From the Departments of Clinical Neurosciences (J.M.W., M.S.D., J.C.,
S.C.L.) and Medical Physics (I.M., J.W.), University of Edinburgh, Western
General Hospital, Edinburgh, Scotland.
Correspondence to Dr J.M. Wardlaw, Department of Clinical Neurosciences, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, UK. E-mail jmw{at}skull.dcn.ed.ac.uk
Methods—Patients with symptoms of a moderate to large cortical
infarct underwent serial proton MRS (Siemens 1.5 Magnetom) within 4
days, from 5 to 10, and from 11 to 35 days after the stroke. A long
echo time PRESS single voxel or chemical shift imaging acquisition was
used. Transcranial Doppler ultrasound was performed
daily in the first week and twice per week thereafter until the final
MRS. Clinical features and baseline demographic data were collected
independently by a stroke physician and 6-month outcome by postal
questionnaire.
Results—Fifty patients underwent at least 1 MRS examination.
Reduced NAA in the infarct within the first 4 days was related to the
clinical stroke syndrome, more extensive infarction, more severely
reduced blood supply to the infarct, and the presence of lactate. The
presence of lactate was related to large infarcts and reduced NAA.
Swelling in the infarct was most closely associated with large infarcts
and reduced blood supply but not reduced NAA or the presence of
lactate. Clinical outcome was most closely related to the extent of the
infarct (more than to the clinical syndrome)-the larger the infarct
the worse the outcome-but not to the metabolite concentrations
alone.
Conclusions—The reduction in NAA (but not the presence of
lactate) in a visible infarct was related to the reduction in blood
flow to the infarct, which in turn was related to infarct extent and
clinical outcome.
MRI and MRS provide assessment of neuronal viability. The presence of
lactate is thought to indicate ischemia (anaerobic
metabolism) and reduced N acetylaspartate (NAA)
to indicate a reduction in the number of viable
neurons.7 Several studies have reported
observations of acute stroke patients at various time points with
MRS.8 9 10 11 12 13 14 15 16 17 Reduced NAA in the visible area of
infarction is a consistent finding from very early after the
stroke (within 2 hours is the earliest
reported).14 The findings for choline and
creatine (detected with proton MRS) vary. Lactate is detected early
(attributed to neuronal ischemia before infarction), then
disappears to reappear at approximately 3 weeks (attributed to
inflammatory cell infiltrate).10
There is little information on the relation between these findings and
infarct size, blood flow, the clinical presentation, or
outcome. Saunders et al14 examined 26 patients
within 72 hours of the stroke and found that mean infarct NAA was
higher in those who were independent at 6 months than in those who were
dead or dependent but did not examine the interaction with other
baseline variables. Federico et al15 studied
14 patients within 1 week of the stroke and found a positive
correlation between reduced NAA and severe neurological deficit at
follow-up as assessed by the Scandinavian Stroke Score. Kugel et
al,16 using MRS and positron emission tomography
(PET) to measure cerebral blood flow, found reduced NAA in areas of
reduced perfusion in 4 patients, though in 2 patients NAA was reduced
in an area with apparently persistent blood flow. Graham et
al17 correlated infarct volume with metabolites,
neurological deficit, clinical outcome, and relative cerebral blood
flow measured by single photon emission computed tomography (SPECT) in
32 patients examined with MRS up to 19 days after the stroke and found
significant associations between the presence or absence of lactate,
reduced NAA, blood flow, and outcome. However, because all
of these studies were small and examined patients at a range of times
after the stroke, the results are likely to be influenced by the case
mix of strokes included and the scan timing and are therefore difficult
to extrapolate to the generality of stroke patients. We hypothesized
that (a) patients with markedly reduced blood flow in the middle
cerebral artery (MCA) would have symptoms of extensive infarction, big
infarcts, reduced NAA, and perhaps more lactate compared with patients
with less abnormal MCA flow; (b) that therefore blood velocity
reduction, or NAA reduction, or the presence of lactate soon after the
stroke might distinguish those with a bad outcome from good; and (c)
that infarct swelling might be proportional to the degree of reduction
in blood flow or NAA or the presence of lactate as well as infarct
size.
Patient Selection
Magnetic Resonance Imaging and Spectroscopy
In the first year of the study we used a point-resolved
spectroscopy localized single voxel MRS
technique,21 placing the 8
cm3 volume of interest (VOI) first over the
infarct and then over the mirror image part of the opposite hemisphere.
In the latter part of the study, we developed a chemical shift
spectroscopic imaging (CSI) sequence that used a PRESS localized
rectangular volume of interest of either 75x75 or 90x90
mm2 and 15 mm thickness. This was placed
over the infarct and as much normal surrounding brain as possible. CSI
has the advantage over single voxel spectroscopy that spectra from a
large proportion of the chosen brain slice image can be collected in 1
acquisition. Before acquisition with either method, a global shim of
the water resonance across the whole head coil was performed followed
by a local shim of the volume of interest. Patients were positioned in
the head coil so as to be comfortable, with foam pads to maintain the
head in as uniform a position as possible for sequential studies. We
found that allowing the patient to adopt their "natural" supine
position in the scanner was the best way to obtain similar positioning
between scans, there being no ideal method.
For the single voxel method, the 8 cm3 VOI was
positioned over the infarct, avoiding ventricles and sulci where
possible. Localized shimming was carried out and a water reference data
set (16 acquisitions) was collected, followed by a
water-suppressed data set (256 acquisitions) collected (TE=135 ms).
This took 7 minutes with a TR of 1600 ms. The positioning, shimming,
and data collection steps were repeated for an 8
cm3 VOI positioned in the mirror image (normal)
part of the contralateral hemisphere. The data were phase corrected
with the use of the water reference data22 and
transformed to the frequency domain. Estimation of choline (at a
chemical shift of 3.2 ppm), creatine (at 3.0 ppm), and NAA (at 2.0 ppm)
peak areas were made by area integration (NUMARIS, Siemens software)
and by frequency domain modeling (WFIT, in-house software), by 1 of 2
experienced operators. We have previously assessed the
repro-ducibility of proton MRS by using this technique and found it
to be fair.23
For the CSI studies, a 240 mm field of view was used. The VOI was
localized with the use of PRESS with 0.8 mT/m in-plane gradients and a
3 mT/m slice selection gradient to give a thickness of 15 mm.
Phase encoding was applied in the sagittal and coronal directions
before acquisition of the spin echo (TR=1600 ms, TE=135 ms, acquisition
time 7 minutes). Data were acquired with and without water
suppression to enable a first-order phase correction for the effects of
eddy currents and field inhomogeneities.22
Data processing was performed on a Sun SPARC 20 with software written
in C and consisted of: voxel shifting of the VOI position,
2-dimensional spatial fast Fourier transforms, phase correction of the
water-suppressed signals with the use of the water reference signal,
residual water removal, and a fast Fourier transform of the time domain
data to give spectra.24 Areas under the spectrum
corresponding to the concentration of the metabolites were calculated
as for the single voxel method. A map of each metabolite was then made
by bilinear interpolation of the areas under the relevant peak
calculated from the spectrum from each voxel. Normalization procedures
were then implemented to correct for the in-slice
variation.25 For anatomic comparisons in
patients, the color spectroscopic image map was superimposed on the
gray-scale T2-weighted image of the brain.
The blood flow to the infarct was estimated with the use of
transcranial Doppler (TCD) ultrasound. We used either
an EME TC 2020 Pioneer or an Acuson 128xp 10v, both functioning with 2
MHz probes and TCD software. The middle, anterior, and posterior
cerebral arteries (MCA, ACA, and PCA, respectively) on both sides were
examined through the temporal bone windows. The peak systolic
and mean velocities and pulsatility index were noted in each artery.
The examinations were performed as soon as possible after admission,
daily in the first week and twice in the subsequent 2 weeks, by 1 of 2
radiographers or a neuroradiologist, where possible blind to the
results of brain imaging and certainly to the MRS results.
Follow-up
Statistical Analysis
The possible associations between neurological deficit, infarct size
and swelling, metabolite levels, and blood velocity were tested for
with the use of
Ethics
Approximately 200 potentially eligible patients were admitted with the
right sort of clinical features during the time of the study, of whom
we were able to do spectroscopy in 50. There were 36 TACI (72%), 10
PACI (20%), and 4 POCI (8%). One patient initially classified as
having a cortical stroke was given an eventual clinical diagnosis of
lacunar infarct, although a cortical infarct was found on the MR. The
mean age was 66 years, range 26 to 90 years. Fourteen (28%) were dead
at 6 months. Thirty-seven (74%) patients were dead or dependent
(Rankin 3 to 6) at 6 months, and 13 (26%) were independent , with this
relatively poor outcome reflecting the severity of the strokes
included.
The earliest MR scans were done at 12 hours after the onset of the
stroke and the latest at 31 days (median 3 days). Fifty had at least 1
out of 3 MRS studies, of whom 43 were scanned within 4 days, 31 between
5 and 10 days, and 13 after 10 days from stroke onset. Failure to scan
all subjects serially was due to the death of the patient, the patients
being too ill to maintain an airway, being discharged home or back to
their referring hospital, or lack of available time on the MR scanner
(main problem). The second MRS was done at a median of 7 days and the
third at a median of 12 days. However, the MRS was only successful in
yielding metabolite results in 22 patients who only had 1 scan, 11
patients who had 2 sequential scans, and 7 patients who had 3
sequential scans (Table 1
We observed a wide range of NAA values in the infarct with respect to
the normal hemisphere from normal to absent in patients scanned within
the first 4 days (Figure 1
Lactate was detected in 28 MRS examinations and was either not detected
or there were lipid contaminants (either from cell membrane breakdown
products in the infarct26 or bone marrow
scalp contaminants) in 39. Lactate was found more often at earlier than
at later examinations (Figure 2
The mean (±SD) choline values in the infarct and contralateral normal
brain were 507 (±253) and 706 (±216), respectively, and likewise the
mean creatine (±SD) values were 140 (±279) and 660 (±211),
respectively. The reduction in choline and creatine between infarcted
and normal brain was highly significant (P<0.0001), though
relatively speaking the infarct choline was not as markedly reduced as
the infarct creatine or NAA with respect to normal brain.
Massive infarct swelling between 5 and 10 days after the stroke was
weakly associated with reduced blood velocity to the infarct
(P=0.07) and large infarcts (P=0.08) but not the
presence of lactate (on the scan within 4 days of the infarct or later)
or the degree of reduction in NAA (on initial and subsequent scans).
However, the number of patients available for this analysis was
very small.
In a univariate analysis, poor clinical outcome at
6 months (Rankin score 3 to 6) was significantly related to the
clinical stroke syndrome (P=0.03), the extent of the
infarct, that is, the more extensive the infarct, the worse the
clinical outcome (P=<0.01), but not to the degree of
reduction in NAA, the amount of swelling in the infarct, blood
velocity, or the presence of lactate. On multivariate
analysis, 6-month poor outcome was significantly related to
large infarcts (P=0.04) but not the clinical syndrome,
lactate, NAA, infarct swelling, or reduced blood velocity within the
first 4 days (Table 2
We have classified the metabolite, blood velocity, infarct extent, and
swelling results into broad categories for the analyses because
too many subdivisions would reduce the statistical power of this
already small sample. We used 2 MRS techniques in the study that vary
in their precision (the single voxel technique is approximately twice
as precise as the CSI method) but used the ratio of metabolite in the
infarct to that in normal brain to circumvent this
problem.25 The use of broad categories should
also help reduce apparent changes in NAA in the infarct caused by
change in its water content as edema develops during the first few days
after the stroke and then resolves. The use of the ratio of NAA in the
infarct to normal brain should also help reduce such effects.
We also recognize that it is difficult if not impossible to perform MRS
with any great degree of success in ill stroke patients because it is
difficult to ensure that they remain still, as evidenced by the number
of unsuccessful MRS examinations and the number of patients in whom we
were unable to repeat the MRS because they had died. The examination
with nonechoplanar MR takes approximately 45 minutes (which many do not
tolerate well), and even in healthy, cooperative volunteers, the
reproducibility of MRS metabolite concentrations is only
fair.23 Despite all this, the present series
is one of the larger ones and one of the few that has attempted to
explain changes in NAA and lactate concentrations in relation to the
stroke pathophysiology.
Several studies have documented reduced NAA in the
infarct,8 9 10 11 12 13 including a further decline on
repeat MRS over the first few weeks,13 which has
been interpreted as indicating continuing ischemic damage,
although the precise explanation is controversial. Previous studies
have suggested that NAA concentration in the infarct is an outcome
predictor (the greater the NAA, the better the outcome) but mainly on
univariate analysis14 15 and
therefore not taking account of the interplay of covariates. As regards
blood flow to the infarct, Kugel et al16 examined
the relation between NAA decrease in the infarct and blood flow
measured by PET in 4 patients and found that the area of NAA decrease
corresponded well with the area of reduced cerebral blood flow but did
not quantify the relation, nor did they examine the relation with
lactate. Graham et al17 examined 32 patients with
MRS and 16 also with SPECT to assess blood flow and found significant
associations between both the presence of lactate and NAA reduction,
stroke lesion volume, and functional outcome at hospital discharge. The
presence of lactate was also associated with the severity of the stroke
and the reduction in blood flow on SPECT. Note, however, that in 3 of
the 16 who had SPECT, the SPECT examination was done several days after
the MRS. Because arterial patency is known to change after
stroke (some spontaneously recanalize, others have progressive or
persistent arterial occlusion), one can really only use a
blood flow assessment before the MRS to infer a causal relation. The
MRS examinations were also done up to 19 days after the stroke (mean 5
days) at a stage too late for early prediction of outcome. Outcome was
assessed at hospital discharge, which ranged from 4 to 35 days, rather
than at 6 months, when clinical recovery has stabilized. Fazekas et
al27 studied 18 patients with acute stroke
scanned within 48 hours of the onset of the stroke and found lower NAA
and the largest amounts of lactate in patients with the most severe
clinical deficits and the largest perfusion defects on SPECT, but there
was no clear relation between the metabolic and perfusion
findings. These studies did not take account of the interplay between
factors that essentially mark the same process. Thus in this study,
although we found associations between metabolites and lesion size,
reduced blood velocity, and the clinical syndrome, even with
multivariate analysis it was difficult to
identify truly independent covariates when all are likely to be
so closely interrelated.
No studies in patients have looked previously at the relations between
metabolite abnormalities, infarct edema, and blood flow changes. We
have not found any clear relations between metabolite abnormalities
(reduced NAA or the presence of lactate) and the amount of infarct
edema within 4 days or between 5 and 10 days of the stroke.
Interestingly, the present findings agree with earlier work by
Hossman and Schuier28 in a cat cerebral infarct
model. They found that the animals with the most pronounced and
sustained reductions in regional cerebral blood flow developed the
largest infarcts but that the amount of edema in the infarct varied
between animals, and there was no clear relation between the edema and
the amount of lactate that could be detected in the infarct.
The explanation for our observation of the apparent increase in NAA
concentration (in the infarct relative to normal brain) in several
patients on their second MRS examination is probably artifactual. In 2
patients the increase was absolutely trivial, but in 3 the increase was
We only detected lactate in 28 of 67 scans, though in some cases it may
have been present but obscured by lipid contaminants from the skull
and subcutaneous tissues or from cell membrane breakdown products
within the infarcted brain. Both the single voxel and CSI sequences
demonstrate lactate reliably in test phantoms, so we know that the
sequences work, but in patients there are numerous sources of lipid
contamination or degradation of the spectra for other reasons that
impair resolution of the lactate part of the spectrum. Lactate editing
sequences are currently under investigation to discern
lactate from lipids. The choline and creatine values were reduced in
the infarct, as has been found previously, the creatine more so than
choline.
Finally, all the studies reporting spectroscopic findings in stroke
published so far are small. Before this report, the largest study with
proton MRS concerned 32 patients,17 reflecting
the fact that such studies are difficult to do-the technology is
complex, the patients are very ill and may not tolerate the whole
examination, and access to equipment may be limited. Thus any
extrapolation from these small studies, with their highly selected
patients and inherent bias (including this one), to the generality of
stroke patients should be performed with caution, particularly in light
of the fact that the reproducibility of MRS may not be as good as
assumed by earlier optimistic views.23 As with
all new techniques, an initial period of enthusiasm should be tempered
by realization of the limitations, drawbacks, and impracticalities but
help to focus on the true utility.30 Now that the
technique is better quantified, studies with proton MRS should be
encouraged because they present a valuable opportunity for the
assessment of human stroke pathophysiology and the influence of new
treatments.
Received February 3, 1998;
revision received May 11, 1998;
accepted May 14, 1998.
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© 1998 American Heart Association, Inc.
Original Contributions
Studies of Acute Ischemic Stroke With Proton Magnetic Resonance Spectroscopy
Relation Between Time From Onset, Neurological Deficit, Metabolite Abnormalities in the Infarct, Blood Flow, and Clinical Outcome
Abstract
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
References
Background and Purpose—Proton
magnetic resonance spectroscopy (MRS) can be used to study metabolite
abnormalities in the brains of stroke patients. We have used it to
examine the relations between the metabolites in the infarct
(N-acetylaspartate [NAA] and lactate) and the time
lapse from stroke to MRS, the presenting neurological deficit,
infarct size and swelling (on MRI), blood flow to the infarct
(estimated by transcranial Doppler ultrasound), and
clinical outcome.
Key Words: cerebral infarct • lactate • magnetic resonance imaging • middle cerebral artery • N-acetylaspartate • spectroscopy, nuclear magnetic resonance • stroke • ultrasound, Doppler, transcranial
Introduction
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
References
Stroke is a common
cause of death and the most common cause of disability in
adults.1 As yet there is no really effective
acute treatment, although aspirin is of marginal
benefit.2 Pathophysiological
studies in animal models are helpful,3 but there
is a need to improve understanding of human stroke because this might
improve the design of clinical trials for new therapeutic agents. For
example, the exact time course of neuronal death after interruption of
the arterial blood supply to part of the brain varies, and
there is evidence that it may take up to several days for all the
neurons to die.4 5 Whether the brain might be
salvageable before this is uncertain,6 but better
definition of the natural history of the brain lesion, and possible
markers of neuronal viability, would be useful.
Subjects and Methods
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
References
The study took place between June 1994 and February 1997 in a
large city teaching hospital without a casualty department but with a
stroke unit.
All patients admitted to our hospital were examined by a stroke
physician, and the clinical syndrome was classified according to the
Oxfordshire Community Stroke Project (OCSP) into a partial or total
anterior circulation stroke (PACI or TACI) corresponding to a small to
medium or large hemispheric cortical infarct, respectively, posterior
circulation infarct (POCI) corresponding to infarction in the occipital
lobes, cerebellum or brain stem, and lacunar syndrome
(LACI).18 Patients admitted within 3 days
of an acute stroke (as defined by WHO
criteria19 ), with symptoms of a medium to
large cortical hemispheric infarct (ie, TACI or "large" PACI or
POCI if it clinically involved the visual cortex) were eligible if
there were no contraindications to MRI and the patient was well enough
to maintain their airway safely.
The intention was to perform MRS as soon as possible after the
stroke but within 4 days at most. MRS was to be repeated where possible
between 5 and 10 days and again between 10 days and 1 month. Access to
the MR scanner, a Siemens 63 SP 1.5 T Magnetom (Siemens AG), was
limited because it provided the main clinical service for neurosciences
in the area. We used a standard circularly-polarized head coil.
T1-weighted sagittal and T2-weighted and proton density (PD)-weighted
axial images were obtained to visualize the infarct, followed by
spectroscopy. The site and extent of any visible infarct, any mass
effect, and hemorrhagic transformation were coded blind to the MRS
results by a neuroradiologist using a previously described coding
system.20 This allows separation of the extent of
the infarct from any mass effect arising from it rather than simply
estimating the volume of the infarct. A "large" infarct was defined
as one occupying half or more of the MCA territory (codes 50 to 80 on
the scan template20 ) and "massive" swelling
was defined as mass effect from the infarct resulting in complete
effacement of the ipsilateral lateral ventricle or more (codes 3 to 6
on the scan template20 ).
The patients were followed up at 6 months with the modified
Rankin scale (0 indicating no symptoms and 6 dead). Follow-up was by
telephone or postal questionnaire by trained staff who were blind to
the imaging results.
The clinical, MRI, MRS, and TCD data were entered into a Dbase4
database and analyzed with SPSS/PC+ (Statistics Package for the
Social Sciences, SPSS UK, SPSS House). The TCD results were simplified
to take account of individual patient variation and the effect of age
by expressing the velocity in the symptomatic artery
(usually the middle cerebral) as a proportion of the velocity in the
asymptomatic contralateral artery: no detected flow in the
symptomatic artery was coded as 0; velocity reduced to less
than half of the asymptomatic side, 1; reduced but to no
worse than approximately half the asymptomatic side, 2; the
same as the asymptomatic side, 3; and greater than the
asymptomatic side, 4. The MRS results were coded in a
similarly simple manner: lactate (present or absent); NAA as a
proportion of the NAA in the contralateral normal brain or remote and
normal-appearing part of the ipsilateral hemisphere. For some of the
analyses, the NAA was categorized as less than or greater than
half of the value of that in the normal area. 
2 tests,
nonparametric tests (Mann-Whitney U test), and
logistic regression.
The study was approved by the local Ethics of Medical
Research Committee.
Results
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
References
During the study period approximately 500 stroke patients were
admitted to the hospital, but many were unsuitable because they either
had the wrong sort of stroke (too mild, lacunar, or posterior fossa),
were admitted too late after their stroke, were too ill to go into the
MR scanner safely, refused to take part in the study, recovered or died
too quickly, had no bone window for TCD, or were found to have a
hemorrhage as the cause of their stroke. In addition, there
were scanner service days, breakdowns, and clinical demand that
precluded inclusion of patients even when a suitable one was available. 
). Failure to
obtain metabolite results was mainly due to the patient being unable to
tolerate the lengthy scanning time (1 hour) and not to technical
factors such as poor signal-to-noise ratios.
View this table:
[in a new window]
Table 1. Timing of MRS Examinations That Were Successful in
Yielding Metabolites (NAA, With or Without Lactate) ). In patients
with successful sequential scans, the NAA value fell in 5, remained the
same in 8, and appeared to increase in 5 patients between the initial
and the follow-up MRS. In a univariate analysis,
reduction in the concentration of NAA in the infarct within 4 days of
the stroke (to less than half the value or worse of normal brain) was
associated with large infarcts (P<0.01) but not the timing
of the scan, reduction in blood velocity to the infarct, infarct
swelling (on the initial or later scan between 5 and 10 days), or the
presence of lactate. In a multiple logistic regression, however,
reduction in NAA was weakly associated with the clinical stroke
syndrome (P=0.08) and the degree of reduction in blood
velocity to the infarct (P=0.06) and was significantly
associated with the extent of the infarct (P=0.03) and the
presence of lactate (P=0.04) but not the timing of the scan
or the amount of swelling in the infarct (Table 2).
View larger version (14K):
[in a new window]
Figure 1. Time course of NAA in infarct (as a proportion of
amount found in normal brain remote from infarct) over 4 weeks after
stroke. Lines join results from sequential investigations in the same
patients.
View this table:
[in a new window]
Table 2. Multivariate Analysis of
Factors That Might Be Associated With Presence of Lactate and Marked
Reduction in NAA in Infarcts Investigated With Proton MRS Within 4 Days
of Onset of Stroke Symptoms and With Poor Outcome at 6 Months (Defined
as Dead or Dependent, ie, Rankin Score 3 to 6) ). The MRS
examinations in which lactate was detected (median 3 days, 95%
confidence intervals [CI] 2 to 5 days) were done significantly sooner
after the stroke than those in which lactate was not detected (median 5
days, 95% CI 4 to 8 days): difference between the medians=1 day, 95%
CI 0 to 4 days (see Figure 3). In
a univariate analysis the presence of lactate in
the infarct within the first 4 days of the stroke was associated with
extensive infarction (P<0.02) but not with the amount of
swelling in the infarct (within 4 days), the degree of reduction in the
blood velocity to the infarct, the clinical stroke syndrome, or the
reduction in NAA. The presence of lactate within 4 days of the stroke
was also not associated with subsequent infarct swelling on brain
imaging at 5 to 10 days. From multiple logistic regression, lactate
detected within 4 days of the infarct was significantly associated with
large infarcts (P=0.05) and reduced NAA (P=0.04)
but not the clinical stroke syndrome, timing of the scan, blood
velocity, or the amount of infarct swelling (Table 2
).
View larger version (17K):
[in a new window]
Figure 2. Time course of lactate detected in the infarct
over 4 weeks after stroke (some patients were scanned more than once).
"Lipid" refers to either lipid contaminants from the skull or from
cell membrane breakdown products in infarct. Lipid usually obscures
lactate peak.
View larger version (67K):
[in a new window]
Figure 3. Example of T2-weighted axial MR images and single
voxel proton MR spectra obtained from a patient with left MCA territory
infarct. Images in a and b were obtained on day 2 and c and d on day 7
after the stroke. a and c are from normal hemisphere and b and d from
infarct. Note presence of lactate (inverted peak arrowed) with
relatively preserved NAA (arrowhead) on day 2. On day 7 there is no
longer any lactate detected and NAA peak is smaller (arrowhead),
indicating further loss of neurons. ).
Discussion
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
References
We have demonstrated, using fairly simple criteria, that large
cerebral infarcts are associated with reduced NAA in the infarct, the
presence of lactate, reduced blood velocity, and a poor clinical
outcome at 6 months but not with the amount of edema in the infarct.
Even in this small series, though larger than any previous human stroke
spectroscopy series, there are important variations in the severity of
the stroke and other baseline variables that have an influence on
long-term outcome and presumably other sequelae of the stroke. 
50%. All were single voxel (not CSI) measurements and all had large
infarcts. It may simply reflect the high coefficient of variation in
the measure of NAA23 with proton MRS. All 3
subjects had a third MRS that showed a return toward the NAA ratio
(infarct: contralateral brain) of the initial MRS. The NAA peaks in the
second MRS were all broad, which could result in errors of quantifying
the peak,23 in turn exaggerated by using the
ratio. It could be due to slight differences in positioning of the
region of interest between studies, though we were very careful to
ensure consistent and accurate voxel positioning. It could be
due to real changes in the stroke (such as changes in the water content
of the infarct), though this latter seems unlikely, or possibly due to
changes in T1 and T2 values influencing the measured NAA (though this
is thought unlikely to occur).29
Acknowledgments
This work was conducted as part of the Medical Research Council
Clinical Research Initiative in Clinical Neurosciences, who funded the
following staff: Dr Joanna M. Wardlaw, Dr Ian Marshall, Jim Wild, Jim
Cannon, Stephanie Lewis, and the Acuson 128xp 10v ultrasound machine.
We would also like to thank the following for their support: The
Lothian Stroke Register (Marion Livingston, Pam McLaren, Mike McDowell,
Dave Charleton) and the Scottish Office Chief Scientist Office for
support of the Lothian Stroke Register; Dr Carl Counsell and Dr Richard
Davenport (supported by Wellcome Trust), Dr Nic Weir, and Dr Paul
Dorman (supported by the Medical Research Council), Dr Mike Watt, Dr
Sunil Narayan, and Dr Tsang for their help in identifying patients;
Martin Connell for image processing and computer systems support; the
radiographers and nurses of the Neuroradiology
Department, and the nurses of the Stroke Unit of the Western General
Hospital in Edinburgh, without whose help and goodwill this project
would not have possible.
References
Top
Abstract
Introduction
Subjects and Methods
Results
Discussion
References
1.
Murray CJL, Lopez AD. Mortality by cause for eight
regions of the world: Global Burden of Disease Study.
Lancet. 1997;349:1269–1276.[Medline]
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