3.07 MRI of the BrainA Horska and DDM Lin, Johns Hopkins University, Baltimore, MD, USA

2014 Elsevier B.V. All rights reserved.

3. 03. tom 03. 23. 33. 53. 53. 63. Inj 83. 03. 1Ac 2Re 2

becomes lower than the diffusion coefficient that would be

measured in the same media without obstacles.

Cerebrovascular accident (stroke) Interruption of vascular

Fluid attenuated inversion recovery (FLAIR) A sequence

used to null the signal from cerebrospinal fluid based upon

its longitudinal relaxation time T1.

B0 Static magnetic field

BMI Body mass index

Lac Lactate

MCA Middle cerebral artery

TR Repetition time

CofMRI Functional MRIBOLD Blood oxygenation level dependent (contrast)

CBF Cerebral blood flow

Cho Choline

CNS Central nervous system

Cr Creatine

CT Computer tomography

DAI Diffuse axonal shearing injury

DSC Dynamic susceptibility contrast

DTI Diffusion tensor imaging

DVA Developmental venous anomaly

DWI Diffusion-weighted imaging

FA Fractional anisotropy

FLAIR Fluid attenuation inversion recovery

MD Mean diffusivity

MRA Magnetic resonance angiography

MRS Magnetic resonance spectroscopy

MRSI Magnetic resonance spectroscopic imaging

NAA N-Acetylaspartate

NEX Number of excitations

NPV Negative predictive value

PLIC Posterior limb of the internal capsule

PPV Positive predictive value

rCBV Relative cerebral blood volume

SWI Susceptibility weighted imaging

TE Echo time

DTE Echo spacingsupply of adequate blood nutrients to the brain can be

due to ischemia (lack of blood supply) caused by

thrombosis or embolism, or due to a hemorrhage

(rupture of blood vessels).

Hypoxic-ischemic encephalopathy Prolonged oxygen

deprivation of the brain, due to reduced oxygen delivery

(hypoxemia) frequently caused by perinatal asphyxia or to

cerebral blood flow (ischemia).

NomenclatureADC Apparent diffusion coefficient

APT Amide proton transfer

FOV Field-of-view

GBM Glioblastoma multiforme

GRE Gradient echoASL Arterial spin labeling (perfusion)mprehensive Biomedical Physics http://dx.doi.org/10.1016/B978-0-444-53632-7Ins Myo-inositol07.1 Introduction07.2 MR-Based Modalities for Assessing Brain Ana07.3 MRI in Normal Brain Development07.4 MRI in Normal Brain Aging07.5 MRI of the Brain in Pathologic Conditions07.5.1 Ischemic Stroke07.5.2 Hypoxic Ischemic Injury in Neonates07.5.3 Intracranial Hemorrhage and Traumatic Brain07.5.4 Brain Tumors07.6 Conclusionknowledgmentferences

GlossaryAngiography Imaging of blood vessels, usually arteries.

Apparent diffusion coefficient The modified coefficient,

which depends on the direction of observation and its value10y 10

1010101010

ury 1011111111

Diffusion-weighted MRI A noninvasive technique able

for imaging the human brain white matter, with the

capability to accurately describe the geometry of

the underlying microstructure and its integrity..00307-5 99

3.07.1 Introduction

Magnetic resonance imaging (MRI) is a noninvasive technique

providing multiplanar images of neuroanatomy and vascular

anatomy. Advanced techniques of MRI further enable interro-

gation of brain function, connectivity, hemodynamic proper-

ties, and diffusion-related phenomena.

In clinical neuroimaging, MRI is a complementary tech-

nique to computerized tomography (CT). CT is fast, more

widely accessible, lower in cost, and provides better detail on

bone structures and has high sensitivity for acute hemorrhage;

it has therefore been routinely used in brain trauma and emer-

gency situations to detect bleeding. CT has a much higher

sensitivity than conventional MRI for intracranial calcifica-

leukodystrophy, and postinfectious encephalitis. In contrast,

these constituents can dominate the image. The basic MRI

contrast relies mainly on proton density, and spinlattice

(T1) and spinspin (T2) relaxation times. Figure 1 illustrates

the contrast among gray matter, white matter, and CSF on an

axial T1-weighted, T2-weighted, and fluid attenuation inversion

recovery (FLAIR) image.

MRI provides detailed views of brain anatomy, previously

unachievable in vivo. Introduction of high-field MRI scanners

accompanied by recent advancements in magnet technology,

detector technology, and application of contrast mechanisms

including flow, diffusion, and T2* opened new possibilities in

studies of brain anatomy (Duyn, 2010). Compared with 3.0-T

MRI systems, scanners operating at ultra-high magnetic fields

of 7.09.4 T enable a two- to threefold improvement in the

FLA

100 MRI of the Brainpatients with obvious white matter abnormalities may have an

entirely normal CT, in particular in the early stages of the

disease. MRI is preferable to CT for evaluating temporal lobe

epilepsy, nonhemorrhagic brain contusions, traumatic shear

injuries, posterior fossa disease, defining congenital malforma-

tions, and imaging vascular disease. MRI is the imaging proce-

dure of choice in situations when early diagnosis is critical for a

favorable outcome, for example, in suspected herpes encepha-

litis (Klein and Hesselink, 1996). In the evaluation of children,

MRI has distinct advantage over CT because of the lack of

ionizing radiation.

This chapter provides an overview of the applications of

clinical and advanced MRI techniques to examine brain anat-

omy, study brain development and aging, and diagnose com-

mon brain pathologies.

3.07.2 MR-Based Modalities for AssessingBrain Anatomy

Conventional morphological MR images of the brain can dif-

ferentiate among four main brain tissue constituents white

matter, gray matter, cerebrospinal fluid (CSF), and blood.

Depending on the imaging sequence used, one or more of

T1T1

Figure 1 Sagittal T1-weighted, axial T1- and T2-weighted spin echo andhealthy child.tions. On the other hand, MRI offers superior intrinsic contrast

of soft tissues compared to CT. MRI is generally more sensitive

than CT for detection of pathologic changes in brain tissue in

the early stages of disease processes, for example, in cerebral

infarctions, brain tumors, or brain infections. MRI is highly

sensitive for detecting white matter pathology, such as in mul-

tiple sclerosis, progressive multifocal leukoencephalopathy,signal-to-noise ratio. This improvement is somewhat dimin-

ished by increases in T1 and reduction in T2* at higher magnetic

fields, but a small gain is achieved from the synergistic effect

from high field and array detectors. Employing multidetector

array coils with parallel imaging techniques can result in scan

time reduction, or improvement in temporal or spatial resolu-

tion. Spatial resolution below 0.1 ml of voxel volume can beachieved at ultra-high fields (Cho et al., 2008a,b; Duyn, 2010),

comparable with resolution of thin slices in vitro (Cho et al.,

2008a,b). Ultra-high field MRI can therefore provide fine de-

tails of brain anatomy and visualize brain structures that were

previously difficult or impossible to delineate (Cho et al.,

2008a,b; Strotmann et al., 2011). At ultra-high fields, images

obtained with gradient echo (GRE) appear more uniform than

spin echo images (Haacke et al., 2009). The T2*-weighted im-

ages allow delineation of venous structures (Robitaille et al.,

2000), iron-rich structures, blood products (Novak et al.,

2005), myelinated white matter fiber bundles (Li et al.,

2006), and cortical layers (Duyn et al., 2007) with high reso-

lution. The origin of the T2* contrast may stem from differences

in iron concentrations, variations in myelin content, and, pos-

sibly, from variations in density and orientations of venous

microvascular elements (Li et al., 2006). High-field MRI of the

brain may therefore enable studies of cytoarchitecture across

functional areas, disease processes, and populations. Figure 2

shows striking contrast differences in the white matter at 7.0 T,

illustrating that the T2*-weighted contrast can be used to differ-

entiate among specific fiber bundles. The border between gray

and white matter appears dark in cortical regions, possibly due

to local U-fibers or blood vessels that follow these fibers.

Figure 3 demonstrates excellent susceptibility contrast that

can be achieved at 7.0 T.

T2 FLAIR

IR images obtained at the level of the basal ganglia in a 5-year-old

CR

MRI of the Brain 101Tapetum

P

SLFU-fiberHigh-field MRI also offers opportunity for more detailed

studies of brain vasculature, including small vessels (Cho et al.,

2008a,b; Nowinski et al., 2011). Using data from 3.0 to 7.0 T

acquisitions, an updated version of the atlas of human cere-

brovasculature was introduced recently (Nowinski et al.,

2011). The atlas includes a total of 1325 vessels, with the

smallest vessel of 80 mm in diameter. A representation of adetailed three-dimensional (3D) model of complete cerebro-

vasculature in human brain is shown in Figure 4.

Figure 2 Left: A T2*-weighted axial image acquired at 7.0 T with repetition t32 kHz, matrix size 1024768, field-of-view (FOV)220165 mm2, slice thA magnified display of the region outlined in the image to illustrate the contraare labeled: tapetum, posterior corona radiata (PCR), superior longitudinal faColor-coded representation of fiber directionality (red: left-to-right, green: anexperiments performed at 3.0 T in a different participant at a similar locationvan Gelderen P, Merkle H, Talagala L, Koretsky AP, and Duyn J (2006). ExtensiMRI of the human brain at 7.0 T. Neuroimage 32(3): 10321040, with permi

0.15

0.1

0.05

0

0.05

0.1

Figure 3 A quantitative susceptibility map reconstructed from a 3Dmultiecho gradient echo (GRE) acquisition (111 mm3 resolution,TR70 ms, TE/DTE2/2 ms, flip angle9). The GRE phaseimages were acquired with four different head orientations.The image clearly depicts the iron-rich globus pallidus (arrow).The scale is in units of ppm. Courtesy of Xu Li, Issel Anne Lim, CraigJones, Deepti Vikram, Jonathan A.D. Farrell, Peter C.M. van Zijl; F. M.Kirby Center for Functional Brain Imaging, Kennedy Krieger Institute,Baltimore, MD, USA.Tapetum

SpleniumSplenium

U-fiber

SLF

PCRImproved contrast and resolution at ultra-high magnetic

fields may result in better accuracy of anatomical localization,

central to the success of functional imaging (Devlin and

Poldrack, 2007). In order to facilitate the transition of ultra-

high field MRI of the brain into widespread clinical use, more

studies need to be carried out to establish the underlying

mechanisms affecting the MRI tissue contrast. In order to take

advantage of the improved resolution achievable at higher

fields, techniques for corrections of physiological factors

ime/echo time (TR/TE)800/30 ms, 30 flip angle, receiver bandwidthickness1 mm, and number of excitations (NEX)1. Right:st difference between the fiber bundles. The following fiber bundlessciculus (SLF), splenium of the corpus callosum, and local U-fibers.terior-to-posterior, blue: out of plane) was obtained from DTI, with spatial resolution 0.90.90.9 mm3. Reproduced from Li TQ,ve heterogeneity in white matter intensity in high-resolution T2*-weightedssion from Elsevier.

Figure 4 Depiction of human cerebrovasculature, color-coded, from a3D atlas (Nowinski et al., 2011). The orientation box is located in theleft upper corner; the anterior (A) and left (L) orientations are shown.Reproduced from Nowinski WL, Chua BC, Marchenko Y, Puspitsari F,Volkau I, and Knopp MV (2011) Three-dimensional reference andstereotactic atlas of human cerebrovasculature from 7 Tesla.Neuroimage 55(3): 986998, with permission from Elsevier.

is 10% larger in boys than in girls (Giedd, 2008). The growth

102 MRI of the Brainof cerebral volume during the first 2 years of life is largely

dominated by increase in gray matter volume while the in-

crease in white matter volume is small (Knickmeyer et al.,affecting signal stability, such as subtle head motion, brain

pulsations, and respiration need to be integrated in the imag-

ing systems (Duyn, 2010).

3.07.3 MRI in Normal Brain Development

Both conventional MRI and advanced MRI techniques are

effective tools for studies of brain development and matura-

tion. The nonionizing, noninvasive nature makes MRI an

attractive technique to study brain development, permitting

longitudinal investigations. Knowledge of patterns of normal

age-related differences in MRI-derived parameters is important

to understand healthy maturation and to interpret findings

associated with abnormal neurodevelopment. Measurement

of developmental changes across brain regions and studying

concurrent development of cognitive and motor function

may further enhance ones understanding of the relationship

between brain structure and brain function. Advanced MRI

techniques have been widely applied in neuropsychological

disorders, many of which originate during childhood and

adolescence (Knickmeyer et al., 2008; Saitoh et al., 2001).

On conventional MRI, postnatal brain development can

be visualized as progress of myelination manifesting as

changes in white matter contrast on T1- and T2-weighted im-

ages (Barkovich, 2000; Ertl-Wagner and Rummeny, 2008;

Leppert et al., 2009). The process of myelination, following

specific chronologic regional patterns, is most active during the

first 2 years after birth. T1-weighted images are more sensitive

to the changes in myelination during the first year, while the

T2-weighted images are more helpful in assessing the degree of

myelination during the second year of life. At term birth, the

following structures are usually myelinated: the medial and

lateral lemnisci, the medial longitudinal fasciculus, the supe-

rior cerebellar peduncle, and the posterior part of the posterior

limb of the internal capsule (PLIC). In general, myelination

progresses from caudal to cranial and from dorsal to ventral

and myelination of functional systems used early in life pre-

cedes myelination of systems that become activated later.

At 2 years of age, the process of myelination appears nearly

complete as visualized on conventional MRI, with the excep-

tion of the terminal zones of myelination (peritrigonal zones

dorsal and superior to the ventricular trigones).

Quantitative MRI has been instrumental in assessment of

total brain volumes and volumes of gray matter, white matter,

and subcortical structures during brain development (Giedd

et al., 1996, 1999; Pfefferbaum et al., 1994). Age-related differ-

ences in brain tissue volumes are highly dynamic during the

first 2 years of life. During the first year of life, total brain

volume doubles and increases by an additional 15% during

the second year of life (Knickmeyer et al., 2008). By 2 years of

age, the brain volume reaches 8090% of adult volume

(Knickmeyer et al., 2008; Pfefferbaum et al., 1994) and by

6 years, 95% of adult volume (Giedd, 2008). Total cerebral

volume further increases until about the age of 10.5 years in

girls and 14.5 years in boys; mean total cerebral volume2008). Cortical gray matter volumes increase during preado-

lescence and decrease in the postadolescence period. The max-

imum cortical gray matter volumes are reached around the age

of 10 years in girls and 12 years in boys in the frontal lobes,

around 10 years in girls and 12 years in boys in the parietal

lobes, and around 17 years in girls and 16 years in boys in

the temporal lobe (Lenroot and Giedd, 2006); the volumes

of occipital cortical gray matter decrease during late childhood

and adolescence (Giedd, 2008). The volumes of white matter

increase linearly during childhood and adolescence, with a

relatively small variability among cerebral lobes (Giedd et al.,

1999, 2010). Dynamic changes in maturation of cortical

regions are illustrated in Figure 5.

Diffusion tensor imaging (DTI) can evaluate age-related

differences in white matter structural integrity and organiza-

tion. Since the DTI contrast is based on structural properties

(water diffusion along white matter tracts), white matter fibers

can be delineated with a better contrast on fractional anisot-

ropy (FA) maps than on conventional T1- and T2-weighted

images, despite a lower resolution of DTI (Huang et al.,

2006). Early myelinating fiber tracts can be differentiated

with DTI even in the fetal brain (Huang et al., 2006;

Figure 6). The most prominent age-related differences in FA

and apparent diffusion coefficient (ADC) are observed within

the first year of life (Gao et al., 2009; Hermoye et al., 2006).

Continuing white matter maturation can be detected during

childhood, adolescence, and adulthood (Bonekamp et al.,

2007; Faria et al., 2010; Giorgio et al., 2008; Lebel et al.,

2008). A recent atlas-based DTI study of age-related develop-

mental differences from infancy to adulthood reported the

largest increases in FA in the brainstem and midbrain white

matter, the thalamus, and the anterior limb of the internal

capsules (Faria et al., 2010). Increase in white matter FA,

as measured with DTI, and increase in white matter volumes,

as measured with quantitative morphometric MRI, may be

attributed to continuing myelination and other factors, includ-

ing increase in the diameter of white matter fibers (Giorgio

et al., 2010a,b). Application of DTI is not limited to white

matter; age-related increases in FA were reported in deep nuclei

(caudate, putamen, and globus pallidus; Lebel et al., 2008).

The study showed relatively prominent increases in white

matter FA over the age range of 530 years; the observed age-

related differences may reflect changes in organization or

degree of myelination of white matter tracts associated with

the deep nuclei (Lebel et al., 2008).

Arterial spin-labeled (ASL) perfusion MRI can provide

a measure of baseline regional function in the developing

brain. However, pediatric perfusion MRI studies in healthy

children have been sparse. In a study of 15 healthy children

(from age 4), 8 adolescents, and 21 adults (up to age 78),

a higher cerebral blood flow (CBF) has been reported in chil-

dren and adolescents than in adults. The differences in CBF

between children and adults were more pronounced in the

gray matter than in the white matter (Biagi et al., 2007). In a

cross-sectional study of infants examined while asleep, without

sedation, ASL perfusion MRI detected relative perfusion in-

crease in the prefrontal cortex and relative perfusion decrease

in the primary motor cortex in 13-month-old children com-

pared with 7-month-old children, using a region-of-interest

(ROI)-based approach (Wang et al., 2008). Using a method

20 years0.3

MRI of the Brain 1035 years

Agethat can extract differences over the whole brain (support

vector machine algorithm), increases in relative CBF were

detected in anterior cingulate gyri, amygdalae, hippocampi,

lateral orbitofrontal cortex, auditory region, and parietal and

occipital regions (Wang et al., 2008). It was suggested that ASL

perfusion MRI may be used for the assessment of functional

localization in the developing brain, by evaluating the rela-

tionship between resting CBF and behavioral performance.

Developmental changes in brain neurometabolism can

be studied with proton magnetic resonance spectroscopy

(1H MRS). The most prominent resonances in the spectrum

are those of N-acetylaspartate (NAA), choline (Cho), creatine

(Cr), and myo-inositol (Ins; Barker et al., 2010). NAA, located

both in the neurons, is considered a marker of neuronal integ-

rity and function. Compounds associated with cell membrane

turnover (mainly glycerophosphocholine, phosphocholine,

and free choline) contribute to the Cho resonance. The Cr

resonance includes Cr and phosphocreatine, compounds in-

volved in high-energy metabolism of the cell. Ins, located

primarily in glial cells, is considered a glial marker (Brand

et al., 1993). Similarly, as in the morphometric MRI or DTI

studies, age-related metabolic differences are most prominent

within the first 2 years of life. In newborns, NAA concentration

is very low and Cho concentration is high, twice of that ob-

served in adults. Increases in NAA and Cr levels and decreases

in Cho and Ins levels were detected in both gray and white

matter regions (Kreis et al., 1993; Panigrahy et al., 2010).

Figure 5 Right lateral and top views of sequence of gray matter maturationof gray matter volume. Fifty-two scans from 13 participants, each examinedfrom Lenroot RK and Giedd JN (2006). Brain development in children and adNeuroscience and Biobehavioral Reviews 30(6): 718729, with permission frGraymattervolume

0.2

0.1

0.0>0.5

0.4In late childhood, adolescence, and early adulthood, age-re-

lated metabolic differences are less prominent (Horska et al.,

2002; Pouwels et al., 1999). Consistent with anteriorposterior

differences in rates of white matter myelination, the white

matter NAA/Cho ratio measured in the centrum semiovale

reached a maximum around 16 years in the posterior regions,

18 years in the central regions, and 22 years in the anterior

regions (Kadota et al., 2001).

3.07.4 MRI in Normal Brain Aging

As average longevity continues to increase, the number of

people at risk of developing neurodegenerative diseases of the

brain is also increasing. While these debilitating diseases are

associated with devastating, progressive loss of neurons, only

a small percentage (10%) of cortical neurons are normallylost over the lifespan (Pakkenberg and Gundersen, 1997;

Pannese, 2011). The cortical volume loss in aging brain can

be accounted for by neuronal shrinkage (Terry et al., 1987).

There is no reduction in the number of glial cells with age

(Pakkenberg et al., 2003). The total length of myelinated fibers

reduces with age, by 4050% (Pakkenberg et al., 2003), reflect-

ing loss of small nerve fibers (Marner et al., 2003). While the

postmortem stereology studies are naturally limited to cross-

sectional examinations, noninvasive MRI studies of normal

aging can be of longitudinal design. The main role of advanced

over the cortical surface. The scale shows a color representation in unitsfour times at approximately 2-year intervals, were used. Reproducedolescents: insights from anatomical magnetic resonance imaging.om Elsevier.

104 MRI of the Brain2 cm 2 cm 2 cmMRI in studies of aging is to identify biomarkers that can

potentially differentiate between normal brain aging and

early onset of neurodegenerative disorders (Bonekamp et al.,

2010; Burggren et al., 2008). Introduction of quantitative tech-

niques such as voxel-based morphometry has allowed for

detection of patterns of regional gray and white matter volume

reductions over the entire brain. Analyses of age-related

regional patterns or morphological changes may help under-

stand the relationship between brain structure and cognitive

function over the lifespan (Sowell et al., 2004).

On conventional MRI, morphologic changes related to nor-

mal aging manifest as increased sulcal prominence, cortical

and white matter volume loss, and ventricular enlargement. A

cross-sectional study using conventional MRI with a 1.5 T

scanner among 76 healthy male and female volunteers aged

3091 revealed a significant inverse effect of age upon total

volumes of the cerebral hemispheres, frontal and temporal

lobes, and the amygdalahippocampal complex and increas-

ing volumes of the third and lateral ventricles with age (Coffey

et al., 1992). However, no or extremely minimal cortical atro-

phy or lateral ventricular enlargement scores were reported in

Figure 6 Axial images of a 19-gestational-week fetal (top row), 0-year(middle row), and 5-year-old (bottom row) brains at the midbrainlevel with anatomical assignment. Abbreviations: ac: anteriorcommissure; alic: anterior limb of the internal capsule; cg: cingulum;cp: cerebellar peduncle; cr: corona radiata; dscp: decussation of thesuperior cerebellar peduncle; ec: external capsule; Fminor: forcepsminor; fx: fornix; GE: ganglionic eminence; ifo: inferior fronto-occipitalpeduncle; ilf: inferior longitudinal fasciculus; oc: optical chiasm; or: opticradiation; ot: optic tract; plic: posterior limb of internal capsule; ss:sagittal stratum; st: stria terminalis; and unc: uncinate fasciculus.Reproduced from Huang H, Zhang J, Wakana S, et al. (2006)White and gray matter development in human fetal, newbornand pediatric brains. Neuroimage 33(1): 2738, with permissionfrom Elsevier.0.20

0.0

-0.20

-0.40

-0.60

-0.80

(b)(a)

(d)(c)over 40% of the participants aged 60 and above. Thus, it was

concluded that such changes are not inevitable consequences

of advancing age (Coffey et al., 1992).

A cross-sectional study of 176 healthy individuals

787 years old reported dramatic nonlinear decline in gray

matter density until 60 years of age, with relatively stable or

slightly declining values thereafter (Sowell et al., 2003). The

effect of age was most prominent in the dorsal aspects of

the frontal and parietal association cortices on both the lateral

and interhemispheric surfaces, and in the orbitofrontal cortex

(Sowell et al., 2003). A greater rate of cortical thickness decline

in the frontal and parietal regions than in the temporal and

occipital regions was also detected in a recent longitudi-

nal study in cognitively normal individuals 6084 years old

(Thambisetty et al., 2010). Figure 7 shows a representation of

outer cortical surface with depiction of mean cortical thickness

trends (Thambisetty et al., 2010). The regional and temporal

MRI has also been used to assess whether sex-related differ-

ences exist in the process of brain aging. An early cross-

sectional study reported that volume reductions in the whole

brain and the frontal and temporal lobes were more prominent

(f)(e)

Figure 7 A typical outer cortical surface with the mean corticalthickness trends for the entire population used to color the entirecorresponding gyral region. The color scale is in mm/decade.A total of 66 healthy volunteers, 6084 years old at baselineparticipated in the study and each individual completed at least sixannual follow-up scans. Frontal and parietal regions show greater ratesof cortical thickness decline than the temporal and occipital regions.Reproduced from Thambisetty M, Wan J, Carass A, An Y, Prince JL,and Resnick SM (2010) Longitudinal changes in cortical thicknessassociated with normal aging. Neuroimage 52(4): 12151223,with permission from Elsevier.

MRI of the Brain 105in men, while in the hippocampus and the parietal lobes,

volume reductions were larger in women (Murphy et al.,

1996). However, longitudinal study design and more ad-

vanced data analysis of regional volumes examined in normal-

ized space permitted for the first time calculations of rates

of tissue loss of gray matter and white matter, and of ventric-

ular enlargement in a group of very healthy participants

5985 years old (Resnick et al., 2003). There were no overall

differences in rates of gray and white matter loss between men

and women (Resnick et al., 2003).

DTI has become a widely applied technique in studies

on brain tissue microstructure and integrity in the aging

brain. Both ROI-based analyses and whole brain voxel-based

approaches have been used. With increasing age, white matter

FA tends to decrease and mean diffusivity (MD) tends to in-

crease (Abe et al., 2002; Charlton et al., 2006; Giorgio et al.,

2010a,b; Pfefferbaum et al., 2000; Salat et al., 2005; Wu et al.,

2011). The pattern of age-related DTI abnormalities is more

pronounced in the frontal regions than in the posterior or

inferior brain regions (Michielse et al., 2010; Pfefferbaum

et al., 2005) and association fibers connecting cortical regions

are more affected by age than projection fibers (Sullivan

et al., 2010). DTI tractography revealed differences in the effect

of age among anatomical subdivisions of the same structure

(corpus callosum, cingulum; Michielse et al., 2010; Sullivan

et al., 2010). In several DTI studies, detected impairment

in white matter integrity was reported to be associated with

deterioration of cognitive performance (Bendlin et al., 2010;

Charlton et al., 2006; Voineskos et al., 2010). One study

examined age-related differences in FA and MD in deep

gray matter nuclei (Pfefferbaum et al., 2010). In the caudate

and the putamen, FA and MD were higher in the older group

(6579 years) than in younger participants (2237 years), pos-

sibly related to age-related increase in brain iron (Pfefferbaum

et al., 2010). In contrast, FA increases and MD decreases in the

caudate and the putamen between 5 and 30 years of age (Lebel

et al., 2008).

Pulsed ASL in conjunction with high-resolution structural

MRI was used to evaluate regional cortical and subcortical

resting CBF measures in a group of cognitively healthy

volunteers 2388 years old (Chen et al., 2011). Age-related

reductions in cortical perfusion were detected throughout the

cortex, while no significant age-related differences in CBF were

detected in subcortical regions. The most important finding,

highly relevant for interpretations of age-related cognitive de-

cline, was that the age-related patterns of CBF reductions were

different from patterns of cortical thinning (Chen et al., 2011).1H MR spectroscopic studies on normal aging have pro-

vided variable results, mainly due to differences in populations

and used spectroscopic techniques. A recent meta-analysis of

MRS literature data in healthy volunteers older than 60 years

concluded that normal aging is associated with decreased fron-

tal NAA and increased parietal Cho and Cr concentrations

(Haga et al., 2009). The finding of lower frontal NAA levels

in normal aging (Haga et al., 2009) is suggestive of impairment

in neuronal integrity, function, or, potentially, with neuronal

loss. A positive correlation between MRS-detected NAA con-

centration and DTI-derived FA in healthy 5090-year-old

volunteers is in agreement with the interpretation of NAA as

a measure of neuronal integrity (Charlton et al., 2006).3.07.5 MRI of the Brain in Pathologic Conditions

3.07.5.1 Ischemic Stroke

A stroke, or cerebrovascular accident, is the rapid loss of brain

function as a result of interruption of vascular supply of

blood to the brain. Stroke can be due to ischemia (lack of blood

supply) caused by thrombosis or embolism, or due to a hemor-

rhage (rupture of blood vessels). Acute stroke is a medical emer-

gency, and imaging is important in confirming the clinical

diagnosis and identifying underlying etiology. While CT has

been the traditional imaging modality of choice because of its

accessibility, speed, and lower cost, MRI is gaining wider utiliza-

tion because of its superb tissue contrast offering a greater sensi-

tivity in acute ischemic stroke, and ability of providing

information on vascular status.

In the evaluation of acute stroke, MRI has been proven in

multiple studies to be more sensitive compared to CT, partic-

ularly in the setting of ischemic stroke (Bryan et al., 1991;

Fiebach et al., 2002; Mohr et al., 1995; Warach et al., 1995).

In the case of hemorrhagic stroke, MRI, by the use of hemo-

siderin sensitive GRE sequence or susceptibility-weighted

imaging (SWI), is at least as sensitive as CT in revealing the

presence of hemorrhage (Bryan et al., 1991; Fiebach et al.,

2002; Kidwell et al., 2004). In a prospective series of blind

comparison of CT and MRI in a consecutive 356 patients

presenting to the emergency department with acute stroke

symptoms, MRI has an estimated sensitivity of 83% as opposed

to 26% by CT for the diagnosis of any acute stroke (Chalela

et al., 2007). In the critical hyperacute stage within 3 h of

symptom onset, MRI detected acute stroke in 46% of cases

compared to 7% by CT in the same study (Chalela et al.,

2007). The ability of MRI to offer such useful information is

in large part owing to the development of diffusion-weighted

imaging (DWI) in the mid-1990s (Warach et al., 1992). DWI is

able to depict the restriction of diffusion of water molecules as

a result of bioenergetic failure and cytotoxic edema, showing

up as hyperintensity on DWI, allowing an immediate diagnosis

of stroke (Gonzalez et al., 1999; Mullins et al., 2002). In the

same MRI session, the inclusion of magnetic resonance angi-

ography (MRA) allows assessment of the status of the intracra-

nial blood vessels, and perfusion-weighted imaging (PWI) to

visualize regional CBF and hemodynamics.

The signal intensity on DW trace image and ADC map

provides a means of dating the acuteness of infarct. Typically,

an acute ischemic stroke shows DWI hyperintensity that lasts

for 1014 days and hypointensity on ADC map for about

710 days, after which the signal gradually normalizes, and

ADC eventually increases above normal in chronic stroke.

Furthermore, by analyzing the evolution of signal changes on

both DWI and T2-weighted/FLAIR sequence allows further

characterization of the stage of evolution of the ischemic injury

(Petkova et al., 2010). This helps establish the time elapsed

since the initial ischemic insult in patients with unknown

onset of symptoms (Petkova et al., 2010), and may help deter-

mine whether the stroke is amenable to thrombolytic treat-

ment or not.

The pattern of infarct on MRI further provides a clue to

the underlying mechanism. For example, a vascular territorial

ischemic infarct indicates a proximal intracranial arterial

thrombosis, while multifocal small infarcts in a bilateral

hemispheric distribution suggest a cardiogenic embolic phe-

nomenon. Alternatively, a unilateral watershed infarction pat-

tern may result from a high-grade stenosis in the ipsilateral

internal carotid artery, and more extensive bilateral watershed

infarcts could indicate a hypotensive or hypovolemic state.

These clues to the underlying pathophysiology can be impor-

tant in directing acute therapy as well as further workup for risk

management.

As mentioned earlier, on the same MRI examination,

PWI (most frequently performed with gadolinium contrast

administration, so-called dynamic susceptibility contrast MR

perfusion imaging) may also offer additional information.

An imaging penumbra is represented by the area of abnormal

perfusion (most commonly depicted as increased time-to-peak

contrast arrival), whether due to vascular occlusion or stenosis,

excluding the ischemic core (DWI abnormality) and indicates

tissues at risk for infarction but still viable and salvageable if

there is timely intervention. Delineating this penumbra has

been useful in widening the window for therapeutic interven-

tion in a number of studies assessing the efficacy of intrave-

nous versus intra-arterial thrombolytics or neuroprotective

agents (Del Zoppo et al., 2009; Schellinger et al., 2007).

Figure 8 illustrates a 74-year-old patient with multifocal

ischemic stroke presenting with acute symptoms. Head CT

and conventional MR T2-weighted image identify multiple

areas of ischemia, the age of which is difficult to determine

on these images. By using the information provided by DWI

cerebral artery and posterior cerebral artery territories likely

results from cross filling from the contralateral side via the

communicating arteries). Compared to the large area of perfu-

sion deficit, only small foci of acute infarction are identified

on DWI. This leaves a large area of diffusionperfusion

mismatch, for which the term imaging penumbra has been

coined.

Occasionally, perfusion-weighted images may show a per-

fusion deficit even in the absence of DWI lesions indicating

acute infarction. This may indicate the need for urgent inter-

vention (e.g., thrombolysis or clot retraction). This is illus-

trated in Figure 10, in a 68-year-old female presenting with

left-sided weakness. MRI shows only subacute infarct and

bilateral chronic small vessel ischemic change, but there is a

much more extensive area of perfusion abnormality involving

the entire right MCA territory, directly related to critical steno-

sis or occlusion of the right M1 segment and likely responsible

for her acute symptoms.

3.07.5.2 Hypoxic Ischemic Injury in Neonates

DWI provides a highly sensitive evaluation of acute stroke in

adults. In addition, arterial and venous infarction in children is

also well visualized on DWI. However, interpretation of DWI

becomes more challenging in the evaluation of neonatal as-

phyxia where there is a more diffuse pattern of hypoxic ische-

mic injury. Hypoxicischemic encephalopathy (HIE) is caused

oncd Moefhe rtionA sh

106 MRI of the Brainand ADC, one can discriminate acute infarction from the back-

ground of subacute to chronic infarct as well as chronic small

vessel ischemic disease.

Figure 9 shows a case of carotid dissection and thrombosis,

resulting in abnormal perfusion to the entire ipsilateral middle

cerebral artery (MCA) territory (preserved flow to the anterior

CT T2

DWI ADC

Figure 8 Seventy-four-year-old male with multiple episodes of stroke. Nand occipital lobes, in addition to periventricular white matter. T2-weightediffusion-weighted imaging (DWI) hyperintensity and apparent diffusion cindicating an acute to subacute ischemic infarction (within 1 week old). Tcorresponding ADC hyperintensity indicating a subacute to chronic infarcshows the same area of perfusion deficits in the right temporal lobe. MRTTP

ontrast head CT shows foci of hypoattenuation in the right temporalRI confirms these two areas of infarction. Restricted diffusion withficient (ADC) hypointensity is demonstrated in the right temporal lobeight occipital lobe infarct, on the other hand, shows mild DWI andthat is at least beyond 2 weeks of age. Time-to-peak (TTP) map of PWIows absence of flow-related enhancement in the right MCA (arrow).by prolonged oxygen deprivation, and may be due to reduced

oxygen delivery (hypoxemia) or CBF (ischemia). In perinatal

asphyxia, which is the most common cause of HIE, hypoxia

rather than ischemia is the primary insult. HIE in neonates is a

major cause of mortality and long-term neurological morbidity

including seizures, motor deficits, and cognitive impairment.

MRA

AMRI of the Brain 107DWI MR

ADCManagement of HIE is mainly supportive care and prevention

of secondary central nervous system (CNS) insults such as

due to seizures and metabolic derangement; however, various

neuroprotective strategies including hypothermia and pharma-

cologic agents that curtail the effects of excitatory neurotoxicity

are under investigation (Gluckman et al., 2001; Shalak and

Perlman, 2004; Vannucci and Perlman, 1997). Prompt and

accurate diagnosis is hence critical for directing neuroprotective

agents and therapeutic intervention as many of these measures

TTP

1

Figure 9 Sixty-year-old male with right carotid dissection. On MRA, there isproximal and distal MCA branches (arrow). On diffusion-weighted imaging, tinvolving the right basal ganglia and right centrum semiovale. On PWI, a muthroughout the right MCA territory. Signal intensity versus time series showsthe left side.

FLAIR

MRA

DWI ADC TTP

Figure 10 Sixty-eight-year-old female presenting with left-sidedweakness. On FLAIR images, there are small areas of signal abnormalityscattered in the bilateral striatocapsular regions and the right centrumsemiovale, demonstrating vague DWI hyperintensity but no evidence ofrestricted diffusion on ADC maps, confirming that these lesionsrepresent subacute and/or chronic small vessel ischemic changes. TTPimages demonstrate a much more extensive area of perfusion deficitinvolving the right MCA territory, directly corresponding to the abruptcutoff of the right M1 segment demonstrated on MRA (arrows).should most effectively be targeted to prevent the onset of

secondary deterioration (i.e., secondary energy failure).

The majority of infants sustain hypoxicischemic injury in

the immediate perinatal period (Gunn and Bennet, 2008).

Various brain regions are particularly susceptible to injury

depending on the maturity of brain, as well as severity and

duration of the insult (Huang and Castillo, 2008). Two major

patterns of injury have been noted in term infants with HIE

(Barkovich et al., 1995). Mild to moderate injury usually pro-

duces a pattern of parasagittal white matter injury occurring in

the vascular boundary zones, and often resulting in neonatal

22

1

a complete lack of flow-related signal in the right internal carotid artery,here are small foci of restricted diffusion indicating acute infarctionch larger area of abnormal perfusion (with prolonged TTP) is identifieddelayed contrast bolus arrival to the right hemisphere compared toseizure but with near normal Apgar scores. Following a pro-

found asphyxia, those infants typically have low Apgar scores

necessitating resuscitation at delivery and usually sustain bilat-

eral deep gray matter injury including ventrolateral thalami,

posterior putamina, hippocampi, corticospinal tracts, and peri-

rolandic gyri (Barkovich, 1992; Huang and Castillo, 2008;

Triulzi et al., 2006).

MR imaging can provide important information about the

site, extent, severity, and etiology of cerebral injury, as well as

prognostic factors (Rutherford et al., 2006). However, conven-

tional (e.g., T1- and T2-weighted) MRI generally lacks sensitiv-

ity in the acute phase, as the abnormalities may not become

apparent until several days after onset of injury on these types

of images. DWI may also appear unremarkable in early stages

of HIE and frequently underestimates the final extent of injury

depending on the time of imaging after acute insult (Barkovich

et al., 1999; Barkovich et al., 2006). 1HMRS, particularly by the

elevation of lactate (Lac), has been used to provide the most

sensitive and useful diagnosis in acute hypoxic-ischemia injury

as early as the first day of life (Barkovich et al., 1999; Barkovich

et al., 2001). However, corresponding to the physiologic re-

sponse and very similar to DWI, MRS also shows temporal

evolution and topological variation of metabolite concentra-

tions (Barkovich et al., 2006).

Ainfant with severe hypoxic ischemic encephalopathy. Diffuse T1 hypointenseternal capsules, and some cortical regions, as well as deep gray, and internal capsules reflecting cytotoxic edema. The bottom panel) MRS (TR/TE 1500/135 ms) performed on the 1-day-old newborn witheak.

DWI

1.5

NM ChoI: 14.2

CrI: 10.4

Cr2I: 7.75

NAAI: 12.7

1.0

0.5*Lac

ADC SWI

108 MRI of the BrainIn the case of severe HIE, both the deep gray matter and

cerebral hemispheres may be affected. Figure 11(a) shows

diffusely decreased T1 and increased T2 signal throughout the

white matter, internal capsules, and some cortical regions, in

addition to edematous deep gray structures in a 1-day-old

infant. Diffusion-weighted images depict areas of hyperinten-

sity including the white matter, corpus callosum, and internal

capsules reflecting cytotoxic edema. MRS with a voxel placed in

the right basal ganglia shows an inverted Lac doublet at 1.33.

In this case, it is consistent with a state of anaerobic metabo-

lism as a consequence of hypoxemia (Figure 11(b)).

Another case of a term neonate presenting with seizures

and profound neurological abnormality is shown in Figure 12.

Conventional MRI and DWI are unremarkable, although mild

ADC hypointensity is seen in the deep gray nuclei. MRS shows

elevation of Lac in the basal ganglia and occipital lobe, support-

ing the diagnosis of severe HIE. SWI also demonstrates sharply

T1

3-day-old, normal MRI

(a)

T2 DWI1-day-old, HIE

Figure 11 MRI and MRS in HIE. (a) Top panel shows MRI of a 1-day-oldand T2 hyperintense signal abnormality is identified in the white matter, instructures, with DWI hyperintensity in the white matter, corpus callosum(for comparison) shows normal MRI findings from a 3-day-old patient. (bHIE with a voxel placed in the right basal ganglia shows an inverted Lac pdelineated hypointensity throughout the intracranial venous

structures, suggesting a profoundly deoxygenated blood con-

tent typically seen in brain death. This child was sustained

by mechanical support and the imaging findings predicted a

poor prognosis.

Seven neonates with encephalopathy following a compli-

cated delivery during the first 24 h of life were evaluated with

conventional MRI, DWI, and single-voxel MRS in a retrospec-

tive case study (Barkovich et al., 2001). Conventional imaging

was largely normal, although some cases showed T2 prolonga-

tion, indicating mild edema, in the basal ganglia or cortex.

DWI findings were also not dramatically abnormal, but in a

few cases showed reduced diffusion in the PLIC and/or lateral

thalami. This subtle abnormality was better assessed by mea-

suring ADC values rather than visual inspection of DWI: a

1520% of decrease in ADC was found throughout the brain

compared to healthy controls. In contrast, 1H MRS showed

more prominent abnormalities, with elevation of Lac/NAA

ratios and reduction of NAA. Furthermore, follow-up imaging

studies suggested that acute MRI and DWI underestimated the

topological extent of injury (Barkovich et al., 2001).(b)

DC

Cho

CrNAA

PPM 4.0 3.0 2.0 1.0

Lac3.07.5.3 Intracranial Hemorrhage and Traumatic BrainInjury

Acute intracranial hemorrhage (ICH) may be effectively

detected by head CT. MRI is also very sensitive for the detection

of ICH; the FLAIR sequence is particularly useful in depicting

subarachnoid hemorrhage for a longer window of time com-

pared to CT, and SWI or other hemosiderin sensitive GRE

sequences are very sensitive for detecting parenchymal hemor-

rhage. MRI furthermore provides a detailed means of dating

the age of a parenchymal hematoma since the appearance of

intracranial hemorrhage depends on different MR contrast by

0.0

4 3 2 1ppm

Figure 12 A term neonate presenting with seizures and abnormalneurological exam at 1 day of life. DWI is unremarkable, butmild hypointensity is suggested on ADC map in the deep gray matter(block arrow). SWI shows distinct hypointensity throughout theintracranial venous structures. MRS (TR/TE 1500/270 ms) from a voxelin the left basal ganglia shows an elevation of Lac at 1.33 ppm (*Lac).

suffering from dementia would be highly suggestive of amy-

loid angiopathy. Multiple scattered foci of lesions, often vary-

ing in size, can be seen in individuals with multiple cerebral

cavernous malformations. A similar pattern in an individual

with a history of previous total brain radiation in early child-

hood may indicate radiation-induced telangiectasia.

In addition to the detection of hemorrhagic lesions, SWI

can be very useful in depicting venous anatomy, as well

as mineralized lesions with either calcification or iron deposi-

tion. SWI takes advantage of intrinsic contrast of the deoxyhe-

moglobin in the veins, so that small, normal cerebral venous

structures are exquisitely depicted. Developmental venous

anomaly (DVA) is the most frequently encountered vascular

malformation in the brain, and can be readily identified on

SWI with a characteristic caput medusa appearance including

a linear transmedullary draining vein. DVA increases in occur-

rence in association with rare disorders such as SturgeWeber

syndrome, hereditary hemorrhagic telangiectasia, and facial

hemangioma. Finally, qualitative and quantitative SWI has

been used in evaluation of iron deposition in neurodegenera-

tive disorders such as Parkinsons disease, Huntingtons

disease, and multiple sclerosis.

and DWI images are shown in three different axial slices: top row at thelevel of the midbrain; middle at the level of the basal ganglia; andbottom row at the level of superior cortex. FLAIR images show multiplefoci of edema in the right dorsal midbrain (arrow), left medial temporallobe (curved arrow), bilateral deep gray (block arrows), splenium of thecorpus callosum (curved block arrow), as well as the superior frontallobes bilaterally (*). The frontal lobe lesions show hypointensity on T2*-weighted gradient echo sequence indicating hemorrhagic contusions thatare also evident on CT (not shown). Restricted diffusion with DWIhyperintensity is evident in the right dorsal brainstem, left temporallobe, bilateral deep gray and bilateral frontal white matter, andmore extensively in the genu as well as splenium of the corpuscallosum.

MRI of the Brain 109T1- or T2-weighting, and varies with the age of the hematoma

(Bradley, 1993). The hemoglobin products evolve with time

through several forms including oxyhemoglobin, deoxyhemo-

globin, intracellular, and extracellular methemoglobin, and

finally, get broken down to ferritin and hemosiderin, which are

sequestered by macrophages and scavenger cells in the chronic

stage. T1-shortening occurs in methemoglobin as a result of

paramagnetic dipoledipole interactions, whereas the magnetic

susceptibility effect is responsible for T2-shortening observed

with deoxyhemoglobin, methemoglobin, and hemosiderin

blood products (Bradley, 1993). T2-shortening or susceptibility

effects are accentuated by increasing the strength of magnetic

field used.

Five stages of hemorrhage are described on conventional

MRI:

1. hyperacute (intracellular oxyhemoglobin, long T1 and T2)

2. acute (intracellular deoxyhemoglobin, long T1, short T2)

3. early subacute (intracellular methemoglobin, short T1,

short T2)

4. late subacute (extracellular methemoglobin, short T1, long

T2)

5. chronic (ferritin and hemosiderin, short T2)

In the setting of trauma, MRI has been demonstrated to be

more useful than CT in detecting abnormalities related to

diffuse axonal shearing injury (DAI) since only about 20% of

DAI present with punctate foci of acute hemorrhage detectable

on CT, and the extent of injury is grossly underestimated by CT

(Gentry et al., 1988; Gentry et al., 1989). This type of injury

results from acute acceleration and deceleration, with rotation

forces and shear strains developing between tissues possessing

different rigidity and composition. Most frequently, the DAI

lesions occur in the lobar white matter at the corticomedullary

junction (67%), corpus callosum (particularly the splenium;

2147%), and in more severe circumstances, dorsolateral

brainstem (Gentry et al., 1988). Those lesions with macro-

scopic hemorrhage may either be inconspicuous or show up

as small areas of hyperdensity on head CT, often in marked

discordance with the clinical status of a comatous or obtunded

patient. MRI in these cases can often reveal multifocal lesions

with signal abnormality on different sequences including

FLAIR, DWI, and SWI (suggesting the presence of vasogenic

edema, cytotoxic edema, and hemorrhage), which may reflect

different stages or characteristics of shearing injury (Hergan

et al., 2002; Parizel et al., 1998). An example is illustrated

in Figure 13 in an 18-year-old female who was involved in a

motor vehicle accident.

As mentioned in the previous section, MRI is at least

as sensitive as CT in detecting hemorrhagic stroke (Chalela

et al., 2007). The use of SWI is particularly helpful in detecting

tiny foci of parenchymal hemorrhagic lesions even in the

chronic stages. Aside from traumatic brain injury, SWI is very

sensitive in depicting multiple punctate foci of hemosiderin

scattered throughout the brain parenchyma that can occur in a

number of pathologic conditions (Tong et al., 2008). For

example, this can be seen in hypertensive vasculopathy, with

distribution following anatomic locations that are prone

to hypertensive hemorrhage such as basal ganglia, thalami,

pons, and cerebellum. A pattern of multiple lesions distributed

more peripherally in an elderly, normotensive individualFLAIR T2* DWI

Figure 13 Severe traumatic brain injury (TBI) in an 18-year-oldfemale following motor vehicle collision with a telephone pole. FLAIR, T2*,

3.07.5.4 Brain Tumors

MRI is indispensable for the diagnosis and characterization

of brain tumors. Anatomic imaging provides important

information for surgical planning, and by combining with

multimodality advanced imaging techniques, physiologic,

hemodynamic, and functional assessment also becomes pos-

sible such by the use of PWI, 1H MRS, and blood oxygenation

level-dependent functional MRI (fMRI). These advanced tech-

niques enhance ones understanding of tumor biology, and

allow increased precision in diagnosis as well as better target

definition and assessment of treatment response.

There is a growing interest among neurosurgeons to incor-

porate the information provided by diffusion tractography,

fMRI, and intraoperative MRI in clinical practice to maximize

safety and assist decisions rendered before, during, and after

surgery (Young et al., 2010). DTI provides microstructural

information and can be helpful in defining axonal tract in-

volvement, whether by tumor infiltration or displacement, and

predicting the functional deficits in order to accurately plan

surgical approach and extent of resection. Task-based fMRI also

helps delineate the eloquent cortex that may be involved in

language, motor, or somatosensory function in relation to the

tumor.

FLAIR has elevated Cho on metabolic maps. This can be use-

ful in directing target for biopsy as well as treatment. While

MRS by itself usually does not contribute to the diagnosis of

tumor type, it often may provide important adjunct informa-

tion, and may be useful in discriminating neoplasms from

nonneoplastic lesions related to infection, inflammation, or

demyelination (Hourani et al., 2008).

Decreased ADC values are correlated with increased cellu-

larity of tumors, and can often be seen in small round blue cell

tumors including lymphoma and primitive neural ectodermal

tumor, as well as in higher grade of astrocytomas. Areas of

restricted diffusion were found to be a consistent feature

(90% of cases) of primary CNS lymphoma in a study of 20

patients prior to treatment, and could be useful in offering the

initial diagnosis as well as prognosis (Zacharia et al., 2008).

In the case of high-grade gliomas, the utility of ADC measure-

ments becomes less certain; ADC values could be used to

distinguish tumors from normal brain tissues, but there was

substantial overlap in values and they were not significantly

different between the tumor and adjacent edema (Castillo

et al., 2001). In a larger study of 51 patients diagnosed with

primary brain gliomas, on the other hand, ADC values or ADC

ratios were deemed helpful in preoperative grading (Arvinda

et al., 2009). More importantly, in several studies, ADC has

L

e m/TEiedy

110 MRI of the Brain1H MRS allows assessment of changes in a number of

metabolites in brain tumors, with elevated Cho (3.20 ppm)

levels reflecting increased cellular density, proliferative index,

and membrane turnover, often correlating with a more aggres-

sive neoplasm (Shimizu et al., 2000; Tamiya et al., 2000).

Figure 14 shows an example of multislice magnetic resonance

spectroscopic imaging (MRSI) of glioblastoma multiforme

(GBM). Markedly elevated Cho levels and diminished NAA,

with increased Cho/Cr ratio compared to the contralateral

normal brain tissue are features consistent with a nonnecrotic,

malignant neoplasm. MRSI has the advantage of displaying

heterogeneity within the large tumor. Note that in Figure 14,

only the posterior aspect of this high-grade tumor seen on

FLAIR Cho

LacNAA

Figure 14 MRSI of GBM. FLAIR image shows an infiltrative hyperintensshows marked hyperintensity on the Cho metabolic map. A spectrum (TRlevels and diminished NAA compared to the contralateral normal brain. RB. Barker, DPhil.been found to be a useful biomarker in the evaluation of

treatment response in brain tumors (Moffat et al., 2005;

Provenzale et al., 2006).

In primary brain glial tumors such as astrocytomas, in-

creased relative cerebral blood volume (rCBV) derived from

MR perfusion has been correlated with progressively higher

grading of the tumor (Arvinda et al., 2009; Rollin et al.,

2006). At the time of initial diagnosis, rCBV values were

found to be greater in high-grade than in low-grade glial tu-

mors (3.871.94 vs. 1.300.42), and were also consistentlyelevated in recurrent tumors (Rollin et al., 2006). Low-grade

gliomas had lower rCBV values than high-grade tumors even

Right

Cho

CrNAA

eft

PPM 4.0 3.0 2.0 1.0

ass in the right temporal lobe. The posterior aspect of this mass2000/280 ms) obtained from this region demonstrates elevated Choand Barker; ASNR Washington, DC; 2003, image courtesy of Peter

when they showed contrast enhancement (a feature more

common in high grade tumors; Rollin et al., 2006). In analyz-

ing perfusion data from a retrospective study of 51 patients

with cerebral gliomas, a threshold rCBV value of 2.91 discrim-

inated high-grade tumors with sensitivity, specificity, positive

predictive value, and negative predictive value of 94.7%,

93.8%, 90.0%, and 96.8%, respectively. The ranges were

0.293.14 for low-grade and 2.8212.86 for high-grade tumors

(Arvinda et al., 2009). Finally, rCBVwas also found to be useful

in monitoring therapeutic response (Cha, 2004; Provenzale

et al., 2006; Rollin et al., 2006; Scarabino et al., 2009).

Primary CNS lymphoma and GBM are both aggressive,

malignant brain tumors and can share many similar features

on MRI. Both affect older individuals, grow by infiltration,

demonstrate contrast enhancement, and preferentially involve

the white matter including the corpus callosum. However,

GBM tends to have a necrotic center, whereas primary CNS

lymphoma in an immunocompetent host typically shows solid

enhancement. Accurate presurgical diagnosis is important

since treatment is different, with lymphomas being virtually

always unresectable yet responsive to chemoradiation.

By multiparametric analysis of ADC values, MRS metabolic

ratios, and rCBV, primary CNS lymphoma can be distin-

guished from high-grade primary gliomas and from metastatic

lesions (Chawla et al., 2010; Hartmann et al., 2003; Toh et al.,

contrast enhancement. Restricted diffusion is identified in

these lesions, indicating hypercellularity that is often seen in

lymphoma. Cerebral blood volume is not particularly elevated

in these lesions, but this may be confounded by steroids ad-

ministration in this patient. Proton MRS from a voxel placed in

the splenium of corpus callosum shows elevated Cho, de-

creased NAA, as well as a prominent Lac doublet. A biopsy

from the right frontal lobe lesion confirmed large B cell

lymphoma.

Amide proton transfer (APT) imaging (Wen et al., 2010) is

an emerging technique that utilizes the endogenous contrast

provided by the protein and peptide contents in the lesion

(Figure 16), which, as suggested by preliminary data, may

correlate with the degree of tumor cellularity and grade.

Although still in the early stages of development, this in-

formation again complements morphological data, and

in the future may be useful in predicting tumor behavior,

and serve as a surrogate marker in monitoring response to

therapy.

3.07.6 Conclusion

The introduction of MRI and MRS into neuroradiology

has opened new possibilities for studies of brain anatomy,

15.4

3

D

lymntrabutd N

MRI of the Brain 1112006). In general, lymphomas show decreased ADC values,

and on MRS they tend to demonstrate prominent lipids and

Lac, in addition to elevated Cho (Chawla et al., 2010; Toh

et al., 2006; Zacharia et al., 2008). The maximum mean

rCBV ratio in lymphoma is significantly lower than that of

the GBM (1.290.18 vs. 4.992.1; Hartmann et al., 2003).An example (Figure 15) of CNS lymphoma is shown in a

71-year-old male who presented with multifocal FLAIR hype-

rintense lesions in the right frontal lobe as well as the splenium

of the corpus callosum, accompanied by heterogeneous

FLAIR

CBV4

ChoI : 20.7

Cr2I : 18.8

CrI :

2

0

4

-2

T1+ C

Figure 15 Seventy-one-year-old male with newly diagnosed primary CNSand the splenium of the corpus callosum, which show heterogeneous cohypointensity is identified in these lesions indicating restricted diffusion,placed in the splenium of corpus callosum shows elevated Cho, decreaseNAAI : 17.1

2 1

phoma. FLAIR image shows hyperintense lesions in the right frontal lobest enhancement (T1C). DWI hyperintensity with corresponding ADCCBV does not appear elevated. MRS (TR/TE 2000/140 ms) with a voxelAA, as well as a prominent inverted Lac doublet.function, and metabolism in living humans, both in health

and disease. As documented in this chapter on current exam-

ples of clinical applications, multimodal MRI protocols are

becoming routine in clinical neuroimaging. The use of high-

field imaging approaches for mapping brain function and

their integration into multimodal neuroimaging protocols

will help better understand brain damage in patients with a

wide range of pathologies, such as tumors, stroke, trauma,

coma, and infectious, inflammatory, and demyelinating disor-

ders (Moseley and Liu, 2008). Furthermore, this integrated

WI ADC

112 MRI of the BrainT2 T1

APTT1+C 5%

5%

Figure 16 APT imaging of GBM. T2-weighted image demonstrates alarge hyperintense tumor in the left frontal lobe with an area of cystformation (black arrow). T1-weighted image shows that the entire tumoris hypointense. Gadolinium-enhanced T1-weighted image (T1C)demonstrates an enhancing tumor core (red arrow) with nonenhancinginformation will facilitate the development of the most timely

and effective interventions.

Acknowledgment

The authors are thankful to Peter Barker for his comments on

the manuscript.

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MRI of the BrainGlossaryIntroductionMR-Based Modalities for Assessing Brain AnatomyMRI in Normal Brain DevelopmentMRI in Normal Brain AgingMRI of the Brain in Pathologic ConditionsIschemic StrokeHypoxic Ischemic Injury in NeonatesIntracranial Hemorrhage and Traumatic Brain InjuryBrain Tumors

ConclusionAcknowledgmentReferences