This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by van Everdingen, K.J. Articles by Mali, W.P.T.M. Search for Related Content PubMed PubMed Citation Articles by van Everdingen, K.J. Articles by Mali, W.P.T.M.

(Stroke. 1998;29:1783-1790.)
© 1998 American Heart Association, Inc.

Original Contributions

Diffusion-Weighted Magnetic Resonance Imaging in Acute Stroke

K.J. van Everdingen, MD; J. van der Grond, PhD; L.J. Kappelle, MD, PhD; L.M.P. Ramos, MD; W.P.T.M. Mali, MD, PhD

From the Departments of Radiology and Neurology (L.J.K.), University Hospital Utrecht (Netherlands).

	Abstract

Top Abstract Introduction Subjects and Methods Results Discussion References

 
Background and Purpose—Diffusion-weighted MRI (DWI) is highly sensitive in detecting early cerebral ischemic changes in acute stroke patients. In this study we compared the sensitivity of DWI with that of conventional MRI techniques. Furthermore, we investigated the prognostic value of the volume of ischemic lesions on DWI scans and of the apparent diffusion coefficient (ADC).

Methods—We performed DWI, fluid-attenuated inversion recovery, spin-echo T2-weighted MRI, and spin-echo proton density–weighted MRI in 42 patients with acute stroke and 15 control subjects. The volume of ischemic lesions was measured on early (<60 hours after onset) and follow-up MRI scans. Clinical outcome was measured 4 months after onset of symptoms with the National Institutes of Health Stroke Scale, the Barthel Index, and the Rankin Scale.

Results—With DWI, 98% of the ischemic lesions were detected, and with fluid-attenuated inversion recovery, 91% were detected, whereas with early T2-weighted or proton density–weighted scans, only 71% (P=0.002, ²) and 80% (P=0.02, ²) of lesions, respectively, were found. Lesion volume on early DWI scans correlated significantly with clinical outcome ratings (P<0.01). In patients with a first-ever stroke, a lesion volume of 22 mL on DWI predicted good outcome with a 75% sensitivity and a 100% specificity. The mean ADC of ischemic lesions was 29% lower than the ADC of normal-appearing parts of the brain (P<0.001). The ADC ratio correlated significantly with clinical outcome (P<0.05).

Conclusions—DWI is a better imaging method than conventional MRI in detecting early ischemic lesions in stroke patients. Lesion size as measured on DWI scans and, to a lesser extent, ADC values are potential parameters for predicting clinical outcome in acute stroke patients.

Key Words: cerebral infarction • magnetic resonance imaging • stroke assessment • stroke, acute

	Introduction

Top Abstract Introduction Subjects and Methods Results Discussion References

 
In stroke patients, imaging of the brain with CT or T2-weighted (T2-w) MRI is an important tool to distinguish between hemorrhagic and nonhemorrhagic stroke. Once the presence of an intracranial hemorrhage is excluded, imaging can also help to classify the stroke subtype by determining the site and size of the ischemic lesion. Eventually, visualization of the lesion may help to predict the functional consequences of the event.

In the ealy stage of ischemia, CT is the technique of choice to distinguish between hemorrhagic and nonhemorrhagic stroke. However, with CT 30% to 60% of the ischemic lesions are still invisible in the acute stage.^{1 2 3 4} During the first 24 hours after an ischemic stroke, proton density–weighted (PD-w) and T2-w MRI have 20% to 30% false-negative results.^{5 6 7} This percentage increases to 30% to 50% during the first 3 to 6 hours after stroke.^{3 8} As a consequence, CT or conventional MRI is not generally used to predict the presence and extent of ischemic damage in the acute stage after stroke.

Cytotoxic edema, which is caused by the accumulation of intracellular water due to cell membrane damage minutes after onset of acute cerebral ischemia, causes a restriction of microscopic proton diffusion. In diffusion-weighted MRI, this decrease in water diffusion is presumably reflected in a decrease of the apparent diffusion coefficient (ADC) on ADC trace maps,^{9 10 11 12 13 14 15} which is visualized as a hyperintensity on the diffusion-weighted images (DWI).^{12 14 15} Previous animal studies showed that DWI is able to visualize cerebral ischemic changes within 5 minutes⁹ to 1 to 3 hours after onset of symptoms.^{10 16 17 18 19} In humans, ischemic changes were detected with DWI as early as 2 to 6 hours after onset of symptoms.^{15 20 21 22} Other advantages of DWI are the low number of false-negative investigations (5%),²³ the clear discrimination between ischemic lesions and the nonischemic brain,^{11 15 24} and the discrimination between acute and chronic ischemic lesions.^{11 23} With these features, DWI facilitates the determination of the type, site, and extent of cerebral ischemia at an early stage. This might help to predict the clinical outcome of stroke patients.

Recent studies showed that in the acute stage after stroke, DWI is more sensitive for early ischemic changes than T2-w MRI.^{11 14 15 20 21 22 25} However, other studies showed that both PD-w imaging^{6 8} and fluid-attenuated inversion recovery (FLAIR) imaging^{26 27} are superior to T2-w imaging in the detection of acute ischemic lesions. Therefore, DWI should be compared with PD-w and FLAIR imaging as well.

The purpose of this observational study was to evaluate the use of DWI in the early phase (<60 hours after onset of symptoms) of ischemic stroke. We therefore investigated the sensitivity of DWI in detecting early cerebral ischemic changes in comparison with T2-w, PD-w, and FLAIR MRI scans. Furthermore, we assessed the prognostic value of lesion volume on early DWI scans with respect to final infarct volume and clinical outcome. Finally, we assessed the prognostic value of ADC measurements in ischemic lesions with respect to clinical outcome.

	Subjects and Methods

Top Abstract Introduction Subjects and Methods Results Discussion References

 
Patients and Controls
Between October 1996 and November 1997 we investigated 47 patients in the early phase of hemispheric ischemia (<60 hours after onset), as diagnosed by a neurologist. After a routine CT scan was performed, MRI was performed after informed consent was obtained from the patient or a representing family member. Patients who needed artificial respiration and patients who were otherwise unable to undergo the MR examinations were excluded. Four patients were treated with low, intermediate, or high intravenous doses of heparinoid (Org 10172, Organon) as part of the EuroTOAST (Trial of Org 10172 in Acute Stroke Treatment) investigation (Table 1, patients 8, 10, 12, and 14). Otherwise, patients received aspirin (n=32) or oral anticoagulants (n=6) together with conventional supportive therapy for acute stroke. Patients receiving experimental neuroprotective agents were not included.

View this table: [in this window] [in a new window]   Table 1. Demographic Data, Clinical Symptoms, and Infarct Location on Follow-up Scan

The control group consisted of 9 men and 6 women who had no history of ischemic neurological deficits and had no other intracranial diseases (mean age, 43 years; range, 22 to 71 years). They underwent the same DWI protocol as the patients. The study was approved by the Human Research Committee of our hospital.

MR Protocol
All MR investigations were performed on a 1.5-T clinical imaging system (Philips Gyroscan ACS-NT 15 whole-body system, Philips Medical Systems) in the early phase (<60 hours) after onset of symptoms. A sagittal spin-echo T1-weighted sequence (repetition time [TR], 427 ms; echo time [TE], 12 ms; 16 slices; slice thickness, 7.0 mm; 0.7-mm interslice gap; 1 average), an axial spin-echo PD-w and T2-w sequence (dual-echo T2-w MRI: TR, 2014 ms; TE, 30 ms and 100 ms; 19 slices; slice thickness, 7.0 mm; 0.7-mm interslice gap; 1 average; matrix size, 256x256; scan reduction, 75%) and an axial FLAIR sequence (Turbo Spin Echo, turbo factor 11 [ie, acquiring 11 echoes per TR]; TR, 5496 ms; TE, 100 ms; inversion time, 2000 ms; 16 slices; slice thickness, 6.4 mm; 1.3-mm interslice gap; 2 averages, matrix size, 256x256; reduced acquisition, 90% [90% of data points acquired]) were performed. For DWI, a fat-suppressed (Spectral Presaturation with Inversion Recovery), multishot, spin-echo/echo planar imaging sequence was used, with a pair of diffusion gradients centered around a 180° pulse (TE, 140 ms; TR, 667 or 1200 ms; 2 averages; matrix size, 128x128; reduced acquisition, 75% [96 of 128 data points acquired]; echo planar imaging factor, 13 [13 readout gradients per TR]). To reduce motion artifacts, the head of the patient was supported with soft supportive wedges and straps. For the DWI scans, navigator echoes were used to compensate for patient movements during the acquisitions, and cardiac triggering was used to reduce artifacts from pulsatile brain motion. Use of this sequence permitted acquisition of 10 to 12 slices (depending on the heart rate), which allowed a total coverage of 72 to 86.4 mm of the brain (slice thickness, 6.0 mm; 1.2-mm interslice gap). DWI scans were acquired with diffusion gradients along each of the three principal axes with 3 different b values (0, 187, and 757 s/mm²). For patient handling and performing the entire imaging protocol, 20 minutes were needed, of which 6 minutes were needed for DWI. A follow-up MRI or CT scan was made 6 days after the onset of symptoms. The follow-up MRI scan consisted of sagittal T1-w and axial PD-w, T2-w, and FLAIR scans. Total study time for the follow-up examination was 10 minutes.

Image Analysis
The early T2-w, PD-w, and FLAIR images were examined separately from the follow-up MRI scans by an experienced neuroradiologist (L.M.P.R.) without knowledge of the patients' symptoms and without reference to the DWI results. The ischemic lesions were measured on a separate workstation: areas of abnormal hyperintensity were traced on each slice of the PD-w (or FLAIR) images and on each slice of the DWI scans. These areas of abnormal hyperintensity were summed and multiplied with the slice thickness (plus interslice gap) to calculate the volumes of the acute ischemic lesions. To measure the lesion size on DWI scans we used the images that were acquired with the highest b value only, and all 3 diffusion directions were considered. Hyperintensities that were visible on only one or two diffusion directions were not considered ischemic lesions, since these hyperintensities are most likely to be caused by diffusion anisotropy.^{28 29 30} If patients had 2 fresh ischemic lesions, the volumes of both lesion were summed to analyze the prognostic value of infarct volume on clinical outcome. Preexistent cerebral infarcts were not included in these measurements.

ADC Measurements
ADC trace maps were calculated off-line afterward on the basis of the DWI that were acquired over the 3 principal axes.¹³ Measurements of the ADC of normal-appearing brain were obtained in patients and in controls from various regions of interest. Regions of interest were between 100 and 300 mm² in size and were carefully placed in an attempt to exclude sulcal or intraventricular cerebrospinal fluid, which has a high ADC value. To calculate the mean ADC of ischemic lesions (ADC_lesion), the region of interest outlining the ischemic lesion on DWI was transferred to the corresponding ADC trace map. Ratios were calculated between the ADC of normal-appearing brain in the right and left hemispheres and between the ADC of the ischemic area and the corresponding contralateral region.

Clinical Assessment
In the early stage, the patients' clinical status was determined with the National Institutes of Health Stroke Scale (NIHSS)³¹ and the modified Rankin Scale (RS). Long-term clinical outcome was determined with the NIHSS, RS, and Barthel Index (BI). The NIHSS is a serial scale of neurological deficit that measures 11 items of the patients' neurological status. The reliability of the NIHSS was previously demonstrated in a number of studies.^{31 32 33 34 35 36} We used the 31-point scale proposed by Goldstein et al.³¹ The modified RS³⁷ is a simplified overall assessment of function. A score of 0 indicates no symptoms, and a score of 5 indicates severe disability. In this study a RS score of 0 to 3 was considered good outcome, whereas a RS score of 4 or 5 was considered poor outcome. The BI³⁸ is a reliable and valid measure of the ability to perform activities of daily living such as eating, dressing, bathing, walking, and using the toilet. A score of 100 indicates no disability, and a score of 0 indicates severe disability.

Statistical Analysis
For statistical analysis, paired analysis of differences was performed with the Students' t test (after the F test was performed) or with the nonparametric Wilcoxon rank sum test. The paired samples t test was used for comparison of infarct volumes. Infarct volumes are expressed as mean and range. Pearson correlations were calculated between lesion volumes on the early MR images and follow-up scans. Spearman rank correlations were calculated between lesion volume and clinical outcome ratings. For the ² test, the Yates correction for continuity was used. For the comparison of outcome ratings between patients with large or small acute ischemic lesions and between patients with high or low ADC of the acute infarct, the Mantel-Haenszel ² test was used. A value of P<0.05 was considered statistically significant. Statistical significance was corrected for repeated measures. Receiver operating characteristics analysis was used to calculate the lesion volume, which determines clinical outcome of patients with optimum sensitivity and specificity.

	Results

Top Abstract Introduction Subjects and Methods Results Discussion References

 
Forty-seven patients initially fulfilled our inclusion criteria, but 3 patients were too uncooperative to undergo the MRI examination, and in 2 patients the DWI failed because of patient motion (n=1) or technical problems (n=1). We therefore analyzed the results of 42 patients with signs and symptoms of hemispheric ischemia of acute onset (25 men, 17 women; mean age, 64 years; range, 36 to 85 years). The demographic data and current clinical symptoms are shown in Table 1. Before the current ischemic event, 9 patients (21%) had suffered from a minor ischemic stroke and 8 patients (19%) had suffered from a transient ischemic attack (TIA). The mean time between the onset of symptoms and the early MR investigations was 23 hours (range, 1.5 to 60 hours). Five patients were imaged in the hyperacute stage (<6 hours after onset), 5 patients were imaged between 6 and 12 hours after onset, 15 patients were imaged between 12 and 24 hours, and 17 patients were imaged between 24 and 60 hours after onset of symptoms. The mean time between the onset of symptoms and the follow-up MRI was 17 days (range, 6 to 49 days). In 3 patients a follow-up CT scan was performed instead of an MRI (patients 5,12, and 42).

The results for the detection of lesions on early T2-w, PD-w, FLAIR, and DWI scans are summarized in Table 2. For this analysis, the follow-up scans were used as the gold standard. Four of the 42 patients (10%) had no lesion evident on the follow-up scans. These patients had transient symptoms and also had no lesions on the early MRI or DWI scans. In 7 patients, 2 infarcts were found on the follow-up MRI. Thus, a total of 45 infarcts were analyzed. During the first 60 hours after stroke, more lesions were detected on the DWI scans (98%) than on the T2-w images (71%; P=0.002, ²) or PD-w images (80%; P=0.02, ²). FLAIR imaging was performed in 32 of the 42 patients (35 lesions). With FLAIR, 91% of the lesions was detected (FLAIR versus DWI; P=NS, ²). No false-positive lesions were found with DWI: all hyperintensities resembling an ischemic lesion on DWI evolved into infarcts on the follow-up scan. A typical example of DWI, T2-w, and PD-w scans of a patient in the hyperacute stage after stroke is shown in Figure 1. Figure 2 shows the DWI, T2-w, PD-w, and FLAIR scans of another patient who was imaged 22 hours after the onset of symptoms.

View this table: [in this window] [in a new window]   Table 2. Number (and Percentage) of Ischemic Lesions Detected on T2-w, PD-w, FLAIR, and DWI Scans in the Acute Stage After Stroke Compared With the Total Number of Infarcts on Follow-Up MRI

View larger version (70K): [in this window] [in a new window]   Figure 1. Fifty-five–year-old man with an acute left-sided hemiparesis 6 hours before the first MRI examination (patient 10). On the early PD-w (A) and T2-w (B) images, no ischemic lesion was visible. The early DWI scan (C) shows a right-sided hyperintensity in the frontal lobe (territory of the pericallosal artery), which can be appreciated as a hypointensity on the ADC trace map (D). The follow-up MRI (E) was performed 6 days after the onset of symptoms and confirms the infarct. However, on the follow-up scan the infarct extended into the corpus callosum.

View larger version (69K): [in this window] [in a new window]   Figure 2. Thirty-six–year-old woman with a right-sided hemiparesis and dysphasia, starting 22 hours before the first MRI examination (patient 28). The left cortical infarct was initially not recognized on the early PD-w (A) and T2-w (B) images. In retrospect, however, the infarct was found on the PD-w images. The early FLAIR (C) and DWI (D) scans clearly show the infarct.

In Table 3, the sizes of the lesions as measured on the DWI scans, the early PD-w/FLAIR scans, and the follow-up MRI scans are summarized. The 3 patients with a follow-up CT scan only were excluded from this analysis. The mean lesion volume was significantly larger on the DWI scans (35 mL) than on the early PD-w/FLAIR images (21 mL) if patients were imaged between 0 and 12 hours after onset of symptoms (P<0.05). In patients who were imaged within 6 hours after stroke the difference in lesion size on the DWI scans (34 mL) and on the PD-w/FLAIR images (15 mL) appears to be even more profound than in patients who were imaged between 6 and 12 hours (36 mL versus 27 mL, respectively). However, this difference did not reach statistical significance because of the limited number of patients. No significant differences in mean lesion volume between the DWI scans and PD-w/FLAIR images were found if patients had the first MRI investigation between 12 and 24 hours after onset of symptoms or 24 hours. Lesions were significantly smaller on the early DWI scans (mean lesion size, 35 mL) than on the follow-up MRI scans (mean lesion size, 45 mL) if patients were imaged <12 hours after onset of symptoms (P<0.05). Again, in patients who were imaged <6 hours or between 6 and 12 hours after onset of symptoms, the difference in lesion size did not reach statistical significance because of the small sample size. The mean volume of lesions imaged 12 hours after onset of symptoms was not significantly altered on the follow-up scans.

View this table: [in this window] [in a new window]   Table 3. Mean Lesion Size (and Range) on Early PD-w/FLAIR Images, DWI Scans, and Follow-Up MRI

Long-term clinical outcome was measured between 7 and 33 weeks after onset of symptoms (mean, 17 weeks). During the follow-up period, 4 patients died. One patient with an infarct on follow-up MRI died from a pneumonia 3 months after onset of symptoms; another patient died from a retroperitoneal bleeding 2 weeks after the cerebral infarct. The other 2 patients had transient symptoms of cerebral ischemia without signs of an ischemic infarct on DWI or follow-up scan. One of these 2 patients died from a recurrent stroke in the posterior fossa 2 weeks after a hemispheric TIA; the other patient died from an unknown cause 3 months after the TIA. These 4 patients were excluded from further analysis because the baseline ischemic event was not the direct cause of their death.

Spearman rank sum correlations of lesion volume, as measured on the early DWI scans and on the follow-up MRI scans, versus clinical outcome ratings are shown in Table 4. The corresponding data are plotted in Figures 3 through 5. Lesion volume on the early DWI scans correlated significantly with the early NIHSS and RS scores (n=38, Figure 3) and with the long-term clinical outcome ratings (n=38, Figure 4). Lesion volume on the follow-up MR scans correlated significantly with the long-term clinical outcome ratings as well (n=36, Figure 5). The correlations between lesion volume on the early DWI scans and long-term clinical outcome ratings were increased when the 9 patients who had an ischemic event before the current event were excluded from the analysis: NIHSS: r=0.71, P<0.001; RS: r=0.70, P<0.001; BI: r=-0.55, P<0.001.

View this table: [in this window] [in a new window]   Table 4. Spearman Rank Sum Correlations Between Lesion Size on DWI, Infarct Size on Follow-Up MRI, and ADC Ratios vs Clinical Outcome Ratings

View larger version (12K): [in this window] [in a new window]   Figure 3. Correlation and 95% CIs for individuals between lesion volume on early DWI scans and early NIHSS (A) (r= 0.63, P<0.001) and RS (B) (r=0.62, P<0.001) scores.

View larger version (10K): [in this window] [in a new window]   Figure 4. Correlation and 95% CIs for individuals between lesion volume on early DWI scans and follow-up NIHSS (A) (r=0.62, P<0.001), BI (B) (r=-0.47, P<0.01), and RS (C) (r=0.62, P<0.001) scores.

View larger version (10K): [in this window] [in a new window]   Figure 5. Correlation and 95% CIs for individuals between lesion volume on follow-up MR scans and follow-up NIHSS (A) (r=0.66, P<0.001), follow-up BI (B) (r=-0.49, P<0.01), and RS (C) (r=0.66, P<0.001) scores.

In Figure 6, patients are grouped by the volume of the ischemic lesion on DWI. Patients with a relatively good outcome (n=29) had significantly smaller ischemic lesions on DWI scans (mean lesion volume, 18 mL) than patients with a poor outcome (n=9; mean lesion volume, 92 mL; P<0.05). With receiver operating characteristics analysis, a lesion volume of 22 mL on early DWI scans was found to determine the patients' outcome to be good with a sensitivity of 79% and a specificity of 89% (95% CI, 0.70 to 0.95). Clinical outcome ratings were significantly worse in patients with infarcts >22 mL on DWI than in patients with smaller infarcts (NIHSS: P=0.001; BI: P=0.01; RS: P=0.001; Figure 5). When the 9 patients who previously suffered from an ischemic stroke were excluded from this analysis, the sensitivity and specificity were 75% and 100%, respectively (95% CI, 0.78 to 0.98).

View larger version (31K): [in this window] [in a new window]   Figure 6. Long-term outcome, as measured with the NIHSS (top), BI (middle), and RS (bottom) scores of acute stroke patients. Patients are categorized as having large (>22 mL, n=14) or small (22 mL, n=24) ischemic lesions on early DWI scans.

Table 5 summarizes the ADC values of patients and control subjects. In both patients and controls, ADC measurements were performed in various normal-appearing parts of the brain. No significant difference in mean ADC was found between patients and controls in corresponding normal-appearing areas in the cerebrum. No significant difference in ADC was found between the various regions in the brain parenchyma of patients or controls. The mean ADC of the ischemic lesions (ADC_lesion) was 29% lower than the mean ADC in corresponding areas of the contralateral hemispheres (ADC_{contralateral}; P<0.001). Significant correlations were found between the ADC ratio (ADCr=ADC_lesion/ADC_{contralateral}) and the follow-up NIHSS, BI, and RS scores (Table 4). Patients with a poor outcome had a significantly lower ADCr of the ischemic lesions (mean ADCr=0.59±0.14) than patients with a good outcome (mean ADCr=0.77±0.15). An ADCr limit of 0.62 was found to determine the patients' outcome to be good or poor with a sensitivity of 83% and a specificity of 75% (95% CI, 0.66 to 0.94). Patients with low ADCr (<0.62) had significantly worse clinical outcome than patients with high ADCr (0.62, NIHSS: P=0.024; BI: P=0.001; RS: P=0.005).

View this table: [in this window] [in a new window]   Table 5. Mean Absolute ADC of Both Hemispheres and Ipsilateral/Contralateral Ratios in Various Normal-Appearing Cerebral Regions in Patients and Controls and Mean Absolute ADC (and Ipsilateral/Contralateral Ratio) of Acute Ischemic Lesions and Corresponding Contralateral Regions

	Discussion

Top Abstract Introduction Subjects and Methods Results Discussion References

 
Our results confirm that DWI is a useful imaging method to detect ischemic lesions in the early stage after stroke. All but one of the infarcts on follow-up MRI were depicted as a hyperintense lesion on DWI, whereas with T2-w or PD-w imaging, 29% and 20% of lesions, respectively, were not found in the early stage. Although less accurate than DWI, the FLAIR imaging provided better results in detecting ischemic lesions than the T2-w or PD-w scans.

The volume of the lesions that were imaged within the first 12 hours after onset of symptoms was significantly increased on the follow-up MRI. Enlargement of cerebral infarcts has been demonstrated previously by Baird and coworkers,³⁹ who defined lesions that were 20% larger on follow-up MRI scans than on early DWI scans as significantly enlarged. When we analyzed our data accordingly, 41% of the lesions were significantly enlarged, which is comparable to the 43% reported by Baird et al. A probable explanation for the enlargement of the ischemic lesions is that areas surrounding the core of the lesion became infarcted after we performed the MRI investigation.⁴⁰ Another explanation for lesion enlargement is the presence of vasogenic edema. Since we performed the follow-up examination between 6 and 49 days (mean, 17 days) after onset of symptoms, vasogenic edema surrounding the infarcted area may have mimicked lesion enlargement.

Our finding that patients with poor outcome had larger lesions than patients with good outcome was confirmed in a previous study in which early T2-w MRI was used.⁴¹ Compared with our results, similar correlations were reported between lesion volume on T2-w images and follow-up BI score⁴² and between infarct size on CT scans, performed between 7 and 10 days after stroke, and the NIHSS score at 3 months after the onset of symptoms.¹ The observed correlations between lesion volume on early DWI scans and clinical severity ratings have been described before^{21 43} and suggest that lesion volume can be predictive of the clinical outcome of stroke patients, particularly in patients without previous ischemic strokes.

For our entire patient population, good outcome could be predicted with a sensitivity of 79% and a specificity of 89% if patients had ischemic lesions of 22 mL on early DWI scans. One of our patients had very poor clinical outcome ratings, although she only had a small infarct. This patient had suffered from an ischemic stroke in the contralateral hemisphere 2 years earlier, from which she was left with a mild left-sided hemiparesis. The presence of infarcts in both hemispheres explained her low clinical outcome ratings. In patients who had never suffered from an ischemic event before or patients who previously had a TIA only, good outcome could be predicted with a specificity of 100%. This means that all patients without a previous stroke had good outcome if the acute ischemic lesion was 22 mL. These results show that lesion size measurements on early DWI scans can provide prognostic information to the clinician. Early information about the prognosis of acute stroke patients is useful if acute treatment with tissue plasminogen activator is considered.⁴⁴ One might speculate that patients with ischemic lesions 22 mL on DWI scans should not be treated with tissue plasminogen activator because the potential benefit is not outweighed by the risk of complications. However, the presented cutoff value of 22 mL should be interpreted with care because ischemic lesions tend to increase in size during the first 12 hours after onset of symptoms. To establish a critical lesion size in the hyperacute stage after stroke (0 to 6 hours), more patients should be investigated.

Our measurements of the ADC were reproducible in controls and in normal-appearing white and gray matter areas of stroke patients. Our ADC measurements of normal-appearing brain tissue were in the same range as the ADC measurements of other studies in human stroke patients.^{11 12 13 15 20 22 45 46} Marks and coworkers¹⁵ reported that the ADC varies within ischemic lesions. Our experience confirmed this finding. In our patient population the ADC varied widely between various locations within ischemic lesions, and the ADC was usually lower in the lesion core than in more peripheral parts. A number of studies^{11 12 20 22 46} determined the ADC of the core of the lesion only, whereas in our study the mean ADC was determined over an entire slice of the ischemic region. This might explain why in our study the ADCr between ischemic regions and corresponding contralateral areas were higher than the ADCr reported elsewhere.^{11 12 20 22 46} The presence of cerebrospinal fluid in the investigated regions might have caused variations in the ADC as well. The variations in ADC within ischemic lesions might become an important issue for future research in acute stroke patients. Animal studies indicate that the variation in ADC corresponds with regional cerebral blood flow,¹⁹ the severity⁴⁷ and extent^{9 47} of neuronal damage, and the degree of regional metabolic alterations.¹⁰ These data suggest that DWI can depict not only severely ischemic lesions but also moderately compromised regions that might be salvageable if therapeutic intervention is applied.

The DWI technique used in this study required 1.5 to 2 minutes for each diffusion direction, which is longer than is required by DWI techniques reported elsewhere.^{12 14 20 22} In our study prolonged scan time was a trade-off with the signal-to-noise ratio and the number of slices. A disadvantage of longer scan time is the higher susceptibility to motion artifacts. However, even though we used this relatively long DWI technique, only 1 patient had to be excluded from our study because of motion artifacts.

We conclude that DWI is a more reliable imaging method than MRI in detecting ischemic lesions in acute stroke patients. Lesion size, as measured on DWI scans, appears to be a potential parameter for predicting clinical outcome in acute stroke patients.

	Acknowledgments

 
Dr van der Grond is clinical investigator of the Netherlands Heart Foundation. We thank Dr A. Algra of the Julius Center for Patient Oriented Research for help in statistical analysis, N.W.A.M. Swinkels-Noppen of the Department of Radiology for assistance in image analysis, and Dr Ir P.J.M. Folkers from Philips Medical Systems for technical assistance in optimizing the MRI protocol.

	Footnotes

 
Reprint requests to K.J. van Everdingen, MD, Department of Radiology, E01.132, University Hospital Utrecht, Heidelberglaan 100, 3584 CX Utrecht, Netherlands.

Received March 23, 1998; revision received May 29, 1998; accepted May 29, 1998.

	References

Top Abstract Introduction Subjects and Methods Results Discussion References

 
1. Brott T, Marler JR, Olinger CP, Adams HP Jr, Tomsick T, Barsan W, Biller J, Eberle R, Hertzberg V, Walker M. Measurements of acute cerebral infarction: lesion size by computed tomography. Stroke. 1989;20:871–875.[Abstract/Free Full Text]

2. von Kummer R, Allen KL, Holle R, Bozzao L, Bastianello S, Manelfe C, Bluhmki E, Ringleb P, Meier DH, Hacke W. Acute stroke: usefulness of early CT findings before thrombolytic therapy. Radiology. 1997;205:327–333.[Abstract/Free Full Text]

3. Mohr JP, Biller J, Hilal SK, Yuh WT, Tatemichi TK, Hedges S, Tali E, Nguyen H, Mun I, Adams HP Jr, Grimsman K, Marler JR. Magnetic resonance versus computed tomographic imaging in acute stroke. Stroke. 1995;26:807–812.[Abstract/Free Full Text]

4. Bozzao L, Bastianello S, Fantozzi L, Angeloni U, Argentino C, Fieschi C. Correlation of angiographic and sequential CT findings in patients with evolving cerebral infarction. AJNR Am J Neuroradiol. 1989;10:1215–1222.[Abstract]

5. Yuh WTC, Crain MR, Loes DJ, Greene GM, Ryals TJ, Sato Y. MR imaging of cerebral ischemia: findings in the first 24 hours. AJNR Am J Neuroradiol. 1991;12:621–629.[Abstract]

6. Bryan RN, Levy LM, Whitlow WD, Killian JM, Preziosi TJ, Rosario JA. Diagnosis of acute cerebral infarction: comparison of CT and MR imaging. AJNR Am J Neuroradiol. 1991;12:611–620.[Abstract]

7. Kertesz A, Black SE, Nicholson L, Carr T. The sensitivity and specificity of MRI in stroke. Neurology. 1987;1580–1585.

8. Shimosegawa E, Inugami A, Okudera T, Hatazawa J, Ogawa T, Fujita H, Toyoshima H, Uemura K. Embolic cerebral infarction: MR findings in the first 3 hours after onset. AJR Am J Roentgenol. 1993;160:1077–1082.[Abstract/Free Full Text]

9. Reith W, Hasegawa Y, Latour LL, Dardzinski BJ, Sotak CH, Fisher M. Multislice diffusion mapping for 3-D evolution of cerebral ischemia in a rat stroke model. Neurology. 1995;45:172–177.[Abstract/Free Full Text]

10. Back T, Hoehn-Berlage M, Kohno K, Hossmann KA. Diffusion nuclear magnetic resonance imaging in experimental stroke: correlation with cerebral metabolites. Stroke. 1994;25:494–500.[Abstract]

11. Lutsep HL, Albers GW, DeCrespigny A, Kamat GN, Marks MP, Moseley ME. Clinical utility of diffusion-weighted magnetic resonance imaging in the assessment of ischemic stroke. Ann Neurol. 1997;41:574–580.[Medline] [Order article via Infotrieve]

12. Schlaug G, Siewert B, Benfield A, Edelman RR, Warach S. Time course of the apparent diffusion coefficient (ADC) abnormality in human stroke. Neurology. 1997;49:113–119.[Abstract/Free Full Text]

13. Ulug AM, Beauchamp N Jr, Bryan RN, van Zijl PC. Absolute quantification of diffusion constants in human stroke. Stroke. 1997;28:483–490.[Abstract/Free Full Text]

14. Warach S, Chien D, Li W, Ronthal M, Edelman RR. Fast magnetic resonance diffusion-weighted imaging of acute human stroke. Neurology. 1992;42:1717–1723.[Abstract/Free Full Text]

15. Marks MP, de Crespigny AJ, Lentz D, Enzmann DR, Albers GW, Moseley ME. Acute and chronic stroke: navigated spin-echo diffusion-weighted MR imaging. Radiology. 1996;199:403–408.[Abstract/Free Full Text]

16. Moseley ME, Kucharczyk J, Mintorovitch J, Cohen Y, Kurhanewicz J, Derugin N, Asgari H, Norman D. Diffusion-weighted MR imaging of acute stroke: correlation with T2-weighted and magnetic susceptibility-enhanced MR imaging in cats. AJNR Am J Neuroradiol. 1990;11:423–429.[Abstract]

17. Sevick RJ, Kanda F, Mintorovitch J, Arieff AI, Kucharczyk J, Tsuruda JS, Norman D, Moseley ME. Cytotoxic brain edema: assessment with diffusion-weighted MR imaging. Radiology. 1992;185:687–690.[Abstract/Free Full Text]

18. Moseley ME, Cohen Y, Mintorovitch J, Chileuitt L, Shimizu H, Kucharczyk J, Wendland MF, Weinstein PR. Early detection of regional cerebral ischemia in cats: comparison of diffusion- and T2-weighted MRI and spectroscopy. Magn Reson Med. 1990;14:330–346.[Medline] [Order article via Infotrieve]

19. Perez Trepichio AD, Xue M, Ng TC, Majors AW, Furlan AJ, Awad IA, Jones SC. Sensitivity of magnetic resonance diffusion-weighted imaging and regional relationship between the apparent diffusion coefficient and cerebral blood flow in rat focal cerebral ischemia. Stroke. 1995;26:667–674.[Abstract/Free Full Text]

20. Sorensen AG, Buonanno FS, Gonzalez RG, Schwamm LH, Lev MH, Huang Hellinger FR, Reese TG, Weisskoff RM, Davis TL, Suwanwela N, Can U, Moreira JA, Copen WA, Look RB, Finklestein SP, Rosen BR, Koroshetz WJ. Hyperacute stroke: evaluation with combined multisection diffusion-weighted and hemodynamically weighted echo-planar MR imaging. Radiology. 1996;199:391–401.[Abstract/Free Full Text]

21. Warach S, Dashe JF, Edelman RR. Clinical outcome in ischemic stroke predicted by early diffusion-weighted and perfusion magnetic resonance imaging: a preliminary analysis. J Cereb Blood Flow Metab. 1996;16:53–59.[Medline] [Order article via Infotrieve]

22. Warach S, Gaa J, Siewert B, Wielopolski P, Edelman RR. Acute human stroke studied by whole brain echo planar diffusion-weighted magnetic resonance imaging. Ann Neurol. 1995;37:231–241.[Medline] [Order article via Infotrieve]

23. Singer MB, Chong J, Dongfeng L, Schonewille W, Tuhrim S, Atlas SW. Diffusion-weighted MRI in acute subcortical infarction. Stroke. 1998;29:133–136.[Abstract/Free Full Text]

24. Koroshetz WJ, Gonzalez G. Diffusion-weighted MRI: an ECG for "brain attack"? Ann Neurol. 1997;41:565–566.[Medline] [Order article via Infotrieve]

25. Ebisu T, Tanaka C, Umeda M, Kitamura M, Fukunaga M, Aoki I, Sato H, Higuchi T, Naruse S, Horikawa Y, Ueda S. Hemorrhagic and nonhemorrhagic stroke: diagnosis with diffusion-weighted and T2-weighted echo-planar MR imaging. Radiology. 1997;203:823–828.[Abstract/Free Full Text]

26. Alexander JA, Sheppard S, Davis PC, Salverda P. Adult cerebrovascular disease: role of modified rapid fluid-attenuated inversion-recovery sequences. AJNR Am J Neuroradiol. 1996;17:1507–1513.[Abstract]

27. Brant-Zawadski M, Atkinson D, Detrick M, Bradley WG, Scidmore G. Fluid-attenuated inversion recovery (FLAIR) for assessment of cerebral infarction: initial clinical experience in 50 patients. Stroke. 1996;27:1187–1191.[Abstract/Free Full Text]

28. Moseley ME, Kucharczyk J, Asgari H, Norman D. Anisotropy in diffusion-weighted MRI. Magn Reson Med. 1991;19:321–326.[Medline] [Order article via Infotrieve]

29. Moseley ME, Cohen Y, Kucharczyk J, Mintorovitch J, Asgari HS, Wendland MF, Tsuruda JS, Norman D. Diffusion-weighted MR imaging of anisotropic water diffusion in cat central nervous system. Radiology. 1990;176:439–445.[Abstract/Free Full Text]

30. Chenevert TL, Brunberg JA, Pipe JG. Anisotropic diffusion in human white matter: demonstration with MR techniques in vivo. Radiology. 1990;177:401–405.[Abstract/Free Full Text]

31. Goldstein LB, Bertels C, Davis JN. Interrater reliability of the NIH Stroke Scale. Arch Neurol. 1989;46:660–662.[Abstract/Free Full Text]

32. Wityk RJ, Pessin MS, Kaplan RF, Caplan LR. Serial assessment of acute stroke using the NIH Stroke Scale. Stroke. 1994;25:362–365.[Abstract]

33. Lyden P, Brott T, Tilley B, Welch KM, Mascha EJ, Levine S, Haley EC, Grotta J, Marler J. Improved reliability of the NIH Stroke Scale using video training: NINDS. Stroke. 1994;25:2220–2226.[Abstract]

34. Goldstein LB, Samsa GP. Reliability of the National Institutes of Health Stroke Scale: extension to non-neurologists in a clinical trial. Stroke. 1997;28:307–310.[Abstract/Free Full Text]

35. Albanese MA, Clarke WR, Adams HP Jr, Woolson RF. Ensuring reliability of outcome measures in multicenter clinical trials of treatments for acute ischemic stroke. the program developed for the Trial of Org 10172 in Acute Stroke Treatment (TOAST). Stroke. 1994;25:1746–1751.[Abstract]

36. Brott T, Adams HP Jr, Olinger CP, Marler JR, Barsan WG, Biller J, Spilker J, Holleran RN, Eberle R, Hertzberg V, Rorick M, Moomaw CJ, Walker M. Measurements of acute cerebral infarction: a clinical examination scale. Stroke. 1989;20:864–870.[Abstract/Free Full Text]

37. van Swieten JC, Koudstaal PJ, Visser MC, Schouten HJA, van Gijn J. Interobserver agreement for the assessment of handicap in stroke patients. Stroke. 1988;19:604–607.[Abstract/Free Full Text]

38. Mahoney FI, Barthel DW. Functional evaluation: the Barthel Index. Md State Med J. 1965;14:61–65.[Medline] [Order article via Infotrieve]

39. Baird AE, Benfield A, Schlaug G, Siewert B, Lovblad KO, Edelman RR, Warach S. Enlargement of human cerebral ischemia lesion volumes measured by diffusion-weighted magnetic resonance imaging. Ann Neurol. 1997;41:581–589.[Medline] [Order article via Infotrieve]

40. Garcia JH, Lassen NA, Weiller C, Sperling B, Nakagawara J. Ischemic stroke and incomplete infarction. Stroke. 1996;27:761–765.[Abstract/Free Full Text]

41. Saunders DE, Clifton AG, Brown MM. Measurement of infarct size using MRI predicts prognosis in middle cerebral artery infarction. Stroke. 1995;26:2272–2276.[Abstract/Free Full Text]

42. Graham GD, Kalvach P, Blamire AM, Brass LM, Fayad PB, Prichard JW. Clinical correlates of proton magnetic resonance spectroscopy findings after acute cerebral infarction. Stroke. 1995;26:225–229.[Abstract/Free Full Text]

43. Lovblad KO, Baird AE, Schlaug G, Benfield A, Siewert B, Voetsch B, Connor A, Burzynski C, Edelman RR, Warach S. Ischemic lesion volumes in acute stroke by diffusion-weighted magnetic resonance imaging correlate with clinical outcome. Ann Neurol. 1997;42:164–170.[Medline] [Order article via Infotrieve]

44. The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. Tissue plasminogen activator for acute ischemic stroke. N Engl J Med. 1995;333:1581–1587.[Abstract/Free Full Text]

45. Chien D, Kwong KK, Gress DR, Buonanno FS, Buxton RB, Rosen BR. MR diffusion imaging of cerebral infarction in humans. AJNR Am J Neuroradiol. 1992;13:1097–1102.[Abstract]

46. Kohno K, Ohta S, Kumon Y, Sakaki S, Okujima S. Early detection of cerebral ischemic lesion using diffusion-weighted MRI. J Comput Assist Tomogr. 1995;19:982–986.[Medline] [Order article via Infotrieve]

47. Knight RA, Dereski MO, Helpern JA, Ordidge RJ, Chopp M. Magnetic resonance imaging assessment of evolving focal cerebral ischemia: comparison with histopathology in rats. Stroke. 1994;25:1252–1262.[Abstract]

This article has been cited by other articles:

				J. R. Sims, L. R. Gharai, P. W. Schaefer, M. Vangel, E. S. Rosenthal, M. H. Lev, and L. H. Schwamm ABC/2 for rapid clinical estimate of infarct, perfusion, and mismatch volumes Neurology, June 16, 2009; 72(24): 2104 - 2110. [Abstract] [Full Text] [PDF]

				M. Ebinger, S. Christensen, D. A. De Silva, M. W. Parsons, C. R. Levi, K. S. Butcher, C. F. Bladin, P. A. Barber, G. A. Donnan, S. M. Davis, et al. Expediting MRI-Based Proof-of-Concept Stroke Trials Using an Earlier Imaging End Point Stroke, April 1, 2009; 40(4): 1353 - 1358. [Abstract] [Full Text] [PDF]

				E. S. Roach, M. R. Golomb, R. Adams, J. Biller, S. Daniels, G. deVeber, D. Ferriero, B. V. Jones, F. J. Kirkham, R. M. Scott, et al. Management of Stroke in Infants and Children: A Scientific Statement From a Special Writing Group of the American Heart Association Stroke Council and the Council on Cardiovascular Disease in the Young Stroke, September 1, 2008; 39(9): 2644 - 2691. [Abstract] [Full Text] [PDF]

				H. P. Adams Jr, G. del Zoppo, M. J. Alberts, D. L. Bhatt, L. Brass, A. Furlan, R. L. Grubb, R. T. Higashida, E. C. Jauch, C. Kidwell, et al. Guidelines for the Early Management of Adults With Ischemic Stroke: A Guideline From the American Heart Association/American Stroke Association Stroke Council, Clinical Cardiology Council, Cardiovascular Radiology and Intervention Council, and the Atherosclerotic Peripheral Vascular Disease and Quality of Care Outcomes in Research Interdisciplinary Working Groups: The American Academy of Neurology affirms the value of this guideline as an educational tool for neurologists. Circulation, May 22, 2007; 115(20): e478 - e534. [Abstract] [Full Text] [PDF]

				J. N.E. Redgrave, S. B. Coutts, U. G. Schulz, D. Briley, and P. M. Rothwell Systematic Review of Associations Between the Presence of Acute Ischemic Lesions on Diffusion-Weighted Imaging and Clinical Predictors of Early Stroke Risk After Transient Ischemic Attack Stroke, May 1, 2007; 38(5): 1482 - 1488. [Abstract] [Full Text] [PDF]

				H. P. Adams Jr, G. del Zoppo, M. J. Alberts, D. L. Bhatt, L. Brass, A. Furlan, R. L. Grubb, R. T. Higashida, E. C. Jauch, C. Kidwell, et al. Guidelines for the Early Management of Adults With Ischemic Stroke: A Guideline From the American Heart Association/ American Stroke Association Stroke Council, Clinical Cardiology Council, Cardiovascular Radiology and Intervention Council, and the Atherosclerotic Peripheral Vascular Disease and Quality of Care Outcomes in Research Interdisciplinary Working Groups: The American Academy of Neurology affirms the value of this guideline as an educational tool for neurologists Stroke, May 1, 2007; 38(5): 1655 - 1711. [Abstract] [Full Text] [PDF]

				D. J. Cook, J. Huston III, M. R. Trenerry, R. D. Brown Jr, K. J. Zehr, and T. M. Sundt III Postcardiac Surgical Cognitive Impairment in the Aged Using Diffusion-Weighted Magnetic Resonance Imaging Ann. Thorac. Surg., April 1, 2007; 83(4): 1389 - 1395. [Abstract] [Full Text] [PDF]

				J. L. Banks and C. A. Marotta Outcomes Validity and Reliability of the Modified Rankin Scale: Implications for Stroke Clinical Trials: A Literature Review and Synthesis Stroke, March 1, 2007; 38(3): 1091 - 1096. [Abstract] [Full Text] [PDF]

				S. K. Schiemanck, G. Kwakkel, M. W. M. Post, and A. J. H. Prevo Predictive Value of Ischemic Lesion Volume Assessed With Magnetic Resonance Imaging for Neurological Deficits and Functional Outcome Poststroke: A Critical Review of the Literature Neurorehabil Neural Repair, December 1, 2006; 20(4): 492 - 502. [Abstract] [PDF]

				M. Luby, J. L. Bykowski, P. D. Schellinger, J. G. Merino, and S. Warach Intra- and Interrater Reliability of Ischemic Lesion Volume Measurements on Diffusion-Weighted, Mean Transit Time and Fluid-Attenuated Inversion Recovery MRI Stroke, December 1, 2006; 37(12): 2951 - 2956. [Abstract] [Full Text] [PDF]

				A. Kastrup, T. Nagele, K. Groschel, F. Schmidt, E. Vogler, J. Schulz, and U. Ernemann Incidence of New Brain Lesions After Carotid Stenting With and Without Cerebral Protection Stroke, September 1, 2006; 37(9): 2312 - 2316. [Abstract] [Full Text] [PDF]

				P. A. Barber and W. Powers MR DWI does not substitute for stroke severity scores in predicting stroke outcome Neurology, April 25, 2006; 66(8): 1138 - 1139. [Full Text] [PDF]

				P. J. Hand, J. M. Wardlaw, C. S. Rivers, P. A. Armitage, M. E. Bastin, R. I. Lindley, and M. S. Dennis MR diffusion-weighted imaging and outcome prediction after ischemic stroke Neurology, April 25, 2006; 66(8): 1159 - 1163. [Abstract] [Full Text] [PDF]

				A. Pierallini, F. Caramia, C. Falcone, E. Tinelli, A. Paonessa, A. B. Ciddio, M. Fiorelli, F. Bianco, S. Natalizi, L. Ferrante, et al. Pituitary Macroadenomas: Preoperative Evaluation of Consistency with Diffusion-weighted MR Imaging--Initial Experience Radiology, April 1, 2006; 239(1): 223 - 231. [Abstract] [Full Text] [PDF]

				S. K. Schiemanck, G. Kwakkel, M. W.M. Post, L. J. Kappelle, and A. J.H. Prevo Predicting Long-Term Independency in Activities of Daily Living After Middle Cerebral Artery Stroke: Does Information From MRI Have Added Predictive Value Compared With Clinical Information? Stroke, April 1, 2006; 37(4): 1050 - 1054. [Abstract] [Full Text] [PDF]

				P L Tan, D King, C J Durkin, T M Meagher, and D Briley Diffusion weighted magnetic resonance imaging for acute stroke: practical and popular. Postgrad. Med. J., April 1, 2006; 82(966): 289 - 292. [Abstract] [Full Text] [PDF]

				P. E. Chen, J. E. Simon, M. D. Hill, C.-H. Sohn, P. Dickhoff, W. F. Morrish, R. J. Sevick, and R. Frayne Acute Ischemic Stroke: Accuracy of Diffusion-weighted MR Imaging--Effects of b Value and Cerebrospinal Fluid Suppression Radiology, January 1, 2006; 238(1): 232 - 239. [Abstract] [Full Text] [PDF]

				O Y Bang, P H Lee, K G Heo, U S Joo, S R Yoon, and S Y Kim Specific DWI lesion patterns predict prognosis after acute ischaemic stroke within the MCA territory J. Neurol. Neurosurg. Psychiatry, September 1, 2005; 76(9): 1222 - 1228. [Abstract] [Full Text] [PDF]

				S. K. Schiemanck, M. W.M. Post, Th. D. Witkamp, L. J. Kappelle, and A. J.H. Prevo Relationship between Ischemic Lesion Volume and Functional Status in the 2nd Week after Middle Cerebral Artery Stroke Neurorehabil Neural Repair, June 1, 2005; 19(2): 133 - 138. [Abstract] [PDF]

				H. J. Kim, C. G. Choi, D. H. Lee, J. H. Lee, S. J. Kim, and D. C. Suh High-b-Value Diffusion-Weighted MR Imaging of Hyperacute Ischemic Stroke at 1.5T AJNR Am. J. Neuroradiol., February 1, 2005; 26(2): 208 - 215. [Abstract] [Full Text] [PDF]

				H. G. Roh, H. S. Byun, J. W. Ryoo, D. G. Na, W.-J. Moon, B. B. Lee, and D.-I. Kim Prospective Analysis of Cerebral Infarction After Carotid Endarterectomy and Carotid Artery Stent Placement by Using Diffusion-Weighted Imaging AJNR Am. J. Neuroradiol., February 1, 2005; 26(2): 376 - 384. [Abstract] [Full Text] [PDF]

				D Chowdhury, J M Wardlaw, and M S Dennis Are multiple acute small subcortical infarctions caused by embolic mechanisms? J. Neurol. Neurosurg. Psychiatry, October 1, 2004; 75(10): 1416 - 1420. [Abstract] [Full Text] [PDF]

				D. M. Somford, M. P. Marks, V. N. Thijs, and D. C. Tong Association of Early CT Abnormalities, Infarct Size, and Apparent Diffusion Coefficient Reduction in Acute Ischemic Stroke AJNR Am. J. Neuroradiol., June 1, 2004; 25(6): 933 - 938. [Abstract] [Full Text] [PDF]

				Y. Ozsunar, P. E. Grant, T. A. G. M. Huisman, P. W. Schaefer, O. Wu, A. G. Sorensen, W. J. Koroshetz, and R. G. Gonzalez Evolution of Water Diffusion and Anisotropy in Hyperacute Stroke: Significant Correlation between Fractional Anisotropy and T2 AJNR Am. J. Neuroradiol., May 1, 2004; 25(5): 699 - 705. [Abstract] [Full Text] [PDF]

				S. T. Engelter, S. G. Wetzel, E. W. Radue, M. Rausch, A. J. Steck, and P. A. Lyrer The clinical significance of diffusion-weighted MR imaging in infratentorial strokes Neurology, February 24, 2004; 62(4): 574 - 580. [Abstract] [Full Text] [PDF]

				R. T. Higashida and A. J. Furlan Trial Design and Reporting Standards for Intra-Arterial Cerebral Thrombolysis for Acute Ischemic Stroke Stroke, August 1, 2003; 34 (8): e109 - e137. [Abstract] [Full Text] [PDF]

				H. P. Adams Jr, R. J. Adams, T. Brott, G. J. del Zoppo, A. Furlan, L. B. Goldstein, R. L. Grubb, R. Higashida, C. Kidwell, T. G. Kwiatkowski, et al. Guidelines for the Early Management of Patients With Ischemic Stroke: A Scientific Statement From the Stroke Council of the American Stroke Association Stroke, April 1, 2003; 34(4): 1056 - 1083. [Full Text] [PDF]

				S. Macdonald and P. A Gaines Current concepts of mechanical cerebral protection during precutaneous carotid intervention Vascular Medicine, February 1, 2003; 8(1): 25 - 32. [Abstract] [PDF]

				K. P. Forbes, J. G. Pipe, J. P. Karis, and J. E. Heiserman Improved Image Quality and Detection of Acute Cerebral Infarction with PROPELLER Diffusion-weighted MR Imaging Radiology, November 1, 2002; 225(2): 551 - 555. [Abstract] [Full Text] [PDF]

				S. Ishikawa, K. Yokoyama, T. Kuroiwa, and K. Makita Apparent diffusion coefficient mapping predicts mortality and outcome in rats with intracerebral haemodynamic disturbance: potential role of intraoperative diffusion and perfusion weighted magnetic resonance imaging to detect cerebral ischaemia Br. J. Anaesth., October 1, 2002; 89(4): 605 - 613. [Abstract] [Full Text] [PDF]

				J. F. Arenillas, A. Rovira, C. A. Molina, E. Grive, J. Montaner, J. Alvarez-Sabin, and K.-O. Lovblad Prediction of Early Neurological Deterioration Using Diffusion- and Perfusion-Weighted Imaging in Hyperacute Middle Cerebral Artery Ischemic Stroke * Editorial Comment Stroke, September 1, 2002; 33(9): 2197 - 2205. [Abstract] [Full Text] [PDF]

				M. E. Mullins, P. W. Schaefer, A. G. Sorensen, E. F. Halpern, H. Ay, J. He, W. J. Koroshetz, and R. G. Gonzalez CT and Conventional and Diffusion-weighted MR Imaging in Acute Stroke: Study in 691 Patients at Presentation to the Emergency Department Radiology, August 1, 2002; 224(2): 353 - 360. [Abstract] [Full Text] [PDF]

				M. Wintermark, M. Reichhart, O. Cuisenaire, P. Maeder, J.-P. Thiran, P. Schnyder, J. Bogousslavsky, and R. Meuli Comparison of Admission Perfusion Computed Tomography and Qualitative Diffusion- and Perfusion-Weighted Magnetic Resonance Imaging in Acute Stroke Patients Stroke, August 1, 2002; 33(8): 2025 - 2031. [Abstract] [Full Text] [PDF]

				J J Marx, A Mika-Gruettner, F Thoemke, S Fitzek, C Fitzek, G Vucurevic, P P Urban, P Stoeter, and H C Hopf Diffusion weighted magnetic resonance imaging in the diagnosis of reversible ischaemic deficits of the brainstem J. Neurol. Neurosurg. Psychiatry, May 1, 2002; 72(5): 572 - 575. [Abstract] [Full Text] [PDF]

				I. Mader, M. Schoning, U. Klose, and W. Kuker Neonatal Cerebral Infarction Diagnosed by Diffusion-Weighted MRI: Pseudonormalization Occurs Early Stroke, April 1, 2002; 33(4): 1142 - 1145. [Abstract] [Full Text] [PDF]

				J. Helenius, L. Soinne, J. Perkio, O. Salonen, A. Kangasmaki, M. Kaste, R. A. D. Carano, H. J Aronen, and T. Tatlisumak Diffusion-Weighted MR Imaging in Normal Human Brains in Various Age Groups AJNR Am. J. Neuroradiol., February 1, 2002; 23(2): 194 - 199. [Abstract] [Full Text] [PDF]

				H. J. Jaeger, K. D. Mathias, E. Hauth, R. Drescher, H. M. Gissler, S. Hennigs, and A. Christmann Cerebral Ischemia Detected with Diffusion-Weighted MR Imaging after Stent Implantation in the Carotid Artery AJNR Am. J. Neuroradiol., February 1, 2002; 23(2): 200 - 207. [Abstract] [Full Text] [PDF]

				V. N. Thijs, A. Adami, T. Neumann-Haefelin, M. E. Moseley, and G. W. Albers Clinical and Radiological Correlates of Reduced Cerebral Blood Flow Measured Using Magnetic Resonance Imaging Arch Neurol, February 1, 2002; 59(2): 233 - 238. [Abstract] [Full Text] [PDF]

				J. Fiehler, M. Foth, T. Kucinski, R. Knab, M. von Bezold, C. Weiller, H. Zeumer, and J. Rother Severe ADC Decreases Do Not Predict Irreversible Tissue Damage In Humans Stroke, January 1, 2002; 33(1): 79 - 86. [Abstract] [Full Text] [PDF]

				C. J. Perkins, E. Kahya, C. T. Roque, P. E. Roche, G. C. Newman, and S. Warach Fluid-Attenuated Inversion Recovery and Diffusion- and Perfusion-Weighted MRI Abnormalities in 117 Consecutive Patients With Stroke Symptoms Editorial Comment Stroke, December 1, 2001; 32(12): 2774 - 2781. [Abstract] [Full Text] [PDF]

				W. A. Copen, L. H. Schwamm, R. G. Gonzalez, O. Wu, C. B. Harmath, P. W. Schaefer, W. J. Koroshetz, and A. G. Sorensen Ischemic Stroke: Effects of Etiology and Patient Age on the Time Course of the Core Apparent Diffusion Coefficient Radiology, October 1, 2001; 221(1): 27 - 34. [Abstract] [Full Text] [PDF]

				P. E. Grant, J. He, E. F. Halpern, O. Wu, P. W. Schaefer, L. H. Schwamm, R. F. Budzik, A. G. Sorensen, W. J. Koroshetz, and R. G. Gonzalez Frequency and Clinical Context of Decreased Apparent Diffusion Coefficient Reversal in the Human Brain Radiology, October 1, 2001; 221(1): 43 - 50. [Abstract] [Full Text] [PDF]

				S. Ishikawa, K. Yokoyama, T. Kuroiwa, and K. Makita Evolution of cerebral ischaemia induced by thromboembolism in rats detected by early sequential MR imaging Br. J. Anaesth., September 1, 2001; 87(3): 469 - 476. [Abstract] [Full Text] [PDF]

				H. J. Jaeger, K. D. Mathias, R. Drescher, E. Hauth, G. Bockisch, E. Demirel, and H. Martin Gissler Diffusion-weighted MR Imaging After Angioplasty or Angioplasty Plus Stenting of Arteries Supplying the Brain AJNR Am. J. Neuroradiol., August 1, 2001; 22(7): 1251 - 1259. [Abstract] [Full Text] [PDF]

				I. A. Staroselskaya, C. Chaves, B. Silver, I. Linfante, R. R. Edelman, L. Caplan, S. Warach, and A. E. Baird Relationship Between Magnetic Resonance Arterial Patency and Perfusion-Diffusion Mismatch in Acute Ischemic Stroke and Its Potential Clinical Use Arch Neurol, July 1, 2001; 58(7): 1069 - 1074. [Abstract] [Full Text] [PDF]

				K. P.N. Forbes, H. A. Shill, P. M. Britt, J. M. Zabramski, R. F. Spetzler, and J. E. Heiserman Assessment of Silent Embolism from Carotid Endarterectomy by Use of Diffusion-weighted Imaging: Work in Progress AJNR Am. J. Neuroradiol., April 1, 2001; 22(4): 650 - 653. [Abstract] [Full Text]

				M. G. Lansberg, M. W. O'Brien, D. C. Tong, M. E. Moseley, and G. W. Albers Evolution of Cerebral Infarct Volume Assessed by Diffusion-Weighted Magnetic Resonance Imaging Arch Neurol, April 1, 2001; 58(4): 613 - 617. [Abstract] [Full Text] [PDF]

				O. Wu, W. J. Koroshetz, L. Ostergaard, F. S. Buonanno, W. A. Copen, R. G. Gonzalez, G. Rordorf, B. R. Rosen, L. H. Schwamm, R. M. Weisskoff, et al. Predicting Tissue Outcome in Acute Human Cerebral Ischemia Using Combined Diffusion- and Perfusion-Weighted MR Imaging Stroke, April 1, 2001; 32(4): 933 - 942. [Abstract] [Full Text] [PDF]

				A. J. Johnson, D. K. Kido, W. D. Shannon, M. M. Bahn, M. H. Gado, B. C. P. Lee, C. J. Moran, F. J. Wippold, and B. Littenberg Evaluation of a Reduced MR Imaging Sequencing Protocol in Adult Patients with Stroke Radiology, March 1, 2001; 218(3): 791 - 797. [Abstract] [Full Text]

				A C Pereira, P J Martin, and E A Warburton Thrombolysis in acute ischaemic stroke Postgrad. Med. J., March 1, 2001; 77(905): 166 - 171. [Full Text]

				P. W. Schaefer, P. E. Grant, and R. G. Gonzalez Diffusion-weighted MR Imaging of the Brain Radiology, November 1, 2000; 217(2): 331 - 345. [Abstract] [Full Text]

				V. N. Thijs, M. G. Lansberg, C. Beaulieu, M. P. Marks, M. E. Moseley, and G. W. Albers Is Early Ischemic Lesion Volume on Diffusion-Weighted Imaging an Independent Predictor of Stroke Outcome? : A Multivariable Analysis Stroke, November 1, 2000; 31(11): 2597 - 2602. [Abstract] [Full Text] [PDF]

				S. L. Keir and J. M. Wardlaw Systematic Review of Diffusion and Perfusion Imaging in Acute Ischemic Stroke Stroke, November 1, 2000; 31(11): 2723 - 2731. [Abstract] [Full Text] [PDF]

				M. G. Lansberg, A. M. Norbash, M. P. Marks, D. C. Tong, M. E. Moseley, and G. W. Albers Advantages of Adding Diffusion-Weighted Magnetic Resonance Imaging to Conventional Magnetic Resonance Imaging for Evaluating Acute Stroke Arch Neurol, September 1, 2000; 57(9): 1311 - 1316. [Abstract] [Full Text] [PDF]

				K. P. N. Forbes, J. G. Pipe, and R. Bird Neonatal Hypoxic-ischemic Encephalopathy: Detection with Diffusion-weighted MR Imaging AJNR Am. J. Neuroradiol., August 1, 2000; 21(8): 1490 - 1496. [Abstract] [Full Text]

				L. J. Lee, C. S. Kidwell, J. Alger, S. Starkman, and J. L. Saver Impact on Stroke Subtype Diagnosis of Early Diffusion-Weighted Magnetic Resonance Imaging and Magnetic Resonance Angiography Stroke, May 1, 2000; 31(5): 1081 - 1089. [Abstract] [Full Text] [PDF]

				G. W. Albers, M. G. Lansberg, A. M. Norbash, D. C. Tong, M. W. O'Brien, A. R. Woolfenden, M. P. Marks, and M. E. Moseley Yield of diffusion-weighted MRI for detection of potentially relevant findings in stroke patients Neurology, April 25, 2000; 54(8): 1562 - 1567. [Abstract] [Full Text] [PDF]

				F. Li, K.-F. Liu, M. D. Silva, T. Omae, C. H. Sotak, J. D. Fenstermacher, M. Fisher, C. Y. Hsu, and W. Lin Transient and Permanent Resolution of Ischemic Lesions on Diffusion-Weighted Imaging After Brief Periods of Focal Ischemia in Rats : Correlation With Histopathology • Editorial Comment: Correlation With Histopathology Stroke, April 1, 2000; 31(4): 946 - 954. [Abstract] [Full Text] [PDF]

				R. Pineiro, S. T. Pendlebury, S. Smith, D. Flitney, A. M. Blamire, P. Styles, and P. M. Matthews Relating MRI Changes to Motor Deficit After Ischemic Stroke by Segmentation of Functional Motor Pathways Stroke, March 1, 2000; 31(3): 672 - 679. [Abstract] [Full Text] [PDF]

				M. Muller, W. Reiche, P. Langenscheidt, J. Ha{beta}feld, and T. Hagen Ischemia after Carotid Endarterectomy: Comparison between Transcranial Doppler Sonography and Diffusion-Weighted MR Imaging AJNR Am. J. Neuroradiol., January 1, 2000; 21(1): 47 - 54. [Abstract] [Full Text] [PDF]

				P. M. Britt, J. E. Heiserman, R. M. Snider, H. A. Shill, C. R. Bird, and R. C. Wallace Incidence of Postangiographic Abnormalities Revealed by Diffusion-Weighted MR Imaging AJNR Am. J. Neuroradiol., January 1, 2000; 21(1): 55 - 59. [Abstract] [Full Text] [PDF]

				W. T. C. Yuh, T. Ueda, M. White, M. E. Schuster, and T. Taoka The Need for Objective Assessment of the New Imaging Techniques and Understanding the Expanding Roles of Stroke Imaging AJNR Am. J. Neuroradiol., November 1, 1999; 20(10): 1779 - 1784. [Full Text]

				Q. Yang, B. M. Tress, P. A. Barber, P. M. Desmond, D. G. Darby, R. P. Gerraty, T. Li, and S. M. Davis Serial Study of Apparent Diffusion Coefficient and Anisotropy in Patients With Acute Stroke Stroke, November 1, 1999; 30(11): 2382 - 2390. [Abstract] [Full Text] [PDF]

				P. A. Barber, D. G. Darby, P. M. Desmond, R. P. Gerraty, Q. Yang, T. Li, D. Jolley, G. A. Donnan, B. M. Tress, and S. M. Davis Identification of Major Ischemic Change : Diffusion-Weighted Imaging Versus Computed Tomography Stroke, October 1, 1999; 30(10): 2059 - 2065. [Abstract] [Full Text] [PDF]

				T. Neumann-Haefelin, H.-J. Wittsack, F. Wenserski, M. Siebler, R. J. Seitz, U. Modder, and H.-J. Freund Diffusion- and Perfusion-Weighted MRI : The DWI/PWI Mismatch Region in Acute Stroke Stroke, August 1, 1999; 30(8): 1591 - 1597. [Abstract] [Full Text] [PDF]

				T. Ueda, W. T. C. Yuh, J. E. Maley, J. P. Quets, P. Y. Hahn, and V. A. Magnotta Outcome of Acute Ischemic Lesions Evaluated by Diffusion and Perfusion MR Imaging AJNR Am. J. Neuroradiol., June 1, 1999; 20(6): 983 - 989. [Abstract] [Full Text]

				K. Okada, L.-H. Wu, and S. Kobayashi Diffusion-Weighted MRI in Severe Leukoaraiosis Stroke, February 1, 1999; 30(2): 478 - 479. [Full Text] [PDF]

				K. P. N. Forbes, J. G. Pipe, and C. R. Bird Changes in Brain Water Diffusion during the 1st Year of Life Radiology, February 1, 2002; 222(2): 405 - 409. [Abstract] [Full Text] [PDF]

				L. S. Medina Changes in Brain Water Diffusion during the 1st Year of Life: Finally Starting to Understand Age- and Brain Tissue-related Normative Data Radiology, February 1, 2002; 222(2): 316 - 318. [Full Text] [PDF]

This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by van Everdingen, K.J. Articles by Mali, W.P.T.M. Search for Related Content PubMed PubMed Citation Articles by van Everdingen, K.J. Articles by Mali, W.P.T.M.