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Research ArticlePEDIATRICS

MR Imaging, MR Spectroscopy, and Diffusion Tensor Imaging of Sequential Studies in Neonates with Encephalopathy

A.J. Barkovich, S.P. Miller, A. Bartha, N. Newton, S.E.G. Hamrick, P. Mukherjee, O.A. Glenn, D. Xu, J.C. Partridge, D.M. Ferriero and D.B. Vigneron
American Journal of Neuroradiology March 2006, 27 (3) 533-547;
A.J. Barkovich
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S.P. Miller
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A. Bartha
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N. Newton
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S.E.G. Hamrick
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P. Mukherjee
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O.A. Glenn
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D. Xu
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J.C. Partridge
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D.M. Ferriero
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D.B. Vigneron
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    Fig 1.

    Locations of regions of interest for DTI and MRSI measurements are marked by rectangles.

    A, Squares showing region of interest locations from which proton spectra ratios were acquired and calculated by automated processing after each MR study of every patient.

    B, Squares and rectangles showing the 18 regions of interest from which Dav and FA values were calculated by automated processing.

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    Fig 2.

    Patient 163. Increasing abnormality from day 1 to day 3.

    A and B, Axial Dav maps at age 22 hours (day 1) show reduced diffusion in the ventrolateral thalami (arrows) and normal-appearing mesial temporal lobes in the region of the uncus.

    C, Proton MR spectroscopy from left thalamus at 22 hours shows elevated lactate peak (Lac) and normal appearing NAA peak. The peak upfield from lactate is propane diol (ethylene glycol), which is administered as the base for antiseizure medications.

    D and E, Axial Dav maps at age 64 hours (day 3) show more extensive reduced diffusivity. The mesial temporal lobes (D, white arrows) show reduced Dav, as do the cingula (E, black arrows) and the entire basal ganglia-thalami-insular region (E, white arrows).

    F, Proton MR spectroscopy from left thalamus at 64 hours shows interval increase in lactate and decrease in NAA and choline (Ch) compared with creatine (Cr).

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    Fig 3.

    Patient 170. Increasing abnormality from day 2 to day 3.

    A, Axial Dav map at age 34 hours shows extensive reduced diffusion in the lateral thalami (T) and, to a lesser extent, in the posterior left putamen (white arrow).

    B, Proton MR spectroscopy from the left thalamus at 34 hours is most remarkable for a moderate lactate peak (arrow).

    C, Axial Dav map at age 61 hours shows that extensive reduced diffusivity has developed within the putamina (arrows).

    D, Proton MR spectroscopy from the left thalamus at 61 hours shows a marked increase in lactate compared with NAA and choline.

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    Fig 4.

    Patient 178. Evolution of T1, diffusivity, and metabolites over 3 scans during 8 days. A–C were performed at day 1 (16 hours), D–F were performed at 4 days (84 hours), and G–I were performed at 8 days (178 hours).

    A, Axial T1-weighted image at age 16 hours is normal.

    B, Axial Dav map at age 16 hours shows a small amount of reduced diffusivity on the ventrolateral thalami (arrows). Measurements showed a reduction in Dav of about 10%.

    C, Proton MR spectroscopy from the right thalamus at age 16 hours shows minimal elevation of lactate (Lac), but is otherwise normal.

    D, Axial T1-weighted image at 84 hours shows that the normal hyperintensity in the posterior limb of the internal capsule is no longer seen. Abnormal hyperintensity is seen in the ventrolateral thalami and posterior putamina.

    E, Axial Dav map at 84 hours shows that reduced diffusivity is now present in the posterior putamina (arrows). Measurements of Dav showed significant reduction since day 1, with values now 50%–60% or normal (40%–50% reduced) in the thalami and putamina, and dorsal brain stem. Lesser reductions of about 25% were found in the cerebral hemispheric white matter.

    F, Proton MR spectroscopy from the right thalamus at 84 hours shows an increase in lactate (Lac) and relative reduction of choline and NAA compared with the first study.

    G, Axial T1-weighted image at 8 days shows that the T1 shortening is becoming less diffuse and more globular (arrows), with the globular regions being located in the globi pallidi, ventrolateral thalami, and at the junction of the anterior globi pallidi and putamina.

    H, Axial Dav map at 84 hours shows that reduced diffusivity is now almost exclusively seen in the posterior putamina (arrows) with the thalamic abnormality nearly completely gone. Measurements showed that the Dav values of the putamina were still about 30% below normal, but those in the thalami had normalized.

    I, Proton MR spectroscopy from the right thalamus at 8 days shows that the lactate peak has gotten significantly smaller. Note that the NAA and choline peaks have continued to decrease in size compared with the creatine peak.

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    Fig 5.

    Patient 193. New involvement of white matter pathways on second study. Studies performed at day 2 and day 7.

    A–C, Axial Dav maps at 34 hours show reduced diffusivity (Dav reduced by about 50%, black arrows) in the ventrolateral thalami, posterior limbs of internal capsules, and corticospinal tracts in centrum semiovale. No other areas of reduced diffusivity are identified.

    D, Proton MR spectroscopy from the left basal ganglia at 34 hours shows mild lactate (Lac) elevation.

    E–H, Axial Dav maps at 148 hours show that diffusivity in the deep gray nuclei has normalized (values were within 5% of normal); however, new areas of reduced diffusivity are seen in what are believed to be the optic radiations (E, medium white arrows), corpus callosum (F, small white arrows; G, smaller white arrows), cingulum (H, medium white arrows), and superior longitudinal fasciculus (G, larger arrows).

    I, Proton MR spectroscopy from left basal ganglia at 148 hours shows that lactate (Lac) has increased in comparison with NAA, choline, and creatine. NAA is the most reduced metabolite.

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    Fig 6.

    Patient 154. Increased volume of injury in vascular boundary zones from 2 to 4 days.

    A and B, Axial Dav maps at 49 hours show reduced diffusivity (Dav reduced by about 20%, black arrows) in the frontal and parietooccipital intervascular boundary zones. Note also some reduced diffusivity in the posterolateral thalami (white arrows).

    C, Proton MR spectroscopy from the left frontal white matter at 49 hours shows mild lactate (Lac) elevation.

    D and E, Axial Dav maps at 91 hours show more extensive reduced diffusivity in the frontal and parieto-occipital intervascular boundary zones and new reduced diffusivity along the optic radiations (black arrows). Dav values were not significantly changed from the prior study at 49 hours.

    F, Although the proton MR spectrum does not look significantly changed, measurements showed a 16% decrease in Lac/NAA and a 36% decrease in Lac/Ch in the frontal white matter compared with the study at 49 hours.

Tables

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    Table 1:

    Clinical, anatomic imaging, and diffusion (manual interrogation) data

    Patient No.Age at ScanClinical BackgroundT1-weighted imagesT2-weighted imagesDiffusion Images (Dav, mm2/s)
    153a2 d (25.5 h)Placental abruption, deep fetal decelerations and poor variability.Slight hyperintensity in basal ganglia and at the depths of several cortical sulci.Diffuse hyperintensity in white matter, basal gangliaReduced diffusivity in lateral thalami (0.70), posterior limbs of internal capsules (0.75)
    Emergent C-section.
    Seizure at 8 hours, required 3 drugsAbsent hyperintensity in PLIC
    153b6 d (124 h)Hyperintensity in dorsal brain stem, posterolateral putamina, lateral thalamiSlight hypointensity in posterolateral putamina and lateral thalamiReduced diffusivity in posterior thalami (0.80), splenium of corpus callosum (0.80), and left more than right hemispheric white matter
    154a2 d (48 h)Tight nuchal cord, variable decelerations.NormalBlurring of cortex and white matter in anterior and posterior watershed zonesReduced diffusivity in bilateral posterior thalami, anterior and posterior watershed cortex, and subcortical white matter
    Multifocal seizures at 10 hours, treated with 4 drugs.
    Negative blood and CSF cultures and PCR
    154b4 d (91 h)NormalBlurring of cortex and white matter in anterior and posterior watershed zonesReduced diffusion in posterior watershed cortex and white matter
    Slight persistent reduced diffusion in anterior watershed cortex
    Minimal persistent reduced diffusion in posterior thalami
    155a1 d (20 h)Oligohydramnios, thick meconium, birth depression.NormalHyperintensity in white matter and thalamiReduced diffusivity in watershed white matter
    Seizure on day of life 2, stopped with phenobarbital.PLIC present
    Negative blood cultures
    155b6 d (124 h)NormalSubtle gray-to-white blurring in posterior watershed cortex. Increased T2 in white matter and thalamiReduced diffusivity in watershed white matter
    PLIC present
    155c8 d (170 h)Hyperintensity in watershed cortexHyperintensity in watershed cortex, posterior more than anteriorNormal
    162a2 d (46 h)Maternal hypotension after epidural placement, fetal decelerations, C-sections, thick meconium. Seizures at 8 hours, treated with phenobarbital. Mom had history of herpes, but no lesions at labor, and PCR was negative for viruses in CSFSlight hyperintensity in VLT, posterior putamenNormalReduced diffusivity in left frontal subcortical white matter (0.50) and cortex, greater than right. Reduced diffusivity in VLT, left more than right (0.60–0.65)
    Faint hyperintensity in PLIC
    162b7 d (146 h)Hyperintensity in left more than right frontal cortex, left GPNormalReduced diffusivity in VLTs only (0.70–0.75)
    163a1 d (22 h)Seizures in utero 3 days before birth. Crash C-section due to flat fetal heart rate. Infant seizing at delivery, nuchal cord1. PCR of CSF was negativeHyperintensity in GP, putamen, caudate, VLTHyperintensity in most of cerebral cortexReduced diffusivity in VLTs (0.40), putamina (0.60), PLIC (0.55), subcortical white matter (0.70–0.75), dorsal BS (0.45–0.50)
    Absent hyperintensity in PLIC
    163b3 d (64 h)Hyperintensity in GP, putamen, caudate, VLT, dorsal BSHypointensity in dorsal BS, VLT, lateral putamenReduced diffusivity in hippocampi (0.45), subcortical white matter (0.45–0.50), basal ganglia (0.45), thalami (0.35), cerebellar vermis (0.50)
    Absent T1 in PLICLong T2 in remainder of thalamus, much of cortex
    167a1 d (19 h)Pre-eclampsia, failed home labor, thick meconium, variable decelerations, crash C-section. After birth, persistent pulmonary hypertension, hypoglycemia, acute tubular necrosis. Blood cultures negativeIncreased T1 in VLTNormalTiny area of reduced diffusivity in VLTs (0.85)
    Normal PLICFocal infarct left frontal lobe
    167b4 d (88 h)NormalSlight T2 prolongation in cortical infarctsSmall amount of reduced diffusivity in VLTs (0.60) and CSTs (0.70). Two focal infarcts, left frontal and left occipital
    170a2 d (34 h)Uterine rupture, deep decelerations.Hypointensity in thalamiHyperintensity in thalami, basal gangliaReduced diffusivity in lateral thalami (0.55), CSTs (0.65), posterior BS (0.65–0.70)
    Seizures at 9 hours. Blood cultures negativeNormal PLIC
    170b3 d (61 h)Hypointensity in basal gangliaHyperintensity in thalami, basal gangliaReduced diffusivity in putamen more than caudate, anterior and lateral thalami (0.40), CSTs (0.45–0.50), subthalamic nuclei, dorsal BS (0.50)
    Hyperintensity not seen in PLIC
    178a1 d (16 h)Maternal septic shock. Fetal tachycardia and abnormal fetal tracing. Thick meconium; no spontaneous activity or respirations at birth. Apgars 0, 0, 1 at 1, 5, and 10 minutes. Transient hepatic and renal dysfunction. Seizures before first MR image. Blood and CSF cultures of infant were negativeHyperintensity in caudate, GP, putamenHypointensity in VLTReduced diffusivity in VLTs (0.65), CSTs (1.0)
    Normal PLICBlurring of perirolandic cortex
    178b4 d (83 h)Hyperintensity in VLT, GP, posterior putamen, posterior insulaNormalReduced diffusivity in posterior putamina (0.55), VLTs (0.50), CSTs (0.70–0.75), CC (0.75), subcortical white matter (0.60)
    Hyperintensity not seen in PLIC
    178c7 d (178 h)Globular hyperintensity in VLTs, GP–putamen junction, posterolateral putamen. Hyperintensity not seen in PLICHeterogeneous basal nuclei. T2 prolongation in cerebral white matterReduced diffusivity in posterior putamen (0.70). Minimally reduced in VLTs (0.90), CSTs (1.0).
    193a2 d (34 h)Home delivery complicated by LGA infant and shoulder dystocia. After prolonged delivery, infant was cyanotic, limp. Infant was given CPR for 40 minutes before spontaneous respirations. Seizures at about 5 hours, treated with phenobarbitalHyperintensity in VLTs, GPs, putamina, caudates, most of cerebral cortex. Normal PLICHyperintensity of BG, thalami. Blurring of perirolandic cortexReduced diffusivity in VLTs (0.45–0.50), CSTs (0.60)
    193b7 d (148 h)Hyperintensity in VLTs, GPs, putamina, caudates, posterior insular cortex, perirolandic cortex, calcarine cortexNormalReduced diffusivity in cingulum (0.65), corpus callosum (0.60), fronto-occipital fasciculus (0.95), optic radiations (0.90), uncinate fasciculus (0.85)
    Hyperintensity not seen in PLIC
    195a2 d (44 h)Jittery baby. Mild hypoglycemia. Low normal ABG pHNormal. Hyperintensity present in PLICNormalNormal
    195b19 d (330 h)Focus of hyperintensity in right frontal periventricular white matterNormalNormal
    • Note:—Dav indicates average diffusivity; PLIC, posterior limb of internal capsule; ABG, arterial blood gas; VLT, ventrolateral thalamus; CST, corticospinal tract; GP, globus pallidus; CC, corpus callosum; LGA, large for gestational age; CPR, cardiopulmonary resuscitation; CSF, cerebrospinal fluid; BS, brain stem; PCR, polymerase chain reaction.

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    Table 2.

    Diffusion data from automated processing

    Patient No.Dav V0Dav V1Dav V2Dav V3Dav V4Dav V5Dav V6Dav V7Dav V8Dav V9Dav V10
    153a1274.241278.57912.551948.1221481.611407.821176.61199.7313441303.291497.69
    153bN/AN/AN/AN/AN/AN/AN/AN/AN/AN/AN/A
    154a1117.531111.89946.773937.831281.961350.271079.621109.051065.621097.971326.35
    154b1237.791199.411110.941077.081364.241348.911140.51206.361179.751300.341125.61
    155a1149.221183.5997.951056.081236.51316.491154.741215.41198.181109.861538.64
    155b845.5824.827768.009712.835956.8551009.75849.545842.436857.864866.35958.491
    155c1287.581280.51157.11118.981428.451420.551222.61231.451553.61337.481691.56
    162a1093.491117.43975.102957.4291231.081279.311108.831121.711032.181165.361292.57
    162b1210.611174.371008.331021.611335.981283.271207.291188.761231.411256.411553.59
    163a1029.651013.39712.633714.3471334.591210.961092.91110.411302.21354.761824.82
    163b693.694674.898649.816583862.429935.776841.918856.878758.776914.2321002.63
    167a1239.981251.21026.67977.1071399.391307.881209.841218.981286.931329.551447.08
    167b1180.671166.731008.43989.7551290.061347.551197.231217.221168.471196.411282.24
    170a1195.671196.51622.429732.8981378.241398.451277.431255962.4081049.691374.71
    170b981.286942.5601.122603.9591400.651484.711158.331112.961436.921424.491346.39
    178a1214.621231.98987.5906.6671524.81545.31160.251274.141195.751249.191572.71
    178b1169.941149.711118.1711941615.11515.71326.111245.221308.751246.691751.57
    178c1179.791180.631129.751128.5815071515.91242.981199.291288.331333.081492.29
    193a1105.361135582.5702.5831439.21357.81141.461126.591089.441066.251423.18
    193b1104.861049.86822.757831200.61181.51174.221296.21088.941078.331280.31
    195a1329.411295.591155.6712171247.51369.81177.221196.141148.331172.121317.49
    195b1154.5111929561076.51340.71335.61123.961264.311094.51134.811330.12
    • Note:—Dav V indicates diffusivity in Voxel; N/A, data not available.

    • View popup
    Table 3:

    Metabolite ratios from the single voxel proton spectroscopy

    Patient No.Age at StudyLac/Ch (BG)Lac/NAA (BG)NAA/Ch (BG)Cr/NAA (BG)Cr/Ch (BG)Lac/Ch (W/M)Lac/NAA (WM)NAA/Ch (WM)Cr/NAA (WM)
    153a2 d0.581.260.460.880.41MDMDMDMD
    153b6 d0.651.890.340.970.33MDMDMDMD
    154a2 d0.140.200.720.690.490.470.670.710.51
    154b4 d0.190.220.830.720.600.300.560.530.78
    155a1 d0.170.220.790.600.470.390.630.620.62
    155b6 d0.120.200.620.800.500.230.400.590.61
    155c8 d0.070.100.720.800.570.120.250.470.73
    162a2 d0.090.120.750.720.540.390.630.620.58
    162b7 d0.040.060.680.550.370.110.190.560.38
    162b7 d0.040.060.680.550.370.110.190.560.38
    163a1 d0.991.730.570.950.541.111.940.570.86
    163b3 d1.062.810.381.090.411.132.780.410.90
    167a1 d0.160.170.930.520.490.130.190.690.61
    167b4 d0.150.210.720.640.460.150.200.740.52
    170a2 dMDMDMDMDMDMDMDMDMD
    170b3 dMDMDMDMDMDMDMDMDMD
    178a1 d0.150.250.600.590.350.280.340.800.48
    178b4 d0.480.900.540.860.460.340.490.690.60
    178c8 d0.230.350.660.850.560.200.370.550.66
    193a2 d0.380.400.950.600.570.400.510.770.43
    193b7 d0.431.170.370.860.320.491.380.350.69
    195a2 d0.040.500.750.570.430.010.020.640.62
    195b14 d0.000.000.910.540.490.010.020.870.37
    • Note:—Ch indicates choline; NAA, N-acetylaspartate; MD, missing data.

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A.J. Barkovich, S.P. Miller, A. Bartha, N. Newton, S.E.G. Hamrick, P. Mukherjee, O.A. Glenn, D. Xu, J.C. Partridge, D.M. Ferriero, D.B. Vigneron
MR Imaging, MR Spectroscopy, and Diffusion Tensor Imaging of Sequential Studies in Neonates with Encephalopathy
American Journal of Neuroradiology Mar 2006, 27 (3) 533-547;

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MR Imaging, MR Spectroscopy, and Diffusion Tensor Imaging of Sequential Studies in Neonates with Encephalopathy
A.J. Barkovich, S.P. Miller, A. Bartha, N. Newton, S.E.G. Hamrick, P. Mukherjee, O.A. Glenn, D. Xu, J.C. Partridge, D.M. Ferriero, D.B. Vigneron
American Journal of Neuroradiology Mar 2006, 27 (3) 533-547;
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