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Pictorial Essay
The Hippocampus: Normal Anatomy and Pathology
L AnneHayman1,
GregoryN.Fuller2,Jos
E.Cavazos3,
MarkJ. Pfleger4,
ChristinaA.Meyers5,EdwardF.Jackson6
T

he hippocampi are unique and vital


regions found in each of the cere
bral hemispheres. In most subjects,

the dominant left hippocampus primarily medi

ates verbal learning and memory, whereasthe


nondominant right side primarily mediates non
verbal memory. Becausebilateral hippocampal
lesionsresult in amnesia(i.e., inability to learn
new information), extensive hippocampal re
search has been undertaken. The advent of sur
gical procedures that can cure medically
intractableseizuresby excisionof hippocampal
abnormalities also has spurred extensive re
@

search directed toward MR analysis of this re

gion. Our purpose is to introduce the reader to


these techniques. This paper is divided into
three parts: normal hippocampal anatomy, MR
imaging techniques,andrefractoryepilepsy.

tenor tail. In humans, this gyms continues as


the vestigial supracallosalgyrus (indusium gri
seum), and anteroinferiorly it is renamed the
vestigial paraterminalgyms.
Anatomic coronal sections are traditionally
shownonly at the mid body ofthe hippocampus

orly, it becomes the cingulate gyms; anteroinfe


riorly, it becomesthe paraterniinal gyms. The
smaller, inner limbic gyms contains the hip
pocampus, which is subdivided into three seg
ments: the bulbous anterior head (also called
the pesor foot), the body, and the slenderpos

@J).

frur@;)-

Paraterminal
gyros

.@-.

Parahippocampal
gyrue

@.

..

Vesti@

-.

gyms

:. ,@

supracallosal

(induseum

griseum)

Tail

Normal Hippocampal Anatomy


The limbic lobe is formed by two gyri on the
medial surface of each cerebral hemisphere.
The larger outer gyms is renamed as it encircles
the corpus callosum (Fig. 1). Posteroinferiorly,
it is calledthe parahippocampal
gyrus;superi

Vestigialparaterminalgyros

Body
Head(foot,pes)

Fig.1.Limbic
lobeanatomy.
Drawings
showsubdivisions
ofouterandinner
limbiclobegyri.

ReceivedJanuary22,1998;acceptedafterrevisionMarch10,1998.
1Department

of Radiology, Baylor College of Medicine,

2 Department

of Neuropathology,

One Baylor Plaza, Houston, TX 77030-3498. Address correspondence

University ofTexas M. D. Anderson

to L A. Hayman.

Cancer Center, Houston, TX 77030.

3Departmentof Neurology,Universityof ColoradoHealthSciencesCenter,Denver,CO80262.


4Departmentof Radiology,OverlakeMedicalCenter,Bellevue,WA98004.
5 Department

of Neuro-oncology,

University of Texas M. D. Anderson

Cancer Center, Houston, TX 77030.

tDepartmentof DiagnosticRadiology,UniversityofTexasM. D.AndersonCancerCenter,Houston,TX77030.


AJR1998;171:1
1391
1460361803X/98/17141
139AmericanRoentgenRaySociety

AJR:171,October1998

1139

Hayman et al.

I
e
m
Temporal Horn

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e
r
n

A
m
b

. .

;. ...

J@.. @.

e
n
t

..

/1'
I

COLLATERAL

.. .

@.

@:

(Fusiform

. \gyrus

SULCUS

Residual cleft with cyst in 10-20% of normals

Dentate
gyrus
(molecular
cell
layer)

CAl

CA2
CA4
(end
folium)

CA = CORNUAMMONS(Ammon's horn)(pyramidalcell layer)

@
A

Fig.2.Hippocampal
anatomy.
A,Drawing
ofaxialsection
oflefthippocampus
seenfrombelowshowsrotation
ofhippocampus
anditsrelationship
withdentate
gyrus.
(Modified
withpermission
from11])
B,Drawingofcoronalsectionatmidbodyoflefthippocampus
showscross-sectional
relationship
betweenhippocampus
andsurrounding
structures.
(Modifiedwithpermis
sionfrom [41)

(Fig. 2) 115].
At this level, it consistsof two in
terlocking laminae of gray matter: the cornu
ammonis (Ammon's horn) and the dentategy
flis. The comu ammonis can be divided into
four microscopic zones of granular cells:

CAl, CA2, CA3, and CA4 (Fig. 2). This


coronal section simplifies the complexity of
these cellular layers and makes this location

long axis of the temporal horn. However, even

high-field-strength I .5-T MR imaging shows


little of the cellular anatomy (Fig. 3). Rather,
it defines the outline of the three major fis

obliterated laterally in utero and may not be


visualized (or only a small portion is visible).
The hippocampal sulcus is found between the

dentate gyrus and the subiculum and cornu

sures: hippocampal, fimbriodentate, and chor


oidal, which allows the reader to infer the

ammonis. Small remnants of the hippocampal

location of the cellular anatomy. The hippo


campal sulcus (fissure) is presentin the head,
body, and tail of the hippocampus.Anteriorly,

sulcus (fissure) should not be mistaken as pa

fore, hippocampal imaging is described in

this fissure merges with the uncal sulcus [ 1].

thology. Figures 46show all of the fissures,


the cellular anatomy of the hippocampus, and
its surrounding structures on colored serial
coronal myelin-stained
sections and on com

coronal sections that are perpendicular to the

The hippocampal sulcus (fissure) is usually

panion serial T2-weighted MR images.

ideal for evaluating the hippocampus. There

k: :i

Ch@

Fig.3.Normal
coronalhippocampus
in24-year-old
man.
A,Fastspin-echo
12-weighted
MRimagethrough
bellyofponsshowschoroidal
fissure
(Ch),fimbriodentate
fissure
(FD),andhippocampal
sulci(H)(fissures)
onleft(also
seeFig.8A).Notethatsmallcysticresidualoffetalhippocampal
sulcus(fissure)isseenonbothsides.
B,Fastspin-echo12-weightedMRimagethroughmiddlecerebellarpeduncleshowscontinuation
ofthreemajorhippocampal
sulci(fissures).Ch=choroidalfissure,
FD=fimbriodentate
fissure,H =hippocampa)
sulcus.Notesmallcysticresidualoffetalhippocampal
sulcus(fissure)(solitaryarrowonrighthippocampus).
1140

AJR:171,October1998

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@,-#

.
Mama

@arybodyd

Uncaf

:@

notch
(tertora@
r@press@on)

@
@

,.

Collateraf

Choroidaf fia
r

.2

S Uncal guiCuS

@UncaI

notch

tentoraf

Imoress;orr)

Collateral
fissure

E
Dsntategynhs
@

CA -

(Ammon's horn)

Comu Ammonia

@en.r
sictor)
:@:@.i.islatIt
zen.)

CM

entorhinal
area

body
of
parahippocampal
gyrus

tail
of
parahippocampal
gyms

vestigial
supracallosal
gyms
(connects parahippocampus with CAl)

amygdala
gyms amblins

!.@::unaris

lanterlorparahlppocampalgyrus)

(becomes cingulate gyrusInot shown])


(induslum griseum)

Fig.4.Normal
anatomy
ofamygdala
andhippocampal
headonpairedserial,myelin-stained
coronalbrainsections
andcompanion
12-weighted
MRimages.
Bothmyelin-stained
sec
tionsandMRimages
areasymmetric,
causing
slightlydifferent
appearance
between
right-andleft-sided
structures,
whichproduces
sixuniquesections.
Colorkeyisguidetoimportant
structuresandlandmarks.

A,Myelin-stained
brainsectionimmediately
rostraltoheadofbothhippocampi.
B,Companion
MRimagerostraltohippocampi
showsdiverging
optictract(Ot),sylvian
fissure(Sf),anduniquebranching
patternofwhitematterinrostraltemporal
lobeonrightRostral
amygdala(A)is seenonleft

C,Myelin-stained
brainsectionofanteriormost
lefthippocampal
headorpes(foot)showscornuammonis
zone1(CAl)belowtemporal
horn.Amygdala
(blue)persists
onrightbuthas
almostdisappearedonleftside.Uncus(pink)is seenaboveandmedialto bothamygdalae.Uncalnotchis postmortemartifact.

D,Companion
MRimageshowsmamilothalamic
tractsconverging
tositeofmamillary
bodies
(Mb),sylvian
fissure(Sf),androstralrightamygdala
(A)asitfadesintouncus.Uncalrecess
(Ur)oftemporal
hornisseenonright(joinedarrows).
UralsoisseeninE.
E,Myelin-stained
brainsectionofleftmidportionofhippocampal
headorpes(foot)showsrelationship
ofuncus(pink)toCAlcells(red).Notethatuncalextension
oftemporal
horn
seenonrightshouldnotbemistaken
forpathology
(Fig.10).Uncalsulcusisshownonleft CAlcellsseparate
uncalsulcusfromuncalrecess.Righthippocampal
headshowscompli
catedalternatingcellularrelationshipsof CAl (red),CA2(turquoise),andCA3(brightyellow)cellsto centrallylocatedamygdala(blue).CA4appearsin Figure5A.

1@
Companion
MRimageshowsinterpeduncularfossa
(If)between
cerebral
peduncles
andvessels
inambient
cistern(Ac)asitmerges
withchoroidalfissure
(Ch)andtemporal
horn(Th).

.-

Al F

\4

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A4

@
@

4'

@----@- Choroidal
fissure

fissure

Collateral fissure

Dentate
gyrus

(connects parahtppocampus with CAl)

CA =
Comu Ammonia

@imer
sector)

amygdala

(Ammon's horn)

@@iaI
rsslstant zone)

gy@u@ambiens

(End
folium)
CA3

entorhina)
area

body
of
parah(ppocampai
gyms

tao
of
parahippocampa)
gyms

vestigial
supracaliosa)
gyrus
anterior parahlppocampat gyrus)

becomescingulategyrus[notshown])

@:@7unaris

)induslum griseum)

Fig.5.Normal
anatomy
ofhippocampal
bodyonpairedserial,myelin-stained
coronalbrainsections
andcompanion
12-weighted
MRimages.
Bothmyelin-stained
sections
andMR
imagesareasymmetric,causingslightlydifferentappearancebetweenright-andleft-sidedstructures,which producessixuniquesections.Colorkeyis guideto importantstructures

andlandmarks.
A,Myelin-stained
brainsectionofbothanteriorhippocampal
bodieshasclassiccellularconfiguration
ofcornuammonis
zone1(CAl,red),zone2(CA2,
turquoise),
zone3(CA3,bright
yellow),andthesmallest
zone4(CA4,
magenta)
showninFigure
2.Largeportionofuncus(pink)continues
tobepresent
onrightbuthasalmostdisappeared
onleftside.
B,Companion
MRimageshowshypointense
whitematterofalveus(Al)andfimbria(F),whichseparate
hippocampal
cortexbelowfromsuperior
brightsignalintensity
ofpartialvolume
ofCSFandchoroidal
plexusinthintemporal
horn.Hypocellular
molecular
layerofdentate
gyrus(arrowheads)
hashypointense
signalintensity
thatissameasthatseeninwhitematter
elsewhere
inbrain.Imageisconfusing
because
intervening
cellsofcornuammonis
zone2(CA2,
turquoise)
anddentate
fibers(darkgreen)that
separate
hypointense
alveusabovefrom
hypointense
molecular
layerbelow(A)arenotresolved
and,therefore,
hypointensity
appears
ascontinuous
band.
C,Myelin-stained
brainsectionofhippocampal
bodyissmallerversionofclassiccellularconfiguration
showninA andinFigure2.UncalsulcusseeninA hasbecome
hippocampal
sulcus(fissure),
andfimbriodentate
fissurehasappeared.
Atthislevel,cellsofentorhinal
area(lightgreen2)havebeenreplaced
bymainbodyofparahippocampal
gyrus(lightgreen2a).
D,Companion
MRimageshowspulvinar
(Pul)ofthalamus,
choroidal
fissure(Ch),collateral
fissure(CoIl),
andtemporal
horn(Th)entering
atriumoflateralventricle.
E,Myelin-stained
brainsectionoflastportionofhippocampal
bodyatantenormost
splenium
ofcorpuscallosum.
Bodyofparahippocampal
gyrus(lightgreen2a),whichispresentin
previous
sections,
islastseenonthislevel.Itisreplaced
inFigure
6Abytailofparahippocampal
gyrus(lightgreen3).
F,Companion
MRimage
shows
splenium
ISpI),caudate
nucleus
)Cn),
andcrusoffornix
)Cfx).

MR Imaging

of the Hippocampus

@,if

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Sp:

@B

I
,@(tk,@@.

Dentate
gynis
@

CA

ComuAmmonia

@sn.r
sector)

(Ammon'.

@@r@aI
nshetuit son.)

horn)

entorhinal
area

body
of
parahlppocampai
gyms

tail
of
parahippocampal
gyms

vestigial
supracaiiosai
gyms
(connects parahlppocampus with CAl)

amygdaia
gyi'tzs amblens

(anterior parahippocampal gyrus)

(becomes cingulate gyrus[not shown])

CA3

@::i@unai1s

(indusiumgriseum)

Fig.6.Normal
anatomyofhippocampal
tailonpairedserial,myelin-stained
coronalbrainsectionsandcompanion
12-weighted
MRimages.Bothmyelin-stained
sections
and MR imagesare asymmetric,causing slightly different appearancebetween right- and left-sided structures, which producesfour uniquesections. Colorkey is guide
to important structures and landmarks.

A,Myelin-stained
brainsectionofjunctionofbodyandhippocampal
tailbelowposteriorspleniumofcorpuscallosum.Cornuammonis
zone1(CAl)cells(red)predominate
and surround dentate gyrus (dark green).Gyrusfasciolaris is composedof CA3cells (yellow). Gyruscinerea is formed by CA4cells (magenta).Body of parahippocampal
gyrus (light green 2a in Figure5E)hasterminated, andtail of parahippocampalgyrus appears(light green 3). Collateralsulcus terminates at this level.

B,Companion
MRimageshowsatriumof lateralventricle,anteriorcalcarinefissure(AC),andsplenium)Spl)of corpuscallosum.Alveus(Al)oftencanbeidentifiedbe
tweenbrightsignalintensityof CSFandcortexofcornuammonis
zone1(CAl)hippocampal
cells.
C,Myelin-stained
brainsectionofhippocampal
tailcontainslastsmallremnantofcorpuscallosumbelowsupracallosal
gyrusonright.Anteriorcalcarinefissureseparates
cornu ammoniszones1 (CAl, red) and 3 (CA3,brightyellow) cellular layers of hippocampusfrom subiculum(light green 1).

D,Companion
MRimageshowsanteriorcalcarinefissure(AC).
MR lmagingTechniques

field of view,256 x 256 matrix, 3- to 5-mm sec

the limbic structures! Considerable disagree

Clinical1-lippocompalImaging

tions with the smallest possible gap); and TI


weighted images (four repetitions, 16-cm field
of view, 3- to 5-mm contiguous sections). A Tl

ment exists relating to how to perform these

High-field-strength MR ( I .5-T) scans are best


suited fbr detailed hippocampal studies. All im

ages must use window settings that optimize


graywhitematter differentiation. Excellent
quality standard axial images of the brain must

be obtainedto detectconcurrentor separateab


normalities. However, the fbllowing coronal
scans of the hippocampus should also be obtamed: fast spin-echo T2- and spin density
weighted images (two repetitions. 20- to 24-cm
AJR:171, October 1998

weighted spoiled gradient-recalledecho in the


steadystate,inversionrecovery,or TI-weighted
fluid-attenuatedinversionrecoverysequencecan
beobtainedifthese capabilitiesareavailable[6].

volumetric studiesand what the results mean.


Currently, these studies are impractical in the
routine clinical setting because highly trained
personnelmust trace the hippocampal outline.
The details of this procedure have been re
viewed recently [7].

Volumetric
Analysis
Over the last few years, more than 90 arti-

Spectroscopy

des have described MR volumetric analysis of

invasive biochemical information in a living pa

MR spectroscopycan be usedto obtain non

1143

Hayman et al.

PC

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Cr

Cr

-,@.

I,,.,

ppm
A

Fig.7.'HMRspectra.
A,Eightcubiccentimeters
ofnormal
frontoparietal
region.
Short-TE
(30msec)MRspectroscopy
showsgoodwatersuppression
andspectral
resolution
ofvarious
bio
chemicals.NAA= N-acetyl-L-aspartate,GABA=y-aminobutyric
acid, glu = glutamate,gIn= glutamine,asp= aspartate,PCr= phosphocreatine,Cr creatine, Cho= choline,

Ins= myo-inositol.
B,Fivecubiccentimetersof normalhippocampus.
Short-TE
(30msec)MRspectroscopy
showsbroaderspectralpeaksandpoorlydefinedbaselineresultingfromlocal
field inhomogeneitiesin region.Useof longerTE(>100msec)would significantly improvebaselineby increasingwater-suppressionefficiency. However,resulting spectral

information
wouldincludeonlyNAA,Cr,PCr,andChobecauseotherbiochemicals
haveshort12relaxationtimes.

CAt2@

.,,

..

.,
.,@

..

.p

:@

i@/P:,,:1@i1@::
A

Fig.8.Hippocampal
sclerosis.
CAl=cornuammonis
zone1.CA2= cornuammonis
zone2.
A,Coronal
section
ofbrainshowsnormal
leftCA2andsevereatrophy
ofleftCAlwithflattening
ofnormal
hippocampal
bulgeintotemporal
horn(curved
arrow)(seenormal
coronalprofileinFig.2).Normalfissures(choroidal,Ch;fimbriodentate,
FD;andhippocampal,
H)aremarkedfororientation.
B,Microscopiccoronalsectionofbodyofhippocampus
showsclassiclossofcellsinCAlofhippocampus
compared
withnormaldarktriangularpyramidalcells(arrows)
in CA2region.(HandE,xlOO)
tient and has been performed in an effort to
detect early onset of Alzheimer's disease and to
study normal age-associated memory impair
ment. MR spectroscopy may be of particular

crowded under optimal conditions, magnetic


field inhomogeneities caused by the bone or air
interfaces(or both) near the hippocampuspro
ducebroadenedspectralpeaksand makequan

Refractory Epilepsy
Epilepsy affects 0.51%of the population in
the United States.Of theseindividuals, 1530%

importance

titative analysis difficult [7] (Fig. 7). However,

tential candidates for surgical resection [8].


Electroencephalographicstudies are the most

in patients with a normal MR scan

and medically intractable epilepsy [7]. How


ever, the clinical usefulness of this technique in
studiesof the limbic systemhasbeenlimited by
many technical pitfalls. For example, in 1H MR

the useof small voxel sizes,obtainedwith spec


troscopicimaging techniquescoupledwith effi
cient magneticfield homogeneityoptimization,

spectroscopy, in which the spectral peaks are

spectroscopyin the limbic system.

1144

may expand

the clinical

applications

of MR

are refractory

to medical treatment

and are po

important localizing tools in these patients. If


imaging shows hippocampal sclerosis at the site

of a temporal lobe electroencephalographicab


normality, the surgical outcome is greatly im

AJR:171,October1998

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,@
,1

.1
I

Fig.9.Hippocampal
sclerosis.
A,Coronal
fastspin-echo
12-weighted
scanshowsabnormal
increased
signalintensity
inbodyoflefthippocampus
(arrow)compared
withnormal
rightside.
B,Coronalfastspin-echo12-weighted
scancaudalto A showsthatatrophyof hippocampus
onleftresultsin subtleincreasedsizeof leftchoroidalfissure(Ch)(arrow).
Normalthinner choroidal fissure on right side also is markedwith arrow for comparison.

Fig.10.Fibrillary
astrocytoma.
A,Coronal
fastspin-echo
12-weighted
scanshowsabnormal
focusofincreased
signalintensity
atjunction
ofrightamygdala
andhippocampal
head(arrow)(seeFig.4C,
left hippocampalsection).This finding should not be mistakenfor uncal recess of temporal horn (see Figs.4D and 4E).

B,Companion
11-weighted
imagesbefore(notshown)andaftergadolinium
administration
donotshowabnormality.

proved (i.e.. 8()9O@7c


of these individuals
becomeseizure-free).This finding is significant
becauseone half of patientswith medically in
tractableseizureshavehippocampalsclerosis.
MR imaging is the technique of choice in
these patients because

@@#@fT 7:

it has a 90% sensitivity

to hippocampal sclerosis,whereasCT is sensi


tive in only 2% of cases (Figs. 8 and 9). MR
imaging also is superior to CT in the detection

of other causesof refractory epilepsy, such as


congenital deformities, low-grade tumors (Fig.
10), trauma, stroke, and infections. Recogni
tion that scalp electroencephalographsmay

tu

falsely localize an abnormality to the hippo


campus is important. In this setting, imaging is

of utmost importance becauseit can prompt


the use of depth electrodes to correctly
the causative lesion (Fig. 1 1).

AJR:171,October1998

localize

Fig. 11.Temporal
lobe ganglioglioma.Fastspin-echo 12-weighted image shows left inferior temporal lobe le

sion(arrow)thatwasnotseenonunenhanced
11-weightedscans.Scalpelectroencephalograph
erroneously
indicated focus in oppositetemporal lobe. Subduralelectrodes correctly localized lesion.

1145

Hayman et al.

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Summary
The hippocampus is a complex and fasci
nating region of the brain that has enormous
clinical significance. Specifically, small imag
ing abnormalities may cause major symp
toms. We believe that the detection of these
lesions will be improved if imaging clinicians
have an organized

reference that facilitates

identification of the cellular zones that com


prise the hippocampus.
Acknowledgments
We thank the Armed ForcesInstitute of Pa
thology, Washington, DC, for providing the

1146

true coronal brain slices. We are extremely


grateful for the expertise and patience provided
for this undertakingby BrendaSchubert.
References
1. DuvernoyHM. The humanhippocampus:
an at
las of applied anatomy. Munich: Bergmann Ver

4. FullerGN,BurgerPC.Centralnervoussystem.In:
Sternberg
SS,ed.Histologyfor pathologists,
2nd
ed.NewYork:LippinconRaven,
1997:243282
5. Tien RD. FelsbergGJ. Cram B. Normal anatomy

of the hippocampusand adjacenttemporallobe:


high-resolution
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MR imagesin vol
unteerscorrelatedwith cadaverichistologicsec
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lag,1988:145
6. Jack CR, Rydberg CH, Krecke KN, et al. Mesial
2. BronenRA, Cheung0. Relationshipof hippo
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campusandamygdala
tocoronalMRI landmarks.
ated inversion-recoveryversusspin-echoMR im
Magn Reson Imaging 1991:9:449457
3. Naidich TP, Daniels DL, Haughton VM, Williams

aging. Radiology 1996;l99:367373


7. Tien RD. Neuroimaging clinics of North Amer

A, Pojunas K, PalaciosE. Hippocampalforma

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tion and related structures of the limbic lobe: ana


tomicMRcorrelation. 1. Surface features and
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thologv. Philadelphia: Saunders, 1997


8. Jack CR. Magnetic resonance imaging in epi

lepsy.MayoClinPmc 1996;7l:695711

AJR:171,October1998

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