Feasibility and logistics of MRI before thrombolytic treatment.

OBJECTIVES: The study analyzes feasibility and time-delays in Magnetic resonance imaging (MRI) based thrombolysis and estimate the impact of MRI on individual tissue plasminogen activator (rtPA) treatment. MATERIALS AND METHODS: Feasibility of MRI and time logistics were prospectively recorded in patients referred with presumed acute stroke over a 2 year time period. Door-to-needle-times (DNT) were compared with those of patients treated with rtPA after conventional CT during the same time period, and to published open label studies. RESULTS: We received 174 patients with presumed stroke. MRI was feasible in 141 of 161 (88%) of those requiring acute imaging. MRI supported the decision to treat 11 patients with mild symptoms or seizures, and not to treat four patients with extensive infarctions. Median 'door-to-needle time' (DNT) in MR scanned patients (70 min), did not differ significantly from DNT after conventional CT (n = 17, DNT = 66 min, P = 0.27) or the Safe Implementation of Thrombolysis in Stroke (SITS-MOST) registry (DNT = 68 min). CONCLUSIONS: Magnetic resonance imaging can be performed in the majority of acute stroke patients without delaying treatment. MRI may affect decision making in a large proportion of patients.

Sensory perception in complete spinal cord injury.

OBJECTIVES: To describe sensations evoked by painful or repetitive stimulation below injury level in patients with a clinically complete (American Spinal Injury Association, ASIA Grade A) spinal cord injury (SCI). MATERIAL AND METHODS: Twenty-four patients (11 with central neuropathic pain and 13 without pain) with a traumatic SCI above the tenth thoracic vertebra were examined using quantitative sensory testing, MR imaging, and somatosensory evoked potentials (SEP). RESULTS: Painful (pressure, pinch, heat or cold) or repetitive (pinprick) stimuli elicited vague localized sensations in 12 patients (50%). Pain, spasticity, and spasms were equally seen in SCI patients with or without localized sensations. SEP and MRI did not differentiate between these two groups. CONCLUSION: The present study suggests retained sensory communication across the injury in complete SCI, i.e. 'sensory discomplete' SCI.

MRI in chronic spinal cord injury patients with and without central pain.

BACKGROUND: Central pain following spinal cord injury (SCI) is common and thought to be related to lesion of the spinothalamic pathways. OBJECTIVE: To examine additional mechanisms of SCI pain. METHODS: Twenty-three SCI patients with traumatic lesions above T10 (14 with central neuropathic pain and 9 without pain) underwent MRI examination. The authors quantitatively assessed extent of cord lesion on axial T2-weighted images as percentage of 1) gray matter, 2) dorsolateral, 3) anterolateral, and 4) dorsolateral columns based on standardized drawings made by a neuroradiologist blinded to patient history. RESULTS: At the level of maximal cord injury, 21 patients had lesions involving the entire cord on axial images except for a small border of lower signal intensity, whereas 2 patients had central lesions. Rostral to the main injury, the first image with an incomplete lesion showed significantly more involvement of gray matter in pain than in pain-free patients. CONCLUSION: Consistent with animal models of SCI, spinothalamic tract lesion together with neuronal hyperexcitability due to lesion of inhibitory interneurons at the rostral end of injury are hypothesized to lead to central pain.

Correlation between diffusion- and perfusion-weighted MRI and neurological deficit measured by the Scandinavian Stroke Scale and Barthel Index in hyperacute subcortical stroke (< or = 6 hours).

OBJECTIVE: We used combined diffusion-weighted (DWI) and perfusion-weighted (PWI) MRI to characterize hyperacute infarctions within 6 h of symptom onset with special reference to subcortical infarctions, and investigated the relation between perfusion-diffusion mismatch volume and functional outcome. MATERIAL AND METHODS: Twenty-two patients presenting with symptoms of acute stroke underwent DWI and PWI within 6 h of symptom onset, and follow-up MRI 30 days later. Twelve of these had a subcortical infarction on acute DWI. Lesion volumes were measured by acute DWI and PWI as well as chronic T(2)-weighted MRI (T2WI). Clinical severity was measured by the Scandinavian Stroke Scale (SSS) and the Barthel Index (BI). RESULTS: In the 12 patients with subcortical infarctions, PWI and especially DWI correlated strongly with acute and chronic neurological SSS score, as well as with final infarct volume. Furthermore, a hyperacute PWI/DWI mismatch in this subgroup predicted lesion growth. There was a weaker correlation between acute DWI/PWI and neurological score among all 22 patients, and patients with a PWI/DWI mismatch larger than 100 ml had a significantly larger lesion growth and a poorer outcome than patients with a smaller mismatch. CONCLUSIONS: Subcortical infarctions may represent a sizeable subgroup of acute stroke patients. Also subcortical infarctions may have a PWI/DWI mismatch and therefore may respond to neuroprotective/thrombolytic therapy. Hyperacute DWI may reflect the acute clinical status and predict the outcome in patients with subcortical infarction.

Viability thresholds of ischemic penumbra of hyperacute stroke defined by perfusion-weighted MRI and apparent diffusion coefficient.

BACKGROUND AND PURPOSE: The penumbra of ischemic stroke consists of hypoperfused, but not irreversibly damaged, tissue surrounding the ischemic core. The purpose of this study was to determine viability thresholds in the ischemic penumbra, defined as the perfusion/diffusion mismatch in hyperacute stroke, by the use of diffusion- and perfusion-weighted MRI (DWI and PWI, respectively). METHODS: DWI and PWI were performed in 11 patients 1.63. Higher sensitivity and accuracy in predicting outcome of the penumbra were obtained from the rCBF maps compared with the rCBV and MTT maps. The initial rCBV and apparent diffusion coefficient ratios did not differentiate between the part of the penumbra that recovered and the part that progressed to infarction. The mean rCBF ratio was optimal in distinguishing the parts of the penumbra recovering or progressing to infarction. CONCLUSIONS: The thresholds found in this study by combined DWI/PWI might aid in the selection of patients suitable for therapeutic intervention within 6 hours. However, these hypothesized thresholds need to be prospectively tested at the voxel level on a larger patient sample before they can be applied clinically.

Prediction of tissue survival after middle cerebral artery occlusion based on changes in the apparent diffusion of water.

OBJECT: In this study the authors tested the hypothesis that the estimate of the apparent diffusion coefficient (ADC) of water is a reliable pathophysiological index of the viability of ischemic brain tissue. METHODS: Cerebral blood flow (CBF) and the cerebral metabolic rates of oxygen and glucose (CMRO2 and CMRglc, respectively) were measured using positron emission tomography (PET) scanning before and after permanent middle cerebral artery occlusion (MCAO) or reperfusion in pigs. The ADC value, which was measured using diffusion-weighted magnetic resonance (DW MR) imaging was compared with physiological variables obtained by PET scanning and with histological findings. After both permanent MCAO and reperfusion, the decrease in the ADC was significantly correlated with decrease in the CMRO2 and CMRglc. The infarction coincided with a CMRO2 threshold of 50% of the value measured on the contralateral side. Thus, an ADC value of 80% or 75% of the contralateral value reflected the CMRO2 threshold after permanent MCAO or reperfusion, respectively. On DW MR images, lesions with ADC values above 80% of the contralateral value are potentially reversible until 6 hours after MCAO, whereas lesions with ADC values below 75% of the contralateral value are irreversible as early as 2 hours after MCAO. CONCLUSIONS: The ADC of water provides a reliable pathophysiological index for tailoring therapy to the condition of individual stroke patients in clinical practice.

[MR scanning in acute apoplexy]. / MR-scanning ved akut apopleksi.

MR is increasingly used as a diagnostic tool in stroke management, especially since new and acute treatments are now available. This article describes the new MR sequences used in the scanning of stroke patients. A scanning protocol is suggested and our preliminary experiences with acute MR scanning of stroke patients are presented. Pros and cons are discussed.

Relationship between residual cerebral blood flow and oxygen metabolism as predictive of ischemic tissue viability: sequential multitracer positron emission tomography scanning of middle cerebral artery occlusion during the critical first 6 hours after stroke in pigs.

OBJECT: The authors tested the hypothesis that oxygen metabolism is the key factor linking the long-term viability of ischemic brain tissue to the magnitude of residual blood flow during the first 6 hours following a stroke. METHODS: Eleven anesthetized pigs underwent a series of positron emission tomography studies to measure cerebral blood flow (CBF) and metabolism before and for 7 hours after the animals were subjected to permanent middle cerebral artery (MCA) occlusion. The extent of collateral blood supply was assessed using angiography. Abnormal metabolism of the ischemic tissue progressed as a function of time in inverse proportion to the magnitude of residual CBF, and the volume of the infarct grew in inverse proportion to the residual blood supply. Ten hours after occlusion of the MCA, the infarct topographically matched the tissue with a cerebral metabolic rate of oxygen consumption below 50% of values measured on the contralateral side. This was also the threshold for the decline of the oxygen extraction fraction below normal, which was critical for the prediction of nonviable ischemic tissue. Mildly ischemic tissue (CBF > 30 ml/100 g/min) did not reach the cerebral metabolic rate of oxygen threshold of viability during the first 6 hours after MCA occlusion; moderately ischemic tissue (CBF 12-30 m1/100 g/ min) reached the threshold of viability in 3 hours; and severely ischemic tissue (CBF < 12 ml/100 g/min) remained viable for less than 1 hour. CONCLUSIONS: The relationship between the residual CBF and both oxygen metabolism and extraction is critical to the evolution of metabolic deficiency and lesion size after stroke.

Comparison of gradient- and spin-echo imaging: CBF, CBV, and MTT measurements by bolus tracking.

The authors measured cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT) in pigs by gadodiamide bolus injections and the bolus tracking technique. Two different pulse sequences were applied and compared: gradient-echo (GE) and spin-echo (SE) echoplanar imaging (EPI). After normalization of CBF and CBV values to the area under the arterial input function (AIF), a linear relation between the two methods was found, suggesting that a previous normalization approach for determining absolute CBF by SE EPI may be extended to GE EPI measurements. The ratio between CBV values measured with GE and SE [CBV (GE)/CBV (SE)] was 2.96. Assuming that the GE acquisition reflects total CBV, our findings suggest that SE is sensitive to 34% (1/2.96) of the total vasculature. The corresponding ratio for CBF was 2.53. There was no significant difference in these two ratios, suggesting that MTT estimates derived from GE and SE EPI measurements are comparable. The findings suggest that SE and GE are equally useful in clinical measurements of functional parameters such as CBF, CBV, and MTT in the brain. J. Magn. Reson. Imaging 2000;12:411-416.

Cerebral blood flow and blood volume measured by magnetic resonance imaging bolus tracking after acute stroke in pigs: comparison with [(15)O]H(2)O positron emission tomography.

BACKGROUND AND PURPOSE: Early and accurate assessments of cerebral ischemia allow therapy to be tailored to individual stroke patients. We examined the feasibility of using a novel method for measuring cerebral blood flow (CBF) of ischemic tissue based on MRI after middle cerebral artery occlusion (MCAO). Moreover, the regional correlations between CBF and cerebral blood volume (CBV) were investigated in the regions with acute ischemic stroke. METHODS: CBF and CBV were measured before and after MCAO or reperfusion by positron emission tomography (PET) in 13 pigs. Just after the PET scans, CBF and CBV were measured by MR bolus tracking and were compared with results obtained by PET at 6 hours after permanent MCAO or reperfusion. The infarction was verified histologically. RESULTS: The MR method yielded parametric CBF and CBV maps with tissue contrast in good agreement with parametric PET images, which demonstrated hypoperfused and hyperperfused areas after MCAO or reperfusion. Both MRI and PET technology showed that CBF values below 60% of the contralateral value induced a reduction of CBV, which committed the tissue to infarction. CONCLUSIONS: The novel MR method provides accurate measurement of CBF and CBV in acute stroke and hence gives useful information for planning the appropriate therapeutic intervention.

Combined diffusion-weighted and perfusion-weighted flow heterogeneity magnetic resonance imaging in acute stroke.

BACKGROUND AND PURPOSE: The heterogeneity of microvascular flows is known to be an important determinant of the efficacy of oxygen delivery to tissue. Studies in animals have demonstrated decreased flow heterogeneity (FH) in states of decreased perfusion pressure. The purpose of the present study was to assess microvascular FH changes in acute stroke with use of a novel perfusion-weighted MRI technique and to evaluate the ability of combined diffusion-weighted MRI and FH measurements to predict final infarct size. METHODS: Cerebral blood flow, FH, and plasma mean transit time (MTT) were measured in 11 patients who presented with acute (<12 hours after symptom onset) stroke. Final infarct size was determined with follow-up MRI or CT scanning. RESULTS: In normal brain tissue, the distribution of relative flows was markedly skewed toward high capillary flow velocities. Within regions of decreased cerebral blood flow, plasma MTT was prolonged. Furthermore, subregions were identified with significant loss of the high-flow component of the flow distribution, thereby causing increased homogeneity of flow velocities. In parametric maps that quantify the acute deviation of FH from that of normal tissue, areas of extreme homogenization of capillary flows predicted final infarct size on follow-up scans of 10 of 11 patients. CONCLUSIONS: Flow heterogeneity and MTT can be rapidly assessed as part of a routine clinical MR examination and may provide a tool for planning of individual stroke treatment, as well as in targeting and evaluation of emerging therapeutic strategies.

Xenon CT cerebral blood flow in patients with head injury: influence of pulmonary trauma on the input function.

The noninvasive xenon-enhanced CT (Xe CT) cerebral blood flow (CBF) method has been used in patients with severe traumatic brain injury (TBI) to identify the blood-flow thresholds for the development of irreversible ischaemia or infarction following severe TBI. Quantitative regional CBF (rCBF) estimates are based on the assumption of identity between the end-tidal xenon concentration curve, used as the input function, and the arterial xenon concentration curve, being the true input function to the brain. Accordingly, rCBF data addressing the issue of ischaemia should be viewed in relation to possible deviations between the end-tidal and arterial xenon concentration curves. To evaluate this possible source of error, we studied five patients with severe TBI (Glasgow coma score < or =7) who also had pulmonary trauma. CBF was studied with the Xe CT CBF method and flow rates were determined by fitting the Kety equation to each CT voxel using either the end-tidal or the arterial xenon curve as input function. In all patients rCBF estimates were lower using the end-tidal xenon curve than with the arterial xenon curve; the mean underestimation was 20.3% in gray metter and 17.3 % in white matter. The deviation between the end-tidal and arterial xenon concentration curves should be considered as a source of error when defining critical flow values according to the flow thresholds of tissue viability.

The influence of the input function on quantitative rCBF by the Xe/CT method.

Measurements of rCBF by the Xe/CT method are based on the assumption of identity between the end-tidal xenon curve which is applied as input function, and the arterial xenon curve being the true input function to the brain. In this study corresponding end-tidal and arterial xenon curves were measured in an experimental animal model (part 1) and in 5 patients with traumatic brain injury (part 2) and used for rCBF calculation. In both studies rCBF was underestimated by using the end-tidal xenon concentration curve as brain input function. In part 1 rCBF underestimation was depended on pulmonary gas exchange; high or low levels of rCBF; tissue type; and xenon inhalation protocols. In part 2 the mean rCBF underestimation was 18.8 +/- 8.3%. In conclusion, non-invasive estimate of the input function should be considered as a source of error when defining quantitative blood flow values e.g. the flow thresholds of ischaemic infarction.

Cerebral blood flow in volunteers measured by PET and Xe CT/CBF. A comparison.

Aim of this study was to compare two quantitative CBF methods. Seven young, healthy volunteers were studied with PET (15-0 labelled water) and afterwards with Xe CT/CBF (30% xenon in oxygen, 3 minutes wash-in, 5 minutes washout protocol). Xe CT/CBF showed greater differences between high and low flow areas than PET CBF. Correlation was found within subjects between ROI's, but no agreement or correlation between the methods could be demonstrated. The disagreement in this study could be due to changes in PCO2.

NC100150-enhanced 3D-SPGR MR angiography of the common carotid artery in a pig vascular stenosis model. Quantification of stenosis and dose optimization.

PURPOSE: NC100150 is a new type of ultra-small iron oxide (USPIO) blood pool agent. The aim of this study was to compare NC100150-enhanced MR angiography (MRA) to time-of-flight (TOF) MRA, phase-contrast (PC) MRA, and digital subtraction angiography (DSA) in experimental stenoses in pigs, and furthermore to determine the optimal dose of the contrast agent. MATERIAL AND METHODS: An experimental stenosis of the right and left common carotid artery (CCA) was applied surgically in 6 Yorkshire pigs. DSA was performed as the gold standard, followed by 3D-TOF, 3D-PC, and NC100150-enhanced MRA. RESULTS: Eleven stenoses of the CCA were successfully applied. The degree of the stenosis, determined by NC100150-enhanced MRA, did not differ significantly from DSA, whereas TOF and PC MRA underestimated it. The image quality of the NC100150-enhanced MRA was superior to both TOF and PC MRA. The optimal dose of NC100150 was 5-6 mg Fe/kg, since higher doses did not further increase signal-to-noise ratio or contrast-to-noise ratio. There was a linear relationship between blood relaxation rate and contrast dose. CONCLUSION: NC100150-enhanced MRA has the potential for quantification of carotid stenoses and provides an alternative to DSA. The optimal dose of NC100150 was 5-6 mg Fe/kg.

CBF and CBV measurements by USPIO bolus tracking: reproducibility and comparison with Gd-based values.

The authors measured cerebral blood flow (CBF) and cerebral blood volume (CBV) by bolus tracking of a novel ultrasmall superparamagnetic iron oxide (USPIO) contrast agent (NC100150) and compared absolute and relative perfusion measurements with those obtained by a standard gadolinium-based contrast agent. They found a linear correlation between the two methods. A dose of 0.4 mg Fe/kg body weight was found to produce a signal drop similar to that of a standard 0.2 mmol/kg gadodiamide injection using spin-echo echoplanar imaging (SE-EPI) at 1.0 T. The measurements showed a high degree of reproducibility of repeated absolute as well as relative CBF and CBV values, lending further hope to the possibility of using magnetic resonance bolus tracking for routine CBF and CBV measurements. Finally, the authors present their initial experience with high-resolution, non-EPI CBV maps obtained from steady-state levels of an intravascular superparamagnetic contrast agent.

Early changes measured by magnetic resonance imaging in cerebral blood flow, blood volume, and blood-brain barrier permeability following dexamethasone treatment in patients with brain tumors.

OBJECT: In this study the authors assessed the early changes in brain tumor physiology associated with glucocorticoid administration. Glucocorticoids have a dramatic effect on symptoms in patients with brain tumors over a time scale ranging from minutes to a few hours. Previous studies have indicated that glucocorticoids may act either by decreasing cerebral blood volume (CBV) or blood-tumor barrier (BTB) permeability and thereby the degree of vasogenic edema. METHODS: Using magnetic resonance (MR) imaging, the authors examined the acute changes in CBV, cerebral blood flow (CBF), and BTB permeability to gadolinium-diethylenetriamine pentaacetic acid after administration of dexamethasone in six patients with brain tumors. In patients with acute decreases in BTB permeability after dexamethasone administration, changes in the degree of edema were assessed using the apparent diffusion coefficient of water. CONCLUSIONS: Dexamethasone was found to cause a dramatic decrease in BTB permeability and regional CBV but no significant changes in CBF or the degree of edema. The authors found that MR imaging provides a powerful tool for investigating the pathophysiological changes associated with the clinical effects of glucocorticoids.

Cerebral blood flow measurements by magnetic resonance imaging bolus tracking: comparison with [(15)O]H2O positron emission tomography in humans.

In six young, healthy volunteers, a novel method to determine cerebral blood flow (CBF) using magnetic resonance (MR) bolus tracking was compared with [(15)O]H2O positron emission tomography (PET). The method yielded parametric CBF images with tissue contrast in good agreement with parametric PET CBF images. Introducing a common conversion factor, MR CBF values could be converted into absolute flow rates, allowing comparison of CBF values among normal subjects.

Absolute cerebral blood flow and blood volume measured by magnetic resonance imaging bolus tracking: comparison with positron emission tomography values.

The authors determined cerebral blood flow (CBF) with magnetic resonance imaging (MRI) of contrast agent bolus passage and compared the results with those obtained by O-15 labeled water (H215O) and positron emission tomography (PET). Six pigs were examined by MRI and PET under normo- and hypercapnic conditions. After dose normalization and introduction of an empirical constant phi Gd, absolute regional CBF was calculated from MRI. The spatial resolution and the signal-to-noise ratio of CBF measurements by MRI were better than by the H215O-PET protocol. Magnetic resonance imaging cerebral blood volume (CBV) estimates obtained using this normalization constant correlated well with values obtained by O-15 labeled carbonmonooxide (C15O) PET. However, PET CBV values were approximately 2.5 times larger than absolute MRI CBV values, supporting the hypothesized sensitivity of MRI to small vessels.

Comparison of the reliability of craniofacial anatomic landmarks based on cephalometric radiographs and three-dimensional CT scans.

OBJECTIVE: Conventional cephalometry is an inexpensive and well-established method for evaluating patients with dentofacial deformities. However, patients with major deformities, and in particular asymmetric cases are difficult to evaluate by conventional cephalometry. Both two- and three-dimensional computed tomography (CT) have been proposed to alleviate some of these difficulties. Only a few studies using metallic markers have indicated 3-D CT to be a useful diagnostic method, whereas no studies have evaluated the reliability of the anatomic cephalometric points used in 3-D CT. The aim of our study therefore was to compare the reliability of anatomic cephalometric points from conventional cephalograms and 3-D CT. METHODS: Nine human dry skulls were CT scanned. In addition standard lateral and frontal cephalograms were obtained. The CT scans were 3-D image reconstructed, and the cephalometric points were recorded as x, y, and z co-ordinates by two investigators. Computerized cephalometrics were performed-on the lateral and frontal cephalograms. Intra- and interindividual variations were calculated for each method and tested for statistical significance. RESULTS: Lateral cephalogram measures were more reliable than 3-D CT, with interobserver variations less than 1 mm for most points compared to about 2 mm for 3-D CT. Lateral cephalometrics also showed significantly less interobserver variation for six variables. This was, however, less obvious when 3-D CT was compared to frontal cephalograms. Frontal cephalometrics showed significantly less interobserver variation for three of the investigated variables. CONCLUSIONS: For standard lateral and frontal cephalometric points, there is no evidence that 3-D CT is more reliable than the conventional cephalometric methods in normal skull, and the benefit of 3-D CT cephalometric is indicated to be in the severe asymmetric craniofacial syndrome patients, as conventional cephalometrics is known to be inferior in these cases.