Priorities for Advancements in Neuroimaging in the Diagnostic Workup of Acute Stroke.

STAIR XII (12th Stroke Treatment Academy Industry Roundtable) included a workshop to discuss the priorities for advancements in neuroimaging in the diagnostic workup of acute ischemic stroke. The workshop brought together representatives from academia, industry, and government. The participants identified 10 critical areas of priority for the advancement of acute stroke imaging. These include enhancing imaging capabilities at primary and comprehensive stroke centers, refining the analysis and characterization of clots, establishing imaging criteria that can predict the response to reperfusion, optimizing the Thrombolysis in Cerebral Infarction scale, predicting first-pass reperfusion outcomes, improving imaging techniques post-reperfusion therapy, detecting early ischemia on noncontrast computed tomography, enhancing cone beam computed tomography, advancing mobile stroke units, and leveraging high-resolution vessel wall imaging to gain deeper insights into pathology. Imaging in acute ischemic stroke treatment has advanced significantly, but important challenges remain that need to be addressed. A combined effort from academic investigators, industry, and regulators is needed to improve imaging technologies and, ultimately, patient outcomes.

Head down tilt 15° to preserve salvageable brain tissue in acute ischemic stroke: A pre-clinical pooled analysis, with focus on cerebral hemodynamics.

Neurological outcome after ischemic stroke depends on residual salvageable brain tissue at the time of recanalization. Head down tilt 15° (HDT15) was proven effective in reducing infarct size and improving functional outcome in rats with transient middle cerebral artery occlusion (t-MCAO) by increasing cerebral perfusion within the ischemic penumbra. In this pooled analysis, individual animal-level data from three experimental series were combined in a study population of 104 t-MCAO rats (45 in HDT15 group and 59 in flat position group). Co-primary outcomes were infarct size and functional outcome at 24 h in both groups. The secondary outcome was hemodynamic change induced by HDT15 in ischemic and non-ischemic hemispheres in a subgroup of animals. Infarct size at 24 h was smaller in HDT15 group than in flat position group (absolute mean difference 31.69 mm3 , 95% CI 9.1-54.2, Cohen's d 0.56, p = 0.006). Functional outcome at 24 h was better in HDT15 group than in flat position group (median [IQR]: 13[10-16] vs. 11), with a shift in the distribution of the neurobehavioural scores in favour of HDT15. Mean cerebral perfusion in the ischemic hemisphere was higher during HDT15 than before its application (Perfusion Unit [P.U.], mean ± SD: 52.5 ± 19.52 P.U. vs. 41.25 ± 14.54 P.U., mean of differences 13.36, 95% CI 7.5-19.18, p = 0.0002). Mean cerebral perfusion in the non-ischemic hemisphere before and during HDT15 was unchanged (P.U., mean ± SD: 94.1 ± 33.8 P.U. vs. 100.25 ± 25.34 P.U., mean of differences 3.95, 95%, CI -1.9 to 9.6, p = 0.1576). This study confirmed that HDT15 improves the outcome in t-MCAO rats by promoting cerebral perfusion in the ischemic territory, without disrupting hemodynamics in non-ischemic areas.

Comorbidities in patients with epilepsy: Frequency, mechanisms and effects on long-term outcome.

OBJECTIVE: To assess frequency, types, and mechanisms of comorbidities in people with epilepsy and verify their association with disease features and outcome. METHODS: This cohort study was performed in 13 Italian epilepsy centers with nationwide distribution and accurate records. Eligible patients were children and adults diagnosed before December 31, 2005, and followed for a minimum of 10 years. Two pairs of raters independently reviewed patients' records and classified each comorbidity. In case of disagreement, a third reviewer made the final decision. Comorbidities were classified according to type (organ/system) and underlying mechanism (causal, shared risk factors, chance association). Comorbidity types and mechanisms were described in the entire sample and according to epilepsy prognostic patterns (sustained remission, relapsing-remitting course, no remission). RESULTS: Of 1006 included patients, 266 (26.4%) had at least one comorbidity. The most common were developmental/perinatal (7.5% of cases), psychiatric (6.2%), cardiovascular (5.3%), and endocrine/metabolic (3.8%). Among 408 reported comorbidities, the underlying mechanisms were, in decreasing order, chance association (42.2%), shared risk factors (31.1%), and causal (26.7%). Psychiatric diseases were present in 13.3% of patients with no remission, 5.9% of patients with relapsing-remitting course, and 4.8% of patients with sustained remission (p = .016). The corresponding numbers for endocrine/metabolic diseases were respectively, 9.6%, 3.4%, and 2.9% (p = .013); for respiratory diseases were 3.6%, .3%, and .3% (p = .001), and for urogenital diseases were 3.6%, .7%, and 1.6% (p = .048). The association of endocrine/metabolic, psychiatric, and respiratory comorbidities with epilepsy prognosis was confirmed by multivariable analysis adjusted for the main demographic and clinical variables, with patients with these comorbidities showing a lower probability of achieving remission. SIGNIFICANCE: Comorbidities in epilepsy are not uncommon and reflect differing underlying mechanisms. Psychiatric, endocrine/metabolic, and respiratory disorders are associated with a worse long-term epileptological outcome.

Discontinuation of antiseizure medications in seizure-free patients with long-term follow-up: Patients' profile, seizure recurrence, and risk factors.

OBJECTIVE: To compare withdrawal of antiseizure medications (ASM) to continued treatment in newly diagnosed individuals achieving seizure freedom, and assess the risk of relapse and factors associated with relapse. METHODS: This is a multicenter retrospective cohort study with long-term follow-up. Patients with newly diagnosed epilepsy were identified from the medical records of 13 Italian epilepsy centers and followed up until the most recent visit or death. Seizure-free patients discontinuing treatment were compared to patients who maintained treatment for baseline characteristics. Treatment was stopped upon clinical judgment. The probability of relapse was calculated with the Kaplan-Meier method. Demographic, clinical, and instrumental variables associated with relapse were assessed with Cox proportional hazards models. RESULTS: One thousand and six patients aged 1 month to 72 years at diagnosis were enrolled and followed up for 17,892 person-years (median follow-up, 9.9 years). Three hundred and twenty patients (31.8%) underwent one or more treatment discontinuations. Factors associated with ASM withdrawal were younger age at remission and normal psychiatric examination. The probability of relapse after the first withdrawal was 16% at six months, 24% at 12 months, and 36%, 45%, and 53% at three, five, and ten years, respectively. The probability of remission after the first relapse was 59% at one month, 67%, 72, and 76% at three, six, and 12 months, respectively. Variables associated with relapse were age 14+ years, structural etiology, abnormal neuroimaging, ASM initiation after a single seizure, and symptomatic/cryptogenic epilepsy. CONCLUSIONS: About one half of seizure-free patients stopping ASM relapse in 10 years. However, the possibility of remission after relapse is high, particularly in children and patients with idiopathic/cryptogenic epilepsy. Treatment deprescription might be encouraged at least in these patients.

Prospects for investigating brain oxygenation in acute stroke: Experience with a non-contrast quantitative BOLD based approach.

Metabolic markers of baseline brain oxygenation and tissue perfusion have an important role to play in the early identification of ischaemic tissue in acute stroke. Although well established MRI techniques exist for mapping brain perfusion, quantitative imaging of brain oxygenation is poorly served. Streamlined-qBOLD (sqBOLD) is a recently developed technique for mapping oxygenation that is well suited to the challenge of investigating acute stroke. In this study a noninvasive serial imaging protocol was implemented, incorporating sqBOLD and arterial spin labelling to map blood oxygenation and perfusion, respectively. The utility of these parameters was investigated using imaging based definitions of tissue outcome (ischaemic core, infarct growth and contralateral tissue). Voxel wise analysis revealed significant differences between all tissue outcomes using pairwise comparisons for the transverse reversible relaxation rate (R 2 '), deoxygenated blood volume (DBV) and deoxyghaemoglobin concentration ([dHb]; p < 0.01 in all cases). At the patient level (n = 9), a significant difference was observed for [dHb] between ischaemic core and contralateral tissue. Furthermore, serial analysis at the patient level (n = 6) revealed significant changes in R 2 ' between the presentation and 1 week scans for both ischaemic core (p < 0.01) and infarct growth (p < 0.05). In conclusion, this study presents evidence supporting the potential of sqBOLD for imaging oxygenation in stroke.

Prognostic patterns and predictors in epilepsy: a multicentre study (PRO-LONG).

OBJECTIVES: To describe the long-term prognosis of epilepsy and prognostic patterns in a large cohort of newly diagnosed patients and identify prognostic factors. METHODS: Study participants were 13 Italian epilepsy centres with accessible records dating back to 2005 or earlier, complete data on seizure outcome and treatments, precise epilepsy diagnosis, and follow-up of at least 10 years. Records were examined by trained neurology residents for demographics, seizure characteristics, neurological signs, psychiatric comorbidity, first electroencephalogram (EEG) and MRI/CT, epilepsy type and aetiology, antiepileptic drugs (AEDs), and 1-year, 2-year, 5-year and 10-year seizure remissions. Five predefined prognostic patterns were identified: early remission, late remission, relapsing-remitting course, worsening course and no remission. Prognostic factors were assessed using multinomial logistic regression models. RESULTS: 1006 children and adults were followed for 17 892 person-years (median 16 years; range 10-57). During follow-up, 923 patients (91.7%) experienced 1-year remission. 2-year, 5-year and 10-year remissions were present in 89.5%, 77.1% and 44.4% of cases. 5-year remission was associated with one to two seizures at diagnosis, generalised epilepsy, no psychiatric comorbidity, and treatment with one or two AEDs during follow-up. 10-year remission was associated with one or two AEDs. The most common prognostic pattern was relapsing-remitting (52.2%), followed by early remission (24.5%). 8.3% of cases experienced no remission. Predictors of a relapsing-remitting course were <6 seizures at diagnosis, (presumed) genetic aetiology and no psychiatric comorbidity. CONCLUSIONS: Few seizures at diagnosis, generalised epilepsy and no psychiatric comorbidity predict early or late seizure freedom in epilepsy. Achieving remission at any time after the diagnosis does not exclude further relapses.

Neurological outcome of postanoxic refractory status epilepticus after aggressive treatment.

Refractory status epilepticus (RSE) occurs in up to 30% of patients following resuscitation after cardiac arrest. The impact of aggressive treatment of postanoxic RSE on long-term neurological outcome remains uncertain. We investigated neurological outcome of cardiac arrest patients with RSE treated with a standardized aggressive protocol with antiepileptic drugs and anesthetics, compared with patients with other electroencephalographic (EEG) patterns. A prospective cohort of 166 consecutive patients with cardiac arrest in coma was stratified according to four independent EEG patterns (benign; RSE; generalized periodic discharges (GPDs); malignant nonepileptiform) and multimodal prognostic indicators. Primary outcomes were survival and cerebral performance category (CPC) at 6 months. Refractory status epilepticus occurred in 36 patients (21.7%) and was treated with an aggressive standardized protocol as long as multimodal prognostic indicators were not unfavorable. Refractory status epilepticus started after 3 ±â€¯2.3 days after cardiac arrest and lasted 4.7 ±â€¯4.3 days. A benign electroencephalographic patterns was recorded in 76 patients (45.8%), a periodic pattern (GPDs) in 13 patients (7.8%), and a malignant nonepileptiform EEG pattern in 41 patients (24.7%). The four EEG patterns were highly associated with different prognostic indicators (low flow time, clinical motor seizures, N20 responses, neuron-specific enolase (NSE), neuroimaging). Survival and good neurological outcome (CPC 1 or 2) at 6 months were 72.4% and 71.1% for benign EEG pattern, 54.3% and 44.4% for RSE, 15.4% and 0% for GPDs, and 2.4% and 0% for malignant nonepileptiform EEG pattern, respectively. Aggressive and prolonged treatment of RSE may be justified in cardiac arrest patients with favorable multimodal prognostic indicators. This article is part of the Special Issue "Proceedings of the 7th London-Innsbruck Colloquium on Status Epilepticus and Acute Seizures".

Quantifying Infarct Growth and Secondary Injury Volumes: Comparing Multimodal Image Registration Measures.

BACKGROUND AND PURPOSE: Lesion expansion in the week after acute stroke involves both infarct growth (IG) and anatomic distortion (AD) because of edema and hemorrhage. Enabling separate quantification would allow clinical trials targeting these distinct pathological processes. We developed an objective and automated approach to quantify these processes at 24 hours and 1 week. METHODS: Patients with acute ischemic stroke were scanned at presentation, 24 hours, and 1 week in a magnetic resonance imaging (MRI) cohort study. IG and AD were calculated from follow-up lesion masks after linear and nonlinear registration to a presenting MRI scan. Performance of IG and AD was compared with edema quantified using cerebrospinal fluid displacement. The use of alternative reference images to define AD, including template MRI, mirrored MRI, and presenting computed tomographic scan, was explored. RESULTS: Thirty-seven patients with nonlacunar stroke were included. AD was responsible for 20% and 36% of lesion expansion at 24 hours (n=30) and 1 week (n=28). Registration-defined IG and AD compared favorably with edema quantified using cerebrospinal fluid displacement, particularly at smaller infarct volumes. Presenting computed tomographic imaging was the preferred alternative reference image to presenting MRI for measuring AD. CONCLUSIONS: The contributions of IG and AD to lesion expansion can be measured separately over time through the use of image registration. This approach can be used to combine imaging outcome data from computed tomography and MRI.

Hand classification of fMRI ICA noise components.

We present a practical "how-to" guide to help determine whether single-subject fMRI independent components (ICs) characterise structured noise or not. Manual identification of signal and noise after ICA decomposition is required for efficient data denoising: to train supervised algorithms, to check the results of unsupervised ones or to manually clean the data. In this paper we describe the main spatial and temporal features of ICs and provide general guidelines on how to evaluate these. Examples of signal and noise components are provided from a wide range of datasets (3T data, including examples from the UK Biobank and the Human Connectome Project, and 7T data), together with practical guidelines for their identification. Finally, we discuss how the data quality, data type and preprocessing can influence the characteristics of the ICs and present examples of particularly challenging datasets.

Long-term applicability of the new ILAE definition of epilepsy. Results from the PRO-LONG study.

OBJECTIVE: The new epilepsy definition adopted by the International League Against Epilepsy (ILAE) includes patients with one unprovoked seizure with a probability of further seizures, similar to the general recurrence risk after two unprovoked seizures, occurring in a 10-year period. Long-term follow-up of patients diagnosed after a single seizure is needed to assess the applicability of the new epilepsy definition in clinical practice. METHODS: Patients with newly diagnosed epilepsy were recruited retrospectively with a minimum follow-up of 10 years. Patients were stratified in two groups depending on the occurrence of one (new definition, ND) or two or more unprovoked seizures (traditional definition, TD) at the time of epilepsy diagnosis and compared for disease characteristics and factors predicting seizure recurrence. The primary outcome was the occurrence of a new unprovoked seizure during follow-up in the ND group. The secondary outcome was the achievement of an early remission in both groups. RESULTS: Among 1,006 patients with newly diagnosed epilepsy, 152 (15.1%) were diagnosed after a single seizure. Compared to patients diagnosed using the TD, patients diagnosed according to the ND showed a higher proportion of subjects with an abnormal neurologic examination (19.9% vs. 13.7%, p = 0.0504) and with focal seizures (69.3% vs. 60.4%, p = 0.0021). The two samples differed in the presence of at least one of the factors predicting seizure recurrence (focal seizures or abnormal findings in at least one among the following: neurologic examination, electroencephalography [EEG], and neuroimaging) (94.6% vs. 89.1%, p = 0.0376). Long-term recurrence in patients diagnosed with the new definition was 83.6% at 10 years and 89.1% at 15 years. The probability of early remission did not differ between the two groups. SIGNIFICANCE: Our results support the applicability of the new epilepsy definition in clinical practice. Individual patient characteristics and a personalized diagnostic approach can justify treatment after a single unprovoked seizure.

Cerebral collateral flow defines topography and evolution of molecular penumbra in experimental ischemic stroke.

Intracranial collaterals are dynamically recruited after arterial occlusion and are emerging as a strong determinant of tissue outcome in both human and experimental ischemic stroke. The relationship between collateral flow and ischemic penumbra remains largely unexplored in pre-clinical studies. The aim of the present study was to investigate the pattern of collateral flow with regard to penumbral tissue after transient middle cerebral artery (MCA) occlusion in rats. MCA was transiently occluded (90min) by intraluminal filament in adult male Wistar rats (n=25). Intracranial collateral flow was studied in terms of perfusion deficit and biosignal fluctuation analyses using multi-site laser Doppler monitoring. Molecular penumbra was defined by topographical mapping and quantitative signal analysis of Heat Shock Protein 70kDa (HSP70) immunohistochemistry. Functional deficit and infarct volume were assessed 24h after ischemia induction. The results show that functional performance of intracranial collaterals during MCA occlusion inversely correlated with HSP70 immunoreactive areas in both the cortex and the striatum, as well as with infarct size and functional deficit. Intracranial collateral flow was associated with reduced areas of both molecular penumbra and ischemic core and increased areas of intact tissue in rats subjected to MCA occlusion followed by reperfusion. Our findings prompt the development of collateral therapeutics to provide tissue-saving strategies in the hyper-acute phase of ischemic stroke prior to recanalization therapy.

Head Down Tilt 15° in Acute Ischemic Stroke with Poor Collaterals: A Randomized Preclinical Trial.

Cerebral collaterals are recruited after arterial occlusion with a protective effect on tissue outcome in acute ischemic stroke. Head down tilt 15° (HDT15) is a simple, low cost and accessible procedure that could be applied as an emergency treatment, before recanalization therapies, with the aim to increase cerebral collateral flow. Spontaneously hypertensive rats have been shown to display anatomical differences in morphology and function of cerebral collaterals, compared to other rat strains, resulting in an overall poor collateral circulation. We investigate the efficacy and safety of HDT15 in spontaneously hypertensive (SHR) rats, which were considered as an animal stroke model with poor collaterals. Cerebral ischemia was induced by 90 minute endovascular occlusion of the middle cerebral artery (MCA). SHR rats were randomized to HDT15 or flat position (n = 19). HDT15 was applied 30 minutes after occlusion and lasted 60 minutes, until reperfusion. HDT15 application increased cerebral perfusion (+16.6% versus +6.1%; p = 0.0040) and resulted in a small reduction of infarct size (83.6 versus 107.1 mm3; - 21.89%; p = 0.0272), but it was not associated with early neurological improvement, compared to flat position. Our study suggests that the response to HDT15 during MCA occlusion is dependent on baseline collaterals. Nonetheless, HDT15 promoted a mild improvement of cerebral hemodynamics even in subjects with poor collaterals, without safety concerns.

Automated quantification of atrophy and acute ischemic volume for outcome prediction in endovascular thrombectomy.

Background: Short- and long-term outcomes from endovascular thrombectomy (EVT) for large vessel occlusion stroke remain variable. Numerous relevant predictors have been identified, including severity of neurological deficits, age, and imaging features. The latter is typically defined as acute changes (most commonly Alberta Stroke Programme Early CT Score, ASPECTS, at presentation), but there is little information on the impact of imaging assessment of premorbid brain health as a determinant of outcome. Aims: To examine the impact of automated measures of stroke severity and underlying brain frailty on short- and long-term outcomes in acute stroke treated with EVT. Methods: In 215 patients with anterior circulation stroke, who subsequently underwent EVT, automated analysis of presenting non-contrast CT scans was used to determine acute ischemic volume (AIV) and e-ASPECTS as markers of stroke severity, and cerebral atrophy as a marker of brain frailty. Univariate and multivariate logistic regression were used to identify significant predictors of NIHSS improvement, modified Rankin scale (mRS) at 90 and 30 days, mortality at 90 days and symptomatic intracranial hemorrhage (sICH) following successful EVT. Results: For long-term outcome, atrophy and presenting NIHSS were significant predictors of mRS 0-2 and death at 90 days, whereas age did not reach significance in multivariate analysis. Conversely, for short-term NIHSS improvement, AIV and age were significant predictors, unlike presenting NIHSS. The interaction between age and NIHSS was similar to the interaction of AIV and atrophy for mRS 0-2 at 90 days. Conclusion: Combinations of automated software-based imaging analysis and clinical data can be useful for predicting short-term neurological outcome and may improve long-term prognostication in EVT. These results provide a basis for future development of predictive tools built into decision-aiding software in stroke.

Selective Cerebrospinal Fluid Hypothermia: Bioengineering Development and In Vivo Study of an Intraventricular Cooling Device (V-COOL).

Hypothermia is a promising therapeutic strategy for severe vasospasm and other types of non-thrombotic cerebral ischemia, but its clinical application is limited by significant systemic side effects. We aimed to develop an intraventricular device for the controlled cooling of the cerebrospinal fluid, to produce a targeted hypothermia in the affected cerebral hemisphere with a minimal effect on systemic temperature. An intraventricular cooling device (acronym: V-COOL) was developed by in silico modelling, in vitro testing, and in vivo proof-of-concept application in healthy Wistar rats (n = 42). Cerebral cortical temperature, rectal temperature, and intracranial pressure were monitored at increasing flow rate (0.2 to 0.8 mL/min) and duration of application (10 to 60 min). Survival, neurological outcome, and MRI volumetric analysis of the ventricular system were assessed during the first 24 h. The V-COOL prototyping was designed to minimize extra-cranial heat transfer and intra-cranial pressure load. In vivo application of the V-COOL device produced a flow rate-dependent decrease in cerebral cortical temperature, without affecting systemic temperature. The target degree of cerebral cooling (- 3.0 °C) was obtained in 4.48 min at the flow rate of 0.4 mL/min, without significant changes in intracranial pressure. Survival and neurological outcome at 24 h showed no significant difference compared to sham-treated rats. MRI study showed a transient dilation of the ventricular system (+ 38%) in a subset of animals. The V-COOL technology provides an effective, rapid, selective, and safe cerebral cooling to a clinically relevant degree of - 3.0 °C.

A Comparison of T2 Relaxation-Based MRI Stroke Timing Methods in Hyperacute Ischemic Stroke Patients: A Pilot Study.

BACKGROUND: T2 relaxation-based magnetic resonance imaging (MRI) signals may provide onset time for acute ischemic strokes with an unknown onset. The ability of visual and quantitative MRI-based methods in a cohort of hyperacute ischemic stroke patients was studied. METHODS: A total of 35 patients underwent 3T (3 Tesla) MRI (<9-hour symptom onset). Diffusion-weighted (DWI), apparent diffusion coefficient (ADC), T1-weighted (T1w), T2-weighted (T2w), and T2 relaxation time (T2) images were acquired. T2-weighted fluid attenuation inversion recovery (FLAIR) images were acquired for 17 of these patients. Image intensity ratios of the average intensities in ischemic and non-ischemic reference regions were calculated for ADC, DWI, T2w, T2 relaxation, and FLAIR images, and optimal image intensity ratio cut-offs were determined. DWI and FLAIR images were assessed visually for DWI/FLAIR mismatch. RESULTS: The T2 relaxation time image intensity ratio was the only parameter with significant correlation with stroke duration (r = 0.49, P = .003), an area under the receiver operating characteristic curve (AUC = 0.77, P < .0001), and an optimal cut-off (T2 ratio = 1.072) that accurately identified patients within the 4.5-hour thrombolysis treatment window with sensitivity of 0.74 and specificity of 0.74. In the patients with the additional FLAIR, areas under the precision-recall-gain curve (AUPRG) and F1 scores showed that the T2 relaxation time ratio (AUPRG = 0.60, F1 = 0.73) performed considerably better than the FLAIR ratio (AUPRG = 0.39, F1 = 0.57) and the visual DWI/FLAIR mismatch (F1 = 0.25). CONCLUSIONS: Quantitative T2 relaxation time is the preferred MRI parameter in the assessment of patients with unknown onset for treatment stratification.

Blocking tactile input to one finger using anaesthetic enhances touch perception and learning in other fingers.

Brain plasticity is a key mechanism for learning and recovery. A striking example of plasticity in the adult brain occurs following input loss, for example, following amputation, whereby the deprived zone is "invaded" by new representations. Although it has long been assumed that such reorganization leads to functional benefits for the invading representation, the behavioral evidence is controversial. Here, we investigate whether a temporary period of somatosensory input loss to one finger, induced by anesthetic block, is sufficient to cause improvements in touch perception ("direct" effects of deafferentation). Further, we determine whether this deprivation can improve touch perception by enhancing sensory learning processes, for example, by training ("interactive" effects). Importantly, we explore whether direct and interactive effects of deprivation are dissociable by directly comparing their effects on touch perception. Using psychophysical thresholds, we found brief deprivation alone caused improvements in tactile perception of a finger adjacent to the blocked finger but not to non-neighboring fingers. Two additional groups underwent minimal tactile training to one finger either during anesthetic block of the neighboring finger or a sham block with saline. Deprivation significantly enhanced the effects of tactile perceptual training, causing greater learning transfer compared with sham block. That is, following deafferentation and training, learning gains were seen in fingers normally outside the boundaries of topographic transfer of tactile perceptual learning. Our results demonstrate that sensory deprivation can improve perceptual abilities, both directly and interactively, when combined with sensory learning. This dissociation provides novel opportunities for future clinical interventions to improve sensation. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Determining T2 relaxation time and stroke onset relationship in ischaemic stroke within apparent diffusion coefficient-defined lesions. A user-independent method for quantifying the impact of stroke in the human brain.

BACKGROUND AND OBJECTIVE: In hyperacute ischaemic stroke, T2 of cerebral water increases with time. Quantifying this change may be informative of the extent of tissue damage and onset time. Our objective was to develop a user-unbiased method to measure the effect of cerebral ischaemia on T2 to study stroke onset time-dependency in human acute stroke lesions. METHODS: Six rats were subjected to permanent middle cerebral occlusion to induce focal ischaemia, and a consecutive cohort of acute stroke patients (n = 38) were recruited within 9 hours from symptom onset. T1-weighted structural, T2 relaxometry, and diffusion MRI for apparent diffusion coefficient (ADC) were acquired. Ischaemic lesions were defined as regions of lowered ADC. The median T2 difference (ΔT2) between lesion and contralateral non-ischaemic control region was determined by the newly-developed spherical reference method, and data compared to that obtained by the mirror reference method. Linear regressions and receiver operating characteristics (ROC) were compared between the two methods. RESULTS: ΔT2 increases linearly in rat brain ischaemia by 1.9 ± 0.8 ms/h during the first 6 hours, as determined by the spherical reference method. In patients, ΔT2 linearly increases by 1.6 ± 1.4 and 1.9 ± 0.9 ms/h in the lesion, as determined by the mirror reference and spherical reference method, respectively. ROC analyses produced areas under the curve of 0.83 and 0.71 for the spherical and mirror reference methods, respectively. CONCLUSIONS: Data from the spherical reference method showed that the median T2 increase in the ischaemic lesion is correlated with stroke onset time in a rat as well as in a human patient cohort, opening the possibility of using the approach as a timing tool in clinics.

Quantifying T 2 relaxation time changes within lesions defined by apparent diffusion coefficient in grey and white matter in acute stroke patients.

The apparent diffusion coefficient (ADC) of cerebral water, as measured by diffusion MRI, rapidly decreases in ischaemia, highlighting a lesion in acute stroke patients. The MRI T 2 relaxation time changes in ischaemic brain such that T 2 in ADC lesions may be informative of the extent of tissue damage, potentially aiding in stratification for treatment. We have developed a novel user-unbiased method of determining the changes in T 2 in ADC lesions as a function of clinical symptom duration based on voxel-wise referencing to a contralateral brain volume. The spherical reference method calculates the most probable pre-ischaemic T 2 on a voxel-wise basis, making use of features of the contralateral hemisphere presumed to be largely unaffected. We studied whether T 2 changes in the two main cerebral tissue types, i.e. in grey matter (GM) and white matter (WM), would differ in stroke. Thirty-eight acute stroke patients were accrued within 9 h of symptom onset and scanned at 3 T for 3D T 1-weighted, multi b-value diffusion and multi-echo spin echo MRI for tissue type segmentation, quantitative ADC and absolute T 2 images, respectively. T 2 changes measured by the spherical reference method were 1.94 ± 0.61, 1.50 ± 0.52 and 1.40 ± 0.54 ms h-1 in the whole, GM, and WM lesions, respectively. Thus, T 2 time courses were comparable between GM and WM independent of brain tissue type involved. We demonstrate that T 2 changes in ADC-delineated lesions can be quantified in the clinical setting in a user unbiased manner and that T 2 change correlated with symptom onset time, opening the possibility of using the approach as a tool to assess severity of tissue damage in the clinical setting.