Perinatal Asphyxia: MR Findings in the First 10 Days

A. James Barkovich, Kaye Westmark, Colin Partridge, Augusto Sola, and Donna M. Ferriero

PURPOSE: To determine whether one can detect hypoxic-ischemic brain injury by MR in the first10 days of life and to identify patterns of injury in affected neonates. METHODS: Standard T1- andT2-weighted MR sequences that were performed in the first 10 days of life in 20 patients whosuffered hypoxia/ischemia in the intrapartum or neonatal periods were reviewed retrospectively.Images were evaluated for patterns of signal changes. RESULTS: Four patients had normalfindings and were clinically healthy. The remaining 16 patients were divided into four groups basedon pattern of injury: (a) primarily deep gray matter involvement; (b) primarily cortical involvement;(c) primarily periventricular white matter injury; and (d) mixed injury pattern. Two patients hadappearances that suggested prepartum injury. T1 shortening was seen in injured tissue as early as3 days after injury. T2 shortening did not appear until 6 or 7 days after injury. CONCLUSION: MRcan show brain damage in asphyxiated neonates during the first 10 days of life and shows earlyappearances of several patterns of brain injury.

Index terms: Asphyxia; Brain, ischemia; Infants, injuries; Magnetic resonance, in infants andchildren

AJNR Am J Neuroradiol 16:427–438, March 1995

Magnetic resonance imaging (MR) has had alarge impact on the evaluation of the asphyxi-ated neonate. MR can show parenchymal andintraventricular hemorrhage (1–3), periven-tricular white matter damage (1, 4–6), and spe-cific patterns of brain damage (7–9) in affectedneonates. Most studies, however, have relied onimages obtained when the infants were in theintermediate or late phase of injury, weeks tomonths after the asphyxic episode. Althoughimaging studies performed in the intermediateor late phase allow identification of injury pat-terns and, to some extent, prognostication oflong-term outcome, they are far removed tem-porally from important decisions concerning

Received June 8, 1994; accepted after revision September 2.Partially supported by grants 1P20NS32553-01 and MO1-RR01271

from the National Institutes of Health.From the Departments of Radiology, Neuroradiology Section (A.J.B.,

K.W.), and Pediatrics (A.J.B., A.S., D.M.F.), University of California SanFrancisco; and the Department of Pediatrics, San Francisco General Hos-pital (C.P.).

Address reprint requests to A. James Barkovich, MD, NeuroradiologySection, Department of Radiology, University of California San Francisco,505 Parnassus Ave, L-371, San Francisco, CA 94143-0628.

AJNR 16:427–438, Mar 1995 0195-6108/95/1603–0427

q American Society of Neuroradiology

42

patient care. The purpose of this study was toevaluate MR studies performed during the first10 days of life of asphyxiated neonates in orderto determine whether MR imaging is sensitive tohypoxic-ischemic brain injury and can showspecific patterns of injury during the earlypostinjury period.

Patients and MethodsOn review of our records, we found MR studies of 20

infants who were examined in the first 10 days of life forevaluation of neonatal hypoxia-ischemia. The MR studieswere reviewed retrospectively and correlated with obstet-rical records and neonatal clinical summaries. Four pa-tients had normal MR findings, obtained between ages 5days and 8 days. The birth histories and umbilical cordblood gases of these four infants did not differ noticeablyfrom those of the 16 patients with abnormal imaging stud-ies; they underwent MR examinations as part of a protocolrelated to their severe birth histories. All 4 had benignpostnatal courses and were healthy at their 3-month fol-low-up clinical examination. In the remaining 16 patients,with whom this article will deal, MR studies were performedon day 2 in 1 patient, on day 3 in 4 patients, on day 4 in 3patients, on day 5 in 2 patients, on day 6 in 2 patients, onday 7 in 2 patients, and on day 10 in 2 patients (Table).Twelve infants were born at term, 2 at 35 weeks of gesta-tional age, and 2 at 32 weeks of gestational age.

7

Clinicalandimaginginform

ationon

16neonates

who

hadhypoxic-ischem

icevents,groupedby

area

ofdamage

Patient/O

bstetricHistory

PostnatalC

linicalData

Blood

Gas

(Umbilicalartery)

Apgar,

1/5/10/20min

Age,

dMRFindings

Group

1,deep

structures

1/Term

infant;cord

prolapse;bradycardia

(HR,30–40beatspermin)for20–25min

Multiorgan

failure

seizures;

recurrentbradycardia/

cyanosis

pH,6.86;BD,19

...

5T1shortening

lateralthalamus,medialand

posteriorlentiform

nuclei,deep

perirolandiccortex

2/Term

infant;uterinerupture

USnorm

alpH

,6.7;

BD,26

1/3/4/6

5T1shortening

lateralthalamus,medialand

posteriorlentiform

nuclei,deep

perirolandiccortex

3/Term;thickmeconium;bradycardia(HR,35

beatspermin)for13

min;totalcordocclusion

Seizuresfor72

hrs;

hypoventilation;

US

norm

al

pH,6.67;BD,22

1/3/.../...

3T1shortening

lateralthalamus,medialand

posteriorlentiform

nuclei;edem

aPLIC;

T2shortening

lateralthalamus,posterior

putamen

4/Term

infant;norm

aldelivery

Cardiorespiratory

arrest

(for

12min)at

age2

hrs;seizures

for48

hrs

prearrestpH

,7.41;

postarrest,6.7;

BD,22

9/10/.../...

3T1shortening

lateralthalamus,medialand

posteriorlentiform

nuclei;edem

aPLIC;

long

T2inwhitematterandbasalganglia

5/34

wk;

emergencycesarean

section;

fetal

bradycardia(HR,

,40

beatspermin);

.50%abruption15

minbefore

intubation

Multiorgan

failure;seizures;

died

atday13

pH,6.7;

P O2,30;

BD,25

0/0/1/2

7DiffuseT1andT2prolongationinwhite

matter;T1shortening

lateralthalami,

posteriorandmediallentiform

nuclei,and

depthof

manycorticalgyri;punctate

periventricularT1,

T2shortening

6/38

wk;

cord

rupture

Multiorgan

failure;seizures;

died

at6wk

pH,6.7;

P O2,30;

BD,21

1/4/.../...

4T1shortening

lateralthalamus,medialand

posteriorlentiform

nuclei,deep

perirolandiccortex,mesencephalon,

cerebellarnuclei;long

T2inbasalganglia

andat

gray-whitematterjunctionof

perirolandicregion

7/32

wk;

emergencycesarean

sectionafterauto

accident

Aspirationof

blood;

airway

obstruction;

USnorm

alpH

,6.6;

BD,24

1/3/.../...

10T1,

T2shortening

globus

pallidus,lateral

thalam

us,peritrigonalwhitematter;long

T1,

T2inallcerebralw

hitematter;

choroidplexus

hemorrhage

8/Term

infant;50%abruption,

eclampsia,

polyhydram

nios

Bilateralpneum

othoraces;

congenitalcontractures;

low-setears,sm

allL

ear;

bilateralsimiancreases

...

3/4/4/6

4Injury

looksold;

atrophy,welllocalized

T1,

T2shortening

9/Term

infant;eclampsia,prem

atureruptureof

mem

branes

for28

hrs;laborfor5d;

thick

meconium;persistent

acidosis

Multiorgan

failure;seizures;

died

atage4mo

pH,7.15;P O

2,62;

BD,9

2/3/.../...

10Long

T1dorsalbrainstem

;shortT1lateral,

posteriorthalam

i;shortT1posteriorand

mediallentiform;shortT1deep

perirolandicgyri;shortT2lateralthalami,

lateralputam

ina;long

T2dorsalbrain

stem

andmedialcerebralcortex

Group

2,cortex

10/Term

infant;em

ergencycesarean

sectionfor

fetalbradycardia(HR,60

beatspermin)for

15min

Meconium,pneumothorax;

transientoliguria;mildly

elevated

liver

function

tests

pH,6.78;BD,22

1/4/4/6

7AnteriorandposteriorT1andT2

prolongationinthevascular

boundary

zones;basalganglianorm

al

(Tab

lecontinues.)

428 BARKOVICH AJNR: 16, March 1995

Tablecontinued Patient/O

bstetricHistory

PostnatalC

linicalData

Blood

Gas

(Umbilicalartery)

Apgar,

1/5/10/20min

Age,

dMRFindings

11/Term

infant;homebirth;

oligohydramnios;

postnataldehydrationandcyanosisfor30

hrTransient

oliguria;elevated

liver

functiontests;

seizures;USnorm

al

...

...

3T1andT2prolongationanterior

and

posteriorboundary

zones;basalnuclei

norm

al12/Term

infant;laborfor4d;

hypovolemia;fetal-

maternaltransfusion;variablelate

decelerations

Systolic

bloodpressure,

20;initialhematocrit,8;

transientoliguria

pH,7.1;

P O2,90;

BD,11

2/3/.../...

3T1shortening

indepths

ofgyriinvascular

boundary

zones;diffuse

corticalT2

prolongation,

greaterinboundary

zones;

severe

whitematteredem

a;basalganglia

norm

alGroup

3,periventricularwhitematter

13/32wk

Prolongedrespiratory

depression;patent

ductus

arteriosis;

hypertonicat

3mo

...

...

6FociofT1,

T2shortening

inperitrigonal

whitematter;diffuse

edem

a

Group

4,mixed

14/35wk;

ruptured

cord

Multiorgan

failure;died

atage16

wk

pH,6.5;

BD,26

1/1/3/4

4Germinalmatrixhemorrhagebilateral

ganglionicem

inence;intraventricular

and

subarachnoidhemorrhage;shortT1,

T2

lateralthalami,posteriorandmedial

lentiform

,andcentralcerebralw

hite

matter;long

T2entirecortex;edem

aPLIC

15/35wk;

meconium

aspiration;

smallfor

gestationalage

Periventricular

leukom

alacia,?previous

injury

pH,6.8;

P O2,52;BD,

16

3/5/.../...

6Diminishedhemisphericwhitematter;short

T1laterallentiform,rightfrontalpole;

smalllentiform

nuclei;shortT2inlateral

thalam

i,posteriorlentiform

,rightcerebral

peduncle,anddeep

perirolandiccortex;

long

T2inmuchof

cerebralcortex;big,

irregularventricles

16/Term

infant;maternalchorioamnionitis;arrest

atage7h,

unknow

nduration

Multiorgan

failure;seizures;

USnorm

al;died

atage

8d

pH,6.5;

P O2,20;BD,

24

1/4/8/...

2T1shortening

inglobus

pallidus,lateral

putamen,andlateralthalami.T2

prolongationinentirecerebralcortex,

basalgangliaT1prolongationPLIC

Note.—BDindicatesbase

deficit;

US,ultrasound;HR,heartrate;andPLIC,posteriorlim

binternalcapsule.

AJNR: 16, March 1995 PERINATAL ASPHYXIA 429

The infants’ charts were reviewed for obstetric history,Apgar scores, umbilical cord blood gases, presence andestimated duration of hypoxic-ischemic episode, and neo-natal course. MR studies were performed at 1.5 T andconsisted of spin-echo axial 4-mm (400–600/11–20/1[repetition time/echo time/excitations]), axial 4-mm(3000/50–60, 100–120), and sagittal 3-mm (500–600/11–20) images in all patients. Coronal spin-echo 4-mm(600/11) images were available in 2 patients.

Results

Obstetric History

A wide variety of obstetric histories werepresent; details are presented in the Table. Twopatients had normal deliveries, but one had acardiocirculatory arrest for unknown reasonsduring the first day of life and the other hadprolonged postnatal dehydration and cyanosis,possibly related to maternal oligohydramnios.Another patient had a complicated delivery, re-covered, then had an unwitnessed arrest of un-known duration at age 7 hours.Three deliveries were complicated by fetal

bradycardia of less than 40 beats per minutefor 13 to approximately 30 minutes (it wasimpossible to obtain exact timing in mostcases) and a fourth by bradycardia of 60beats per minute for approximately 15 min-utes. Three patients were born through thickmeconium. Two deliveries were complicatedby rupture of the umbilical cord, one by uter-ine rupture, and one by complete umbilicalcord occlusion. Other factors leading to thehypoxic-ischemic injury in these neonateswere maternal eclampsia (two patients), pla-cental abruption (two patients), polyhydram-nios (one patient), and fetal-maternal transfu-sion with resultant hypovolemia (one patient).

Neonatal History (see Table)

One-minute and 5-minute Apgar scores wereavailable in 12 patients. Ten-minute Apgarscores were available in 6 of the 12 and 20-minute Apgars were available in 5 of those 6patients. Other than patient 4, who had a nor-mal delivery and arrested later, the availableApgar scores were uniformly poor, ranging from0 to 3 at 1 minute and from 0 to 5 at 5 minutes.Umbilical cord blood gases were obtained in

13 patients. Excluding the patient with normaldelivery, the pH of the blood ranged from 6.5 to7.15, with 10 of the 13 below 6.9. Base deficits

430 BARKOVICH

ranged from 11 to 26. Seizures were presentwithin the first 24 hours in 8 patients, multior-gan failure was present in 6 patients, transientoliguria in 2 patients, and congenital contrac-tures in 1. Five of the patients died within a fewmonths of birth.

Imaging

We have separated the patients into fourgroups based on patterns of damage. In onegroup, abnormal signal was primarily in deepstructures, in the second, signal abnormalitieswere primarily cortical, in the third, abnormalsignal was in the periventricular white matter,and in the fourth, the pattern was mixed.Group 1. The largest group consisted of nine

patients. Images of these patients showed T1shortening, predominantly in the lateral thal-ami, globi pallidi, and posterior putamina; T2-weighted images showed diffuse T2 prolonga-tion, presumably caused by edema. The lateralthalami, globi pallidi, and posterior putamina(Figs 1–3) were hyperintense on T1-weightedimages in all patients except patient 7, in whomonly the globi pallidi and lateral thalami wereaffected. T1 shortening of the caudate nucleiwas seen in three patients (Fig 2). The T1 short-ening in the basal nuclei was diffuse and homo-geneous in all except patient 8, in whom it wasvery localized in the lateral thalami and poste-rior putamen and associated with T2 shorteningin the same regions (Fig 4). Patient 8 also hadsmall basal nuclei and very prominent ventri-cles and subarachnoid spaces. The posteriorlimb of the internal capsule, which is usuallyhyperintense on T1-weighted images in neo-nates, was conspicuously hypointense in all pa-tients (Figs 1–3). In five patients, the cerebralcortex was involved at the depths of sulci; inmost patients, the perirolandic region was par-ticularly affected (Fig 1B). In two patients, ab-normal signal intensity was present in the dorsalbrain stem, hypointensity (Fig 3B) in patient 9and patchy hyperintensity in patient 6. In pa-tient 6, the cerebellar white matter showed hy-perintensity as well. Patient 9 also had T1 short-ening in the claustra (Fig 3A).Group 2. Images of the three patients in the

second group (patients 10, 11, and 12) hadabnormal signal, predominantly hypointensityon T1-weighted images and hyperintensity onT2-weighted images, in the cerebral cortex andsubcortical white matter. The vascular bound-

AJNR: 16, March 1995

Fig 1. Patient 1, group 1, born at term. Images at 5 days.A, Axial spin-echo (500/19) image shows diffuse hyperintensity in the lentiform nuclei and lateral thalami, highlighted by the low

intensity of the posterior limb of the internal capsule, which is normally the brightest structure in the brain at this age.B, Axial spin-echo (500/19) image at the convexity level shows hyperintensity (arrows) at the deep portions of the cortical gyri,

primarily in the perirolandic region.C, Axial spin-echo (3000/120) image is normal other than slight hyperintensity of the basal nuclei.

AJNR: 16, March 1995 PERINATAL ASPHYXIA 431

Fig 2. Patient 5, group 1, born at 34 weeks. Image at age 7days. Axial spin-echo (600/12) image shows abnormal hyperin-tensity of the thalami, lentiform nuclei (solid white arrows) andcaudate heads (curved arrows), highlighted by abnormal hypoin-tensity of the posterior limb of the internal capsule (open blackarrows). The cortex at the depths of many sulci (open whitearrows) are abnormally hyperintense.

ary zones (“watershed zones”) between the ma-jor cerebral vessels were predominantly in-volved (Fig 5), although all of the cerebralcortex was involved in patient 12 (Fig 6). Pa-tient 12 had T1 shortening in some of the af-fected cortex (Fig 6).Group 3. Images of patient 13 had T1 and T2

shortening limited to the periventricular whitematter (Fig 7) in conjunction with T1 and T2prolongation diffusely throughout the cerebralwhite matter. The deep structures of the brainand the cerebral cortex appeared spared.Group 4. Images of patients 14, 15, and 16

showed a combination of findings seen in theother groups. Patient 14 had abnormal T1 andT2 prolongation in the lateral thalami, globi pal-lidi, and posterior putamina, T2 prolongation ofthe entire cerebral cortex, and T1 and T2 short-ening in the cerebral white matter, particularlyin the frontal and parietal lobes (Fig 8). Germi-nal matrix and intraventricular hemorrhage waspresent as well. Patient 15 had T1 shortening inthe putamina and heterogeneous T2 shorteningand prolongation (Fig 9) in the lateral thalami,posterior lentiform nuclei, right cerebral pedun-cle, and deep perirolandic cortex. The cerebralcortex showed diffuse T2 prolongation (Fig 9D).Of interest, patient 15 was small for gestationalage and had enlarged lateral ventricles with ir-

Fig 3. Patient 9, group 1, born at term.Images at age 10 days.

A, Axial spin-echo (500/12) imageshows abnormal hyperintensity of the lateralthalami (short arrows), lentiform nuclei(long arrows), and claustra (small arrows).The abnormal hypointensity of the posteriorlimb of the internal capsule highlights thehyperintensity of the adjacent structures.

B, Axial spin-echo (500/12) at the levelof the mesencephalon shows abnormal hy-pointensity of the tegmentum (curvedarrows).

432 BARKOVICH AJNR: 16, March 1995

regular ventricular margins (Fig 9), indicatingprior injury. Patient 16 had T1 prolongation inthe posterior limb of the internal capsule andslight T1 shortening of the lateral thalami inaddition to T2 prolongation in the basal nucleiand the entire cerebral cortex.

Discussion

Modern medical technology and pharmacol-ogy allow neonatologists to sustain very sickneonates, such as those who have sufferedhypoxic-ischemic injury, until they can main-tain homeostasis independently. These drugsand technology are expensive, however, andsocioeconomic factors are forcing neonatolo-gists to establish criteria for selecting those pa-tients who are most likely to benefit from inten-

sive therapy. The status of the nervous systemis a crucial factor in decisions about treatmentof these patients. A recent study of 97 medicalrecords from 111 deaths in an intensive carenursery revealed that central nervous systemdamage was the most common reason (35% ofcases) for withdrawal of life support (10). Un-fortunately, differentiation of patients with gooddevelopmental prognoses from those with poorprognoses by clinical or laboratory criteria isoften difficult. Therefore, finding new methodsfor the early detection and determination of theextent of brain injury caused by asphyxia is ofgreat importance in the treatment of asphyxi-ated newborns.Transfontanel sonography is the imaging

study used at most institutions for the initial

Fig 4. Patient 8, group 1, born at term.Images at age 4 days.

A, Axial spin-echo (400/11) imageshows punctate hyperintensity in the inferiorlentiform nuclei (open arrows) and inferolat-eral thalami (solid arrows). The third ventri-cle and subarachnoid spaces are prominent.

B, Axial spin-echo (3000/100) imageshows punctate hypointensity in the inferiorlentiform nuclei (open arrows) and inferolat-eral thalami (solid arrows). Soft tissue swell-ing is present in the right frontal region.Cerebrospinal fluid spaces are prominent.

Fig 5. Patient 11, group 2, born at term.Images at age 3 days.

A, Axial spin-echo (3000/120) imageshows loss of normal cortical hypointensity inthe anterior (single arrows) and posterior(double arrows) vascular boundary zones.Basal ganglia were normal.

B, Axial spin-echo (3000/120) at age 10weeks shows shrunken cortex with abnormalhyperintensity of the cortex and subcorticalwhite matter.

AJNR: 16, March 1995 PERINATAL ASPHYXIA 433

assessment of the asphyxiated neonate. Al-though MR imaging has been established as auseful technique in the assessment of asphyxi-ated neonates in the intermediate (1, 4, 5, 7)and late (8, 11) stages, little has been writtenabout the usefulness of MR imaging in the firstweek or 10 days of life. In this study, standardspin-echo MR imaging showed symmetric,sometimes subtle, abnormalities that were de-tected as early as the second day after birth.Moreover, transfontanel sonograms in five ofthe patients (all performed within 24 hours ofthe MR) were all interpreted as normal, even inretrospect, by experienced neurosonographers.Thus, this study suggests that MR imaging is a

useful technique in the evaluation of the asphyx-iated neonate during the first few days of life.Birth and perinatal histories differed among

patients in different groups. Most (7 of 9) group1 patients suffered severe mishaps such as rup-tured umbilical cord, occluded umbilical cord,ruptured uterus, profound bradycardia (,40beats per minute), or cardiocirculatory arrest.The pattern of injury in these patients fits thedescription of “profound asphyxia” (7). Pre-sumably, the involved brain regions are specif-ically affected because they are myelinated(12); these regions have higher metabolic re-quirements (as shown by fludeoxyglucose F 18positron emission studies [13]).

Fig 6. Patient 12, group 2, born at term.Images at age 3 days.

A, Axial spin-echo (600/20) imageshows small ventricles and sulci. T1 short-ening is seen in the cortex in some regions.The basal ganglia and internal capsule arenormal.

B, Axial spin-echo (3000/120) imageshows almost total lack of contrast betweencerebral cortex and underlying white mat-ter, presumably secondary to hyperinten-sity of the cortex resulting from edema.

Fig 7. Patient 13, group 3, born at 32weeks. Images at 6 days.

A, Axial spin-echo (600/16) imageshows punctate hyperintensity (arrows) inthe peritrigonal white matter. Basal gangliaand thalami are normal for age.

B, Axial spin-echo (3000/120) imageshows punctate hypointensity (arrows) inthe peritrigonal white matter. The high sig-nal intensity in the right temporooccipitalregion is shading artifact from static fieldinhomogeneity.

434 BARKOVICH AJNR: 16, March 1995

Fig 8. Patient 14, group 4, born at 35 weeks. Images at 4 days.A, Axial spin-echo (600/15) image shows hemorrhage in the left ganglionic

eminence (open arrow) and layering in the occipital horns of the lateral ventricles(solid arrows). The appearance of the basal ganglia is similar to that in the patients ingroup 1 (Figs 1–3).

B, Axial spin-echo (600/15) image shows large areas of hyperintensity in thecerebral white matter (curved arrows).

C, Axial spin-echo (3000/120) image shows marked hypointensity in the cerebralwhite matter (curved arrows). The cortex is hyperintense and is difficult to differen-tiate from underlying white matter.

D, Sagittal spin-echo (500/15) image shows apparent occlusion of the torcula(arrows) and superior sagittal sinus. Flow was not seen in the superior sagittal sinusor torcula on any sequences. No flow sequences were performed to confirm thepresumed diagnosis of sinus thrombosis.

Fig 9. Patient 15, group 4, born at 35 weeks. Images at 6 days.A, Axial spin-echo (400/20) image shows hyperintensity in the right lateral thala-

mus (open black arrow) and posterolateral putamina (white arrows).B, Axial spin-echo (3000/120) image shows heterogeneous hyperintensity and

hypointensity in the basal ganglia and thalami. The cerebral cortex is poorly seen inmultiple areas.

C, Axial spin-echo (400/20) image shows enlarged ventricles with irregular poste-rior borders (arrows) and diminished white matter between the lateral ventricularmargin and the posterior body of the lateral ventricles.

D, Axial spin-echo (3000/120) image shows prominent subarachnoid spaces andabnormal signal intensity in the cerebral cortex. Much of the cortex is isointense withunderlying white matter (it should normally be hypointense), whereas the perirolandicareas (arrows) appear to be very hypointense.

AJNR: 16, March 1995 PERINATAL ASPHYXIA 435

Two patients in group 1 had atypical MR fea-tures. In contrast to the diffuse T1 shortening inthe lateral thalami and lentiform nuclei in theother patients, there was focal T1 shortening inthe lateral thalami and posterior putamina inpatient 8 (Fig 4), similar to what has been de-scribed in the intermediate period, weeks afterinjury (1, 4, 7). Moreover, the thalami and dor-sal brain stem were small (perhaps atrophic),the subarachnoid spaces were large, the patienthad congenital contractures and dysmorphicfeatures, and the pregnancy was complicatedby polyhydramnios and eclampsia. These fac-tors suggest an in utero injury, before the ab-ruption at the time of delivery. Patient 9 wasatypical in that the dorsal brain stem exhibitedprolonged T1 (Fig 3B) and T2 relaxation times,and the umbilical cord blood gases were con-

siderably less abnormal than the other patientsin this group. This patient was also born after acomplicated prenatal and perinatal course (seeTable); thus, it is possible that a significantevent occurred some time before delivery, re-sulting in a less severe acidosis at the time ofbirth. The very protracted and complicated la-bor may have contributed to the severity of thedorsal brain stem injury as well. Reports of MRidentification of brain stem injury in asphyxiatedneonates is uncommon (1, 4, 7, 9), in contrastto reports in the pathology literature, which in-dicate that dorsal brain stem injury is commonin profound asphyxia (14–16). This discrep-ancy may result from a lack of sensitivity of MRto brain stem injury or from selection bias; brainstem–injured infants presumably suffer higherearly mortality and thus may be less likely to

undergo MR imaging and more likely to un-dergo autopsy. Further elucidation is dependenton more patients undergoing MR relatively earlyin the postnatal course.The Apgar scores and umbilical cord blood

gases of patients in group 2 are not remarkablydifferent from those in group 1. However, theinfants in this group had either less severe bra-dycardia than group 1 patients (60 beats perminute in patient 5, in contrast to less than 40beats per minute in group 1 patients) or hypo-volemia or anemia; these conditions lead to re-duced cerebral blood flow, but not completecessation of flow. Blood gets shunted to thedeep structures of the brain under conditions ofreduced flow (17, 18); therefore, it is not unex-pected that the basal ganglia, brain stem, andcerebellum are spared while the cerebral cortexis injured. The amount of cortical injury seemedgrossly proportional to the duration of the re-duced cerebral blood flow. Patient 10, who hadreduced blood flow for only about 15 minutes,had small areas of injury, whereas patient 11,who had progressive dehydration and cyanosisover 30 hours, had large areas of injury, andpatient 12, who had hypotension and severeanemia for several days secondary to fetal-maternal transfusion, had abnormal signal ofthe entire cerebral cortex.T1 and T2 shortening in the periventricular

white matter of premature infants with periven-tricular leukomalacia, such as patient 13, hasbeen noted previously (4) with the observationthat the signal changes persist for 1 through 6weeks. The authors did not comment on howearly the signal changes might be seen. If weextrapolate from our data on the infants ingroup 1 of this study, periventricular T1 short-ening in premature neonates might be expectedas early as day 3 after injury. However, thesonographic diagnosis of periventricular leu-komalacia is not conclusively made until cavi-tation is seen, usually at the age of 2 to 3 weeks(19). In addition, ultrasound is insensitive tononcavitary periventricular leukomalacia (20).Thus, MR may be more sensitive than ultra-sound to the detection of periventricular leu-komalacia in the early phases of injury. Obvi-ously, large prospective studies must beperformed to confirm this suspicion.The severity of the blood gas abnormalities

was not significantly different in the group 4patients than in the group 1 patients. Theseresults suggest that the degree of acidosis does

436 BARKOVICH

not correlate well with extent of injury; this ob-servation is in agreement with the findings ofother studies (21–23). One possible explana-tion for the marked T2 prolongation in the ce-rebral cortex of these patients, as comparedwith group 1 patients, is the duration of theinjury. As discussed earlier, we believe that thefirst structures injured in profound asphyxia arethose with the highest metabolic demands. Withmore prolonged cessation of cerebral bloodflow, however, the cerebral cortex will eventu-ally be injured as well. This is the most likelyexplanation for diffuse T2 prolongation of thecortex in patient 16, who had an unwitnessedarrest of uncertain (but likely prolonged) dura-tion. Evaluation of the injury pattern of patient14 is more complex because of his prematurityand the significant white matter and germinalmatrix hemorrhage that was present. Closerscrutiny of the images of patient 14 showedabsence of a normal signal void in the superiorsagittal sinus and torcula and acute thrombus inthe straight sinus near the torcula. We believethat the hemorrhage in the white matter, and,perhaps, the cortical edema are the result ofhemorrhagic venous infarction that was super-imposed upon the asphyxic injury affecting thedeep gray matter structures. Finally, patient 15was small for gestational age, indicating that hewas subjected to some degree of stress in utero.His MR (Fig 9) findings were diagnostic of end-stage periventricular leukomalacia (24, 25) andare evidence that brain injury occurred beforebirth. We postulate that the acute injury in theperinatal period (causing damage to the deepgray matter) was superimposed on the morechronic injury (causing damage to the cerebralcortex and white matter) in this patient.Only patients 7, 8, 9, and 15 had T2 short-

ening in the lentiform nuclei and lateral thalami.Patients 7 and 9 had imaging on day 10, andpatient 15 had imaging on day 6, whereas, aspreviously discussed, patient 8 (imaging on day4) most likely had prenatal injuries. (Most likely,patient 15 also had prenatal injury, as describedearlier.) T2 shortening was not seen in any otherpatient imaged day 5 or earlier or in patient 5,imaged at 7 days. Therefore, we think it is rea-sonable to postulate that T2 shortening devel-ops in the brains of asphyxiated neonatessometime between 6 and 10 days after injury.This is consistent with observations of T2 short-ening in the intermediate phase, weeks tomonths after injury (1, 7) and with the observa-

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AJNR: 16, March 1995 PERINATAL ASPHYXIA 437

tions of Keeney et al (4), who noted T2 short-ening as early as the “end of the first week.” Thecause of the T1 and T2 shortening is still ob-scure (1, 7), but the fact that the T2 shorteningdevelops several days after the T1 shorteningmakes hemorrhage, as suggested by some au-thors (4), an unlikely cause.The locations of injuries in our group 1 pa-

tients do not correspond to the location of in-jured tissues in profoundly asphyxiated neo-nates who undergo imaging later in life (7, 26).The previous reports have emphasized focal in-jury in the lateral thalami and posterolateral pu-tamina, whereas, in this series, we noted diffuseabnormality affecting the lateral thalami, globipallidi, putamina, and caudate nuclei. More-over, we have done sequential imaging of pa-tients (not included in this study) who had sig-nal abnormality in the globi pallidi in the first 20days of life, but show abnormal T2 prolongationand atrophy in the lateral thalami and posteriorputamina, but not in the globi pallidi, on imageslater in life. We do not have an adequate expla-nation for this observation. One possibility isthat the caudate nuclei and globi pallidi partiallyor completely recover and that the lateral thal-ami and posterior putamina recover less be-cause they are more completely myelinated (itis known that certain protein components ofmyelin inhibit neurite outgrowth [27]). Anotherpossibility is that the lateral thalamus and pos-terolateral putamen are more seriously injuredthan the other regions because they are morecompletely myelinated and, therefore, havehigher metabolic demands. Finally, astrocyticresponse may be more mature in the lateralthalamus and posterior putamen. If so, theseregions would be expected to undergo morereactive astrocytosis after injury and thus ap-pear hyperintense on T2-weighted images; theother regions, where the damaged tissue isresorbed with little or no astrocytosis, would notbe expected to show signal abnormality. Thiswill be an interesting area for future research.An important aspect of the early imaging

evaluation of asphyxiated neonates is the cor-relation of imaging findings with outcome. It isnot the purpose of this communication to pro-vide that correlation; the number of patients istoo small to establish proper correlations, andsome of the patients have had imaging too re-cently to allow adequate follow-up. We arepresently involved in a prospective study thatwill address the issue of outcome.

One final topic that must be mentioned is thesafety of sedating, transporting, and imagingthese infants, who are often very sick and un-stable. We did not scan patients until they werejudged to be adequately stable for transporta-tion by the principle caretaking physicians.Each of our patients was sedated, transported,and monitored by physicians and nurses fromthe intensive care nursery, who remained withthe infant at all times. During the imaging pro-cedure, the infants were wrapped in blankets, toimmobilize them and keep temperature con-stant, and monitored by a pulse oximeter, whichmeasures oxygen saturation, and a capnometerthat measures expired carbon dioxide concen-tration. We had no complications. If furtherstudies prove that MR is a valuable tool in theassessment of these infants, we believe thatequipment can be developed to facilitate evensafer transportation and imaging of thesepatients.In summary, we have reviewed MR studies

performed during the first 10 days of life in 16infants who had hypoxic-ischemic brain injuryin the perinatal period. MR showed bilateral,symmetric signal abnormalities in all. We haveattempted to correlate the pattern of signal ab-normality with obstetric, intrapartum, and post-natal events. Our results indicate that MR isuseful in evaluating the extent of brain damagein these infants during the first week of life. Thisinformation should prove useful in patient treat-ment. Further studies that correlate MR appear-ance with patient outcome are under way.

AcknowledgmentsWe thank Carol Sheldon, MD, David Seidenwurm, MD,

and Wallace Peck, MD, for providing information for thisstudy.

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