Topical Reviews

Section Editors: Larry Goldstein, MD, FAAN, FANA, FAHA, and Anne Abbott, PhD, MBBS, FRACP

Neuroimaging in Intracerebral Hemorrhage

Federica Macellari, MD; Maurizio Paciaroni, MD; Giancarlo Agnelli, MD; Valeria Caso, PhD, MD

I ntracerebral hemorrhage (ICH) is described as spontaneous

extravasation of blood into the brain parenchyma. This clinical
entity is present in 10% to 15% of all stroke cases1 in the Western
population, with reported incidence rates higher in Asia.24 It is
also associated with a higher mortality rate compared with either
ischemic stroke (IS) or subarachnoid hemorrhage.5
ICH is classified according to its primary (80% to 85%)
or secondary (15% to 20%) causes. More than 50% of pri-
mary ICH events are directly correlated with hypertension
as a risk factor, whereas 30% are known to be associated
with cerebral amyloid angiopathy (CAA). The causes of
secondary ICH include hemorrhage conversion of IS, amy-
loid angiopathy, stimulant drugs, vascular malformations
(aneurysms, arterovenous malformations, venous angioma,
cavernoma, dural arteriovenous fistula), coagulopathy (hered-
itary, acquired, induced by anticoagulants or antiplatelets),
neoplasms, trauma, vasculitis, Moyamoya disease, or sinus
venous thrombosis (Table1).
Currently, ICH is classified as either primary or secondary
according to only causes. However, this classification does not
take into account the inherent differences of underlying vascu-
lar pathologies. Hence, a more systematic stratification based
on new criteria is currently being developed.1 Specifically,
Meretoja etal6 have proposed the SMASH-U classification,
based on the underlying diseases of ICH: Structural lesions
(cavernomas and arterovenous malformations), Medication
(anticoagulation), Amyloid angiopathy, Systemic diseases
(liver cirrhosis, thrombocytopenia, and various rare conditions),
Hypertension, and Undetermined causes. This classification
has proven to be feasible and is also associated with survival
prognosis.6 Another classification used in clinical practice dis-
tinguishes between deep and lobar ICHs according to location.
Deep ICHs are located in the basal ganglia, thalamus, internal
capsule, cerebellum, or brain stem and are generally related to
hypertension. Whereas, lobar ICHs usually require more exten-
sive diagnostic testing because of their wider range of causes.7
Regarding clinical outcome, ICH is commonly characterized
by hematoma expansion and early neurological deterioration
within the first few hours of onset.8 Thus, rapid management
including diagnostic work-up needs to be performed.
We reviewed the available neuroimaging tools for ICH, as
well as the changes in ICH in response to blood breakdown
products, seen on CT and MR at various stages (Table2).9 Both
catheter angiogram and CT angiography (CTA) methods were
also analyzed and compared for their advantages in different
clinical situations. The purpose of our neuroimaging review
of ICHs was to provide a framework for choosing a rational
diagnostic imaging plan, taking into account the clinical char-
acteristics of the presenting patients. Because of the fact that
a myriad of imaging modalities is available, it is important to
understand the indications and limitations of each technique
in order to select the most appropriate study for each patient.
Computed Tomography
Contemporary CT, including noncontrast CT (NCCT), per-
fusion CT, and CTA, is generally used for hyperacute stroke
imaging. In fact, NCCT is commonly used in an emergency
room setting for acute stroke because of its convenience and its
high sensitivity for detecting ICH, which is a contraindication
to thrombolytic therapy.10 Moreover, NCCT allows to quantify
hematoma volume and monitor hemorrhage evolution in ICH
accurately.11 That is, ICH volume can be calculated by using the
ABC/2 method,12 derived from an approximation, according to
the formula for ellipsoids, where A is the greatest hemorrhage
diameter; B, the diameter at 90 to A; and C, the approximate
number of CT slices with hemorrhage multiplied by slice thick-
nesses13 (Figure1). Nonetheless, some studies assessing the
reliability of the ABC/2 method have shown that it produces
a larger percentage of error compared with other measure-
ment techniques, particularly for irregular-shaped objects.14
In fact, comparing the ABC/2 method with the manual plani-
metric method, the former consistently overestimated infarct
volume by a median false increase of 7.33 cm3.15 Whereas,
the Quantomo method for quantitative tomography has been
reported to more reliably detect smaller changes in ICH volume
compared with the ABC/2 method. This is because Quantomo
method measures the geometry of individual hematoma vol-
umes, whereas the ABC/2 method approximates all hema-
toma volumes such as ellipsoid.16 To this regard, Huttner etal12
reported an overestimation of 32.1% in hematoma volume cal-
culations for irregular and dichotomized shapes of hematomas
among ICH patients with a history of warfarin use. Both initial
hematoma volume and hematoma growth are independent pre-
dictors of clinical outcome and mortality.8,17 To date, though the
ABC/2 method is the most readily available assessment at bed-
side, protocols for accurate assessment of hematoma volume

Received September 30, 2013; final revision received November 28, 2013; accepted December 3, 2013.
From the Stroke Unit and Division of Cardiovascular Medicine, University of Perugia, Perugia, Italy.
Correspondence to Valeria Caso, PhD, MD, Stroke Unit and Division of Cardiovascular Medicine, University of Perugia, Santa Maria della Misericordia
Hospital, Sant Andrea delle Fratte, 06126 Perugia, Italy. E-mail vcaso@hotmail.com
(Stroke. 2014;45:903-908.)
2014 American Heart Association, Inc.
Stroke is available at http://stroke.ahajournals.org DOI: 10.1161/STROKEAHA.113.003701

903
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904StrokeMarch 2014

Table 1. Intracerebral Hemorrhage (ICH) Classification
According to Causes
Primary Causes Secondary Causes
Hypertension Hemorrhage conversion of ischemic stroke
Cerebral amyloid angiopathy Stimulant drugs
Vascular malformation
Aneurysms
Arteriovenous malformation
Venous angioma
Cavernoma
Dural arteriovenous fistula
Coagulopathy
Hereditary
Acquired
Iatrogenic (anticoagulants, antiplatelets)
Neoplasms
Trauma
Vasculitis
Moyamoya disease
Sinus venous thrombosis
and its characteristics should be incorporated into the CT scan-
ner consoles, because this can allow the operator to obtain such
information accurately in a timely manner.14 CT scan is also
able to determine the approximate age of hematomas, by eval-
uating for the density of the lesions measured in Houndsfield
units, according to the value of x-ray attenuation corrected for
the attenuation coefficient of water. The Houndsfield units for
water is equal to 0, blood is between 30 and 45, gray substance
is between 37 and 45, white substance is between 20 and 30,
whereas bone is between 700 and 3000.18,19 At onset, hematoma
is commonly seen as uniform and smooth hyperintense signals
on CT. Over the course of the first 48 hours, large hematomas
tend to show fluid levels, indicating that they are not solidified
yet.20 To this regard, fluid blood levels have been defined as a
horizontal interface between hypodense bloody serum layered
above hyperdense settled blood. Fluid blood levels in acute ICH
are moderately sensitive (59%) to the presence of coagulopa-
thy (ie, abnormal prothrombin time and partial thromboplas-
tin time) and highly specific (98%) for this condition.21 Blood/
fluid levels are also frequent in thrombolysis-related ICH and
associated with higher hemorrhage volumes.22 Over the first 72
hours, a hypodense region can be detected around lesions, as a
result of the edema that surrounds the brain tissue; a noteworthy
mass effect can be detected as well. Three to 20 days after onset,
the lesion area tends to shrink and become less intense, los-
ing 1.5 Houndsfield units per day. The periphery of the lesion
tends to take on an uneven profile, which acquires a pseudoab-
scess (ring-like) appearance, as seen on contrast. Reductions in
edema and mass effect can also occur up until the ninth week,
when only a confined region of modest hypodensity can be
observed on CT.23
Contrast-enhanced CTA is able to identify patients at high
risk of hemorrhage enlargement (HE), by revealing a spot
sign, which is a contrast medium extravasation within the
hematoma.24 Spot sign is highly predictive of HE and has been
reported to have a positive predictive value of 73%, a negative
predictive value of 84%, sensitivity of 63%, and specificity of
90%.25 HE usually occurs in 30% of patients with ICH <3 hours
of symptom onset,26 and the frequency of spot sign is highest
in patients presenting <3 hours, but its accuracy in predicting
HE remains high, regardless of time from symptom onset.27
Furthermore, spot sign is associated with poor prognosis, high
rates of early clinical deterioration, high mortality, more severe
clinical presentation, and decompression of the hemorrhage into
the intraventricular space.25,2833 ICH volume 30 cm3 together
with Glasgow Coma Scale score, presence of intraventricular
blood, and age 80 years have been included as independent
variables for 30-day mortality in the ICH score developed by
Hemphill etal.34 The utility of detecting the spot sign on clinical
decision making and outcome improvement remains question-
able. So, patients with spot sign are amenable to other studies,35
with the purpose of demonstrating the feasibility of CTA in
the hyperacute phase and the reliability of spot sign in emer-
gency setting for guiding the therapy with factor VII or other
prothrombotic to avoid HE and, therefore, a worse outcome.36
CTAs performed <96 hours from symptom onset have a
high accuracy for predicting underlying vascular anoma-
lies, with sensitivities 95% and specificities approaching
100%. Positive and negative predictive values have also been
reported to be in excess of 97%.37,38 Even so, CTA exposes
patients to the risks of radiation, as well as risks associated
with contrast-induced nephropathy (CIN) and allergic reac-
tion, which can lead to death. Furthermore, the risk of contrast
on bloodbrain barrier permeability has unknown effects on
bleeding risks and the worsening of vasogenic edema.3943
CIN is defined as a 25% elevation from baseline serum
creatinine levels or an absolute increase of 0.5 mg/dL <48 to
72 hours of contrast administration.44 CIN is associated with

Table 2. Appearance of Intracerebral Hemorrhage on Noncontrast CT (NCCT) and MR by Stage9

Phase of Blood NCCT T1-Weighted MR T2-Weighted MR T2*-Weighted MR
Hyperacute Oxyhemoglobin Smooth, hyperdense Hypointense or isointense Hyperintense Marked hypointensity
Acute (1248 h) Deoxyhemoglobin Hyperdense with fluid levels Isointensity or slight hypointensity Hypointense with Marked hypointensity
with thin hyperintense rim in the hyperintense
periphery perilesional rim
Early subacute Methemoglobin Hypodense region of edema Hyperintensity Hypointensity Hypointensity
(72 h) intracellular with mass effect
Late subacute Methemoglobin Less intense with ring-like Hyperintensity Hyperintensity Hypointensity
(320 d) extracellular profile
Chronic (9 wk) Hemosiderin and Isodense or modest Hypointensity Hypointensity Hyperintense or isointense core
ferritin confined hypodensity surrounded by hypointense rim

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Figure 1. Intracerebral hemorrhage evidenced on CT (ABC/2
formula by CT).
5-fold higher risks of prolonged hospitalization and mortal-
ity.4547 In an emergency setting, it is neither feasible to adopt
preventive measures such as prehydration with the addition
of acetylcysteine48nor possible to fully know patient history.
However, the incidence of CIN, even in emergency settings,
has been reported to be low (2%).49
Magnetic Resonance
Stroke MR protocols should include T1, T2, T2* or gradient echo
(GE), fluid-attenuated inversion recovery, contrast-enhanced,
diffusion-weighted, and p erfusion-weighted images, as well
as MR angiography.50 The appearance of ICH on MR is pri-
marily affected by the age of hematoma, as well as the type
of MR contrast used. The substrate responsible for early
hemorrhage identification on MR scan is deoxyhemoglobin,
a blood degradation product with paramagnetic properties,
because of its unpaired electrons. On GE images, a few areas
of hyperintensity can be detected in the lesion core, and of
these, most are usually surrounded by hypointense bound-
aries. Hyperintense signals are commonly found bordering
the central lesion on T2-weighted and GE images, whereas
a hypointense signal is commonly observed on T1-weighted
images, thereby indicating perifocal vasogenic edema.50
There is strong evidence supporting the diagnostic accuracy
of MR in the hyperacute setting51,52 even after only 20 min-
utes of symptom onset.53 A randomized trial investigating the
role of MR in detecting ICH54 has reported that hyperacute
ICH is detectable with excellent accuracy even when the rat-
ers had only limited experience. Moreover, GE is as sensitive
as NCCT in the detection of acute ICH, whereas a complete
MR in patients with acute stroke has higher sensitivities for IS
(diffusion-weighted imaging sequences) and chronic hemor-
rhage.55,56 However, in the case of minor bleeding, GE MR
may not be sufficient to distinguish acute bleeding from
chronic bleeding (ie, microbleeds [MBs]), and for this, NCCT
should be performed.56 Furthermore, patient factors (ie, clini-
cal instability, presence of pacemaker, claustrophobia) and
hospital factors (availability of MR) may cause obtaining an
MR impossible or impractical in the acute setting, and there-
fore, NCCT remains the neuroimaging modality of choice for
the diagnosis of acute stroke.57,58
MR is also a neuroradiological tool for distinguishing
between hemorrhagic transformation and primary ICH.
In fact, most HTs are smaller than their fields of ischemic
infarct; thus, MR can provide information on nonhemorrhagic
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Macellari etal Neuroimaging in ICH 905
regions and evidence whether blood is within the larger isch-
emic infarct.59 A primary hematoma tends to be round and
have a larger surrounding edema than would be seen on IS.
Furthermore, hematomas do not necessarily respect vascular
territories.59 In case of hemorrhagic transformation of IS, MR
angiography can identify the location of vascular occlusion.
MR has a high diagnostic rate for detecting underlying
causes of secondary hemorrhages, including vascular mal-
formations, tumors, and cerebral vein thrombosis, as well as
a high diagnostic yield for young patients having lobar ICH
and no history of hypertension.60 Thus, MR is the most sen-
sitive tool for detecting cerebral venous thrombosis in the
acute, subacute, and chronic phases.61 Contrast-enhanced MR
venography is able to show the thrombosed segment of the
venous sinus and is generally well correlated with conven-
tional angiographic findings.62 It also assists in distinguishing
anatomic variants, such as a hypoplastic sinus, from cerebral
venous thrombosis.63
MR is the most sensitive and specific neuroradiologic
modality for detecting cavernomas, the abnormal capillary-like
vessels with intermingled connective tissue whose rupture
can lead to ICH.64 Cavernoma has a hyperintense popcorn
balllike appearance at T2-weighted imaging. The central
component, hyperintense, indicates subrecent bleeding; the
hypointense halo consists of hemosiderin and is the outcome
of remote bleeding.
With MR, it is possible to detect previously existing and
clinically silent cerebral MBs that are not detectable on CT.
MBs provide a lifetime history of hemorrhage. MBs are small
dot-like lesions having a hypointense appearance on GE
sequences and are usually smaller than 5 to 10 mm (Figure2).
Pathological studies have proven that MBs correspond to
hemosiderin-laden macrophages adjacent to small vessels,
suggesting previous extravasations of blood. MBs can have
numerous types of mimics, such as the calcification of the
basal ganglia, diffused axonal injury, metastatic melanoma,
cavernous malformation, and small perforating arteries.65
MBs are considered markers of vascular pathology, includ-
ing hypertensive vasculopathy and CAA, as identified from
histopathologic analyses of the vessels surrounding MBs.
Furthermore, MBs have been reported to be predictors of
ICH in prospective observational studies on both ICH66,67 and
IS.68,69 MBs can indicate bleeding-prone angiopathy and a high
rate of hemorrhagic transformation in patients on anticoagu-
lation, antithrombotic, or thrombolytic therapies.70 However,
Figure 2. Intracerebral hemorrhage evidenced on gradient echo
MR in patients with deep microbleeds (black arrows).
906StrokeMarch 2014

MBs are thought to be more than markers for minor episodes
of cerebrovascular extravasation. In fact, a recent pathologi-
cal study by Janaway etal71 has reported that a large putamen
haemosiderin, correlated with more MBs, was significantly
associated with putaminal indices of small-vessel ischemia
(microinfarcts, arteriolosclerosis, perivascular attenuation),
as well as lacunes in each examined brain region but neither
with large-vessel disease nor whole-brain neurodegenerative
pathologies. These findings suggest that basal ganglia MR
MBs are a surrogate for ischemic small-vessel disease rather
than exclusively a hemorrhagic diathesis.
Lobar localization of MBs and their associations with lobar
ICH, especially in the elderly patients, render MBs possible
indicators of CAA. To this regard, the Boston criteria for prob-
able CAA specify that this diagnosis should not be made when
MBs are located in the basal ganglia, thalamus, or brain stem,
the regions atypical for CAA pathology.72
MR angiogram/venogram along with CT angiogram/veno-
gram are reliable tools for confirming secondary causes of
hemorrhage. Thus, these are reliable substitutes for catheter
angiogram, which is an invasive procedure that is not always
readily available. In fact, catheter angiogram is associated
with the risks of transient and permanent neurological deficits,
0.9% and 0.5%, respectively.79 It is expensive and time- and
labor-intensive, as well as requires patient cooperation, a sta-
ble patient condition, and continuous monitoring. Radiation
doses of catheter angiography (5 times higher than CTA)80 are
delivered to both patients and operators. For this reason, CTA
should be considered the better initial screening approach for
identifying secondary vascular lesions, compared with cathe-
ter angiogram.81 Nonetheless, catheter angiogram remains the
diagnostic tool of choice for the treatment of aneurysms and
arteriovenous malformation (Figure3).

Catheter Angiogram
Subarachnoid hemorrhage, atypical (noncircular) hematoma
configuration, edema out of proportion seen on CT at admis-
sion, unusual hemorrhage location, or the presence of other
abnormal structures in the brain, including masses, are all dis-
tinctive radiological features of secondary causes of ICH.10 In
these cases, a catheter angiogram is necessary to best reveal
underlying conditions, including arteriovenous malforma-
tions, Moyamoya disease, tumors, vasculitis, reversible cere-
bral vasoconstriction syndrome, and cerebral vein thromboses.
Angiography may also be indicated in patients with no
obvious cause of bleeding. The angiographic yield has shown
to be significantly high in young patients without pre-existing
hypertension.73 Young age followed by the absence of hyper-
tension and lobar hemorrhage have been proven to be the main
factors influencing diagnostic choices in clinical practice.74
The presence of intraventricular hemorrhage in patients with
acute spontaneous ICH is not associated with an increased risk
of an underlying vascular lesion and should not be used to
select patients for neurovascular evaluation.75 Timing of cere-
bral angiography should take into consideration the clinical
state of the patient and the neurosurgeons judgment regarding
urgency of surgery.76 There is a tendency to perform diagnos-
tic investigations <1 or 2 days in younger patients.74 Delayed
angiography can also show unexpected underlying structural
lesions in patients without radiological suspicion of second-
ary causes of ICH,77 and therefore, a follow-up angiography
should be considered for all patients with a first-negative
angiogram, in the absence of a specific cause of hemorrhage.78

Figure 3. Catheter angiogram: Left temporal arteriovenous mal- Figure 4. Diagnostic work-up flowchart of intracerebral
formation before and after treatment (black arrows). hemorrhage.

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Conclusions
An optimal neuroradiological diagnosis and management
of ICH requires more than defining the size, location, and
presence of intraventricular blood. In fact, knowing the
causes of ICH will allow us to better diagnose and treat ICH.
Specifically, the pathogenesis provides more accurate infor-
mation on predictive factors that can influence the clinical out-
come and mortality: risk of hematoma expansion, presence of
underlying diseases, and previous lesions such as MBs.
Here, we propose a diagnostic flowchart that incorporates
size, location, clinical risk factors, and pathogenesis that, when
considered together, can lead to a more accurate diagnosis
and, thus, a better management of ICH (Figure4). Regarding
those who may do without further imaging w ork-up, this deci-
sion, according to the authors, should be based on a careful
assessment of age, functional outcome, life expectancy, as
well as the will of the patient.
Disclosures
Dr Caso received honoraria as a member of the speaker bureau and
advisory board of Boehringer Ingelheim. The other authors have no
conflicts to report.
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Key Words: CT angiography CT scan digital angiography intra
cerebral hemorrhage MR
 Neuroimaging in Intracerebral Hemorrhage
Federica Macellari, Maurizio Paciaroni, Giancarlo Agnelli and Valeria Caso

Stroke. 2014;45:903-908; originally published online January 14, 2014;

doi: 10.1161/STROKEAHA.113.003701
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