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1.  Gradient echo MRI correlates with clinical measures and allows visualization of veins within MS lesions 
Background
Conventional MRI methods do not quantify the severity of MS white matter lesions or measure pathology within normal-appearing white matter (NAWM).
Objective
Gradient Echo Plural Contrast Imaging (GEPCI), a fast MRI technique producing inherently co-registered images for qualitative and quantitative assessment of MS, was used to 1) correlate with disability; 2) distinguish clinical MS subtypes; 3) determine prevalence of veins co-localized within lesions in WM.
Methods
Thirty subjects representing RRMS, SPMS and PPMS subtypes were scanned with clinical and GEPCI protocols. Standard measures of physical disability and cognition were correlated with MR metrics. Lesions with central veins were counted for RRMS subjects.
Results
Tissue damage load (TDL-GEPCI) and lesion load (LL-GEPCI) derived with GEPCI correlated better with MS functional composite (MSFC) measures and most other neurologic measures than lesion load derived with FLAIR (LL-FLAIR). GEPCI correctly classified clinical subtypes in 70% subjects. A central vein could be identified in 76% of WM lesions in RRMS subjects on GEPCI T2*-SWI images.
Conclusion
GEPCI lesion metrics correlated better with neurologic disability than lesion load derived using FLAIR imaging, and showed promise in classifying clinical subtypes of MS. These improvements are likely attributable to the ability of GEPCI to quantify tissue damage.
doi:10.1177/1352458513495935
PMCID: PMC4366944  PMID: 23836876
Multiple Sclerosis; quantitative MRI; CNS white matter; MS clinical subtypes; perivascular cuffs
2.  Spinal cord tract diffusion tensor imaging reveals disability substrate in demyelinating disease 
Neurology  2013;80(24):2201-2209.
Objective:
This study assessed the tissue integrity of major cervical cord tracts by using diffusion tensor imaging (DTI) to determine the relationship with specific clinical functions carried by those tracts.
Methods:
This was a cross-sectional study of 37 patients with multiple sclerosis or neuromyelitis optica with remote cervical cord disease. Finger vibratory thresholds, 25-foot timed walk (25FTW), 9-hole peg test (9HPT), and Expanded Disability Status Scale were determined. DTI covered cervical regions C1 through C6 with 17 5-mm slices (0.9 × 0.9 mm in-plane resolution). Regions of interest included posterior columns (PCs) and lateral corticospinal tracts (CSTs). Hierarchical linear mixed-effect modeling included covariates of disease subtype (multiple sclerosis vs neuromyelitis optica), disease duration, and sex.
Results:
Vibration thresholds were associated with radial diffusivity (RD) and fractional anisotropy (FA) in the PCs (both p < 0.01), but not CSTs (RD, p = 0.29; FA, p = 0.14). RD and FA in PCs, and RD in CSTs were related to 9HPT (each p < 0.0001). 25FTW was associated with RD and FA in PCs (p < 0.0001) and RD in CSTs (p = 0.008). Expanded Disability Status Scale was related to RD and FA in PCs and CSTs (p < 0.0001). Moderate/severe impairments in 9HPT (p = 0.006) and 25FTW (p = 0.017) were more likely to show combined moderate/severe tissue injury within both PCs and CSTs by DTI.
Conclusions:
DTI can serve as an imaging biomarker of spinal cord tissue injury at the tract level. RD and FA demonstrate strong and consistent relationships with clinical outcomes, specific to the clinical modality.
doi:10.1212/WNL.0b013e318296e8f1
PMCID: PMC3721096  PMID: 23667060
3.  Increased Radial Diffusivity in Spinal Cord Lesions in Neuromyelitis Optica Compared to Multiple Sclerosis 
Background
Multiple sclerosis (MS) and neuromyelitis optica (NMO) both affect spinal cord with notable differences in pathology.
Objective
Determine the utility of diffusion tensor imaging (DTI) to differentiate the spinal cord lesions of NMO from MS within and outside T2 lesions.
Methods
Subjects ≥12 months from a clinical episode of transverse myelitis underwent a novel transaxial cervical spinal cord DTI sequence. Ten subjects with NMO, 10 with MS, and 10 healthy controls were included.
Results
Within T2 affected white matter regions, radial diffusivity was increased in both NMO and MS compared to healthy controls (p<0.001, respectively), and to a greater extent in NMO than MS (p<0.001). Axial diffusivity was decreased in T2 lesions in both NMO and MS compared to controls (p<0.001, p=0.001), but did not differ between the two diseases. Radial diffusivity and FA within white matter regions upstream and downstream of T2 lesions were different from controls in each disease.
Conclusions
Higher radial diffusivity, within spinal cord white matter tracts derived from diffusion tensor imaging were appreciated in NMO compared to MS, consistent with the known greater tissue destruction seen in NMO. DTI also detected tissue alterations outside T2 lesions, and may be a surrogate of anterograde and retrograde degeneration.
doi:10.1177/1352458512436593
PMCID: PMC3360125  PMID: 22354742
diffusion tensor imaging; neuromyelitis optica (NMO); multiple sclerosis (MS); spinal cord; MRI
4.  Association of Neuromyelitis Optica With Severe and Intractable Pain 
Archives of neurology  2012;69(11):1482-1487.
Objective
To contrast differences in pain and treatment outcomes between neuromyelitis optica (NMO) and multiple sclerosis (MS).
Design
Retrospective, cross-sectional cohort study.
Setting
Academic MS center.
Patients
Complete ascertainment of an academic MS center cohort of NMO and an MS comparison sample cohort.
Main Outcome Measures
Current pain was quantified by a 10-point scale and the McGill Pain Questionnaire. Expanded Disability Status Scale score and number of involved spinal cord levels were collected in addition to testing for cognition, fatigue, depression, and quality of life. Number and types of pain medications were tabulated.
Results
Current pain was more common in subjects with NMO (n=29) vs MS (n=66) (86.2% vs 40.9%; P<.001) and more severe on a 10-point scale (5.38 vs 1.85; P <.001). Pain remained more common after controlling for disability and number of spinal cord segments (P=.03). Prescription pain medication was used more frequently in subjects with NMO compared with subjects with MS (75.9% vs 37.8%; P<.001), often requiring more than 1 medication (65.5% vs 15.2%; P<.001). No subject with NMO taking pain medication (22 of 29) rated their current pain as 0 of 10, whereas almost half of those taking pain medication with MS were currently free of pain (0% vs 48%; P=.006).
Conclusions
Neuromyelitis optica is frequently associated with severe pain that appears insufficiently controlled by pharmacologic interventions. Future studies should evaluate the efficacy of a multidisciplinary and multimodal approach to pain management.
doi:10.1001/archneurol.2012.768
PMCID: PMC3561507  PMID: 22926050
5.  Diffusion Tensor Imaging in Acute Optic Neuropathies 
Archives of neurology  2011;69(1):65-71.
Objective
To evaluate directional diffusivities within the optic nerve in a first event of acute optic neuritis to determine whether decreased axial diffusivity (AD) would predict 6-month visual outcome and optic nerve integrity measures.
Design
Cohort study.
Setting
Academic multiple sclerosis center.
Patients
Referred sample of 25 individuals who presented within 31 days after acute visual symptoms consistent with optic neuritis. Visits were scheduled at baseline, 2 weeks, and 1, 3, 6, and 12 months.
Main Outcome Measures
Visual acuity, contrast sensitivity, visual evoked potentials (VEPs), and thickness of the retinal nerve fiber layer (RNFL).
Results
An incomplete 6-month visual recovery was associated with a lower baseline AD (1.50 μm2/ms [95% confidence interval {CI}, 1.36–1.64 μm2/ms for incomplete recovery vs 1.75 μm2/ms [95% CI, 1.67–1.83 μm2/ms] for complete recovery). Odds of complete recovery decreased by 53% (95% CI, 27%–70%) for every 0.1-unit decrease in baseline AD. A lower baseline AD correlated with worse 6-month visual outcomes in visual acuity (r=0.40, P=.03), contrast sensitivity (r=0.41, P=.02), VEP amplitude (r=0.55, P<.01), VEP latency (r=−0.38, P=.04), and RNFL thickness (r=0.53, P=.02). Radial diffusivity increased between months 1 and 3 to become higher in those with incomplete recovery at 12 months than in those with complete recovery (1.45 μm2/ms [95% CI, 1.31–1.59 μm2/ms] vs 1.19 μm2/ms [95% CI, 1.10–1.28 μm2/ms]).
Conclusions
Decreased AD in acute optic neuritis was associated with a worse 6-month visual outcome and correlated with VEP and RNFL measures of axon and myelin injury. Axial diffusivity may serve as a marker of axon injury in acute white matter injury.
doi:10.1001/archneurol.2011.243
PMCID: PMC3489058  PMID: 21911658

Results 1-5 (5)