Value of Susceptibility-Weighted Imaging in the Evaluation of Altered Brain Perfusion in Children^[*]

Susceptibility-Weighted Magnetic Resonance Imaging Findings of Two Pediatric Migraine Patients with Aura

Susceptibility-weighted imaging (SWI) is a high-spatial-resolution, three-dimensional, fully velocity compensated, T2*-weighted gradient-echo magnetic resonance imaging (MRI) technique with a wide number of applications in pediatric neuroimaging.[1] The versatility of SWI is based on its unique magnetic susceptibility for various molecules and differences relative to background or surrounding tissues, such as (1) blood oxygen level dependent (BOLD) effect, (2) paramagnetic effects of blood products, (3) diamagnetic effects of calcium, and (4) iron-laden tissue susceptibility.[2] SWI was originally referred to as high-resolution BOLD venography[3]; however, its broad application beyond veins has occurred in the last decade. According to the BOLD principle, veins with a relative increase in paramagnetic deoxyhemoglobin appear hypointense, whereas veins with a relative decrease in deoxyhemoglobin or increase in diamagnetic oxyhemoglobin appear isointense in relation to subjacent brain parenchyma.

Brain perfusion can be measured noninvasively using techniques such as positron emission tomography (PET) or dynamic susceptibility contrast MRI. However, these approaches require administration of contrast material and/or exposure to ionizing radiation. The functional information related to the BOLD effect in SWI is a noninvasive, ionizing radiation and contrast material free method to evaluate brain perfusion in children. The relationship between cerebral blood flow (CBF) and oxygen extraction fraction (OEF) has been shown in both animal stroke models and humans using PET.[4] Pediatric neurovascular diseases with altered brain perfusion include hemiplegic migraine (HM), arterial ischemic stroke (AIS), moyamoya vasculopathy, vascular malformations, and epilepsy.

In this issue of Neuropediatrics, Gocmen et al have shown the value of SWI along with diffusion-weighted imaging (DWI) in the diagnosis of HM without headache in two children.[5] HM is a rare subtype of migraine with aura as defined by the International Classification of Headaches.[6] Migraine aura is generally indicative of a reversible cerebral cortical dysfunction that is most probably caused by cortical spreading depression.[7] Cortical spreading depression is characterized by a neuronal excitation followed by a prolonged inhibition of the neuronal activity.[8] In the excitatory phase, neuronal tissue requires higher oxygen consumption resulting in higher OEF. The subsequent lower oxygen saturation results in prominent hypointense veins on SWI as shown in the two patients reported by Gocmen et al as well as in previous articles.[5] [6] In addition, cortical spreading depression is associated with changes in CBF characterized by hypoperfusion,[6] followed by hyperemia.[9] As shown in the article by Gocmen et al, MRI findings of SWI hypointense veins, normal DWI, cerebral hypo- or hyperperfusion in a child suggest the diagnosis of HM and exclude acute AIS. SWI is especially helpful in differentiation of HM from AIS in a child with no prior history of migraine and the absence of headache.[5] [10] SWI hypointense veins have been demonstrated between 2 hours and 4 hours and 30 minutes following the onset of symptoms.[5] [6] [10] In addition, all children with aura or improving symptoms at the time of MRI demonstrated SWI hypointense veins.[5] [6] [10] Hence, SWI has a high sensitivity in the diagnosis of HM. As shown in the article by Gocmen et al, SWI abnormality in HM normalizes typically with resolution of symptoms, which is typically less than 24 hours in HM. Hence, SWI should be performed when symptomatic or improving to distinguish HM from AIS. Follow-up MRI has been important in understanding the pathophysiology of HM; however, it is not required as a clinical routine after symptom resolution.

In AIS, reduction in CBF is associated with increased OEF, which results in increased deoxyhemoglobin levels and prominent SWI hypointense veins. SWI can define the hypoperfused salvageable territory beyond the ischemic core (diffusion restriction) by presence of hypointense veins secondary to increased OEF. Mismatch between diffusion restriction (ischemic core) and SWI hypointensity (hypoperfused region) may predict progression of infarct.[11] On the contrary, increase in CBF from luxury perfusion after AIS results in reduction of OEF, a higher concentration of oxygenated hemoglobin and resultant SWI isointense—hyperintense venous signal. Luxury perfusion is associated with a risk for malignant brain edema.[12]

In addition to ischemic pathologies, SWI also helps in evaluating various types of vascular malformations. Slow-flow venous malformation such as developmental venous anomalies demonstrate hypointense veins due to increase in deoxyhemoglobin. On the contrary, high-flow shunting in an arteriovenous malformation shows SWI hyperintensity due to an increased concentration of oxyhemoglobin.[1] Moyamoya vasculopathy may be associated with decreased CBF, increased OEF, and prominent hypointense veins on SWI.

Furthermore, SWI helps in evaluating children with status epilepticus which causes excessive neuronal activity and concomitant increased perfusion as a compensatory mechanism to the increased metabolic demand.[13] This results in a focal SWI hyperintense region due to relative decreased deoxyhemoglobin and increased oxyhemoglobin.

Apart from neurovascular disease, a potential pitfall of SWI in children undergoing neuroimaging under general anesthesia should be recognized.[14] Supplemental oxygenation during anesthesia results in SWI isointense or hyperintense veins secondary to the relative increased oxyhemoglobin in the veins.

SWI is helpful in distinguishing HM from AIS in a child, in particular, in the absence of headache or prior history of migraine. SWI should ideally be performed when symptoms are present or improving. SWI after symptom resolution is typically normal and does not require to be repeated. In conclusion, SWI is becoming an important clinically helpful functional MR sequence influenced by alterations in brain perfusion.

^* This article is an editorial on “Susceptibility-Weighted Magnetic Resonance Imaging Findings of Two Pediatric Migraine Patients with Aura” by Gocmen et al (Neuropediatrics 2016;47(1):46–50).

• References

• 1 Bosemani T, Poretti A, Huisman TA. Susceptibility-weighted imaging in pediatric neuroimaging. J Magn Reson Imaging 2014; 40 (3) 530-544
• 2 Haacke EM, Xu Y, Cheng YC, Reichenbach JR. Susceptibility weighted imaging (SWI). Magn Reson Med 2004; 52 (3) 612-618
• 3 Reichenbach JR, Venkatesan R, Schillinger DJ, Kido DK, Haacke EM. Small vessels in the human brain: MR venography with deoxyhemoglobin as an intrinsic contrast agent. Radiology 1997; 204 (1) 272-277
• 4 Baron JC. Mapping the ischaemic penumbra with PET: implications for acute stroke treatment. Cerebrovasc Dis 1999; 9 (4) 193-201
• 5 Gocmen R, Gunbey C, Karli MA, Kader Karli, Oguz KK, Haliloglu G. Susceptibility-weighted magnetic resonance imaging findings of two pediatric migraine patients with aura. Neuropediatrics 2016; 47 (1) 46-50
• 6 Bosemani T, Burton VJ, Felling RJ , et al. Pediatric hemiplegic migraine: role of multiple MRI techniques in evaluation of reversible hypoperfusion. Cephalalgia 2014; 34 (4) 311-315
• 7 Hadjikhani N, Sanchez Del Rio M, Wu O , et al. Mechanisms of migraine aura revealed by functional MRI in human visual cortex. Proc Natl Acad Sci U S A 2001; 98 (8) 4687-4692
• 8 Tfelt-Hansen PC. History of migraine with aura and cortical spreading depression from 1941 and onwards. Cephalalgia 2010; 30 (7) 780-792
• 9 Hsu DA, Stafstrom CE, Rowley HA, Kiff JE, Dulli DA. Hemiplegic migraine: hyperperfusion and abortive therapy with intravenous verapamil. Brain Dev 2008; 30 (1) 86-90
• 10 Fedak EM, Zumberge NA, Heyer GL. The diagnostic role for susceptibility-weighted MRI during sporadic hemiplegic migraine. Cephalalgia 2013; 33 (15) 1258-1263
• 11 Polan RM, Poretti A, Huisman TA, Bosemani T. Susceptibility-weighted imaging in pediatric arterial ischemic stroke: a valuable alternative for the noninvasive evaluation of altered cerebral hemodynamics. AJNR Am J Neuroradiol 2015; 36 (4) 783-788
• 12 Bosemani T, Poretti A, Orman G, Meoded A, Huisman TA. Pediatric cerebral stroke: susceptibility-weighted imaging may predict post-ischemic malignant edema. Neuroradiol J 2013; 26 (5) 579-583
• 13 Aellen J, Abela E, Buerki SE , et al. Focal hemodynamic patterns of status epilepticus detected by susceptibility weighted imaging (SWI). Eur Radiol 2014; 24 (11) 2980-2988
• 14 Bosemani T, Verschuuren SI, Poretti A, Huisman TA. Pitfalls in susceptibility-weighted imaging of the pediatric brain. J Neuroimaging 2014; 24 (3) 221-225