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Biomedical subjects

Simon J Hickman

Publications and source records attributed to Simon J Hickman.

10 recordsLinked to original sources

Adaptive cortical plasticity in higher visual areas after acute optic neuritis.

The ability to distinguish adaptive cortical reorganization may help to target future therapeutic strategies after neurological insult. We investigated cortical plasticity by prospectively applying visual functional magnetic resonance imaging (fMRI) and optic nerve MRI to 20 patients with acute optic neuritis at baseline, 1, 3, 6, and 12 months. We performed three types of correlation analyses to investigate the relationships between fMRI activity, clinical function, and optic nerve structure. The first analysis directly correlated the fMRI response to clinical function or optic nerve structure and found dynamic relations especially within the first 3 months. The second analysis used a novel technique that modeled the fMRI response and optic nerve structure together with clinical function, to determine the contribution fMRI made to clinical function after accounting for structural factors. Significant effects were found at baseline only, within the right peristriate cortex, and bilaterally in the lateral occipital complexes, which are normally involved in higher order visual processing. The third analysis investigated the relation between the modeled visual recovery rate and fMRI response but found no significant effects. The key findings of this study are from the second analysis and suggest a genuine adaptive role for cortical reorganization within extrastriate visual areas early after optic neuritis.

Adaptation, Physiological↗

Optic radiation changes after optic neuritis detected by tractography-based group mapping.

Postmortem data suggest that trans-synaptic degeneration occurs in the lateral geniculate nucleus after optic nerve injury. This study investigated in vivo the optic radiations in patients affected by optic neuritis using fast marching tractography (FMT), a diffusion magnetic resonance imaging (MRI) fiber tracking method, and group mapping techniques, which allow statistical comparisons between subjects. Seven patients, 1 year after isolated unilateral optic neuritis, and ten age and gender-matched controls underwent whole-brain diffusion tensor MR imaging. The FMT algorithm was used to generate voxel-scale connectivity (VSC) maps in the optic radiations in each subject in native space. Group maps of the left and right optic radiations were created in the patient and control group in a standardized reference frame using statistical parametric mapping (SPM99). The reconstructed optic radiations in the patient group were localized more laterally in the posterior part of the tracts and more inferiorly than in the control group. Patients showed reduced VSC values in both tracts compared with controls. These findings suggest that the group mapping techniques might be used to assess changes in the optic radiations in patients after an episode of optic neuritis. The changes we have observed may be secondary to the optic nerve damage.

Adult↗

Optic nerve diffusion measurement from diffusion-weighted imaging in optic neuritis.

BACKGROUND AND PURPOSE: Increases in apparent diffusion coefficient (ADC) from diffusion-weighted (DW) imaging are thought to be due to axonal disruption, and changes have been well documented in multiple sclerosis lesions. DW imaging of the optic nerves, however, presents many challenges. The goal of this study was to measure ADC in patients with optic neuritis by using zonal oblique multisection echoplanar imaging. METHODS: The optic nerves of eighteen patients who had experienced an attack of optic neuritis 1 year previously and 11 control subjects were imaged with the diffusion sequence (usable data were available from 16 patients and 10 control subjects). The orbital optic nerves were segmented by a blinded observer by using a computer-assisted threshold-based contouring technique, and the mean ADC was determined. RESULTS: The mean ADC from diseased optic nerves was 1324 x 10(-6) mm2/s, compared with 990 x 10(-6) mm2/s from healthy contralateral optic nerves (P = .005 versus diseased optic nerves) and 928 x 10(-6) mm2/s from control optic nerves (P = .006 versus diseased optic nerves and P = .40 versus healthy contralateral optic nerves). The diseased optic nerve ADC correlated with both visual (e.g., r(S) = 0.73; P = .001 for logMAR visual acuity) and electrophysiological parameters (e.g., r(S) = -0.57, P = .021 for visual evoked potential central field amplitude [VEP]). CONCLUSION: It has been possible to apply DW imaging in a patient population, and, in the chronic phase following optic neuritis, the correlation of mean ADC with the clinical and electrophysiological parameters suggests that the ADC is giving a surrogate measure of axonal disruption in the chronic, postinflammatory optic nerve lesion.

Adult↗

A serial MRI study following optic nerve mean area in acute optic neuritis.

This study assessed optic nerve mean area on serial MRI in a cohort of patients with a first episode of acute unilateral optic neuritis to assess the effects of a single acute inflammatory demyelinating lesion. Twenty-nine patients with a median delay from onset of visual symptoms of 13 days (range 7-24 days) were recruited. After a clinical examination and visual evoked potential (VEP) measurement, each patient had their optic nerves imaged with a coronal fat-saturated short echo fast fluid-attenuated inversion recovery sequence. Twenty-one patients had serial examinations after 2, 4, 8, 12, 26 and 52 weeks. In addition, 32 control subjects had their optic nerves imaged up to three times. The mean cross-sectional area of the intra-orbital portion of each optic nerve was calculated by a blinded observer using a computer-assisted contouring technique. At baseline, the mean area of diseased optic nerves was 16.1 mm2 compared with 13.4 mm2 for healthy contralateral optic nerves (20.1% higher, P < 0.0001) and 13.6 mm2 for controls (18.4% higher, P = 0.0003). The diseased optic nerve mean area declined over time, from initial swelling to later atrophy. The mean decline at 52 weeks was -0.0018 mm2/day (95% confidence interval -0.0038 to -0.00051). At 52 weeks, the mean area of diseased optic nerves was 11.3 mm2 compared with 12.8 mm2 for healthy contralateral optic nerves (11.7% lower, P = 0.032) and 13.1 mm2 for controls (13.7% lower, P = 0.008). The 52 week diseased optic nerve mean area was not significantly affected by the baseline mean area. There was an association between baseline optic nerve mean area and logMAR visual acuity (rS = 0.46, P = 0.012) and visual field mean deviation (rS = -0.55, P = 0.002), but there was no evidence of an association between 1 year mean area and visual outcome. There was no evidence of association between baseline, rates of decline or 1 year diseased optic nerve mean areas and any of the baseline, 1 year or time-averaged VEP variables. The present study shows a consistent pattern of changes associated with individual inflammatory demyelinating lesions in the optic nerve. Acutely, there was swelling, consistent with the presence of acute inflammation, which was related to visual impairment. Over the longer term, there was loss of tissue. The lack of association between 1 year optic nerve mean area and visual outcome may reflect a mild loss of tissue, redundancy or remodelling of function.

Acute Disease↗

Visual recovery following acute optic neuritis--a clinical, electrophysiological and magnetic resonance imaging study.

This study reports the prospective follow-up of a cohort of patients with acute optic neuritis examined with serial visual tests, visual evoked potentials (VEPs), conventional and triple-dose gadolinium (Gd)-enhanced magnetic resonance imaging (MRI) to examine which factors are important in visual recovery. Thirty-three patients were recruited with acute unilateral optic neuritis. A clinical and VEP assessment was performed on each. Optic nerve MRI was performed using fast spin echo (FSE) (on all) and triple-dose Gd-enhanced T1-weighted sequences (n = 28). Optic nerve lesion lengths were measured. Serial assessments were performed on 22 of the patients up to one-year. Serial Gd-enhanced optic nerve imaging was performed on 15 of the patients until enhancement ceased. The final 30-2 Humphrey visual field mean deviation (MD) was 2.55 dB higher in patients in the lowest quartile of initial Gd-enhanced lesion length compared with the other quartiles (p < 0.01) but recovery was not related to the duration of enhancement. The initial recovery of Humphrey MD was 4.60 dB units per day in patients with good eventual recoveries (MD > -6.0 dB) and 0.99 dB per day in poor-recovery patients (p = 0.02).Good-recovery patients had mean central field VEP amplitudes 2.29 microV higher during recovery than poor-recovery patients (p = 0.047). The results suggest that factors which are associated with a better prognosis are: having a short acute lesion on triple-dose gadolinium enhanced imaging, higher VEP amplitudes during recovery and a steep gradient of the initial improvement in vision.

Adult↗

Application of a B-spline active surface technique to the measurement of cervical cord volume in multiple sclerosis from three-dimensional MR images.

PURPOSE: To evaluate the ability of a B-spline active surface technique to detect cervical spinal cord atrophy due to multiple sclerosis (MS) compared with intensity-based contouring. MATERIALS AND METHODS: In a previously reported study, the cervical spinal cords of 28 MS patients and 13 age-matched controls were imaged with a volume-acquired inversion-prepared fast spoiled gradient echo sequence at baseline and after one year. The images were reanalyzed using the B-spline technique and the results compared with the results obtained in the original report using intensity-based contouring. RESULTS: The mean cervical spinal cord volume determined by the active surface programme was 6487 mm(3) in 28 patients compared with 7117 mm(3) in controls (P = 0.002, corrected for age and gender). The patients' cervical spinal cord volumes were associated with expanded disability status scale scores (parameter estimate = -1.21 x 10(-3), r(2) = 0.39, P = 0.001). The patients' cervical spinal cord volumes did not decrease significantly over one year, unlike the mean cervical spinal cord areas at C2/3 calculated using intensity-based contouring. CONCLUSION: The active surface technique can detect cervical spinal cord atrophy due to MS, which has functional significance. However, this methodology is less sensitive at detecting small serial changes compared with the previously reported method.

Atrophy↗

Application of the new McDonald criteria to patients with clinically isolated syndromes suggestive of multiple sclerosis.

Traditionally, multiple sclerosis (MS) has been diagnosed on the basis of clinical evidence of dissemination in time and space. Previously, it could not be diagnosed in patients with single clinical episodes of demyelination known as clinically isolated syndromes. New diagnostic criteria from the International Panel of McDonald and colleagues incorporate MRI evidence of dissemination in time and space to allow a diagnosis of MS in patients with clinically isolated syndromes. From clinical and MRI examinations performed prospectively at baseline, 3 months, 1 year, and 3 years of follow-up, the frequency of developing MS was ascertained by the application of both the new McDonald criteria and the Poser criteria for clinically definite MS. The specificity, sensitivity, positive and negative predictive value, and accuracy of the new criteria for the development of clinically definite MS were assessed. At 3 months, 20 of 95 (21%) patients had MS with the McDonald criteria, whereas only 7 of 95 (7%) had developed clinically definite MS. After 1 year, the corresponding figures were 38 of 79 (48%) and 16 of 79 (20%), and after 3 years, they were 29 of 50 (58%) and 19 of 50 (38%). The development of MS with the new MRI criteria after 1 year had a high sensitivity (83%), specificity (83%), positive predicative value (75%), negative predictive value (89%), and accuracy (83%) for clinically definite MS at 3 years. Use of the new McDonald criteria more than doubled the rate of diagnosis of MS within a year of presentation with a clinically isolated syndrome. The high specificity, positive predictive value, and accuracy of the new criteria for clinically definite MS support their clinical relevance.

Adolescent↗

ADC mapping of the human optic nerve: increased resolution, coverage, and reliability with CSF-suppressed ZOOM-EPI.

The mean apparent diffusion coefficient (ADC) of the human optic nerve (ON) has been quantified in vivo, and mean ADC maps are shown along the complete length of the nerve from the globe to the optic chiasm. The mean ADC, over the whole nerve, is shown to be 1058 x 10(-6) mm(2) s(-1) (standard deviation (SD), over nine 3-mm slices, 101x10(-6) mm(2) s(-1); range (833-1178)x10(-6) mm(2) s(-1)). The robustness of the method relies on acquisition of high-resolution coronal images of the ON using the ZOOM-EPI technique, which makes use of a shortened echo train length for increased resolution with decreased susceptibility-induced distortions. Suppression of the cerebrospinal fluid (CSF) and fat signals from tissues that surround the ON also helps successful identification and delineation of the nerve. Averaging of magnitude images is used to compensate for the inherently low signal-to-noise ratio (SNR) of the acquired images; the effects of the Rayleigh distributed noise in such images are allowed for during ADC calculations.

Cerebrospinal Fluid↗

Investigating cervical spinal cord structure using axial diffusion tensor imaging.

This study describes a new technique for Diffusion Tensor Imaging (DTI) that acquires axial (transverse) images of the cervical spinal cord. The DTI images depict axonal fiber orientation, enable quantification of diffusion characteristics along the spinal cord, and have the potential to demonstrate the connectivity of cord white matter tracts. Because of the high sensitivity to motion of diffusion-weighted magnetic resonance imaging and the small size of the spinal cord, a fast imaging method with high in-plane resolution was developed. Images were acquired with a single-shot EPI technique, named ZOOM-EPI (zonally magnified oblique multislice echo planar imaging), which selects localized areas and reduces artefacts caused by susceptibility changes between soft tissue and the adjacent vertebrae. Cardiac gating was used to reduce pulsatile flow artefacts from the surrounding cerebrospinal fluid. Voxel resolution was 1.25 x 1.25 mm(2) in-plane with 5-mm slice thickness. Both the mean diffusivity (MD) and the fractional anisotropy (FA) indices of the cervical spinal cord were measured. The FA index demonstrated high anisotropy of the spinal cord with an average value of 0.61 +/- 0.05 (highest value of 0.66 +/- 0.03 at C3), comparable to white matter tracts in the brain. The diffusivity components parallel and orthogonal to the longitudinal axes of the cord were lambda( parallel) = (1648 +/- 123) x 10(-6) mm(2)s(-1) and lambda( perpendicular) = (570 +/- 47) x 10(-6) mm(2) s(-1), respectively. The high axial resolution allowed preliminary evaluation of fiber connectivity using the fast-marching tractography algorithm, which generated traces of fiber paths consistent with the well-known cord anatomy.

Algorithms↗