MR

imaging

of

therapy-induced

changes

of

bone

marrow

MR

imaging

of

bone

marrow

infiltration

by

hematologic

malignancies

provides

non-invasive

assays

of

bone

marrow

cellularity

and

vascularity

to

supplement

the

information

provided

by

bone

marrow

biopsies

This

article

will

review

the

MR

imaging

findings

of

bone

marrow

infiltration

by

hematologic

malignancies

with

special

focus

on

treatment

effects

MR

imaging

findings

of

the

bone

marrow

after

radiation

therapy

and

chemotherapy

will

be

described

In

addition

changes

in

bone

marrow

microcirculation

and

metabolism

after

anti-angiogenesis

treatment

will

be

reviewed

Finally

new

specific

imaging

techniques

for

the

depiction

of

regulatory

events

that

control

blood

vessel

growth

and

cell

proliferation

will

be

discussed

Future

developments

are

directed

to

yield

comprehensive

information

about

bone

marrow

structure

function

and

microenvironment

Introduction

Bone

marrow

is

the

fourth

largest

organ

of

the

human

body

Its

main

function

is

the

hematopoiesis

i.e.

it

provides

the

body

with

erythrocytes

leukocytes

and

platelets

in

order

to

maintain

the

oxygenation

immune

function

and

auto-restoration

of

the

body

MR

imaging

provides

a

non-invasive

visualization

of

the

bone

marrow

and

may

be

used

to

define

its

cellular

or

fat

content

as

well

as

its

vascularity

and

metabolism

Treatment

effects

due

to

irradiation

chemotherapy

or

other

new

treatment

regimens

may

change

one

or

several

of

these

components

thereby

causing

local

or

generalized

changes

in

bone

marrow

signal

intensity

on

MR

images

This

article

will

provide

an

overview

over

such

treatment-related

bone

marrow

signal

changes

on

MR

imaging

In

order

to

recognize

these

treatment

effects

one

has

to

be

familiar

with

the

MR

imaging

features

of

the

normal

and

non-treated

pathologic

marrow

Thus

this

article

will

first

provide

a

brief

overview

over

MR

imaging

features

of

the

normal

and

non-treated

pathologic

marrow

as

a

basis

for

subsequent

descriptions

of

the

bone

marrow

after

conservative

or

new

treatments

Indications

to

study

treatment

effects

In

patients

with

hematopoietic

malignancies

the

diagnosis

of

neoplastic

bone

marrow

infiltration

is

crucial

to

determine

prognosis

and

to

identify

suitable

treatment

protocols

-LSB-

-RSB-

This

diagnosis

is

usually

obtained

by

iliac

crest

biopsy

which

is

mandatory

for

staging

and

histopathologic

classification

of

the

disease

-LSB-

-RSB-

In

non-Hodgkin

's

lymphoma

-LRB-

NHL

-RRB-

a

neoplastic

bone

marrow

infiltration

indicates

the

highest

stage

-LRB-

stage

four

-RRB-

according

to

the

Ann

Arbor

Classification

In

cases

of

myeloma

the

extent

of

bone

marrow

infiltration

may

be

associated

with

any

stage

of

the

Salmon

and

Durie

classification

-LSB-

-RSB-

In

both

instances

iliac

crest

biopsy

may

be

false

negative

when

the

bone

marrow

infiltration

is

focal

rather

than

diffuse

-LSB-

-RSB-

The

role

of

MR

imaging

for

the

depiction

of

bone

marrow

infiltration

by

hematologic

malignancies

is

controversial

and

depends

on

the

type

stage

and

clinical

course

of

the

malignancy

For

patients

with

multiple

myeloma

MR

has

been

established

in

some

centers

as

an

integrative

technique

for

staging

and

treatment

monitoring

since

it

proved

to

be

highly

sensitive

for

the

detection

of

bone

marrow

infiltrates

and

provided

important

additional

information

to

conventional

bone

surveys

In

several

studies

MR

showed

a

higher

sensitivity

than

conventional

bone

surveys

and

bone

scintigraphy

for

the

detection

of

focal

bone

marrow

lesions

-LSB-

-RSB-

Thirty-three

percent

of

patients

with

myeloma

were

understaged

based

on

the

skeletal

survey

when

compared

to

MR

-LSB-

-RSB-

And

some

MR

findings

have

been

shown

to

have

direct

prognostic

relevance

In

patients

with

stage

disease

according

to

Salmon

and

Durie

a

pathologic

bone

marrow

MR

and

normal

bone

survey

was

associated

with

a

worse

prognosis

than

a

normal

MR

and

normal

bone

survey

-LSB-

-RSB-

And

in

patients

with

stage

disease

according

to

Salmon

and

Durie

a

diffuse

bone

marrow

infiltration

as

shown

on

MR

images

was

associated

with

a

worse

prognosis

than

a

multifocal

bone

marrow

infiltration

-LSB-

-RSB-

For

patients

with

Hodgkin

's

lymphomas

and

high-grade

NHL

FDG-PET

has

been

established

as

the

imaging

modality

of

choice

for

staging

and

treatment

monitoring

and

MR

imaging

should

only

be

considered

in

selected

cases

with

high

risk

of

bone

marrow

involvement

and

equivocal

findings

on

PET

or

extracompartmental

tumor

growth

Neither

MR

nor

FDG-PET

is

meant

to

replace

marrow

biopsy

because

the

histopathologic

subtype

of

lymphoma

has

to

be

defined

and

because

minimally

diffuse

microscopic

marrow

involvement

can

be

false

negative

with

either

imaging

technique

-LSB-

-RSB-

On

the

other

hand

routinely

performed

iliac

crest

biopsies

cover

only

a

small

portion

of

the

entire

bone

marrow

and

also

provide

potential

false-negative

findings

-LSB-

-RSB-

Thus

in

selected

patients

with

a

high

risk

of

bone

marrow

involvement

MR

imaging

may

contribute

clinically

significant

information

In

a

study

by

Hoane

et

al.

in

patients

with

malignant

lymphoma

up

to

one-third

of

the

patients

evaluated

with

routine

iliac

crest

biopsies

had

occult

marrow

tumor

detectable

with

MRI

-LSB-

-RSB-

In

addition

patients

with

negative

marrow

biopsies

but

pathologic

MR

were

found

to

have

a

worse

prognosis

than

patients

with

negative

marrow

biopsies

and

normal

MR

-LSB-

-RSB-

Thus

since

the

diagnosis

of

bone

marrow

involvement

affects

treatment

decisions

and

prognosis

these

authors

concluded

that

optimal

bone

marrow

evaluation

in

such

patients

should

include

both

biopsy

and

MR

-LSB-

-RSB-

Another

valuable

contribution

of

MR

is

its

capacity

to

detect

soft-tissue

paravertebral

masses

as

well

as

epidural

masses

and

neural

foramen

invasion

which

may

accompany

vertebral

disease

In

case

of

clinical

symptoms

such

as

unexplained

back

pain

or

new

neurological

symptoms

MR

is

the

modality

of

choice

to

detect

paravertebral

and

epidural

masses

which

may

accompany

bone

marrow

infiltration

of

the

spine

For

patients

with

leukemia

there

is

currently

no

role

for

routine

bone

marrow

evaluation

with

MR

imaging

neither

before

nor

after

therapy

Particular

questions

in

these

patients

that

may

be

addressed

by

MR

are

the

search

for

biopsy

sites

in

patients

with

suspected

new

or

relapsed

disease

but

negative

bone

marrow

biopsy

as

well

as

the

diagnosis

of

treatment

complications

such

as

treatment

induced

bone

marrow

infarcts

or

avascular

necroses

when

conventional

radiographs

are

negative

or

equivocal

-LSB-

-RSB-

In

summary

dedicated

MR

imaging

of

the

bone

marrow

in

patients

with

hematologic

malignancies

is

currently

restricted

to

applications

in

patients

with

multiple

myeloma

selected

patients

with

other

malignant

lymphomas

with

a

high

risk

of

bone

marrow

infiltration

and/or

extracompartmental

tumor

growth

as

well

as

patients

with

potential

treatment

complications

Additional

patients

with

hematologic

malignancies

may

undergo

MR

imaging

for

evaluations

of

other

pathologies

outside

the

bone

marrow

And

since

the

bone

marrow

is

depicted

on

nearly

any

MR

examination

throughout

the

body

the

knowledge

of

the

normal

and

pathologic

marrow

of

these

patients

before

and

after

therapy

is

crucial

for

the

radiologist

in

order

to

provide

a

comprehensive

diagnosis

Such

secondary

evaluations

of

the

bone

marrow

may

outperform

above

mentioned

primary

indications

in

this

patient

population

Technique

Standard

techniques

to

depict

the

bone

marrow

at

T

and

T

clinical

scanners

comprise

plain

spinecho

-LRB-

SE

-RRB-

or

fast-SE

-LRB-

FSE

-RRB-

sequences

as

well

as

short

TI

inversion

recovery

-LRB-

STIR

-RRB-

sequences

The

non-fat-saturated

spinecho

-LRB-

SE

-RRB-

or

FSE

sequences

are

best

suited

to

define

the

cellular

content

of

the

bone

marrow

and

should

be

included

in

any

protocol

for

MR

imaging

of

the

bone

marrow

STIR

sequences

are

useful

as

a

screening

sequence

to

search

for

abnormalities

in

the

bone

marrow

most

of

which

appear

with

a

very

high

signal

intensity

on

these

sequences

There

is

some

debate

about

the

optimal

inversion

time

-LRB-

TI

-RRB-

for

depiction

of

the

bone

marrow

abnormalities

with

STIR

sequences

-LSB-

-RSB-

Some

authors

prefer

a

TI

that

causes

a

suppression

of

all

normal

structures

and

provides

a

maximal

contrast

between

normal

-LRB-

no

signal

-RRB-

and

pathologic

-LRB-

high

signal

-RRB-

tissues

Other

authors

prefer

a

TI

which

is

slightly

higher

in

order

to

provide

some

additional

background

signal

of

normal

tissues

-LRB-

low

signal

-RRB-

and

thus

improved

anatomical

information

The

advantages

of

STIR

sequences

are

that

they

provide

a

very

high

tissue

contrast

and

that

they

are

insensitive

to

magnetic

field

inhomogeneities

The

disadvantages

are

that

STIR

sequences

have

a

limited

signal-to-noise

ratio

and

that

the

fat

suppression

technique

is

non-specific

The

signal

from

tissue

or

fluid

with

a

similar

to

that

of

fat

will

also

be

suppressed

for

example

mucoid

tissue

hemorrhage

proteinaceous

fluid

and

gadolinium

-LSB-

-RSB-

Selective

fat-suppressed

images

are

an

alternative

to

STIR-images

at

high

field

MR

scanners

Selective

fat

saturation

is

lipid

specific

usually

provides

a

higher

signal-to-noise

ratio

than

STIR

sequences

and

does

not

suppress

gadolinium-based

contrast

agent

-LRB-

i.e.

can

be

added

after

contrast

medium

administration

-RRB-

However

selective

fat

saturation

is

susceptible

to

magnetic

field

inhomogeneities

To

achieve

reliable

fat

saturation

the

frequency

of

the

frequency-selective

saturation

pulse

must

equal

the

resonance

frequency

of

lipid

Inhomogeneities

of

the

static

magnetic

field

will

shift

the

resonance

frequencies

of

both

water

and

lipid

this

discrepancy

would

result

in

poor

fat

suppression

or

even

worse

saturation

of

the

water

signal

instead

of

the

lipid

signal

Static

field

inhomogeneities

inherent

in

magnet

design

are

relatively

small

in

modern

magnets

and

can

be

reduced

by

decreasing

the

field

of

view

centering

over

the

region

of

interest

and

autoshimming

However

substantial

inhomogeneities

can

be

caused

by

local

magnetic

susceptibility

differences

such

as

those

found

at

air-bone

interfaces

or

around

foreign

bodies

like

metal

or

air

collections

-LSB-

-RSB-

Of

note

FSE

sequences

without

fat

saturation

are

probably

the

worst

sequences

for

evaluation

of

the

bone

marrow

since

both

lesions

and

normal

fatty

marrow

appear

hyperintense

on

these

sequences

Other

MR

imaging

techniques

have

been

developed

to

improve

the

detection

and

quantification

of

diffuse

bone

marrow

involvement

These

techniques

include

chemical-shift

imaging

bulk

relaxation

time

measurement

and

hydrogen

spectroscopy

-LSB-

-RSB-

All

of

these

methods

were

used

to

measure

the

fat

content

or

the

water/fat

fraction

more

accurately

However

these

measurements

have

so

far

not

demonstrated

clinical

significance

and

hence

these

techniques

are

currently

not

used

for

routine

imaging

Diffusion-weighted

MR

imaging

techniques

have

been

reported

to

be

useful

for

the

differentiation

of

neoplastic

marrow

infiltration

and

pathologic

vertebral

fractures

-LSB-

-RSB-

Recently

further

advanced

diffusion-weighted

whole

body

scans

have

been

described

for

treatment

monitoring

of

patients

with

leukemia

-LSB-

-RSB-

The

technique

relies

on

selective

excitation

of

the

water

resonance

and

generation

of

image

contrast

that

is

dependent

upon

differential

nuclear

relaxation

times

and

self-diffusion

coefficients

Contrast-agent

enhanced

scans

In

most

instances

the

administration

of

Gd-based

contrast

agents

is

not

necessary

for

evaluation

of

bone

marrow

disorders

Administration

of

Gd-DTPA

can

be

helpful

to

differentiate

cysts

and

tumors

to

differentiate

necrotic

and

viable

tumor

tissue

before

a

biopsy

in

suspected

osteomyelitis

or

in

equivocal

cases

of

bone

infarcts

If

Gd-DTPA-enhanced

scans

are

performed

fat

saturated

sequences

should

be

used

in

order

to

suppress

the

fatty

components

of

the

bone

marrow

with

intrinsic

high

signal

intensity

and

thus

to

provide

an

optimal

depiction

of

the

Gd-enhancement

The

diagnosis

of

lesion

vascularization

based

on

comparisons

between

plain

non-fat-saturated

and

fat-saturated

Gd-enhanced

sequences

is

no

problem

if

the

investigated

focal

lesion

shows

a

marked

enhancement

However

it

may

be

difficult

to

determine

if

a

certain

lesion

shows

minimal

or

no

contrast

enhancement

based

on

comparisons

of

plain

non-fat-saturated

and

fat-saturated

Gd-enhanced

sequences

In

these

cases

we

recommend

to

obtain

additional

Gd-enhanced

non-fat-saturated

MR

sequences

with

identical

pulse

sequence

parameters

as

the

plain

sequences

A

subtraction

of

pre

and

post

sequences

can

then

identify

a

presence

or

absence

of

contrast

enhancement

of

certain

focal

lesions

listed

above

Additional

dynamic

contrast

enhanced

scans

after

administration

of

Gd-DTPA

have

been

applied

by

some

investigators

in

order

to

generate

estimates

of

the

blood

volume

of

the

normal

or

pathologic

bone

marrow

before

and

after

treatment

-LSB-

-RSB-

Such

dynamic

contrast

enhanced

MR

studies

with

gadolinium

chelates

should

be

performed

with

rapid

acquisition

techniques

producing

interscan

intervals

as

short

as

possible

to

best

measure

the

rapidly

evolving

distribution

patterns

of

these

small

molecular

probes

-LRB-

daltons

-RRB-

Although

investigated

since

-LSB-

-RSB-

dynamic

Gd-DTPA-enhanced

MR

studies

have

not

shown

clinical

significance

so

far

In

addition

to

bone

marrow

perfusion

the

amount

of

contrast

agent

at

any

time

within

the

bone

marrow

depends

on

several

additional

inter-related

variables

including

microvessel

permeability

endothelial

surface

area

hydrostatic

pressure

osmotic

pressure

diffusion

convective

forces

interstitial

pressure

and

clearance

Clearly

contrast

media

kinetics

in

the

bone

marrow

is

not

a

simple

matter

and

shows

a

high

interindividual

and

intraindividual

variability

with

respect

to

the

mentioned

influencing

factors

-LSB-

-RSB-

This

may

be

one

reason

why

it

did

not

find

wide

clinical

application

to

date

New

macromolecular

contrast

media

-LRB-

MMCM

-RRB-

may

provide

more

specific

information

on

bone

marrow

blood

volume

and

sinus

permeability

which

may

be

more

useful

to

study

treatment

effects

Small

molecular

Gd-chelates

can

only

estimate

the

blood

volume

-LRB-

immediate

post-contrast

scans

-RRB-

and

extracellular

space

-LRB-

later

post-contrast

scans

-RRB-

of

the

normal

or

abnormal

bone

marrow

because

these

small

molecules

permeate

readily

and

non-selectively

across

normal

and

abnormal

capillaries

in

the

bone

marrow

MMCM

can

also

estimate

the

blood

volume

based

on

immediate

post-contrast

scans

In

addition

MMCM

are

so

large

that

their

diffusion

across

microvessels

is

affected

by

the

permeability

of

these

vessels

This

may

be

helpful

for

treatment

monitoring

of

anti-angiogenesis

drugs

which

specifically

and

readily

decrease

microvascular

permeability

but

which

have

no

immediate

effect

on

the

blood

volume

Thus

MMCM

may

be

able

to

predict

a

response

to

anti-angiogenic

treatment

before

a

subsequent

arrest

in

tumor

vessel

growth

-LRB-

decrease

in

blood

volume

-RRB-

and

before

clinical

signs

of

response

-LRB-

laboratory

parameters

-RRB-

are

apparent

-LSB-

-RSB-

At

this

time

of

the

MMCMs

are

yet

FDA

approved

but

several

of

these

agents

are

currently

in

advanced

stages

of

development

for

applications

in

patients

-LRB-

phase

II

and

III

clinical

trials

-RRB-

such

as

Vasovist

-LRB-

Epix

and

Schering

approved

in

Europe

-RRB-

-LRB-

Schering

-RRB-

-LRB-

Schering

-RRB-

Sinerem/Combidex

-LRB-

Guerbet/Advanced

Magnetics

-RRB-

-LRB-

Bracco

-RRB-

and

Code

-LRB-

Advanced

Magnetics

-RRB-

In

order

to

acquire

useful

kinetic

information

from

MMCM-enhanced

studies

a

series

of

images

spanning

at

least

minutes

after

contrast

medium

administration

is

required

-LSB-

-RSB-

On

the

other

hand

since

the

transendothelial

diffusion

of

MMCM

is

a

rather

slow

process

it

is

usually

sufficient

to

acquire

MMCM-enhanced

dynamic

data

with

intervals

of

one

to

two

minutes

or

for

specific

questions

even

to

obtain

just

one

delayed

contrast

enhanced

scan

Applications

of

potential

clinical

interest

will

be

mentioned

in

the

specific

sections

below

One

new

class

of

contrast

agents

particularly

noteworthy

with

respect

to

bone

marrow

imaging

is

the

group

of

ultra

small

superparamagnetic

iron

oxide

particles

-LRB-

USPIO

-RRB-

These

particulate

iron

oxide

contrast

agents

are

phagocytosed

by

macrophages

in

the

normal

bone

marrow

where

they

induce

a

effect

The

principle

is

similar

to

MR

imaging

of

the

liver

with

superparamagnetic

iron

oxide

particles

-LRB-

SPIO

-RRB-

However

SPIO

used

for

liver

imaging

have

a

diameter

of

nm

whereas

USPIO

used

for

bone

marrow

imaging

have

a

diameter

of

nm

USPIO

particles

are

not

taken

up

in

neoplastic

marrow

infiltrates

which

do

not

contain

macrophages

-LSB-

-RSB-

Thus

USPIO

may

be

used

to

differentiate

hypercellular

normal

and

neoplastic

marrow

After

infusion

of

USPIO

at

a

dose

of

mg/kg

body

weight

the

normal

marrow

shows

a

USPIO

induced

signal

loss

as

opposed

to

focal

neoplastic

infiltrates

which

do

not

show

any

signal

loss

and

thus

stand

out

as

bright

lesions

-LSB-

-RSB-

STIR

or

fat

saturated

sequences

are

best

suited

for

such

USPIO-enhanced

MR

scans

Metz

et

al.

found

a

significantly

increased

number

of

detected

focal

bone

marrow

lesions

-LRB-

cm

-RRB-

in

patients

with

lymphoproliferative

disorders

on

these

sequences

after

administration

of

USPIO

compared

to

non-enhanced

scans

-LSB-

-RSB-

The

USPIO

-LRB-

Sinerem/Combidex

Guerbet

Advanced

Magnetics

-RRB-

is

expected

to

become

approved

for

clinical

applications

in

in

Europe

and

has

already

shown

its

ability

to

differentiate

normal

and

pathologic

hypercellular

marrow

and

to

detect

multifocal

lesions

within

the

bone

marrow

-LSB-

-RSB-

Other

USPIOs

which

are

in

different

stages

of

preclinical

and

clinical

trials

are

S

-LRB-

Schering

-RRB-

Code

-LRB-

Advanced

Magnetics

-RRB-

VSOP

-LRB-

Ferropharm

-RRB-

and

Clariscan

-LRB-

Amersham/GE

-RRB-

Future

imaging

developments

are

likely

to

generate

combined

techniques

that

will

maximize

the

information

to

be

extracted

from

the

image

Tumor

location

morphology

and

function

will

be

integrated

For

example

both

dynamic

contrast-enhanced

MR

imaging

and

MR

spectroscopy

can

be

acquired

in

a

single

diagnostic

session

to

define

bone

marrow

vascular

and

metabolic

characteristics

-LSB-

-RSB-

New

developments

for

whole

body

MR

imaging

such

as

parallel

imaging

techniques

dedicated

coils

-LRB-

Angio-SURF

-RRB-

and

the

total

imaging

matrix

-LRB-

Siemens

systems

Avanto

-RRB-

may

provide

a

screening

of

the

whole

red

bone

marrow

for

tumor

infiltration

within

a

reasonable

time

Additional

development

is

being

directed

towards

combined

PET

and

MR

imaging

either

by

retrospective

spatial

registration

of

data

from

PET

and

MR

images

obtained

on

separate

PET

and

MR

machines

or

by

sequential

data

acquisitions

on

combined

PET-MR

scanners

-LSB-

-RSB-

PET-MR

imaging

has

been

described

as

superior

a

least

for

some

applications

compared

to

PET-CT

because

of

the

improved

intrinsic

soft

tissue

contrast

and

potential

direct

bone

marrow

depiction

provided

by

MR.

Normal

bone

marrow

The

normal

bone

marrow

undergoes

age-related

changes

of

its

cellular

content

with

increasing

age

of

the

patient

In

adults

the

normal

bone

marrow

is

characterized

by

a

partial

or

complete

fatty

conversion

and

low

cellularity

which

leads

to

a

relatively

high

signal

intensity

on

plain

images

and

low

signal

intensity

on

STIR

or

fat

saturated

MR

images

-LSB-

-RSB-

In

children

the

normal

bone

marrow

is

highly

cellular

which

leads

to

a

low

signal

intensity

on

plain

images

and

high

signal

intensity

on

STIR

or

fat

saturated

MR

images

With

increasing

age

a

conversion

from

this

highly

cellular

marrow

in

children

to

fatty

marrow

in

adults

occurs

with

a

gradual

increase

of

the

bone

marrow

signal

on

MR

images

and

a

gradual

decline

of

the

bone

marrow

signal

on

STIR

or

fat

saturated

MR

images

over

time

This

conversion

also

follows

a

particular

distribution

pattern

within

the

skeleton

it

starts

in

the

peripheral

skeleton

and

progresses

centrally

-LSB-

-RSB-

Within

long

bones

it

first

involves

the

epiphyses

then

the

diaphyses

and

finally

the

metaphyses

-LSB-

-RSB-

In

the

vertebrae

it

starts

in

the

center

around

the

venous

plexus

and

progresses

peripherally

-LSB-

-RSB-

In

adults

the

signal

intensity

of

the

normal

bone

marrow

is

typically

hyperintense

to

surrounding

muscle

and

intervertebral

disks

on

MR

images

and

hypointense

to

surrounding

muscle

on

STIR

or

fat

saturated

MR

images

The

knowledge

of

this

pattern

of

conversion

is

useful

to

differentiate

normal

cellular

marrow

from

focal

or

diffuse

neoplastic

involvement

and

to

recognize

treatment

effects

and

tumor

recurrence

The

enhancement

of

the

normal

bone

marrow

in

healthy

persons

after

administration

of

standard

small

molecular

Gd-chelates

can

vary

greatly

-LRB-

range

mean

SD

-RRB-

and

decreases

with

increasing

age

-LSB-

-RSB-

As

a

rule

of

thumb

a

signal

Gd-enhancement

of

less

than

on

MR

images

was

reported

to

be

normal

in

adults

of

more

than

years

However

this

threshold

is

dependent

on

the

applied

field

strength

and

pulse

sequence

parameters

The

relative

enhancement

of

both

normal

and

abnormal

marrow

may

be

higher

with

new

more

sensitive

pulse

sequences

-LSB-

-RSB-

Thus

each

investigator

should

establish

the

specific

threshold

for

normal

bone

marrow

enhancement

for

the

technique

used

at

his

particular

MR

scanner

and

institution

Pathologic

bone

marrow

in

hematologic

malignancies

Neoplastic

infiltration

of

the

bone

marrow

in

MR

images

results

in

a

replacement

of

the

fatty

converted

marrow

by

neoplastic

cells

thereby

increasing

the

cellular

content

of

the

bone

marrow

which

results

in

a

prolongation

of

and

times

and

subsequent

decreased

and

increased

of

the

bone

marrow

The

detection

of

neoplastic

bone

marrow

infiltrations

with

MR

imaging

depends

on

the

quantity

and

distribution

of

cellular

infiltration

The

distribution

of

neoplastic

bone

marrow

involvement

in

patients

with

hematologic

malignancies

may

be

focal

multifocal

or

diffuse

In

patients

with

NHL

a

focal

or

multifocal

involvement

is

more

common

than

the

diffuse

infiltration

pattern

In

patients

with

myeloma

an

additional

typical

salt

and

pepper

or

variegated

distribution

may

be

observed

most

frequently

in

stage

I

disease

according

to

Salmon

and

Durie

In

patients

with

leukemia

the

bone

marrow

is

usually

involved

in

a

diffuse

fashion

A

multifocal

involvement

may

be

seen

in

a

small

proportion

of

patients

particularly

those

with

AML

The

detection

of

focal

multifocal

and

salt

and

pepper

or

variegated

infiltrations

of

the

bone

marrow

in

patients

with

NHL

is

straight

forward

The

MR

signal

intensity

of

focal

bone

marrow

lesions

is

typically

iso

or

hypointense

to

surrounding

muscle

and

intervertebral

disks

on

MR

images

and

hyperintense

to

surrounding

muscle

on

STIR

or

fat

saturated

MR

images

Since

these

focal

lesions

are

also

associated

with

an

increased

angiogenesis

they

show

an

increased

signal

enhancement

compared

to

the

surrounding

bone

marrow

on

fat

saturated

MR

images

The

detection

of

a

diffuse

bone

marrow

infiltration

with

MR

imaging

is

limited

Using

standard

MR

scanners

and

pulse

sequences

an

infiltration

of

the

bone

marrow

with

more

than

of

neoplastic

cells

can

be

readily

detected

by

a

diffusely

decreased

and

a

diffusely

increased

-LSB-

-RSB-

An

infiltration

with

less

than

neoplastic

cells

can

not

be

distinguished

from

normal

marrow

with

standard

MR

pulse

sequences

Several

authors

reported

a

normal

bone

marrow

MR

signal

in

patients

with

leukemia

in

patients

with

early

stages

of

bone

marrow

invasion

by

lymphoproliferative

diseases

and

even

in

up

to

one-quarter

of

patients

with

stage

III

multiple

myeloma

-LSB-

-RSB-

The

administration

of

Gd-DTPA

is

not

necessary

for

staging

of

focal

multifocal

and

salt

and

pepper

lesions

which

can

be

readily

detected

on

plain

MR

scans

Dynamic

Gd-DTPA-enhanced

MR

scans

documented

repetitively

an

increased

blood

volume

-LRB-

i.e.

increased

enhancement

-RRB-

of

neoplastic

infiltrations

compared

to

the

normal

bone

marrow

-LSB-

-RSB-

As

one

would

expect

the

Gd-enhancement

was

significantly

higher

in

marked

bone

marrow

infiltrations

than

in

mild

or

no

infiltration

-LRB-

P

-RRB-

and

the

enhancement

was

higher

in

lesions

with

high

vessel-density

than

in

lesions

with

low

vessel-density

at

histology

-LRB-

P

-RRB-

In

addition

a

higher

enhancement

was

found

in

the

presence

of

increased

serum

immunoglobulins

-LSB-

-RSB-

However

the

Gd-DTPA

enhancement

of

focal

neoplastic

lesions

has

not

shown

additional

clinically

significant

information

for

staging

purposes

so

far

In

some

cases

Gd-administration

may

help

to

diagnose

a

diffuse

bone

marrow

infiltration

According

to

studies

from

Staebler

et

al.

a

bone

marrow

signal

intensity

increase

exceeding

indicates

a

diffuse

infiltration

in

adult

patients

-LSB-

-RSB-

Irradiation

MR

signal

changes

of

the

bone

marrow

during

and

after

irradiation

are

time

and

dose

dependent

In

the

acute

phase

-LRB-

day

of

irradiation

-RRB-

the

bone

marrow

develops

an

edema

which

appears

hypointense

on

MR

images

and

hyperintense

on

fat-saturated

and

STIR-images

Contrast

enhanced

images

show

a

transiently

increased

enhancement

of

the

bone

marrow

during

this

phase

Subsequently

-LRB-

day

-RRB-

focal

and

areas

of

hemorrhage

may

occur

The

bone

marrow

ultimately

undergoes

a

conversion

to

fatty

marrow

which

closely

represents

the

irradiation

field

and

which

appears

very

bright

on

MR

images

-LRB-

close

to

subcutaneous

fat

-RRB-

and

dark

on

fat

suppressed

images

-LRB-

Fig.

-RRB-

Dependent

on

the

applied

dose

this

fatty

transformation

of

the

bone

marrow

may

be

detected

with

MR

imaging

as

early

as

days

after

therapeutic

irradiation

-LSB-

-RSB-

In

other

cases

the

edema

may

persist

for

weeks

and

a

fatty

conversion

may

only

become

apparent

months

after

the

irradiation

This

fatty

conversion

is

reversible

after

an

irradiation

of

less

than

Gy

and

irreversible

after

an

irradiation

with

more

than

Gy

The

time

frame

of

reconversion

after

low

dose

irradiation

has

not

been

specified

so

far

and

will

be

most

likely

highly

variable

with

respect

to

potential

additional

chemotherapy

or

GCSF-treatment

location

and

extend

of

the

affected

anatomical

area

and

age

of

the

patient

Contrast

enhanced

scans

show

a

markedly

decreased

enhancement

of

the

fatty

converted

bone

marrow

Fig.

non-enhanced

-LRB-

a

-RRB-

and

fat

saturated

contrast

enhanced

-LRB-

b

-RRB-

MR

images

after

radiation

therapy

of

a

focal

PNET

tumor

infiltration

in

L

Note

the

fatty

conversion

of

the

bone

marrow

in

the

irradiation

field

to

is

only

apparent

on

the

non-fat

saturated

non-enhanced

MR

image

The

tumor

in

shows

a

mild

Gd-enhancement

after

radiotherapy

on

contrast-enhanced

scans

In

addition

to

these

bone

marrow

signal

changes

in

the

irradiation

field

several

authors

also

reported

an

additional

small

but

measurable

fatty

conversion

of

the

adjacent

bone

marrow

outside

of

the

irradiation

field

The

bone

marrow

outside

the

irradiation

field

showed

similar

MR

signal

intensity

changes

compared

to

the

bone

marrow

within

the

irradiation

field

but

to

a

much

lower

degree

Interpretations

of

these

findings

differ

the

most

appealing

explanation

is

a

fatty

conversion

due

to

scatter

irradiation

-LSB-

-RSB-

In

children

irradiation

may

also

cause

impairment

or

stop

in

skeletal

maturation

Local

irradiation

may

impair

the

growth

at

the

growth

plate

of

the

irradiated

bone

after

doses

as

little

as

Gy

-LSB-

-RSB-

In

parallel

to

the

above

described

changes

of

the

bone

marrow

in

general

the

metaphyses

and

growth

plates

of

the

affected

bones

may

also

show

an

edema

on

MR

images

initially

and

later

a

fatty

conversion

The

severity

of

impairment

in

bone

growth

is

dependent

on

the

age

of

the

patient

at

the

time

of

the

irradiation

and

the

administered

dose

High

doses

may

lead

to

marked

epimetaphyseal

deformities

The

affected

metaphyses

of

long

bones

may

show

horizontal

or

longitudinal

areas

of

signal

loss

of

on

and

MR

images

which

resemble

metaphyseal

bands

and

striations

seen

on

conventional

radiographs

-LSB-

-RSB-

Irradiation

of

the

spine

may

cause

a

scoliosis

which

is

typically

concave

to

the

irradiation

field

if

only

one

side

of

the

spine

was

irradiated

In

children

irradiation

of

the

whole

spine

may

also

result

in

a

scoliosis

There

is

usually

an

associated

impairment

of

the

growth

of

paraspinal

muscles

as

well

as

an

impaired

vertical

growth

of

the

irradiated

vertebrae

Depending

on

the

applied

dose

the

bone

marrow

of

the

vertebrae

may

undergo

a

usually

transient

or

-LRB-

rarely

-RRB-

persistent

fatty

conversion

and

the

bone

marrow

in

the

peripheral

skeleton

may

show

a

compensatory

hypercellularity

Irradiation

of

the

brain

in

children

with

acute

leukemia

may

result

in

growth

arrest

due

to

a

deficiency

in

growth

hormone

-LSB-

-RSB-

In

these

patients

the

bone

marrow

usually

appears

normal

-LRB-

in

case

of

remission

of

the

leukemia

-RRB-

on

MR

images

In

children

irradiation

of

the

proximal

femur

may

cause

a

slipped

capital

epiphysis

-LSB-

-RSB-

This

may

be

diagnosed

early

on

MR

images

by

an

asymmetry

and

typical

widening

of

the

center

or

posteromedial

region

of

the

affected

physis

which

is

best

seen

on

plain

MR

images

A

potential

subsequent

closure

of

the

physis

may

be

diagnosed

by

sequential

MRI

it

typically

develops

from

the

posterior

portion

anteriorly

In

adults

a

short-term

complication

of

local

irradiation

may

be

the

development

of

an

irradiation

osteitis

which

presents

as

a

inhomogeneous

edema

on

MR

images

in

the

irradiation

field

and

which

shows

a

narrow

zone

of

transition

to

the

adjacent

non-irradiated

bone

marrow

There

is

no

associated

extraosseous

soft

tissue

mass

The

irradiation

osteitis

may

be

associated

with

insufficiency

fractures

which

may

sometimes

be

better

apparent

on

MR

and

sometimes

be

better

apparent

on

conventional

radiographs

Thus

imaging

of

a

suspected

irradiation

osteitis

should

always

also

include

conventional

radiographs

of

the

affected

bone

Irradiation

osteitis

is

rare

in

children

-LSB-

-RSB-

Other

short-term

complications

of

irradiation

are

insufficiency

fractures

and

avascular

necroses

-LRB-

AVN

-RRB-

in

the

irradiated

bone

Insufficiency

fractures

are

caused

by

normal

stress

on

weight-bearing

bones

with

an

irradiation-induced

decreased

elastic

resistance

Depending

on

the

acuteness

of

the

fracture

and

the

time

interval

after

irradiation

MR

may

show

a

more

predominant

edema

or

a

more

predominant

fatty

conversion

of

the

bone

marrow

The

fracture

line

may

be

seen

as

a

bright

line

on

and

contrast

enhanced

MR

images

if

it

is

surrounded

by

adjacent

marrow

edema

-LRB-

Fig.

-RRB-

AVN

is

caused

by

an

irradiation

induced

arteritis

with

fibrosis

and

endothelial

proliferation

blocked

arterial

inflow

or

venous

outflow

rise

in

intramedullary

pressure

compromised

perfusion

and

finally

anoxia

and

death

of

bone

marrow

cells

The

MR

imaging

findings

of

AVN

are

described

in

detail

below

Fig.

fat

saturated

-LRB-

ms

-RRB-

-LRB-

a

-RRB-

-LRB-

ms

-RRB-

-LRB-

b

-RRB-

and

fat

saturated

-LRB-

ms

-RRB-

contrast-enhanced

-LRB-

c

-RRB-

MR

images

of

the

knee

of

a

year-old

patient

who

underwent

radiation

therapy

of

the

lower

femur

and

poplitea

region

Note

fatty

bone

marrow

conversion

and

fracture

lines

at

the

distal

femur

and

proximal

tibia

-LRB-

arrows

-RRB-

consistent

with

irradiation

induced

insufficiency

fractures

As

long-term

complications

benign

or

malignant

tumors

may

occur

after

irradiation

of

the

bone

and

bone

marrow

Osteochondromas

are

the

most

common

tumors

that

may

develop

after

total

body

irradiation

-LRB-

TBI

-RRB-

The

irradiation

induced

development

of

osteochondromas

is

inversely

related

to

the

age

of

the

patient

at

the

time

of

the

TBI

In

children

osteochondromas

developed

in

about

after

TBI

The

latency

for

the

development

of

osteochondromas

after

TBI

is

highly

variable

but

generally

shorter

than

the

latency

for

the

development

of

malignant

tumors

-LSB-

-RSB-

On

MR

imaging

a

continuity

of

the

bone

marrow

space

with

the

lesion

and

a

cartilage

cap

with

a

thickness

of

not

more

than

mm

are

criteria

to

prove

a

benign

osteochondroma

and

to

exclude

a

malignancy

Of

note

sarcomatous

degeneration

of

an

irradiation

induced

osteochondroma

is

extremely

rare

although

incidental

cases

have

been

reported

-LSB-

-RSB-

Other

benign

bone

tumors

that

may

develop

after

TBI

are

fibrous

dysplasia

and

aneurysmal

bone

cysts

-LSB-

-RSB-

Radiation-induced

sarcoma

is

a

rare

late

complication

of

irradiation

which

develops

after

a

latency

period

of

about

years

in

the

previous

irradiation

field

Irradiation

induced

sarcomas

are

not

directly

related

to

the

local

radiation

dose

Osteosarcomas

fibrosarcomas

malignant

fibrous

histiocytomas

and

other

sarcomas

may

occur

-LSB-

-RSB-

Cortisone

treatment

Ischemic

-LRB-

avascular

-RRB-

necrosis

is

a

well

recognized

complication

of

high

dose

cortisone

treatment

seen

in

of

patients

in

the

initial

treatment

phase

for

leukemias

or

lymphomas

-LRB-

Fig.

-RRB-

In

addition

AVN

occurs

in

of

long-term

survivors

of

bone

marrow

transplantation

-LRB-

Fig.

-RRB-

who

received

high

doses

of

steroids

for

the

prevention

or

treatment

of

graft-versus-host

disease

AVN

has

been

also

described

after

chemotherapy

or

irradiation

-LSB-

-RSB-

The

apparently

increasing

prevalence

of

this

complication

may

be

due

to

increasing

recognition

based

on

increasing

use

of

MR

imaging

Fig.

fat

saturated

Spinecho

-LRB-

ms

-RRB-

MR

images

of

the

knee

joint

of

a

year

old

boy

with

ALL

after

treatment

with

high

dose

cortisone

There

are

multiple

bone

infarctions

in

the

distal

femur

and

proximal

tibia

-LRB-

arrows

-RRB-

MR

studies

were

obtained

months

-LRB-

a

-RRB-

and

months

-LRB-

b

-RRB-

after

onset

of

treatment

Note

that

the

infarcts

decrease

in

sizeFig

radiograph

-LRB-

a

-RRB-

sagittal

-LRB-

ms

-RRB-

-LRB-

b

-RRB-

and

sagittal

STIR

sequence

-LRB-

ms

TI

ms

-RRB-

-LRB-

c

-RRB-

of

the

ankle

in

a

patient

with

a

history

of

chronic

myeloid

leukemia

and

bone

marrow

transplantation

showing

multiple

infarcts

in

the

distal

tibia

the

talus

and

the

calcaneus

-LRB-

arrows

-RRB-

which

are

not

visualized

on

the

radiograph

AVN

is

caused

by

vascular

insufficiency

compromised

bone

marrow

perfusion

and

finally

anoxia

and

death

of

bone

marrow

cells

Bones

with

end-arterial

vascular

supply

and

poor

collaterals

are

particularly

prone

to

develop

an

AVN

such

as

the

femoral

head

distal

femur

and

proximal

tibia

proximal

humeri

tali

scaphoid

and

lunate

bones

Usually

the

cartilage

is

not

affected

because

it

is

nourished

by

synovial

fluid

MRI

is

the

most

sensitive

non-invasive

method

for

diagnosis

of

bone

marrow

infarction

Early

forms

of

AVN

are

characterized

by

a

diffuse

marrow

edema

These

and

areas

of

edema

may

be

extensive

and

are

non-specific

in

their

MR

appearance

Potential

causes

which

may

all

be

related

to

steroid

administration

are

transient

osteoporosis

osteomyelitis

occult

intraosseous

fracture

and

stress

fracture

However

in

patients

under

high

dose

steroid

treatment

these

areas

of

edema

may

represent

an

early

stage

of

AVN

and

should

be

considered

a

marker

for

potential

progression

to

advanced

osteonecrosis

Therefore

careful

examinations

for

osteonecrosis

are

necessary

when

bone

marrow

edema

is

seen

is

these

patients

-LSB-

-RSB-

The

classic

MR

appearance

of

advanced

bone

marrow

infarction

is

characterized

by

a

segmental

area

of

low

signal

intensity

in

the

subchondral

bone

on

plain

pulse

sequences

outlining

a

central

area

of

marrow

which

may

have

variable

signal

intensities

-LSB-

-RSB-

This

crescentic

ring-like

well

defined

band

of

low

signal

intensity

on

images

is

thought

to

represent

the

reactive

interface

between

the

necrotic

and

reparative

zones

and

typically

extends

to

the

subchondral

plate

On

images

this

peripheral

band

classically

appears

hypointense

with

an

adjacent

hyperintense

line

the

double

line

sign

The

hyperintense

inner

zone

represents

hyperemic

granulation

tissue

the

hypointense

outer

zone

represents

adjacent

sclerotic

bone

Though

characteristic

of

AVN

this

sign

is

uncommon

with

the

use

of

fast

spin-echo

sequences

with

or

without

fat

suppression

and

is

not

necessary

for

diagnosis

of

the

disease

There

is

no

need

to

perform

conventional

sequences

to

find

this

sign

On

STIR

images

the

band-like

signal

alterations

of

the

bone

marrow

-LRB-

corresponding

to

the

inner

zone

-RRB-

usually

appear

hyperintense

Mitchell

et

al.

described

four

stages

of

AVN

based

on

MR

imaging

findings

-LSB-

-RSB-

The

knowledge

of

these

stages

may

be

helpful

in

the

recognition

of

AVN

Class

A

lesions

had

signal

intensity

characteristics

analogous

to

those

of

fat

i.e.

high

signal

intensity

on

images

and

intermediate

signal

intensity

on

images

Class

B

lesions

demonstrated

signal

intensity

characteristics

similar

to

those

of

blood

i.e.

high

signal

intensity

on

both

and

images

Class

C

lesions

had

signal

intensity

properties

similar

to

those

of

fluid

i.e.

low

signal

intensity

on

images

and

high

signal

intensity

on

images

Class

D

lesions

had

signal

intensity

properties

similar

to

those

of

fibrous

tissue

i.e.

low

signal

intensity

on

both

and

images

-LRB-

-RRB-

Class

A

signal

intensity

tended

to

reflect

early

disease

and

class

D

signal

intensity

tended

to

reflect

late

disease

However

these

stages

may

not

occur

in

a

chronological

order

and

did

not

show

prognostic

significance

-LSB-

-RSB-

There

is

currently

no

established

role

for

Gd-administration

in

non-traumatic

AVN

Of

note

in

children

the

proximal

femur

epiphyses

may

show

a

residual

small

subcortical

rim

of

hematopoietic

marrow

which

typically

appears

brighter

than

adjacent

muscles

on

plain

MR

images

This

should

not

be

confused

with

the

double

line

sign

in

early

AVN

which

is

characterized

by

a

subcortical

rim

which

is

iso

or

hypointense

compared

to

surrounding

muscle

The

percentage

of

the

affected

weight

bearing

surface

occupied

by

the

AVN

is

the

most

reliable

factor

for

predicting

outcome

-LSB-

-RSB-

AVN

that

are

entirely

circumscribed

and

that

do

not

extend

cranially

to

the

cortical

subchondral

margin

have

a

good

outcome

independent

of

the

overall

size

of

the

AVN

lesion

AVN

that

do

extend

to

the

subchondral

margin

and

are

associated

with

epiphyseal

collapse

are

at

risk

to

result

in

permanent

disability

AVN

may

present

in

an

atypical

fashion

For

example

AVN

of

the

spine

typically

involves

a

single

vertebrae

The

MRI

findings

of

a

wedge-shaped

lesion

with

fluid

intensity

-LRB-

hyperintense

signal

like

that

of

cerebrospinal

fluid

on

images

-RRB-

are

characteristic

for

AVN

However

AVN

may

involve

two

contiguous

vertebrae

and

the

intervening

disc

and

can

then

be

confused

with

infective

or

neoplastic

processes

-LSB-

-RSB-

Chemotherapy

Chemotherapy

in

patients

with

leukemia

results

in

typical

signal

changes

of

the

bone

marrow

on

MR

images

which

reflect

the

underlying

changes

in

the

cellular

composition

and

vascularity

of

the

bone

marrow

-LSB-

-RSB-

During

the

first

week

of

treatment

the

bone

marrow

sinus

becomes

dilated

and

hyperpermeable

leading

to

an

edema

The

edematous

bone

marrow

shows

a

low

signal

intensity

on

plain

MR

images

and

a

high

signal

intensity

on

plain

and

STIR-images

This

bone

marrow

edema

was

reported

to

be

more

pronounced

in

patients

with

AML

than

in

patients

with

ALL

probably

reflecting

the

higher

bone

marrow

toxicity

of

the

chemotherapeutic

drugs

applied

for

the

treatment

of

AML

-LRB-

e.g.

cytosine

arabinoside

which

has

a

known

high

bone

marrow

toxicity

-RRB-

as

opposed

to

ALL

Subsequently

a

marked

decrease

in

bone

marrow

cellularity

and

a

fatty

conversion

of

the

bone

marrow

develops

which

is

characterized

by

an

increase

in

and

times

an

increased

signal

intensity

on

plain

MR

images

-LRB-

Fig.

-RRB-

and

decreased

signal

intensity

on

fat

saturated

and

STIR-images

After

successful

therapy

a

normalization

of

the

MR

signal

occurs

with

regeneration

of

normal

hematopoietic

cells

in

the

bone

marrow

This

regeneration

often

occurs

in

a

multifocal

pattern

i.e.

within

the

fatty

converted

marrow

multiple

diffuse

small

foci

of

decreased

signal

on

images

and

increased

signal

on

or

STIR-images

develop

Fig.

spinecho

-LRB-

ms

-RRB-

images

of

the

pelvis

before

-LRB-

a

-RRB-

and

after

-LRB-

b

-RRB-

chemotherapy

for

a

fibrosarcoma

of

the

pelvis

-LRB-

arrow

-RRB-

Note

a

decrease

of

hematopoietic

bone

marrow

and

an

increased

fatty

conversion

in

the

pelvis

and

bilateral

proximal

femurs

while

the

tumor

size

shrinks

Hodgkin

's

and

non-Hodgkin

's

lymphomas

low

and

high-grade

lymphomas

as

well

as

distinct

subgroups

of

NHL

differ

markedly

in

response

to

treatment

In

Hodgkin

's

lymphoma

a

bone

marrow

infiltration

at

diagnosis

is

rare

and

expected

to

resolve

after

treatment

Patients

with

residual

active

bone

marrow

lesions

need

additional

dedicated

treatment

MR

is

non-specific

in

differentiating

residual

viable

from

non-viable

disease

FDG-PET

or

-LRB-

in

equivocal

cases

-RRB-

biopsy

are

preferable

diagnostic

methods

to

answer

these

questions

There

are

about

subtypes

of

NHL

About

of

patients

with

NHL

develop

a

diffuse

large

B-cell

lymphoma

an

aggressive

B-cell

lymphoma

About

of

patients

with

NHL

develop

a

follicular

lymphoma

an

indolent

B-cell

lymphoma

-LSB-

-RSB-

About

of

patients

with

NHL

develop

a

mantle

cell

lymphoma

an

aggressive

B-cell

lymphoma

that

is

often

widespread

at

diagnosis

Low-grade

lymphomas

are

considered

incurable

and

are

often

followed

by

watchful

waiting

The

aggressive

high-grade

lymphomas

are

treated

with

aggressive

therapy

regimens

chemotherapy

irradiation

often

a

combination

of

both

and/or

autologous

bone

marrow

transplantation

Bone

marrow

lesions

in

these

patients

are

expected

to

change

under

therapy

on

MR

images

In

general

MR

images

of

patients

with

Hodgkin

's

lymphoma

and

NHL

including

myeloma

show

a

conversion

from

hypercellular

hypervascularized

to

normocellular

and

less

vascularized

marrow

after

chemotherapy

However

the

ideal

evolution

from

hypercellular

to

normocellular

marrow

may

not

occur

in

all

patients

with

malignant

lymphomas

Rahmouni

et

al.

reported

that

the

marrow

often

returned

to

normal

after

treatment

when

the

pattern

was

diffuse

or

variegated

before

treatment

-LSB-

-RSB-

But

residual

signal

alterations

of

the

bone

marrow

have

been

also

reported

after

the

end

of

therapy

particularly

in

patients

with

a

focal

pattern

before

treatment

-LRB-

Fig.

-RRB-

-LSB-

-RSB-

A

conversion

of

a

diffuse

to

a

focal

MR

imaging

pattern

of

marrow

involvement

reduction

but

not

disappearance

in

lesion

size

and

number

and

persistant

peripheral

lesion

enhancement

on

contrast-enhanced

MR

images

-LRB-

Fig.

-RRB-

have

been

described

in

association

with

a

response

to

standard

chemotherapy

-LSB-

-RSB-

In

addition

focal

bone

marrow

lesions

in

patients

with

lymphoma

may

show

a

persistent

abnormal

signal

and/or

a

cystic

or

fatty

degeneration

A

fatty

or

cystic

conversion

of

focal

lesions

has

been

reported

as

an

indication

for

a

response

to

treatment

-LRB-

Fig.

-RRB-

-LSB-

-RSB-

Low

signal

intensity

on

post-therapeutic

images

is

usually

associated

with

fibrosis

and

rules

out

relapse

A

persistent

intermediate

hyperintense

signal

of

focal

bone

marrow

lesions

on

MR

images

-LRB-

non-cystic

non-fatty

-RRB-

has

been

described

in

association

with

treatment

induced

necrosis

and

inflammation

and

was

found

in

both

responding

and

non-responding

patients

-LSB-

-RSB-

Fig.

Spinecho

sequences

-LRB-

ms

-RRB-

with

-LRB-

a

c

-RRB-

and

without

-LRB-

b

d

-RRB-

contrast

before

-LRB-

a

b

-RRB-

and

after

c

d

-RRB-

chemotherapy

for

lymphoma

Note

decrease

in

size

of

the

soft

tissue

component

after

chemotherapy

yet

still

significant

contrast

enhancement

in

the

bone

marrowFig

MR

images

of

a

patient

with

malignant

lymphoma

and

multifocal

bone

marrow

infiltration

Sagittal

STIR

-LRB-

a

-RRB-

and

contrast

enhanced

fat

saturated

fast

SE

sequences

-LRB-

ms

-RRB-

were

obtained

before

chemotherapy

-LRB-

a

b

-RRB-

Fat

saturated

fast

SE

-LRB-

ms

-RRB-

contrast

enhanced

fat

saturated

fast

SE

sequences

and

non-contrast

enhanced

SE

sequences

-LRB-

ms

-RRB-

were

obtained

after

chemotherapy

-LRB-

c

e

-RRB-

After

therapy

the

areas

of

previous

tumor

infiltration

show

a

decreased

signal

on

images

a

decreased

contrast

enhancement

and

fatty

degeneration

-LRB-

arrows

-RRB-

In

patients

with

myeloma

new

or

progressive

vertebral

compression

fractures

may

occur

as

a

complication

of

treatment

response

in

vertebrae

that

had

extensive

marrow

disease

before

treatment

-LSB-

-RSB-

With

response

to

treatment

the

tumor

mass

that

had

replaced

the

trabeculae

may

resolve

and

the

unsupported

vertebrae

can

collapse

An

increasing

back

pain

in

patients

with

myeloma

after

treatment

may

be

caused

by

such

vertebral

compression

fractures

or

tumor

progression

Relapse

and

poor

response

to

treatment

are

well

evaluated

with

MR

imaging

In

patients

with

clinical

relapse

new

focal

lesions

an

increase

in

the

size

of

previously

identified

focal

lesions

or

a

change

from

focal

to

diffuse

infiltration

may

be

seen

Additional

signs

of

tumor

progression

are

increasing

paraosseous

soft

tissue

masses

or

increased

Gd-enhancement

of

focal

lesions

after

chemotherapy

A

progress

of

focal

to

diffuse

bone

marrow

neoplasias

may

be

sometimes

more

difficult

to

assess

since

a

diffuse

bone

marrow

infiltration

may

be

indistinguishable

from

reconverted

hematopoietic

marrow

after

e.g.

GCSF-treatment

As

specified

above

a

new

Gd-enhancement

of

or

lack

of

USPIO

uptake

in

a

hypercellular

marrow

may

indicate

a

tumor

progress

or

recurrence

in

these

cases

A

rare

form

of

progression

in

myeloma

under

therapy

is

leptomeningeal

spread

within

the

central

nervous

system

reported

in

out

of

a

series

of

patients

-LSB-

-RSB-

MR

findings

of

leptomeningeal

enhancement

in

the

brain

or

spine

helped

to

establish

the

diagnosis

which

was

subsequently

confirmed

by

cytologic

analysis

of

cerebrospinal

fluid

Myelofibrosis

and

amyloidosis

can

also

develop

as

a

consequence

of

treatment

in

patients

with

myeloma

Myelofibrosis

can

be

suggested

on

MR

studies

as

a

conversion

of

the

entire

bone

marrow

to

diffuse

hypointensity

on

both

and

STIR

images

Amyloidosis

can

be

seen

as

focal

areas

of

hypointensity

on

both

and

STIR

images

-LSB-

-RSB-

Perfusion

studies

using

MR

enhanced

with

standard

small

molecular

Gd-based

contrast

agents

provide

functional

information

concerning

the

response

of

bone

marrow

neoplasias

to

chemotherapy

Conventional

cytotoxic

drugs

have

direct

or

indirect

effects

on

angiogenesis

and

cause

a

decrease

in

bone

marrow

contrast

medium

uptake

within

weeks

or

months

-LSB-

-RSB-

However

though

these

techniques

are

clinically

available

for

more

than

a

decade

perfusion

studies

are

used

infrequently

or

not

at

all

in

clinical

practice

since

the

obtained

functional

changes

in

bone

marrow

vascularity

do

not

or

only

slightly

precede

the

obvious

and

readily

apparent

clinical

parameters

for

treatment

response

Treatment

effects

of

various

chemotherapeutic

regimen

on

the

bone

marrow

in

patients

with

leukemia

and

lymphomas

could

be

also

detected

with

MR

spectroscopy

A

treatment

induced

change

in

tumor

pH

with

an

alkaline

shift

was

related

temporally

to

increases

in

the

phosphodiester/beta-adenosine

triphosphate

ratio

and

occurred

before

alterations

in

tumor

size

were

documented

-LSB-

-RSB-

And

interestingly

changes

in

the

MR

spectral

profile

could

not

only

be

detected

by

direct

investigations

of

the

bone

marrow

itself

but

also

by

MR

spectroscopy

of

the

serum

of

the

patients

The

MR

spectral

profile

of

the

serum

changed

in

responding

patients

to

resemble

that

of

normal

serum

with

typical

higher

peak

intensities

as

compared

to

non-treated

and

non-responding

patients

-LSB-

-RSB-

Bone

marrow

reconversion

after

standard

therapy

After

successful

cytotoxic

therapy

and/or

irradiation

the

normal

bone

marrow

may

undergo

a

reconversion

from

fatty

to

highly

cellular

hematopoietic

marrow

This

reconversion

occurs

in

a

reverse

fashion

compared

to

the

conversion

from

hematopoietic

marrow

to

fatty

marrow

described

above

i.e.

the

reconversion

progresses

from

the

central

skeleton

to

the

periphery

Within

long

bones

it

involves

first

the

metaphyses

and

then

the

diaphyses

The

presence

of

cellular

marrow

within

the

epiphyses

in

an

adult

patient

with

hematologic

malignancies

is

always

suspicious

for

neoplastic

infiltration

especially

when

the

rest

of

the

bone

marrow

did

not

undergo

a

complete

reconversion

A

reconversion

of

marrow

within

the

epiphyses

is

only

rarely

seen

usually

in

conjunction

with

an

extensive

reconversion

of

the

hematoietic

marrow

of

the

whole

bone

In

patients

with

lymphoma

the

reconversion

process

may

be

enhanced

by

administration

of

granulocyte

colony

stimulating

factor

-LRB-

GCSF

-RRB-

which

activates

the

hematopoietic

marrow

and

decreases

the

period

of

aplasia

after

chemotherapy

-LSB-

-RSB-

The

differentiation

between

this

reconverted

highly

cellular

normal

hematopoietic

marrow

and

recurrent

tumor

after

chemotherapy

is

not

possible

with

conventional

MR

techniques

since

relaxation

rates

and

MR

signal

characteristics

of

highly

cellular

hematopoietic

and

highly

cellular

neoplastic

bone

marrow

are

similar

-LSB-

-RSB-

Various

investigators

have

addressed

this

problem

but

were

not

able

to

differentiate

reconverted

hypercellular

hematopoietic

marrow

and

tumor

infiltration

using

a

variety

of

pulse

sequences

static

post-contrast

MR

images

and

MR

spectroscopy

-LRB-

Fig.

-RRB-

-LSB-

-RSB-

Fig.

patient

with

myeloma

at

different

stages

of

therapy

a

-RRB-

After

chemotherapy

and

irradiation

the

bone

marrow

of

the

pelvis

and

proximal

femurs

shows

a

major

fatty

conversion

with

small

areas

of

hypointense

cellular

marrow

of

uncertain

significance

on

plain

MR

images

b

-RRB-

After

high-dose

chemotherapy

and

GCSF

treatment

several

areas

of

hypercellular

hypointense

marrow

are

seen

in

the

marrow

of

the

pelvis

and

proximal

femurs

The

lower

row

of

images

shows

that

these

areas

appear

bright

on

images

-LRB-

-RRB-

hypointense

on

plain

images

-LRB-

-RRB-

and

show

a

marked

enhancement

on

Gd-enhanced

scans

-LRB-

-RRB-

A

follow

up

study

months

after

the

study

in

-LRB-

c

-RRB-

shows

again

a

fatty

conversion

of

the

bone

marrow

In

retrospect

the

lesions

in

B

were

most

likely

due

to

reconverted

hematopoietic

marrow

Dynamic

MR

images

after

intravenous

bolus

injection

of

standard

small

molecular

Gd-chelates

may

be

helpful

in

the

differentiation

between

normal

hypercellular

hematopoietic

and

neoplastic

marrow

When

compared

with

red

marrow

enhancement

of

abnormal

bone

marrow

occurred

earlier

was

steeper

and

did

not

last

as

long

in

neoplastic

bone

marrow

infiltrations

-LSB-

-RSB-

However

in

our

experience

the

Gd-enhancement

of

the

GCSF-treated

markedly

hypercellular

marrow

and

neoplastic

marrow

in

patients

with

hematologic

malignancies

shows

considerable

overlap

and

is

of

limited

clinical

value

for

a

definitive

differentiation

of

these

entities

USPIO

contrast

agents

may

be

more

useful

for

such

a

differentiation

of

reconverted

marrow

and

tumor

recurrence

The

pathophysiologic

basis

for

this

is

the

distribution

of

RES

cells

in

the

bone

marrow

and

their

ability

to

phagocytose

exogenous

iron

oxides

After

chemotherapy

especially

after

GCSF

treatment

the

bone

marrow

reconversion

causes

an

increased

quantity

of

all

hematopoietic

cell

lines

in

the

bone

marrow

including

RES

cells

-LSB-

-RSB-

In

bone

marrow

neoplasia

on

the

other

hand

the

hematopoietic

marrow

is

replaced

by

tumor

cells

and

the

number

of

RES

cells

is

substantially

reduced

-LSB-

-RSB-

Thus

USPIO-enhanced

MRI

can

differentiate

these

entities

by

depicting

iron

oxide-targeted

RES

cells

which

are

present

in

the

reconverted

hematopoietic

marrow

but

not

present

or

substantially

reduced

in

focal

or

multifocal

tumor

deposits

-LSB-

-RSB-

Before

USPIO

administration

both

the

hypercellular

hematopoietic

and

neoplastic

marrow

appear

of

low

signal

intensity

on

plain

MR

images

and

of

high

signal

intensity

on

STIR

and

fat

saturated

MR

images

-LRB-

Fig.

-RRB-

After

USPIO

administration

however

the

normal

marrow

which

takes

up

the

USPIO

shows

an

iron

oxide

induced

signal

loss

whereas

focal

neoplastic

marrow

infiltrates

which

do

not

take

up

the

USPIO

stand

out

as

bright

lesions

on

STIR

and

fat

saturated

MR

images

-LRB-

Fig.

-RRB-

-LSB-

-RSB-

The

technique

can

also

be

applied

in

case

of

a

diffuse

marked

hypercellularity

of

the

bone

marrow

-LRB-

Fig.

-RRB-

Diffuse

or

focal

cell

components

of

the

normal

non-neoplastic

bone

marrow

which

appear

iso

or

hypointense

to

intervertebral

disks

or

skeletal

muscle

on

plain

MR

images

do

show

a

substantial

signal

loss

on

USPIO-enhanced

STIR

images

If

this

signal

loss

is

not

observed

a

malignant

infiltration

is

present

-LRB-

Fig.

-RRB-

On

the

other

hand

a

USPIO-administration

is

not

meaningful

in

patients

with

a

fatty

marrow

on

MR

images

because

there

are

obviously

no

cells

present

which

could

take

up

these

particulate

contrast

agents

Thus

USPIO

may

be

applied

in

specific

patients

where

a

differentiation

of

hypercellular

normal

marrow

and

neoplastic

infiltration

is

warranted

Fig.

patient

after

recurrent

chemotherapy

and

GCSF

treatment

with

reconverted

hyperplastic

hematopoietic

marrow

and

multifocal

bone

marrow

infiltration

by

lymphoma

Both

hematopoietic

marrow

and

focal

tumor

infiltration

show

a

low

signal

intensity

on

plain

images

-LRB-

a

-RRB-

as

well

as

an

increased

signal

intensity

on

plain

STIR

images

-LRB-

b

-RRB-

however

STIR

images

after

iron

oxide

administration

-LRB-

c

-RRB-

show

a

marked

signal

decrease

of

the

hematopoietic

marrow

whereas

focal

tumors

-LRB-

arrows

-RRB-

do

not

show

any

iron

oxide

uptake

thus

the

tumor-to-bone

marrow

contrast

increases

substantially

-LRB-

figure

from

-LSB-

-RSB-

-RRB-

Fig.

patient

with

myeloma

after

chemotherapy

and

GCSF

treatment

images

before

-LRB-

a

-RRB-

show

a

pathologic

fracture

of

Th

-LRB-

arrow

-RRB-

and

a

diffuse

hypointense

signal

intensity

of

the

bone

marrow

in

all

vertebrae

compatible

with

a

high

bone

marrow

cellularity

Unenhanced

STIR

images

-LRB-

b

-RRB-

show

a

diffuse

hyperintense

bone

marrow

also

compatible

with

high

bone

marrow

cellularity

After

iron

oxide

infusion

the

hypercellular

bone

marrow

shows

only

minimal

changes

in

signal

intensity

on

STIR

images

-LRB-

c

-RRB-

indicative

of

a

diffuse

tumor

infiltration

Iliac

crest

biopsy

revealed

tumor

cells

in

the

bone

marrow

-LRB-

figure

from

-LSB-

-RSB-

-RRB-

New

therapy

regimens

Angiogenesis-inhibiting

drugs

such

as

thalidomide

may

be

useful

for

treating

hematologic

malignancies

that

depend

on

neovascularization

and

these

agents

were

recently

added

to

some

treatment

regimens

for

patients

with

advanced

myeloma

-LSB-

-RSB-

The

anti-angiogenic

therapy

is

intended

to

stop

cancer

progression

by

suppressing

the

tumor

recruitment

of

new

blood

supply

As

such

the

anti-angiogenic

drugs

are

generally

tumorostatic

not

cytotoxic

Thus

a

successful

therapeutic

inhibition

of

angiogenesis

can

be

expected

to

slow

or

stop

tumor

growth

but

not

to

cause

tumor

regression

or

disappearance

Accordingly

MR

imaging

may

show

a

persistent

high

bone

marrow

cellularity

under

anti-angiogenic

treatment

Signs

of

a

response

to

this

treatment

are

rather

a

delayed

less

steep

and

smaller

bone

marrow

enhancement

after

intravenous

administration

of

small

molecular

Gd-chelates

compared

to

pretreatment

studies

New

macromolecular

contrast

agents

-LRB-

MMCM

-RRB-

may

provide

an

earlier

diagnosis

of

response

or

failure

of

anti-angiogenic

treatment

than

standard

small

molecular

contrast

agents

MMCM

are

more

sensitive

in

the

detection

of

changes

in

vascular

permeability

than

small

molecular

contrast

agents

And

such

changes

in

the

permeability

of

bone

marrow

sinus

occurs

earlier

than

changes

in

perfusion

and

blood

volume

typically

assessed

with

small

molecular

contrast

agents

In

animal

models

MMCM-enhanced

MRI

was

able

to

define

anti-VEGF

effects

of

certain

angiogenesis

inhibitors

as

early

as

one

day

after

initiation

of

therapy

-LSB-

-RSB-

Future

studies

have

to

show

if

these

results

can

be

also

obtained

in

patients

and

if

so

they

would

be

obviously

of

high

clinical

significance

for

treatment

monitoring

and

management

In

clinical

practice

anti-angiogenic

therapy

regimens

will

almost

certainly

combine

anti-angiogenic

drugs

with

cytotoxic

drugs

The

effect

of

such

combined

therapies

on

the

tumor

accumulation

and

therapeutic

effect

of

the

individual

drugs

are

complex

and

currently

investigated

in

several

experimental

and

clinical

trials

Again

imaging

techniques

are

the

only

available

tool

to

provide

a

non-invasive

and

serial

assessment

of

such

combined

therapy

regimens

Some

angiogenesis

inhibitors

such

as

anti-VEGF

antibody

decrease

microvessel

permeability

and

thereby

reduce

tumoral

delivery

of

large

molecular

cytotoxic

drugs

but

not

small

molecular

cytotoxic

drugs

-LSB-

-RSB-

MRI

assays

of

angiogenesis

can

monitor

such

anti-angiogenesis

therapy

induced

changes

in

tumor

microvascular

structure

and

optimize

the

choice

and

timing

of

cytotoxic

drug

administration

Other

inhibitors

of

angiogenesis

such

as

anti-angiogenic

steroids

-LRB-

tetrahydrocortisol

cortisone

acetate

-RRB-

cyclodextrin

derivates

-LRB-

cyclodextrin

tetradecasulfate

-RRB-

and

tetracycline

derivates

-LRB-

minocycline

-RRB-

may

increase

tumor

microvascular

permeability

and

thus

potentiate

certain

cytotoxic

therapies

-LSB-

-RSB-

In

addition

inhibitors

of

angiogenesis

have

been

shown

to

effectively

potentiate

tumor

irradiation

effects

-LSB-

-RSB-

This

possible

synergy

between

these

anti-angiogenesis

drugs

and

cytotoxic

drugs

or

irradiation

as

a

function

of

apparent

tumor

microvascular

hyperpermeability

can

also

be

interrogated

with

MMCM-enhanced

MR

imaging

Stem

cell

transplantation

The

most

commonly

used

therapy

for

patients

with

lymphoma

is

autologous

stem

cell

transplantation

For

this

the

patient

receives

a

conditioning

therapy

then

his

or

her

own

stem

cells

are

collected

by

leukapheresis

the

patient

subsequently

receives

a

high-dose

chemotherapy

or

irradiation

and

his

previously

collected

stem

cells

are

reinfused

With

some

types

of

lymphoma

an

autologous

transplant

may

not

be

possible

in

case

of

persistent

malignant

bone

marrow

infiltration

Even

after

purging

-LRB-

treatment

of

the

stem

cells

in

the

lab

to

kill

or

remove

lymphoma

cells

-RRB-

reinfusion

of

some

lymphoma

cells

with

the

stem

cell

transplant

is

possible

It

would

therefore

be

of

high

clinical

significance

to

be

able

to

differentiate

patients

with

still

viable

lymphoma

cells

in

their

bone

marrow

at

the

time

of

leukapheresis

from

patients

in

true

complete

remission

In

refractory

diseases

or

in

aplastic

anemia

allogenic

marrow

transplantation

or

chord

cell

transplantation

are

also

used

This

much

more

aggressive

procedure

is

initiated

by

a

conditioning

high

dose

chemotherapy

and/or

total

body

irradiation

and

subsequent

reinfusion

of

allogenic

donor

cells

i.e.

stem

cells

from

a

matched

sibling

or

unrelated

donor

Allogenic

transplantation

has

limited

applications

because

of

the

need

for

a

matched

donor

Another

drawback

is

that

side

effects

of

this

treatment

are

too

severe

for

most

people

over

years

old

After

the

conditioning

therapy

for

allogenic

marrow

transplantation

the

patients

reach

complete

aplasia

are

usually

isolated

on

a

bone

marrow

transplantation

unit

and

should

only

undergo

MR

imaging

for

vital

indications

Only

limited

studies

exist

about

the

evaluation

of

bone

marrow

with

MR

imaging

in

the

setting

of

bone

marrow

transplantation

in

patients

with

hematologic

disorders

Based

on

these

data

the

MR

imaging

characteristics

of

the

bone

marrow

after

autologous

or

allogenic

marrow

transplantation

are

apparently

quite

similar

-LSB-

-RSB-

After

the

conditioning

therapy

and

before

bone

marrow

transplantation

the

bone

marrow

would

be

assumed

to

be

depleted

of

tumor

cells

Ideally

a

conversion

from

focal

or

diffuse

hypercellular

marrow

to

normocellular

or

fatty

marrow

would

be

expected

to

occur

after

the

induction

high-dose

chemotherapy

However

MR

studies

in

patients

before

bone

marrow

transplantation

showed

that

some

patients

have

persistent

focal

lesions

Metz

et

al.

described

residual

focal

bone

marrow

lesions

in

patients

with

lymphomas

right

before

leukapheresis

-LSB-

-RSB-

Negendak

and

Soulen

found

that

patients

with

residual

lesions

on

MR

before

bone

marrow

transplantation

had

a

significantly

shorter

median

time

until

relapse

compared

to

patients

who

did

not

show

any

residual

bone

marrow

disease

on

MR

images

-LSB-

-RSB-

By

contrast

Lecouvet

et

al.

reported

that

patients

with

an

apparently

normal

marrow

and

patients

with

a

persistent

pathologic

bone

marrow

right

before

autologous

or

allogenic

transplantation

did

not

show

differences

in

survival

-LSB-

-RSB-

One

reason

for

this

difference

in

observation

may

be

the

limitation

of

the

MR

imaging

technique

to

detect

and

differentiate

viable

and

non-viable

tumor

cells

Some

patients

with

a

clean

bone

marrow

may

have

residual

microscopic

active

tumor

cells

while

macroscopic

residual

lesions

on

MR

imaging

in

other

patients

may

or

may

not

be

viable

In

our

opinion

it

would

be

highly

significant

to

investigate

MR

imaging

criteria

-LRB-

e.g.

diffusion

weighted

MR

dynamic

MR

new

contrast

agents

spectroscopy

-RRB-

for

the

differentiation

of

such

persistent

focal

bone

marrow

lesions

that

may

or

may

not

develop

to

recurrent

disease

after

stem

cell

transplantation

After

bone

marrow

transplantation

the

evolution

of

distinct

MR

signal

patterns

of

the

bone

marrow

has

been

described

-LSB-

-RSB-

During

the

first

post-transplantation

days

the

bone

marrow

shows

a

decline

in

signal

intensity

on

images

and

an

increased

signal

intensity

on

images

probably

due

to

a

treatment-induced

edema

Within

months

from

bone

marrow

transplantation

a

characteristic

band

pattern

appears

on

MR

images

of

the

spine

This

band

pattern

consists

of

a

peripheral

zone

and

a

central

zone

At

histologic

examination

the

peripheral

zone

corresponded

to

repopulating

hematopoietic

marrow

and

the

central

zone

to

marrow

fat

This

band

pattern

may

be

seen

for

several

months

-LSB-

-RSB-

Subsequently

the

band

pattern

gradually

evolves

into

a

homogeneous

appearance

of

the

marrow

after

successful

bone

marrow

transplantation

On

late

post-transplant

MR

studies

years

after

bone

marrow

transplantation

the

bone

marrow

shows

the

fatty

conversion

of

adult

marrow

The

signal

intensity

of

the

post-transplant

bone

marrow

on

MR

images

is

usually

increased

compared

to

age-matched

controls

-LSB-

-RSB-

In

some

patients

residual

marrow

abnormalities

may

be

observed

on

MR

images

after

bone

marrow

transplantation

and

the

administration

of

high-dose

myeloablative

chemotherapy

in

the

same

way

that

they

may

occur

after

conventional

chemotherapy

and

conditioning

chemotherapy

regimens

described

above

-LRB-

Fig.

-RRB-

For

example

sharply

defined

focal

low

signal

intensity

areas

of

bone

marrow

on

images

have

been

reported

in

patients

who

are

in

complete

remission

after

transplantation

-LSB-

-RSB-

Patients

with

these

abnormalities

did

not

have

a

poorer

outcome

than

those

with

normal

post-transplantation

MR

imaging

findings

-LSB-

-RSB-

These

data

show

that

there

is

clearly

a

need

for

the

MR

imaging

technique

to

add

some

functional

information

to

the

anatomical

data

e.g.

by

adding

spectroscopy

perfusion

studies

or

markers

for

tumor

cell

proliferation

Fig.

with

malignant

lymphoma

after

TBI

and

bone

marrow

transplantation

Plain

MR

image

-LRB-

center

-RRB-

shows

residual

hypointense

bone

marrow

lesions

in

the

pelvis

and

proximal

femur

Some

of

these

lesions

may

be

residual

marrow

abnormalities

of

uncertain

significance

Other

lesions

such

as

the

serpiginous

lesions

in

both

proximal

femurs

represent

therapy-induced

bone

infarcts

These

lesions

show

a

corresponding

serpiginous

hyperintense

area

on

STIR

images

-LRB-

left

-RRB-

and

a

minor

serpiginous

enhancement

on

Gd-enhanced

scans

-LRB-

right

-RRB-

Of

note

iron

overload

commonly

accompanies

bone

marrow

transplantation

and

may

result

in

a

diffusely

decreased

signal

intensity

of

the

liver

-LRB-

reported

in

of

pediatric

cases

after

bone

marrow

transplantation

-RRB-

spleen

-LRB-

-RRB-

and

bone

marrow

-LRB-

-RRB-

on

and

STIR

MR

images

-LRB-

Fig.

-RRB-

The

degree

of

hepatic

iron

overload

correlated

significantly

and

splenic

iron

overload

correlated

weakly

with

the

number

of

blood

transfusions

-LSB-

-RSB-

Fig.

patient

with

myeloma

after

bone

marrow

transplantation

The

bone

marrow

of

the

lumbar

spine

shows

a

diffuse

hypointense

signal

intensity

on

both

plain

-LRB-

left

-RRB-

and

fat-saturated

-LRB-

right

-RRB-

MR

images

TBI

can

cause

irradiation

induced

signal

changes

and

complications

described

above

-LRB-

Fig.

-RRB-

Long-term

complications

of

TBI

applied

as

part

of

the

conditioning

regimen

for

a

bone

marrow

transplantation

are

the

development

of

osteochondromas

or

sarcomas

In

summary

MR

imaging

can

be

a

useful

tool

to

aid

in

the

treatment

monitoring

of

patients

with

hematologic

malignancies

by

monitoring

treatment

response

detecting

treatment

complications

differentiating

normal

and

neoplastic

hypercellular

marrow

and

by

diagnosing

residual

or

recurrent

tumor

deposits

In

order

to

achieve

clinical

significance

and

cost-effectiveness

the

MR

imaging

technique

should

be

clearly

tailored

to

specific

patients

and

the

specific

questions

described

in

detail

above

New

MR

imaging

techniques

may

serve

to

depict

those

molecular

pathways

and

regulatory

events

that

control

blood

vessel

growth

and

proliferation

Non-invasive

monitoring

of

anti-angiogenic

therapies

has

found

success

by

defining

tumor

microvascular

and

metabolic

changes

while

treatment-related

changes

in

bone

marrow

morphology

tend

to

occur

rather

late

and

are

non-specific

Already

established

in

many

institutions

future

developments

will

almost

certainly

include

fusion

or

hybrid

imaging

methods

such

as

PET-CT

and

PET-MR

in

the

treatment

monitoring

of

patients

with

malignant

lymphomas

bone marrow
treatment effects
mr imaging
contrast agents


Bilateral pedicle stress fracture in the lumbar spine of a sedentary office worker A case of bilateral pedicle fracture in the lumbar spine of a sedentary office worker is being presented . No such case has been reported in the literature previously . Bilateral pedicle fracture is a rare entity . Few cases have been reported in literature . All the reported cases had some underlying causative factors like degenerative spine disease , previous spinal surgery or stress-related activities , e.g. athletes . Our case is a 36-year-old sedentary office worker with none of the factors mentioned . We present a case of a 36-year-old sedentary worker with long-standing low backache . There were no root tension signs . Plain radiographs were inconclusive . The patient had a CT scan . The CT scan revealed long-standing defects in the pedicles of L2 vertebra with pseudoarthrosis . Infiltration with anaesthetic relieved the symptoms . Our patient was managed conservatively with spine rehabilitation physiotherapy program . Pedicle fracture can develop due to abnormal stresses in the pedicle either because of previous spinal surgery or spondylitic changes in the spine . Bilateral pedicle fracture in the absence of these conditions is extremely rare . Introduction Isolated pedicle fracture in the spine is uncommon . It has been reported in association with previous spine surgery , or in highly active athletic individuals . We report a case of bilateral pedicle fracture in a patient with chronic backache without the history of trauma or any of the above-mentioned conditions . The patient was a sedentary worker with minimal physical demands . Case report We present a case of a 36-year-old female with a history of chronic backache . Her symptoms were of mild to moderate in intensity . Discomfort was mainly related to activity but she was performing her normal duties as an office manager without significant problems . On examination there were no neurological deficit or root tension signs . Plain radiographs were inconclusive . Clinical examination revealed localized deep tenderness at L2 ; therefore , a CT scan was performed . The CT scan showed bilateral long-standing defects through the pedicles of 2nd lumbar vertebra with pseudoarthrosis and sclerosis -LRB- Fig. 1a , b -RRB- . Infiltration with local anaesthetic , under the X-ray guidance , in the involved area relieved the symptoms . Surgical management was discussed with the patient , which was declined . The patient underwent spine rehabilitation physiotherapy program , which resulted in the improvement of the symptoms . Fig. 1a CT scan of the vertebra showing bilateral pedicle fracture . b CT scan showing bilateral pedicle fracture with pseudoarthrosis Discussion Bilateral pedicle stress fracture in the spine is a rare finding . Traughber and Havlina -LSB- 10 -RSB- reported the first case of a bilateral pedicle stress fracture . Cyron et al. -LSB- 2 -RSB- demonstrated that the parsintereticularis is thought to be the weakest site in the neural arch , followed by the pedicle . In cases with established unilateral stress fracture , there is a redistribution of forces in the neural arch , which leads to compensatory sclerosis of contralateral bony structures . A compensatory hypertrophy of the contralateral pedicle has been documented -LSB- 1 , 8 -RSB- . This entity was first described by Wilkinson and Hall -LSB- 11 -RSB- in 1974 . These authors reported on seven patients whose radiographs were suspicious for a neoplastic process occurring in a pedicle -LRB- e.g. osteoid osteoma or osteoblastoma -RRB- . Further investigation revealed unilateral spondylolysis with sclerosis of the contralateral posterior elements . The incidence of bilateral pedicle stress fracture is unknown in an otherwise normal spine . Gunzburg and Fraser -LSB- 3 -RSB- introduced the term pediculolysis in 1991 in a patient with multilevel facet joint osteoarthritis and minimal spondylolisthesis at L4 -- L5 . Pedicle fracture has been reported in cases following posterolateral instrumented spinal fusion -LSB- 4 , 5 , 7 -RSB- . Bilateral pedicle stress fractures or pediculolysis have been documented in an athlete of high physical demand -LSB- 6 -RSB- . Stanley and Smith -LSB- 9 -RSB- reported a case of pedicle fracture following laminectomy . In our patient the fractures appear to be old with evidence of sclerosis at the fracture margins along with pseudoarthrosis . This type of bilateral pedicle stress fracture has not been documented in a normal spine of a sedentary office worker without a history of major trauma or surgery . Conclusion Pedicle fracture is uncommon but has been reported in association with degenerative spondylolisthesis , unilateral spondylolysis , following spinal surgery but not in an otherwise normal spine . Pedicle stress fracture may show either as a recent fracture or may have signs of established pseudoarthrosis . So far there is no case of bilateral pedicle stress fracture in an otherwise normal spine .

B O B I O O O O O O O O O O O O B B I O O O O O O O O O O O O O O O O O O O O O O O O B B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O B B I O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B B I O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B B I O O O O O B B I O O O B O B I O O O O O O O O O O O O O O O O O O O O B O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O B O B I O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O B O B I O O O O O O

pedicle fracture
stress fracture
backache
bilateral