Brain choline concentration. Early quantitative marker of ischemia and infarct expansion?

OBJECTIVE: Better prediction of tissue prognosis in acute stroke might improve treatment decisions. We hypothesized that there are metabolic ischemic disturbances measurable noninvasively by proton magnetic resonance spectroscopy ((1)H MRS) that occur earlier than any structural changes visible on diffusion-tensor imaging (DTI), which may therefore serve for territorial identification of tissue at risk. METHODS: We performed multivoxel (1)H MRS plus DTI within a maximum of 26 hours, and DTI at 3-7 days, after ischemic stroke. We compared choline, lactate, N-acetylaspartate, and creatine concentrations in normal-appearing voxels that became infarcted (infarct expansion) with normal-appearing voxels around the infarct that remained "healthy" (nonexpansion) on follow-up DTI. Each infarct expansion voxel was additionally classified as either complete infarct expansion (infarcted tissue on follow-up DTI covered > or =50% of the voxel) or partial infarct expansion (<50% of voxel). RESULTS: In 31 patients (NIH Stroke Scale score 0-28), there were 108 infarct nonexpansion voxels and 113 infarct expansion voxels (of which 80 were complete expansion and 33 partial expansion voxels). Brain choline concentration increased for each change in expansion category from nonexpansion, via partial expansion to complete expansion (2,423, 3,843, 4,158 IU; p < 0.05). Changes in lactate, N-acetylaspartate, and creatine concentrations in expansion category were insignificant although for lactate there was a tendency to such association. CONCLUSIONS: Choline concentration measurable with (1)H MRS was elevated in peri-ischemic normal-appearing brain that became infarcted by 3-7 days. The degree of elevation was associated with the amount of infarct expansion. (1)H MRS might identify DTI-normal-appearing tissue at risk of conversion to infarction in early stroke.

Development and initial testing of normal reference MR images for the brain at ages 65-70 and 75-80 years.

Interpretation of brain images from older patients requires knowledge of changes that occur with healthy ageing. We constructed and tested a reference template for older subjects. We used MR images from normal subjects aged 65-70 and 75-80 to generate average age-specific images. We ranked the T2-weighted images by worsening brain tissue loss to create a diagram of key centiles. Two neuroradiologists tested the template during routine reporting; eight radiologists read 99 MR examinations without and then with the template. Fifty-four subjects (65-70 years) and 25 subjects (75-80 years) formed the reference images. For the two neuroradiologists, the reference template reduced the abnormal scan reporting from 28/42 without to 3/42 with the template. Of 99 MR examinations assessed by eight radiologists, 39/58 scans (67%) reported as moderate or severe atrophy without the template were reported as normal with the template (p = 0.00011). Reference templates of the brain at older ages can "calibrate" radiology reporting. They could also be useful for research into ageing and related conditions. Larger numbers of examinations from more diverse populations and at different ages are required to increase the versatility of these templates.

Changes in NAA and lactate following ischemic stroke: a serial MR spectroscopic imaging study.

OBJECTIVE: Although much tissue damage may occur within the first few hours of ischemic stroke, the duration of tissue injury is not well defined. We assessed the temporal pattern of neuronal loss and ischemia after ischemic stroke using magnetic resonance spectroscopic imaging (MRSI) and diffusion-weighted imaging (DWI). METHODS: We measured N-acetylaspartate (NAA) and lactate in 51 patients with acute ischemic stroke at five time points, from admission to 3 months, in voxels classified as normal, possibly or definitely abnormal (ischemic) according to the appearance of the stroke lesion on the admission DWI. We compared changes in NAA and lactate in different voxel classes using linear mixed models. RESULTS: NAA was significantly reduced from admission in definitely and possibly abnormal (p < 0.01) compared to contralateral normal voxels, reaching a nadir by 2 weeks and remaining reduced at 3 months. Lactate was significantly increased in definitely and possibly abnormal voxels (p < 0.01) during the first 5 days, falling to normal at 2 weeks, rising again later in these voxels. CONCLUSION: The progressive fall in N-acetylaspartate suggests that some additional neuronal death may continue beyond the first few hours for up to 2 weeks or longer. The mechanism is unclear but, if correct, then it is possible that interventions to limit this ongoing subacute tissue damage might add to the benefit of hyperacute treatment, making further improvements in outcome possible.

MR diffusion-weighted imaging and outcome prediction after ischemic stroke.

BACKGROUND: MR diffusion-weighted imaging (DWI) shows acute ischemic lesions early after stroke so it might improve outcome prediction and reduce sample sizes in stroke treatment trials. Previous studies of DWI and outcome produced conflicting results. OBJECTIVE: To determine whether DWI lesion characteristics independently predict outcome in a broad range of patients with acute stroke. METHODS: The authors recruited hospital-admitted patients with all severities of suspected stroke, assessed stroke severity on the NIH Stroke Scale (NIHSS), performed early brain DWI, and assessed outcome at 3 months (modified Rankin Scale). Clinical data and DWI lesion parameters were evaluated in a logistic regression model to identify independent predictors of outcome at 3 months and a previously described "Three-Item Scale" (including DWI) was tested for outcome prediction. RESULTS: Among 82 patients (mean NIHSS 7.1 [+/-6.3 SD]), the only independent outcome predictors were age and stroke severity. Neither DWI lesion volume nor apparent diffusion coefficient nor the previously described Three-Item Scale predicted outcome independently. Comparison with previous studies suggested that DWI may predict outcome only in patients with more severe cortical ischemic strokes. CONCLUSIONS: Across a broad range of stroke severities, diffusion-weighted imaging (DWI) did not predict outcome beyond that of key clinical variables. Thus, DWI is unlikely to reduce sample sizes in acute stroke trials assessing functional outcome, especially where estimated treatment effects are modest.

Effects of dexamethasone on cerebral perfusion and water diffusion in patients with high-grade glioma.

BACKGROUND AND PURPOSE: The mechanisms by which the glucocorticoid dexamethasone produces its therapeutic action in patients with intracranial tumors still remain unclear. The purpose of this study was to investigate whether dexamethasone affects cerebral perfusion and water molecule diffusion by using quantitative dynamic susceptibility contrast perfusion MR imaging (DSC-MR imaging) and diffusion tensor MR imaging (DT-MR imaging). METHODS: Ten consecutive patients with glioblastoma multiforme underwent DSC-MR imaging and DT-MR imaging before and 48-72 hours after dexamethasone treatment (16 mg/day). Cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT), and water mean diffusivity () were measured for enhancing tumor, nonenhancing peritumoral edematous brain, and normal-appearing contralateral white matter before and after steroid therapy. The percentage change in CBF, CBV, MTT, and for the 3 tissue types was calculated for each patient, a mean value obtained for the population, and the statistical significance determined by using a paired-samples Student t test. RESULTS: After dexamethasone treatment, there was no significant change in tumor CBF, CBV, or MTT. Edematous brain CBV and MTT were also unchanged. There was, however, an increase in edematous brain CBF (11.6%; P = .05). was reduced in both enhancing tumor (-5.8%; P = .001) and edematous brain (-6.0%; P < .001). There was no significant change in CBF, CBV, MTT, or for normal-appearing contralateral white matter after treatment. CONCLUSION: These data suggest that dexamethasone does not significantly affect tumor blood flow but may, by reducing peritumoral water content and local tissue pressure, subtly increase perfusion in the edematous brain.

Do acute diffusion- and perfusion-weighted MRI lesions identify final infarct volume in ischemic stroke?

BACKGROUND AND PURPOSE: An acute mismatch on diffusion-weighted MRI (DWI) and perfusion-weighted MRI (PWI) may represent the "tissue-at-risk." It is unclear which "semiquantitative" perfusion parameter most closely identifies final infarct volume. METHODS: Acute stroke patients underwent DWI and PWI (dynamic-susceptibility contrast imaging) on admission (baseline), and T2-weighted imaging (T2WI) at 1 or 3 months after stroke. "Semiquantitative" mean transit time (MTTsq=first moment of concentration/time curve), cerebral blood volume (CBVsq=area under concentration/time curve), and cerebral blood flow (CBFsq=CBVsq/MTTsq) were calculated. DWI and PWI lesions were measured at baseline and final infarct volume on T2WI acquired > or =1 month after stroke. Baseline DWI, CBFsq, and MTTsq lesion volumes were compared with final T2WI lesion volume. RESULTS: Among 46 patients, baseline DWI and CBFsq lesions were not significantly different from final T2WI lesion volume, but baseline MTTsq lesions were significantly larger. The correlation with final T2WI lesion volume was strongest for DWI (Spearman rank correlation coefficient rho=0.68), intermediate for CBFsq (rho=0.55), and weakest for MTTsq (rho=0.49) baseline lesion volumes. Neither DWI/CBFsq nor DWI/MTTsq mismatch predicted lesion growth; lesion growth was equally common in those with and without mismatch. CONCLUSIONS: Of the 2 PWI parameters, CBFsq lesions most closely identifies, and MTTsq overestimates, final T2WI lesion volume. "DWI/PWI mismatch" does not identify lesion growth. Patients without "DWI/PWI mismatch" are equally likely to have lesion growth as those with mismatch and should not be excluded from acute stroke treatment.

Temporal evolution of water diffusion parameters is different in grey and white matter in human ischaemic stroke.

OBJECTIVES: Our purpose was to investigate whether differences exist in the values and temporal evolution of mean diffusivity () and fractional anisotropy (FA) of grey and white matter after human ischaemic stroke. METHODS: Thirty two patients with lesions affecting both grey and white matter underwent serial diffusion tensor magnetic resonance imaging (DT-MRI) within 24 hours, and at 4-7 days, 10-14 days, 1 month, and 3 months after stroke. Multiple small circular regions of interest (ROI) were placed in the grey and white matter within the lesion and in the contralateral hemisphere. Values of [grey], [white], FA[grey] and FA[white] were measured in these ROI at each time point and the ratios of ischaemic to normal contralateral values (R and FAR) calculated. RESULTS: and FA showed different patterns of evolution after stroke. After an initial decline, the rate of increase of [grey] was faster than [white] from 4-7 to 10-14 days. FA[white] decreased more rapidly than FA[grey] during the first week, thereafter for both tissue types the FA decreased gradually. However, FA[white] was still higher than FA[grey] at three months indicating that some organised axonal structure remained. This effect was more marked in some patients than in others. R[grey] was significantly higher than R[white] within 24 hours and at 10-14 days (p<0.05), and FAR[white] was significantly more reduced than FAR[grey] at all time points (p<0.001). CONCLUSIONS: The values and temporal evolution of and FA are different for grey and white matter after human ischaemic stroke. The observation that there is patient-to-patient variability in the degree of white matter structure remaining within the infarct at three months may have implications for predicting patient outcome.

Effects of dexamethasone on peritumoural oedematous brain: a DT-MRI study.

OBJECTIVES: Glucocorticoids (dexamethasone) are thought to reduce peritumoural brain oedema by decreasing the permeability of neoplastic capillaries and/or enhancing the clearance of extracellular water. Diffusion tensor magnetic resonance imaging (DT-MRI) was used to measure the water diffusion parameters of oedematous and normal brain in a group of patients with intracranial tumours before and after steroid treatment. METHODS: Fifteen patients with intracranial tumours (seven with high-grade glioma, four with metastatic carcinoma and four with meningioma) were examined before and 48-72 h after dexamethasone treatment (16 mg/day). The mean diffusivity () and fractional anisotropy (FA) were measured for oedematous brain and apparently normal contralateral white matter before and after steroid therapy. RESULTS: In all three patient groups there was a significant decrease in of oedematous brain after steroid treatment (p<0.01). There was no significant change in FA of oedematous brain after treatment in any of the three groups. There was also no significant change in either or FA of apparently normal contralateral white matter after treatment. CONCLUSION: These data indicate that dexamethasone produces a localised reduction in the magnitude of extracellular water molecule mobility, and hence water content, in peritumoural oedematous brain. Furthermore, the magnitude of these changes is similar for both intra- and extra-axial tumours.

Fusion of contrast-enhanced breast MR and mammographic imaging data.

Increasing use is being made of Gd-DTPA contrast-enhanced MRI (CE-MRI) for breast cancer assessment since it provides three-dimensional (3D) functional information via pharmacokinetic interaction between contrast agent and tumour vascularity, and because it is applicable to women of all ages as well as patients with post-operative scarring. CE-MRI is complementary to conventional X-ray mammography, since it is a relatively low-resolution functional counterpart of a comparatively high-resolution 2D structural representation. However, despite the additional information provided by MRI, mammography is still an extremely important diagnostic imaging modality, particularly for several common conditions such as ductal carcinoma in situ (DCIS) where it has been shown that there is a strong correlation between microcalcification clusters and malignancy. Pathological indicators such as calcifications and fine spiculations are not visible in CE-MRI and therefore there is clinical and diagnostic value in fusing the high-resolution structural information available from mammography with the functional data acquired from MRI. This article is a clinical overview of the results of a technique to transform the coordinates of regions of interest (ROIs) from the 2D mammograms to the spatial reference frame of the contrast-enhanced MRI volume. An evaluation of the fusion framework is demonstrated with a series of clinical cases and a total of 14 patient examples.

Is diffusion imaging appearance an independent predictor of outcome after ischemic stroke?

BACKGROUND: MR diffusion-weighted imaging (DWI) in ischemic stroke can be quantified by calculating the apparent diffusion coefficient (ADC) or measuring lesion volume. OBJECTIVE: To clarify the association between DWI lesion parameters, clinical stroke severity at baseline, and the relationship with functional outcome. METHODS: Consecutive patients with stroke were categorized for stroke type (Oxford Community Stroke Project Classification [OCSP]) and severity (Canadian Neurologic Scale [CN Scale]) before DWI. The ratio of the trace of the apparent diffusion tensor in the ischemic lesion to the mirror image area in the contralateral hemisphere was calculated (r). The volume of the visible lesion on DWI was measured. Any visible lesion on T2-weighted imaging (T2WI) was noted. All assessments were blind to all other information. A blinded observer obtained a 6-month Rankin score. Univariate and multivariate analyses were performed to test for independent associations with outcome. RESULTS: In 108 patients, those with lower (i.e., more abnormal) r values had more severe strokes according to the CN Scale (p = 0.01) and the OCSP stroke type (p = 0.002), a large lesion on DWI (p = 0.05), a visible lesion on T2WI (p = 0.001), and poor 6-month functional outcome (p = 0.009). However, on logistic regression, neither r nor DWI lesion volume were independent predictors of 6-month outcome over and above age and stroke severity. CONCLUSION: The r is associated with functional outcome, but that is because it and DWI lesion volume are also associated with stroke severity. Although DWI lesion features are univariate surrogate outcome predictors, the authors were unable to show that they were independent outcome predictors in the current study. Differences between these and other results may be due to differences in study design, sample size, and case mix.

Utilizing the diffusion-to-noise ratio to optimize magnetic resonance diffusion tensor acquisition strategies for improving measurements of diffusion anisotropy.

It is well known that quantitative anisotropy measurements derived from the diffusion tensor are extremely sensitive to noise contamination. The level of noise in the diffusion tensor imaging (DTI) experiment is usually measured from some estimate of the signal-to-noise ratio (SNR) in the component diffusion-weighted (DW) images. This measure is, however, highly dependent on experimental parameters, such as the diffusion attenuation b-value and the diffusion coefficient of the subject. Conversely, the diffusion-to-noise ratio (DNR), defined as the SNR of the calculated diffusion tensor trace map, provides a reliable estimate of noise contamination, which is largely independent of such parameters. In this work it is demonstrated how reliable anisotropy measurements can be obtained using an image acquisition strategy that optimizes the DNR of the DTI experiment. This acquisition scheme is shown to provide noise-independent measurements of typical diffusion anisotropy values found in the human brain.

A study of the apparent diffusion coefficient of grey and white matter in human ischaemic stroke.

We examined whether there was any difference in the value, and temporal evolution, of the apparent diffusion tensor trace (ADC) in acute and subacute grey and white matter lesions. Thirty-seven patients underwent diffusion imaging once (up to 3 days), 15 patients were scanned twice (up to 7 days), and seven patients were scanned three times (up to 14 days) after stroke. Values of the ratio of ischaemic to contralateral ADC (ADCr) were reduced on average by 30% (p<0.001) in the whole hyperintense region up to 7 days post-ictus. No difference was seen between ADCr values of grey and white matter in individual subjects within the patient groups scanned up to 7 days. However, in the subgroup of patients scanned beyond 7 days, ADCr for grey matter rose significantly (p=0.02) from ADCr approximately 0.7 (< 7 days) to 0.95 (> or = 10 days). This increase did not occur in white matter whose ADCr remained fairly constant (ADCr approximately 0.7) over the time course of the study.

On the use of water phantom images to calibrate and correct eddy current induced artefacts in MR diffusion tensor imaging.

The accurate determination of absolute measures of diffusion anisotropy in vivo using single-shot, echo-planar imaging techniques requires the acquisition of a set of high signal-to-noise ratio, diffusion-weighted images that are free from eddy current induced image distortions. Such geometric distortions can be characterized and corrected in brain imaging data using magnification (M), translation (T), and shear (S) distortion parameters derived from separate water phantom calibration experiments. Here we examine the practicalities of using separate phantom calibration data to correct high b-value diffusion tensor imaging data by investigating the stability of these distortion parameters, and hence the eddy currents, with time. It is found that M, T, and S vary only slowly with time (i.e., on the order of weeks), so that calibration scans need not be performed after every patient examination. This not only minimises the scan time required to collect the calibration data, but also the computational time needed to characterize these eddy current induced distortions. Examples of how measurements of diffusion anisotropy are improved using this post-processing scheme are also presented.

Selecting an appropriate anisotropy index for displaying diffusion tensor imaging data with improved contrast and sensitivity.

A review of the behavior of different diffusion anisotropy indices (DAIs) to changes in diffusion anisotropy was undertaken and the limitations of several previously proposed DAIs are discussed. A mathematical representation of anisotropy sensitivity was used to enable image contrast and sensitivity to noise to be predicted. This technique was utilized to devise a new DAI, the gamma-variate anisotropy, which has a low sensitivity to noise and an improved contrast range for human brain imaging. This index can be easily modified for other applications, in that the range of anisotropy values to which it is highly sensitive can be altered. Magn Reson Med 44:117-121, 2000.

Accuracy of a miniature intracranial pressure monitor, its function during magnetic resonance scanning, and assessment of image artifact generation.

OBJECTIVE: We examined the accuracy and repeatability of an intracranial pressure (ICP) monitor (Codman MicroSensor; Johnson & Johnson Professional, Inc., Raynham, MA) in a nonmagnetic environment and during magnetic resonance imaging (MRI). The resulting image artifact generation was calculated. ICP monitoring is essential in management of severe head injury, but few ICP monitoring devices are compatible with use in an MRI scanner. The use of MRI to assess head injury is increasing, and developing safe methods of continuously monitoring ICP may improve patient care. METHODS: A water manometer was used as the standard for comparison. We assessed pressure readings from the ICP monitor in a nonmagnetic environment using a standard and a long connector cable between the pressure transducer and display unit. This long cable permitted testing during MRI sequences because the display unit could be distanced from the magnet. Accuracy was determined during T2-weighted imaging, proton spectroscopy, and diffusion-weighted imaging, and artifact generation was assessed. RESULTS: We found a high degree of accuracy for repeated measurements over a clinical pressure range using both standard and long connector cables outside the MRI room. During MRI scanning, the ICP monitor was accurate during T2 and proton spectroscopy sequences. Accuracy during diffusion-weighted imaging, however, was clinically unacceptable. This ICP monitor creates a reduction in signal-to-noise ratio in the received signal during T2-weighted imaging and proton spectroscopic imaging, with the obtained images still radiologically interpretable. CONCLUSION: The Codman ICP monitor is sufficiently accurate and free of artifact generation to be used during most clinical MRI applications. This could enhance patient monitoring and safety.

A theoretical study of the effect of experimental noise on the measurement of anisotropy in diffusion imaging.

Diffusion tensor imaging (DTI) is a modality known to be highly sensitive to the detrimental effects of experimental noise. Here, using Monte Carlo simulations, we compare and contrast how noise complicates the measurement of diffusion anisotropy in diffusion tensor and conventional diffusion-weighted imaging (DWI). As the signal-to-noise ratio (SNR) decreases below a value of approximately 20, the eigenvalues (lambda(i)) of the diffusion tensor D are found to diverge rapidly from their true values, with the result that the measured anisotropy can be significantly in error and isotropic structures falsely assigned a high level of anisotropy. The effect of noise on the rotationally variant indices, calculated from a conventional diffusion-weighted imaging experiment, is found to be much less insidious, because the apparent diffusion coefficients (ADCs) diverge only slowly as the signal-to-noise decreases. Thus, although rotationally variant indices almost always underestimate the true diffusion anisotropy, they show only a small susceptibility to experimental noise and hence, are preferred to their rotationally invariant counterparts when the signal-to-noise ratio is small.

Diffusion anisotropy measurements in ischaemic stroke of the human brain.

Magnetic resonance diffusion imaging was performed on 12 patients presenting with symptoms of acute ischaemic stroke (1-6 days post-ictus). Apparent diffusion coefficient (ADC) and diffusion anisotropy measurements were obtained from ischaemic and contralateral normal regions. ADC measurements were decreased by around 40% in ischaemic regions, indicated by an average stroke to normal ratio of 0.56 +/- 0.04 (p < 0.0001). The measured anisotropy was shown to be significantly increased in ischaemic regions, using both standard deviation and volume ratio anisotropy indices, which gave stroke to normal ratios of 1.78 +/- 0.27 (p = 0.003) and 0.87 +/- 0.05 (p = 0.005) respectively. The effects of gradient interactions, image registration, noise contamination and rotational variance and their implications for the results obtained in this study are discussed.