Download Characterization of Cortical Microvascularization in Adult Moyamoya

Characterization of Cortical Microvascularization in Adult
Moyamoya Disease
Marcus Czabanka, MD; Pablo Peña-Tapia, MD; Gerrit A. Schubert, MD; Johannes Woitzik, MD;
Peter Vajkoczy, MD; Peter Schmiedek, MD
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Background and Purpose—Increased cortical microvascularization has been proposed to be a Moyamoya disease
(MMD)–specific characteristic. It was the aim of our study to characterize the anatomic pattern and microhemodynamics
of cortical microvascularization in MMD.
Methods—Intraoperative indocyanine green videoangiography was performed in 16 adult MMD patients, 15 patients with
atherosclerotic cerebrovascular disease (ACVD), and 10 control patients. Cortical microvascularization and microvascular hemodynamics were categorized and analyzed according to anatomic and functional indocyanine green
angiographic aspects. Anatomic analysis included microvascular density, microvascular diameter, and microvascular
surface per analyzed area. Microhemodynamic analysis included microvascular transit time, arterial microvascular
transit time, and venous microvascular transit time.
Results—Microvascular density and diameter were significantly increased in MMD patients (1.8⫾0.2 mm/mm2 and
0.24⫾0.03 mm, respectively) compared with those in ACVD patients (1.5⫾0.2 mm/mm2 and 0.20⫾0.02 mm,
respectively) and controls (1.5⫾0.1 mm/mm2 and 0.19⫾0.03 mm, respectively). This resulted in significantly increased
microvascular surface per analyzed area in MMD (67⫾13%) vs ACVD patients (47⫾7%) and controls (45⫾6%).
Anatomic changes were paralleled by significantly increased microvascular and arterial microvascular transit times in
MMD patients (11.55⫾3.50 and 6.79⫾2.96 seconds, respectively) compared with those in ACVD patients (8.13⫾1.78
and 4.34⫾1.30 seconds, respectively) and controls (8.04⫾2.16 and 4.50⫾1.87 seconds, respectively).
Conclusion—Cortical microvascularization in MMD is characterized by significantly increased microvascular density and
microvascular diameter, leading to increased microvascular surface. These anatomic alterations are accompanied by
prolonged microvascular hemodynamics. These observations might represent an MMD-specific compensation mechanism for impaired cerebral blood flow. (Stroke. 2008;39:1703-1709.)
Key Words: Moyamoya disease 䡲 cortical vascularization 䡲 indocyanine green videoangiography
䡲 cerebral blood flow 䡲 compensation mechanism
M
oyamoya disease (MMD) is a rare and unique cerebrovascular disease. It is characterized by progressive
occlusion of the basal arteries of the circle of Willis in
association with a network of fine “moyamoya vessels” at the
base of the brain.1 Furthermore, there are several additional
mechanisms in MMD, like transdural and extracranialintracranial collateral formation, dilation of peripheral cerebral
arteries, or the development of leptomeningeal anastomoses, that
compensate for the reduced cerebral blood flow (CBF).2 Despite
those compensating mechanisms, MMD patients have chronic
cerebral ischemia with cerebrovascular hemodynamic insufficiency. Therefore, surgical revascularization represents an effective treatment option for this disease.
Cortical vascularization plays an important role in regulating cerebral perfusion and blood flow.3 Many reports suggest
increased cortical microvascularization in MMD as a compensating mechanism for chronically impaired CBF.2,4 However, cortical microvascularization has not been thoroughly
analyzed in MMD so far, and consequently, there is little
knowledge about cortical microvascularization and microhemodynamics in this form of cerebrovascular disease. With the
introduction of intraoperative indocyanine green (ICG)
videoangiography, visualization and investigation of cortical
vascularization have become possible.5,6 With this technique,
it was the aim of our study to characterize the anatomic and
microhemodynamic aspects of cortical microvascularization
Received September 4, 2007; final revision received October 22, 2007; accepted October 30, 2007.
From the Department of Neurosurgery (M.C., P.P.-T., G.A.S., P.S.), Klinikum Mannheim, Medical Faculty Mannheim, University of Heidelberg,
Heidelberg, and the Department of Neurosurgery (M.C., J.W., P.V.), Charité-Universitätsmedizin Berlin, Berlin, Germany.
Correspondence to Marcus Czabanka, MD, Department of Neurosurgery, Charité-Universitätsmedizin Berlin, Campus Virchow Klinikum, Am
Augustenburgerplatz 1, 13353 Berlin, Germany. E-mail [email protected]
© 2008 American Heart Association, Inc.
Stroke is available at http://stroke.ahajournals.org
DOI: 10.1161/STROKEAHA.107.501759
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A
A2
23 sec.
14 sec.
10 sec.
x1
A2
Arterial peak
fluorescence activity
x3
x2
V1
V2
Parenchym peak
fluorescence activity
Venous peak
fluorescence activity
B
100
MVTT
AMVTT
80
x1
60
VMVTT
x3
x2
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40
20
0
0
5
10
15
20
25
Figure 1. A, Photographs of the analysis procedure: example of postoperative analysis of
microvascular hemodynamics in an MMD
patient. Left image, ICG videoangiography 10
seconds after start of the analysis process,
showing peak fluorescence activity in A2 vessels (arterial compartment). x1 encircles the
analysis-relevant A2 vessel. Middle image, ICG
videoangiography 14 seconds after start of the
analysis process, showing peak fluorescence
activity in the cortical parenchyma (capillary
compartment). x2 indicates the analysisrelevant brain parenchyma; delineation of
microvascularization illustrates analysis of MD
(length of microvessels per ROI), with 3 ROIs
and the corresponding microvessels within
those areas. Right image, ICG videoangiography 23 seconds after start of the analysis process, showing peak fluorescence activity in V2
vessels (venous compartment). x3 encircles the
analysis-relevant V2 vessel. B, Schematic illustration of intravascular fluorescence evaluation
(x1 indicates arterial compartment; x2, capillary
compartment; and x3, venous compartment).
Arrows demonstrate calculation of MVTT,
AMVTT, and VMVTT.
Time (sec.)
in MMD. As a reference, we analyzed cortical microvascularization and microhemodynamics in patients with atherosclerotic cerebrovascular disease (ACVD) with coexisting
hemodynamic compromise and in control patients with physiologic cortical angioarchitecture and microhemodynamics.
cerebral surface before intraoperative ICG videoangiography guaranteed dimensional accuracy during postoperative analysis. During
application of the fluorescent marker, blood pressure monitoring was
recorded and evaluated to exclude hemodynamic alterations that
could interfere with cerebral perfusion during ICG injection.
Cortical Vascularization
Subjects and Methods
Patient Population and Surgical Procedures
Between March 2006 and February 2007, a total of 41 patients were
included in our study. Of these, 16 patients were diagnosed with
MMD according to diagnostic criteria.7 MMD patients received
combined cerebral revascularization by standard extracranialintracranial bypass surgery in combination with encephalomyosynangiosis. Fifteen patients with ACVD and hemodynamic compromise were included in our study. All ACVD patients received
standard extraintracranial arterial bypass surgery.
As a control group, 10 patients with physiologic cortical angioarchitecture and microhemodynamics were analyzed. Nine of these
patients underwent surgery for an unruptured intracranial aneurysm,
and 1 patient underwent surgery via a transtentorial approach for a
cerebellar tumor. All surgeries were performed with use of the
Pentero OPMI surgical microscope (Carl Zeiss AG, Jena, Germany)
with an integrated ICG videoangiography system.
Preoperatively, MMD and ACVD patients underwent conventional catheter digital subtraction angiography and morphological
imaging by magnetic resonance imaging. Functional regional cerebral blood flow (rCBF) measurements were made at rest and after the
administration of acetazolamide (15 mg/kg body weight) by stable
xenon computed tomography (Xe-CT; DDP Inc, Houston, Tex).
Cerebrovascular reserve capacity (CVRC) was calculated as described elsewhere in detail.8 To obtain CBF values for the region
analyzed by ICG videoangiography, regions of interest (ROIs) on the
Xe-CT images were located in the vascular territory under investigation (eg, vascular territory of the middle cerebral artery).
ICG Videoangiography
In all patients, ICG videoangiography was performed according to
the surgical indications. Placement of a millimeter-scale grid on the
For analysis of cortical vascularization, we categorized arterial and
venous macrovascularization as well as cortical microvascularization
according to the functional ICG angiographic aspects. The early
filling arteries (A1) and their direct branches (A2) and the last
draining veins (V1) and their direct branches (V2) were referred to
as cortical macrovascularization. All vessels that appeared between
A2 and V2 vessels were regarded as cortical microvascularization
(Figure 1).
Microvascularization was quantified postoperatively by a
computer-assisted analysis system (CAPIMAGE, Zeintl Software
Engineering, Heidelberg, Germany). For quantification of cortical
microvascularization, we analyzed 3 suitable ROIs per cerebral
cortex. ROIs were characterized as an area of 25 to 100 mm2 without
A1, A2, V1, or V2 vessels within that area. According to a
previously described procedure,9 quantification of microvascular
density (MD) was performed by measuring the length of all
microvessels per analyzed ROI (Figure 1). Furthermore, microvascular diameter (D) was analyzed, and microvascular surface area
(MVS) per analyzed ROI was calculated from the following formula:
MVS⫽␲⫻D/2⫻MD.
Microhemodynamic Analysis of
Cortical Microvascularization
Microhemodynamic analysis was performed postoperatively with
IC-CALC 1.1 software (Pulsion Medical Systems). For analysis of
cortical microhemodynamics, we analyzed fluorescence intensity in
3 distinct compartments in a time-dependent manner: ie, the arterial
compartment (A2 vessels), capillary compartment (brain parenchyma), and venous compartment (V2 vessels). Figure 1A demonstrates the different compartments during ICG videoangiography. By
comparing the time points of peak fluorescence intensity in the
arterial (A2 vessels) and venous (V2 vessels) compartments, we
Czabanka et al
Cortical Microvascularization in Adult Moyamoya Disease
were able to measure the time required for the fluorescent dye to pass
the cortical microvascularization. This time was defined as microvascular transit time (MVTT). Furthermore, we analyzed the time
difference of peak fluorescence intensity between the arterial (A2
vessels) and capillary compartments. This time was defined as
arterial microvascular transit time (AMVTT). According to this
procedure, venous microvascular transit time (VMVTT) was defined
as the time difference between the capillary and venous (V2 vessels)
compartments. Figure 1B demonstrates microhemodynamic definitions and illustrates the analysis procedure.
Statistical Analysis
For comparisons between 3 groups, 1-way ANOVA and subsequent
comparison with Fisher’s least significant difference test were used.
Student’s t test was applied for comparisons of CBF values between
MMD and ACVD patients. Differences were considered statistically
significant for P⬍0.05. All values are given as mean⫾SD.
Results
Patient Population
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The mean age of the MMD patient group was 41⫾12 years.
In the ACVD patient group, the mean age was 57⫾10 years,
and the mean age of control patients was 53⫾9 years. There
was a significant difference in mean age between the MMD
patients and the ACVD and control patients. No difference
was observed between ACVD patients and controls. Detailed
descriptions of the patient groups are illustrated in Table.
rCBF Assessed by Xe-CT
We analyzed rCBF in 13 MMD patients. Measurement of
CBF could not be performed in 3 patients due to intolerance
of the procedure: nausea and vomiting in 2 cases and asthma
bronchiale in 1 patient. Therefore, a total of 13 CBF measurements were included in our study. Mean basal CBF was
52⫾20 mL/100 g per min, and mean stimulated CBF was
55⫾22 mL/100 g per min. CVRC was 7⫾25%.
In the ACVD patient group, we included 14 CBF measurements, as 1 patient did not tolerate the Xe-CT due to nausea
and vomiting. Mean basal CBF was 49⫾10 mL/100 g per
min, and mean stimulated CBF was 53⫾18 mL/100 g per
min. CVRC was 6⫾26%. There was no significant difference
in rCBF and CVRC values between both patient groups.
Table summarizes CBF values of the ACVD and MMD
patients.
Intraoperative Blood Pressure Monitoring
Mean systolic blood pressure during ICG videoangiography
in MMD patients was 134⫾16 mm Hg, and mean diastolic
blood pressure was 69⫾10 mm Hg (Table). In ACVD patients, mean systolic blood pressure was 129⫾11 mm Hg,
whereas mean diastolic blood pressure was 66⫾8 mm Hg
(Table). Mean systolic blood pressure in control patients was
129⫾8 mm Hg, and mean diastolic pressure was
69⫾6 mm Hg (Table). There was no statistical difference in
systolic and diastolic blood pressures between all groups.
Cortical Microvascularization
Cortical MD of MMD patients was 1.8⫾0.2 mm/mm2. In
ACVD patients, cortical MD was 1.5⫾0.2 mm/mm2, and
control patients showed an MD of 1.5⫾0.1 mm/mm2. There
was a statistically significant difference between MMD patients and the 2 other groups. We found no difference
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between ACVD patients and controls. Furthermore, D in
MMD patients was 0.24⫾0.03 mm. In ACVD patients, D was
0.20⫾0.02 mm, and in controls, 0.19⫾0.03 mm. There was a
statistically significant difference in D between MMD patients versus ACVD and patients controls.
MVS was found to be 67⫾13% in MMD patients compared with 47⫾7% in ACVD and 45⫾6% in control groups.
There was a statistically significant difference in MVS
between MMD patients and the other 2 groups. We found no
significant differences in MD, D, and MVS between ACVD
patients and control patients. Figure 2A comprises intraoperative images of cortical microvascularization and the corresponding ICG videoangiogram; Figure 2B is a graphical
illustration of our results for MD, D, and MVS.
Cortical Microhemodynamics
Functional analysis revealed an MVTT for MMD patients of
11⫾3 seconds. MVTT in ACVD patients was 8⫾2 seconds,
and in controls, it was 8⫾2 seconds. Statistical analysis
revealed a significantly increased MVTT in MMD patients
compared with the 2 other patient groups. There was no
statistically significant difference between ACVD patients
and controls.
In terms of AMVTT, functional analysis revealed an
AMVTT for MMD patients of 6⫾3 seconds. ACVD patients
displayed an AMVTT of 4⫾1 seconds, and in control
patients, AMVTT was 4⫾2 seconds. There was a statistically
significant difference in AMVTT between MMD patients
versus ACVD patients and controls. We found no difference
in AMVTT between ACVD patients and controls. VMVTT in
MMD patients was 5⫾2 seconds. In ACVD patients VMVTT
was 4⫾2 seconds, and in control patients it was 3⫾2 seconds.
We found no significant differences in VMVTT between all
patient groups. Figure 3 demonstrates the graphical results of
microhemodynamic analysis.
Discussion
In our study, we observed significant increases in MD, D,
MVS, and MVTT in adult MMD patients compared with
ACVD patients and controls. Adult MMD patients are additionally characterized by significantly prolonged AMVTT
compared with that in ACVD patients and controls. In terms
of VMVTT, we found no differences between our patient
groups. Therefore, we have demonstrated an MMD-specific
structural increase in cortical microvessels and significantly
prolonged cortical microhemodynamics in MMD. These
observations might represent an MMD-specific compensation
mechanism for the reduced CBF and oxygen supply.
The brain uses a number of compensating mechanisms to
adapt to chronic ischemia, like collateral blood flow from the
other hemisphere via the circle of Willis, a reduction in
cerebral metabolism, maximal dilation of basal cerebral
arteries, and the development of leptomeningeal and extraintracranial anastomoses.10 However, these mechanisms vary
on an individual basis10 and often do not completely restore
CBF. Patients with chronically decreased CVRC are at
particular risk for ischemic stroke.11,12 In our study, MMD as
well as ACVD patients displayed typical features of hemodynamic cerebral ischemia11 with impaired CVRC.13
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Table.
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Summary of Patient Groups Included in our Study
Case
Age, y, Sex
CBF, Basal/Stimulated,
mL/100 g per min
CVRC, %
Blood Pressure,
mm Hg
Diagnosis
Surgical Procedure
1
45, M
44.68/36.30
⫺7.38
150/70
MMD
Bypass/EMS
2
34, F
32.50/40.87
8.37
140/80
MMD
Bypass/EMS
3
20, F
NP (COPD)
130/70
MMD
Bypass/EMS
4
38, F
57.19/59.77
2.58
130/70
MMD
Bypass/EMS
5
44, F
58.00/37.70
⫺20.30
150/80
MMD
Bypass/EMS
6
50, F
NP (N&V)
NP (N&V)
140/70
MMD
Bypass/EMS
7
26, F
76.70/95.70
19.00
140/75
MMD
Bypass/EMS
8
42, F
74.10/84.97
10.69
120/60
MMD
Bypass/EMS
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9
51, F
36.30/38.08
10
30, F
NP (N&V)
11
50, F
12
43, F
13
14
NP (COPD)
1.78
150/70
MMD
Bypass/EMS
NP (N&V)
105/50
MMD
Bypass/EMS
33.04/47.60
14.56
125/65
MMD
Bypass/EMS
91.74/84.79
⫺6.95
110/60
MMD
Bypass/EMS
48, M
28.62/23.98
⫺4.64
140/80
MMD
Bypass/EMS
22, F
43.66/65.32
21.66
120/60
MMD
Bypass/EMS
15
47, M
63.90/56.24
⫺7.66
160/90
MMD
Bypass/EMS
16
64, M
43.56/50.54
6.98
140/60
MMD
Bypass/EMS
17
59, M
NP (N&V)
NP (N&V)
120/60
L ICA occlusion
Bypass
18
50, M
54.59/54.5
⫺0.09
140/70
L ICA occlusion
Bypass
19
63, F
37.06/27.28
⫺9.78
130/60
R ICA stenosis
Bypass
20
50, F
58.42/70.72
12.3
130/70
R ICA occlusion
Bypass
21
72, M
69.60/67.76
⫺1.84
140/70
R ICA occlusion
Bypass
22
65, M
42.55/50.70
8.15
120/60
L ICA occlusion
Bypass
23
67, M
43.40/30.59
⫺12.81
140/70
L ICA stenosis
Bypass
24
65, M
41.44/31.00
⫺10.44
140/70
R ICA occlusion
Bypass
25
53, M
53.10/60.96
7.86
110/60
R ICA T-stenosis
Bypass
26
43, F
35.36/33.35
⫺2.01
110/50
L ICA occlusion
Bypass
27
38, F
55.90/69.56
13.66
120/80
R ICA stenosis
Bypass
28
60, F
42.35/61.06
18.71
130/60
R ICA stenosis
Bypass
29
48, M
40.30/47.36
7.06
140/70
R ICA occlusion
Bypass
30
51, F
58.22/45.44
⫺12.78
140/80
R ICA occlusion
Bypass
31
39, F
NP
NP
140/80
R MCA aneurysm
Clipping
32
60, F
NP
NP
125/60
R MCA aneurysm
Clipping
34
62, F
NP
NP
120/55
Cerebellar tumor
Resection
35
55, M
NP
NP
120/70
R MCA aneurysm
Clipping
36
47, F
NP
NP
144/80
R MCA aneurysm
Clipping
37
57, F
NP
NP
120/70
R MCA aneurysm
Clipping
38
49, M
NP
NP
130/70
L MCA aneurysm
Clipping
39
68, M
NP
NP
130/70
L MCA aneurysm
Clipping
40
40, F
NP
NP
125/60
R MCA aneurysm
Clipping
41
50, M
NP
NP
135/70
L MCA aneurysm
Clipping
M indicates male; F, female; NP, not performed; COPD, chronic obstructive pulmonary disease; N&V, nausea and vomiting; Bypass, standard
extraintracranial arterial bypass; EMS, encephalomyosynangiosis; R, right; L, left; ICA, internal carotid artery; and MCA, middle cerebral artery. A
negative CVRC value indicates steal phenomenon during acetazolamide stimulation.
Extracranial-intracranial bypass surgery has been shown to
restore CVRC and thus, represents an efficient treatment
option for patients with such reductions.11 Especially in
MMD, surgical revascularization represents a very effective
treatment option for restoring CBF and for preventing cerebral ischemia. In MMD, cortical microvascularization is of
special interest, as Takeuchi et al4 described surgically
exposed cortical surfaces that appeared reddish intraoperatively due to multiple leptomeningeal anastomoses and dilated pial arteries. Our surgical experience in the treatment of
MMD confirms this observation.2
Intraoperative ICG videoangiography allows excellent visualization of cortical vascularization and has already been
applied successfully to study cortical perfusion after decom-
Czabanka et al
ACVD
Control
A
Cortical Microvascularization in Adult Moyamoya Disease
MMD
B
15
10
5
Control ACVD MMD
Microvascular surface (%)
*
Microvascular diameter (mm)
20
100
0,4
#
0
*#
0,3
0,2
0,1
*#
80
60
18
16
14
20
0
0,0
Control ACVD MMD
AMVTT
VMVTT
MVTT
Control ACVD MMD
*#
12
*#
10
8
6
4
2
0
Control
Figure 2. A, Photographs of intraoperative cortical microvascularization and corresponding ICG
videoangiograms. B, Graphs of MD, D, and
microvascular surface per ROI. Left graph demonstrates MD in controls (n⫽10), ACVD patients
(n⫽15), and MMD patients (n⫽16). *#Significant
differences vs controls and ACVD patients,
respectively. Middle graph demonstrates D in
controls (n⫽10), ACVD patients (n⫽15), and
MMD patients (n⫽16). *#Significant differences
vs controls and ACVD patients, respectively.
Right graph demonstrates MVS per analyzed
ROI in controls (n⫽10), ACVD patients (n⫽15),
and MMD patients (n⫽16). *#Significant differences vs controls and ACVD patients,
respectively.
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pressive craniectomy for malignant stroke.5 Using this technique, we observed a 20% increase in MD paralleled by
significantly increased D and MVS in MMD patients,
whereas ACVD patients with a comparable ischemic deficit
displayed values comparable to those of controls. MMD has
significant neoangiogenic potential, which might explain our
observation of increased MD, D, and MVS.14,15 However,
until now, no molecular mechanism has been identified, and
it remains unclear whether MMD-associated neovascularization is a result of a distinct disease-related molecular pathway
or an adaptive mechanism to cope with impaired cerebral
hemodynamics.
Cerebral hemodynamics in MMD differs substantially from
hemodynamics in ACVD. First of all, MMD is defined by
bilateral steno-occlusive lesions of the basal cerebral arteries.16
ACVD does not refer to bilateral steno-occlusive lesions but it
Microvascular transit time (sec.)
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Microvascular density (cm/cm²)
25
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ACVD
MMD
Figure 3. Graph illustrating results for MVTT, AMVTT, and
VMVTT in controls (n⫽10), ACVD patients (n⫽15), and MMD
patients (n⫽16). *#Significant differences vs controls and ACVD
patients, respectively.
includes unilateral steno-occlusive lesions. In MMD, the posterior circulation may also be affected; therefore, compensation for
low CBF by cross-flow through the circle of Willis might be
more limited in certain MMD patients.
In atherosclerosis, leptomeningeal arteries and ophthalmic
collaterals play a major role in compensating for low CBF.17
In MMD, collateralization via the ophthalmic artery is not
possible, as the definition of MMD includes supraophthalmic
steno-occlusive lesions of basal cerebral arteries.7 However,
leptomeningeal anastomoses are also observed in MMD
patients and are regarded as significant contributors to the
collateral blood supply.18 We evaluated the vascular territory
of the middle cerebral artery in all cases except for one.
Leptomeningeal anastomoses are defined as arteries between
2 major cerebral arteries that supply 2 different cortical
territories.18 Therefore, cortical microvascularization according to our definition does not refer to leptomeningeal anastomoses. However, we expect similar effects, as observed in
our study, on the level of leptomeningeal anastomoses.
In contrast to ACVD patients, compensation for low CBF
in MMD is achieved by a unique MMD-specific neoangiogenic process. Neovascularization in the form of moyamoya
vessels at the base of the brain has been demonstrated to lead
to significantly increased CBF and cerebrovascular CO2
reactivity in the basal ganglia of MMD compared with
ACVD patients.19 Because cortical vascularization plays an
important role in regulating CBF,3 increased MD, D, and
MVS might exert significant effects on cerebral microhemodynamics and thus, contribute to the compensation for hemodynamic impairment. Increased MD, D, and MVS might
consequently compensate for the impaired CBF either by
increasing collateral blood flow or by reducing microvascular
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resistance. As mentioned earlier, MMD is characterized by
multiple stenotic lesions of the circle of Willis20,21; therefore,
increasing collateral blood flow might represent a rather
inefficient mechanism.7 In this scenario, decreasing microvascular resistance might be the more efficient mechanism
for compensating for impaired CBF.
To investigate cerebral microhemodynamics, we measured
MVTT, AMVTT, and VMVTT. According to our definitions,
MVTT indirectly represents microvascular blood flow velocity, as the time from maximum fluorescence intensity in A2 to
V2 vessels represents the time required for peak blood flow to
pass the cortical microvascularization. This parameter was
significantly increased in MMD patients compared with
ACVD and control groups. Our results are supported by
results from Taki et al,22 who demonstrated prolonged cerebral circulation time in MMD patients.
Cortical arterial microvascularization plays an important
role in regulating cerebral perfusion, as more than half of the
total cerebrovascular resistance is located in the extraparenchymal vessel segments.3 An increase in arteriolar resistance
vessels leads to an increase in microvascular cross-sectional
area and thus, decreased peripheral microvascular resistance.
Therefore, conductance of the microvascular segment in the
organ vasculature is increased, resulting in decreased blood
flow velocity. By measuring AMVTT and VMVTT, we were
able to localize the vascular compartment responsible for the
reduction in MVTT. According to our results, MVTT was
lost in the arterial compartment in MMD patients. The
observation of increased AMVTT in combination with increased MD, D, and MVS suggests decreased peripheral
microvascular resistance as the mechanism of choice. In
support of this hypothesis, Okada et al23,24 were able to
demonstrate diminished vascular resistance between cortical
arteries of the middle cerebral artery territory and the corresponding veins in MMD patients.
Moreover, there is experimental evidence that an increase
in cortical arterial microvascularization represents a suitable
mechanism for the compensation of reduced CBF. Schneider
et al25 demonstrated an increase in the number of extraparenchymal and intraparenchymal arterioles in response to application of granulocyte-macrophage colony stimulating factor
in a rat model of cerebrovascular occlusive disease. The
authors showed that increasing the number of pial arterial
resistance vessels led to decreased total peripheral resistance
and a concomitant restoration of CVRC.25
Therefore, we propose a potentially new compensation mechanism in MMD: ie, increased MD, D, and MVS at the level of
cerebral microvascularization, potentially resulting in decreased
peripheral vascular resistance. Further studies will be needed
to investigate and characterize the clinical significance of this
potential new compensation mechanism in MMD.
Summary
Intraoperative ICG videoangiography was used to investigate
and characterize cortical microvascularization and microhemodynamics in MMD compared with ACVD patients and in
subjects with normal cerebral microvascularization. On an
anatomic level, we demonstrated increases in MD, D, and
MVS in MMD patients compared with the other 2 groups. In
terms of microhemodynamic characteristics, we demonstrated increases in MVTT and AMVTT in MMD patients
compared with ACVD patients and controls. Our observations might represent an MMD-specific compensation mechanism for reduced CBF, either by increasing collateral blood
flow or by reducing peripheral vascular resistance.
Acknowledgment
We thank Peter Horn, MD, for revisions to the manuscript and
substantial advice.
Disclosures
None.
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Downloaded from http://stroke.ahajournals.org/ by guest on June 17, 2017
Characterization of Cortical Microvascularization in Adult Moyamoya Disease
Marcus Czabanka, Pablo Peña-Tapia, Gerrit A. Schubert, Johannes Woitzik, Peter Vajkoczy and
Peter Schmiedek
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Stroke. 2008;39:1703-1709; originally published online April 10, 2008;
doi: 10.1161/STROKEAHA.107.501759
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