Context Noncontrast computed tomography (CT) is the standard brain imaging study
for the initial evaluation of patients with acute stroke symptoms. Multimodal
magnetic resonance imaging (MRI) has been proposed as an alternative to CT
in the emergency stroke setting. However, the accuracy of MRI relative to
CT for the detection of hyperacute intracerebral hemorrhage has not been demonstrated.
Objective To compare the accuracy of MRI and CT for detection of acute intracerebral
hemorrhage in patients presenting with acute focal stroke symptoms.
Design, Setting, and Patients A prospective, multicenter study was performed at 2 stroke centers (UCLA
Medical Center and Suburban Hospital, Bethesda, Md), between October 2000
and February 2003. Patients presenting with focal stroke symptoms within 6
hours of onset underwent brain MRI followed by noncontrast CT.
Main Outcome Measures Acute intracerebral hemorrhage and any intracerebral hemorrhage diagnosed
on gradient recalled echo (GRE) MRI and CT scans by a consensus of 4 blinded
readers.
Results The study was stopped early, after 200 patients were enrolled, when
it became apparent at the time of an unplanned interim analysis that MRI was
detecting cases of hemorrhagic transformation not detected by CT. For the
diagnosis of any hemorrhage, MRI was positive in 71 patients with CT positive
in 29 (P<.001). For the diagnosis of acute hemorrhage,
MRI and CT were equivalent (96% concordance). Acute hemorrhage was diagnosed
in 25 patients on both MRI and CT. In 4 other patients, acute hemorrhage was
present on MRI but not on the corresponding CT—each of these 4 cases
was interpreted as hemorrhagic transformation of an ischemic infarct. In 3
patients, regions interpreted as acute hemorrhage on CT were interpreted as
chronic hemorrhage on MRI. In 1 patient, subarachnoid hemorrhage was diagnosed
on CT but not on MRI. In 49 patients, chronic hemorrhage, most often microbleeds,
was visualized on MRI but not on CT.
Conclusion MRI may be as accurate as CT for the detection of acute hemorrhage in
patients presenting with acute focal stroke symptoms and is more accurate
than CT for the detection of chronic intracerebral hemorrhage.
Noncontrast computed tomography (CT) has been the standard imaging modality
for the initial evaluation of patients presenting with acute stroke symptoms.1,2 The primary diagnostic advantage of
CT in the hyperacute phase (0 to 6 hours) is its ability to rule out the presence
of hemorrhage. Accurate early detection of blood is crucial since a history
of intracerebral hemorrhage is a contraindication to the use of thrombolytic
agents. However, a major disadvantage of conventional CT within the first
few hours of symptom onset is its limited sensitivity for identifying early
evidence of cerebral ischemia.
Conversely, multimodal magnetic resonance imaging (MRI), including diffusion-weighted
imaging (DWI), has excellent capacity to delineate the presence, size, location,
and extent of hyperacute ischemia,3 but unproven
reliability in identifying early parenchymal hemorrhage. The advent of thrombolytic
therapy and other interventional therapies for acute ischemic stroke has led
to increasing interest in using MRI to select and stratify candidates for
treatments.4 Currently, many stroke centers
obtain both CT and MRI in the initial evaluation of patients with stroke.
The use of both modalities is time-consuming and expensive.
While conventional T1- and T2-weighted MRI pulse sequences are sensitive
for the detection of subacute and chronic blood, they are less sensitive to
parenchymal hemorrhage during the initial 6 hours after stroke symptom onset.
A growing body of data have suggested that hyperacute parenchymal blood can
be accurately detected using gradient recalled echo (GRE) pulse sequences
that are sensitive to static magnetic field inhomogeneity (ie, T2*-sensitive).5-9 These
sequences detect the paramagnetic effects of deoxyhemoglobin and methemoglobin.
The hyperacute lesion on GRE/T2* typically consists of a core of heterogeneous
signal intensity, reflecting the most recently extravasated blood that may
still contain significant amounts of diamagnetic oxyhemoglobin, surrounded
by a rim of hypointensity, signifying parenchymal blood that has had time
to become more fully deoxygenated and paramagnetic (Figure 1).7,10
We undertook a prospective comparison study of MRI vs CT in a large
cohort of patients with acute stroke to establish that GRE MRI sequences are
sensitive to acute hemorrhage.
The Hemorrhage and Early MRI Evaluation (HEME) study was performed at
2 academic stroke centers (UCLA Medical Center and National Institutes of
Health [NIH] Stroke Center at Suburban Hospital, Bethesda, Md). Initially,
2 additional centers were involved but subsequently discontinued participation
in the study because of inadequate patient enrollment. Patients presenting
with focal stroke symptoms within 6 hours of onset were screened for enrollment.
Only symptomatic patients with a definite last known well time when initial
imaging took place were eligible. Patients were excluded if any of the following
were present: coma; pacemaker or other contraindication to MRI; symptoms suggestive
of subarachnoid hemorrhage (SAH); inability to obtain MRI within 6 hours from
last known well time; initiation of thrombolytic therapy, intravenous antithrombotics
or anticoagulants, or antithrombotic investigational drug prior to completion
of both imaging studies; or cardiorespiratory instability precluding MRI.
Site participation in the study was contingent upon the site’s
current routine clinical practice of obtaining MRI followed by CT for patients
with potential acute stroke. The institutional review board (IRB) at each
site gave approval to prospectively collect and analyze clinical and imaging
data with identifying information removed. At UCLA, the IRB waived consent;
at Suburban Hospital, the study was performed under an IRB approved natural
history of stroke protocol in which waiver was permitted in individual cases
if waiver of consent could not be obtained.
All patients underwent MRI followed by CT. Imaging time goals were completion
of both MRI and CT within 90 minutes of presentation to the emergency department,
with no more than 30 minutes between the end of MRI and the start of CT. Each
site was required to keep a monthly log of all patients presenting within
6 hours of stroke symptom onset to ensure that at least 50% of all fully eligible
patients were being enrolled. To qualify for enrollment, both GRE and DWI
had to be completed.
All MRIs were performed on 1.5-T scanners equipped with echo-planar
imaging capability: UCLA, Siemens Vision (Siemens Medical System, Iselin,
NJ); and Suburban Hospital, GE Signa scanner (General Electric Medical Systems,
Milwaukee, Wis). Computed tomographic scans were performed on 1 of the following
fourth-generation scanners: Somatom Plus scanner (Siemens), High Speed Advantage
scanner (General Electric), or Lightspeed scanner (General Electric). Images
were acquired following the orbito-meatal plane with 5 mm thickness for the
entire examination. Both scanners used the following pulse sequence parameters:
slice thickness, 7 mm (GRE and DWI); repetition time (TR), 800 ms (GRE); flip
angle 30° (GRE); acquisition matrix, 256×192 (GRE) and 128×128
(DWI). Pulse parameters at UCLA and at Suburban Hospital, respectively, were:
field of view, 24 cm and 22 cm (GRE and DWI); echo time (TE), 20 ms and 15
ms (GRE); TR, 6000 ms and 60 000 ms (DWI) (20 contiguous slices, interleaved,
and co-localized); and TE, 100 ms and 72 ms (DWI).
A panel of 4 readers (2 neuroradiologists and 2 stroke neurologists)
independently evaluated each scan blinded to the clinical information and
all patient identifiers. None of the 4 readers was involved in the clinical
care or evaluation of the enrolled patients. Before performing study interpretations,
the readers were given examples (compiled from an independent data set) of
each hemorrhage type to ensure consistency of interpretation to a common standard.
Interpretations for each imaging modality (CT vs MRI) for a single patient
were performed on different days to avoid reader recognition or recall of
findings from the other modality. The order of presentation of the films was
randomized and differed for each modality. The following data were recorded
by each reader for each scan: hemorrhage present or absent; if hemorrhage
present, hemorrhage age (acute or chronic), type(s) (subarachnoid, subdural,
epidural, intraventricular, intraparenchymal), location (cortical, subcortical
white matter, basal ganglia, brainstem, cerebellum, thalamus), and number
(single or multiple). For MRI interpretations, readers had access to DWI b0,
trace DWI b1000, and GRE images.
Intraparenchymal hemorrhage was further classified as hematoma, hemorrhagic
transformation, or microbleed. Microbleeds were defined as rounded, punctate,
homogeneous hypointensities generally less than 0.5 cm in size within the
parenchyma, visualized on GRE MRI scans, and thought to represent regions
of chronic hemosiderin deposition.11-13 Hemorrhagic
transformation (petechial hemorrhage) was defined as a region of hyperdensity
(CT) or hypointensity (GRE MRI) occurring within an acute, subacute, or chronic
ischemic lesion. Chronic hematoma was defined as a slit-like region of hypodensity
(CT) or hypointensity (GRE MRI) thought to be due to hemosiderin deposition
from a remote hematoma. Computed tomographic acute hemorrhage volumes were
subsequently calculated (by C.S.K.) using a volumetric imaging analysis program.
If unanimous agreement regarding the presence and acuity of hemorrhage
on an individual scan was not achieved by each of the 4 readers, the interpretation
of the majority of readers was used as the final imaging diagnosis. In evenly
distributed disagreements (2 vs 2), final interpretation was reached by group
consensus discussion.Final hospital discharge diagnosis incorporating all
available clinical, laboratory, and imaging data was made at the time of discharge
by the attending physician.
The primary objective of the study was to compare the accuracy of MRI
vs CT for the detection of acute hemorrhage. Secondary objectives were to
compare the accuracy of MRI vs CT for any hemorrhage (acute or chronic) and
for chronic hemorrhage alone.
Initial sample size calculations assumed that CT was 100% accurate for
hemorrhage and sought to demonstrate that MRI was also 100% accurate. In this
noninferiority design, the sample size required to narrow the difference in
the 95% confidence interval (CI) between MRI and CT to less than 5% was exact
concordance between MRI and CT on 55 hemorrhages. The selected software was
Microsoft Excel, using binomial theory. The a priori confidence level is 95%;
however, an a priori significance level is unavailable since we are making
a confidence bound, not significance testing.
In early 2003, an unplanned interim analysis was performed when preliminary
results of a complementary study became available.14 During
the interim analysis, it became apparent that MRI was detecting acute hemorrhages
not visualized on CT and, therefore, the initial sample size, based on the
assumption of using CT as the criterion standard, was not valid. Accordingly,
the primary analysis plan was changed to bidirectional comparison of CT vs
MRI without assuming that one technique was inherently a criterion standard.
In addition, at this juncture, the study was stopped early after 200 patients
were enrolled, as the investigators believed it would be important to expedite,
complete, and report the analysis of these patients because of the potential
major impact the findings could have on current acute stroke management.
Interrater reliability was calculated for paired observers of both CT
and MRI interpretations using the kappa (κ) statistic. The McNemar test
for paired proportions was used to determine if one imaging modality diagnosed
hemorrhage more frequently than the other.
Between October 2000 and February 2003, 391 consecutive patients presenting
with focal stroke symptoms within 6 hours of onset were screened for enrollment
in the study and a total of 200 patients were enrolled. Reasons for exclusion
of the 191 patients who were not enrolled include: pacemaker or other contraindication
to MRI (43); medical instability for MRI such as vomiting, coma, or cardiorespiratory
instability (10); nonavailability of both imaging techniques within the time
window (99); initiation of thrombolytic or anticoagulant therapy before or
between scans (9); and other reasons (30).
Characteristics of enrolled patients are summarized in Table 1. The comparisons between CT and MRI performance for any
hemorrhage, acute hemorrhage, and chronic hemorrhage are shown in Table 2 and Table
3. Ranges for interrater reliability based on the κ statistic
for paired observers were: 0.75 to 0.82 for acute hemorrhage on MRI and 0.87
to 0.94 for acute hemorrhage on CT; 0.42 to 0.66 for chronic hemorrhage on
MRI (not applicable for CT); 0.58 to 0.80 for any hemorrhage on MRI and 0.85
to 0.92 for any hemorrhage on CT.
The panel read acute hemorrhage in 25 patients on both CT and MRI. In
4 additional patients, acute hemorrhage was interpreted as being present on
MRI but not on the corresponding CT (Figure 2). In all 4 of these patients, regions of hypointensity were seen
on the GRE images within an ischemic field (identified by DWI). Each of these
cases was interpreted as hemorrhagic transformation of an ischemic infarct
by the treating physicians based on all clinical and radiologic data.
In 4 patients, acute hemorrhage was read by the panel on CT but not
the corresponding MRI (Figure 3). In
3 of these patients, the region of acute hemorrhage apparent on CT was also
apparent on MRI but was interpreted as “chronic hemorrhage” rather
than acute. In the fourth patient, a region of hyperdensity on CT in the left
frontal lobe was interpreted as subarachnoid blood by 2 of 4 readers on CT;
on MRI this abnormality was clearly apparent as a serpiginous, hypointense
lesion in a sulcus on GRE images. Although 1 of the readers did initially
interpret this lesion as acute SAH on MRI, 3 did not. The final discharge
diagnosis for this patient was acute ischemic stroke with SAH.
For the 26 primary intraparenchymal hematomas visualized on CT, median
hematoma volume was 20.8 mL (range, 0.2-157.2 mL). Subarachnoid blood was
visualized in 2 cases, including 1 isolated SAH associated with acute ischemic
stroke (case above) and 1 SAH with an intracerebral and intraventricular hemorrhage.
In the latter, the subarachnoid blood component was noted on CT only, although
both CT and MRI detected the intraparenchymal and intraventricular components.
Intraventricular blood was interpreted as being present in 16 patients, all
with intraparenchymal hematomas. The intraventricular blood was apparent on
both CT and MRI in 11 cases, on MRI only in 1, and on CT only in 4. Subdural
hemorrhage was seen in only 1 patient and was identified on both MRI and CT.
No epidural hematomas were identified.
Chronic hemorrhage was seen in 52 patients on MRI and in no patients
on CT. Of these 52 MRI patients, 4 were interpreted as regions of chronic
hemorrhagic transformation, 9 as chronic hematomas, 34 as 1 or more microbleeds
(Figure 4), and 7 as both one or more
microbleeds and one or more hematomas. Three of the cases interpreted as chronic
hematoma on MRI were visualized as acute blood on CT. Of the 41 patients with
MRI-evident microbleeds, 10 had single lesions and 31 multiple lesions—with
none visualized on CT.
Compared with final discharge diagnosis, which incorporated information
from both imaging studies as well as additional laboratory, pathologic, and
clinical data, CT and MRI performed equally well with no significant difference
in the accuracy of the scans obtained from UCLA Medical Center vs Suburban
Hospital (Table 4).
A first imaging study was performed within 3 hours of onset for 129
patients. Nineteen of the cases with a final discharge diagnosis of hemorrhage
and 6 of the 8 discordant hemorrhage cases (3 each for CT negative, and MRI
negative) were within this cohort. Thirty-four patients were treated with
intravenous tissue plasminogen activator (tPA) within 3 hours of onset. The
remaining patients were not treated due to rapidly resolving or nondisabling
deficits, or other contraindication to thrombolytic therapy.
Neuroimaging plays a crucial role in the evaluation of patients presenting
with acute stroke symptoms. While patient symptoms and clinical examinations
may suggest the diagnosis, only brain imaging studies can confirm the diagnosis
and differentiate hemorrhage from ischemia with high accuracy. This differentiation
is critical in making acute treatment decisions, including patient eligibility
for thrombolytic therapy. Although noncontrast CT has been considered the
criterion standard for assessing intracerebral hemorrhage, formal studies
have never been performed to validate the accuracy of this technique compared
to the true criterion standard, pathology. In our study, hemorrhage was accurately
identified on MRI in all cases of CT positive acute intraparenchymal hematomas;
in 25 cases, the blood was interpreted as acute and in 3 cases as chronic.
The HEME study provides complementary data to that of a recently published
study performed by the German Stroke Competence Network (B5 Hemorrhage Study).14 This group evaluated the accuracy of CT vs MRI in
distinguishing acute intracerebral hemorrhage (50 patients) from acute ischemic
stroke (50 patients) using a design in which patients were randomized to either
CT or MRI first. The HEME study enrolled all eligible patients, rather than
simply an equal number of patients with hemorrhagic and ischemic stroke.
Our panel of readers identified acute hemorrhage on MRI in 4 cases in
which hemorrhage was not apparent on CT. Each of these was interpreted as
a region of hemorrhagic transformation (petechial blood) within an acute ischemic
infarct field. These results are supported by recent case reports of “CT-negative
intracerebral hemorrhages.”16-18 It
is possible that hyperacute hemorrhagic transformation of ischemic infarcts
is an underrecognized phenomenon.
The implication of this finding for the neuroimaging evaluation of acute
stroke patients who are candidates for thrombolytic therapy is unclear. In
the National Institute of Neurological Disorders and Stroke (NINDS) trial,
intravenous tPA was shown to be effective based on CT enrollment criteria.19 While it may be hypothesized that patients with MRI
evidence of hemorrhagic transformation are at higher risk of developing symptomatic
hemorrhage if treated with thrombolytics, it is also possible that overall
this group of patients may receive net benefit from therapy. A prospective
study will be needed to answer this question.
All 3 acute hemorrhages that the panel misclassified as chronic on MRI
were relatively small, but none were classified as chronic microbleeds. In
these cases, the typical pattern of acute hemorrhage on GRE was more difficult
for reviewers to appreciate (2 patients) or not present (1 patient). Physicians
should be aware that in cases of small hemorrhages (non-microbleeds), it may
be difficult to make an exact distinction between acute and chronic hemorrhage
based on GRE images alone. A noncontrast CT may be necessary in these cases
to determine hemorrhage age. With acute medium-large hemorrhages, the characteristic
appearance of mixed signal intensity and the surrounding hyperintensity due
to edema is very specific and will make the age of the hemorrhage apparent.7 However, small hemorrhages may have similar characteristics
to calcifications and intravascular thrombus and have minimal edema making
the determination of hemorrhage age as well as the distinction of hemorrhage
vs nonhemorrhage more difficult.10,20
The HEME study confirms the superiority of GRE MRI sequences for the
identification of chronic hemorrhage. In 49 patients, GRE demonstrated chronic
blood not apparent on CT. The majority of these chronic hemorrhages were categorized
as microbleeds—clinically silent, small, punctate hemosiderin lesions
appearing hypointense on GRE sequences.13 The
role of microbleeds in determining patient eligibility for thrombolytic therapy
remains unknown. However, prior studies suggest that the presence of microbleeds
may be an independent risk factor for hemorrhage in patients treated with
antithrombotic or thrombolytic therapy.11,21-23
Our study has several limitations. We initiated the study using CT as
the criterion standard for diagnosis of hemorrhage. However, following the
unplanned interim analysis indicating that GRE sequences were detecting hemorrhage
not seen on CT, we switched to a 2-sided analysis based on the assumption
that these MRI findings represented genuine acute hemorrhage. We also specifically
excluded any patient with symptoms suggestive of SAH. Although prior studies
have suggested that both GRE MRI and fluid-attenuated inversion recovery images
may be accurate in identifying subarachnoid blood, this will need to be prospectively
confirmed in a future study.24-26 Because
neither CT nor MRI can exclude SAH with 100% reliability, the clinician should
pursue an extensive evaluation in any patient with whom SAH is contemplated,
including CT as well as lumbar puncture if CT is negative.
Interreader reliability (κ statistic) for detection of hemorrhage
was better for CT than for MRI. This is likely due to several factors, including
less experience of the readers in interpreting acute MRI for hemorrhage and
differences in the intrinsic conspicuity of hemorrhage appearance on CT and
MRI. Therefore, a comprehensive educational program should be undertaken at
any institution choosing to perform only MRI and not CT for the evaluation
of acute stroke patients.
Recent reports have indicated widespread availability of advanced MRI
techniques in the United States for the evaluation of patients with acute
stroke.27,28 However, concerns
have been raised regarding the logistical aspects of acquiring multimodal
MRI in the acute stroke setting, particularly with regard to image acquisition
times (and potential delays in initiating thrombolytic therapy). Based on
our overall experience, the comprehensive MRI stroke protocol we used generally
takes 10 to 15 minutes. An abbreviated protocol, including DWI, GRE, and perfusion
weighted imaging (PWI), takes less than 5 minutes and still provides substantially
more information than a noncontrast CT.
Our study may have implications for the imaging evaluation of patients
with acute stroke symptoms. Our findings support prior studies suggesting
that MRI is as accurate as CT for the detection of hyperacute hemorrhage.14 One important caveat is that with small hemorrhages,
blood that appears as acute on CT may appear as chronic on GRE MRI and a noncontrast
CT may be required to confirm the diagnosis in these cases. Our study suggests
that GRE MRI may be able to detect regions of hemorrhagic transformation of
an acute ischemic stroke not evident on CT. Our study confirms the superiority
of MRI for detection of chronic hemorrhage, particularly microbleeds. The
role of these findings in the decision-making process for treatment of patients
who are candidates for thrombolytic therapy is currently unknown. Due to its
advantages in delineating ischemic pathophysiology, in combination with the
findings suggesting equivalency to CT for detecting acute hemorrhage, MRI
may be acceptable as the sole imaging technique for acute stroke at centers
with expertise in interpreting these findings.
Corresponding Author: Chelsea S. Kidwell,
MD, Washington Hospital Center Stroke Center, 100 Irving St NW, East Bldg
Room 6126, Washington, DC 20010 (ckidwell@ucla.edu).
Author Contributions: Dr Kidwell had full access
to all of the data in the study and takes full responsibility for the integrity
of the data and the accuracy of the data analysis.
Study concept and design: Kidwell, Chalela,
Saver, Starkman, Warach.
Acquisition of data: Kidwell, Chalela, Saver, Starkman,
Hill, Demchuk, Patronas, Alger, Latour, Baird, Leary, Tremwel, Ovbiagele,
Fredieu, Suzuki, Villablanca, Davis, Dunn, Todd, Ezzeddine, Haymore, Lynch,
Davis, Warach.
Analysis and interpretation of data: Kidwell,
Chalela, Saver, Butman, Patronas, Alger, Latour, Luby, Villablanca, Davis,
Warach.
Drafting of the manuscript: Kidwell, Chalela,
Fredieu, Davis Warach, Saver.
Critical revision of the manuscript for important
intellectual content: Kidwell, Chalela, Saver, Starkman, Hill, Demchuk,
Butman, Patronas, Alger, Latour, Luby, Baird, Leary, Tremwel, Ovbiagele, Suzuki,Villablanca,
Davis, Dunn, Todd, Ezzeddine, Haymore, Lynch, Davis, Warach.
Statistical analysis: Kidwell, Chalela, Saver,
Luby, Warach.
Obtained funding: Kidwell, Saver, Warach.
Administrative, technical, or material support:
Kidwell, Saver, Starkman, Hill, Alger, Latour, Luby, Leary, Fredieu, Davis,
Todd, Haymore, Warach.
Study supervision: Kidwell, Chalela, Starkman,
Baird, Ezzeddine, Warach.
Funding/Support:This study was supported in
part by the Division of Intramural Research, National Institute of Neurological
Disorders and Stroke (NINDS) and grants from the American Heart Association
(0170033N, Dr Kidwell; AHA Western States Affiliate Fellowship Award, Dr Leary)
and NINDS (K23 NS 02088, Dr Kidwell; NS 39498/EB 002087, Dr Alger; K24 NS
02092, Dr Saver). Dr Hill was supported in part by the Heart & Stroke
Foundation of Alberta/NWT/NU and the Canadian Institutes for Health Research.
Role of the Sponsor: The study was wholly designed,
conducted, analyzed, and reported by the authors without any input from industrial
sponsors.
Acknowledgment: We would like to acknowledge
the invaluable assistance provided by Patricia Lyall, BA, Vickie Hyneman,
Elisa Landis, BA, and Sarah Hilton, BS, for the completion of this project.
1.Broderick JP, Adams HP Jr, Barsan W.
et al. Guidelines for the management of spontaneous intracerebral hemorrhage.
Stroke. 1999;30:905-91510187901
Google ScholarCrossref 2.Adams HP Jr, Adams RJ, Brott T.
et al. Guidelines for the early management of patients with ischemic stroke.
Stroke. 2003;34:1056-108312677087
Google ScholarCrossref 3.Baird AE, Warach S. Magnetic resonance imaging of acute stroke.
J Cereb Blood Flow Metab. 1998;18:583-6099626183
Google ScholarCrossref 4.Albers GW. Expanding the window for thrombolytic therapy in acute stroke.
Stroke. 1999;30:2230-223710512933
Google ScholarCrossref 5.Edelman RR, Johnson K, Buxton R.
et al. MR of hemorrhage: a new approach.
AJNR Am J Neuroradiol. 1986;7:751-7563096097
Google Scholar 6.Patel MR, Edelman RR, Warach S. Detection of hyperacute primary intraparenchymal hemorrhage by magnetic
resonance imaging.
Stroke. 1996;27:2321-23248969800
Google ScholarCrossref 7.Linfante I, Llinas RH, Caplan LR, Warach S. MRI features of intracerebral hemorrhage within 2 hours from symptom
onset.
Stroke. 1999;30:2263-226710548654
Google ScholarCrossref 8.Schellinger PD, Jansen O, Fiebach JB, Hacke W, Sartor K. A standardized MRI stroke protocol.
Stroke. 1999;30:765-76810187876
Google ScholarCrossref 9.Kidwell CS, Saver JL, Mattiello J.
et al. Diffusion-perfusion MR evaluation of perihematomal injury in hyperacute
intracerebral hemorrhage.
Neurology. 2001;57:1611-161711706101
Google ScholarCrossref 10.Atlas SW, Thulborn KR. MR detection of hyperacute parenchymal hemorrhage of the brain.
AJNR Am J Neuroradiol. 1998;19:1471-14779763380
Google Scholar 11.Kidwell CS, Saver JL, Villablanca JP.
et al. Magnetic resonance imaging detection of microbleeds before thrombolysis.
Stroke. 2002;33:95-9811779895
Google ScholarCrossref 12.Roob G, Fazekas F. Magnetic resonance imaging of cerebral microbleeds.
Curr Opin Neurol. 2000;13:69-7310719653
Google ScholarCrossref 13.Fazekas F, Kleinert R, Roob G.
et al. Histopathologic analysis of foci of signal loss on gradient-echo T2*-weighted
MR images in patients with spontaneous intracerebral hemorrhage.
AJNR Am J Neuroradiol. 1999;20:637-64210319975
Google Scholar 14.Fiebach JB, Schellinger PD, Gass A.
et al. Stroke magnetic resonance imaging is accurate in hyperacute intracerebral
hemorrhage.
Stroke. 2004;35:502-50614739410
Google ScholarCrossref 16.Packard AS, Kase CS, Aly AS, Barest GD. “Computed tomography-negative” intracerebral hemorrhage.
Arch Neurol. 2003;60:1156-115912925375
Google ScholarCrossref 17.Sandercock P, Foy PM, Brock LG. Negative computerised tomographic scan in patient with intracerebral
haematoma.
Lancet. 1986;1:506-5072869246
Google ScholarCrossref 18.Nakada T, Kwee IL. Computed tomography-negative acute thalamic hematoma.
J Neuroimaging. 1996;6:119-1218634486
Google Scholar 19.NINDS rt-PA Stroke Group. Tissue plasminogen activator for acute ischemic stroke.
N Engl J Med. 1995;333:1581-15877477192
Google ScholarCrossref 20.Hermier M, Nighoghossian N. Contribution of susceptibility-weighted imaging to acute stroke assessment.
Stroke. 2004;35:1989-199415192245
Google ScholarCrossref 21.Chalela JA, Kang DW, Warach S. Multiple cerebral microbleeds.
J Neuroimaging. 2004;14:54-5714748209
Google Scholar 22.Fan YH, Zhang L, Lam WW, Mok VC, Wong KS. Cerebral microbleeds as a risk factor for subsequent intracerebral
hemorrhages among patients with acute ischemic stroke.
Stroke. 2003;34:2459-246212958325
Google ScholarCrossref 23.Wong KS, Chan YL, Liu JY, Gao S, Lam WW. Asymptomatic microbleeds as a risk factor for aspirin-associated intracerebral
hemorrhages.
Neurology. 2003;60:511-51312578941
Google ScholarCrossref 24.Wiesmann M, Mayer TE, Yousry I, Medele R, Hamann GF, Bruckmann H. Detection of hyperacute subarachnoid hemorrhage of the brain by using
magnetic resonance imaging.
J Neurosurg. 2002;96:684-68911990808
Google ScholarCrossref 25.Singer MB, Atlas SW, Drayer BP. Subarachnoid space disease.
Radiology. 1998;208:417-4229680570
Google Scholar 26.Mitchell P, Wilkinson ID, Hoggard N.
et al. Detection of subarachnoid haemorrhage with magnetic resonance imaging.
J Neurol Neurosurg Psychiatry. 2001;70:205-21111160469
Google ScholarCrossref 27.Liebeskind DS, Yang CK, Sayre J, Bakshi R. Neuroimaging of cerebral ischemia in clinical practice [abstract].
Stroke. 2003;34:255
Google ScholarCrossref 28.Ruland S, Gorelick PB, Schneck M, Kim D, Moore CG, Leurgans S. Acute stroke care in Illinois.
Stroke. 2002;33:1334-133911988612
Google ScholarCrossref