Ignite Creation Date:
2024-10-26 @ 3:41 PM
Last Modification Date:
2024-10-26 @ 3:41 PM
Study NCT ID:
NCT06610175
Status:
NOT_YET_RECRUITING
Last Update Posted:
None
First Post:
2024-05-22
Brief Title:
Quantitative Imaging of Cervical Spinal Structures - the DISC Pilot Study -
Sponsor:
None
Organization:
None
Study Overview
Official Title:
Quantitative Imaging of Cervical Spinal Structures in Healthy Participants and Patients with Cervical Degenerative Disc Disease - the DISC Pilot Study -
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
DISC
Brief Summary:
The aim of this study is to explore a multi-parametric quantitative MRI approach to measure cervical intervertebral discs the spinal cord and its nerve roots in healthy participants and patients with cervical degenerative disc disease CDDD
CDDD is the consequence of degeneration of intervertebral discs and joints leading to symptoms of cervical radiculopathy myelopathy or a combination of both The incidence of symptomatic CDDD is rising with the aging population and consequently a significant increase in surgeries for symptomatic CDDD is predicted in the upcoming years However the decision for- and optimal timing of surgery remain challenging
Currently the decision for surgery in patients with symptomatic CDDD is related to symptoms as well as position and size of disc herniation on conventional Magnetic Resonance Imaging MRI However conventional MRI only enables qualitative morphological evaluation leaving space for subjective individual interpretation Also disc herniations on conventional MRI are frequently found in asymptomatic individuals while in symptomatic individuals type and extent of disc herniation does not correlate to severity of symptoms Altogether the current standard using conventional MRI cannot optimally predict response to surgery for patients with symptomatic CDDD
The primary aim of this project is to investigate whether a combination of different quantitative imaging sequences can provide more detailed information on disc herniation related compression and potentially aid in determining more objective cut-offs to stage disc herniation in patients with symptomatic CDDD as well as to analyze whether differences exist in quantitative imaging parameters of discs in healthy participants versus patients with symptomatic CDDD These novel techniques are promising as they are noninvasive and could potentially aid in determining objective cut-offs to stage disc herniation Since no single measurement has been proven to be the golden standard in previous studies it is likely that a combination of measurements is needed for clinical application
CDDD is the consequence of degeneration of intervertebral discs and joints leading to symptoms of cervical radiculopathy myelopathy or a combination of both The incidence of symptomatic CDDD is rising with the aging population and consequently a significant increase in surgeries for symptomatic CDDD is predicted in the upcoming years However the decision for- and optimal timing of surgery remain challenging
Currently the decision for surgery in patients with symptomatic CDDD is related to symptoms as well as position and size of disc herniation on conventional Magnetic Resonance Imaging MRI However conventional MRI only enables qualitative morphological evaluation leaving space for subjective individual interpretation Also disc herniations on conventional MRI are frequently found in asymptomatic individuals while in symptomatic individuals type and extent of disc herniation does not correlate to severity of symptoms Altogether the current standard using conventional MRI cannot optimally predict response to surgery for patients with symptomatic CDDD
The primary aim of this project is to investigate whether a combination of different quantitative imaging sequences can provide more detailed information on disc herniation related compression and potentially aid in determining more objective cut-offs to stage disc herniation in patients with symptomatic CDDD as well as to analyze whether differences exist in quantitative imaging parameters of discs in healthy participants versus patients with symptomatic CDDD These novel techniques are promising as they are noninvasive and could potentially aid in determining objective cut-offs to stage disc herniation Since no single measurement has been proven to be the golden standard in previous studies it is likely that a combination of measurements is needed for clinical application
Detailed Description:
RATIONALE
Cervical degenerative disc disease CDDD is the consequence of degeneration of intervertebral discs and joints and can result in compression of the cervical nerve root leading to clinical symptoms of radiculopathy compression of the spinal cord with symptoms of myelopathy or a combination of bothThe incidence of CDDD is rising with the aging population and consequently a significant increase insurgeries for symptomatic CDDD is predicted in the upcoming years As such the decision for- and optimal timing of surgery remain challenging
Currently the decision for surgery in patients with symptomatic CDDD is related to symptoms as well as position and size of disc herniation on conventional Magnetic Resonance Imaging MRI However conventional MRI only enables qualitative morphological evaluation leaving space for subjective individual interpretation Also disc herniations on conventional MRI are frequently found in asymptomatic individuals while in symptomatic individuals type and extent of disc herniation does not correlate to severity of symptoms Altogether the current standard using conventional MRI cannot optimally predict response to surgery for patients with symptomatic CDDD
Quantitative imaging is rapidly being recognized as a supplement to conventional MRI and refers to the direct measurement of physical properties of tissue These novel techniques are promising as they are noninvasive and could potentially aid in determining objective cut-offs to stage disc herniation Diffusion tensor imaging DTI is one of the most studied quantitative techniques and allows for evaluation of microstructural changes The DTI fractional anisotropy FA metric was demonstrated as valid biomarker for recovery after surgery in cervical myelopathy as well as surgical selection in lumbar radiculopathy Moreover recent introduction of zoomed-DTI z-DTI could lead to greater imaging accuracy while proven feasible in the cervical spine
Furthermore the cervical spinal cord and its nerve roots are highly vascularized and their perfusion could be compromised by disc-herniation related compression Using the endogenous perfusion technique arterial spin labeling ASL as well as contrast-based perfusion techniques such as susceptibility contrast DSC and dynamic contrast enhanced DCE degree of ischemia hypoxia as well as signal enhancement can be estimated ASL has been studied twice for spinal cord perfusion mapping and DSC was demonstrated feasible in the spine of healthy participants as well as patients with cervical myelopathy Additionally increased signal enhancement was observed for DCE in degenerative discs of the lumbar spine To our best knowledge no studies have been conducted to assess perfusion of the cervical nerve roots which are compromised in cervical radiculopathy due to CDDD
Besides microstructure and perfusion viscoelastic properties of cervical spinal structures may change in relation to disc herniation-related compression Therefore it would be interesting to study mechanical properties such as stiffness and viscosity which can be measured with Tomo-MRElastography TMRE To our best knowledge no previous study has assessed cervical intervertebral discs and spinal structures using TMRE making this a promising first study
Finally imaging is a relatively time-consuming matter and including additional sequences will only increase its lengthiness Therefore several methods are being developed to perform imaging in a more efficient manner One novel method is Synthetic MRI SyMRI Advantages of SyMRI are a reduced acquisition time possibility of performing automatic tissue segmentation and volume estimation and acquisition of quantitative parameters SyMRI has been studied once in the spine and significant differences in quantitative intervertebral disc values were found in relation to hydration-status of the disc
Since no single measurement has been proven to be the golden standard in previous studies it is likely that a combination of measurements is needed for clinical application Therefore the aim of this pilot study is to explore a multi-parametric quantitative MRI approach including z-DTI ASL DSC DCE TMRE and SyMRI to measure cervical intervertebral discs the spinal cord and its nerve roots
OBJECTIVE
This study will consist of three parts The primary objective of part 1 is to evaluate feasibility of the quantitative MRI sequences eg z-DTI ASL DSC DCE TMRE and SyMRI for assessment of cervical spinal structures eg intervertebral discs spinal cord and nerve roots in healthy participants and patients with symptomatic CDDD The primary objective of part 2 is to determine a correlation between the quantitative MRI sequences of cervical spinal structures to clinical outcome in patients with symptomatic CDDD Finally the primary aim of part 3 is to establish a correlation between quantitative MRI sequences of cervical spinal structures and surgical treatment within 6 months of follow-up
STUDY DESIGN
A prospective pilot study
STUDY POPULATION
The study population consists of healthy participants and patients with symptomatic CDDD with radiculopathy myelopathy or radiculomyelopathy Age-matched healthy participants will be included Participants have no previous history of cervical disc herniation or cervical surgery a sufficient understanding of the Dutch language and no contraindications for an MRI scan
INTERVENTION
All participants will be subjected to several MRI sequences using a state of the art 3T Siemens MRI Scanner available in the UMCG First all participants healthy participants and patients with symptomatic CDDD undergo baseline neurologic examination Additionally participants fill out the following questionnaires Neck Disability Index NDI Visual Analogue Scale VAS for arm and neck pain modified Japanese Orthopedic Association mJOA Nurick grade EuroQol 5-Dimension 5-Level EQ-5D-5L Work Ability Single Item WAI-SI and Central Sensitisation Inventory CSI All participants undergo MRI scanning localizer T2-weighted anatomical conventional MRI z-DTI ASL DSC DCE TMRE and SyMR The total scanning time will be approximately 40 minutes For assessment of reproducibility 10 healthy participants and 10 patients will be scanned 2 times on different daystimes The patients with symptomatic CDDD will have another study visit after 6 months of follow-up to assess their treatment status having had surgery yesno in case of yes also the surgery characteristics to fill out the abovementioned questionnaires and have an MRI with additional sequences
MAIN STUDY PARAMETERSENDPOINTS
Primary endpoints are the technical feasibility and repeatability for the quantitative MRI sequences ie z_DTI ASL DSC DCE TMRE and SyMRI of cervical spinal structures ie intervertebral discs spinal cord and nerve roots in healthy participants and patients with symptomatic CDDD Also a correlation of quantitative MRI sequences of cervical spinal structures to clinical impairment in patients with symptomatic CDDD will be determined Clinical impairment will be measured with the Neck Disability Index NDI for cervical radiculopathy modified Japanese Orthopaedic Association Score mJOA for cervical myelopathy and NDI as well as mJOA for radiculomyelopathy
NATURE AND EXTENT OF THE BURDER AND RISKS ASSOCIATED WITH PARTICIPATION BENEFIT AND GROUP RELATEDNESS
All participants healthy and patients will need a conventional MRI scan with quantitative MRI sequences which will take approximately 40 minutes Most MRI sequences used in this study are noninvasive and do not involve any ionizing radiation However DSC and DCE require administration of a bolus contrast The contrast agent that will be used is Dotarem Without any contra-indications for an MRI scan or contrast agent health is not at risk There is an overall negligible risk for participants as based on the Risk Classification Checklist of the NFU Therefore the investigators can conclude that this study is a low-risk study
Cervical degenerative disc disease CDDD is the consequence of degeneration of intervertebral discs and joints and can result in compression of the cervical nerve root leading to clinical symptoms of radiculopathy compression of the spinal cord with symptoms of myelopathy or a combination of bothThe incidence of CDDD is rising with the aging population and consequently a significant increase insurgeries for symptomatic CDDD is predicted in the upcoming years As such the decision for- and optimal timing of surgery remain challenging
Currently the decision for surgery in patients with symptomatic CDDD is related to symptoms as well as position and size of disc herniation on conventional Magnetic Resonance Imaging MRI However conventional MRI only enables qualitative morphological evaluation leaving space for subjective individual interpretation Also disc herniations on conventional MRI are frequently found in asymptomatic individuals while in symptomatic individuals type and extent of disc herniation does not correlate to severity of symptoms Altogether the current standard using conventional MRI cannot optimally predict response to surgery for patients with symptomatic CDDD
Quantitative imaging is rapidly being recognized as a supplement to conventional MRI and refers to the direct measurement of physical properties of tissue These novel techniques are promising as they are noninvasive and could potentially aid in determining objective cut-offs to stage disc herniation Diffusion tensor imaging DTI is one of the most studied quantitative techniques and allows for evaluation of microstructural changes The DTI fractional anisotropy FA metric was demonstrated as valid biomarker for recovery after surgery in cervical myelopathy as well as surgical selection in lumbar radiculopathy Moreover recent introduction of zoomed-DTI z-DTI could lead to greater imaging accuracy while proven feasible in the cervical spine
Furthermore the cervical spinal cord and its nerve roots are highly vascularized and their perfusion could be compromised by disc-herniation related compression Using the endogenous perfusion technique arterial spin labeling ASL as well as contrast-based perfusion techniques such as susceptibility contrast DSC and dynamic contrast enhanced DCE degree of ischemia hypoxia as well as signal enhancement can be estimated ASL has been studied twice for spinal cord perfusion mapping and DSC was demonstrated feasible in the spine of healthy participants as well as patients with cervical myelopathy Additionally increased signal enhancement was observed for DCE in degenerative discs of the lumbar spine To our best knowledge no studies have been conducted to assess perfusion of the cervical nerve roots which are compromised in cervical radiculopathy due to CDDD
Besides microstructure and perfusion viscoelastic properties of cervical spinal structures may change in relation to disc herniation-related compression Therefore it would be interesting to study mechanical properties such as stiffness and viscosity which can be measured with Tomo-MRElastography TMRE To our best knowledge no previous study has assessed cervical intervertebral discs and spinal structures using TMRE making this a promising first study
Finally imaging is a relatively time-consuming matter and including additional sequences will only increase its lengthiness Therefore several methods are being developed to perform imaging in a more efficient manner One novel method is Synthetic MRI SyMRI Advantages of SyMRI are a reduced acquisition time possibility of performing automatic tissue segmentation and volume estimation and acquisition of quantitative parameters SyMRI has been studied once in the spine and significant differences in quantitative intervertebral disc values were found in relation to hydration-status of the disc
Since no single measurement has been proven to be the golden standard in previous studies it is likely that a combination of measurements is needed for clinical application Therefore the aim of this pilot study is to explore a multi-parametric quantitative MRI approach including z-DTI ASL DSC DCE TMRE and SyMRI to measure cervical intervertebral discs the spinal cord and its nerve roots
OBJECTIVE
This study will consist of three parts The primary objective of part 1 is to evaluate feasibility of the quantitative MRI sequences eg z-DTI ASL DSC DCE TMRE and SyMRI for assessment of cervical spinal structures eg intervertebral discs spinal cord and nerve roots in healthy participants and patients with symptomatic CDDD The primary objective of part 2 is to determine a correlation between the quantitative MRI sequences of cervical spinal structures to clinical outcome in patients with symptomatic CDDD Finally the primary aim of part 3 is to establish a correlation between quantitative MRI sequences of cervical spinal structures and surgical treatment within 6 months of follow-up
STUDY DESIGN
A prospective pilot study
STUDY POPULATION
The study population consists of healthy participants and patients with symptomatic CDDD with radiculopathy myelopathy or radiculomyelopathy Age-matched healthy participants will be included Participants have no previous history of cervical disc herniation or cervical surgery a sufficient understanding of the Dutch language and no contraindications for an MRI scan
INTERVENTION
All participants will be subjected to several MRI sequences using a state of the art 3T Siemens MRI Scanner available in the UMCG First all participants healthy participants and patients with symptomatic CDDD undergo baseline neurologic examination Additionally participants fill out the following questionnaires Neck Disability Index NDI Visual Analogue Scale VAS for arm and neck pain modified Japanese Orthopedic Association mJOA Nurick grade EuroQol 5-Dimension 5-Level EQ-5D-5L Work Ability Single Item WAI-SI and Central Sensitisation Inventory CSI All participants undergo MRI scanning localizer T2-weighted anatomical conventional MRI z-DTI ASL DSC DCE TMRE and SyMR The total scanning time will be approximately 40 minutes For assessment of reproducibility 10 healthy participants and 10 patients will be scanned 2 times on different daystimes The patients with symptomatic CDDD will have another study visit after 6 months of follow-up to assess their treatment status having had surgery yesno in case of yes also the surgery characteristics to fill out the abovementioned questionnaires and have an MRI with additional sequences
MAIN STUDY PARAMETERSENDPOINTS
Primary endpoints are the technical feasibility and repeatability for the quantitative MRI sequences ie z_DTI ASL DSC DCE TMRE and SyMRI of cervical spinal structures ie intervertebral discs spinal cord and nerve roots in healthy participants and patients with symptomatic CDDD Also a correlation of quantitative MRI sequences of cervical spinal structures to clinical impairment in patients with symptomatic CDDD will be determined Clinical impairment will be measured with the Neck Disability Index NDI for cervical radiculopathy modified Japanese Orthopaedic Association Score mJOA for cervical myelopathy and NDI as well as mJOA for radiculomyelopathy
NATURE AND EXTENT OF THE BURDER AND RISKS ASSOCIATED WITH PARTICIPATION BENEFIT AND GROUP RELATEDNESS
All participants healthy and patients will need a conventional MRI scan with quantitative MRI sequences which will take approximately 40 minutes Most MRI sequences used in this study are noninvasive and do not involve any ionizing radiation However DSC and DCE require administration of a bolus contrast The contrast agent that will be used is Dotarem Without any contra-indications for an MRI scan or contrast agent health is not at risk There is an overall negligible risk for participants as based on the Risk Classification Checklist of the NFU Therefore the investigators can conclude that this study is a low-risk study
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None