Susceptibility-weighted imaging in intracranial hemorrhage: not all bleeds are black

Abstract

To correctly recognize intracranial hemorrhage (ICH) and differentiate it from other lesions, knowledge of the imaging characteristics of an ICH on susceptibility weighted imaging (SWI) is essential. It is a common misconception that blood is always black on SWI, and it is important to realize that hemorrhage has a variable appearance in different stages on SWI. Furthermore, the presence of a low signal on SWI does not equal the presence of blood products.

In this review, the appearance of ICH on SWI during all its stages and common other causes of a low signal on SWI are further discussed and illustrated.

Introduction

Susceptibility weighted imaging (SWI) is an increasingly used technique in daily practice, since it can provide useful information which is complementary to conventional MR imaging sequences. SWI has a higher sensitivity compared to T2* techniques for the detection of intracranial blood products. ^1,2 SWI mainly gained its popularity due to its ability to detect microbleeds and other late-stage blood products with high resolution and high sensitivity. SWI is most commonly used to detect microbleeds and late-stage blood products, for instance in post-traumatic patients or patients with amyloid angiopathy with microbleeds and superficial siderosis.

Since microbleeds and late-stage blood products appear black on SWI, it is a common misconception that all bleeds are black on SWI. The variable signal intensity on T₁- and T₂ -weighted MR images are well known for the different stages of intracranial hemorrhage (ICH). ^3–5 The same processes leading to these signal changes also lead to variable appearances of aging blood on SWI. ^6,7 This can lead to confusion, misinterpretation and ultimately misdiagnosis. For instance, the signal characteristics of a hyperacute bleeding can be confusing, especially when hemorrhage is not suspected clinically. Furthermore, other pathology might mimic an ICH as they can appear (partially) black on SWI. In this review, we describe the underlying physiological processes and signal characteristics of aging blood on MRI with a focus on SWI. Furthermore, we will discuss pathology that can mimic blood products on SWI. This knowledge will help both residents as well as radiologists to correctly diagnose ICH and prevent misinterpretations.

Susceptibility weighted imaging

SWI is generated with a gradient-echo (GRE) pulse sequences. An important feature of GRE sequences is their sensitivity for detection of magnetic field inhomogeneities due to the T2* effect. ⁸ T2* effects allow the detection of i.e., blood products and calcium, which cause field inhomogeneity. SWI is a high-resolution flow-compensated 3D GRE sequence which uses both magnitude and phase information to depict these field inhomogeneities. ⁸ The distortion of the magnetic field changes the precessional frequency and leads to a signal loss due to T2* dephasing and spatial mismapping, resulting in a susceptibility artefact. ^9,10 As a result of the spatial mismapping, blooming occurs. The blooming effect results in a susceptibility artefact bigger in size when compared to the size of the lesion on conventional MRI images.

A hallmark of SWI is the display of magnitude and phase images both separately and combined. ^8,11 The magnitude image shows the background tissue with a contrast similar to a proton density sequence. The phase information is processed into a filtered phase image and can be used to differentiate hemorrhage from calcification. This differentiation can be made due to opposite susceptibilities of the paramagnetic blood products and diamagnetic calcifications. ¹² Diamagnetic substances have negative susceptibility and therefore oppose the applied magnetic field, whereas paramagnetic substances have positive susceptibility and reinforce the magnetic field. ^9,13 On the final SWI images, both paramagnetic and diamagnetic substances are black. However, with use of the phase information the difference in susceptibility can be used to distinguish diamagnetic substances from paramagnetic substances. ^12,13 It is important to realize that the “colors” of blood and calcium on the phase images are vendor dependent. Furthermore, in larger lesions aliasing can occur, leading to a conversion of the signal with bright areas in an otherwise low signal lesion. ¹⁴ To establish a reference, blood or calcification in an anatomical location can be used, i.e., the signal of blood in venous structures or calcium in the choroid plexus. Subsequently, a phase mask is created. This phase mask results from processing the data from the filtered phase images into a mask that accentuates tissues with different susceptibilities. ⁸ Finally, the phase mask and the magnitude image are combined into the susceptibility weighted image, which thus contains both magnitude and phase information. ⁸ A potential confusing finding is the signal intensity of the major dural sinus. The T2* effect in venous blood, due to presence of deoxyhemoglobin, interacts with and cancels the signal intensity of the surrounding brain parenchyma within the same voxel leading to a low signal. A voxel with only intravenous signal does not show this effect and has a high signal intensity, resulting in a high signal intensity centrally with a hypointense rim. In smaller veins, this appearance is corrected during the phase mask application, but in larger veins the signal remains high centrally. ¹⁵ The combination of magnitude and phase information makes SWI more sensitive for the detection and differentiation of field inhomogeneities compared to T2* imaging. ^11,15 Thus, SWI is more sensitive for the detection of blood products. ^2,16

SWI signal in relation to T1, T2 and diffusion at different stages of ICH

Blood consists of plasma, red blood cells, white blood cells and platelets. Red blood cells contain hemoglobin, which is responsible for the oxygen binding capacity. Hemoglobin exists in four different forms, oxyhemoglobin, deoxyhemoglobin, methemoglobin and hemichromes. The different forms of hemoglobin have considerably different magnetic properties resulting in the different appearances of hematomas on MR imaging. ⁴ In general, the paramagnetic effect of hemoglobin derivates depends on the presence of unpaired electrons. A higher number of unpaired atoms having greater paramagnetic effects (Table 1). ³

Table 1.

Magnetic properties of hemoglobin derivates ^3,17

Hemoglobin derivates	Number of unpaired electrons	Magnetic susceptibility
Oxyhemoglobin	0a	Diamagnetic
Deoxyhemoglobin	4a	Paramagnetic
Methemoglobin	5a	Paramagnetic
Ferritin	>10,000 bx	Superparamagnetic
Hemosiderin	>100,000 b	Superparamagnetic

^anumber of unpaired electrons per atom

^bnumber of unpaired electrons per molecule

Paramagnetic molecules have little effect on T1 signal intensity, which is predominantly determined by the presence of blood proteins. The T2 signal depends on (1) the T2* effect caused by different hemoglobin oxygenation states and (2) whether or not lysis of the cells and blood clot has occurred. The signal on SWI depends both on T2* effects and on the T1 signal intensity of the blood products, allowing the staging of an ICH. We will discuss the imaging characteristics for different stages of aging blood for SWI, T1, T2 and DWI, and the underlying physiological processes (Table 2). ^6,7 An overview of the presentations of ICH at different time points is displayed in Figure 1.

Table 2.

Overview of signal characteristics in parenchymal cerebral hemorrhage over time

Stage	Blood products	T1W1	T2WI	b1000	ADC	SWI
Hyper acute (<24 h)	Oxyhemoglobin	Iso	High	High	Low	High a
Acute (1–3 days)	Deoxyhemoglobin	Iso	Low	Low	Low	Low
Early subacute (3–7 days)	Intracellular methemoglobin	High	Low	Low	Low	Low
Late subacute (7–28 days)	Extracellular methemoglobin	High	High	High	Variable	High
Chronic (>1 month)	Hemosiderin	Low	High center, low rim	Variable	High	Variable

^aEven in the hyperacute stage a low signal rim is often present. This rim is also visible in the late subacute stage and is most prominent in the chronic stage

Figure 1.

Imaging characteristics of different stages of hematoma evolution. Axial brain images showing different stages of an ICH. A: hyperacute stage (<24 h), B: acute stage (1–3 days), C: early subacute stage (3–7 days), D: late subacute stage (7–28 days), E: chronic stage (>1 month).

Hyperacute stage

The hyperacute phase is often arbitrarily defined as the first 12–24 h after the onset of hemorrhage. Oxyhemoglobin is mainly responsible for the signal on MRI in both arterial and venous hemorrhages. In arterial blood over 95% of the hemoglobin molecules is in the form of oxyhemoglobin. In venous blood, the amount of oxyhemoglobin is lower, but still 70%. Therefore, oxyhemoglobin is the strongest contributor to the MRI signal in not only arterial but also venous hemorrhage. Oxyhemoglobin has diamagnetic properties with no unpaired electrons. It causes little T2* effects and only mild shortening of the T1 relaxation time. ³ The diamagnetic properties of oxyhemoglobin and subsequently the lack of paramagnetic effects lead to an intermediate to high signal on SWI (Figure 2). ^6,18 The reduced extracellular space in clot formation leads to restricted diffusion most prominent in the center of the clot. ¹⁹ On the other hand, formation of deoxyhemoglobin occurs in the periphery of the ICH within the first hours after onset. ^20,21 The paramagnetic deoxyhemoglobin forms when oxygen molecules dissociate from the oxyhemoglobin molecule, resulting in the low signal rim on SWI ⁴ In some cases, a dual rim with a high signal rim surrounding the low signal rim is present. The high signal rim represents vasogenic edema. ²⁰ The T1 and T2 signals are determined by the clot formation and presence of blood proteins. Clot formation leads to decreased “free” water content, which reduces T1 and T2 relaxation times, resulting in an isointense T1 signal. The T2 signal is slightly lowered compared to the “free water” signal of the CSF, but remains hyperintense compared to the brain parenchyma.

Figure 2.

ICH in the hyperacute stage. Axial brain T1WI (A), T2WI (B), b1000(C), ADC (D) and SWI (E) of a patient with Posterior Reversible Encephalopathy Syndrome who developed a lobar ICH in the left frontal lobe. SWI shows an intermediate signal central in the ICH with a hypointense rim. Furthermore, the formation of a clot in the ICH leads to restricted diffusion with a high signal on the b1000 image and a low signal on the corresponding ADC map.

Acute stage

The acute stage is defined as 1–3 days after onset of the ICH. In the acute stage, the process of transformation of oxyhemoglobin into the paramagnetic deoxyhemoglobin continues and eventually reaches the center of the hematoma, which results in a low signal on SWI images in the entire hematoma (Figure 3). ^3,6 Diffusion-weighted imaging also shows a low signal in the hematoma on b1000 and ADC images. This so-called T2-blackout effect is caused by a very low T2 signal on B0 images due to the paramagnetic deoxyhemoglobin. ^19,22 The low signal on ADC images is, therefore, not indicating true diffusion restriction, but represents the loss of signal due to the susceptibility effects. ²³ The T1 signal remains isointense due to the decrease in “free” water content in the ICH similar to the hyperacute stage. The T2 signal is strongly lowered due to the strong paramagnetic effects of deoxyhemoglobin.

Figure 3.

Acute ICH. Axial brain T1WI (A), T2WI (B), b1000 (C), ADC (D) and SWI (E) of a 57-year-old patient with hypertension two days after the onset of symptoms. Initial CT imaging showed a bleeding in the region of the right basal ganglia (not shown). MRI showed evolution of the ICH to the acute stage, showing a low signal on SWI. A low signal is present on both b1000 and ADC imaging, representing the T2-blackout effect due to the presence of strong paramagnetic molecules.

Early subacute stage

In the early subacute stage, 3–7 days after onset of the ICH, methemoglobin forms when the deoxyhemoglobin molecules leave the circulation. In absence of the high-oxygen environment of the circulation, various metabolic pathways start to fail. This results in the oxidation of the heme iron to the ferric (Fe⁺³) form: the strongly paramagnetic methemoglobin. ³ The confinement of the methemoglobin to the intracellular compartment of the red blood cell leads to a magnetic gradient which disturbs the local magnetic field causing a low signal on SWI and T2 images (Figure 4I). ⁶ The low signal on DWI and ADC images remains present due to the persisting T2-blackout effect. ^19,23 The newly formed iron molecule interacts with water molecules, leading to inner-sphere relaxation. This causes shortening of the T1 relaxation time resulting in a high T1 signal. ⁴ The T2 signal remains low due the paramagnetic effects of methemoglobin.

Figure 4.

ICH in the early and late subacute stage. I: Axial brain T1WI (A), T2WI (B), b1000 (C), ADC (D) and SWI (E) performed six days after the symptoms developed, at initial CT imaging a hypertensive bleeding at the right frontal lobe and basal ganglia was present. MRI shows a low signal on SWI, corresponding with the early subacute stage. A low signal is present on the b1000 images as a result of the T2-blackout effect caused by the very low T2 signal due to the presence of methemoglobin. A low signal is also present on the ADC, representing the signal loss due to the susceptibility effects. Due to the size of the hematoma, the T1 only started to increase in signal at the periphery and centrally. II: Images of the same patient approximately two weeks later, 20 days after symptom onset, showing evolution of the ICH to the late subacute stage with a high signal centrally and a low signal rim on SWI. Due to liquefaction of the hematoma, a high signal is present on the b1000 images as a result of T2 shine-through effects. The variable, and in this case intermediate, signal on the ADC images is due to the same process of liquefaction of the ICH and is a result of different molecular processes occurring at the same time.

Late subacute stage

The late subacute stage is defined as 7–28 days after the initial bleeding. Methemoglobin is still the dominant hemoglobin derivate at this stage. ³ Lysis of the clot and red blood cells occurs in the late subacute stage. This causes the spread of methemoglobin to the extracellular space. If an even distribution of methemoglobin is reached in both the intracellular and extracellular space, the magnetic gradient disappears and the T2/T2* effects are eliminated without altering the T1 relaxivity. ²⁴ The methemoglobin molecule itself remains intact and the inner-sphere bonding of water resulting in a high T1 signal remains present. ⁵ This mechanism also influences the signal on SWI. With the decline of the susceptibility effect, the T1 signal becomes dominant on SWI imaging. This is known as the T1 shine-through effect, which leads to a high signal on SWI centrally in the ICH (Figure 4II). ^6,7,25 At the same time, accumulation of hemosiderin and ferritin at the periphery of the ICH occurs due to the presence of macrophages. This leads to a low signal rim. ⁴ With liquefaction of the hematoma, there is a decrease in diffusion restriction with a higher signal on b1000 as a result of T2 shine-through effects. The signal on ADC images is variable. ²² Several concurrent processes may influence the molecular diffusion and contribute to the variability of the ADC signal such as lysis of the red blood cells, loss of compartmentalization of the methemoglobin, increase of the viscosity of the ICH and infiltration of inflammatory cells and macrophages. ^3,4,22 The T1 signal remains high due to the persistent presence of inner sphere relaxation. The T2 signal increases due to the loss of compartmentalization of the methemoglobin and the increased water contents of the lysed red blood cells. ⁵

Chronic stage

The chronic stage begins approximately one month after the ICH occurred. Methemoglobin molecules release a superoxide radical and are converted to the non-paramagnetic hemichromes during this stage. ¹⁷ Due to different pathways, the heme units and the iron molecules dissociate in separate components. ¹⁷ Iron is scavenged by macrophages and glial cells and is transformed into the strongly paramagnetic ferritin and hemoglobin at the border of the hematoma. This results in a low signal rim on SWI, T2WI and b1000 images (Figure 5). ^3,6,22

Figure 5.

Chronic ICH. Axial brain T1WI (A), T2WI (B), b1000 (C), ADC (D) and SWI (E) obtained in a patient with an ICH 10 weeks after symptom onset. The SWI shows an ICH with a hypointense rim with mixed to high signal intensity in the center representing a chronic ICH.

Hemichromes, proteins and water are present at the center of the hematoma, The transformation of the hematoma into a cystic cavity leads to a variable appearance on SWI and b1000 images. With the increase of water content, the signal becomes higher on the ADC images. ²² Furthermore, the presence of water leads to a high signal on T2WI and a low signal on T1WI, although in the latter the signal can be iso- or hyperintense due to residual methemoglobin or iron molecules in the solution. ^3,4

Pathology mimicking hemorrhage on SWI

Apart from hemoglobin derivates, other substances such as calcifications, non-heme iron and gas may cause artifacts on SWI and present a potential diagnostic pitfall. ^15,26

With regard to calcifications and non-heme iron, age of the patient, location and pattern can be helpful in the diagnostic process. ²⁷ Calcification and/or iron in the basal ganglia will usually not cause a diagnostic problem. Symmetrical calcifications in the basal ganglia are (usually) physiological in the elderly while in younger patients they may result from metabolic diseases, i.e., Fahr syndrome (or Fahr disease). ^28,29 Calcifications can also be seen with vascular malformations, infections, inflammation and tumors. As described previously, the phase images can be useful in distinguishing the diamagnetic calcification from paramagnetic blood products. In the context of recent head trauma, it is especially important to realize that pneumocephaly and ICH both result in a low signal on SWI. In pneumocephaly the susceptibility artifacts are caused by the presence of molecular oxygen making the air slightly paramagnetic, resulting in T2 shortening. ³⁰ The low signal on T1WI in pneumocephaly is helpful for correct interpretation, as it contrasts with the isointense to high signal in hyperacute and acute ICH. A similar misinterpretation of pneumocephaly is possible after a recent craniotomy or lumbar puncture (Figure 6A–C).

Figure 6.

Pneumocephaly, fat embolism and lipoma mimicking hemorrhage on SWI. Axial brain SWI (A), T1WI (B), T2WI (C) of a patient with small amount of pneumocephaly in the left frontal horn of the lateral ventricle system after a lumbar puncture the day before the MRI. Susceptibility artifacts are seen on SWI (A). Accompanying low signal on T2 and T1 is very faintly seen (B and C). Axial brain SWI (D), T1WI (E), T2WI (F) of a patient with fat embolism 16 days after cervical spine surgery. Susceptibility artifacts are shown on SWI (D). T1 and T2 demonstrate hyperintense signal in the frontal horns of the ventricle system and in the left sylvian fissure (E-F). Axial brain SWI (G), T1WI (H), FLAIR (I), a patient with an intracranial lipoma in the right quadrigeminal cistern. Susceptibility artifacts on SWI are shown (G), T1 hyperintense (H) and low signal on the FLAIR with fat suppression (I) confirm the diagnosis of a lipoma.

Intracranial fat depositions (lipoma, fat embolism, ruptured dermoid cyst), can have similar imaging features as a late subacute hemorrhage on SWI, T1WI and T2WI. The appearance of fat on SWI is characterized by high signal intensity in the center of the lesion with a surrounding peripheral dark rim. The dark rim is caused by the fat-water interface (chemical shift artefact) (Figure 6D–F). ^31,32 Images with fat suppression can help in differentiating intracranial fat depositions from ICH. (Figure 6G–I). ³³

Another mimicker of an ICH is a pyogenic abscess which shows a dual rim sign on SWI with a relative high signal central in the abscess and therefore can be confused with a late subacute hemorrhage (Figure 7). The susceptibility artifacts in the rim can be explained by the production of free radicals by macrophages. ³⁴ Diffusion-weighted images can help to differentiate an abscess from an ICH, as a hematoma shows a high signal on DWI with a variable signal on ADC images. On the other hand, an abscess shows the typical central high signal on DWI and low signal on ADC images. These mimickers underline the importance of the availability of clinical information and the combination of different MRI sequences to differentiate an ICH from other lesions.

Figure 7.

Abscess mimicking hemorrhage on SWI. Axial SWI (A), b1000 (B), ADC (C), T2WI (D),T1WI (E), T1WI with Gadolinium (F), showing dual-rim susceptibility artifacts, central diffusion restriction, T2 hypointense rim with central hyperintensity, slight T1 hypointensity and rim-enhancement in a 74-year-old patient with a pyogenic abscess.

Conclusion

It is important to realize that not all bleeds are black on SWI. In the hyperacute stage, an ICH appears as a bright lesion on SWI due to the lack of paramagnetic substances. In the late subacute stage, ICH has a high signal on SWI caused by the T1 shine-through effect. In the acute and late subacute setting/stage strong paramagnetic effects predominate, leading to the well-known low signal on SWI imaging. The chronic stage of an ICH shows a variable signal at the center of the ICH due to the varying presence of breakdown products of hemoglobin. The rim of the chronic ICH shows a low signal due to iron deposition. The knowledge on different appearances of an ICH can be helpful in making a differential diagnosis, since a bright lesion on SWI is not always a mass but can be an hyperacute or late-stage ICH.

Furthermore, not everything that is black on SWI is blood. Calcifications, non-heme iron, gas, lipids and free radicals in abscesses may mimic hemorrhage on SWI. Clinical information, fat suppression sequences or a non-contrast CT may be helpful to make the correct diagnosis.