Dynamic changes in corticospinal tracts after stroke detected by fibretracking.

BACKGROUND AND AIMS: The integrity of motor pathways and functional connectivity patterns are important in assessing plastic changes related to successful recovery, to obtain prognostic information and to monitor future therapeutic strategies of stroke patients. We tested the following hypotheses: (1) that changes in axonal integrity along the corticospinal tract after stroke can be detected as a reduction in fractional anisotropy; and (2) that sustained low fractional anisotropy is indicative of axonal loss and therefore is correlated with poor motor outcome, as measured by specific neurological motor scores. METHODS: We developed a segmentation tool based on magnetic resonance diffusion tensor imaging in conjunction with three dimensional fibretracking for longitudinal studies of the corticospinal tract, and used specific neurological motor scores to test the hypotheses in five stroke patients within the first week and 30 and 90 days after the stroke. RESULTS: Reduction in fractional anisotropy within the first weeks after stroke reflected a decline in axonal integrity, leading to Wallerian degeneration, and demonstrated a correlation between the temporal evolution of fractional anisotropy and motor function in patients with poor motor outcome. CONCLUSION: The study demonstrated the feasibility of fibretracking as a segmentation tool for mapping distal parts of the corticospinal motor pathways and showed that fractional anisotropy in the segmented corticospinal tract is a sensitive measure of structural changes after stroke.

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.

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.

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.

Isokinetic eccentric exercise as a model to induce and reproduce pathophysiological alterations related to delayed onset muscle soreness.

Physiological alterations following unaccustomed eccentric exercise in an isokinetic dynamometer of the right m. quadriceps until exhaustion were studied, in order to create a model in which the physiological responses to physiotherapy could be measured. In experiment I (exp. I), seven selected parameters were measured bilaterally in 7 healthy subjects at day 0 as a control value. Then after a standardized bout of eccentric exercise the same parameters were measured daily for the following 7 d (test values). The measured parameters were: the ratio of phosphocreatine to inorganic phosphate (PCr/Pi), the ratio of inorganic phosphate to adenosintriphosphate (Pi/ATP), the ratio of phosphocreatine to adenosintriphosphate (PCr/ATP) (all three ratios measured with 31P-nuclear magnetic resonance spectroscopy), dynamic muscle strength, plasma creatine kinase (CK), degree of pain and "muscle" blood flow rate (133Xenon washout technique). This was repeated in experiment II (exp. II) 6-12 months later in order to study reproducibility. In experiment III (exp. III), the normal fluctuations over 8 d of the seven parameters were measured, without intervention with eccentric exercise in 6 other subjects. All subjects experienced pain, reaching a maximum 48 h after eccentric exercise in both exp. I and II. A systematic effect over time for CK (increasing 278% resp. 308%), muscle strength (decreasing more than 10%), PCr/Pi (decreasing 31% resp. 43%) and Pi/ATP (increasing 55% resp. 99%) was found in both exp. I and II (P < 0.05), but not in exp. III. No significant difference was observed between exp. I and II for CK, blood-flow rate, concentric muscle strength, PCr/Pi, Pi/ATP and PCr/ATP. It is concluded that pathophysiological alterations in m. quadriceps following eccentric exercise can be induced and can be reproduced after an interval of 6 months. Thus, this model can be used to study the effects of physiotherapy.

The effect of passive stretching on delayed onset muscle soreness, and other detrimental effects following eccentric exercise.

The aim of this study was to measure if passive stretching would influence delayed onset muscle soreness (DOMS), dynamic muscle strength, plasma creatine kinase concentration (CK) and the ratio of phosphocreatine to inorganic phosphate (PCr/P(i)) following eccentric exercise. Seven healthy untrained women, 28-46 years old, performed eccentric exercise with the right m. quadriceps in an isokinetic dynamometer (Biodex, angle velocity: 60 degrees.s-1) until exhaustion, in two different experiments, with an interval of 13-23 months. In both experiments the PCr/P(i) ratio, dynamic muscle strength, CK and muscle pain were measured before the eccentric exercise (day 0) and the following 7 d. In the second experiment daily passive stretching (3 times of 30 s duration, with a pause of 30 s in between) of m. quadriceps was included in the protocol. The stretching was performed before and immediately after the eccentric exercise at day 0, and before measurements of the dependent variables daily for the following 7 d. The eccentric exercise alone led to significant decreases in PCr/P(i) ratio (P < 0.001) and muscle strength (P < 0.001), and an increase in CK concentration (P < 0.01). All subjects reported pain in the right m. quadriceps with a peak 48 h after exercise. There was no difference in the reported variables between experiments one and two. It is concluded that passive stretching did not have any significant influence on increased plasma-CK, muscle pain, muscle strength and the PCr/P(i) ratio, indicating that passive stretching after eccentric exercise cannot prevent secondary pathological alterations.

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.

Simultaneous 31P-NMR spectroscopy and EMG in exercising and recovering human skeletal muscle: a correlation study.

A large number of studies have shown amplitude and spectral changes of the electromyogram during exercise, leading to several theories of how these changes might be related to the underlying metabolic changes. The amplitude and spectral changes are generally interpreted as changes in motor unit recruitment and a reduction of the muscle fiber conduction velocity due to proton or lactate accumulation. This study focuses on the causality of spectral changes of the surface electromyogram and proton or lactate accumulation and how the changes in motor unit recruitment are related to the metabolic status of the muscle. Simultaneous 31P-nuclear magnetic resonance spectroscopy and surface electromyography were performed during sustained static exercise and recovery in healthy volunteers and a patient with McArdle's disease. A clear dissociation between the median power frequency of the surface electromyogram and pH was seen in the healthy volunteers during recovery and during exercise in the patient with McArdle's disease. The results indicate that proton or lactate accumulation is not primarily responsible for the spectral changes of the surface electromyogram as previously suggested. The motor unit recruitment (as judged by the root mean square of the surface electromyogram) increased hyperbolically during the submaximal static exercise, with decreasing phosphocreatine-to-P(i) ratio reaching maximum at 0.6 (exhaustion), and seems to constitute a consistent metabolic limit to the exercise. The increased myoelectrical activity seen after exercise is not caused by an incomplete recovery of phosphorous metabolism, pH, or lactate but could probably be an impairment of the excitation-contraction coupling.

Muscle strength, voluntary activation and cross-sectional muscle area in patients with fibromyalgia.

The objectives were to determine whether the low muscle strength in fibromyalgia is due to lack of exertion and to determine the relation between strength and muscle area. Secondarily we examined the voluntary muscle strength of the different muscles of the leg. The twitch interpolation technique was used to estimate the degree of central activation and the 'true' quadriceps muscle strength. Muscle cross-sectional area was determined with magnetic resonance imaging (MRI). The estimated 'true' muscle strength was 91 Nm (S.D. = 34 Nm) in 15 fibromyalgia patients compared with 125 Nm (28 Nm) in 14 healthy controls (P < 0.02). The 'true' strength divided by the sum of the maximal areas of the four bellies of the quadriceps muscle was lower, being 1.56 Nm/cm2 (0.32 Nm/cm2) in fibromyalgia patients compared with 2.11 Nm/cm2 (0.39 Nm/cm2) in the controls (P < 0.001). The voluntary muscle strength of the flexor muscles of the knee and of the plantar flexors of the ankle was markedly reduced in patients, but no significant differences could be observed in the strength of the dorsal flexors of the ankle. In conclusion, a reduction of the estimated 'true' quadriceps muscle strength per unit area of about 35% was found in fibromyalgia patients.

31P NMR spectroscopy and electromyography during exercise and recovery in patients with fibromyalgia.

OBJECTIVE: To investigate whether patients with fibromyalgia (FM) have normal motor unit recruitment in relation to muscle metabolism during exhausting exercise and recovery, and whether the reduced voluntary muscle force normally seen is related to a smaller muscle size. METHODS: Female patients with FM and sedentary controls were examined using simultaneous 31P nuclear magnetic resonance spectroscopy (NMR) and surface electromyography (SEMG) during exhaustive static exercise of the anterior tibial muscle and during recovery. The maximum voluntary contraction force was estimated, and the maximum cross sectional muscle area was evaluated using 1H NMR imaging. The sedentary controls were matched to patients for sex, age and, as far as possible, daily physical activity levels. RESULTS: Patients with FM had reduced maximum voluntary contraction force in relation to the sedentary controls, despite having similar muscle size. In general the myoelectrical-metabolic relation during exercise and recovery was normal in patients with FM. CONCLUSION: The less extreme changes in motor unit recruitment and metabolism during exhaustive exercise indicated a lower exercise tolerance that could be connected with the lower physical activity levels.

Simultaneous 31P NMR spectroscopy and EMG in exercising and recovering human skeletal muscle: technical aspects.

The bioenergetics of human skeletal muscle can be studied by 31P NMR spectroscopy (31P-MRS) and by surface electromyography (SEMG). Simultaneous 31P-MRS and SEMG permit accurate and noninvasive studies of the correlation between metabolic and electrical changes in exercising and recovering human skeletal muscle, a relationship that is still poorly understood. This study describes the optimization of skeletal muscle 31P-MRS in a whole-body magnet, involving surface coil design, utilization of adiabatic radio frequency pulses and advanced time-domain fitting, to the technical design of SEMG. A nonmagnetic ergometer was used for ankle dorsiflexions that activated only the anterior tibial muscle as verified by post exercise imaging. The coil design and the adiabatic sech/tanh pulse improved sensitivity by 45% and 56% respectively, compared with standard techniques. Simultaneous electromyographic recordings did not deteriorate the NMR spectra. The VARPRO time domain fitting routine was very suitable for estimating 31P muscle spectra. With these methods it was possible to accurately estimate parameters describing metabolic and electrical changes during rest, exercise and the entire recovery period with a 20-s time resolution on a standard 1.5 T whole-body NMR scanner.

Simultaneous electromyography and 31P nuclear magnetic resonance spectroscopy--with application to muscle fatigue.

The electromyogram (EMG) is often used to study human muscle fatigue, but the changes in the electromyographic signals during muscle contraction are not well understood in relation to muscle metabolism. The 31P NMR spectroscopy is a semi-quantitative non-invasive method for studying the metabolic changes in human muscle. The aim of this study was to develop a method by which EMG and NMR spectroscopy measurements could be performed simultaneously. All measurements were performed in a whole body 1.5 Tesla NMR scanner. A calf muscle ergometer, designed for use in a whole body NMR scanner, was used. The subject had the left foot strapped to the ergometer. The anterior tibial EMG was recorded by bipolar surface electrodes. A surface coil was strapped to the anterior tibial muscle next to the EMG electrodes. Simultaneous measurements of surface EMG and surface coil 31P NMR spectroscopy were performed in the scanner during an isometric submaximal voluntary contraction until exhaustion, in 6 normal volunteers. Concentrations of phosphocreatine (PCr), inorganic phosphate (P(i)) and pH were analysed together with root mean square (RMS) and median frequency of the EMG. The fatiguing contractions (endured 5-13 min) produced a rapid decline in PCr and pH accompanied by a rapid rise in P(i). The RMS was approximately constant until the normalized PCr concentration declined below 0.6-0.7 and the pH declined below 6.75-6.85; exceeding these metabolic limits was associated with a rapidly increasing RMS value (2-3 times the previous level by exhaustion). The median frequency declined linearly with time and was found to be highly linearly correlated with the pH value (r = 0.82).(ABSTRACT TRUNCATED AT 250 WORDS)