(Stroke. 2000;31:726.)
© 2000 American Heart Association, Inc.
Original Contributions |
Diffusion-Weighted MRI and Proton MR Spectroscopic Imaging in the Study of Secondary Neuronal Injury After Intracerebral Hemorrhage
From the Divisions of Neurosciences Critical Care (J.R.C., D.F.H.) and Neuroradiology (P.Y.W., N.J.B., P.B.B.) and the Department of Emergency Medicine (P.M.K.), The Johns Hopkins Medical Institutions, Baltimore, Md.
Correspondence to Juan R. Carhuapoma, MD, Division of Neurosciences Critical Care, Meyer 8–140, Johns Hopkins Hospital, 600 N Wolfe St, Baltimore, MD 21287-7840. E-mail jrcarhuapoma{at}sprintmail.com
 |
Abstract |
|---|
 Top Abstract IntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
Background and Purpose—Cerebral ischemia has been proposed as contributing mechanism to secondary neuronal injury after intracerebral hemorrhage (ICH). Possible tools for investigating this hypothesis are diffusion-weighted (DWI) and proton magnetic resonance spectroscopic imaging (1H-MRSI). However, magnetic field inhomogeneity induced by paramagnetic blood products may prohibit the application of such techniques on perihematoma tissue. We report on the feasibility of DWI and 1H-MRSI in the study of human ICH and present preliminary data on their contribution to understanding perihematoma tissue functional and metabolic profiles.
Methods—Patients with acute supratentorial ICH were prospectively evaluated using DWI and 1H-MRSI. Obscuration of perihematoma tissue with both sequences was assessed. Obtainable apparent diffusion coefficient (Dav) and lactate spectra in perihematoma brain tissue were recorded and analyzed.
Results—Nine patients with mean age of 63.4 (36 to 87) years were enrolled. Mean time from symptom onset to initial MRI was 3.4 (1 to 9) days; mean hematoma volume was 35.4 (5 to 80) cm3. Perihematoma diffusion values were attainable in 9 of 9 patients, and 1H-MRSI measures were obtainable in 5 of 9 cases. Dav in perihematoma regions was 172.5 (120.0 to 302.5)x10-5 mm2/s and 87.6 (76.5 to 102.1)x10-5 mm2/s in contralateral corresponding regions of interest (P=0.002). One patient showed an additional area of reduced Dav with normal T2 intensity, which suggests ischemia. 1H-MRSI revealed lactate surrounding the hematoma in 2 patients.
Conclusions—DWI and 1H-MRSI can be used in the study of ICH patients. Our preliminary data are inconsistent with ischemia as the primary mechanism for perihematoma tissue injury. Further investigation with advanced MRI techniques will give a clearer understanding of the role that ischemia plays in tissue injury after ICH.
Key Words: intracerebral hemorrhage • magnetic resonance imaging, diffusion-weighted • neuronal damage • spectroscopy, nuclear magnetic resonance
|
Introduction |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
Patients with intracerebral hemorrhage (ICH) are at increased risk of death and long-term functional disability compared with ischemic stroke victims, despite relatively similar volumes of neuronal tissue at risk of injury.1 This poor outcome could be related to various factors, such as hemorrhage extension, elevated intracranial pressure with subsequent herniation, or possibly cellular damage that develops over a period of hours or days after the initial damage –(secondary neuronal injury) in the perihematoma tissue, as recent evidence seems to suggest.2 3 4 5
Although early animal studies suggested the existence of an ischemic penumbra that surrounded the hematoma, more recent clinical and experimental investigations have failed to demonstrate consistent presence of neuronal ischemia in remaining viable tissue peripheral to the hematoma.2 3 4 5 6 For this reason, other nonischemic mechanisms of neuronal injury after ICH, such as thrombin-induced neurotoxicity and inflammation, are now being investigated and may offer new avenues for therapeutic research in ICH patients if validated.7
Currently available advanced MRI techniques may enable clarification of mechanisms that mediate injury to perihematoma brain tissue. Diffusion-weighted MRI (DWI) and 1H-magnetic resonance spectroscopic imaging (1H-MRSI) have already proved valuable in the diagnosis and study of the natural history of ischemic stroke.8 These tools have enabled us to delineate areas of essentially irreversible injury soon after the ictus and have shown that progression of ischemic tissue to infarction continues beyond the current treatment window.9 10 However, use of these techniques to assess mechanisms of neuronal injury after ICH has been limited, in part because of concerns about magnetic field inhomogeneity generated by the presence of intraparenchymal hemorrhage that limited the study of regions adjacent to blood products.
In the present study, we demonstrate the feasibility of DWI and 1H-MRSI in the study of perihematoma brain tissue and report our initial results of early (acute and subacute) functional and metabolic profiles of brain parenchyma surrounding ICH. Because the ultimate diagnosis of secondary neuronal damage is based on histopathology, these perilesional brain tissue MRI profiles are interpreted in the present article to be surrogate MRI markers of secondary brain injury after ICH.
|
Subjects and Methods |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
Patients
With approval from the Johns Hopkins Hospital’s investigational review board and after informed consent was obtained from patients or their relatives, consecutive subjects with a diagnosis of acute, nontraumatic supratentorial ICH were screened and enrolled in the pilot study. Inclusion criteria were as follows: patients admitted to the NeuroCritical Care Unit at the Johns Hopkins Hospital with new onset of a measurable neurological deficit and a head CT compatible with acute supratentorial ICH. Patient exclusion criteria included any contraindication of MRI, evidence of allergy to gadolinium documented in a previous exposure to the contrast agent, or ICH secondary to known anticoagulation or abnormal prothrombin/partial thromboplastin time. Similarly, the following patients also were excluded: those with ICH due to bleeding into a tumoral lesion that was secondary to traumatic brain injury or due to subarachnoid hemorrhage and those with hemorrhagic infarction and prior ischemic stroke in the same distribution of the current ICH. Women of childbearing age were screened for pregnancy before being considered candidates for the study. All subjects enrolled received standard care for ICH patients with or without secondary IVH. Studies were performed only after patients were deemed clinically stable to be safely transported to the MRI facility. A NeuroCritical Care Unit staff member accompanied every patient during the MRI studies, and continuous neurodynamic, hemodynamic, and respiratory monitoring was performed.
MRI Techniques
All MRI experiments were performed on a 1.5-T General Electric
scanner with quadrature head coil that was located in the MRI
facilities at Johns Hopkins Hospital. The following MR sequences were
recorded: (1) sagittal T1-weighted localizer
images, (2) axial spin-echo spin density and
T2-weighted images, (3) diffusion-echo planar
imaging (EPI), and (4) 2D 1H-MRSI. All sequences
(except 1) were recorded in an oblique-axial plane parallel to the
anterior-posterior commissure line and at the same slice locations and
thickness (5 mm [except the spectroscopic images, which were
performed with a 15-mm slice thickness]).
Conventional MR Sequences
Sagittal and axial spin-density images were recorded with
standard spin-echo sequences. For T1-weighted
images, acquisition parameters were field of view (FOV),
24 mm; 5-mm slice thickness; 1-mm gap; repetition time (TR), 535
ms; echo time (TE), 10 ms; 256x192 matrix; and 1 excitation. For
SD/T2 weighted images, parameters
were FOV, 24 mm; 5-mm slice thickness; TR, 3000 ms; TE, 30/100 ms;
256x192 matrix; 0.75 excitation; flow compensation; and variable
bandwidth.
DWI-EPI
Multi-slice, single-shot, diffusion-weighted EPI of the
whole brain was performed. The following parameters were
used: FOV, 24 mm; 5-mm slice thickness; TR, 4000 ms; TE, 100 ms;
128x128 matrix; and 1 excitation, with a diffusion time of 40 ms and a
diffusion gradient length of 25 ms. Diffusion gradient strengths of
0.1, 1.1, 1.5, 1.9, and 2.2 g/cm were used, which gave
b-values of 2, 216.5, 433, 649.5, and 866
mm2/s, respectively, applied sequentially in the
x, y, and z gradient directions.
Isotropic DWI and images of the average diffusion constant (Dav) were
reconstructed as follows:
 |
MR Spectroscopic Imaging
1H-MRSI was performed in 5 patients by use of a
spin-echo sequence with 2D phase encoding and outer-volume saturation
pulses for lipid suppression.11 Four 15–mm-thick slices
were recorded, with the following parameters: TR, 2300
ms; TE, 272 ms; FOV, 24 cm; 32x32 circular-phase encoding; 1-kHz sweep
width; 256 data points; and 1 excitation. Nominal voxel size was
approximately 0.8 cm3. Water suppression was
accomplished with a single "CHESS" pulse at a bandwidth of
110 Hz, and extracranial lipid signals were suppressed by use of 8
outer-volume saturation pulses arranged in an octagonal pattern.
T1-weighted MR images (TR, 400 ms; TE, 20 ms)
were recorded at the same slice locations and thickness (15
mm) for anatomic registration of the MRSI data.
Spectroscopic Imaging Data Processing
1H-MRSI data were reconstructed by use of
3D Fourier transformation. Before Fourier transformation, a cosine
filter was applied in the spatial dimensions. Exponential line
broadening was set at 3 Hz zero-filling to 8192 data points, and a
high-pass convolution filter was used to remove the residual water
signal (50-Hz stop bands were applied in the time
domain).12 Absolute quantification of lactate levels was
performed as described previously by use of phantom replacement
methodology.13 Magnitude spectra were used to reconstruct
metabolic images on the basis of integrated signal
intensities of the metabolites in regions 3.34 to 3.24 ppm (Cho), 3.14
to 2.94 ppm (Cr), 2.22 to 1.82 ppm (NAA), and 1.55 to 1.15 ppm
(lactate). Metabolic images were linear interpolations from
the original 32x32-matrix size to 256x256 points. A signal was only
assigned to lactate if it had a chemical shift of exactly 1.33 ppm and
a scalar coupling of 7 Hz.
Image Analysis
Quantitative image analysis was performed on an Apple
Macintosh G3 computer (Apple Computer) using the program NIH
Image (version 1.61, Wayne Rasband, NIH, Bethesda, Md). Feasibility of
assessment was based on ability to obtain spectroscopic and diffusion
data in perihematoma brain regions. Images were evaluated for the
presence of obscuration secondary to susceptibility artifact. The
hematoma was visualized on conventional T2 MRI in
all cases; all cases also exhibited T2
hyperintensity in brain parenchyma surrounding the hematoma. These
regions (hematoma and T2 hyperintense rim) were
outlined on the low b-value DWI-EPI images manually by 2
investigators (J.R.C., P.B.B.). The low b-value DWI-EPI
images are essentially T2-weighed images with the
same slice locations and spatial distortions as the high
b-value DWI-EPI images. Coordinates of these regions of
interest (ROIs) were then transferred to the calculated Dav images for
measurement of hematoma and perihematoma diffusion constants. Dav was
also measured in identical ROIs in the contralateral hemisphere. Dav
images were screened by 2 investigators (J.R.C., P.B.B.) for focal
abnormalities beyond the regions identified on T2
MRI.
Statistical Methods
The Stata 6 statistical software package was used for data
analysis. A paired t test was used to determine
whether a significant difference existed in Dav between perihematoma
and corresponding contralateral brain areas, and a 95% confidence
interval was calculated for the mean difference.
|
Results |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
Between August 1997 and December 1998, 9 consecutive patients were enrolled in this pilot study. The following demographic and clinical characteristics of the study cohort are summarized in Table 1
.
|
Demographic Characteristics
The mean±SD age of the study cohort was 63.4±17.7 (range, 36
to 87) years, and the men/women ratio was 5:4. Mean time from symptom
onset to initial MRI evaluation was 3.4±2.6 (range, 1 to 9) days in
all 9 patients. Follow-up MRI studies were obtained in patients 1, 2,
and 7 at 6, 9, and 4 days, respectively.
Clinical Features
The cause of ICH was systemic hypertension in 6 patients,
probable vascular malformation in 1, and probable amyloid angiopathy in
1 and was associated with cocaine use in 1 patient. The hematoma was
located in the basal ganglia or thalamus in 6 patients and was lobar in
3. No blood pressure or ventilatory manipulation was performed
immediately before or during the MRI studies. Mean arterial
pressure in the study cohort at the time of first MRI study was
102.2±15.2 (range, 85 to 130) mm Hg.
Radiological Features
The initial mean hematoma volume was 35.4±31.4 (range, 5 to 80)
cm3 as measured on admission head CT. Values were
obtained by use of a method described previously.14
Conventional MRI sequences and DWI studies were performed in every
patient at initial investigation; 1H-MRSI was
performed in 5 patients. High-intensity signal on
T2 MRI was found predominantly in the white
matter surrounding the hematoma in every patient studied. Increased Dav
values (relative to homologous brain regions in the contralateral
hemisphere) that matched areas of high T2 signal
intensity were found surrounding the hematoma in every patient, with a
mean Dav of 172.5±302.5 (range, 120.0 to
302.5)x10-5 mm2/s
and 87.6±7.8 (range, 76.5 to 102.1)x10-5
mm2/s in the ipsilateral and contralateral ROI,
respectively. Using paired t test, the obtained t
statistic and P value was 4.65 and 0.002, respectively. The
95% confidence interval for the mean difference was 43 to 127. In
addition to T2 high-intensity signal associated
with elevated Dav surrounding the hematoma, patient 3 showed an area of
reduced Dav in a location superior to the blood clot
(51.5±8.9x10-5
mm2/s) with corresponding normal
T2 signal intensity (Figure 1). Three patients had repeat DWI
studies (patients 1, 2, and 7) at 6.3 (range, 4 to 9) days after
hemorrhage (Table 2). At
1H-MRSI, patients 1 (after surgical ICH
evacuation) and 5 showed incomplete halos of elevated lactate
concentration in regions surrounding the hematoma 6 and 4 days after
the stroke, respectively (Table 3, Figure 2).
|
|
|
|
Hematoma mass could not be studied with the application of
1H-MRSI as a result of presence of susceptibility
artifacts that interfered with hematoma imaging and data
interpretation. In 3 cases, susceptibility effects and
T2 shortening precluded reliable Dav measurement
of the hematoma mass. However, the blood clot was
amenable to study with DWI in patients 2, 3, 4, 6, 8, and 9. In these
cases, reduced Dav values were obtained (35.7±14.2 [range, 8 to
47.9])x10-5 cm2/s
(Figure 3 shows patient 4).
|
|
Discussion |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
We report 9 ICH patients studied with functional MRI techniques during the acute and subacute stages of the disease. A primary objective was to assess the feasibility of use of advanced MR imaging techniques in the presence of intraparenchymal blood. Magnetic properties of blood and associated breakdown products in intraparenchymal hematomas are complex and depend on several factors, which include hemoglobin oxygenation and time after hemorrhage.15 In particular, deoxyhemoglobin is strongly paramagnetic and can shorten both T1 and T2 relaxation times as well as disrupt magnetic field homogeneity. Thus, it would be reasonable to anticipate sequences that require consistent field homogeneity, such as 1H-MRSI and single-shot EPI, to be limited in either hematoma or perihematoma regions because of the presence of deoxyhemoglobin. In all cases examined by use of 1H-MRSI, the magnetic field homogeneity within the hematoma was not sufficient to allow detection of interpretable spectra. However, in tissue adjacent to the hematoma (
1 cm from the
margins of the hematoma), interpretable spectra were obtained in all 5
cases. Although interpretable, 1H-MRSI signal in
ROIs near the hematoma had larger line widths than spectra from remote
brain regions in 1 case. We did not identify consistent evidence of neuronal ischemic damage in our patient cohort, as defined by the simultaneous presence of surrogate MRI markers of recent cerebral ischemia (reduced Dav values and presence of lactate) in areas surrounding the hematoma. Instead, we found uniformly elevated Dav values that matched regions of increased T2 signal intensity in brain tissue around the blood clot, which suggested the presence of vasogenic edema. In only 1 instance (patient 3) of a large basal ganglia hematoma (80 cm3) was a superimposed region of reduced Dav located superior to the hematoma and associated with normal T2 signal intensity, which indicates additional ischemic injury (cytotoxic edema). Our results therefore suggest that mechanisms other than ischemia might play an important role in secondary neuronal injury after ICH. Inflammation emerges as a probable mechanism, but occasionally ischemia, when present, and may add further to this process.
Recent interest has focused on the presence of secondary neuronal injury in ICH patients.16 17 18 19 20 21 22 23 24 25 26 27 The hypothesis of an ischemic penumbra is the commonly held explanation for the progressive injury occurring with ICH. Most of the evidence for a superimposed ischemic insult originates from animal experiments, but only a few clinical studies support this theory. In 1988, Tanizaki28 reported his experience with 13 patients studied with 133Xe inhalation and single-photon emission computed tomography who underwent stereotactic evacuation of the ICH.28 CBF was measured within 1 week before and after the surgical evacuation of the hematoma. A statistically significant increase in postoperative CBF on the affected side was noted in the hemispheric CBF ipsilateral to the hematoma in one third of the patients studied, particularly in the region of the thalamus and basal ganglia and in the anterior territory of the middle cerebral artery. Unfortunately, the presence of ischemia in this study could not be definitively established because of the absence of a putative indicator of tissue neuronal anaerobic metabolism.
Reductions in CBF metabolism can also be seen coupled to the presence of decreased neuronal activity and metabolism after acute brain injury. Diringer and coworkers2 studied 12 patients with ICH using PET and was unable to demonstrate secondary ischemic injury despite pharmacological lowering of the blood pressure. They also described symmetric CBF decrements in both the affected and the contralateral hemisphere associated with decreased oxygen extraction ratio. On the basis of these results, one could hypothesize that the presence of blood or its products produces neuronal injury, dysfunction, or metabolic suppression but not ischemia in regions near the hematoma and perhaps even distant to it.
A competing hypothesis has been suggested on the basis of recognition of the proinflammatory effect that certain blood products have on neuronal tissue. Specifically, there is growing interest in inflammation as a mechanism for secondary brain injury. One of the blood components recognized as playing a major role in the development of acute and perhaps chronic brain injury and neuronal degeneration is thrombin. At the cellular level, several cell lines, such as neurons,16 21 23 24 27 29 30 glial/ependymal cells,26 and endothelium,25 are known to express receptors for this protein in the CNS.31 Hoff and coworkers17 32 33 34 35 36 studied the effects that blood and its components have on rodent brain tissue and concluded that thrombin induces vasogenic edema as well as direct neurotoxicity.
The consistently elevated Dav and T2 signal intensity in the perimeter of the hematoma in our study cohort appears consistent with the notion of vasogenic edema as an indicator of the inflammatory response induced by the hematoma. Kuroiwa and coworkers37 have demonstrated the relationship between increased Dav with the presence and severity of blood brain barrier breakdown associated with vasogenic brain edema in a feline cold cortical lesion model. Similar DWI profiles of elevated Dav were independently reported in humans by Ay and coworkers38 and Schaefer and coworkers39 on the vasogenic edema induced by posterior leukoencephalopathy syndrome and eclampsia, respectively. However, in the present cohort, delayed DWI expression of ischemic injury cannot be entirely excluded. Apparent diffusion coefficient (ADC) values are well known to be able to "normalize" and even "supranormalize" 9 to 10 days after the original ischemic insult,40 41 42 although the precise time that this process takes to occur has not been uniformly established in humans.43 Nevertheless, we consider this to be a less likely occurrence in the present study, on the basis of our current knowledge of the time course of ADC progression after human focal ischemic injury. Six of 9 patients in our cohort were studied within the initial 48 hours, 1 of them within the first 24 hours after the stroke; all the DWI studies in these and the remaining 3 patients showed significant Dav elevation surrounding the hematoma region. Although cerebral ischemia can induce heterogeneous ADC values in human ischemic stoke, including rapidly progressing early Dav reduction followed by its supranormalization in nearly 8% of the ischemic tissue within the first 10 hours after injury,44 early blood-brain barrier breakdown is presented here as an alternative mechanism for the uniformly observed Dav elevation in our patient cohort.
Lactate, the end product of anaerobic glycolysis, is widely recognized as a reliable indicator of tissue ischemia, as seen in human stroke.45 Nevertheless, anaerobic glycolysis induced by nonischemic mechanisms can also be observed in areas of vasogenic edema as demonstrated by Mun-Bryce and coworkers46 after they studied the effects of blood on the surrounding brain tissue with 1H-MRSI in a collagenase rat model of ICH. Similar experience with lactate elevation in areas of vasogenic edema has been reported in the absence of energy failure by other authors.47 48 Our findings of lactate signal in areas that surround the blood clot in only 2 patients (surrounding the surgical site in patient 1) do not support a prominent role of ischemia as a predominant mechanism of secondary neuronal injury. Furthermore, the presence of increased rather than reduced Dav argues against the presence of ischemia as the cause for lactate generation.
We found the blood clot itself to be amenable to study with DWI in 6 of
9 cases. Although the hematoma in some cases appeared dark on low
b-value images, sufficient signal was present to allow
reliable Dav determinations (Figure 3
). The reduced Dav values
obtained are likely the result of the different stages of dehydration
of blood clots in these patients. Nevertheless, presence of islets of
remaining, marginally perfused brain tissue cannot be entirely
excluded. This occurrence has been reported in a canine model of ICH by
Qureshi and coworkers.3
Limitations of this study include assessment of patients beyond the hyperacute period, when greatest potential for meaningful intervention could be anticipated. However, given the demonstrated feasibility of assessment in the acute and subacute stages when paramagnetic properties of the hemorrhage are more pronounced, assessment in the hyperacute period should not be limited as a result of magnetic field inhomogeneity. Also, the limited sample size restricts our ability to exclude definitively that ischemia plays a central role in secondary tissue injury.
In summary, we have demonstrated the feasibility of MRI assessment of perihematoma viable brain tissue with DWI and 1H-MRSI. In our pilot population, we did not find evidence of widespread ischemia. Our preliminary results suggest that inflammation surrounding the hematoma, and perhaps ischemia in isolated cases, may develop during the acute and subacute stages (72 to 96 hours) of the disease process in ICH patients. If so, the precise onset and progression and the presence of a subsequent late inflammatory and delayed cell death process remain to be explored. The definition, identification, severity grading, and understanding of the temporal evolution of these pathologic mechanisms are necessary steps to first design and later assess supportive treatments and directed management in ICH patients. New, advanced MRI techniques may help in the achievement of these goals.
|
Acknowledgments |
|---|
Dr Carhuapoma is supported in part by the David A. Dana Research Prize in Neurosciences Critical Care, Johns Hopkins University School of Medicine, and by the Daland Fellowship for Clinical Research Award from the American Philosophical Society. Dr Barker is supported by an Established Investigator Award from the American Heart Association. Dr Beauchamp is supported by a grant from the American Roentgen Ray Society. We thank Dr Aziz Ulu
and Dr Peter van Zijl for the DWI
sequence and Dr Jeff Duyn (NIH) for the MRSI sequences. Received September 23, 1999; revision received November 15, 1999; accepted December 2, 1999.
|
References |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
1. Broderick JP, Brott TG, Tomsick T, Miller R, Huster G. Intracerebral hemorrhage more than twice as common than subarachnoid hemorrhage. J Neurosurg. 1993;78:188–191.[Medline] [Order article via Infotrieve]
2. Diringer MN, Adams RE, Dunford-Shore JE, Videen TO, Yundt KD, Powers WJ. Cerebral blood flow is symmetrically reduced in patients with intracerebral hemorrhage. Neurology. 1998;50:A338–S45.001. Abstract.
3.
Qureshi AI, Wilson DA, Hanley DF, Traystman RJ. No
evidence for an ischemic penumbra in massive experimental
intracerebral hemorrhage. Neurology. 1999;52:266–272.
4. Ropper AH, Zervas NT. Cerebral blood flow after experimental basal ganglia hemorrhage. Ann Neurol. 1982;11:266–271.[Medline] [Order article via Infotrieve]
5. Sinar EJ, Mendelow AD, Graham DI, Path FRC, Teasdale GM. Experimental intracerebral hemorrhage: effects of a temporary mass lesion. J Neurosurg. 1987;66:568–576.[Medline] [Order article via Infotrieve]
6. Nehls DG, Mendelow AD, Graham DI, Sinar EJ, Teasdale GM. Experimental intracerebral hemorrhage: progression of hemodynamic changes production of a spontaneous mass lesion. Neurosurgery. 1988;23:439–444.[Medline] [Order article via Infotrieve]
7. Mun-Bryce S, Rosenberg GA. Matrix metalloproteinases in cerebrovascular disease. J Cereb Blood Flow Metab. 1998;18:1163–1172.[Medline] [Order article via Infotrieve]
8. Baird AE, Warach S. Magnetic resonance imaging of acute stroke. J Cereb Blood Flow Metab. 1998;18:583–609.[Medline] [Order article via Infotrieve]
9.
Beauchamp NJ, Bryan RN. Acute cerebral
ischemic infarction: a pathophysiologic review and radiologic
perspective. Am J Roentgenol. 1998;171:73–84.
10.
Graham GD, Blamire AM, Rothman DL, Brass LM, Petroff
OA, Prichard JW. Early temporal variation of cerebral metabolites after
human stroke: a proton magnetic resonance spectroscopy study.
Stroke. 1993;24:1891–1896.
11.
Duyn JH, Gillen J, Sobering G, van Zijl PCM, Moonen C.
Multislice proton spectroscopic imaging in the human brain.
Radiology. 1993;188:277–282.
12. Marion D, Ikura M, Bax A. Improved solvent suppression in one- and two-dimensional NMR spectra by convolution of time-domain data. J Magn Reson Imaging. 1989;84:28–41.
13. Soher BJ, van Zijl PCM, Duyn JH, Barker PB. Quantitative proton MR spectroscopic imaging of the human brain. MRM. 1996;35:356–363.
14.
Kothari RU, Brott TG, Broderick JP, Barsan W, Sauerbeck
LR, Zuccarello M, Khoury J. The ABCs of measuring intracranial
hemorrhage volumes. Stroke. 1996;27:1304–1305.
15. Osborn AG. Intracranial hemorrhage. In: Neuroradiology. 1st ed. St Louis, Mo: Mosby; 1994:154–198.
16.
Gurwitz D, Cunningham DD. Thrombin modulates and
reverses neuroblastoma neurite overgrowth. Proc Natl Acad Sci
U S A. 1988;85:3440–3444.
17. Lee KR, Lorris Betz A, Keep RF, Chenevert TL, Kim S, Hoff JT. Intracerebral infusion of thrombin as a cause of brain edema. J Neurosurg. 1995;83:1045–1050.[Medline] [Order article via Infotrieve]
18. Nishino A, Suzuki M, Ohtani H, Motohashi O, Umezawa K, Nagura H, Yoshimoto T. Thrombin may contribute to the pathophysiology of central nervous system injury. J Neurotrauma. 1993;10:167–179.[Medline] [Order article via Infotrieve]
19. Bizios R, Lai L, Fenton J, Sonder S, Malik A. Thrombin-induced aggregation of lymphocytes: non-enzymic induction by a hirudin-blocked thrombin exosite. Thromb Res. 1985;38:425–431.[Medline] [Order article via Infotrieve]
20.
Chen LB, Buchanan JM. Mitogenic activity of
blood components. Proc Natl Acad Sci U S A. 1975;72:131–135.
21. Grabham PW, Monard D, Gallimore PH, Grand RJA. Modulation of human neurite outgrowth by serine proteases: a comparison of the interaction of thrombin and prothrombin with glia-derived nexin. Eur J Neurosci. 1991;3:663–668.[Medline] [Order article via Infotrieve]
22. Smith-Swintowski VL, Zimmer S, Fenton J, Mattson MP. Opposing actions of thrombin and protease nexin-1 on amyloid beta-peptide toxicity in and on accumulation of peroxides and calcium in hippocampal neurons. J Neurochem. 1995;65:1415–1418.[Medline] [Order article via Infotrieve]
23. Smith-Swintowski VL, Zimmer S, Fenton JW, Mattson MP. Protease nexin-1 and thrombin modulate neuronal Ca homeostasis and sensitivity to glucose deprivation-induced injury. J Neurosci. 1995;15:5840–5850.[Abstract]
24. Vaughan PJ, Pike CJ, Cotman CW, Cunningham DD. Thrombin receptor activation protects neurons and astrocytes from cell death produced by environmental insults. J Neurosci. 1995;15:5389–5401.[Abstract]
25. Vu TKH, Hung DT, Wheaton VI, Coughlin SR. Molecular cloning of a functional thrombin receptor reveals a novel proteolytic mechanism of receptor activation. Cell. 1991;64:1057–1068.[Medline] [Order article via Infotrieve]
26. Weinstein JR, Gold SJ, Cunningham DD, Gall CM. Cellular localization of thrombin receptor mRNA in rat brain: expression by mesencephalic dopaminergic neurons and codistribution with prothrombin mRNA. J Neurosci. 1995;15:2906–2919.[Abstract]
27. Zurn AD, Nick H, Monard D. A glia-derived nexin promotes neurite overgrowth in cultured chick sympathetic neurons. Dev Neurosci. 1998;10:17–24.
28. Tanizaki Y. Improvement of cerebral blood flow following stereotactic surgery in patients with putaminal hemorrhage. Acta Neurochir. 1988;90:103–110.[Medline] [Order article via Infotrieve]
29.
Jalink K, Moolenaar WH. Thrombin receptor activation
causes rapid neural cell rounding and neurite retraction independent of
classic second messengers. J Cell Biol. 1992;118:411–419.
30. Suidan HS, Stone SR, Hemmings BA, Monard D. Thrombin causes neurite retraction in neuronal cells through activation of cell surface receptors. Neuron. 1992;8:363–375.[Medline] [Order article via Infotrieve]
31. Nishino A, Suzuki M, Yoshimoto T, Otani H, Nagura H. A novel aspect of thrombin in the tissue reaction following central nervous system injury. Acta Neurochir. 1994;60:86–88.
32. Lee KR, Betz AL, Kim S, Keep RF, Hoff JT. The role of the coagulation cascade in brain edema formation after intracerebral hemorrhage. Acta Neurochir. 1996;138:396–401.[Medline] [Order article via Infotrieve]
33. Lee KR, Colon GP, Betz AL, Keep RF, Kim S, Hoff JT. Edema from intracerebral hemorrhage: the role of thrombin. J Neurosurg. 1996;84:91–96.[Medline] [Order article via Infotrieve]
34. Lee KR, Kawai N, Kim S, Sagher O, Hoff JT. Mechanisms of edema formation after intracerebral hemorrhage: effects of thrombin on cerebral blood flow, blood-brain barrier permeability, and cell survival in a rat model. J Neurosurg. 1997;86:272–278.[Medline] [Order article via Infotrieve]
35. Yang GY, Betz AL, Chenevert TL, Brunberg JA, Hoff JT. Experimental intracerebral hemorrhage: relationship between brain edema, blood flow, and blood-brain barrier permeability in rats. J Neurosurg. 1994;81:93–102.[Medline] [Order article via Infotrieve]
36. Yang GY, Betz AL, Hoff JT. The effects of blood or plasma clot on brain edema in the rat with intracerebral hemorrhage. Acta Neurochir. 1994;60:555–557.
37. Kuroiwa T, Nagaoka T, Ueki M, Yamada I, Miyasaka N, Akimoto H, Ichinose S, Okeda R, Hirakawa K. Correlations between the apparent diffusion coefficient, water content, and ultrastructure after induction of vasogenic brain edema in cats. J Neurosurg. 1999;90:499–503.[Medline] [Order article via Infotrieve]
38.
Ay H, Buonanno FS, Schaefer PW, Le DA, Wang B, Gonzalez
RG, Koroshetz WJ. Posterior leukoencephalopathy without severe
hypertension: utility of diffusion-weighted MRI. Neurology. 1998;51:1369–1376.
39.
Schaefer PW, Buonanno FS, Gonzales RG, Schwamm LH.
Diffusion-weighted imaging discriminates between cytotoxic and
vasogenic edema in a patient with eclampsia. Stroke. 1997;28:1082–1085.
40.
Warach S, Chien D, Ronthal M, Edelman RR. Fast magnetic
resonance diffusion-weighted imaging of acute human stroke.
Neurology. 1992;42:1717–1723.
41. 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]
42. Warach S, Moseley ME, Sorensen AG, Koroshetz W. Time course of diffusion imaging abnormalities in human stroke. Stroke. 1996;27:1254–1255.
43.
Welch KMA, Windham J, Knight RA, Nagesh V, Hugg JW,
Jacobs M, Peck D, Booker P, Dereski MO, Levine SR. A model to predict
the histopathology of human stroke using diffusion and T2-weighted
magnetic resonance imaging. Stroke. 1995;26:1983–1989.
44.
Nagesh V, Welch KMA, Windham J, Patel S, Levine SR,
Hearshen D, Peck D, Robbins K, D’Olhaberriague L, Soltanian-Zadeh H,
Boska MD. Time course of ADCw changes in ischemic stroke:
beyond the human eye! Stroke.. 1998;29:1778–1782.
45.
Barker PB, Gillard JH, van Zijl PCM, Soher BJ, Hanley
DF, Agildere AM, Oppenheimer SM, Bryan RN. Acute stroke: evaluation
with serial proton MR spectroscopic imaging. Radiology. 1994;192:723–732.
46.
Mun-Bryce S, Kroh FO, White J, Rosenberg GA. Brain
lactate and pH dissociation in edema: H- and P-NMR in
collagenase-induced hemorrhage in rats.
Am J Physiol. 1993;265:R697–R702.
47. Okada Y, Kloiber O, Hossman KA. Regional metabolism in experimental brain tumors in cats: relationship with acid/base, water, and electrolyte homeostasis. J Neurosurg. 1992;77:917–926.[Medline] [Order article via Infotrieve]
48. Sutton LN, Welsh F, Bruce DA. Bioenergetics of acute vasogenic edema. J Neurosurg. 1980;53:470–476.[Medline] [Order article via Infotrieve]
This article has been cited by other articles:
 |
|
 |
|
  D. Rhoney and W. F. Peacock Intravenous therapy for hypertensive emergencies, part 2 Am. J. Health Syst. Pharm., August 15, 2009; 66(16): 1448 - 1457. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Delgado, E. Cuadrado, A. Rosell, J. Alvarez-Sabin, A. Ortega-Aznar, M. Hernandez-Guillamon, A. Penalba, C. A. Molina, and J. Montaner Fas System Activation in Perihematomal Areas After Spontaneous Intracerebral Hemorrhage Stroke, June 1, 2008; 39(6): 1730 - 1734. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Wada, R. I. Aviv, A. J. Fox, D. J. Sahlas, D. J. Gladstone, G. Tomlinson, and S. P. Symons CT Angiography "Spot Sign" Predicts Hematoma Expansion in Acute Intracerebral Hemorrhage Stroke, April 1, 2007; 38(4): 1257 - 1262. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
NINDS ICH Workshop Participants Priorities for Clinical Research in Intracerebral Hemorrhage: Report From a National Institute of Neurological Disorders and Stroke Workshop Stroke, March 1, 2005; 36(3): e23 - e41. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W.-J. Moon, D. G. Na, S. S. Kim, J. W. Ryoo, and E. C. Chung Diffusion Abnormality of Deep Gray Matter in External Capsular Hemorrhage AJNR Am. J. Neuroradiol., February 1, 2005; 26(2): 229 - 235. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. S. Butcher, T. Baird, L. MacGregor, P. Desmond, B. Tress, and S. Davis Perihematomal Edema in Primary Intracerebral Hemorrhage Is Plasma Derived Stroke, August 1, 2004; 35(8): 1879 - 1885. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. D. Schellinger, J. B. Fiebach, K. Hoffmann, K. Becker, B. Orakcioglu, R. Kollmar, E. Juttler, P. Schramm, S. Schwab, K. Sartor, et al. Stroke MRI in Intracerebral Hemorrhage: Is There a Perihemorrhagic Penumbra? Stroke, July 1, 2003; 34(7): 1674 - 1679. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. K. Kamal, J. P. Dyke, J. M. Katz, B. Liberato, C. G. Filippi, R. D. Zimmerman, and A. M. Ulug Temporal Evolution of Diffusion after Spontaneous Supratentorial Intracranial Hemorrhage AJNR Am. J. Neuroradiol., May 1, 2003; 24(5): 895 - 901. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. A. Mayer Ultra-Early Hemostatic Therapy for Intracerebral Hemorrhage Stroke, January 1, 2003; 34(1): 224 - 229. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. R. Carhuapoma, P. B. Barker, D. F. Hanley, P. Wang, and N. J. Beauchamp Human Brain Hemorrhage: Quantification of Perihematoma Edema by Use of Diffusion-Weighted MR Imaging AJNR Am. J. Neuroradiol., September 1, 2002; 23(8): 1322 - 1326. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Castillo, A. Davalos, J. Alvarez-Sabin, J. M. Pumar, R. Leira, Y. Silva, J. Montaner, and C.S. Kase Molecular signatures of brain injury after intracerebral hemorrhage Neurology, February 26, 2002; 58(4): 624 - 629. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Xi, Y. Hua, R. R. Bhasin, S. R. Ennis, R. F. Keep, and J. T. Hoff Mechanisms of Edema Formation After Intracerebral Hemorrhage: Effects of Extravasated Red Blood Cells on Blood Flow and Blood-Brain Barrier Integrity Stroke, December 1, 2001; 32(12): 2932 - 2938. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. S. Kidwell, J. L. Saver, J. Mattiello, S. Warach, D. S. Liebeskind, S. Starkman, P. M. Vespa, J. P. Villablanca, N. A. Martin, J. Frazee, et al. Diffusion-perfusion MR evaluation of perihematomal injury in hyperacute intracerebral hemorrhage Neurology, November 13, 2001; 57(9): 1611 - 1617. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Kobayashi, H. Takayama, S. Suga, B. Mihara, G. A. Rosenberg, and W. M. Brooks Longitudinal Changes of Metabolites in Frontal Lobes After Hemorrhagic Stroke of Basal Ganglia: A Proton Magnetic Resonance Spectroscopy Study Editorial Comment: A Proton Magnetic Resonance Spectroscopy Study Stroke, October 1, 2001; 32(10): 2237 - 2245. [Abstract] [Full Text] [PDF]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||