Allan R. Martin

Translating state-of-the-art spinal cord MRI techniques to clinical use: A systematic review of clinical studies utilizing DTI, MT, MWF, MRS, and fMRI

Background A recent meeting of international imaging experts sponsored by the International Spinal Research Trust (ISRT) and the Wings for Life Foundation identified 5 state-of-the-art MRI techniques with potential to transform the field of spinal cord imaging by elucidating elements of the microstructure and function: diffusion tensor imaging (DTI), magnetization transfer (MT), myelin water fraction (MWF), MR spectroscopy (MRS), and functional MRI (fMRI). However, the progress toward clinical translation of these techniques has not been established. Methods A systematic review of the English literature was conducted using MEDLINE, MEDLINE-in-Progress, Embase, and Cochrane databases to identify all human studies that investigated utility, in terms of diagnosis, correlation with disability, and prediction of outcomes, of these promising techniques in pathologies affecting the spinal cord. Data regarding study design, subject characteristics, MRI methods, clinical measures of impairment, and analysis techniques were extracted and tabulated to identify trends and commonalities. The studies were assessed for risk of bias, and the overall quality of evidence was assessed for each specific finding using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. Results A total of 6597 unique citations were identified in the database search, and after full-text review of 274 articles, a total of 104 relevant studies were identified for final inclusion (97% from the initial database search). Among these, 69 studies utilized DTI and 25 used MT, with both techniques showing an increased number of publications in recent years. The review also identified 1 MWF study, 11 MRS studies, and 8 fMRI studies. Most of the studies were exploratory in nature, lacking a priori hypotheses and showing a high (72%) or moderately high (20%) risk of bias, due to issues with study design, acquisition techniques, and analysis methods. The acquisitions for each technique varied widely across studies, rendering direct comparisons of metrics invalid. The DTI metric fractional anisotropy (FA) had the strongest evidence of utility, with moderate quality evidence for its use as a biomarker showing correlation with disability in several clinical pathologies, and a low level of evidence that it identifies tissue injury (in terms of group differences) compared with healthy controls. However, insufficient evidence exists to determine its utility as a sensitive and specific diagnostic test or as a tool to predict clinical outcomes. Very low quality evidence suggests that other metrics also show group differences compared with controls, including DTI metrics mean diffusivity (MD) and radial diffusivity (RD), the diffusional kurtosis imaging (DKI) metric mean kurtosis (MK), MT metrics MT ratio (MTR) and MT cerebrospinal fluid ratio (MTCSF), and the MRS metric of N-acetylaspartate (NAA) concentration, although these results were somewhat inconsistent. Conclusions State-of-the-art spinal cord MRI techniques are emerging with great potential to improve the diagnosis and management of various spinal pathologies, but the current body of evidence has only showed limited clinical utility to date. Among these imaging tools DTI is the most mature, but further work is necessary to standardize and validate its use before it will be adopted in the clinical realm. Large, well-designed studies with a priori hypotheses, standardized acquisition methods, detailed clinical data collection, and robust automated analysis techniques are needed to fully demonstrate the potential of these rapidly evolving techniques.

The pipeline flow-diverting stent for exclusion of ruptured intracranial aneurysms with difficult morphologies.

BACKGROUND: The Pipeline Embolization Device (PED) is a flow-diverting stent that may represent a new therapeutic tool for difficult-to-treat intracranial aneurysms, including those that present with subarachnoid hemorrhage (SAH). OBJECTIVE: To demonstrate the feasibility of utilizing the PED as a primary treatment for ruptured aneurysms with challenging morphologies. METHODS: Three patients with ruptured intracranial aneurysms presented with SAH. Three distinct and difficult-to-treat aneurysm morphologies were encountered: (1) a small basilar trunk pseudoaneurysm, (2) a carotid artery blister aneurysm, and (3) an A1/A2 junction-dissecting-type aneurysm. All were treated with deployment of one or more PEDs across the aneurysm. RESULTS: PEDs were successfully deployed in all 3 cases. Two patients were treated with 2 overlapping PEDs, and the third patient was treated with a single device. Aneurysm obliteration was achieved in all 3 cases with no early rehemorrhage or other clinically adverse event. CONCLUSION: Endovascular treatment with the pipeline flow-diverting stent may be a viable treatment option for otherwise difficult-to-treat aneurysm morphologies in the context of acute SAH.

Recent advances in managing a spinal cord injury secondary to trauma.

Traumatic spinal cord injuries (SCIs) affect 1.3 million North Americans, producing devastating physical, social, and vocational impairment. Pathophysiologically, the initial mechanical trauma is followed by a significant secondary injury which includes local ischemia, pro-apoptotic signaling, release of cytotoxic factors, and inflammatory cell infiltration. Expedient delivery of medical and surgical care during this critical period can improve long-term functional outcomes, engendering the concept of “Time is Spine”. We emphasize the importance of expeditious care while outlining the initial clinical and radiographic assessment of patients. Key evidence-based early interventions (surgical decompression, blood pressure augmentation, and methylprednisolone) are also reviewed, including findings of the landmark Surgical Timing in Acute Spinal Cord Injury Study (STASCIS). We then describe other neuroprotective approaches on the edge of translation such as the sodium-channel blocker riluzole, the anti-inflammatory minocycline, and therapeutic hypothermia. We also review promising neuroregenerative therapies that are likely to influence management practices over the next decade including chondroitinase, Rho-ROCK pathway inhibition, and bioengineered strategies. The importance of emerging neural stem cell therapies to remyelinate denuded axons and regenerate neural circuits is also discussed. Finally, we outline future directions for research and patient care.

Magnetic resonance imaging assessment of degenerative cervical myelopathy: a review of structural changes and measurement techniques

Degenerative cervical myelopathy encompasses a spectrum of age-related structural changes of the cervical spine that result in static and dynamic injury to the spinal cord and collectively represent the most common cause of myelopathy in adults. Although cervical myelopathy is determined clinically, the diagnosis requires confirmation via imaging, and MRI is the preferred modality. Because of the heterogeneity of the condition and evolution of MRI technology, multiple techniques have been developed over the years in an attempt to quantify the degree of baseline severity and potential for neurological recovery. In this review, these techniques are categorized anatomically into those that focus on bone, ligaments, discs, and the spinal cord. In addition, measurements for the cervical spine canal size and sagittal alignment are also described briefly. These tools have resulted collectively in the identification of numerous useful parameters. However, the development of multiple techniques for assessing the same feature, such as cord compression, has also resulted in a number of challenges, including introducing ambiguity in terms of which methods to use and hindering effective comparisons of analysis in the literature. In addition, newer techniques that use advanced MRI are emerging and providing exciting new tools for assessing the spinal cord in patients with degenerative cervical myelopathy.

Clinically Feasible Microstructural MRI to Quantify Cervical Spinal Cord Tissue Injury Using DTI, MT, and T2*-Weighted Imaging: Assessment of Normative Data and Reliability

Forty healthy subjects underwent T2WI, DTI, magnetization transfer, and T2*WI at 3T in <35 minutes using standard hardware and pulse sequences. Cross-sectional area, fractional anisotropy, magnetization transfer ratio, and T2*WI WM/GM signal intensity ratio were calculated. Reliable multiparametric assessment of spinal cord microstructure is possible by using clinically suitable methods. These results establish normalization procedures and pave the way for clinical studies. BACKGROUND AND PURPOSE: DTI, magnetization transfer, T2*-weighted imaging, and cross-sectional area can quantify aspects of spinal cord microstructure. However, clinical adoption remains elusive due to complex acquisitions, cumbersome analysis, limited reliability, and wide ranges of normal values. We propose a simple multiparametric protocol with automated analysis and report normative data, analysis of confounding variables, and reliability. MATERIALS AND METHODS: Forty healthy subjects underwent T2WI, DTI, magnetization transfer, and T2*WI at 3T in <35 minutes using standard hardware and pulse sequences. Cross-sectional area, fractional anisotropy, magnetization transfer ratio, and T2*WI WM/GM signal intensity ratio were calculated. Relationships between MR imaging metrics and age, sex, height, weight, cervical cord length, and rostrocaudal level were analyzed. Test-retest coefficient of variation measured reliability in 24 DTI, 17 magnetization transfer, and 16 T2*WI datasets. DTI with and without cardiac triggering was compared in 10 subjects. RESULTS: T2*WI WM/GM showed lower intersubject coefficient of variation (3.5%) compared with magnetization transfer ratio (5.8%), fractional anisotropy (6.0%), and cross-sectional area (12.2%). Linear correction of cross-sectional area with cervical cord length, fractional anisotropy with age, and magnetization transfer ratio with age and height led to decreased coefficients of variation (4.8%, 5.4%, and 10.2%, respectively). Acceptable reliability was achieved for all metrics/levels (test-retest coefficient of variation < 5%), with T2*WI WM/GM comparing favorably with fractional anisotropy and magnetization transfer ratio. DTI with and without cardiac triggering showed no significant differences for fractional anisotropy and test-retest coefficient of variation. CONCLUSIONS: Reliable multiparametric assessment of spinal cord microstructure is possible by using clinically suitable methods. These results establish normalization procedures and pave the way for clinical studies, with the potential for improving diagnostics, objectively monitoring disease progression, and predicting outcomes in spinal pathologies.

A Clinical Practice Guideline for the Management of Patients With Degenerative Cervical Myelopathy: Recommendations for Patients With Mild, Moderate, and Severe Disease and Nonmyelopathic Patients With Evidence of Cord Compression

Study Design: Guideline development. Objectives: The objective of this study is to develop guidelines that outline how to best manage (1) patients with mild, moderate, and severe myelopathy and (2) nonmyelopathic patients with evidence of cord compression with or without clinical symptoms of radiculopathy. Methods: Five systematic reviews of the literature were conducted to synthesize evidence on disease natural history; risk factors of disease progression; the efficacy, effectiveness, and safety of nonoperative and surgical management; the impact of preoperative duration of symptoms and myelopathy severity on treatment outcomes; and the frequency, timing, and predictors of symptom development. A multidisciplinary guideline development group used this information, and their clinical expertise, to develop recommendations for the management of degenerative cervical myelopathy (DCM). Results: Our recommendations were as follows: (1) “We recommend surgical intervention for patients with moderate and severe DCM.” (2) “We suggest offering surgical intervention or a supervised trial of structured rehabilitation for patients with mild DCM. If initial nonoperative management is pursued, we recommend operative intervention if there is neurological deterioration and suggest operative intervention if the patient fails to improve.” (3) “We suggest not offering prophylactic surgery for non-myelopathic patients with evidence of cervical cord compression without signs or symptoms of radiculopathy. We suggest that these patients be counseled as to potential risks of progression, educated about relevant signs and symptoms of myelopathy, and be followed clinically.” (4) “Non-myelopathic patients with cord compression and clinical evidence of radiculopathy with or without electrophysiological confirmation are at a higher risk of developing myelopathy and should be counselled about this risk. We suggest offering either surgical intervention or nonoperative treatment consisting of close serial follow-up or a supervised trial of structured rehabilitation. In the event of myelopathic development, the patient should be managed according to the recommendations above.” Conclusions: These guidelines will promote standardization of care for patients with DCM, decrease the heterogeneity of management strategies and encourage clinicians to make evidence-informed decisions.

Dropped head syndrome: diagnosis and management.

Dropped head syndrome (DHS) is a relatively rare condition, with a broad differential diagnosis. This deformity has significant implications on the health and quality of life of affected individuals. While surgery seems to be an obvious therapeutic option, there is a paucity of information on surgical intervention with no clear consensus on an optimal approach or timing. We present a case of DHS in a young woman to illustrate this condition, and review the current literature. Although at present the only definitive solution for correction and stabilization of DHS is surgical intervention involving multilevel instrumented fixation and fusion, this condition requires a persistent medical workup and treatment of reversible causes before surgical intervention is contemplated.

Exploring the role of 3-dimensional simulation in surgical training: feedback from a pilot study.

Study Design Randomized control study assessing the efficacy of a pedicle screw insertion simulator. Objectives To evaluate the efficacy of an in-house developed 3-dimensional software simulation tool for teaching pedicle screw insertion, to gather feedback about the utility of the simulator, and to help identify the context and role such simulation has in surgical education. Summary of Background Data Traditional instruction for pedicle screw insertion technique consists of didactic teaching and limited hands-on training on artificial or cadaveric models before guided supervision within the operating room. Three- dimensional computer simulation can provide a valuable tool for practicing challenging surgical procedures; however, its potential lies in its effective integration into student learning. Methods Surgical residents were recruited from 2 sequential years of a spine surgery course. Patient and control groups both received standard training on pedicle screw insertion. The patient group received an additional 1-hour session of training on the simulator using a CT-based 3-dimensional model of their assigned cadavers spine. Qualitative feedback about the simulator was gathered from the trainees, fellows, and staff surgeons, and all pedicles screws physically inserted into the cadavers during the courses were evaluated through CT. Results A total of 185 thoracic and lumbar pedicle screws were inserted by 37 trainees. Eighty-two percent of the 28 trainees who responded to the questionnaire and all fellows and staff surgeons felt the simulator to be a beneficial educational tool. However, the 1-hour training session did not yield improved performance in screw placement. Conclusions A 3-dimensional computer-based simulation for pedicle screw insertion was integrated into a cadaveric spine surgery instructional course. Overall, the tool was positively regarded by the trainees, fellows, and staff surgeons. However, the limited training with the simulator did not translate into widespread comfort with its operation or into improvement in physical screw placement.

A Novel MRI Biomarker of Spinal Cord White Matter Injury: T2*-Weighted White Matter to Gray Matter Signal Intensity Ratio

BACKGROUND AND PURPOSE: T2*-weighted imaging provides sharp contrast between spinal cord GM and WM, allowing their segmentation and cross-sectional area measurement. Injured WM demonstrates T2*WI hyperintensity but requires normalization for quantitative use. We introduce T2*WI WM/GM signal-intensity ratio and compare it against cross-sectional area, the DTI metric fractional anisotropy, and magnetization transfer ratio in degenerative cervical myelopathy. MATERIALS AND METHODS: Fifty-eight patients with degenerative cervical myelopathy and 40 healthy subjects underwent 3T MR imaging, covering C1–C7. Metrics were automatically extracted at maximally compressed and uncompressed rostral/caudal levels. Normalized metrics were compared with t tests, area under the curve, and logistic regression. Relationships with clinical measures were analyzed by using Pearson correlation and multiple linear regression. RESULTS: The maximally compressed level cross-sectional area demonstrated superior differences (P = 1 × 10−13), diagnostic accuracy (area under the curve = 0.890), and univariate correlation with the modified Japanese Orthopedic Association score (0.66). T2*WI WM/GM showed strong differences (rostral: P = 8 × 10−7; maximally compressed level: P = 1 × 10−11; caudal: P = 1 × 10−4), correlations (modified Japanese Orthopedic Association score; rostral: −0.52; maximally compressed level: −0.59; caudal: −0.36), and diagnostic accuracy (rostral: 0.775; maximally compressed level: 0.860; caudal: 0.721), outperforming fractional anisotropy and magnetization transfer ratio in most comparisons and cross-sectional area at rostral/caudal levels. Rostral T2*WI WM/GM showed the strongest correlations with focal motor (−0.45) and sensory (−0.49) deficits and was the strongest independent predictor of the modified Japanese Orthopedic Association score (P = .01) and diagnosis (P = .02) in multivariate models (R2 = 0.59, P = 8 × 10−13; area under the curve = 0.954, respectively). CONCLUSIONS: T2*WI WM/GM shows promise as a novel biomarker of WM injury. It detects damage in compressed and uncompressed regions and contributes substantially to multivariate models for diagnosis and correlation with impairment. Our multiparametric approach overcomes limitations of individual measures, having the potential to improve diagnostics, monitor progression, and predict outcomes.

Small Pipes: Preliminary Experience with 3-mm or Smaller Pipeline Flow-Diverting Stents for Aneurysm Repair prior to Regulatory Approval

SUMMARY: Flow diversion has become an established treatment option for challenging intracranial aneurysms. The use of small devices of ≤3-mm diameter remains unapproved by major regulatory bodies. A retrospective review of patients treated with Pipeline Embolization Devices of ≤3-mm diameter at 3 Canadian institutions was conducted. Clinical and radiologic follow-up data were collected and reported. Twelve cases were treated with ≥1 Pipeline Embolization Device of ≤3-mm diameter, including 2 with adjunctive coiling, with a median follow-up of 18 months (range, 4–42 months). One patient experienced a posttreatment minor complication (8%) due to an embolic infarct. No posttreatment hemorrhage or delayed complications such as in-stent stenosis/thrombosis were observed. Radiologic occlusion was seen in 9/12 cases (75%) and near-occlusion in 2/12 cases (17%). Intracranial aneurysm treatment with small-diameter flow-diverting stents provided safe and effective aneurysm closure in this small selected sample. These devices should be further studied and considered for regulatory approval.