Phase-based metamorphosis of diffusion lesion in relation to perfusion values in acute ischemic stroke.

Examining the dynamics of stroke ischemia is limited by the standard use of 2D-volume or voxel-based analysis techniques. Recently developed spatiotemporal models such as the 4D metamorphosis model showed promise for capturing ischemia dynamics. We used a 4D metamorphosis model to evaluate acute ischemic stroke lesion morphology from the acute diffusion-weighted imaging (DWI) to final T2-weighted imaging (T2-w). In 20 representative patients, we metamorphosed the acute lesion to subacute lesion to final infarct. From the DWI lesion deformation maps we identified dynamic lesion areas and examined their association with perfusion values inside and around the lesion edges, blinded to reperfusion status. We then tested the model in ten independent patients from the STroke Imaging Repository (STIR). Perfusion values varied widely between and within patients, and were similar in contracting and expanding DWI areas in many patients in both datasets. In 25% of patients, the perfusion values were higher in DWI-contracting than DWI-expanding areas. A similar wide range of perfusion values and ongoing expansion and contraction of the DWI lesion were seen subacutely. There was more DWI contraction and less expansion in patients who received thrombolysis, although with widely ranging perfusion values that did not differ. 4D metamorphosis modeling shows promise as a method to improve use of multimodal imaging to understand the evolution of acute ischemic tissue towards its fate.

Using longitudinal metamorphosis to examine ischemic stroke lesion dynamics on perfusion-weighted images and in relation to final outcome on T2-w images.

We extend the image-to-image metamorphosis into constrained longitudinal metamorphosis. We apply it to estimate an evolution scenario, in patients with acute ischemic stroke, of both scattered and solitary ischemic lesions visible on serial MR perfusion weighted imaging from acute to subacute stages. We then estimate a patient-specific residual map that enables us to capture the most relevant shape and intensity changes, continuously, as the lesion evolves from acute through subacute to chronic timepoints until merging into the final image. We detect areas with high residuals (i.e., high dynamics) and identify areas that became part of the final T2-w lesion obtained at ≥ 1 month after stroke. This allows the investigation of the dynamic influence of perfusion values on the final lesion outcome as seen on T2-w imaging. The model provides detailed insights into stroke lesion dynamic evolution in space and time that will help identify factors that determine final outcome and identify targets for interventions to improve outcome.

Corrigendum to "Medical image analysis methods in MR/CT-imaged acute-subacute ischemic stroke lesion: Segmentation, prediction and insights into dynamic evolution simulation models. A critical appraisal" [NeuroImage: Clinical 1 (2012) 164-178].

[This corrects the article DOI: 10.1016/j.nicl.2012.10.003.].

Relationships between brain and body temperature, clinical and imaging outcomes after ischemic stroke.

Pyrexia soon after stroke is associated with severe stroke and poor functional outcome. Few studies have assessed brain temperature after stroke in patients, so little is known of its associations with body temperature, stroke severity, or outcome. We measured temperatures in ischemic and normal-appearing brain using (1)H-magnetic resonance spectroscopy and its correlations with body (tympanic) temperature measured four-hourly, infarct growth by 5 days, early neurologic (National Institute of Health Stroke Scale, NIHSS) and late functional outcome (death or dependency). Among 40 patients (mean age 73 years, median NIHSS 7, imaged at median 17 hours), temperature in ischemic brain was higher than in normal-appearing brain on admission (38.6°C-core, 37.9°C-contralateral hemisphere, P=0.03) but both were equally elevated by 5 days; both were higher than tympanic temperature. Ischemic lesion temperature was not associated with NIHSS or 3-month functional outcome; in contrast, higher contralateral normal-appearing brain temperature was associated with worse NIHSS, infarct expansion and poor functional outcome, similar to associations for tympanic temperature. We conclude that brain temperature is higher than body temperature; that elevated temperature in ischemic brain reflects a local tissue response to ischemia, whereas pyrexia reflects the systemic response to stroke, occurs later, and is associated with adverse outcomes.

Medical image analysis methods in MR/CT-imaged acute-subacute ischemic stroke lesion: Segmentation, prediction and insights into dynamic evolution simulation models. A critical appraisal.

Over the last 15 years, basic thresholding techniques in combination with standard statistical correlation-based data analysis tools have been widely used to investigate different aspects of evolution of acute or subacute to late stage ischemic stroke in both human and animal data. Yet, a wave of biology-dependent and imaging-dependent issues is still untackled pointing towards the key question: "how does an ischemic stroke evolve?" Paving the way for potential answers to this question, both magnetic resonance (MRI) and CT (computed tomography) images have been used to visualize the lesion extent, either with or without spatial distinction between dead and salvageable tissue. Combining diffusion and perfusion imaging modalities may provide the possibility of predicting further tissue recovery or eventual necrosis. Going beyond these basic thresholding techniques, in this critical appraisal, we explore different semi-automatic or fully automatic 2D/3D medical image analysis methods and mathematical models applied to human, animal (rats/rodents) and/or synthetic ischemic stroke to tackle one of the following three problems: (1) segmentation of infarcted and/or salvageable (also called penumbral) tissue, (2) prediction of final ischemic tissue fate (death or recovery) and (3) dynamic simulation of the lesion core and/or penumbra evolution. To highlight the key features in the reviewed segmentation and prediction methods, we propose a common categorization pattern. We also emphasize some key aspects of the methods such as the imaging modalities required to build and test the presented approach, the number of patients/animals or synthetic samples, the use of external user interaction and the methods of assessment (clinical or imaging-based). Furthermore, we investigate how any key difficulties, posed by the evolution of stroke such as swelling or reperfusion, were detected (or not) by each method. In the absence of any imaging-based macroscopic dynamic model applied to ischemic stroke, we have insights into relevant microscopic dynamic models simulating the evolution of brain ischemia in the hope to further promising and challenging 4D imaging-based dynamic models. By depicting the major pitfalls and the advanced aspects of the different reviewed methods, we present an overall critique of their performances and concluded our discussion by suggesting some recommendations for future research work focusing on one or more of the three addressed problems.

Use of dynamic contrast-enhanced MRI to measure subtle blood-brain barrier abnormalities.

There is growing interest in investigating the role of subtle changes in blood-brain barrier (BBB) function in common neurological disorders and the possible use of imaging techniques to assess these abnormalities. Some studies have used dynamic contrast-enhanced MR imaging (DCE-MRI) and these have demonstrated much smaller signal changes than obtained from more traditional applications of the technique, such as in intracranial tumors and multiple sclerosis. In this work, preliminary results are presented from a DCE-MRI study of patients with mild stroke classified according to the extent of visible underlying white matter abnormalities. These data are used to estimate typical signal enhancement profiles in different tissue types and by degrees of white matter abnormality. The effect of scanner noise, drift and different intrinsic tissue properties on signal enhancement data is also investigated and the likely implications for interpreting the enhancement profiles are discussed. No significant differences in average signal enhancement or contrast agent concentration were observed between patients with different degrees of white matter abnormality, although there was a trend towards greater signal enhancement with more abnormal white matter. Furthermore, the results suggest that many of the factors considered introduce uncertainty of a similar magnitude to expected effect sizes, making it unclear whether differences in signal enhancement are truly reflective of an underlying BBB abnormality or due to an unrelated effect. As the ultimate aim is to achieve a reliable quantification of BBB function in subtle disorders, this study highlights the factors which may influence signal enhancement and suggests that further work is required to address the challenging problems of quantifying contrast agent concentration in healthy and diseased living human tissue and of establishing a suitable model to enable quantification of relevant physiological parameters. Meanwhile, it is essential that future studies use an appropriate control group to minimize these influences.

Associations between diffusion and perfusion parameters, N-acetyl aspartate, and lactate in acute ischemic stroke.

BACKGROUND AND PURPOSE: In acute ischemic stroke, the amount of neuronal damage in hyperintense areas on MR diffusion imaging (DWI) is unclear. We used spectroscopic imaging to measure N-acetyl aspartate (NAA, a marker of normal neurons) and lactate (a marker of ischemia) to compare with diffusion and perfusion values in the diffusion lesion in acute ischemic stroke. METHODS: We recruited patients with acute ischemic stroke prospectively and performed MR diffusion weighted (DWI), perfusion, and spectroscopic imaging. We coregistered the images, outlined the visible diffusion lesion, and extracted metabolite, perfusion, and apparent diffusion coefficient (ADC) values from the diffusion lesion. RESULTS: 42 patients were imaged, from 1.5 to 24 hours after stroke. In the DWI lesion, although NAA was reduced, there was no correlation between NAA and ADC or perfusion values. However, raised lactate correlated with reduced ADC (Spearman rho=0.32, P=0.04) and prolonged mean transit time (MTT, rho=0.31, P=0.04). Increasing DWI lesion size was associated with lower NAA and higher lactate (rho=-0.44, P=0.003; rho=0.49, P=0.001 respectively); NAA fell with increasing times to imaging (rho=-0.3, P=0.03), but lactate did not change. CONCLUSIONS: Although larger confirmatory studies are needed, the correlation of ADC and MTT with lactate but not NAA suggests that ADC and MTT are better markers of the presence of ischemia than of cumulative neuronal loss. Further studies should define more precisely the rate of neuronal loss and relationship to diffusion and perfusion parameters with respect to the depth and duration of ischemia.

DSC perfusion MRI-Quantification and reduction of systematic errors arising in areas of reduced cerebral blood flow.

Dynamic susceptibility contrast (DSC)-MRI is commonly used to measure cerebral perfusion in acute ischemic stroke. Quantification of perfusion parameters involves deconvolution of the tissue concentration-time curves with an arterial input function (AIF), typically with the use of singular value decomposition (SVD). To mitigate the effects of noise on the estimated cerebral blood flow (CBF), a regularization parameter or threshold is used. Often a single global threshold is applied to every voxel, and its value has a dramatic effect on the CBF values obtained. When a single global threshold was applied to simulated concentration-time curves produced using exponential, triangular, and boxcar residue functions, significant systematic errors were found in the measured perfusion parameters. We estimate the errors obtained for different sampling intervals and signal-to-noise ratios (SNRs), and discuss the source of the systematic error. We present a method that partially corrects for the systematic error in the presence of an exponential residue function by applying a linear fit, which removes underestimates of long mean transit time (MTT) and overestimates of short MTT. For example, the correction reduced the error at a temporal resolution of 2.5 s and an SNR of 30 from 29.1% to 11.7%. However, the error is largest in the presence of noise and at MTTs that are likely to be encountered in areas of hypoperfusion; furthermore, even though it is reduced, it cannot be corrected for exactly.

Persistent infarct hyperintensity on diffusion-weighted imaging late after stroke indicates heterogeneous, delayed, infarct evolution.

BACKGROUND AND PURPOSE: Some infarcts have persistently hyperintense areas on diffusion-weighted MRI (DWI) even at 1 month after stroke, whereas others have become isointense to normal brain. We hypothesized that late DWI hyperintensity reflected different infarct evolution compared with areas that were isointense by 1 month. METHODS: We recruited patients prospectively with ischemic stroke, performed DWI and perfusion-weighted MRI (PWI) on admission, at 5 days, 14 days, and 1 month after stroke, and assessed functional outcome at 3 months (Rankin Scale). Patient characteristics and DWI/PWI values were compared for patients with or without "still hyperintense" infarct areas on 1-month DWI. RESULTS: Among 42 patients, 27 (64%) had "still hyperintense" infarct regions at 1 month, mostly in white matter. Patients with "still hyperintense" regions at 1 month had lower baseline apparent diffusion coefficient ratio (ADCr; mean+/-SD 0.76+/-0.12 versus 0.85+/-0.12; hyperintense versus isointense; P<0.05), prolonged reduction of ADCr (repeated-measures ANOVA; P<0.01), no difference in baseline perfusion but delayed normalization of mean transit time (P<0.05) and cerebral blood flow ratios (repeated measures ANOVA; P<0.05), initially more severe stroke, and worse 3-month outcome than patients whose lesions were isointense by 1 month. CONCLUSIONS: The late DWI lesion hyperintensity emphasizes the heterogeneity in temporal evolution of stroke injury and suggests ongoing "ischemia." Lower baseline ADCr precedes delayed perfusion normalization, suggesting that worse cell swelling impedes reperfusion. Further study is required to determine underlying mechanisms and any potential for subacute intervention to improve recovery.