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Benjamin M. Ellingson, Noriko Salamon, Davis C. Woodworth, Hajime Yokota, and Langston T. Holly

OBJECTIVE

The purpose of this study was to quantify the reproducibility, temporal stability, and functional correlation of diffusion MR characteristics in the spinal cord in patients with cervical stenosis with or without myelopathy. The association between longitudinal diffusion tensor imaging (DTI) measurements and serial neurological function assessment was explored at both the group and individual level.

METHODS

Sixty-six nonoperatively treated patients with cervical stenosis were prospectively followed (3 months to > 5 years) using synchronous serial MRI and functional outcome assessment. A total of 183 separate MRI examinations were performed, separated by at least 3 months, and each patient had a minimum of 2 MRI scans (range 2–5 scans). Anatomical and DTI measurements were performed within the spinal cord at the C1–2 region as well as at the area of highest compression. Coefficients of variance (COVs) were compared across measurements in both reference tissue and areas of compression for anatomical measurements, fractional anisotropy (FA), and mean diffusivity (MD). The correlation between diffusion MR measures at the site of compression and evaluations of neurological function assessed using the modified Japanese Orthopaedic Association (mJOA) scale at multiple time points was evaluated.

RESULTS

The COVs for anatomical measurements (Torg ratio and canal diameter) were between 7% and 10%. The median COV for FA measurements at the site of compression was 9%, and for reference tissue at C1–2 it was 6%. The median COV for MD at the site of compression was approximately 12%, and for reference tissue at C1–2 it was 10%. The FA and MD measurements of C1–2 averaged 0.61 and 0.91 μm2/msec, respectively, whereas the FA and MD measurements at the site of compression averaged 0.51 and 1.26 μm2/msec, respectively. Both FA (slope = 0.037; R2 = 0.3281, p < 0.0001) and MD (slope = −0.074; R2 = 0.1101, p = 0.0084) were significantly correlated with the mJOA score. The FA decreased by approximately 0.032 units per mJOA unit decrease (R2 = 0.2037, p < 0.0001), whereas the MD was increased by approximately 0.084 μm2/msec for every mJOA unit decrease (R2 = 0.1016, p < 0.0001).

CONCLUSIONS

Quantitative DTI measurements of the spinal cord in patients with cervical stenosis with or without myelopathy have a median COV of 5%–10%, similar to anatomical measurements. The reproducibility of these measurements and significant correlation with functional outcome status suggest a potential role in the evaluation and longitudinal surveillance of nonoperatively treated patients. With respect to the specific DTI measurements, FA within the spinal cord appears slightly more sensitive to neurological function and more stable than measures of MD. Therefore, DTI of the spinal cord may be a clinically feasible imaging technique for longitudinally monitoring patients with cervical spondylotic myelopathy.

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Benjamin M. Ellingson, Noriko Salamon, Davis C. Woodworth, and Langston T. Holly

OBJECT

The purpose of this study was to explore the use of super-resolution tract density images derived from probabilistic diffusion tensor imaging (DTI) tractography of the spinal cord as an imaging surrogate for microstructural integrity and functional impairment in patients with cervical spondylosis.

METHODS

Structural MRI and DTI images were collected for 27 patients with cervical spondylosis with (n= 21) and without (n= 6) functional impairment as defined by the modified Japanese Orthopaedic Association Scale (mJOA). DTI was performed axially through the site of compression in a total of 20 directions with 10 averages. Probabilistic tractography was performed at 0.5-mm isotropic spatial resolution using the streamline technique combined with constrained spherical deconvolution. The following measurements were calculated for each patient: maximum tract density at the site of compression, average tract density in rostral normal-appearing spinal cord, and the ratio of maximum density to normal density.

RESULTS

Compared with normal tissue, the site of compression exhibited elevated fiber tract density in all patients, and a higher fiber tract density was also noted in focal areas at the site of compression in patients with functional impairment. There was a strong negative correlation between maximum tract density and mJOA score (R2= 0.6324, p < 0.0001) and the ratio of maximum tract density to normal tract density (R2= 0.6647, p < 0.0001). When grouped according to severity of neurological impairment (asymptomatic, mJOA score of 18; mild, mJOA score of 15–17; moderate, mJOA score of 11–14; and severe, mJOA score < 11), the results showed a significant difference in the ratio between severe and both no impairment (p= 0.0009) and any impairment (p= 0.036). A ratio of maximum fiber tract density at the site of compression to fiber tract density at C-2 greater than 1.45 had 82% sensitivity and 70% specificity for identifying patients with moderate to severe impairment (ROC AUC= 0.8882, p= 0.0009).

CONCLUSIONS

These results support the use of DTI as a surrogate for determining spinal cord integrity in patients with cervical spondylosis. Probabilistic tractography provides spinal cord microstructural information that can help discern clinical status in cervical spondylosis patients with varying degrees of neurological impairment.

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Langston T. Holly, Bonnie Freitas, David L. McArthur, and Noriko Salamon

Object

Magnetic resonance spectroscopy is commonly used to provide cellular and metabolic information in the management of a variety of pathological processes that affect the brain, and its application recently has been expanded to the cervical spine. The majority of radiographic investigations into the pathophysiology of cervical spondylotic myelopathy (CSM) have been focused on the spinal cord macrostructure. The authors sought to determine the feasibility of using MR spectroscopy to analyze spinal cord biochemical function in patients with CSM.

Methods

Twenty-one patients with clinical and radiographic evidence of CSM were prospectively enrolled in this study. The patients underwent preoperative neurological examination, functional assessment, and cervical spine MR spectroscopy. Voxels were placed at the C-2 level, and the MR spectroscopy spectra peaks for N-acetylaspartate (NAA), choline, lactate (Lac), and creatine (Cr) were measured. Thirteen age-matched healthy volunteers served as controls.

Results

The NAA/Cr ratio was significantly lower in patients with CSM than in controls (1.27 vs 1.83, respectively, p < 0.0001). The choline/Cr ratio was not significantly different between the 2 groups. Seven of the patients with CSM had a Lac peak, whereas no peaks were noted in the control group (p < 0.05). There was no correlation between the severity of myelopathy and the NAA/Cr ratio in the CSM cohort.

Conclusions

Data in this study demonstrated the feasibility of using MR spectroscopy to evaluate the cellular biochemistry of the spinal cord in patients with CSM. Patients with CSM had a significantly lower NAA/Cr ratio than healthy controls, likely because of axonal and neuronal loss. The presence of Lac peaks in one-third of the patients in the CSM cohort further supports the role of ischemia in the pathophysiology of CSM.

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Aichi Chien, Feng Liang, James Sayre, Noriko Salamon, Pablo Villablanca, and Fernando Viñuela

Object

This study was performed to investigate the risk factors related to the growth of small, asymptomatic, unruptured aneurysms in patients with no history of subarachnoid hemorrhage (SAH).

Methods

Between January 2005 and December 2010, a total of 508 patients in whom unruptured intracranial aneurysms were diagnosed at the University of California, Los Angeles medical center did not receive treatment to prevent rupture. Of these, 235 patients with no history of SAH who had asymptomatic, small, unruptured aneurysms (< 7 mm) were monitored with 3D CT angiography images. Follow-up images of the lesions were used to measure aneurysm size changes. Patient medical history, family history of SAH, aneurysm size, and location were studied to find the risk factors associated with small aneurysm growth.

Results

A total of 319 small aneurysms were included, with follow-up durations of 29.2 ± 20.6 months. Forty-two aneurysms increased in size during the follow-up; 5 aneurysms grew to become ≥ 7 mm within 38.2 ± 18.3 months. A trend of higher growth rates was found in single aneurysms than in multiple aneurysms (p = 0.07). A history of stroke was the only factor associated with single aneurysm growth (p = 0.03). The number of aneurysms (p = 0.011), number of aneurysms located within the posterior circulation (p = 0.030), and patient history of transient ischemic attack (p = 0.044) were related to multiple aneurysm growth.

Conclusions

Multiple small aneurysms are more likely to grow, and multiple aneurysms located in the posterior circulation may require additional attention. Although single aneurysms have a lower risk of growth, a trend of higher growth rates in single aneurysms was found.

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Chencai Wang, Benjamin M. Ellingson, Sabah Islam, Azim Laiwalla, Noriko Salamon, and Langston T. Holly

OBJECTIVE

The aim of this study was to investigate cerebral reorganization, both structurally and functionally, occurring in patients with degenerative cervical myelopathy (DCM) after surgical decompression.

METHODS

In the current observational study of 19 patients, high-resolution T1-weighted structural MRI and resting-state functional MRI scans were obtained pre- and postoperatively in patients with DCM and healthy controls (HCs). The resting-state functional MRI data were utilized to perform region-of-interest (ROI)–to-ROI and ROI-to-voxel functional connectivity (FC) analysis and were similarly compared between and within cohorts. Macroscopic structural plasticity was evaluated by assessing for changes in cortical thickness within the DCM cohort after decompression surgery.

RESULTS

Prior to surgery, FC patterns were significantly different between DCM patients and HCs in cerebral areas responsible for postural control, motor regulation, and perception and integration of sensory information. Significantly stronger FC between the cerebellum and frontal lobes was identified in DCM patients postoperatively compared with DCM patients preoperatively. Additionally, increased FC between the cerebellum and primary sensorimotor areas was found to be positively associated with neurological improvement in patients with DCM. No macroscopic structural changes were observed in the DCM patients after surgery.

CONCLUSIONS

These results support the authors’ hypothesis that functional changes within the brain are associated with effective postoperative recovery, particularly in regions associated with motor regulation and with perception and integration of sensory information. In particular, increased FC between the cerebellum and the primary sensorimotor after surgery appears to be associated with neurological improvement. Macroscopic morphological changes may be too subtle to be detected within 3 months after surgery.

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Arne Ekstrom, Nanthia Suthana, Eric Behnke, B.S.E., Noriko Salamon, Susan Bookheimer, and Itzhak Fried

✓Localization and targeting of depth electrodes in specific regions of the human brain is critical for accurate clinical diagnoses and treatment as well as for neuroscientific electrophysiological research. By using high-resolution magnetic resonance imaging combined with 2D computational unfolding, the authors present a method that improves electrode localization in the medial temporal lobe. This method permits visualization of electrode placements in subregions of the hippocampus and parahippocampal gyrus, allowing for greater specificity in relating electrophysiological and anatomical features in the human medial temporal lobe. Such methods may be extended to therapeutic procedures targeting specific neuronal circuitry in subfields of structures deep in the human brain.

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Jason S. Hauptman, Andrew Dadour, Taemin Oh, Christine B. Baca, Barbara G. Vickrey, Stefanie D. Vassar, Raman Sankar, Noriko Salamon, Harry V. Vinters, and Gary W. Mathern

Object

Low income, government insurance, and minority status are associated with delayed treatment for neurosurgery patients. Less is known about the influence of referral location and how socioeconomic factors and referral patterns evolve over time. For pediatric epilepsy surgery patients at the University of California, Los Angeles (UCLA), this study determined how referral location and sociodemographic features have evolved over 25 years.

Methods

Children undergoing epilepsy neurosurgery at UCLA (453 patients) were classified by location of residence and compared with clinical epilepsy and sociodemographic factors.

Results

From 1986 to 2010, referrals from Southern California increased (+33%) and referrals from outside of California decreased (−19%). Over the same period, the number of patients with preferred provider organization (PPO) and health maintenance organization (HMO) insurance increased (+148% and +69%, respectively) and indemnity insurance decreased (−96%). Likewise, the number of Hispanics (+117%) and Asians (100%) increased and Caucasians/whites decreased (−24%). The number of insurance companies decreased from 52 carriers per 100 surgical patients in 1986–1990 to 19 per 100 in 2006–2010. Patients living in the Eastern US had a younger age at surgery (−46%), shorter intervals from seizure onset to referral for evaluation (−28%) and from presurgical evaluation to surgery (−61%) compared with patients from Southern California. The interval from seizure onset to evaluation was shorter (−33%) for patients from Los Angeles County compared with those living in non-California Western US states.

Conclusions

Referral locations evolved over 25 years at UCLA, with more cases coming from local regions; the percentage of minority patients also increased. The interval from seizures onset to surgery was shortest for patients living farthest from UCLA but still within the US. Geographic location and race/ethnicity was not associated with differences in becoming seizure free after epilepsy surgery in children.

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Aichi Chien, Rashida A. Callender, Hajime Yokota, Noriko Salamon, Geoffrey P. Colby, Anthony C. Wang, Viktor Szeder, Reza Jahan, Satoshi Tateshima, Juan Villablanca, Gary Duckwiler, Fernando Vinuela, Yuanqing Ye, and Michelle A. T. Hildebrandt

OBJECTIVE

As imaging technology has improved, more unruptured intracranial aneurysms (UIAs) are detected incidentally. However, there is limited information regarding how UIAs change over time to provide stratified, patient-specific UIA follow-up management. The authors sought to enrich understanding of the natural history of UIAs and identify basic UIA growth trajectories, that is, the speed at which various UIAs increase in size.

METHODS

From January 2005 to December 2015, 382 patients diagnosed with UIAs (n = 520) were followed up at UCLA Medical Center through serial imaging. UIA characteristics and patient-specific variables were studied to identify risk factors associated with aneurysm growth and create a predicted aneurysm trajectory (PAT) model to differentiate aneurysm growth behavior.

RESULTS

The PAT model indicated that smoking and hypothyroidism had a large effect on the growth rate of large UIAs (≥ 7 mm), while UIAs < 7 mm were less influenced by smoking and hypothyroidism. Analysis of risk factors related to growth showed that initial size and multiplicity were significant factors related to aneurysm growth and were consistent across different definitions of growth. A 1.09-fold increase in risk of growth was found for every 1-mm increase in initial size (95% CI 1.04–1.15; p = 0.001). Aneurysms in patients with multiple aneurysms were 2.43-fold more likely to grow than those in patients with single aneurysms (95% CI 1.36–4.35; p = 0.003). The growth rate (speed) for large UIAs (≥ 7 mm; 0.085 mm/month) was significantly faster than that for UIAs < 3 mm (0.030 mm/month) and for males than for females (0.089 and 0.045 mm/month, respectively; p = 0.048).

CONCLUSIONS

Analyzing longitudinal UIA data as continuous data points can be useful to study the risk of growth and predict the aneurysm growth trajectory. Individual patient characteristics (demographics, behavior, medical history) may have a significant effect on the speed of UIA growth, and predictive models such as PAT may help optimize follow-up frequency for UIA management.