The MRI Imaging of Cerebral Cavernous Malformation With
Practical Use of Diffusion Weighted Image
Nobukata
Kazawa, Yuta Shibamoto
Nobukata
Kazawa,Yuta Shibamoto, Department
of Radiology, Nagoya City University Hospital, 1 Kawasumi Mizuho Mizuho Ward, Nagoya City, Aichi prefecture, 467-0061, Japan
Correspondence to: Nobukata Kazawa, MD
phD, Department of Radiology, Nagoya City
University Hospital, 1 Kawasumi Mizuho Mizuho Ward,
Nagoya City, Aichi prefecture, 467-0061, Japan
Email: nobukaz@med.nagoya-cu.ac.jp
Telephone: + 81-052-853-8276
Received: March 14,
2015
Revised: April 10, 2015
Accepted: April 19, 2015
Published online: June 2, 2015
ABSTRACT
Aim: To evaluate the
significance of diffusion weighted image(DWI) of the cerebral cavernous
malformation in clinical practice.
Materials and Methods: Thirty patients with 66 lesions (multiple 5 cases) were
included in this study. The signal,
configuration, anatomical location, size, and the number on each T1WI, T2WI, FLAIR, T2WI*,
DWI, Gd (gadolinium)-T1WI,and the sequential signal change of DWI(central and
peripheral area in cavernoma)were recorded.
Results: The cerebral
cavernous malformation (CCM) shows the signal of various phase of hematoma
(hemorrhage)on both T1WI and T2WI MRI. On the diffusion weighted imaging (DWI),
they showed the marked low (43.3%)and mixed high and low signal intensity
(33.3%)even if they were very small appearing as areas of decreased signal
(black dots) on T2WI.The low intense signal area on DWI assumed to reflect the
hemosiderin or susceptibility effect and blood oxygen level dependent
(BOLD)effect by the deoxyhemoglobin and T2 black out effect. The transient high
signal foci on DWI were observed in 2(6.7%) cases in whom the intratumoral
(re)hemorrhage were suspected.
Conclusions: The CCM tends to
exhibit almost low signal intensity on DWI.DWI is a useful method like T2*WI
and SWI for the detection of the tiny CCM.
© 2015 ACT. All
rights reserved.
Key words: Cerebral cavernous malformation; Diffusion weighted
image; Intratumoral hemorrhage; Signal Intensity; Maganetic resonance image
Kazawa N, Yuta
Shibamoto. The MRI Imaging of Cerebral Cavernous Malformation With Practical Use of
Diffusion Weighted Image. International
Journal of Radiology 2015; 2(1): 24-28 Available from: URL:
http://www.ghrnet.org/index.php/ijr/article/view/1108
Introduction
The cerebral cavernous malformation(CCM) is thought to be congenital
abnormality of the cerebral vessels that affect 0.5% to 0.7% of the population[1,2].
It occurs in two forms: a sporadic form characterized by isolated lesions, and
a familial form characterized by multiple lesions with an autosomal dominant
mode of inheritance. As compared with computed tomography(CT) and angiography,
magnetic resonance imaging(MRI) was more sensitive in detecting cerebral
cavernous malformations. Therefore, MRI is the most reliable clinical choice
for the identification and follow-up of cavernous malformation. On T2-weighted
image of MRI, the combination of a reticulated core of mixed high and low
signals with a surrounding rim of low intensity suggests the diagnosis of a cavernous
malformation. In the clinical practice, DWI(diffusion weighted image) is a very
useful pulse sequence for the diagnosis of cerebral vascular disease including
acute infarction or tumor characteristics. It is ultrasensitive to the motion
of water protons and can detect ischemic lesions as early as 15 minutes after
an occlusion of artery. This is the first study evaluating the usefulness of
DWI of cerebral cavernous malformations(cavernoma).
Material
and Methods
In order to elucidate the characteristics of brain CCM on MRI imaging,
consecutive 30 patients of 2 institutions were evaluated. The mean age was
53.4±13.5 years (mean±SD), with a range of 23 to 87 years. In which open
surgical biopsies were performed on 3cases, and the total 66 lesions (multiple
5 cases) diagnosed by the CT/MRI with the clinical course were included in this
study. We excluded the tiny lesions smaller than 1mm in diameter or bright high
intensity spot only on T1WI, because we can not rule out the calcified lesions,
micro bleed scar, slow flow, stagnation or thrombosis of varying time course.
The examinations were performed from August 2007 to March 2011 at Yoshikawa
Hospital (n=15),and from April 2011 to December 2014 at NCU (Nagoya City
University) Hospital (n=15).In both institutions, MRI were scanned by
the same 1.5 Tesla supermagnestic unit [Intera Achieva(Philips Best
Netherland)].The IRB (Institutional Review Board) approval and the informed
consent of each patients were obtained in each institutions. The pulse sequences
and parameters were as follows; plain and gadolinium-DTPA enhanced T1WI
[TR/TE=600 msec/20msec flip angle (FA) 69 degree], T2WI (TR/TE=3000/100 FA 90),
fluid-attenuated inversion recovery (FLAIR) (TR/TE=6000/100 FA90IR 2000).
DWI(TR/TE/TI=3125-5050/70/230FA90,b=1000s/m2) and, GRE- T2*(T2*
SENSE TR/TE=600/20 FA15) (slice thickness 5mm 1mm gap) or EPI-T2* WI
(TR/TE=1071.2/14.148 FA 90) were scanned in all patients. The DWI signal and
sequential change were also evaluated on all lesions .Susceptibility weighted
imaging(SWI TR/TE=28/20, FA15 acquisition matrix 384×202) were scanned
in 12 lesions of 9 patients manly due to the restriction of the scan time.
Plain time-of-flight (TOF) MR angiography (TR/TE=17/6904 FA20.1.2mm space gap
0.6mm were scanned in 15 cases, CT(MDCT) (slice thickness5-7mm) examinations
were also performed in 15 lesions of 9 cases. The signal,configuration,
anatomical location,size,and number on eachT1WI,T2WI,FLAIR,T2WI*, DWI, Gd
(gadolinium) enhanced -T1WI,SWI and their sequential signal changes,especially
DWI were recorded.
Results
The site of the lesions were as follows; medulla oblongta1,
medulla/pons 2, pons3, midbrain/pons1 middle brain3, cerebellum18,
thalamus4,internal capsule2, basal ganglia6, frontal lobe10, parietal lobe6,
temporal lobe6, occipital lobe4 (Table 1). In cerebral parenchyma,almost all
lesions were located in the deep white matter or subcortical white matter
measuring about 4mm- to 23×19×17mm (mean 8.4mm)
in diameter. The so-called mass effect (peri-tumoral edema)were only seen in 3
cases (5.2%). The hemorrhage perforated to the aqueduct of midbrain and
subarachnoid hemorrhage was observed in each one case. On T1WI ,they showed
low(n=10),slightly low-iso (n=24), high and low mixed (n=16),
high (n=16) intensity. On T2WI, they exhibited low (n=30), mixed
(n=27) (Figure 1, 2),slightly high (n=4) and very high (n=5)
signal intensities. T2WI low intensity rim (Figure1) and permeative peripheral low
signal area outside the tumor were observed in 30 (45%) and 5 lesions (7.6%).On
FLAIR images, they exhibited indistinct (n=8), low (n=24), mixed
(n=31) (Figure 2), and high (n=3) signal intensities. On T2WI*
indistinct (n=10), low (n=34), mixed (n=19), and high (n=3)
signal intensities were observed. On the diffusion weighted imaging
(TR/TE/FA=3125-5050/70/90. b=1000sec/mm²), they showed indistinct (n=3,
10%),marked low intensity (n=13, 43.3%) (Figure1), mixed high and low
intensity [n=10, 33.3% (central high and peripherally low=6, 20%)], high
intensity (n=2, 6.7%) (Table 2). In both 2 cases, transient high signal
were observed in which we suspected intra-lesional hemorrhage (Figure 2).
The signal was
decreased and unclear with residual ambiguous peripheral low signal rim after17
days.
On CT,they exhibited
low(n=1),iso(n=3), and high(n=11)density (Figure1). The
calcification(old clot or dystrophic calcification)were observed in 5 (33.4%)
of 15 CT scanned lesions. In 32
lesions of 11 (48.4%)cases,they showed multilobular cystic round nodule or mass
lesion.And uni-locular single nodular lesions were observed in 34 lesions of 19
(51.5%) cases.
Discussion
The cerebral cavernous malformation(CCM) is usually composed of large
sinusoidal vascular spaces closely clustered together. There is no normal
intervening tissue and the dilated sinusoids lack normal endothelial tight
junctions. In the advent of endovascular surgery, cerebrovascular malformations
have recently been reclassified according to the presence of arteriovenous
shunting within the malformation. Therefore, AVM, dural A-V fistula,vein of
Galen malformation,developmental venous anomaly(DVA) (venous malformation),CCM
and capillary telangiectasia are classified.The CCM was composed of dilated capillary
blood vessels(angiogenically immature lesions with endothelial proliferation)
and is separated by normal neural tissues.This lack of a normal endothelium
readily allows leakage of blood elements. The CCM represents about 15% of all
vascular malformations with an estimated incidence of about 0.1 percent1-2).
Not all CCM are associated with symptoms, but once they become symptomatic 40
to 50 percent present with seizures, 20 percent with focal neurological
deficit, and 9-10 percent with hemorrhage[1,2]. The risk of
hemorrhage has been estimated between 0.2and 2.5% per lesion per year[3].
These number may be higher for patients with brain stem CCM[4] and
the symptoms may worse when it occurs.
Most of the
lesions are supratentorial in location.However,in 10-25% are infratentorial(the
cerebellum or brain stem). According to the MRI study of autopsied cases,
cavernoma exists in 0.4-0.7% of all subjects .They are often found in 3-5
decades and multiple CCMs are seen about 15-50% (up to 80% of affected family
members) of patients[3,5]. Familial form is inheritated as an
autosomal dominant trait with variable expression. The mutation of genes
(CCM1-3) have been mapped at as follows; KRIT1 of CCM1 at
7q11.2-q21,malcavernin of CCM2 at 7p15-p13, PDCD10 of CCM3at 3q26-1. The
developmental venous anomaly(DVA) so called venous angioma are sometimes noted
in association with cavernomas[6]. In CCM, angiography is usually
normal,although prolonged injection may demonstrate an abnormal capillary blush[7].
CT findings
consist of iso to high density area/mass and often partially calcified lesion
which shows mild to moderate enhancement except the thrombosed portions. The
lesion shows no mass effect or surrounding edema except when recent hemorrhage
or enlargement has occurred.
The MRI
appearance of cerebral cavernous malformation (CCM or cavernoma) has been well
described. The typical CCM is a mixed signal lesions on all sequences encircled
by a hemosiderin/ferritin rim. because they contain blood products at various
stages of evolution like our study. Usually CCM shows no mas effect except
rapid growth or intratumoral hemorrhage in our study because it is a kind of
benign vascular hamartoma histologically. Their appearances have been described
as resembling “popcorn “or”mulberries” and can be enhanced by gradient –echo
imaging. The T1WI high intensity foci was occasionally observed. It was thought
to reflect the extremely slow flow or stagnation or thrombosis of varying
stage(mainly subacute phase). Encapsulated hematoma or resolving hematoma were
also mimicking lesions on MRI images. An MRI classification for CCM has been
proposed which combines the MRI findings with clinical and pathological
characteristics[10,11]. That is: type 1 lesions are characterized by
subacute hemorrhage and exhibit a hyperintense core onT1WI (methemoglobin),
whereas on T2WI the initial hyperintense signal changes to hypointensity in
time with a faint hypointense rim.
The hemorrhage are
ongoing in repetitive processes. The type II lesions demonstrate loculated
areas of hemorrhage of varying age and thrombus surrounded by gliosis and
hemosiderin. On T1 and T2WI a reticulated core with high and low signal
intensities is seen surrounded by gliosis and/or hemosiderin. On T1 and T2WI a
reticulated core with high and low signal intensities (Figure2) was surrounded
by a hypointense ring. Clinically these lesions are active, and thrombosis and
hemorrhage are ongoing in a repetitive process, The type III lesions represent
chronic mostly inactive lesions with residual hemosiderin in and around the
lesions creating hypointensity on T1 and T2WI.The type IV lesions are poorly
visualized on T1 and T2 and are best seen with gradient echo sequences as small
punctuate hypointense foci. Subacute hemorrhage associated with a
microarteriovenous malformations or brain tumor may mimic a type I lesions, and
follow-up MRI and angiography is indicated under such circumstances. The type
II lesions were thought to be pathognomonic for cavernoma, but thrombosed AVM and
hemorrhagic metastases may have a similar appearance[12], type III
and IV lesions may be mimicked by radiation-induced telangiectasis[13].
T2* W I which
is sensitive to inhomogeneity of magnetic field represents the apparent T2 due
to dispersion of spins on the rotating frame.
Susceptibility
weighted imaging(SWI) is derived from the paramagnetic susceptibility effect in
order to visualize venous structures and iron in the brain and to study diverse
various conditions. However, structures with higher susceptibility effect
appear significantly larger than their actual size. Although, CT has proved to
be more sensitive than MRI in delineating
small calcified lesion besides fresh hemorrhage. Both CT and MRI can be
used in the follow-up of patients with known cavernous malformation in particular when hemorrhagic events are suspected because
CCM probably undergo occult hemorrhage. Thus,diffusion weighted MRI signal is
helpful in predicting intratumoral bleeding(acute-subacute hemorrhage) which
occur mostly within the core area as we often observed in the patients of the
cerebral hemorrhage (Table 3). And the low intense signal area on T2WI assumed
to reflect the hemosiderin leakage to the brain parenchyma.
Due to the
magnetic susceptibility effect and deposition of deoxyhemoglobin or
methemoglobin induced by slow flow in CCM they show the low signal intensity on
T2*WI(BOLD: blood oxygenation level dependent) effect[14]. T2
shortening can also be produced by hemoglobin concentration and clot
retraction. Therefore, the differential diagnosis of CCM from the viewpoint of
MRI signal are as follows;chronic hemorrhage, thrombosed AVM,developmental
venous anomaly,hemorrhagic brain meta (renal cell carcinoma,lung
cancer,melanoma etc.), amyloid angiopathy,microanurysm or microbleed related
with angitis, radiation induced cerebral hemorrhage,coaglopathy (DICetc.),
toxoplasmosis (calcified granuloma).
The low
intense signal area on DWI assumed to represent the hemosiderin or
susceptibility effect and blood oxygen level dependent (BOLD) effect by the
deoxyhemoglobin of hematoma Moreover there are some characteristics of its
local extension; no apparent mass effect (peri-focal edema) or no apparent
interval growth except hemorrhagic events. On DWI they usually showed high
signal due to the highly viscosity due to change of the concentration of
hemoglobin or diminishment of the extra celluar space by the regression of
thrombus[8].
However,
excessive deoxyhemoglobin and methhemoglobin evoke the susceptibility effect
like hemosiderin. They show low signal on T2WI and T2* WI (called as T2 black
out phenomenon), old hemorrhage shows very low signal on DWI and ADC map due to
the effect of T2* relating hemosiderin.
The low signal
area of GRET2* weighted images and DWI is more broad than that of T2WI due to the effect of
susceptibility blooming and diffusion of hemosiderin/ferritin into the adjacent
brain parenchyma. The GRE images showed marked low signal by the susceptibility
and blood oxygen level dependent(BOLD)effect by the deoxyhemoglobin[16].
The defection rate of GRE T2*WI on intracranial hemorrhage was 1.9 fold higher
than that of CT,especially in the brainstem and cerebellum where beam hardening
artifact occurs on CT[15]. As a matter of fact, we could recognize
CCM more easily in DWI images than the conventional MRI scan. The transient
high signal foci were observed in 2 cases that intratumoral (re)hemorrhage were
suspected. So,we also think diffusion weighted MRI signal is helpful in
predicting intralesional bleeding(acute-subacute hemorrhage) which mostly occurwithin the core area which
observed in cases ofcerebral hemorrhage cases in our preliminary data (Table3).
In comparison
with hypertensive hemorrhages which frequently occurs at basal
ganglia,thalamus,cerebellar hemisphere,and pontine (brain stem) ,its locations
were more diverse in CCM. And cerebral subcortical locations which are
frequently observed in amyloid angiopathy were only observed in 6 (9.1%) cases
in our study.
The major
discriminating points between the hemorrhagic metastatic tumor such as renal
cell carcinoma or melanoma are as follows;the absence of the perifocal edema
and the presence of T2WI low intense rim. In addition, DWI assumes to be able
to detect more easily and sensitively the hyperacute or late subacute phase of
intra and/or perilesional hemorrhage as a high intensity foci than the
conventional T1WI and T2WI.The limitation of this study was that: although 2
subjects were suspected of recent intratumoral hemorrhage, there were no
evidence because the high signal change were diminished spontaneously.
Therefore, we have to perform the DWI scan in all patients in clinical
follow-up with CCM. Of course, DWI is also thought to be useful in detecting
the secondary peritumoral ischemia or infarction due to the high sensitivity
for the cytotoxic edema.
Conclusion
The cerebral cavernous malformation (CCM) shows the signal of various
phase of hematoma (hemorrhage) on both T1WI and T2WI MRI. On the diffusion
weighted image (DWI), they tend to show the very low signal intensity by the
BOLD effect of the deoxyhemoglobin and T2 black out effect. So by using DWI, we
can detect CCM more easily than the conventional MRI scan with T1WI, T2WI,
FlAIRwith/without T2*WI.
The low signal
area of DWI is more broad than that of T2WI due to the effect of susceptibility
blooming and leak of hemosiderin/ferritin into the adjacent parenchyma. The
transient high signal foci were observed in 2 cases in whom
intratumoral(re)hemorrhage were suspected. DWI is a useful method like T2*WI
and SWI for the early detection even if they are very small and has the ability
to know the occurrence of the intratumoral hemorrhage (bleeding) or the
secondary infarction.
CONFLICT OF INTEREST
The author of the manuscript entitled ‘The MRI Imaging of Cerebral
Cavernous malformation with Practical Use of DWI(diffusion weighted image)’
declare that there is no conflict of interest with regard to equipment,
contrast materials.
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Peer reviewers: Hui-Xiong Xu,
Professor, Department of Medical Ultrasound, Shanghai Tenth People's Hospital,
Tenth People's Hospital of Tongji University, No. 301 Yanchangzhong Road,
Shanghai, 200072, China; Lin Ma, Professor, Department of Radiology, PLA
General Hospital, 28 Fuxing Road, Beijing 100853, China.
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