CT perfusion (CTP) is widely and rapidly accessible for imaging acute ischemic stroke but has limited validation. Cerebral blood volume (CBV) has been proposed as the best predictor of infarct core. ...We tested CBV against other common CTP parameters using contemporaneous diffusion MRI.
Patients with acute ischemic stroke<6 hours after onset had CTP and diffusion MRI<1 hour apart, before any reperfusion therapies. CTP maps of time to peak (TTP), absolute and relative CBV, cerebral blood flow (CBF), mean transit time (MTT), and time to peak of the deconvolved tissue residue function (Tmax) were generated. The diffusion lesion was manually outlined to its maximal visual extent. Receiver operating characteristic (ROC) analysis area under the curve (AUC) was used to quantify the correspondence of each perfusion parameter to the coregistered diffusion-weighted imaging lesion. Optimal thresholds were determined (Youden index).
In analysis of 98 CTP slabs (54 patients, median onset to CT 190 minutes, median CT to MR 30 minutes), relative CBF performed best (AUC, 0.79; 95% CI, 0.77-81), significantly better than absolute CBV (AUC, 0.74; 95% CI, 0.73-0.76). The optimal threshold was <31% of mean contralateral CBF. Specificity was reduced by low CBF/CBV in noninfarcted white matter in cases with reduced contrast bolus intensity and leukoaraiosis.
In contrast to previous reports, CBF corresponded with the acute diffusion-weighted imaging lesion better than CBV, although no single threshold avoids detection of false-positive regions in unaffected white matter. This relates to low signal-to-noise ratio in CTP maps and emphasizes the need for optimized acquisition and postprocessing.
Cerebral microbleeds (microbleeds) are small, punctuate hypointense lesions seen in T2* Gradient-Recall Echo (GRE) and Susceptibility-Weighted (SWI) Magnetic Resonance Imaging (MRI) sequences, ...corresponding to areas of hemosiderin breakdown products from prior microscopic hemorrhages. They occur in the setting of impaired small vessel integrity, commonly due to either hypertensive vasculopathy or cerebral amyloid angiopathy. Microbleeds are more prevalent in individuals with Alzheimer's disease (AD) dementia and in those with both ischemic and hemorrhagic stroke. However they are also found in asymptomatic individuals, with increasing prevalence with age, particularly in carriers of the Apolipoprotein (APOE) ε4 allele. Other neuroimaging findings that have been linked with microbleeds include lacunar infarcts and white matter hyperintensities on MRI, and increased cerebral β-amyloid burden using (11)C-PiB Positron Emission Tomography. The presence of microbleeds has been suggested to confer increased risk of incident intracerebral hemorrhage - particularly in the setting of anticoagulation - and of complications of immunotherapy for AD. Prospective data regarding the natural history and sequelae of microbleeds are currently limited, however there is a growing evidence base that will serve to inform clinical decision-making in the future.
Perfusion imaging has the potential to select patients most likely to respond to thrombolysis. We tested the correspondence of computed tomography perfusion (CTP)-derived mismatch with ...contemporaneous perfusion-diffusion magnetic resonance imaging (MRI).
Acute ischemic stroke patients 3 to 6 hours after onset had CTP and perfusion-diffusion MRI within 1 hour, before thrombolysis. Relative cerebral blood flow (relCBF) and time to peak of the deconvolved tissue residue function (Tmax) were calculated. The diffusion lesion (diffusion-weighted imaging) was registered to the CTP slabs and manually outlined to its maximal visual extent. Volumetric accuracy of CT-relCBF infarct core (compared with diffusion-weighted imaging) was tested. To reduce false-positive low CBF regions, relCBF core was restricted to voxels within a relative time-to-peak (relTTP) >4 seconds for lesion region of interest. The MR-Tmax >6 seconds perfusion lesion was automatically segmented and registered to CTP. Receiver-operating characteristic analysis determined the optimal CT-Tmax threshold to match MR-Tmax >6 seconds. Agreement of these CT parameters with MR perfusion-diffusion mismatch in coregistered slabs was assessed (mismatch ratio >1.2, absolute mismatch >10 mL, infarct core <70 mL).
In analysis of 49 patients (mean onset to CT, 213 minutes; mean CT to MR, 31 minutes), constraining relCBF <31% within the automated relTTP perfusion lesion region of interest reduced the median magnitude of volumetric error (vs diffusion-weighted imaging) from 47.5 mL to 15.8 mL (P<0.001). The optimal CT-Tmax threshold to match MR-Tmax >6 seconds was 6.2 seconds (95% confidence interval, 5.6-7.3 seconds; sensitivity, 91%; specificity, 70%; area under the curve, 0.87). Using CT-Tmax >6 seconds "penumbra" and relTTP-constrained relCBF "core," CT-based and MRI-based mismatch status was concordant in 90% (kappa=0.80).
Quantitative CTP mismatch classification using relCBF and Tmax is similar to perfusion-diffusion MRI. The greater accessibility of CTP may facilitate generalizability of mismatch-based selection in clinical practice and trials.
The default mode network (DMN) is the main large-scale network of the resting brain and the PCC/precuneus is a major hub of this network. Glutamate and GABA (γ-amino butyric acid) are the main ...excitatory and inhibitory neurotransmitters in the CNS, respectively. We studied glutamate and GABA concentrations in the PCC/precuneus via magnetic resonance spectroscopy (MRS) at 7T in relation to age and correlated them with functional connectivity between this region and other DMN nodes in ten healthy right-handed volunteers ranging in age between 23-68 years. Mean functional connectivity of the PCC/precuneus to the other DMN nodes and the glutamate/GABA ratio significantly correlated with age (r = 0.802, p = 0.005 and r = 0.793, p = 0.006, respectively) but not with each other. Glutamate and GABA alone did not significantly correlate with age nor with functional connectivity within the DMN. The glutamate/GABA ratio and functional connectivity of the PCC/precuneus are, therefore, independent age-related biomarkers of the DMN and may be combined in a multimodal pipeline to study DMN alterations in various disease states.
Summary Background Whether intravenous tissue plasminogen activator (alteplase) is effective beyond 3 h after onset of acute ischaemic stroke is unclear. We aimed to test whether alteplase given 3–6 ...h after stroke onset promotes reperfusion and attenuates infarct growth in patients who have a mismatch in perfusion-weighted MRI (PWI) and diffusion-weighted MRI (DWI). Methods We prospectively and randomly assigned 101 patients to receive alteplase or placebo 3–6 h after onset of ischaemic stroke. PWI and DWI were done before and 3–5 days after therapy, with T2-weighted MRI at around day 90. The primary endpoint was infarct growth between baseline DWI and the day 90 T2 lesion in mismatch patients. Major secondary endpoints were reperfusion, good neurological outcome, and good functional outcome. Patients, caregivers, and investigators were unaware of treatment allocations. Primary analysis was per protocol. This study is registered with ClinicalTrials.gov , number NCT00238537. Findings We randomly assigned 52 patients to alteplase and 49 patients to placebo. Mean age was 71·6 years, and median score on the National Institutes of Health stroke scale was 13. 85 of 99 (86%) patients had mismatch of PWI and DWI. The geometric mean infarct growth (exponential of the mean log of relative growth) was 1·24 with alteplase and 1·78 with placebo (ratio 0·69, 95% CI 0·38–1·28; Student's t test p=0·239); the median relative infarct growth was 1·18 with alteplase and 1·79 with placebo (ratio 0·66, 0·36–0·92; Wilcoxon's test p=0·054). Reperfusion was more common with alteplase than with placebo and was associated with less infarct growth (p=0·001), better neurological outcome (p<0·0001), and better functional outcome (p=0·010) than was no reperfusion. Interpretation Alteplase was non-significantly associated with lower infarct growth and significantly associated with increased reperfusion in patients who had mismatch. Because reperfusion was associated with improved clinical outcomes, phase III trials beyond 3 h after treatment are warranted. Funding National Health and Medical Research Council, Australia; National Stroke Foundation, Australia; Heart Foundation of Australia.
Edema may worsen outcome after intracerebral hemorrhage (ICH). We assessed its natural history, factors influencing growth, and association with outcome.
We estimated edema volumes in ICH patients ...from the Helsinki ICH study using semiautomated planimetry. We assessed the correlation between edema extension distance (EED) and time from ICH onset, creating an edema growth trajectory model up to 3 weeks. We interpolated expected EED at 72 hours and identified clinical and imaging characteristics associated with faster edema growth. Association of EED and mortality was assessed using logistic regression adjusting for predictors of ICH outcome.
From 1013 consecutive patients, 861 were included. There was a strong inverse correlation between EED growth rate (cm/d) and time from onset (days): EED growth=0.162*days exp(-0.927),
=0.82. Baseline factors associated with larger than expected EED were older age (71 versus 68;
=0.002), higher National Institutes of Health Stroke Scale score (14 versus 8;
<0.001), and lower Glasgow Coma scale score (13 versus 15;
<0.001), larger ICH volume (19.7 versus 12.7 mL;
<0.001), larger initial EED (0.42 versus 0.30;
<0.001), irregularly shaped hematoma (55% versus 42%;
<0.001), and higher glucose (7.6 versus 6.9 mmol/L;
=0.001). Patients with faster edema growth had more midline shift (50% versus 31%;
<0.001), herniation (12% versus 4%;
<0.001), and higher 6-month (46% versus 26%;
<0.001) mortality. In the logistic regression model, higher-than-expected EED was associated with 6-month mortality (odds ratio, 1.60; 95% confidence interval, 1.04-2.46;
=0.032).
Edema growth can be readily monitored and is an independent determinant of mortality after ICH, providing an important treatment target for strategies to improve patient outcome.
Many perfusion-related MRI parameters are used to investigate the penumbra in stroke. Although time-to-maximum (Tmax) of the residue function has been suggested as a very promising parameter, its ...physiological meaning and sensitivity to experimental conditions are not well-understood.
We used simulations to further our understanding of the practical meaning of Tmax and to provide recommendations for its use in clinical investigations. We interpret in vivo examples guided by the simulation findings.
Whereas Tmax has several attractive properties for clinical use, it is shown that its physiological interpretation is complex and affected by experimental conditions. Tmax is found to reflect a combination of delay, dispersion, and, to a lesser degree, mean transit time. It should therefore mainly be considered a measure of macrovascular characteristics. Furthermore, based on the simulations, use of temporal-interpolation is highly recommended, as is correction for slice-acquisition timing differences.
Special care should be taken when setting-up Tmax thresholds for data acquired with different protocols (eg, multicenter studies) because various factors can influence the measured Tmax. Because of its complementary information, used in conjunction with delay-insensitive cerebral blood-flow, cerebral blood volume, and mean transit time maps, Tmax should provide important additional information on brain hemodynamic status.
MRI in transverse myelitis Goh, Christine; Desmond, Patricia M.; Phal, Pramit M.
Journal of magnetic resonance imaging,
12/2014, Volume:
40, Issue:
6
Journal Article
Factors contributing to cerebral edema in the post-hyperacute period of ischemic stroke (first 24-72 hours) are poorly understood. Blood-brain barrier (BBB) disruption and postischemic hyperperfusion ...reflect microvascular dysfunction and are associated with hemorrhagic transformation. We investigated the relationships between BBB integrity, cerebral blood flow, and space-occupying cerebral edema in patients who received acute reperfusion therapy.
We performed a pooled analysis of patients treated for anterior circulation large vessel occlusion in the EXTEND-IA TNK and EXTEND-IA TNK part 2 trials who had MRI with dynamic susceptibility contrast-enhanced perfusion-weighted imaging 24 hours after treatment. We investigated the associations between BBB disruption and cerebral blood flow within the infarct with cerebral edema assessed using 2 metrics: first midline shift (MLS) trichotomized as an ordinal scale of negligible (<1 mm), mild (≥1 to <5 mm), or severe (≥5 mm), and second relative hemispheric volume (rHV), defined as the ratio of the 3-dimensional volume of the ischemic hemisphere relative to the contralateral hemisphere.
Of 238 patients analyzed, 133 (55.9%) had negligible, 93 (39.1%) mild, and 12 (5.0%) severe MLS at 24 hours. The associated median rHV was 1.01 (IQR, 1.00-1.028), 1.03 (IQR, 1.01-1.077), and 1.15 (IQR, 1.08-1.22), respectively. MLS and rHV were associated with poor functional outcome at 90 days (
.002). Increased BBB permeability was independently associated with more edema after adjusting for age, occlusion location, reperfusion, parenchymal hematoma, and thrombolytic agent used (MLS cOR, 1.12 95% CI, 1.03-1.20,
=0.005; rHV β, 0.39 95% CI, 0.24-0.55,
<0.0001), as was reduced cerebral blood flow (MLS cOR, 0.25 95% CI, 0.10-0.58,
=0.001; rHV β, -2.95 95% CI, -4.61 to -11.29,
=0.0006). In subgroup analysis of patients with successful reperfusion (extended Treatment in Cerebral Ischemia 2b-3, n=200), reduced cerebral blood flow remained significantly associated with edema (MLS cOR, 0.37 95% CI, 0.14-0.98,
=0.045; rHV β, -2.59 95% CI, -4.32 to -0.86,
=0.004).
BBB disruption and persistent hypoperfusion in the infarct after reperfusion treatment is associated with space-occupying cerebral edema. Further studies evaluating microvascular dysfunction during the post-hyperacute period as biomarkers of poststroke edema and potential therapeutic targets are warranted.
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