743CHAPTER 61 Neuroimaging ultrasound As edema develops, usually after several hours, in creased echogenicity of brain parenchyma can be seen, but this measure is nonspecific, relative, and often is d[.]
CHAPTER 61 Neuroimaging ultrasound As edema develops, usually after several hours, increased echogenicity of brain parenchyma can be seen, but this measure is nonspecific, relative, and often is difficult to appreciate Blood associated with a hemorrhagic infarct also will appear as increased echogenicity As mass effect develops secondary to edema, ventricular and sulcal effacement can be seen Later, vascular and perivascular mineralization can result in linear thalamic and basal ganglia echogenicity (lenticulostriate vasculopathy or mineralizing angiopathy).26 Ultrasound Doppler evaluation of newborn ischemia has shown some utility Brain perfusion can be investigated by determining the resistive index (RI) RI in the normal neonate (0.75 0.1) is higher than that seen in the older infant before (0.65 0.5) and after (0.55 0.5) fontanelle closure.25 An increase in the RI with a decrease in the peak systolic velocity and end-diastolic velocity in infants with HIE within the first 12 hours of life as measured in the anterior and middle cerebral arteries correlated with a poor prognosis at year of life A decrease in RI to less than 0.60 at 12 hours (anterior and middle cerebral arteries) and 24 hours (all insonated arteries, including basilar artery) after neonatal asphyxia, which is thought to be a result of the decreased vascular tone associated with loss of autoregulation, has been associated with a poorer outcome at 12 to 18 months of life.27,28 Approximately half of patients with low RI scores have normal grayscale images There is a host of other reasons for low RI scores, however, including cardiac disease, extracorporeal membrane oxygenation, ongoing hypoxemia, hypercapnia, and technical issues It also should be noted that increased fontanelle pressure can increase the RI measure by 20%; hence, there is considerable user dependence to this application If hyperemia persists and as HIE evolves, cytotoxic edema increases and leads to increased intracranial pressure and increased RI measurements A high RI score on the first day of life with evidence of neonatal insult suggests an in utero injury Although some centers have continued to pursue the use of ultrasound, MRI has supplanted much of this evaluation CT detection of acute ischemic injury also depends on edema resulting from the injury Edema is seen as decreased attenuation and loss of gray-white differentiation, usually detected several hours postinsult.29 Small or early infarcts can be missed with CT, and detection of ischemia in the newborn is made more difficult by the generally lower attenuation of the relatively “watery” unmyelinated newborn brain For this reason, in some instances of neonatal ischemic injury, there may actually be an increase in the attenuation of this watery unmyelinated white matter because of an outpouring of serum proteins from damaged blood vessels As brain swelling develops in the first few days, there can be a loss of CSF spaces seen as ventricular compression, sulcal effacement, and loss of perimesencephalic cisterns Acute thrombotic stroke associated with arterial thrombosis can at times be appreciated acutely as a hyperdense artery, most commonly the middle cerebral artery on noncontrast CT Acute hemorrhage, such as with hemorrhagic arterial (from reperfusion) or venous infarcts, will be hyperdense initially on CT, evolving to isodense over the first week Standard MR sequences exploiting T1 and T2 relaxation times also depend on the development of edema to appreciate acute ischemic injury, which results in hyperintensity on T2-weighted and FLAIR images and hypointensity on T1-weighted images This change typically takes at least several hours to develop, and, although generally more sensitive than CT in adults, evaluation of the newborn is again made somewhat difficult by the lack of myelination As a result, ischemia can sometimes be more conspicuous on CT than on T1- or T2-weighted MRI (Fig 61.8) The 743 FLAIR sequence has proved to be more sensitive than T1 and T2 to ischemic changes in older myelinated children and adults DWI is more sensitive than T2 and FLAIR sequences and correlates well with at least short-term neurologic outcomes in neonates and infants.30 These sequences, as previously discussed, have been shown to be acutely sensitive to the cytotoxic edema associated with ischemia.12 This cytotoxic edema results in diminished diffusion of water in the affected area DWI in experimental models can detect ischemia in minutes after onset as a region of restricted diffusion.31,32 These sequences have now become widely implemented in adult and pediatric neuroimaging, where differentiation of acute ischemic stroke from other neurologic disorders permits appropriate and timely implementation of stroke therapies The restricted diffusion associated with ischemia evolves over a 1- to 3-week period, at which time the diffusion image usually normalizes If sufficient tissue destruction has occurred, the diffusion ultimately will increase because of the greater amount of free water following necrosis This change in diffusion is also useful in distinguishing a new stroke (which will show decreased diffusion) from an older lesion (which will have increased diffusion), whereas both lesions may be of similar signal intensity on standard T1 and T2 imaging (Fig 61.9) Timelines for relative T2 and diffusion changes have been shown to differ in neonates and infants versus older children and adults Animal models have suggested that diffusion changes in neonates and infants with HIE not necessarily precede T2 changes This finding is presumably a result of age-dependent differences in brain water content and changes therein as a result of differences in vascular permeability in response to hypoxic-ischemic insult.33,34 The initial diffusion abnormality may increase over the first day, and the extent of the diffusion abnormality can encompass both the core infarct and penumbra, potentially overestimating the ultimate infarct This potential overestimation could be an indication for MR perfusion, which can separate the areas of core infarction and penumbra.35 The identification of lactate on MRS is also evolving as a useful tool that may serve as a predictor for the severity of perinatal asphyxia, although considerable complexity is involved, which has limited application of this technology.31,36 As previously mentioned, the pattern of hypoxic-ischemic injury varies with the etiology of the insult and the developmental state of the brain Early in utero insults result in tissue resorption, without the ability to mount a gliotic response that is not seen until the third trimester During early brain development, insults can result in congenital malformations HIE or injury in the early to middle second trimester may result in polymicrogyria with or without associated schizencephaly In the 24th to 25th week of gestation range, HIE can preferentially injure the deep gray matter nuclei in the setting of total asphyxia PVL is the pattern of injury seen with prolonged partial hypoxia at 24 to 34 weeks Typically with PVL on neonatal grayscale ultrasound, there may be increased echogenicity in the periventricular white matter, an appearance that is indistinguishable at this stage from edema or from parenchymal hemorrhage, which also may be seen As PVL progresses, cystic change occurs that progresses to coalescent cavitation of the involved white matter Collapse of these spaces ultimately results in the thinning and volume loss of the white matter, particularly in the posterior periventricular white matter Although cranial ultrasound affords better resolution for the visualization of cystic change of early PVL in the premature neonate, MRI has overall greater sensitivity to white matter injury, especially in the more advanced stages of PVL, and demonstrates an 744 S E C T I O N V I Pediatric Critical Care: Neurologic A B C D • Fig 61.8 Abusive head trauma with diffuse cerebral ischemia (A) Axial noncontrast computed tomog- raphy (CT), (B) axial T2-weighted, and (C) diffusion-weighted magnetic resonance imaging (MRI) (A) CT shows a thin layer of acute subdural blood (arrowheads) and diffuse loss of gray-white demarcation in the cerebral hemispheres (B) Although the T2 image appears remarkably normal with appropriate lack of myelination in this 3-month-old child, the relative brightness of the cerebral hemispheres compared with the central gray on diffusion-weighted images (C) is consistent with a diffuse ischemic insult (D) Gradientrecalled echo MRI in another 4-month-old with abusive head trauma demonstrates dark, low-signal areas in the right frontal subdural space and left posterior parafalcine regions, consistent with subdural hematomas undulating ventricular margin with associated periventricular T2/ FLAIR signal abnormality with or without a paucity of white matter However, it is not yet clear whether this increased sensitivity is of significant prognostic value Ischemic insults to the term child demonstrate different patterns of injury, determined by the specifics of the insult and the vulnerability of various areas Profound hypoxia in the term infant results in injury largely to areas that are most actively myelinating—in particular, the perirolandic white matter and the associated corticospinal tracts and white matter tracts associated with the occipital cortex, as well as other areas with high energy demands, such as the putamina, thalami, hippocampi, and brainstem In contrast, a watershed pattern of injury discussed in the next section develops with prolonged partial ischemia that is not sufficient to cause an infarct of the cerebrum, with shunting to the high-energy demand areas Current recommendations for the encephalopathic term infant have included early CT to assess for intracranial hemorrhage, with consideration for MRI with DWI and GRE sequences later in the first postnatal week to assess the extent of injury.24 Imaging of Neurovascular Disorders Ischemic Stroke MRI, specifically DWI sequences, is critical for detecting cerebral ischemic infarcts (Fig 61.10) and distinguishing acute, subacute, CHAPTER 61 Neuroimaging A B 745 C • Fig 61.9 Remote and acute infarcts (A and B) Axial T2-weighted magnetic resonance imaging (MRI) shows cerebral volume loss with encephalomalacia and gliosis (arrows) associated with an old stroke in this child with new onset of progressive left-sided weakness (C) Diffusion-weighted MRI reveals a new area of infarct (arrowheads) at the edge of the remote abnormality A B C • Fig 61.10 Basal ganglia acute infarct Axial T2-weighted magnetic resonance imaging (A) shows subtle increased T2 signal in left basal ganglia (arrows) More conspicuously shown on the apparent diffusion coefficient map (B) and diffusion-weighted images (C) is restricted diffusion (arrows) associated with an early infarct involving the left caudate and lentiform nuclei and remote infarcts (see Fig 61.9) The area of restricted diffusion on DWI is generally thought to represent irreversible injury, especially when associated with T2/FLAIR signal abnormality, although there may be some cases in which the lesions are at least potentially reversible In the setting of acute stroke, perfusion MRI may have a contributory role in demonstrating the total region of brain at risk (penumbra) and predicting the ultimate extent of infarct.35 The area of perfusion abnormality beyond that of diffusion abnormality is thought to represent the penumbra and to be at risk but potentially salvageable A diagnosis of acute ischemic stroke is usually suspected based on clinical presentation, and neuroimaging can confirm the diagnosis.37 Moreover, the imaging pattern can help determine stroke etiology A watershed distribution is consistent with a low flow/ hypotensive cause (Fig 61.11) Specifically, changes of ischemic injury are seen at the boundary regions between the major cerebral distributions—that is, between anterior and middle cerebral territories and between middle and posterior cerebral arterial territories Lesions involving multiple arterial distributions suggest a central thrombotic source, although other causes such as a vasculitis or demyelinating diseases also can have this multivessel or multifocal picture (Fig 61.12) Classically, embolic lesions will tend to be seen at the gray-white junction and most commonly in the MCA distribution Individual variability of boundary regions38 and pathology-induced alteration in flow limit the definitiveness of arterial distribution categorization following vascular insult Arterial dissections as a cause for ischemic stroke can be diagnosed with MRI and MRA or with CTA Visualization of methemoglobin in the false lumen with fat-saturated T1-weighted or proton density–weighted MRI sequences detects most dissections, although subtle lesions may still require catheter angiogram for diagnosis On CTA, the false lumen is detected by the absent or diminished enhancement compared with the true lumen Suspicion for dissection is raised in the setting of multiple apparent embolic strokes in a single carotid distribution or within the 746 S E C T I O N V I Pediatric Critical Care: Neurologic A B • Fig 61.11 Watershed infarct (A) Axial T2-weighted magnetic resonance imaging shows some loss of the gray-white interface on the left posteriorly (arrows) (B) Diffusion-weighted image shows bilateral restricted diffusion consistent with ischemic injury in a watershed distribution (arrows) A B • Fig 61.12 Acute disseminated encephalomyelitis (ADEM) T2-weighted magnetic resonance imaging (A) and fluid-attenuated inversion recovery (B) images show multiple foci of hyperintensity In addition to ADEM, vasculitis and multiple emboli could have this imaging appearance posterior circulation when there is a history of trauma, although spontaneous dissections are seen occasionally As previously mentioned, the presence of emboli in multiple circulations raises the question of a more central etiology, such as a heart valve vegetation Vasculopathy/Vasculitis Acquired vasculopathies can be a result of known infectious or noninfectious causes or of unknown pathophysiology, such as in primary cerebral vasculitis, which tends to involve medium and small vessels, or moyamoya syndrome, which demonstrates greatest involvement of the central cerebral vessels Vasculopathy involving large and medium-sized vessels can be seen on MRA, although more subtle irregularities and small-vessel involvement still requires a catheter angiogram, which remains the gold standard imaging modality In transient cerebral angiopathy of childhood, classically a basal ganglia infarct resulting from M1 MCA segment narrowing and occlusion of lenticulostriate vessels is seen, with cortical injury being less common Narrowing typically of the terminal carotid and proximal M1 MCA segment of the affected side often can be delineated on MRA A lack of well-developed collaterals CHAPTER 61 Neuroimaging also will be noted, in contrast to the typical presentation of moyamoya syndrome, where the vessel occlusion has been more slowly progressive over a longer period Moyamoya “syndrome” denotes the pattern of vessel involvement that can be associated with type neurofibromatosis, radiation injury, sickle cell disease, trisomy 21 syndrome, or other pathology When this pattern is idiopathic, the term moyamoya disease is used More commonly, moyamoya syndrome/disease will be bilateral, and MRI will demonstrate evidence of chronic ischemic insult The enlarged lenticulostriate collaterals generally will be appreciable on both MRA (correlating with the “puff of smoke appearance” initially described with catheter arteriography) and as flow voids through the basal ganglia and basal cisterns on MRI (Fig 61.13) These apparent flow voids need to be distinguished from enlarged perivascular spaces that also are seen in this region Vasculitic changes can accompany infections, including meningitis, either through direct invasion of vessels or by an immune response to the particular pathogen Parenchymal injury, if present, is mediated by ischemic changes The pattern of involvement B A in the immune-mediated mechanism may be fairly symmetric, as can be seen in acute disseminated encephalomyelitis (ADEM) or some metabolic diseases Noninfectious vasculitides, including those associated with systemic disease—for example, systemic lupus erythematosus and, in particular, primary CNS vasculitis— can be more problematic in diagnosis Classically, a catheter angiogram and occasionally a brain biopsy have been used to evaluate the possibility of primary CNS vasculitis Most cases of symptomatic vasculitis will demonstrate abnormality on standard MRI (T2, FLAIR, and DWI) sequences; thus, a completely normal MRI makes the likelihood of CNS vasculitis low Occasionally, however, there can be a vasculitic process in the presence of a normal MRI.39 Furthermore, cases have been reported of biopsyproven CNS vasculitis in which the MRI was abnormal and results of a catheter angiogram were normal.40 Because medium and small vessels often are involved in the setting of CNS vasculitis, to which MRA has less sensitivity, a catheter angiogram may be indicated in the setting of very strong concern for vasculitis with a normal MRA and occasionally even a normal MRI C E D • Fig 61.13 Moyamoya 747 syndrome in a 15-year-old girl (A) Axial T1-weighted magnetic resonance imaging (MRI) shows flow voids (circle) associated with enlarged lenticulostriate collaterals (B) Axial fluidattenuated inversion recovery image shows gliosis in the right anterior periventricular white matter (arrow) with leptomeningeal linear hyperintensities corresponding to collaterals (C) Axial T1 postcontrast MRI demonstrates enhancing right lenticulostriate and leptomeningeal collaterals (arrows) (D) Coronal maximum intensity projection image from a magnetic resonance angiogram shows no flow distal to the terminal internal carotid artery (ICA) and nonvisualization of right and left proximal posterior cerebral arteries. (E) Lateral view from a right ICA catheter angiogram showing occlusion of the ICA below the siphon (arrow) and extensive thalamostriate collateral vessels (arrowheads) ... radiation injury, sickle cell disease, trisomy 21 syndrome, or other pathology When this pattern is idiopathic, the term moyamoya disease is used More commonly, moyamoya syndrome/disease will... hemispheres (B) Although the T2 image appears remarkably normal with appropriate lack of myelination in this 3-month-old child, the relative brightness of the cerebral hemispheres compared with the central... signal abnormality with or without a paucity of white matter However, it is not yet clear whether this increased sensitivity is of significant prognostic value Ischemic insults to the term child