Pallavi Sagar, M.D.; P. Ellen Grant, M.D. Diffusion Weighted Imaging in Pediatric Neuroradiology Massachusetts General Hospital, Boston, MA • Harvard Medical School, Boston, MA

I. Cerebrovascular disease IV. TOXIC AND METABOLIC DISORDERS V. DEMYELINATING DISORDERS

1) Arterial Ischemic Stroke (AIS) 3) Global and Hypoperfusion 1) Methotrexate Neurotoxicity 1) Multiple Sclerosis (MS) INTRODUCTION Pediatric AIS is less common and almost 50% of the pediatric AIS are Perinatal Hypoxic Ischemic Injury Intrathecal or intravenous methotrexate can cross blood brain barrier and cause diffuse or multifocal Figure 9. Methotrexate toxicity. Axial (a) T2 and (b) DWI. There is MS is an inflammatory demyelinating process, Diffusion-weighted magnetic resonance idiopathic. Pediatric strokes can be classified as perinatal (between 28 weeks changes typically in the periventricular region. Alteration in faint T2 hyperintensity in the left posterior centrum semiovale. which can be reversible due to reparative imaging (DWI) provides image contrast DWI is more sensitive in demonstrating increased signal in this of gestation and 28 days of postnatal life) or childhood (between 30 days and Hypoxic ischemic brain injury results from a combination of global and hypoperfusion. Two patterns have causing axonal swelling and intramyelinic edema has been proposed. In acute encephalopathy region and an additional lesion on the right side presumably remyelination or become irreversible with that is dependent on the molecular motion 18 year of life) ( Figure 1) . been described. Partial asphyxia or peripheral pattern with bilateral white matter injury and a profound or central pattern with transient and reversible lesions with decreased diffusion can be observed. (Figure 9) due to intramyelinic edema which can be reversible. tissue loss. Destruction of myelin sheath and of water. This gets substantially altered corticospinal tract, VL thalamus, and perirolandic involvement. Conventional imaging may be negative until 3-7 days after the axonal loss leads to expansion of extracellular by many CNS diseases . It has become a insult. DWI provides a means of earlier detection of injury especially in the first hours after the insult (Figures 3 and 4). 2) Heroin Induced Leukoencephalopathy space with a quantitative increase in water useful tool for probing tissue physiology diffusion. Occasionally acute MS lesions may at the cellular level. It enables detection Figure 3. Neonatal Profound hypoxic ischemic injury with central asphyxia pattern. Axial (a) T2 , (b) DWI and (c) ADC. Inhaled or intravenous heroin vapor causes spongiform vacuolar degeneration of cerebral white have decreased ADC values presumably due of otherwise subtle abnormalities, narrows Loss of the normal low T2 signal is noted in the posterior limb matter. This results in DWI hyperintensity with reduced ADCs due to vacuolar white matter to more rapid demyelination. (Figure 17) a b c d the differential diagnosis and provides of the internal capsule and VL thalamus. Bright DWI signal and degeneration. (Figure 10) a b Figure 17. Multiple sclerosis. Axial (a) T2, (b) post contrast increased diffusion, but also shows that the region with additional relevant information when decreased ADCs are seen in these regions presumably due to enhanced T1, (c) DWI and (d) ADC. There are multiple foci of T2 brightest DWI signal has decreased diffusion. The region of cytotoxic edema. 2) Acute disseminated encephalomyelitis combined with routine MR imaging. As hyperintensites in the centrum semiovale, the largest lesion on decreased ADC does not match the area of enhancement and 3) (ADEM) the right with partial enhancement. DWI shows heterogenous may represent a subtype of active demyelination. a result, DWI plays an important role increased signal and the ADC map demonstrates predominantly in pediatric neuroimaging in better Excitotoxic brain damage can occur with ADEM is also an inflammatory demyelinating characterizing the disease process. a b c severe hypoglycemia with a blood disease that develops in close temporal Figure 1. Neonatal Stroke. Axial (a) T2, (b) DWI lesion with low ADCs in a vascular distribution concentration below 30mg/dl. Decrease diffusion relationship to a viral illness or vaccination. The In this poster we will demonstrate the and (c) ADC performed on day 2. There is loss of consistent with acute arterial ischemic infarct a b c grey white matter differentiation in the left MCA and associated cytotoxic edema. with a posterior predominance involving the neurologic picture of ADEM usually reflects a expanded clinical applications of DWI in a Figure 4. Neonatal Hypoxic ischemic injury with peripheral territory. DWI there is a sharply marginated bright parieto-occipital lobes is typically observed, multifocal but often monophasic involvement. number of pediatric brain disorders. partial asphyxia pattern. Axial (a) T2, (b)DWI and (c) ADC. Faint loss of grey white matter differentiation is noted in the hypothesized secondary to excitotoxic neuronal Mostly elevated ADC values in acute lesions 2) Sinus Venous Infarction (SVT) posterior and parasagittal occipital lobes which can be easily injury from glutamate and aspartate on the are seen. Although decreased ADC values due overlooked. Diffuse bilateral hyperintense DWI signal with NMDA receptors. (Figure 11) to aggressive demyelination has also been PATHOPHYSIOLOGY decreased ADCs are easily identified involving primarily the SVT can occur due to infections, extrinsic compression of the venous sinus by occipital cortex and white matter. reported. (Figure 18) a b c d intracranial mass, dehydration, trauma, and hypercoagable. Venous occlusion a b c a b c DWI provides a more direct way to assess Figure 18. ADEM. Axial (a) T2, (b) Flair, (c) DWI and (d) ADC. The ADC map shows signal heterogeneity with decreased ADC causes regional venous hypertension with breakdown of the blood brain Figure 10. Heroin induced encephalopathy. Axial (a) T2, (b) DWI and (c) ADC. There is Figure 11. Neonatal hypoglycemia. Axial (a) T2, (b) DWI and (c) ADC. There is subtle loss of grey 3) Wallerian degeneration There are multiple bilateral scattered foci of T2 and flair values around the periphery of the lesion possibly secondary the extent of tissue injury by measuring T2 prolongation in the centrum semiovale bilaterally. DWI shows bright DWI signal and white matter differentiation posteriorly. Bright DWI signal and decreased ADC values are noted in barrier causing vasogenic edema. (Figure 2). hyperintensities involving the subcortical white matter. On DWI, to a subtype of active demyelination. the apparent diffusion coefficient (ADC) of reduced ADCs presumably due to spongiform degeneration of the white matter with the bioccipital cortex and subcortical white matter. This is secondary degeneration of axons the lesions are bright, predominantly due to T2 shine through. water within the imaged voxel. In the brain, a b c 4) Mitochondrial encephalopathy, lactic intramyelinic edema that is known to occur in this disorder. Figure 2. Neonatal Deep Vein and myelin sheaths of the descending white factors contributing to the measured ADC thrombosis. Axial (a) T2, (b) acidosis and stroke like syndromes (MELAS) Susceptibility, (c) DWI, (d) ADC. matter tracts, due to cortical or subcortical include true random diffusion, tortuosity There is extensive thrombosis of the Hypoxic Ischemic Injury in the Young Child injury. Cortical injury leads to cellular energy of the diffusion space, cytosolic streaming, internal cerebral veins with edema MELAS is a heterogeneous group of disorders Figure 12. MELAS. Axial (a) Flair, (b) DWI (c) ADC and (d) Single voxel MR spectroscopy at TE 135 ms depletion of the cell bodies of exchange times between compartments of the basal ganglia. There is diffuse Most of the hypoxic or anoxic injuries in young child affecting the CNS and skeletal muscles. This is diffusion signal abnormality of the on the abnormality. A transient lesion in a patient resulting in axonal swelling. This results in and restriction by cell membranes. caused by defect in mitochondrial respiratory with MELAS presenting with seizures. Note the white matter with a combination of are a result of choking or near drowning. The initial myelin fragmentation and vacuolization into vasogenic (arrowhead) and cytotoxic DWI hyperintensities start in the posterior lentiform chain leading to cellular energy depletion involvement of the crest of the of the right frontal lobe on Flair, with corresponding bright ellipsoids and spheres causing decreased ADC edema (arrows) due to venous nucleus and VL thalamus and can progress over resulting in anaerobic glycolysis with lactate hypertension. DWI and isointense cortical ADCs in addition values. This process occurs within 4 weeks CLINICAL APPLICATIONS time. Imaging studies performed on the 3-4 day after production. MRI shows signal change both there is elevated subcortical ADCs. Targeted MR a b in the grey and white matter in a nonvascular Spectroscopy identified lactate. (arrow) of injury, during which conventional MRI is insult best correlate with clinical outcome. Therefore usually negative. (Figure 19) a b c d The practical applications of DWI are in distribution. MRS usually demonstrate a lactate if the initial imaging in the first 1-2 days is negative, Figure 19. Neonatal Wallarian degeneration. Axial (a & b) DWI brain stem, on the left side along the course of corticospinal identifying regions and patterns of abnormal repeat imaging is warranted to convincingly rule peak in the affected area. (Figure 12) and (c & d) ADC map at the level of basal ganglia and brain tract. This patient had a grade 4 intraparenchymal bleed a b c d DWI signal and further characterizing them out hypoxic brain injury. ( Figure 5) stem is showing focal hyperintensities with decreased ADC with post hemorrhagic venous infarction involving the left to low or high ADC’s values. In this poster we a b c 5) Kearns-Sayer Syndrome (KSS) values in the posterior limb of internal capsule and anterior periventricular region. will demonstrate various disease processes associated with bright DWI and variable KSS is a rare mitochondrial deletion syndrome Figure 13. Kearns Sayer syndrome. Axial (a ) Flair, (b & c) DWI and (d) involving the muscle, eye and . MRI ADC. Symmetric increased T2 and DWI signal is noted in the deep white ADC values. matter and globus pallidus. The corresponding ADC values are isoin- VI. PEDIATRIC BRAIN TUMORS Figure 5. Cardiopulmonary arrest in a 10 year old. Axial (a & d) T2 , shows abnormal signal in the subcortical and tense to slightly decreased. These findings remained unchanged over (b & e) DWI and (c &f) ADC within 12 hours of injury and follow-up periventricular white matter and deep grey nuclei years. The cause of bright T2 signal and isointense to decreased ADCs The most common pediatric c d MR 2 days . The T2 is falsely negative. On DWI there are bright foci is unknown, yet suggests that the increased fluid is not in the extracel- involving the posterior putamina and VL thalamus that correspond (globus pallidus and caudate) with decreased lular space. brain tumors include PNET, diffusion that may persist for years probably due Causes of Decreased ADC Values to foci of decreased ADCs consistent with cytotoxic edema. After ependymomas, astrocytomas 2 days there is interval progression to involve the bilateral basal to spongiform change.( Figure 13) ganglia, thalami and posterior consistent with and glioblastomas. DWI provides information about tumor 1) Cytotoxic edema causing cellular swell- delayed cytotoxic edema. The child succumbed to diffuse cerebral d e f ing and decreased extracellular space injury within 4 days. cellularity and thereby helps in 6) Congenital muscle dystrophy with Merosin a b c d e.g. arterial ischemic stroke differentiation of different tumor deficiency (CMD) II. Disorders of alteration in autoregulation III. TRAUMA subtypes. PNET are densely 2) Spongiform /vacuole formation packed cellular tumors with between the myelin lamellae and CMD involves CNS in form of white matter signal Figure 14. Merosin deficient congenital muscular disorder. a b c d Axial (a) T1, (b) T2, (c) DWI and (d) ADC. There is bilateral decreased extracellular space intramyelinic edema causing myelin 1) Status Epilepticus abnormalities. Merosin is a protein present in Figure 20. Brain stem PNET. Axial (a) Post contrast T1, (b) DWI, (c) ADC voxel from a Multivoxel MRS demonstrates elevated Cho/Cr ratio and 1) Diffuse Axonal Injury (DAI) diffuse decreased T1 and increased T2 signal in the white and cause decreased diffusion compartmentalization the basal lamina of the vessel walls and blood matter sparing the corpus callosum and internal capsule. The and (d) targeted Multivoxel MR Spectroscopy at TE 135 ms. There is an a decreased NAA peak but not the classic marked Cho/Cr elevation, in comparison to other tumors expansile nonenhancing pontine mass that is DWI bright with isointense possibly due to volume averaging. e.g. prion disease. It is a hypermetabolic state with imbalance brain barrier, which links the extracellular areas of white matter involvement correspond to decreased DAI refers to traumatic white matter injury induced by sudden acceleration- DWI signal and increased ADC values, presumably due to types. Evolving ADC changes to slightly decreased ADCs suggesting a highly cellular tumor. A targeted in excitatory and matrix. Its deficiency causes vascular hyper deceleration, rotational and shearing forces leading to axonal stretching, increased extracellular water. with treatment may also provide 3) High cellular density with overall local hyperperfusion due to loss of permeability and deficient myelin leading to disruption and eventual separation of nerve fibres. DWI is more sensitive valuable information about tumor response. (Figure 20) reduction in extracellular space, autoregulation. Prolonged seizures can increased extracellular water with elevated and shows variable diffusion. Decreased ADC values are due to axotomy e.g. PNET. cause decreased diffusion. Cortical DWI ADC. (Figure 14) with formation of traction balls and elevated ADC values are secondary to VII. INFECTIONS hyperintensity that does not respect 4) Increased viscosity vasogenic edema. (Figure 8) vascular boundaries with iso to mildly 7) Urea Cycle Defects a b c d e.g. abcesses, empyema. a b c decreased ADC values are seen in the Bacterial meningitis is a clinical diagnosis Disorders of urea cycle leads to hyperammonemia Figure 15. Neonatal Urea cycle defect. Axial (a) T2, (b) DWI and (c) ADC. There is subtle immediate post ictal period. (Figure 6) and the use of MR is in identifying resulting in brain edema. There is often stripe of increased T2 signal coursing through the lentiform nucleus bilaterally. These findings are more conspicuous on DWI with increased DWI signal and low ADCs. In complications, such as arterial and venous involvement of the bilateral , Figure 6. Status Epilepticus. Axial Flair (a & d), DWI (b & e) addition, decreased diffusion is noted extending to the caudate and in the VL thalamus, infarcts secondary to septic arteritis and and ADC ( c & f) few hours after seizure and follow up MR subcortical white matter and deep grey nuclei. presumably due to cytotoxic edema. Causes of Increased ADC Values phlebitis. DWI is more sensitive in acute done 3 days later. There is subtle increased cortical signal Decreased ADCs are seen with neonatal onset of in the right parieto-occipital region and pulvinar thalamus infections by demonstrating more lesions disease and although similar to profound hypoxic 1) Vasogenic edema causing expansion on the flair sequence. DWI and ADC map demonstrates and its complications. In addition DWI bright DWI signal and normal to mildly reduced ADCs in ischemic brain injury, the pattern of basal ganglia of the extra cellular space is useful at detecting purulent debris in the same regions. Follow up MR performed 3 days later involvement is different. (Figure 15) e.g. PRES demonstrates near complete resolution of the signal the ventricles, brain abscess and subdural abnormalities suggesting a transient phenomenon of empyemas. (Figure 21) a b c d decreased diffusion due to a metabolic stress. d e f a b c a b c 2) Glial scarring or myelin loss 8) Sulfite Oxidase Deficiency Figure 21. Neonatal Citrobacter Abscess. Axial (a) T2, (b) T1, (c) evident on T1 pre and post contrast images with debris a combination of viscous coagulative necrosis and possibly e.g demyelinating diseases Posterior Reversible Encephalopathy Syndrome (PRES) post contrast T1 and (d) DWI. There is bifrontal T2 prolongation, layering in the posterior aspect of the cavities with peripheral hypercellularity from polynucleated neutrophils in the pus. Sulfite oxidase is a mitochondrial enzyme responsible for oxidation of sulfite to sulfate, which is an more prominent on the right side with central region of low rim enhancement. The debris shows bright DWI signal, which (Images courtesy of Charles Glasier, MD, UAMS, Little Rock, Arkansas) T2 signal. Findings of white matter liquefaction are more corresponded to decreased ADC (not shown) likely due to PRES occurs with seizures, hypertension and uremic encephalopathy due to impaired autoregulation with vasodilatation important step in metabolism of sulphur containing amino acids. The acute findings are of diffuse leading to vasogenic edema. It is characterized by transient posterior cortical and subcortical lesions of increased T2 signal with cerebral edema with rapid progression to cystic encephalomacia, cortical necrosis and extensive increased or rarely decreased ADC values. (Figure 7) cavitating necrosis. (Figure 16) CONCLUSIONS References Figure 7. Posterior reversible leukoencephalopathy. Axial (a) 9) Leukodystrophies DWI with accompanying ADC map provides Lovblad KO, Schneider J, Ruoss K, Steinlin M, Fusch C, Schroth G: Kim JA, Chung JI, Yoon PH, Kim DI, Chung TS, Kim EJ, et al: Flair, (b) DWI, (c) ADC and 3D TOF additional useful information to the standard Isotropic apparent diffusion coefficient mapping of postnatal Transient MR signal changes in patients with generalized MRA. There is focal subcortical T2 Leukodystrophies are genetically determined metabolic diseases caused by enzyme deficiencies cerebral development. Neuroradiology 45:400-403, 2003 tonicoclonic seizure or status epilepticus: periictal diffusion- hyperintensity involving the right imaging sequences. Pathophysiological weighted imaging. AJNR Am J Neuroradiol 22:1149-1160, 2001 d e f leading to biochemical abnormality which results in hypomyelination or dysmyelination, both of which occipital region (arrow). DWI b c d mechanisms resulting in both baseline normal Lynch JK, Hirtz DG, DeVeber G, Nelson KB: Report of the National shows increased subcortical ADCs a Institute of Neurological Disorders and Stroke workshop on Majoie CB, Akkerman EM, Blank C, Barth PG, Poll-The BT, den Figure 8. Diffuse axonal injury. Axial (a & d) Flair, (b & e) DWI and (c & f) ADC. A right frontal-parietal can progress to demyelination. They are mostly characterized by myelin instability and destruction values with regional narrowing ADC values and changes with disease processes perinatal and childhood stroke. Pediatrics 109:116-123, 2002 Heeten GJ: Mitochondrial encephalomyopathy: comparison contusion results in increased signal in the cortex and subcortical white matter on FLAIR and with increased extracellular water. However, decreased diffusion with low ADCs has been reported Figure 16. Neonatal Sulfite oxidase deficiency. Axial (a) T2, (b) DWI, (c) ADC on day 4 and (d) follow up T2 after 4 months. of the right posterior cerebral of conventional MR imaging with diffusion-weighted and predominately increased ADC values (arrows). Additional subtle hazy increased FLAIR signal is seen There is subtle loss of grey white matter differentiation posteriorly. On DWI there is extensive signal increase and on ADC are not well understood and therefore caution artery on MRA. These findings are in a number of leukodystrophies such as Canavan’s disease, acute stages of adrenoleukodystrophy Grant PE, Yu D: Acute injury to the immature brain with diffusion tensor imaging: case report. in the right greater than left centrum semiovale and splenium with associated increased DWI signal marked signal decrease involving the cortex and subcortical white matter diffusely. Similar but less marked findings are also should be used when prognosticating the consistent with vasogenic edema hypoxia +/- hypoperfusionMagn Reson Imaging Clin N Am In and decreased ADC values due to axonal shear injury. Only mild volume loss was present in these and in metachromatic leukodystrophy, probably due to ongoing inflammation and intramyelinic noted in the bilateral basal ganglia and portions of the thalamus likely secondary to cytotoxic edema. On followup imaging, and associated vasculopathy. outcome of regions with abnormal ADC. Press, 2005 regions on follow-up. edema. The role of DWI is still evolving in this area. there is marked volume loss of the white matter, basal ganglia and to a lesser extent thalami. In addition diffuse ulegyria is a b c d noted. The subdural collections are secondary to the marked interval volume loss.