Fractional anisotropy correlates with auditory simple reaction time performance.

During the last two decades, modern imaging studies focused intensively on the broad field of reaction time paradigms and significantly enhanced the understanding of behavioral performance. However, interindividual variations of simple reaction time (SRT) have been barely investigated. In this study, we intended to identify neural correlates of interindividual variation in auditory SRT (aSRT) employing the Poffenberger paradigm with auditory stimuli, in order to investigate neural processing speed performance. We conducted a whole-head voxel based morphometry analysis of fractional anisotropy (FA) in 19 healthy, right handed subjects. Simple regression analysis between FA and interindividual aSRT measures was performed for each voxel. Significant positive correlation (R(2): 0.44/0.78 min/max) for FA vs. individual mean aSRT was found in the right central cerebellum dorso-cranial of the dentate nucleus. A significant correlation (R(2): 0.453/0.633 min/max) was also detected between FA and the hand performance index, which characterizes the intraindividual RT difference between left and right hand, within the precentral portion of the pyramidal tract in the left hemisphere. Fast right handed response correlated with high local FA values located within neural structures participating in right hand control. Against the background of only right handed participants in our study, the hypothesis of local myelination as one basic condition influencing reaction time performance is strongly supported. The presented results identify brain areas involved in the processing speed of the aSRT tasks. We propose that the presented findings are due to an influence of participants' right hand preference on both FA and aSRT measures.

Iomazenil-single-photon emission computed tomography reveals selective neuronal loss in magnetic resonance-defined mismatch areas.

BACKGROUND AND PURPOSE: The mismatch of hypoperfused tissue on perfusion imaging and ischemic tissue on diffusion-weighted imaging is used as a surrogate marker for thrombolytic therapy in the extended time window. Mismatch tissue may recover completely, progress toward infarction, or proceed toward incomplete infarction with selective loss of cortical neurons. We used [(123)I]iomazenil-single-photon emission computed tomography (IMZ-SPECT) to characterize the neuronal integrity of reperfused "tissue at risk of infarction" that appeared morphologically intact on follow-up magnetic resonance imaging (MRI). METHODS: Twelve patients with acute stroke with striatocapsular (SC) infarctions were examined with multimodal MRI at days 0, 1, and 7; IMZ-SPECT was performed at days 5 to 15. The PI at day 0, fluid-attenuated inversion recovery (FLAIR) image at day 7, and IMZ-SPECT were coregistered and stereotactically normalized. The mismatch volume of interest (VOI) was defined as the initial PI lesion subtracted by the FLAIR lesion at day 7. An asymmetry ratio (AR) was computed by dividing the mean IMZ uptake of the mismatch VOI by the unaffected mirror VOI. The same AR was computed for signal intensity on FLAIR images at day 7. Three patients with cortical infarctions were included for calibration of the AR. In this group, the VOI consisted of the FLAIR lesion at day 7. RESULTS: All patients with SC infarctions had a large mismatch of initially hypoperfused (112+/-31 mL; mean+/-SD) and finally infarcted tissue (19+/-14 mL). Mean AR of cortical IMZ uptake was 0.85+/-0.01 in cortical infarctions and 0.95+/-0.03 in SC infarctions; thereby AR showed a continuous distribution from clearly reduced (0.89) to normal (1.01) in SC infarctions. Mean AR for FLAIR signal intensity was 1.84+/-0.14 for cortical infarctions and normal (1.01+0.03) for SC infarctions. CONCLUSIONS: IMZ-SPECT detected a selective loss of cortical neurons in patients with SC infarctions in transient hypoperfused tissue, which was morphologically intact on MRI.

Tissue at risk is overestimated in perfusion-weighted imaging: MR imaging in acute stroke patients without vessel recanalization.

BACKGROUND AND PURPOSE: The volume of decreased cerebral blood flow (CBF) in acute stroke perfusion-weighted imaging frequently overestimates final infarct volume. We hypothesized that surviving tissue exists even in patients without recanalization and tried to determine perfusion thresholds from initial MR imaging. METHODS: Stroke MR imaging including MR angiography was carried out at days 0, 1, and 7 after stroke onset in 19 patients without recanalization at least until day 1. The following lesions were defined: L0 = diffusion restriction at day 0; LG1 = lesion growth until day 1; LG7 = lesion growth until day 7; ST7 = initially hypoperfused, but surviving tissue. These lesions were transferred on initial MR imaging within 4.7 hours and perfusion values at day 0 were determined. RESULTS: Median lesion volume L0 at day 0 was 18.2 mL and increased to 39.4 and 43.8 mL at days 1 and 7. Volume of decreased rCBF not progressing to infarction was 148.5 mL (ST7). Mean ST7 perfusion values were different from L0 and LG1, but only mean relative cerebral blood volume (rCBV) was different from LG7, discriminating survival against death of tissue. A threshold value of 0.82 CBV for death versus survival was determined with a sensitivity of 0.56 and specificity of 0.95. Carotid T occlusions showed the greatest potential of lesion growth. CONCLUSION: Even when vessel occlusion persists, hypoperfused tissue on MR imaging does not necessarily progress toward infarction. The most conclusive inferences can be drawn from CBV images. The site of arterial occlusion also determines progression to infarction.

Prediction of malignant middle cerebral artery infarction by early perfusion- and diffusion-weighted magnetic resonance imaging.

BACKGROUND AND PURPOSE: We tested the hypothesis that early diffusion- and perfusion-weighted MRI (DWI and PWI, respectively) allows the prediction of malignant middle cerebral artery (MCA) infarction (MMI). METHODS: Thirty-seven patients with acute MCA infarction and proximal vessel occlusion (carotid-T, MCA main stem) were studied by DWI, PWI, and MR angiography within 6 hours of symptom onset. Eleven patients developed MMI, defined by decline of consciousness and radiological signs of space-occupying brain edema. Lesion volumes were retrospectively defined as apparent diffusion coefficient <80% (ADC<80%) and time to peak >+4 seconds (TTP>+4s) compared with the unaffected hemisphere. ADC decrease within the infarct core (ADCcore) and relative ADC within the ADC<80% lesion (rADClesion) were measured. Neurological deficit at admission was assessed with the National Institutes of Health Stroke Scale (NIHSS). RESULTS: Patients with MMI showed larger ADC<80% (median, 157 versus 22 mL; P<0.001) and TTP>+4s (208 versus 125 mL; P<0.001) lesion volumes, smaller TTP/ADC mismatch ratio (1.5 versus 5.5; P<0.001), lower ADCcore values (290 versus 411 mm2/s; P<0.001), lower rADClesion (0.60 versus 0.66; P=0.001), higher frequency of carotid-T occlusion (64% versus 15%; P=0.006), and higher NIHSS score at admission (20 versus 15; P=0.001). Predictors of MMI were as follows for sensitivity and specificity, respectively: ADC<80% >82 mL, 87%, 91%; TTP>+4s >162 mL, 83%, 75%; TTP/ADC mismatch ratio <2.4, 80%, 79%; ADCcore <300 mm2/s, 83%, 85%; rADClesion <0.62, 79%, 74%; and NIHSS score at admission > or =19, 96%, 72%. CONCLUSIONS: Quantitative analysis of early DWI and PWI parameters allows the prediction of MMI and can help in the selection of patients for aggressive tissue-protective therapy.

Cerebral blood flow predicts lesion growth in acute stroke patients.

BACKGROUND AND PURPOSE: We sought to study the role of MRI-derived cerebral blood flow (CBF) measurements for the prediction of lesion development in acute stroke patients. METHODS: Thirty-two patients were treated with tissue plasminogen activator. Diffusion-weighted (DWI) and perfusion-weighted MRI, T2-weighted imaging, and MR angiography were performed before treatment (2.8+/-0.9 hours after symptom onset) and on follow-up (days 1 and 7). CBF thresholds (12 and 22 mL/100 g per minute) were applied to bolus tracking MRI maps to determine predictive cutoff levels. RESULTS: In 21 patients (group A), the terminal lesion volume (T2-weighted imaging) was larger than the initial DWI lesion volume (89+/-93 versus 21+/-38 mL). In 11 patients (group B), the terminal lesion volume was smaller than the initial DWI lesion volume (7+/-27 versus 15+/-29 mL). The initial DWI lesion volume did not differ between both groups. The presence of a tissue volume > or =50 mL with a CBF value < or =12 mL/100 g per minute was predictive for lesion enlargement to day 7 in T2-weighted imaging (positive predictive value, 0.80). CONCLUSIONS: The presence of a tissue volume > or =50 mL with a CBF value < or =12 mL/100 g per minute predicts further lesion growth in hyperacute stroke patients. MRI-derived CBF values, with all their present limitations, are valuable in early estimation of prognosis of stroke patients.

Transient ischemic attacks before ischemic stroke: preconditioning the human brain? A multicenter magnetic resonance imaging study.

BACKGROUND AND PURPOSE: We investigated whether transient ischemic attacks (TIAs) before stroke can induce tolerance by raising the threshold of tissue vulnerability in the human brain. METHODS: Sixty-five patients with first-ever ischemic territorial stroke received diffusion- and perfusion-weighted MRI within 12 hours of symptom onset. Epidemiological and clinical data, lesion volumes in T2, apparent diffusion coefficient (ADC) maps and perfusion maps, and cerebral blood flow and cerebral blood volume values were compared between patients with and without a prodromal TIA. RESULTS: Despite similar size and severity of the perfusion deficit, initial diffusion lesions tended to be smaller and final infarct volumes were significantly reduced (final T2: 9.1 [interquartile range, 19.7] versus 36.5 [91.2] mL; P=0.014) in patients with a history of TIA (n=16). This was associated with milder clinical deficits. CONCLUSIONS: The beneficial effect of TIAs on lesion size in ADC and T2 suggests the existence of endogenous neuroprotection in the human brain.

Magnetic resonance imaging and clinical patterns of patients with 'spectacular shrinking deficit' after acute middle cerebral artery stroke.

BACKGROUND: Rapid resolution of neurological deficits after severe middle cerebral artery (MCA) stroke has been coined spectacular shrinking deficit (SSD). We studied clinical and MRI patterns in patients with SSD. METHODS: Patients with acute MCA stroke <6 h were examined by stroke MRI (perfusion- and diffusion-weighted imaging (PWI, DWI), MR angiography (MRA)) at admission, day 1 and day 7. SSD was defined as a > or =8-point-reduction of neurological deficit in the National Institute of Health Stroke Scale (NIHSS) to a score of < or =4 within 24 h. PWI and DWI lesion volumes were measured on ADC (ADC < 80%) and time to peak maps (TTP > +4 s). Recanalization was assessed by MRA after 24 h. Final infarct volumes were defined on T2 weighted images at day seven. Outcome was assessed after 90 days using modified Rankin Scale (mRS) and Barthel Index (BI). RESULTS: SSD was present in 14 of 104 patients. Initial DWI and PWI lesion volumes were smaller in SSD patients - ADC < 80%: 8.9 (4.3-20.5) vs. 30 (0-266.7) ml; TTP > +4 s: 91.6 (29.7-205.8) vs. 131.5 (0-311.5) ml. Early recanalization was associated with SSD resulted in smaller final infarct volumes (11.9 (2.4-25.9) vs. 47.7 (1.2-288.5)). All SSD patients were independent at day 90 (mRS 0 (0-2); BI 100). CONCLUSION: The clinical syndrome of SSD is reflected by a typical MRI pattern with small initial DWI and PWI lesion volumes, timely recanalization and small final infarct volumes.

The influence of extra- and intracranial artery disease on the BOLD signal in FMRI.

Functional MRI is based on the vascular response due to neuronal activation. The underlying mechanism of fMRI is the blood oxygenation level-dependent (BOLD) effect-a complex interplay between changes in the cerebral metabolisation rate of oxygen (CMRO2), neurovascular coupling, and the resulting hemodynamic response. An intact neurovascular coupling is essential for the detection of the BOLD signal and it seems likely that a disturbed cerebrovascular reserve capacity (CVRC) alters the BOLD response. We tested the hypothesis that extra- or intracranial artery disease influences the BOLD signal. Twenty-one patients with extra- or intracranial stenosis were studied with BOLD sensitive T2*-weighted MRI. All patients presented with transient or prolonged reversible ischemic symptoms ipsilateral to the artery disease but were asymptomatic at the time point of the MRI study. fMRI was performed employing a simple motor task (fist closure right and left). Additionally, the CVRC was assessed applying carbogen gas during serial T2*-weighted MRI for the calculation of CO(2) reactivity maps of the relative signal change. Signal differences between both hemispheres were compared in individual subjects and with healthy subjects. Patients with disturbed CVRC in the CO(2) reactivity maps showed either a significantly reduced (n = 5) or a negative (n = 1) BOLD signal in the affected compared to the unaffected primary sensorimotor cortex during fist closure. Patients with intact CVRC showed no significant BOLD signal differences between affected and unaffected hemisphere. Extra- or intracranial artery disease influences CVRC and consequently the BOLD signal. This observation is important for the clinical application of fMRI paradigms.

Cerebral perfusion impairment correlates with the decrease of CT density in acute ischaemic stroke.

Within the first 6 h of ischaemic stroke, changes on computed tomography (CT) scans are known as early ischaemic signs. We tested the hypothesis that the severity of perfusion impairment correlates with the degree of CT density decrease. Water uptake in ischaemic brain tissue results in a subtle decrease of CT density, and was quantified by delineation of the corresponding decrease of the apparent diffusion coefficient (ADC). Regions of decreased ADC and CT density in 29 acute-stroke patients were superimposed on the corresponding magnetic resonance perfusion images. Mean values of ADC and CT density decrease were correlated with the corresponding relative changes of cerebral blood flow (rCBF) and volume (rCBV), mean transit time (rMTT) and time-to-peak (rTTP). The decrease of CT density was 1.2 +/- 0.6 Hounsfield units and showed a linear correlation with rCBF (0.42, p < 0.01) as well as rCBV (0.62, p < 0.01), but not with the prolongation of rMTT (1.43, p = 0.78) or rTTP (1.34, p = 0.26). Therefore, the reduction of rCBF determines the severity of the early ischaemic oedema (EIOE) on CT, as well as reduction of the ADC. These findings provide a coherent view on the pathophysiology of the EIOE.

Negative dip in BOLD fMRI is caused by blood flow--oxygen consumption uncoupling in humans.

The sensitivity of MRI for local changes in the deoxyhemoglobin concentration is the basis of the blood oxygen level dependent (BOLD) effect. Time-resolved fMRI studies during visual activation show an early signal intensity (SI) decrease indicating a short lasting uncoupling of oxygen consumption and cerebral blood flow (CBF) before a SI increase due to the overcompensating hemodynamic response occurs. Normal neuronal activity may be preserved despite absent vascular responsiveness. Here we show that a negative BOLD effect occurs during motor activation in an asymptomatic patient with severely disturbed cerebral autoregulation due to extracranial artery disease. This is thought to be due to oxygen consumption in the absence of a hemodynamic response. This rare case of a persisting uncoupling of oxygen metabolism and CBF serves as a model that supports changes of the cerebral blood oxygen saturation as the major contributor of the BOLD effect.