating the scan with mask removed produces a small subject-specific bias in BOLD baseline signal from nasal air supply, which may be due to cognitive influence of airflow or cannula-induced hypoxia. Measurements with capnography demonstrate wearing a mask induces an average increase in ETCO2 of 7.4%. Altogether, these results demonstrate that wearing a face mask during gradient-echo fMRI can alter BOLD baseline signal but minimally affects task activation.
View details for DOI 10.1016/j.neuroimage.2021.117752
View details for PubMedID 33460795
Association between temporal summation and conditioned pain modulation in chronic low back pain: baseline results from 2 clinical trials.
2021; 6 (4): e975
Temporal summation (TS) and conditioned pain modulation (CPM) represent different aspects of central pain processing. Their relationship and differential performance within distinct body locations are not well understood.To examine the association between TS and CPM in chronic low back pain and the influence of testing location on this relationship.We analyzed baseline data from 2 clinical trials on participants with chronic low back pain (n = 264; 47.3% female; mean age = 41 years, SD = 12; mean pain = 5.3/10, SD = 1.4). Measures used included questionnaires assessing pain and negative affect, phasic thermal TS at the hand (thenar) and the lower back (lumbar), followed by CPM that included a thermal testing stimulus (Heat-6, the temperature where pain rating is 6/10) and a cold-pressor conditioning stimulus. Nonparametric, proportional odds logistic regression was used to model thenar, and separately, lumbar TS, using CPM, Heat-6, negative affect, and demographics.Our models revealed a small association (βs = 0.17, P = 0.01) between reduced CPM and heightened TS at both testing sites, regardless of demographics or negative affect.Results suggest a modest association between TS and CPM, irrespective of anatomical testing location, demographics, and negative affect. These findings will help improve the methodology and interpretation of TS and CPM measurement in clinical pain populations.
View details for DOI 10.1097/PR9.0000000000000975
View details for PubMedID 34901679
View details for PubMedCentralID PMC8660006
Quantification of cerebral blood volume changes caused by visual stimulation at 3 T using DANTE-prepared dual-echo EPI.
Magnetic resonance in medicine
We investigate the influence of moving blood-attenuation effects when using "delay alternating with nutation for tailored excitation" (DANTE) pulses in conjunction with blood oxygen level dependent (BOLD) of functional MRI (fMRI) at 3 T. Based on the effects of including DANTE pulses, we propose quantification of cerebral blood volume (CBV) changes following functional stimulation.Eighteen volunteers in total underwent fMRI scans at 3 T. Seven volunteers were scanned to investigate the effects of DANTE pulses on the fMRI signal. CBV changes in response to visual stimulation were quantified in 11 volunteers using a DANTE-prepared dual-echo EPI sequence.The inflow effects from flowing blood in arteries and draining vein effects from flowing blood in large veins can be suppressed by use of a DANTE preparation module. Using DANTE-prepared dual-echo EPI, we quantitatively measured intravascular-weighted microvascular CBV changes of 25.4%, 29.8%, and 32.6% evoked by 1, 5, and 10 Hz visual stimulation, respectively. The extravascular fraction (∆S/S)extra at TE = 30 ms in total BOLD signal was determined to be 64.8 ± 3.4%, which is in line with previous extravascular component estimation at 3 T. Results show that the microvascular CBV changes are linearly dependent on total BOLD changes at TE = 30 ms with a slope of 0.113, and this relation is independent of stimulation frequency and subject.The DANTE preparation pulses can be incorporated into a standard EPI fMRI sequence for the purpose of minimizing inflow effects and reducing draining veins effects in large vessels. Additionally, the DANTE-prepared dual-echo EPI sequence is a promising fast imaging tool for quantification of intravascular-weighted CBV change in the microvascular space at 3 T.
View details for DOI 10.1002/mrm.29099
View details for PubMedID 34817081
Generic acquisition protocol for quantitative MRI of the spinal cord.
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 https://github.com/spine-generic/protocols . 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.
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 https://spine-generic.rtfd.io/ . 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
- Author Correction: Open-access quantitative MRI data of the spinal cord and reproducibility across participants, sites and manufacturers. Scientific data 2021; 8 (1): 251
Brain Strength: Multi-Modal Brain MRI Predicts Grip Strength
WILEY. 2020: S223–S224
View details for Web of Science ID 000572509100411
Assessing the Spatial Distribution of Cervical Spinal Cord Activity during Tactile Stimulation of the Upper Extremity in Humans with Functional Magnetic Resonance Imaging.
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
Resting State Functional Connectivity Machine Learning Classification of Chronic Back Pain
WILEY. 2019: S266
View details for Web of Science ID 000488891800418
- Dynamic per slice shimming for simultaneous brain and spinal cord fMRI MAGNETIC RESONANCE IN MEDICINE 2019; 81 (2): 825–38
Central mechanisms of real and sham electroacupuncture in the treatment of chronic low back pain: study protocol for a randomized, placebo-controlled clinical trial.
2018; 19 (1): 685
BACKGROUND: Chronic low back pain (CLBP) is the most common chronic pain condition and is often resistant to conventional treatments. Acupuncture is a popular alternative for treating CLBP but its mechanisms of action remain poorly understood. Evidence suggests that pain regulatory mechanisms (particularly the ascending and secondarily the descending pain modulatory pathways) and psychological mechanisms (e.g., expectations, pain catastrophizing and self-efficacy) may be involved in the pathogenesis of CLBP and its response to treatments. We will examine these mechanisms in the treatment of CLBP by electroacupuncture (EA).METHODS: We present the aims and methods of a placebo-controlled, participant-blinded and assessor-blinded mechanistic study. Adult patients with CLBP will be randomized to receiving 16 sessions of real (active) or sham (placebo) EA over the course of 8weeks. The primary pain regulatory measure for which the study was powered is temporal summation (TS), which approximates ascending pain facilitation. Conditioned pain modulation (CPM), representing a descending pain modulatory pathway, will be our secondary pain regulatory measure. The primary psychological measure is expectations of benefit, and the secondary psychological measures are pain catastrophizing and self-efficacy in managing pain. Main clinical outcomes are back pain bothersomeness on a 0-100 visual analog scale (primary), Roland Morris Disability Questionnaire (secondary), and relevant items from the National Institutes of Health (NIH) Patient-Reported Outcome Measures Information System (secondary). We hypothesize that compared to sham, real EA will lead to greater reduction in TS after 8 treatment sessions (4weeks); and that reduction in TS (and secondarily, increase in CPM) after 8 treatment sessions will mediate reduction in back pain bothersomeness from baseline to week 10 (clinical response) to EA. We also hypothesize that the three psychological factors are moderators of clinical response. With 100 treatment completers, the study is designed to have 80% power to detect a medium-sized between-group effect (d=0.5) on temporal summation.DISCUSSION: To the best of our knowledge, this is the first appropriately powered, placebo-controlled clinical trial evaluating mechanisms of EA in the treatment of CLBP.TRIAL REGISTRATION: ClinicalTrials.gov, NCT02503475 . Registered on 15 July 15 2015. Retrospectively registered.
View details for PubMedID 30541586
- Central mechanisms of real and sham electroacupuncture in the treatment of chronic low back pain: study protocol for a randomized, placebo-controlled clinical trial TRIALS 2018; 19
Technical note: can resting state functional MRI assist in routine clinical diagnosis?
BJR case reports
2018; 4 (4): 20180030
Despite some differences in clinical presentation, it is often difficult to differentiate between dementia with Lewy bodies (DLB), clinical Alzheimer's dementia (AD) and Parkinson's disease dementia. However, differentiation can be crucial, especially as patients with DLB characteristically have a hypersensitivity to most antiemetic and neuroleptic drugs as they affect the cholinergic and dopaminergic system, potentially leading to life-threatening catatonia, loss of cognitive function and muscle rigidity. The aim of this study is to evaluate if resting state (RS) functional MRI (fMRI) can be used in routine practice on a 1.5 T scanner to differentiate between AD and DLB on an individual basis. We age- and gender-matched a known DLB patient with an AD patient and a human control (HC). Individual independent component analysis was carried out. Region of interest seeds were chosen from the midcingulate and insula regions. Functional connectivity from insula to midcingulate and within the midcingulate network (part of the Salience network) was lower in DLB than AD or HC. RS-fMRI on a 1.5 T scanner, in a routine clinical setting, detected abnormal functional connectivity patterns and allowed differentiation of DLB and AD in a routine clinical setting. This is the first evaluation of RS-fMRI in a routine clinical setting. It shows that incorporating RS-fMRI into the clinical scanning protocol can assist in early diagnosis and likely assist in monitoring the natural history of the disease or disease modifying treatments.
View details for DOI 10.1259/bjrcr.20180030
View details for PubMedID 30931142
View details for PubMedCentralID PMC6438408
Dynamic per slice Shimming for Simultaneous Brain and Spinal Cord fMRI.
Magnetic resonance in medicine
PURPOSE: Simultaneous brain and spinal cord functional MRI is emerging as a new tool to study the central nervous system but is challenging. Poor B0 homogeneity and small size of the spinal cord are principal obstacles to this nascent technology. Here we extend a dynamic shimming approach, first posed by Finsterbusch, by shimming per slice for both the brain and spinal cord.METHODS: We shim dynamically by a simple and fast optimization of linear field gradients and frequency offset separately for each slice in order to minimize off-resonance for both the brain and spinal cord. Simultaneous acquisition of brain and spinal cord fMRI is achieved with high spatial resolution in the spinal cord by means of an echo-planar RF pulse for reduced FOV. Brain slice acquisition is full FOV.RESULTS: T2*-weighted images of brain and spinal cord are acquired with high clarity and minimal observable image artifacts. Fist-clenching fMRI experiments reveal task-consistent activation in motor cortices, cerebellum, and C6-T1 spinal segments.CONCLUSIONS: High quality functional results are obtained for a sensory-motor task. Consistent activation in both the brain and spinal cord is observed at individual levels, not only at group level. Because reduced FOV excitation is applicable to any spinal cord section, future continuation of these methods holds great potential.
View details for PubMedID 30284730
- Technical note: can resting state functional MRI assist in routine clinical diagnosis? BJR CASE REPORTS 2018; 4 (4)
Interleaved Spiral-In/Out With Application to Functional MRI (fMRI)
MAGNETIC RESONANCE IN MEDICINE
2009; 62 (3): 829-834
The conventional spiral-in/out trajectory samples k-space sufficiently in the spiral-in path and sufficiently in the spiral-out path to enable creation of separate images. We propose an "interleaved spiral-in/out" trajectory comprising a spiral-in path that gathers one half of the k-space data, and a complimentary spiral-out path that gathers the other half. The readout duration is thereby reduced by approximately half, offering two distinct advantages: reduction of signal dropout due to susceptibility-induced field gradients (at the expense of signal-to-noise ratio [SNR]), and the ability to achieve higher spatial resolution when the readout duration is identical to the conventional method. Two reconstruction methods are described; both involve temporal filtering to remove aliasing artifacts. Empirically, interleaved spiral-in/out images are free from false activation resulting from signal pileup around the air/tissue interface, which is common in the conventional spiral-out method. Comparisons with conventional methods using a hyperoxia stimulus reveal greater frontal-orbital activation volumes but a slight reduction of overall activation in other brain regions.
View details for DOI 10.1002/mrm.22056
View details for Web of Science ID 000269404900033
View details for PubMedID 19449373
View details for PubMedCentralID PMC2763441
Sliding-Window Sensitivity Encoding (SENSE) Calibration for Reducing Noise in Functional MRI (fMRI)
MAGNETIC RESONANCE IN MEDICINE
2008; 60 (5): 1090-1103
Functional magnetic resonance imaging (fMRI) at high magnetic field with parallel imaging (PI) has become increasingly popular for high-resolution imaging. We present a method of self-calibrated PI-fMRI in which sensitivity profiles are calculated using a sliding window of fully sampled multishot imaging data. We show that by updating these sensitivity profiles in a sliding fashion, thermal noise is reduced in the reconstructed image time series. This is accomplished by retaining thermal noise in the sensitivity profiles; no spatial smoothing is performed. These noisy profiles actually provide a closer match to those required for thermal noise-free reconstruction than conventional sensitivity map generation. Our proposed technique is especially applicable for acquiring high-spatial-resolution images, where thermal noise exceeds physiological noise. With conventional sensitivity calculation, PI-fMRI sensitivity is preserved only when using a voxel size large enough such that physiological noise predominates. With small voxel size, our technique reveals activation from visual stimulation where conventional sensitivity calculation techniques falter. Our technique enhances fMRI detection, especially when higher spatial resolution is desired.
View details for DOI 10.1002/mrm.21701
View details for PubMedID 18956461
Spiral-in/out BOLD fMRI for increased SNR and reduced susceptibility artifacts
MAGNETIC RESONANCE IN MEDICINE
2001; 46 (3): 515-522
BOLD fMRI is hampered by dropout of signal in the orbitofrontal and parietal brain regions due to magnetic field gradients near air-tissue interfaces. This work reports the use of spiral-in trajectories that begin at the edge of k-space and end at the origin, and spiral in/out trajectories in which a spiral-in readout is followed by a conventional spiral-out trajectory. The spiral-in trajectory reduces the dropout and increases the BOLD contrast. The spiral-in and spiral-out images can be combined in several ways to simultaneously achieve increased signal-to-noise ratio (SNR) and reduced dropout artifacts. Activation experiments employing an olfaction task demonstrate significantly increased activation volumes due to reduced dropout, and overall increased SNR in all regions.
View details for Web of Science ID 000170740300016
View details for PubMedID 11550244