Biomed Imaging Interv J 2006; 2(2):e16
© 2006 Biomedical Imaging and
CT perfusion as a useful tool in the evaluation of leuko-araiosis
MBBS, FRCR, KL Ho,
MBBS, MRad, O Nawawi,
MBBS, MRad, FRCR, HT Chong,
MBBS, MRCP, CT Tan,
Departments of Biomedical Imaging and Medicine, University Malaya
Medical Centre, Kuala Lumpur, Malaysia
Background: Leuko-araiosis (LA) and dementia are
common geriatric conditions but their pathogenesis and clinical significance
are not completely understood. An evaluation of CT perfusion (CTP) in both
these conditions can further enhance the understanding of these diseases.
Methods: Twenty-one patients with LA and 21 age-matched
controls were studied with CTP and assessed for their cognitive function. The
subjects were classified into four groups: Group 1, with LA (n = 21); Group 2,
without LA (n = 21); Group 3, with dementia (n = 7); Group 4, without dementia
(n = 11). The mean cerebral blood flow (CBF), cerebral blood volume (CBV) and
mean transit time (MTT) values were compared between groups 1 and 2, while mean
CBF values were compared between groups 3 and 4.
Results: Mean white matter CBF was considerably
reduced in patients with LA in the frontal region by 42% (p = 0.000), basal
ganglia by 37% (p = 0.000) and occipital region by 18% (p = 0.019). The mean
white matter CBV was reduced in patients with LA in the frontal region by 36% (p
= 0.000) and basal ganglia by 28% (p = 0.017). The mean white matter CBF was
dramatically reduced in patients with dementia in the frontal region by 44% (p
= 0.000), basal ganglia by 32% (p = 0.038) and occipital regions by 24% (p =
Conclusion: The CTP showed reduced white matter CBF
and CBV in patients with LA. This is consistent with chronic ischemia as the
pathogenesis of LA. The CTP is also a potentially important technique in the
diagnosis and management of dementia, because of its ability to reveal cerebral
hypoperfusion. � 2006 Biomedical Imaging and Intervention Journal. All rights
Keywords: CT perfusion; chronic ischemia; dementia;
Leuko-araiosis (LA) is the term introduced by Hachinski et
al to designate periventricular or subcortical (centrum semiovale) areas of
hypodensity on computed tomography (CT) or hyperintensity on T2-weighted
magnetic resonance imaging (MRI). LA is a common condition, with
epidemiological studies demonstrating a high prevalence in subjects over 65
years of age, as evaluated by CT or MRI. It is probably caused by chronic
cerebral ischemia but the pathogenesis and its clinical significance are not
completely understood. Some individuals remain asymptomatic for prolonged
periods, while others develop gait disturbance, cognitive impairment, mood
disorders, disability, and even dementia. LA increases overall morbidity and
mortality and also the risk of stroke. Further understanding of the
pathogenesis of LA is essential because it is potentially preventable and modifiable
Dementia is a highly widespread and morbid condition
frequently found in the elderly, especially those affected by LA. Clinical
identification and diagnosis of dementia or predementia is especially difficult
in the early stages. However, the early and accurate diagnosis is important
because early treatment is now possible. Functional brain imaging techniques
such as PET and SPECT can provide substantial assistance in the initial
diagnosis of dementia, but are limited because of factors such as low
availability and high costs [3,4,5].
Recent developments in helical and high-speed continuous
data technology have enabled CTP using iodinated contrast material. CTP of the
brain is a proven tool, especially in acute stroke and oncology cases [6,7].
With the evolution of spiral multi-slice CT technology and its increasing
availability, CTP can play an important role in clinical techniques. Our study
examined the correlation of cerebral perfusion with LA and dementia, to prove
that the pathogenesis of the LA is chronic cerebral ischaemia. We also tested
the hypotheses, that the mean cerebral blood flow (CBF) in the cerebral white
matter in patients with LA is lower than in patients without, within the same
age group; and that the mean CBF in the cerebral white matter of patients with
dementia is lower than in patients without.
MATERIALS AND METHODOLOGY
The subjects were selected from a group of patients who were
referred to our department for CT examination of the brain. The reasons for
referral were stroke (n = 18), dementia or cognitive impairment (n
= 14), headache (n = 6), giddiness (n = 5), psychiatric disorder
(n = 4), syncope (n = 1) and metastatic malignancy of the brain (n
=1). The subjects were selected based on the identification of LA in
non-contrasted CT brain using standard window (Figure 1). A total of 23
patients with LA were identified and they underwent CTP on the same day as the
scam. A total of 26 patients without LA were also selected for CTP as an
age-matched control sample. All subjects were assessed with Mini Mental State
Examination (MMSE) either before or after the procedure. Patients with an MMSE
score of less than 24 and with clinical features of dementia or cognitive
impairment were used for the sample with dementia. The following information
was collected from the patients: age, sex and risk factors (diabetes mellitus,
hypertension and cardiovascular disease). Based on the non-contrasted CT
findings and MMSE scores, the subjects were classified into four groups: Group
1, patients with LA (n = 21, 10 Male, 11 Female); Group 2, patients
without LA (n = 21, 9 Male, 12 Female); Group 3, patients with dementia
(n = 7, 3 Male, 4 Female; 3 with LA, 4 without LA); Group 4, patients
without dementia (n = 11, 6 Male, 5 Female; all with no LA).
[View this figure]
| Figure 1 Plain CT brain at the
basal ganglia (A) and corona radiata (B) levels showing
periventricular white matter lucency in a patient
The clearance from the Ethical Committee was obtained prior
to the commencement of this study, along with informed consent from the
subjects or their next of kin. Those patients with contraindication to contrast
agents, history of allergy, renal impairment, or with intracranial bleed or
massive mass effect on non-contrasted CT brain were excluded from the study.
All CT examinations were performed on a 16 slice
multidetector CT scanner (GE Lightspeed; GE Medical Systems, Milwaukee, WI, USA).
The non-contrasted CT examinations were done using either 3 or 5 mm
transverse sections through the posterior fossa and 5 or 10 mm
transverse sections through the supratentorial region.
For the CTP protocol, continuous scanning of four adjacent
5-mm axial sections was performed with a 45-s cine with a 1-s
interval, retrospectively reconstructed to a 0.5-s interval, and
acquired at 80 kVp using 190 mAs to 200 mAs. For this examination a
bolus of 40 ml contrast material (Ultravist, Schering, Berlin) injected at 4 ml s-1
was used. A 25-cm field of view was used for all the scans, which were
reconstructed with a matrix of 512 x 512 pixels. The scans were
obtained in the transverse plane, and the examination covered the
common areas of LA, which are the basal ganglia and the corona radiata.
Analysis of Scans
Two radiologists independently reviewed the non-contrasted
CT scans on an imaging workstation (Advantage Windows; GE Medical Systems,
Milwaukee, Wisconsin). The presence of LA and other lesions such as focal
infarcts were documented. The CTP scans were analyzed by two
radiologists using the same imaging workstation, with commercial CTP analysis
software (CTP; GE Medical Systems, Milwaukee, Wisconsin), to create maps of
CBF, CBV and mean transit time (MTT). The more cephalad section of
the 10 mm sections (x 2) or 5 mm sections (x 4) were analyzed to maintain a
uniform number of sections in all subjects.
Both the radiologists placed ROI (3�7 mm2) on the
input arteries and veins at the time of evaluation of the scan by
using the same protocol, for which contrast-enhancement curves were generated.
For most patients, the larger of the two anterior cerebral arteries
was chosen for placement of the ROI, providing the arterial input
function, and the superior sagittal sinus was chosen for placement of
the ROI, providing the venous outflow function. These vessels were
chosen because they can be identified in most subjects and also
because their courses run almost perpendicular to the transverse
plane of the section used for the CT scanning of the brain. By
choosing such vessels errors due to volume-averaging artifacts would
For the measurement of the brain parenchyma perfusion
parameters (CBF, CBV, MTT), six small circular ROI were drawn on the white
matter regions of frontal, basal ganglia and occipital lobes. The size of the
ROI was standardized in all samples, at 120�125 mm2 (Figure 2). The
specifications were because an ROI of this size is technically easy to create
and highly reproducible during the post-processing time, and is optimal for
inclusion and coverage of most representative areas showing white matter
changes in LA.
[View this figure]
| Figure 2 Axial CTP scan showing
six circular ROI (in purple) placed at both frontal,
basal ganglia and occipital regions, indicating location
of CTP measurement.
Next, the perfusion maps were created in the following
order: CBF, CBV and MTT (Figure 3), following which the mean value of that
perfusion parameter contained within each of the six ROI was recorded. These
mean values were compared between groups 1 and 2, and groups 3 and 4. For
statistical analysis we used the Mann-Whitney test, with a statistical
significance level set at p<0.05.
[View this figure]
| Figure 3 CBF (A), CBV (B) and
MTT (C) maps of a patient with leuko-araiosis.
A total of 49 patients underwent plain CT brain scan, CTA and CTP in this study.
There were 23 subjects in the LA group and 26 in the control
group. The study population comprised 27 females (55.1%) and
22 males (44.9%). The mean age for study population was 70.1
years (70.19 in LA group; 69.86 in non-LA; p-value>0.05).
The risk factor profile for patients with and without LA is shown in Table
1. Patients with LA showed higher prevalence of hypertension,
diabetes mellitus, cardiovascular disease and cerebrovascular
accidents. The mean MMSE score was also lower in the LA group
(23.53), as compared to the control group (27.8), but this is
not a considerable statistical difference (p-value>0.05).
[View this table]
| Table 1 Risk factors profile for
patients with or without leukoaraiosis
CTP was successfully performed in 85.7% (n = 42; LA
21, Non-LA = 21) of the cases. However, it was unsuccessful in seven cases (LA
2, non LA 5), because of motion artifacts and technical errors encountered
during the procedure.
We found no dramatic difference between the right and left
hemisphere CTP parameter values, and therefore the values of the regions of
interest from both sides were pooled. Mean white matter values of frontal,
basal ganglia and occipital regions were obtained by averaging values from both
sides of these regions.
�(a) Comparison of mean perfusion parameter values
between LA (Group1) and non-LA (Group 2)
There was a considerable difference between of the mean
white matter CBF between groups 1 and 2. In Group 1, it was dramatically
reduced in patients with LA in the frontal by 42% (p =
0.000), basal ganglia by 37% (p = 0.000), and occipital regions by 18% (p
= 0.019), as compared with Group 2 (Table 2).
[View this table]
| Table 2 Mean CBF values (ml/min/100g),
Mean CBV values (ml/100g) and MTT (sec) in the leukoaraiosis
and the non- leukoaraiosis groups
The mean white matter CBV was also considerably reduced in
patients with LA in the frontal region by 36% (p = 0.000) and the
basal ganglia by 28% (p = 0.017), but not in the occipital region (p =
0.289). As for the mean MTT values, there was no significant difference between
groups 1 and 2 for all the regions measured.
(b) Comparison of mean perfusion parameter values between
dementia (group 3) and non-dementia (group 4)
When compared with Group 4, the mean white matter CBF of the
patients in Group 3 were greatly reduced in the frontal region by
44% (p = 0.000), basal ganglia� by 32% (p = 0.038) and occipital
region by 24% (p = 0.001). The mean white CBV of patients with dementia
were also greatly reduced in the frontal region by 40% (p = 0.011)
compared with the control group. The mean white matter MTT values were also not
considerably different between these two groups (Table 3).
[View this table]
| Table 3 Mean CBF values ( ml/min/100g),
Mean CBV values (ml/100g) and MTT (sec) in dementia
and non-dementia patients
The nature, pathogenesis and clinical significance of LA are
not well understood. Many studies have emphasized the significant correlation
of this condition with aging, hypertension, diabetes mellitus, cardiovascular disease,
cerebrovascular accident and cognitive impairment [1,2,8-11]. Our study
revealed similar results. LA is mainly seen in the elderly in this study, with
a mean age of 70.1 years, compared to 73.7 years in a study by Wiszniewska et
al . Higher prevalence of hypertension, diabetes mellitus,
cardiovascular disease and cerebrovascular accident are noted in the LA group
as compared with the control group. Aging, hypertension and diabetes mellitus
induce arteriosclerotic changes on the small penetrating arteries and
arterioles of white matter, suggesting that LA is primarily a small vessels
disease. The correlation between LA and cognitive impairment is well
established [12-14] and consistent results are observed in this study, where
the mean MMSE score in the LA group is lower than in the control group.
In the past, many researchers have attempted to prove
chronic ischemia as the pathogenesis of this entity using various imaging
modalities. Markus et al had shown reduced cerebral blood flow in white
matter in LA using quantitative exogenous contrast-based perfusion MRI . By
using single photon emission computed tomography, Starkstein et al found
that patients with Alzheimer�s disease, and LA had significant lower bilateral
perfusion in the basal ganglia, thalamus, and frontal lobes than in Alzheimer
patients without LA . Miyazawa et al demonstrated reduced CBF in
centrum semiovale of asymptomatic individuals with LA, using xenon-contrasted
CT. Their study also demonstrated that the CBF values were much reduced in
cases with more severe white matter changes . CTP is a new imaging method
that allows rapid qualitative and quantitative evaluation of cerebral
perfusion, which has not been used in the evaluation of LA.
We have shown significant reduction of white matter CBF and
CBV in patients with LA. In chronic ischemia, reduction in CBF is associated
with reduction in CBV due to the loss of the autoregulatory mechanism of the
involved vessels, in contrast to acute ischemia where the CBV is maintained or
elevated due to an intact autoregulatory function. Prolongation of MTT is
always noted in cerebral infarction due to vascular obstruction or sluggish
flow . No significant prolongation of MTT was noted in this study sample,
possibly due to the establishment of effective collateral pathways in chronic
ischemia that has shortened the transit time of blood flow. Overall, these
results provide further evidence for the role of chronic ischemia in the
pathogenesis of LA. The absolute values of CBF obtained in the LA group were
similar to those in previous studies [15,16]. The mean frontal white matter CBF
value in our LA group were 10.61 ml/min/100g, compared with 13.65 ml/min/100g
measured by Markus, with perfusion MRI . Miyazawa et al showed mean
centrum semiovale CBF values ranging from 11.31-24.27 ml/min/100g  while
our study obtained values of 10.61-20.33 ml/min/100g. These findings suggest
the validity of the CBF measurement using CTP.
Our study also showed a considerable reduction of CBF in all
regions, in Group 3. A correlation between cognitive ability and cerebral
perfusion had been demonstrated using xenon-contrasted CT, PET and SPECT in
previous studies [18-20]. Meyer et al used xenon-contrasted CT and found
that reduced mean Cognitive Capacity Screening examination (CCSE) scores
correlated directly with CBF reductions in patients with multi-infarct dementia
and dementia of the Alzheimer�s type . Terayama et al, also using
xenon-contrasted CT, showed that the perfusion of cerebral white matter was
diffusely and severely reduced in the frontal, temporal and occipital regions
of 12 patients with dementia . Few authors have also found that SPECT is
able to reveal a specific pattern of cerebral perfusion defects, depending upon
the type of dementia, allowing for specific diagnosis of dementia [20,21]. Our
study has shown that CTP is a valid and useful imaging modality with the
ability to demonstrate cerebral perfusion changes in patients with dementia.
Thus, coupled with clinical assessment, CTP should potentially enhance the
diagnostic accuracy of dementia. However, our study has not been designed to
analyze CTP among the various types of dementia, and clinical grading of
dementia from mild to severe is expected to affect the CTP data. Further study
with a larger sample of patients with dementia, and a study design that allows
differentiation of various types of dementia is warranted. This can further
investigate the feasibility of CTP as a useful imaging method in diagnosing
specific types of dementia, which had been shown possible with SPECT.�
CTP is a non-invasive, fast, easy-to-perform imaging tool,
which is valid and comparable with other imaging modalities in measuring
cerebral perfusion in patients with LA and dementia. By using CTP, we have
shown significant reduced white matter CBF and CBV in patients with LA. This is
consistent with chronic ischemia as the pathogenesis of LA. We have also
demonstrated that CTP is a potentially important clinical imaging technique in the
diagnosis and management of dementia, in view of its ability to show
significant cerebral hypoperfusion in these patients.
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|Received 18 August 2005; received in revised form 20 February 2006; accepted 8 March 2006
Department of Biomedical Imaging, University Malaya Medical Centre, 59100 Kuala Lumpur, Malaysia. Tel: +6012-6316681; Fax: +603-79581973; E-mail: email@example.com (Norlisah Ramli).
Please cite as: Ramli N, Ho KL, Nawawi O, Chong HT, Tan CT, CT perfusion as a useful tool in the evaluation of leuko-araiosis, Biomed Imaging Interv J 2006;2(2):e16
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