Improved Assessment of Longitudinal Spinal Cord Atrophy in Multiple Sclerosis Using a Registration-Based Approach: Relevance for Clinical Studies.

BACKGROUND: Reliable measurements of cervical cord atrophy progression may be useful for monitoring neurodegeneration in multiple sclerosis (MS). PURPOSE: To compare a new, registration-based (Reg) method with two existing methods (active surface [AS] and propagation segmentation [PropSeg]) to measure cord atrophy changes over time in MS. STUDY TYPE: Retrospective. SUBJECTS: Cohort I: Eight healthy controls (HC) and 28 MS patients enrolled at a single institution, and cohort II: 25 HC and 63 MS patients enrolled at three European sites. FIELD STRENGTH/SEQUENCE: 3D T1-weighted gradient echo sequence, acquired at 1.5 T (cohort I) and 3.0 T (cohort II). ASSESSMENT: Percentage cord area changes (PCACs) between baseline and follow-up (cohort I: 2.34 years [interquartile range = 2.00-2.55 years], cohort II: 1.05 years [interquartile range = 1.01-1.18 years]) were evaluated for all subjects using Reg, AS, and PropSeg. Reg included an accurate registration of baseline and follow-up straightened cord images, followed by AS-based optimized cord segmentation. A subset of studies was analyzed twice by two observers. STATISTICAL TESTS: Linear regression models were used to estimate annualized PCAC, and effect sizes expressed as the ratio between the estimated differences and HC error term (P < 0.05). Reproducibility was assessed by linear mixed-effect models. Annualized PCACs were used for sample size calculations (significance: α = 0.05, power: 1 - ß = 0.80). RESULTS: Annualized PCACs and related standard errors (SEs) were lower with Reg than with other methods: PCAC in MS patients at 1.5 T was -1.12% (SE = 0.22) with Reg, -1.32% (SE = 0.30) with AS, and -1.40% (SE = 0.33) with PropSeg, while at 3.0 T PCAC was -0.83% (SE = 0.25) with Reg, -0.92% (SE = 0.32) with AS, and -1.18 (SE = 0.53) with PropSeg. This was reflected in larger effect sizes and lower sample sizes. Intra- and inter-observer agreement range was 0.72-0.91 with AS, and it was >0.96 with Reg. DATA CONCLUSION: The results support the use of the registration method to measure cervical cord atrophy progression in future MS clinical studies. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY STAGE: 2.

Structural connectivity in multiple sclerosis and modeling of disconnection.

BACKGROUND: Multiple sclerosis (MS) is characterized by focal white matter damage, and when the brain is modeled as a network, lesions can be treated as disconnection events. OBJECTIVE: To evaluate whether modeling disconnection caused by lesions helps explain motor and cognitive impairment in MS. METHODS: Pathways connecting 116 cortical regions were reconstructed with magnetic resonance imaging (MRI) tractography from diffusion tensors averaged across healthy controls (HCs); maps of pathways were applied to 227 relapse-onset MS patients and 50 HCs to derive structural connectivity. Then, the likelihood of individual connections passing through lesions was used to model disconnection. Patients were grouped according to clinical phenotype (113 relapsing-remitting multiple sclerosis (RRMS), 69 secondary progressive multiple sclerosis (SPMS), 45 benign MS), and then network metrics were compared between groups (analysis of variance (ANOVA)) and correlated with motor and cognitive scores (linear regression). RESULTS: Global metrics differentiated RRMS from SPMS and benign MS patients, but not benign from SPMS patients. Nodal connectivity strength replicated global results. After disconnection, few nodes were significantly different between benign MS and RRMS patients. Correlations revealed nodes pertinent to motor and cognitive dysfunctions; these became slightly stronger after disconnection. CONCLUSION: Connectivity did not change greatly after modeled disconnection, suggesting that the brain network is robust against damage caused by MS lesions.

Perioperative Cerebral Microbleeds After Adult Cardiac Surgery.

Background and Purpose- Cerebral microbleeds (CMBs) have been observed using magnetic resonance imaging in patients with cardiovascular risk factors, cognitive deterioration, small vessel disease, and dementia. They are a well-known consequence of cerebral amyloid angiopathy, chronic hypertension, and diffuse axonal injury, among other causes. However, the frequency and location of new CMBs postadult cardiac surgery, in association with cognition and perioperative risk factors, have yet to be studied. Methods- Pre- and postsurgery magnetic resonance susceptibility-weighted images and neuropsychological tests were analyzed from a total of 75 patients undergoing cardiac surgery (70 men; mean age, 63±10 years). CMBs were identified by a neuroradiologist blinded to clinical details who independently assessed the presence and location of CMBs using standardized criteria. Results- New CMBs were identified in 76% of patients after cardiac surgery. The majority of new CMBs were located in the frontal lobe (46%) followed by the parietal lobe (15%), cerebellum (13%), occipital lobe (12%), and temporal lobe (8%). Patients with new CMBs typically began with a higher prevalence of preexisting CMBs ( P=0.02). New CMBs were associated with longer cardiopulmonary bypass times ( P=0.003), and there was a borderline association with lower percentage hematocrit ( P=0.04). Logistic regression analysis suggested a ≈2% increase in the odds of acquiring new CMBs during cardiac surgery for every minute of bypass time (odds ratio, 1.02; 95% CI, 1.00-1.05; P=0.04). Postoperative neuropsychological decline was observed in 44% of patients and seemed to be unrelated to new CMBs. Conclusions- New CMBs identified using susceptibility-weighted images were found in 76% of patients who underwent cardiac surgery. CMBs were globally distributed with the highest numbers in the frontal and parietal lobes. Our regression analysis indicated that length of cardiopulmonary bypass time and lowered hematocrit may be significant predictors for new CMBs after cardiac surgery. Clinical Trial Registration- URL: http://www.isrctn.com . Unique identifier: 66022965.

Aortic stiffness in aortic stenosis assessed by cardiovascular MRI: a comparison between bicuspid and tricuspid valves.

OBJECTIVES: To compare aortic size and stiffness parameters on MRI between bicuspid aortic valve (BAV) and tricuspid aortic valve (TAV) patients with aortic stenosis (AS). METHODS: MRI was performed in 174 patients with asymptomatic moderate-severe AS (mean AVAI 0.57 ± 0.14 cm2/m2) and 23 controls on 3T scanners. Valve morphology was available/analysable in 169 patients: 63 BAV (41 type-I, 22 type-II) and 106 TAV. Aortic cross-sectional areas were measured at the level of the pulmonary artery bifurcation. The ascending and descending aorta (AA, DA) distensibility, and pulse wave velocity (PWV) around the aortic arch were calculated. RESULTS: The AA and DA areas were lower in the controls, with no difference in DA distensibility or PWV, but slightly lower AA distensibility than in the patient group. With increasing age, there was a decrease in distensibility and an increase in PWV. After correcting for age, the AA maximum cross-sectional area was higher in bicuspid vs. tricuspid patients (12.97 [11.10, 15.59] vs. 10.06 [8.57, 12.04] cm2, p < 0.001), but there were no significant differences in AA distensibility (p = 0.099), DA distensibility (p = 0.498) or PWV (p = 0.235). Patients with BAV type-II valves demonstrated a significantly higher AA distensibility and lower PWV compared to type-I, despite a trend towards higher AA area. CONCLUSIONS: In patients with significant AS, BAV patients do not have increased aortic stiffness compared to those with TAV despite increased ascending aortic dimensions. Those with type-II BAV have less aortic stiffness despite greater dimensions. These results demonstrate a dissociation between aortic dilatation and stiffness and suggest that altered flow patterns may play a role. KEY POINTS: • Both cellular abnormalities secondary to genetic differences and abnormal flow patterns have been implicated in the pathophysiology of aortic dilatation and increased vascular complications associated with bicuspid aortic valves (BAV). • We demonstrate an increased ascending aortic size in patients with BAV and moderate to severe AS compared to TAV and controls, but no difference in aortic stiffness parameters, therefore suggesting a dissociation between dilatation and stiffness. • Sub-group analysis showed greater aortic size but lower stiffness parameters in those with BAV type-II AS compared to BAV type-I.

Measurement of Whole-Brain and Gray Matter Atrophy in Multiple Sclerosis: Assessment with MR Imaging.

Purpose To compare available methods for whole-brain and gray matter (GM) atrophy estimation in multiple sclerosis (MS) in terms of repeatability (same magnetic resonance [MR] imaging unit) and reproducibility (different system/field strength) for their potential clinical applications. Materials and Methods The softwares ANTs-v1.9, CIVET-v2.1, FSL-SIENAX/SIENA-5.0.1, Icometrix-MSmetrix-1.7, and SPM-v12 were compared. This retrospective study, performed between March 2015 and March 2017, collected data from (a) eight simulated MR images and longitudinal data (2 weeks) from 10 healthy control subjects to assess the cross-sectional and longitudinal accuracy of atrophy measures, (b) test-retest MR images in 29 patients with MS acquired within the same day at different imaging unit field strengths/manufacturers to evaluate precision, and (c) longitudinal data (1 year) in 24 patients with MS for the agreement between methods. Tissue segmentation, image registration, and white matter (WM) lesion filling were also evaluated. Multiple paired t tests were used for comparisons. Results High values of accuracy (0.87-0.97) for whole-brain and GM volumes were found, with the lowest values for MSmetrix. ANTs showed the lowest mean error (0.02%) for whole-brain atrophy in healthy control subjects, with a coefficient of variation of 0.5%. SPM showed the smallest mean error (0.07%) and coefficient of variation (0.08%) for GM atrophy. Globally, good repeatability (P > .05) but poor reproducibility (P < .05) were found for all methods. WM lesion filling technique mainly affected ANTs, MSmetrix, and SPM results (P < .05). Conclusion From this comparison, it would be possible to select a software for atrophy measurement, depending on the requirements of the application (research center, clinical trial) and its goal (accuracy and repeatability or reproducibility). An improved reproducibility is required for clinical application. © RSNA, 2018 Online supplemental material is available for this article.

Characterisation of cardiomyopathy by cardiac and aortic magnetic resonance in patients new to hemodialysis.

OBJECTIVES: Cardiomyopathy is a key factor in accelerated cardiovascular mortality in haemodialysis (HD) patients. We aimed to phenotype cardiac and vascular dysfunction by tagged cardiovascular magnetic resonance (CMR) imaging in patients recently commencing HD. METHODS: Fifty-four HD patients and 29 age and sex-matched controls without kidney disease were studied. Left ventricular (LV) mass, volumes, ejection fraction (EF), concentric remodelling, peak-systolic circumferential strain (PSS), peak diastolic strain rate (PDSR), LV dyssynchrony, aortic distensibility and aortic pulse wave velocity were determined. RESULTS: Global systolic function was reduced (EF 51 ± 10%, HD versus 59 ± 5%, controls, p < 0.001; PSS 15.9 ± 3.7% versus 19.5 ± 3.3%, p < 0.001). Diastolic function was decreased (PDSR 1.07 ± 0.33s(-1) versus 1.31 ± 0.38s(-1), p = 0.003). LV mass index was increased (63[54,79]g/m(2) versus 46[42,53]g/m(2), p < 0.001). Anteroseptal reductions in PSS were apparent. These abnormalities remained prevalent in the subset of HD patients with preserved EF >50% (n = 35) and the subset of HD patients without diabetes (n = 40). LV dyssynchrony was inversely correlated to diastolic function, EF and aortic distensibility. Diastolic function was inversely correlated to LV dyssynchrony, concentric remodelling, age and aortic pulse wave velocity. CONCLUSION: Patients new to HD have multiple cardiac and aortic abnormalities as characterised by tagged CMR. Cardio-protective interventions are required from initiation of therapy. KEY POINTS: • First characterisation of cardiomyopathy by tagged CMR in haemodialysis patients. • Diastolic function was correlated to LV dyssynchrony, concentric remodelling and aortic PWV. • Reductions in strain localised to the septal and anterior wall. • Bioimpedance measures were unrelated to LV strain, suggesting volume-independent pathogenetic mechanisms. • Multiple abnormalities persisted in the HD patient subset with preserved EF or without diabetes.

Impact of perioperative infarcts after cardiac surgery.

BACKGROUND AND PURPOSE: Brain injury after cardiac surgery is a serious concern for patients and their families. The purpose of this study was to use 3-T fluid attenuated inversion recovery MRI to characterize new and preexisting cerebral ischemic lesions in patients undergoing cardiac surgery and to test whether the accumulation of new ischemic lesions adversely affects cognition. METHODS: Digital comparison of before and after fluid attenuated inversion recovery MRI images was performed for 77 cardiac surgery patients. The burden of preexisting versus new ischemic lesions was quantified and compared with the results of baseline and postoperative neuropsychological testing. RESULTS: After surgery, new lesions were identified in 31% of patients, averaging 0.5 lesions per patient (67 mm(3) [0.004%] of brain tissue). Patients with preexisting lesions were 10× more likely to receive new lesions after surgery than patients without preexisting lesions. Preexisting ischemic lesions were observed in 64% of patients, averaging 19.4 lesions (1542 mm(3) [0.1%] of brain tissue). New lesions in the left hemisphere were significantly smaller and more numerous (29 lesions; median volume, 44 mm(3); volume range, 5-404 mm(3)) than those on the right (10 lesions; median volume, 128 mm(3); volume range, 13-1383 mm(3)), which is consistent with a cardioembolic source of particulate emboli. Overall, the incidence of postoperative cognitive decline was 46% and was independent of whether new lesions were present. CONCLUSIONS: New lesions after cardiac surgery added a small (≈4%) contribution to the burden of preexisting cerebrovascular disease and did not seem to affect cognitive function. CLINICAL TRIAL REGISTRATION URL: http://public.ukcrn.org.uk. Unique identifier: UKCRN ID: 11702.

Intertechnique agreement and interstudy reproducibility of strain and diastolic strain rate at 1.5 and 3 Tesla: a comparison of feature-tracking and tagging in patients with aortic stenosis.

PURPOSE: To determine the interstudy reproducibility of myocardial strain and peak early-diastolic strain rate (PEDSR) measurement on cardiovascular magnetic resonance imaging (MRI) assessed with feature tracking (FT) and tagging, in patients with aortic stenosis (AS). MATERIALS AND METHODS: Cardiac MRI was performed twice (1-14 days apart) in 18 patients (8 at 1.5 Tesla [T], 10 at 3T) with moderate-severe AS. Circumferential peak systolic strain (PSS) and PEDSR were measured in all patients. Longitudinal PSS and PEDSR were assessed using FT in all patients, and tagging in the 3T sub-group. RESULTS: PSS was higher with FT than tagging (21.0 ± 1.9% versus 17.0 ± 3.4% at 1.5T, 21.4 ± 4.0% versus 17.7 ± 3.0% at 3T, P < 0.05), as was PEDSR (1.3 ± 0.3 s(-1) versus 1.0 ± 0.3 s(-1) , P = 0.10 at 1.5T and 1.3 ± 0.4 s(-1) versus 0.8 ± 0.3 s(-1) , P < 0.05 at 3T). The reproducibility of PSS was excellent with FT (coefficient of variation [CoV] 9-10%) and good with tagging at 1.5T (13-19%). Reproducibility of circumferential PEDSR was best at 1.5T when only basal/mid slices were included (CoV 12%), but moderate to poor at 3T (29-35%). Reproducibility of longitudinal strain was good with FT (10-16%) but moderate for PEDSR (∼30%). CONCLUSION: In patients with AS, FT consistently produces higher values compared with tagging. The interstudy reproducibility of PSS is excellent with FT and good with tagging. The reproducibility of circumferential PEDSR at 1.5T is good when only basal and mid slices are used.

T1- vs. T2-based MRI measures of spinal cord volume in healthy subjects and patients with multiple sclerosis.

BACKGROUND: The reliable and efficient measurement of spinal cord atrophy is of growing interest in monitoring disease progression in multiple sclerosis (MS). METHODS: We compared T1- and T2-weighted MRI for measuring cervical spinal cord volume in 31 patients with MS and 18 age-matched controls (NC) from T1-weighted gradient recalled echo and T2-weighted fast spin-echo 1.5 T axial acquisitions. The two sequences were matched on slice thickness, signal averages and voxel size. An active surface software tool determined the normalized mean cervical cord cross-sectional area. RESULTS: T1-derived cord areas were higher than T2 areas in the whole cohort (estimated mean difference = 7.03 mm(2) (8.89%); 95% Confidence Interval (CI): 5.91, 8.14; p < 0.0001) and in both groups separately. There were trends for lower spinal cord areas in MS vs. NC with both sequences. For the T1 cord area, the mean difference was 3.7 mm(2) (4.55%) (95% CI: -1.36, 8.78; p = 0.15). For the T2 cord area, the difference was larger [mean difference 4.9 mm(2) (6.52%) (95% CI: -0.83, 10.67); p = 0.091]. The T1 and T2 cord areas showed similar weak to moderate correlations with measures of clinical status and T2 spinal cord lesion volume in the MS group. Superficial spinal cord T2 lesions had no apparent confounding effect on the outlining tool. The mean intra-rater and inter-rater coefficients of variation ranged from 0.27 to 0.91% for T1- and 0.66 to 0.99% for T2-derived cord areas. CONCLUSION: T2-weighted images may prove efficient for measuring cervical spinal cord atrophy in MS, with the added advantage of lesion detectability.

Intranetwork and internetwork functional connectivity abnormalities in pediatric multiple sclerosis.

Active motor functional magnetic resonance imaging (fMRI) studies have shown that pediatric multiple sclerosis (MS) patients have a strictly lateralized pattern of activations and a preserved functional connectivity (FC) within the motor system when compared to age-matched healthy controls. However, it is still not clear whether a preserved FC in pediatric MS is present only in the motor system, or involves other relevant functional system. Resting-state (RS) fMRI is a valuable tool for an unbiased investigation of FC abnormalities of multiple networks. This study explored abnormalities of RS FC within and between large-scale neuronal networks from 44 pediatric MS patients and 27 controls and their correlation with clinical, neuropsychological, and conventional MRI measures. Compared to controls, pediatric MS patients had a decreased FC of several regions of the sensorimotor, secondary visual, default-mode (DMN), executive control, and bilateral working memory (WMN) networks. They also experienced an increased FC in the right medial frontal gyrus of the attention network, which was correlated with T2 lesion volume. Cognitively impaired patients had decreased RS FC of the right precuneus of the left WMN. An increased FC between the sensorimotor network and the DMN, and between the L WMN and the attention network as well as a decreased FC between L WMN and the DMN were also found. A distributed pattern of FC abnormalities within large-scale neuronal networks occurs in pediatric MS patients, contributes to their cognitive status, and is partially driven by focal white matter lesions. Internetwork connectivity is relatively preserved in these patients.

Ultra-high-field MR imaging in multiple sclerosis.

In multiple sclerosis (MS), MRI is the most important paraclinical tool used to inform diagnosis and for monitoring disease evolution, either natural or modified by treatment. The increased availability of ultra-high-field magnets (7 Tesla or higher) gives rise to questions about the main benefits of and challenges for their use in patients with MS. The main advantages of ultra-high-field MRI are the improved signal-to-noise ratio, greater chemical shift dispersion, and improved contrast due to magnetic susceptibility variations, which lead to increased sensitivity to the heterogeneous pathological substrates of the disease. At present, ultra-high-field MRI is mainly used to improve our understanding of MS pathogenesis. This review discusses the main achievements that have so far come from the use of these scanners, which are: better visualisation of white matter lesions and their morphological characteristics; an improvement in the ability to visualise grey matter lesions and their exact location; the quantification of 'novel' metabolites which may have a role in axonal degeneration; and greater sensitivity to iron accumulation. The application of ultra-high-field systems in standard clinical practice is still some way off since their role in the diagnostic work-up of patients at presentation with clinically isolated syndromes, or in monitoring disease progression or treatment response in patients with definite MS, needs to be established. Additional challenges remain in the development of morphological, quantitative and functional imaging methods at these field strengths, techniques which may ultimately lead to novel biomarkers for monitoring disease evolution and treatment response.

Dynamic contrast-enhanced MRI parameters as biomarkers for the effect of vatalanib in patients with non-small-cell lung cancer.

AIMS: To assess the utility of dynamic contrast-enhanced MRI parameters in the demonstration of early antiangiogenic effects and as prognostic biomarkers in second-line treatment of advanced-stage non-small-cell lung cancer with vatalanib. PATIENTS & METHODS: The transfer constant (K(trans)) and the initial area under the contrast concentration-time curve at 60 s (AUC60) were assessed in 46 patients. Changes were compared with response evaluation from computed tomography imaging and Response Evaluation Criteria In Solid Tumors guidelines. RESULTS: Statistically significant mean reductions in K(trans) (38.4%; p < 0.0001) and AUC60 (24.9%; p < 0.0001) were found at day 2. After 12 weeks, 16 patients (35%) demonstrated stable disease and 30 (65%) demonstrated progressive disease. No statistically significant differences in day 2 K(trans) and AUC60 reductions between stable disease and progressive disease patients were found. CONCLUSION: Dynamic contrast-enhanced MRI can demonstrate a statistically significant reduction in vascular parameters of non-small-cell lung cancer, but does not predict patient outcome.

Regional cervical cord atrophy and disability in multiple sclerosis: a voxel-based analysis.

PURPOSE: To (a) apply an active surface method to map the regional distribution of cord atrophy across levels and sectors in a relatively large group of patients with multiple sclerosis (MS), (b) compare the anatomic location of cord atrophy between patients with relapsing-remitting (RR) MS and those with secondary progressive (SP) MS, and (c) assess correlations between atrophy and disability. MATERIALS AND METHODS: This study was approved by the local ethical committee, and written informed consent was obtained from each participant. High-spatial-resolution magnetic resonance (MR) images of the cervical cord were acquired from 45 patients with RR MS, 26 patients with SP MS, and 67 age-matched healthy control subjects. The active surface method segmented the cord surface from C1 to C7 and created output images reformatted in planes perpendicular to the estimated cord center line. These unfolded cervical cord images were coregistered into a common standard space, and smoothed cord binary masks were used as input images for spatial statistics. Voxel-wise between-group comparisons and the correlation between regional cord atrophy versus clinical and conventional MR imaging variables were assessed with software. RESULTS: Compared with control subjects, patients with RR MS showed localized clusters of atrophy in the posterior cord. Conversely, patients with SP MS showed a widespread pattern of cord atrophy, predominantly in the posterior and lateral cord columns. In patients with MS, cervical cord atrophy was correlated with clinical disability, disease duration, and, to a lesser extent, conventional MR imaging measures of brain injury. No correlation was found between cord atrophy and the presence of focal cord lesions. CONCLUSION: Voxel-wise assessment of the regional distribution of damage in the cervical cord is feasible and might improve our understanding of the mechanisms related to the development of irreversible clinical disability in MS.

Cortical abnormalities in patients with migraine: a surface-based analysis.

PURPOSE: To explore the patterns of cortical thickness and cortical surface area abnormalities in patients with migraine (with the expectation of seeing reduced cortical thickness and surface area in regions subserving nociception and increased cortical thickness and surface area in regions involved in migraine pathogenesis) and to assess their correlation with clinical and radiologic manifestations of the disease. MATERIALS AND METHODS: Approval of the local ethical committee was obtained, as well as written informed consent from each participant. T2-weighted and three-dimensional T1-weighted magnetic resonance images of the brain were acquired in 63 migraineurs and 18 matched healthy control subjects. Cortical thickness and cortical surface area were estimated. By using a general linear model approach, a vertex-by-vertex statistical analysis (P < .01) was used to assess between-group comparisons (migraineurs vs control subjects, the aura effect, the effect of white matter hyperintensities [WMHs]) and the correlations between cortical thickness and surface area measurements and patients' clinical and radiologic characteristics. RESULTS: Compared with control subjects, patients with migraine showed reduced cortical thickness and surface area in regions subserving pain processing (P < .01). These two metrics were increased in regions involved in executive functions and visual motion processing (P < .01). The anatomic overlap of cortical thickness and cortical surface area abnormalities was only minimal, with cortical surface area abnormalities being more pronounced and more widely distributed than cortical thickness abnormalities. Cortical thickness and surface area abnormalities were related to aura and WMHs (P < .01) but not to disease duration and attack frequency. CONCLUSION: Cortical abnormalities occur in migraineurs and may represent the results of a balance between an intrinsic predisposition, as suggested by cortical surface area abnormalities, and disease-related processes, as indicated by cortical thickness abnormalities.

Voxel-wise mapping of cervical cord damage in multiple sclerosis patients with different clinical phenotypes.

OBJECTIVE: To apply voxel-based methods to map the regional distribution of atrophy and T2 hyperintense lesions in the cervical cord of multiple sclerosis (MS) patients with different clinical phenotypes. METHODS: Brain and cervical cord 3D T1-weighted and T2-weighted scans were acquired from 31 healthy controls (HC) and 77 MS patients (15 clinically isolated syndromes (CIS), 15 relapsing-remitting (RR), 19 benign (B), 15 primary progressive (PP) and 13 secondary progressive (SP) MS). Hyperintense cord lesions were outlined on T2-weighted scans. The T2- and 3D T1-weighted cord images were then analysed using an active surface method which created output images reformatted in planes perpendicular to the estimated cord centre line. These unfolded cervical cord images were co-registered into a common space; then smoothed binary cord masks and lesion masks underwent spatial statistic analysis (SPM8). RESULTS: No cord atrophy was found in CIS patients versus HC, while PPMS had significant cord atrophy. Clusters of cord atrophy were found in BMS versus RRMS, and in SPMS versus RRMS, BMS and PPMS patients, mainly involving the posterior and lateral cord segments. Cord lesion probability maps showed a significantly greater likelihood of abnormalities in RRMS, PPMS and SPMS than in CIS and BMS patients. The spatial distributions of cord atrophy and cord lesions were not correlated. In progressive MS, regional cord atrophy was correlated with clinical disability and impairment in the pyramidal system. CONCLUSIONS: Voxel-based assessment of cervical cord damage is feasible and may contribute to a better characterisation of the clinical heterogeneity of MS patients.

Does stroke subtype and measurement technique influence estimation of cerebral autoregulation in acute ischaemic stroke?

BACKGROUND: It is known that dynamic cerebral autoregulation (dCA) is acutely impaired following ischaemic stroke (IS). However, the influence of stroke subtype, the affected (AF) and unaffected (UA) hemispheres, and the effects of a methodological approach on dCA estimates in stroke are all inconclusive. Therefore, we studied cortical and subcortical acute IS (AIS) patients to test the primary hypotheses that (1) dCA is impaired in stroke subtypes when compared to controls, (2) dCA impairment is more pronounced in the AF compared with the UA hemisphere, and (3) similar results are obtained with both spontaneous blood pressure (BP) fluctuation techniques, and sudden induced BP changes by thigh cuff deflation. METHODS: We assessed the dCA values in AIS patients and in healthy controls (n = 10). The AIS patient group consisted of anterior circulation cortical (n = 11) and subcortical (n = 11) strokes within 48 h of symptom onset. Cerebral blood flow velocity was measured using transcranial Doppler ultrasound, and BP measurements were recorded before, during and after the release of bilateral thigh cuffs in 10 controls (7 males) of a mean age of 59 ±15 years (range 31-75), 11 cortical strokes (7 males) of a mean of age 65 ± 19 years (range 25-88) and 11 subcortical strokes (7 males) of a mean age of 60 ± 18 years (range 39-85). Autoregulation index (ARI) estimates, calculated using spontaneous fluctuations and thigh cuff manoeuvre, were derived. Differences in ARI (Tiecks' model) were tested with repeated-measures ANOVA. RESULTS: A total of 22 patients were included, comprising 11 subcortical (lacunar clinical syndrome) and 11 cortical strokes (total anterior circulation stroke/partial anterior circulation syndrome). Of the 10 control subjects, 1 later withdrew because of intolerance to the thigh cuffs. Similar ARI estimates were obtained in both groups, whether assessed from spontaneous fluctuations or thigh cuff measurements (p = 0.37). ARI differences were not significantly different between hemispheres for both control and stroke populations. ARI was significantly impaired in AIS patients compared to age-, sex- and BP-matched control subjects, with a greater impairment of dCA observed in cortical IS. CONCLUSIONS: The results of this study suggest that both spontaneous fluctuations and thigh cuff deflation techniques are able to provide reliable estimates of ARI, with the estimates from both spontaneous fluctuations and thigh cuff deflation techniques being in keeping with those reported elsewhere in the literature. dCA was impaired following AIS compared to controls when stroke subtype was considered. Importantly, no differences were observed between UA and AF. This has implications for the assessment of CA after stroke and reinforces the need to define a 'gold standard' test for the investigation of CA.

Dynamic variations in the ultrasound greyscale median of carotid artery plaques.

BACKGROUND: Several studies have found that the ultrasound greyscale median (GSM) of carotid artery plaques may be useful for predicting the risk of cerebrovascular events. However, measurements of GSM are typically performed on still ultrasound images ignoring any variations that may be observed on a frame-by-frame basis. The aim of this study was to establish the existence and investigate the nature and extent of these variations. METHODS: Employing a novel method that enabled plaque boundaries to be tracked semi-automatically, variations in the plaque GSM and observed cross-sectional area were measured for 27 carotid artery plaques (19 consecutive patients, stenosis range 10%-80%) over image sequences of up to 10 seconds in length acquired with a mean frame rate of 32 frames per second. RESULTS: Our results showed a mean inter-frame coefficient of variation (CV) of 5.2% (s.d. 2.5%) for GSM and 4.2% (s.d. 2.9%) for the plaque area. Thirteen of the 27 plaques (48%) exhibited CV in GSM greater than 5% whereas only six plaques (22%) had CV in plaque area of greater than 5%. There was no significant correlation between the CV of GSM and plaque area. CONCLUSIONS: Inter-frame variations in the plaque GSM such as those found in this study have implications on the reproducibility of GSM measurements and their clinical utility. Studies assessing the GSM of carotid artery plaques should consider these variations.

Quantitative assessment of carotid plaque surface irregularities and correlation to cerebrovascular symptoms.

BACKGROUND: The purpose of this study was to determine whether surface irregularities measured from ultrasound images of carotid artery plaques and quantified using a novel method, correlate with the presence of ipsilateral hemispheric cerebrovascular symptoms. METHODS: A plaque surface irregularity index (SII) was measured in 47 carotid artery plaques (32 subjects, stenosis range 10% -95%, 49% symptomatic) using ultrasound image sequences spanning several cardiac cycles. The differences in the distribution of SII in plaques with ipsilateral hemispheric symptoms versus those without symptoms and the correlation between the SII of plaques and the degrees of stenosis of the corresponding arteries were assessed. Diagnostic performance of plaque SII was evaluated on its own and in combination with the degree of stenosis. RESULTS: The mean SII was significantly greater for plaques with ipsilateral hemispheric symptoms (1.89 radians/mm) than for asymptomatic plaques (1.67 radians/mm, p = 0.03). There was no statistically significant association between the SII and the degree of stenosis (p = 0.30). SII predicted the presence of cerebrovascular symptoms with an accuracy of 66% (sensitivity 65%, specificity 67%) on its own and with an accuracy of 83% (sensitivity 96%, specificity 71%) in combination with the degree of stenosis. CONCLUSIONS: Quantitative assessment of carotid plaque surface irregularities using a novel SII parameter correlates with the presence ipsilateral hemispheric cerebrovascular symptoms and may increase diagnostic performance beyond that provided by the degree of stenosis.

Wall motion in the stenotic carotid artery: association with greyscale plaque characteristics, the degree of stenosis and cerebrovascular symptoms.

BACKGROUND: Systolic dilation of the atherosclerotic carotid artery depends on several factors including arterial compliance and the haemodynamic environment. The purpose of this study was to quantify wall motion in stenotic carotid arteries and investigate any associations with the ultrasound greyscale plaque characteristics, the degree of stenosis, and the presence of cerebrovascular symptoms. METHODS: Variations in the lumen diameters of 61 stenotic carotid arteries (stenosis range 10%-95%) from 47 patients were measured before the proximal shoulder of the atherosclerotic plaque using ultrasound image sequences over several cardiac cycles. Absolute and percentage diameter changes from diastole to systole were calculated and their relationship to the degree of stenosis, greyscale plaque characteristics, and the presence of ipsilateral hemispheric symptoms were studied. RESULTS: The mean absolute diameter change from diastole to systole was 0.45 mm (s.d. 0.17), and the mean percentage diameter change was 6.9% (s.d. 3.1%). Absolute and percentage diameter changes did not have a statistically significant relationship to the degree of stenosis, greyscale plaque characteristics, or the presence of ipsilateral hemispheric symptoms (p > 0.05). Parameters significantly correlated with the presence of symptoms were the degree of stenosis (p = 0.01), plaque greyscale median (p = 0.02) and the plaque surface irregularity index (p = 0.02). CONCLUSIONS: Our study confirmed the degree of stenosis, plaque greyscale median and our surface irregularity index were significant predictors of symptoms, but found no significant correlation between diameter changes of stenosed carotid arteries and the presence of ipsilateral hemispheric symptoms.

Brain tissue motion in acute hemorrhagic stroke using amplified MRI (aMRI).

Brain tissue pulsates with each cardiac cycle, however the effect of disease on this natural motion is still unclear. Current literature mainly focuses on healthy brain tissue, with only limited studies looking at disease states such as Chiari malformation and acute ischemic stroke. This case report advances on recent literature by describing the case of a patient with an acute intracerebral hemorrhage and demonstrating an amplified MRI cine of the brain's motion. A clearer understanding of the effects of disease on brain motion may guide clinical application of pulsation measurement.