Multi-detector

row

computed

tomography

angiography

of

peripheral

arterial

disease

With

the

introduction

of

multi-detector

row

computed

tomography

-LRB-

MDCT

-RRB-

scan

speed

and

image

quality

has

improved

considerably

Since

the

longitudinal

coverage

is

no

longer

a

limitation

multi-detector

row

computed

tomography

angiography

-LRB-

MDCTA

-RRB-

is

increasingly

used

to

depict

the

peripheral

arterial

runoff

Hence

it

is

important

to

know

the

advantages

and

limitations

of

this

new

non-invasive

alternative

for

the

reference

test

digital

subtraction

angiography

Optimization

of

the

acquisition

parameters

and

the

contrast

delivery

is

important

to

achieve

a

reliable

enhancement

of

the

entire

arterial

runoff

in

patients

with

peripheral

arterial

disease

-LRB-

PAD

-RRB-

using

fast

CT

scanners

The

purpose

of

this

review

is

to

discuss

the

different

scanning

and

injection

protocols

using

and

row

CT

scanners

to

propose

effective

methods

to

evaluate

and

to

present

large

data

sets

to

discuss

its

clinical

value

and

major

limitations

and

to

review

the

literature

on

the

validity

reliability

and

cost-effectiveness

of

multi-detector

row

CT

in

the

evaluation

of

PAD

Introduction

Before

multi-detector

row

CT

-LRB-

MDCT

-RRB-

technology

was

available

the

evaluation

of

peripheral

arterial

disease

-LRB-

PAD

-RRB-

using

CT

was

restricted

to

imaging

only

a

portion

of

the

peripheral

arterial

tree

-LSB-

-RSB-

With

the

introduction

of

four-detector

row

CT

-LRB-

-RRB-

in

this

major

limitation

was

overcome

A

complete

coverage

of

the

lower

extremity

inflow

and

runoff

arteries

was

possible

with

one

acquisition

using

a

single-contrast

bolus

With

the

launch

of

the

row

CT

-LRB-

-RRB-

the

spatial

resolution

increased

to

near

isotropic

voxels

and

the

contrast

medium

efficiency

improved

-LSB-

-RSB-

True

isotropic

high

spatial

resolution

of

the

entire

volume

was

possible

using

the

row

CT

-LRB-

-RRB-

scanner

In

addition

improved

X-ray

tube

capacity

and

scan

speed

allow

submillimeter

acquisition

of

a

large

coverage

without

limitations

These

developments

made

multi-detector

row

CT

angiography

-LRB-

MDCTA

-RRB-

an

accurate

alternative

for

the

assessment

of

the

peripheral

arteries

-LSB-

-RSB-

Using

standardized

scanning

and

reviewing

protocols

peripheral

CT

angiography

is

a

robust

non-invasive

technique

for

evaluating

chronic

and

acute

disease

of

the

peripheral

arteries

We

present

a

review

concerning

our

experience

with

and

row

CT

scanners

in

patients

with

PAD

Technique

Preparation

There

are

no

specific

prescanning

preparations

necessary

for

MDCTA

of

the

peripheral

arteries

The

patient

is

placed

comfortably

to

avoid

movement

in

the

supine

position

with

raised

arms

on

the

CT

table

The

legs

are

stabilized

with

cushions

around

the

legs

and

slightly

strapped

with

adhesive

tape

distally

It

is

important

that

the

patient

does

not

wear

metal

zippers

or

buttons

on

their

clothing

since

this

can

have

a

negative

influence

on

the

image

quality

especially

when

using

postprocessed

images

Oral

contrast

should

not

be

used

as

this

complicates

postprocessing

display

-LRB-

Table

-RRB-

Contrast

material

needs

to

be

administered

at

body

temperature

to

decrease

the

viscosity

The

protocol

can

be

completely

programmed

into

the

scanner

Table

preparationParameterDescriptionClothingNo

metal

parts

on

clothingOral

contrastNoneI.V

cannula

antecubitalMinimally

G

-LRB-

mm

inner

diameter

blue

valve

-RRB-

PositioningSupine

stabilized

and

lightly

strapped

feet-first

and

arms

elevatedRespiratory

phaseInspiration

during

abdominal-pelvic

range

Technical

parameters

The

main

challenge

for

peripheral

CT

angiography

is

the

great

range

of

the

vascular

system

that

needs

to

be

depicted

Using

a

scanogram

of

approximately

length

the

coverage

of

the

acquisition

is

planned

from

the

celiac

trunk

-LRB-

vertebral

body

-RRB-

to

the

level

of

the

talus

using

or

to

the

level

of

the

feet

using

or

higher

-LRB-

Fig.

-RRB-

Fig.

-LRB-

a

-RRB-

Scout

image

with

three

planned

reconstruction

batches

of

the

abdomen

the

upper

legs

and

the

lower

legs

to

preserve

postprocessed

image

resolution

The

frames

and

depict

the

field

of

view

of

the

three

data

sets

which

need

to

be

as

narrow

as

possible

to

optimize

pixel

size

Whole-body

volume

maximum

intensity

projection

-LRB-

MIP

-RRB-

images

after

semiautomated

bone

removal

of

the

abdominal

data

set

-LRB-

b

-RRB-

the

femoral

data

set

-LRB-

c

-RRB-

and

the

crural

data

set

-LRB-

d

-RRB-

Scan

duration

The

optimal

scan

duration

for

peripheral

CT

angiography

varies

between

approximately

to

s

depending

on

the

number

of

detector

rows

and

the

collimation

-LRB-

Table

-RRB-

The

velocity

of

a

contrast

bolus

to

travel

from

the

aorta

to

the

popliteal

arteries

varies

from

to

mm/s

in

patients

with

PAD

-LSB-

-RSB-

This

large

variability

is

unpredictable

and

does

not

correspond

to

the

severity

of

PAD

Based

on

these

bolus

travel

times

it

is

recommended

to

limit

the

maximum

table

speed

on

faster

scanners

to

mm/s

to

avoid

outrunning

the

bolus

leading

to

poor

distal

vessel

opacification

This

can

be

obtained

for

example

by

limiting

the

gantry

rotation

speed

from

to

rotations

per

second

or

reducing

the

pitch

-LRB-

Table

-RRB-

Moreover

it

is

advised

to

program

a

second

acquisition

protocol

into

the

scanner

to

start

immediately

if

delayed

distal

enhancement

is

detected

-LRB-

Fig.

-RRB-

Because

the

time

of

the

contrast

bolus

to

travel

from

the

aorta

to

the

ankles

varies

from

to

s

a

longer

scan

duration

increases

the

risk

of

venous

contamination

especially

when

there

is

critical

ischemia

and

inflammation

-LSB-

-RSB-

Nevertheless

the

discrimination

of

the

arteries

from

the

veins

is

often

possible

due

to

the

stronger

arterial

enhancement

and

the

anatomic

information

-LSB-

-RSB-

Table

parameters

for

various

multi-detector

row

computed

tomography

-LRB-

MDCT

-RRB-

configurations

for

the

angiography

of

peripheral

arteriesType

of

scannerSection

collimation

width

-LRB-

mm

-RRB-

bRotation

time

-LRB-

s

-RRB-

PitchcTable

feed

-LRB-

mm

rotation

-RRB-

Table

speed

-LRB-

mm/s

-RRB-

Scan

duration

-LRB-

s

-RRB-

Slow

scan

protocol

thick

minimal

slice

Slow

scan

protocol

high

Slow

scan

protocol

less

resolution

better

in

obese

Fast

scan

protocol

less

resolution

reduction

of

contrast

Slow

scan

protocol

high

resolution

isotropic

voxel

double

z-sampling

scanning

of

obese

patients

Fast

scan

protocol

reduction

of

contrast

media

high

resolution

isotropic

voxel

double

z-sampling

scanning

of

obese

patients

Fast

scan

protocol

reduction

of

contrast

media

high

resolution

isotropic

voxel

double

z-sampling

scanning

of

obese

patients

possible

risk

of

outrunning

the

bolusaProtocols

designed

for

Siemens

CT

scanners

-LRB-

Siemens

Medical

Systems

Erlangen

Germany

-RRB-

and

should

be

modified

appropriately

for

other

models

and

manufacturersbValues

are

number

of

sections

times

section

widthcPitch

as

the

ratio

of

the

table

feed

per

rotation

over

the

total

width

of

the

collimated

beamdScan

times

representing

a

scanned

range

of

cmFig

from

the

first

and

second

delayed

acquisition

of

a

old

male

with

blue

toe

syndrome

of

the

left

hallux

-LRB-

a

and

b

-RRB-

VRT

images

of

the

first

acquisition

show

in

the

aneurysmatic

abdominal

aorta

a

short

occlusion

of

the

left

femoral

artery

-LRB-

white

arrows

-RRB-

due

to

thrombo-embolism

and

an

occlusion

of

the

entire

right

superficial

femoral

artery

The

anterior

tibial

arteries

seem

occluded

in

both

legs

-LRB-

c

and

d

-RRB-

VRT

image

of

the

feet

with

the

first

and

the

delayed

second

acquisition

The

first

acquisition

-LRB-

c

-RRB-

shows

that

the

arteries

of

the

feet

are

not

enhanced

yet

due

to

slow

flow

-LRB-

asterisk

-RRB-

The

delayed

acquisition

-LRB-

d

-RRB-

shows

that

both

dorsal

pedal

arteries

are

patent

and

that

the

proximal

arcuate

artery

and

the

first

dorsal

metatarsal

artery

-LRB-

black

arrows

-RRB-

of

the

left

foot

are

occluded

due

to

thrombo-embolism

Using

recent

MDCT

scanners

fast

scans

-LRB-

s

or

less

-RRB-

can

be

performed

of

the

peripheral

arteries

to

reduce

the

amount

of

contrast

media

To

allow

fast

scan

speed

using

row

CT

-LRB-

-RRB-

scanners

a

wider

collimation

must

be

used

-LRB-

Table

-RRB-

The

row

CT

-LRB-

-RRB-

even

allows

to

perform

fast

scans

while

maintaining

submillimeter

collimation

However

to

ensure

distal

opacification

the

scanning

delay

must

be

increased

appropriately

in

fast

scans

Another

difficulty

of

a

fast

scan

is

that

there

is

a

greater

risk

of

asymmetric

enhancement

in

patients

with

severe

unilateral

vascular

disease

Therefore

it

is

safer

to

choose

a

slower

scan

speed

Collimation

To

aim

for

maximal

spatial

resolution

a

thin

section

collimation

width

allows

a

narrow

effective

slice

width

Furthermore

the

partial

volume

effect

and

blooming

effect

of

calcium

will

be

reduced

-LRB-

Fig.

-RRB-

-LSB-

-RSB-

The

collimation

should

be

chosen

as

narrow

as

possible

but

still

allowing

for

a

table

speed

of

mm/s

and

depends

on

the

number

of

detector-rows

and

heat

capacity

On

a

row

CT

-LRB-

-RRB-

the

collimation

is

limited

to

mm

whereas

the

and

row

CT

-LRB-

-RRB-

allow

a

submillimeter

collimation

of

mm

and

mm

respectively

Fig.

bImages

of

row

CT

-LRB-

-RRB-

acquired

with

a

collimation

of

mm

showing

the

effect

of

slice

width

-LRB-

SW

-RRB-

on

the

blooming

of

the

arterial

wall

calcifications

-LRB-

a

-RRB-

Reconstructed

axial

image

of

the

right

external

and

internal

iliac

artery

with

SW

of

mm

using

a

reconstruction

kernel

shows

more

blooming

of

the

calcifications

than

-LRB-

b

-RRB-

-LRB-

b

-RRB-

Reconstructed

axial

image

of

the

right

external

and

internal

iliac

artery

with

SW

of

mm

using

a

reconstruction

kernel

with

less

blooming

of

calcifications

Using

in

obese

patients

the

thin

collimation

protocol

leads

to

unacceptable

noise

levels

in

the

abdomen

and

pelvis

because

the

tube

is

unable

to

deliver

the

necessary

dose

in

this

submillimeter

configuration

In

order

to

enable

the

tube

to

deliver

a

higher

dose

a

wider

collimation

-LRB-

mm

-RRB-

with

a

reduced

pitch

factor

of

-LRB-

Table

-RRB-

is

used

to

improve

the

image

quality

in

obese

patients

For

the

scanner

there

is

no

longer

a

tradeoff

between

resolution

and

scan

speed

and

it

allows

even

in

obese

patients

a

fast

submillimeter

scan

protocol

Contrast

injection

It

is

important

in

peripheral

CT

angiography

to

obtain

a

high

and

homogenous

enhancement

of

the

arterial

tree

and

to

synchronize

the

acquisition

with

the

enhancement

The

optimization

of

acquisition

timing

and

contrast

medium

delivery

is

essential

for

vascular

assessment

and

image

postprocessing

Normally

attenuation

values

higher

than

HU

in

the

arteries

is

considered

suitable

in

MDCTA

-LSB-

-RSB-

For

the

intravenous

injection

of

contrast

medium

in

the

antecubital

vein

and

intravenous

cannulas

are

needed

for

the

maximal

flow

rates

of

and

mL/s

respectively

Acquisition

timing

Due

to

the

interindividual

hemodynamic

variability

in

peripheral

CT

angiography

reliable

timing

techniques

are

preferred

over

using

a

fixed

delay

The

test-bolus

technique

relies

on

the

dynamic

monitoring

of

small

contrast

boluses

to

measure

the

contrast

arrival

and

travel

time

at

the

proximal

and

distal

arteries

respectively

The

bolus-triggering

technique

is

a

commonly

used

timing

technique

that

is

based

on

repetitive

low-dose

sequential

scans

at

the

level

of

the

abdominal

aorta

to

monitor

the

arrival

time

of

the

contrast

media

The

acquisition

starts

automatically

when

the

preferred

threshold

is

reached

approximately

to

HU

above

the

baseline

value

During

a

transition

delay

which

is

the

time

needed

for

the

table

to

move

and

start

the

scan

of

approximately

s

breathing

instructions

can

be

given

to

the

patient

During

this

delay

the

enhancement

of

the

aorta

will

further

increase

to

an

absolute

value

of

more

than

HU

For

a

fast

scan

protocol

an

extra

delay

must

be

added

to

the

contrast

arrival

time

to

ensure

distal

arterial

opacification

-LSB-

-RSB-

This

extra

delay

can

be

calculated

as

s

minus

the

scanning

time

Thus

for

a

scan

time

of

s

a

extra

delay

of

s.

must

be

added

Another

option

is

to

monitor

at

the

proximal

level

of

the

popliteal

artery

and

to

start

the

scan

manually

when

enhancement

is

visualized

Consequently

the

time

of

contrast

arrival

increases

by

approximately

s

-LSB-

-RSB-

and

the

transition

delay

of

the

scanner

increases

to

s

to

travel

from

the

knees

to

the

diaphragm

and

then

starting

the

acquisition

Contrast

injection

The

volume

of

contrast

material

ranges

from

to

ml

for

a

typical

scan

duration

of

s

The

amount

of

contrast

media

depends

on

the

scan

duration

and

on

the

flow

rate

Because

the

last

volume

of

the

bolus

will

not

contribute

to

the

enhancement

when

scanning

below

the

knees

the

injection

duration

can

be

shortened

by

s

e.g.

a

injection

time

is

used

for

an

acquisition

of

s.

However

to

ensure

the

enhancement

of

all

arteries

the

injection

duration

should

not

be

shorter

than

s

and

in

fast

scan

protocols

a

delay

time

needs

to

be

added

appropriately

to

prevent

outrunning

the

contrast

bolus

A

flow

rate

of

to

ml/s

is

necessary

for

adequate

arterial

enhancement

-LSB-

-RSB-

This

corresponds

to

an

iodine

administration

rate

of

to

g/s

using

a

contrast

media

concentration

of

approximately

to

mg

I/mL

Based

on

the

reported

literature

the

average

values

of

contrast

media

volume

concentration

injection

rate

and

administration

rate

are

ml

mg

I/mL

ml/s

and

g/s

respectively

-LSB-

-RSB-

By

increasing

the

iodine

concentration

to

a

concentration

of

mg

I

mL

the

iodine

administration

rate

can

be

increased

to

g/s

to

increase

the

enhancement

-LSB-

-RSB-

To

optimize

the

enhancement

to

mL

of

saline

is

injected

immediately

after

the

contrast

media

A

tighter

bolus

can

be

obtained

to

increase

the

attenuation

Using

a

monophasic

injection

rate

the

arterial

enhancement

increases

over

time

to

decrease

at

the

end

of

the

bolus

Consequently

the

Hounsfield

values

of

the

enhanced

arteries

start

lower

at

the

level

of

the

aorta

and

increase

at

the

level

of

the

popliteal

artery

to

the

highest

attenuation

value

and

subsequently

decrease

distally

in

the

runoff

arteries

especially

for

longer

scan

durations

-LSB-

-RSB-

A

more

homogenous

enhancement

can

be

achieved

using

a

biphasic

injection

rate

using

a

higher

rate

-LRB-

ml/s

-RRB-

at

the

beginning

-LRB-

during

the

first

s

-RRB-

of

the

injection

and

a

lower

rate

-LRB-

ml/s

-RRB-

for

the

remaining

volume

In

clinical

practice

a

monophasic

injection

rate

is

often

used

because

it

is

a

simple

method

and

has

resulted

in

adequate

image

quality

-LSB-

-RSB-

Patient

dose

in

MDCT

A

particular

concern

with

MDCT

scanners

is

delivering

potentially

higher

radiation

doses

To

maintain

the

noise

level

in

submillimeter

slices

the

dose

needs

to

increase

proportionally

On

the

other

hand

with

the

increasing

number

of

detector

rows

the

z-axis

efficiency

improves

since

the

overbeamed

area

decreases

Current

MDCT

scanners

present

an

indication

of

patient

dose

on

the

scanner

console

for

dose

awareness

and

to

help

optimize

the

scan

protocol

Useful

in

CT

angiography

is

that

when

reducing

the

X-ray

energy

the

contrast-to-noise

ratio

increases

Compared

to

a

standard

scan

with

kVp

selecting

kVp

results

in

a

dose

saving

of

approximately

-LSB-

-RSB-

Furthermore

dose

reduction

can

be

achieved

by

decreasing

the

tube

current

using

automatic

tube

current

modulation

With

angular

tube

current

modulation

the

tube

current

varies

during

the

course

of

a

rotation

The

changing

attenuation

through

different

projections

around

the

patient

-LRB-

e.g.

at

the

level

of

the

pelvis

-RRB-

can

be

used

to

reduce

unnecessary

x-rays

in

the

anterior

posterior

projection

without

any

substantial

effect

on

image

quality

-LSB-

-RSB-

With

longitudinal

tube

current

modulation

the

tube

current

varies

along

the

z-axis

based

on

the

size

shape

and

attenuation

to

maintain

a

predefined

noise

ratio

Compared

with

constant

tube

current

this

technique

results

in

acceptable

image

noise

and

a

dose

reduction

of

or

more

without

compromising

diagnostic

image

quality

-LSB-

-RSB-

The

average

patient

dose

reported

in

the

literature

in

the

assessment

of

PAD

with

CT

angiography

is

mSv

-LSB-

-RSB-

The

radiation

risk

from

these

doses

is

not

a

major

concern

in

patients

with

PAD

Their

life

expectancy

is

shorter

than

the

latency

period

of

a

radiation-induced

fatal

malignancy

-LSB-

-RSB-

Display

and

evaluation

Image

reconstruction

The

raw

data

set

is

reconstructed

using

an

increment

with

to

overlap

Peripheral

CT

angiography

generates

more

than

axial

images

depending

on

slice

width

and

reconstruction

increment

It

is

recommended

to

reconstruct

separate

data

sets

Routinely

we

calculate

three

separate

data

sets

of

the

peripheral

runoff

-LRB-

Fig.

-RRB-

The

first

advantage

is

that

it

allows

us

to

reconstruct

thicker

slices

e.g.

of

mm

for

the

abdominal

and

femoral

data

set

and

thinner

slices

for

the

crural

data

set

to

optimize

the

resolution

and

to

minimize

the

data

load

-LSB-

-RSB-

Secondly

longitudinal

images

that

are

calculated

from

the

entire

data

set

have

a

decreased

resolution

due

to

the

limited

display

matrix

-LRB-

e.g.

-RRB-

-LSB-

-RSB-

Images

that

are

reconstructed

from

the

separate

data

sets

will

preserve

the

initial

longitudinal

resolution

A

smooth

kernel

-LRB-

for

Siemens

CT

scanners

-RRB-

is

generally

used

in

CT

angiography

and

leads

to

an

accurate

depiction

of

the

diameter

of

the

vessels

and

is

very

appropriate

for

postprocessing

A

sharp

kernel

-LRB-

-RRB-

is

used

when

stents

or

severe

vessel

wall

calcifications

are

present

as

it

minimizes

the

blooming

effect

at

the

cost

of

some

increase

in

the

noise

level

-LSB-

-RSB-

The

field

of

view

-LRB-

FOV

-RRB-

is

selected

as

small

as

possible

to

optimize

pixel

size

A

FOV

of

mm

mm

and

mm

for

the

abdominal

femoral

and

crural

data

sets

results

in

pixel

sizes

of

approximately

mm

mm

and

mm

respectively

Also

the

FOV

can

be

further

decreased

to

mm

by

including

only

one

leg

leading

to

a

pixel

size

of

mm

Advanced

postprocessing

and

image

evaluation

Additional

two-dimensional

-LRB-

-RRB-

and

three-dimensional

-LRB-

-RRB-

postprocessing

techniques

are

required

to

facilitate

interpretation

and

presentation

Reviewing

exclusively

the

transverse

images

is

inefficient

and

less

accurate

than

reviewing

a

combination

of

reformatted

images

To

preserve

the

study

quality

for

clinical

decision

making

a

standard

set

of

postprocessed

images

needs

to

be

included

in

the

protocol

These

include

thin-slab

maximum-intensity

projections

-LRB-

MIPs

-RRB-

through

visceral

and

renal

arteries

and

the

abdominal

aorta

through

femoropopliteal

arteries

and

through

crural

arteries

-LRB-

Fig.

-RRB-

whole-volume

MIPs

of

the

separate

data

sets

after

bone

removal

-LRB-

Fig.

-RRB-

and

when

necessary

after

removal

of

vessel

wall

calcifications

-LRB-

Fig.

-RRB-

and

curved

planar

reformations

-LRB-

CPRs

-RRB-

e.g.

through

the

iliac

arteries

Volume-rendered

-LRB-

VR

-RRB-

images

are

fast

and

effortless

created

to

present

the

pathology

to

clinicians

who

normally

do

not

have

the

possibility

to

review

the

data

set

interactively

Fig.

dStandard

slab

MIP

images

in

the

postprocessing

protocol

make

MDCTA

of

peripheral

arteries

on

a

routine

basis

feasible

Slab

MIPs

are

easy

and

fast

to

create

and

to

evaluate

The

images

depict

the

vasculature

without

superimposing

bones

-LRB-

a

and

b

-RRB-

From

the

abdominal

data

set

MIP

images

are

created

in

coronal

projection

to

depict

the

renal

arteries

-LRB-

b

-RRB-

and

in

sagittal

projection

to

depict

the

celiac

trunk

and

mesenteric

arteries

-LRB-

d

-RRB-

The

aorta

is

also

depicted

for

evaluation

-LRB-

c

-RRB-

Standard

coronal

slab

MIPs

from

the

data

set

of

the

upper

legs

are

created

which

are

parallel

to

the

superficial

femoral

and

popliteal

artery

-LRB-

d

-RRB-

Standard

coronal

slab

MIPS

from

the

data

set

of

the

lower

legs

display

the

crural

arteriesFig

dVolume

MIP

images

in

anteroposterior

projection

show

the

result

of

three

different

threshold

levels

used

for

the

segmentation

of

arterial

wall

calcifications

-LRB-

a

-RRB-

Volume

MIP

before

removal

of

the

calcifications

shows

that

the

lumen

is

not

visible

-LRB-

b

-RRB-

Volume

MIP

after

removal

of

the

calcifications

shows

that

still

many

voxels

of

calcification

are

present

hampering

lumen

assessment

-LRB-

arrows

-RRB-

-LRB-

c

-RRB-

Volume

MIP

shows

angiogram

after

calcium

segmentation

using

a

correct

threshold

level

allowing

lumen

assessment

The

rest

of

the

voxels

of

the

burden

of

calcifications

are

just

visible

as

unesthetical

noise

which

is

however

preferable

to

introducing

pseudo-stenoses

-LRB-

d

-RRB-

-LRB-

arrows

-RRB-

by

using

a

too

low

threshold

level

The

data

sets

are

reviewed

effectively

by

evaluating

the

standard

set

of

postprocessed

images

and

interactively

exploring

the

data

set

using

multiplanar

reformations

-LRB-

MPRs

-RRB-

The

transverse

images

-LRB-

or

true

cross-sectional

images

-RRB-

need

to

be

considered

to

verify

diseased

segments

-LSB-

-RSB-

When

extensive

calcifications

or

stents

are

present

the

vessel

lumen

visibility

and

the

clinicians

confidence

in

the

CT

images

will

decrease

-LSB-

-RSB-

In

whole-volume

MIPs

superimposing

calcifications

can

be

selected

to

be

removed

digitally

from

the

data

set

using

thresholding

and

region-growing

techniques

-LRB-

Fig.

-RRB-

However

the

removal

of

the

numerous

arterial

wall

calcifications

can

be

very

time

consuming

Another

limitation

of

these

segmentation

techniques

is

that

readers

should

be

aware

of

artificial

stenoses

and

occlusions

These

can

be

introduced

when

voxels

that

represent

lumen

are

inadvertently

removed

when

in

close

contact

with

the

bones

-LRB-

Figs.

and

-RRB-

or

when

a

too

low

threshold

value

is

used

-LRB-

Fig.

-RRB-

In

addition

in

VR

images

the

lumen

is

also

obscured

by

vessel

wall

calcifications

and

as

a

result

should

not

be

used

for

the

lumen

assessment

-LRB-

Fig.

-RRB-

A

more

reliable

technique

for

stenosis

detection

in

extensive

calcified

arteries

is

CPR

which

displays

the

lumen

as

a

longitudinal

cross-section

-LRB-

Fig.

-RRB-

When

using

an

application

that

semi-automatically

traces

the

vessel

lumen

the

risk

of

an

inaccurately

positioned

central

lumen

line

is

minimized

The

CPR

projection

should

include

at

least

two

perpendicular

longitudinal

projections

and

true

cross-sectional

images

can

be

viewed

for

lumen

assessment

-LSB-

-RSB-

Software

tools

are

available

for

automatic

quantitative

evaluation

of

the

traced

lumen

and

to

generate

a

graphical

presentation

of

luminal

diameter

-LRB-

Fig.

-RRB-

Multipath

CPRs

are

under

development

and

could

enhance

image

evaluation

Fig.

dInfluence

of

vessel

wall

calcifications

on

postprocessed

images

and

the

ability

for

lumen

assessment

-LRB-

a

-RRB-

VRT

image

-LRB-

medial

view

-RRB-

of

right

femoropopliteal

segment

showing

arterial

wall

calcification

does

not

allow

luminal

assessment

-LRB-

b

-RRB-

CPR

image

-LRB-

anteroposterior

view

-RRB-

shows

the

interior

of

blood

vessels

as

a

longitudinal

cross-section

even

in

the

presence

of

the

arterial

wall

calcifications

This

is

the

preferred

imaging

technique

when

extensive

calcifications

of

the

vessel

wall

are

present

Volume

MIP

-LRB-

anteroposterior

view

-RRB-

after

bone

removal

using

region-growing

and

threshold

techniques

-LRB-

c

-RRB-

does

not

allow

lumen

evaluation

Volume

MIP

after

additional

calcification

removal

-LRB-

d

-RRB-

removes

superimposing

calcification

to

enable

lumen

evaluationFig

cImages

of

segmentation

artifacts

due

to

bone

removal

in

-LRB-

a

-RRB-

Volume

MIP

after

bone

segmentation

of

the

lower

legs

showing

a

pseudo-occlusion

of

both

distal

anterior

crural

arteries

-LRB-

arrows

-RRB-

which

is

caused

by

segmentation

of

the

bones

-LRB-

b

-RRB-

MIP

of

the

lower

legs

showing

the

anterior

tibial

arteries

in

close

proximity

to

the

tibia

-LRB-

arrows

-RRB-

which

is

the

cause

of

the

false

positive

pseudo-occlusion

-LRB-

c

-RRB-

Axial

image

of

the

lower

legs

just

caudal

from

the

pseudo-occlusion

showing

the

patency

of

both

anterior

tibial

arteries

of

both

legs

in

close

proximity

of

the

tibia

-LRB-

arrows

-RRB-

Fig.

cApplying

blue

color

to

the

voxels

selected

for

removal

helps

to

identify

the

sites

of

segmentation

artifacts

in

VRT

images

-LRB-

a

-RRB-

VRT

image

before

bone

segmentation

of

the

lower

legs

showing

patent

proximal

anterior

tibial

arteries

-LRB-

b

-RRB-

VRT

with

blue

bones

to

indicate

the

voxels

to

be

removed

shows

the

voxels

of

the

bone

which

are

in

contact

with

the

proximal

anterior

tibial

artery

are

not

selected

for

removal

and

shows

the

voxels

of

the

artery

which

are

selected

for

removal

-LRB-

c

-RRB-

Segmented

VRT

image

showing

the

pseudo-occlusion

of

the

anterior

tibial

arteryFig

bResults

of

semiautomated

quantitative

lumen

assessment

in

aortoiliac

arteries

of

a

patient

with

in

stent

thrombosis

-LRB-

a

-RRB-

Graph

-LRB-

upper

section

-RRB-

displaying

the

maximum

and

minimum

diameters

of

the

lumen

to

quantify

stenosis

CPR

-LRB-

lower

section

-RRB-

through

the

aortoiliac

arteries

which

can

be

rotated

around

its

longitudinal

axis

depicts

the

luminal

obstruction

-LRB-

asterisk

-RRB-

due

to

a

thrombus

inside

an

iliac

stent

-LRB-

b

-RRB-

Corresponding

transverse

image

confirms

the

occlusion

of

the

iliac

stent

Wall

calcification

problem

The

depiction

of

vessel

wall

calcifications

using

MDCT

can

be

valuable

since

severely

calcified

arteries

may

have

consequences

for

bypass

surgery

On

the

other

hand

these

wall

calcifications

are

known

to

hamper

the

assessment

of

the

lumen

-LSB-

-RSB-

Approximately

to

of

the

vascular

segments

contain

wall

calcifications

of

which

severely

calcified

-LSB-

-RSB-

Patients

with

a

history

of

diabetes

mellitus

cardiac

disease

or

elderly

age

are

very

likely

to

have

extensive

calcifications

-LSB-

-RSB-

Furthermore

we

found

that

patients

with

Fontaine

stage

III/IV

have

more

infrapopliteal

arterial

wall

calcifications

compared

to

stage

IIb

How

can

we

deal

with

the

vessel

wall

calcifications

depicted

with

MDCTA

It

is

important

to

use

a

wider

window

width

-LRB-

WW

-RRB-

and

higher

window

center

-LRB-

WC

-RRB-

level

settings

from

the

usual

CT

angiography

level

of

around

WC

WW

to

WC

WW

for

a

better

differentiation

of

calcifications

and

stents

from

the

enhanced

lumen

and

to

minimize

the

effect

of

blooming

A

further

minimization

of

blooming

is

reached

by

using

a

sharper

reconstruction

kernel

and

higher

spatial

resolution

Especially

in

MIP

images

the

lumen

is

hidden

by

the

circumferential

calcifications

In

these

circumstances

transverse

images

CPR

images

and

the

digital

removal

of

the

calcifications

help

to

depict

the

lumen

at

least

for

the

larger

arteries

Despite

all

of

the

available

tools

in

particular

in

the

smaller

crural

arteries

the

concentric

calcifications

still

hamper

lumen

assessment

-LSB-

-RSB-

Recent

publications

showed

that

a

subtraction

technique

using

two

acquisitions

is

feasible

in

some

patients

with

PAD

using

MDCTA

-LSB-

-RSB-

In

the

near

future

automated

applications

could

help

to

minimize

the

impediment

of

the

calcifications

-LSB-

-RSB-

Whether

dual-energy

CT

angiography

can

improve

this

limitation

of

CT

needs

to

be

evaluated

Clinical

value

Because

MDCT

angiography

for

the

imaging

of

the

peripheral

arteries

is

a

rather

new

non-invasive

technique

there

are

a

small

number

of

studies

published

on

its

performance

and

reproducibility

-LRB-

Table

-RRB-

The

majority

report

on

two

authors

report

on

There

are

no

reports

of

the

assessment

of

PAD

using

In

our

meta-analysis

soon

appearing

in

Radiology

which

included

patients

and

arterial

segments

a

pooled

sensitivity

and

specificity

for

detecting

a

stenosis

of

and

was

estimated

respectively

Table

of

CT

angiography

in

peripheral

arterial

disease

-LRB-

PAD

-RRB-

AuthoraNo

of

patientsNo

of

analyzed

segmentsNo

of

detectorsReported

sensitivity

-LRB-

-RRB-

eReported

specificity

-LRB-

-RRB-

eAssessed

segmentsStenosis

category

-LRB-

-RRB-

hRichter

et

al.

et

al.

et

al.

et

al.

et

al.

et

al.

et

al.

graftsnsBourlet

et

al.

et

al.

et

al.

graftsnsOfer

et

al.

tree

et

al.

tree

et

al.

Total

et

al.

Total

tree

et

al.

tree

et

al.

tree

et

al.

et

al.

treearea

et

al.

Total

treensRomano

et

al.

Total

treensStueckle

et

al.

treensEdwards

et

al.

Total

et

al.

et

al.

et

al.

Total

tree

on

references

-LSB-

-RSB-

bFor

various

anatomic

levelscCalculated

from

the

datadBased

only

on

subtracted

MDCTA

images

the

positive

predictive

value

was

eSensitivity

as

published

or

calculated

overall

mean.fDiameter

stenosis

is

mentioned

unless

specified

-LRB-

means

stenosis

more

than

including

occlusion

-RRB-

gFor

subtracted

and

nonsubtracted

segments

respectivelyhDepending

on

the

MDCTA

protocol

with

varying

mAs

Publications

on

the

reproducibility

of

CT

angiography

reported

a

good

intertest

agreement

between

MDCTA

and

DSA

-LRB-

Table

-RRB-

and

a

good

to

excellent

interobserver

agreement

for

-LSB-

-RSB-

and

-LRB-

Table

-RRB-

-LSB-

-RSB-

A

few

studies

provide

stratified

data

on

the

aortoiliac

femoropopliteal

and

crural

tract

and

show

that

the

accuracy

and

reproducibility

of

the

crural

tract

is

lower

than

for

the

aortoiliac

and

femoropopliteal

tracts

-LSB-

-RSB-

Table

agreement

between

CT

angiography

and

digital

subtraction

angiography

in

PADAuthoraNo

of

patientsNo

of

assessed

segmentsNo

of

detectorsReported

intertest

agreementdAssessed

segmentsRaptopoulos

et

al.

AortoiliacBeregi

et

al.

PoplitealTins

et

al.

AortoiliacWalter

et

al.

-LRB-

-RRB-

cTotal

treeRubin

et

al.

Total

treeHeuschmid

et

al.

Total

treeOfer

et

al.

Total

treeRomano

et

al.

κ

Total

treeRomano

et

al.

κ

Total

treeaBased

on

references

-LSB-

-RSB-

bBased

on

of

the

segmentscAverage

of

the

reported

kappa

values

-LRB-

ranges

-RRB-

of

the

individual

anatomical

segmentsdAn

unweighted

kappa

statistic

-LRB-

κ

-RRB-

is

reported

for

percentage

agreementTable

agreement

of

CT

angiography

in

PADAuthoraNo

of

patientsNo

of

analyzed

segmentsNo

of

detectorsReported

interobserver

agreementbAssessed

segmentsRieker

et

al.

AortofemoralWalter

et

al.

cTotal

treeTins

et

al.

AortofemoralMartin

et

al.

κw

Total

treeRomano

et

al.

κ

dTotal

treeRomano

et

al.

κ

κ

eTotal

treeCatalano

et

al.

κ

Total

treeOta

et

al.

IliacPortugaller

et

al.

Total

treeKock

et

κw

Total

treeOuwendijk

et

al.

κw

Total

treeWillmann

et

al.

κ

treeaBased

on

references

-LSB-

-RSB-

bAn

unweighted

kappa

statistic

-LRB-

κ

-RRB-

is

reported

unless

indicated

-LRB-

κw

weighted

kappa

statistic

ρ

intraclass

agreement

coefficients

as

a

measure

of

agreement

for

ordinal

or

quantitative

data

-RRB-

A

linear

weighting

was

used

except

in

one

paper

-LSB-

-RSB-

where

a

quadratic

weighting

was

usedcRange

of

kappa

values

of

the

individual

anatomical

segmentsdFor

reader

one

and

two

respectivelyeFor

intraobserver

-LRB-

two

readers

-RRB-

and

interobserver

agreement

respectivelyfBased

on

unpublished

data

MDCTA

leads

to

adequate

decision

making

for

treatment

recommendations

concerning

both

the

anatomical

level

and

the

technique

of

revascularization

-LSB-

-RSB-

A

cost-effectiveness

study

showed

that

MDCTA

is

a

cost-effective

diagnostic

strategy

in

the

work-up

of

PAD

-LSB-

-RSB-

Randomized

controlled

trials

confirmed

that

MDCTA

in

PAD

is

the

optimal

diagnostic

imaging

technique

-LSB-

-RSB-

and

reduces

the

diagnostic

costs

when

compared

to

DSA

and

CEMRA

with

comparable

clinical

utility

and

patient

outcomes

Besides

these

evidence-based

results

local

expertise

and

availability

also

define

which

modality

to

use

in

clinical

practice

-LRB-

Table

-RRB-

Table

and

limitations

of

multi-detector

row

CT

angiography

-LRB-

MDCTA

-RRB-

contrast

enhanced

MR

angiography

-LRB-

CEMRA

-RRB-

and

digital

subtraction

angiography

-LRB-

DSA

-RRB-

MDCTACEMRADSAIntermittent

claudication

-LRB-

Fontaine

II

-RRB-

Chronic

critical

ischemia

-LRB-

Fontaine

III

or

IV

-RRB-

Short

examination

time

Short

postprocessing

time

Outpatient

setting

Availability

Non-invasive

technique/patient

comfortb

Low

diagnostic

imaging

costs

Contrast

media

tolerance

Three-dimensional

imaging

Non-interference

of

stentsc

Radiation

risk

-LRB-

-RRB-

d

-LRB-

-RRB-

dAcute

clinical

setting

Hemodynamic

assessment

a

Extraluminal

pathology

visualization

a

aIs

only

possible

when

using

additional

sequencesbFrom

-LSB-

-RSB-

cFrom

-LSB-

-RSB-

dNegligible

risk

in

population

with

chronic

obstructive

PAD

It

is

reported

that

arterial

wall

calcifications

lead

to

false-positive

interpretations

and

a

decreased

reproducibility

in

reading

MDCTA

-LSB-

-RSB-

We

have

to

acknowledge

this

limitation

with

current

technology

A

preferential

indication

for

MDCTA

in

patients

with

intermittent

claudication

-LRB-

Fontaine

stage

IIb

-RRB-

is

clearly

justified

However

patients

with

critical

limb

ischemia

-LRB-

Fontaine

stage

III/IV

-RRB-

who

are

likely

to

have

extensive

calcifications

of

the

smaller

arteries

could

be

better

off

undergoing

contrast-enhanced

magnetic

resonance

angiography

-LRB-

CEMRA

-RRB-

or

digital

subtraction

angiography

-LRB-

DSA

-RRB-

Finally

MDCTA

is

an

accurate

technique

to

evaluate

the

patency

after

revascularization

procedures

-LSB-

-RSB-

The

technique

can

be

used

in

the

evaluation

of

acute

ischemia

e.g.

after

a

revascularization

procedure

or

in

thrombo-embolic

disease

-LRB-

Fig.

-RRB-

For

aneurysmatic

popliteal

artery

disease

or

entrapment

syndromes

of

the

popliteal

artery

MDCTA

is

the

preferred

imaging

modality

-LRB-

Fig.

-RRB-

-LSB-

-RSB-

Fig.

bAcute

thrombosis

of

the

crural

arteries

in

a

woman

with

an

acutely

cold

left

leg

after

stopping

anticoagulation

therapy

The

patient

refused

angiography

-LRB-

a

-RRB-

VRT

image

-LRB-

posteroanterior

view

-RRB-

of

MDCTA

at

the

level

of

the

crural

arteries

shows

abrupt

stoppage

of

arterial

opacification

in

the

left

peroneal

anterior

and

posterior

tibial

artery

-LRB-

arrows

-RRB-

The

contralateral

right

crural

arteries

are

patent

-LRB-

b

-RRB-

Selective

anterograde

DSA

image

-LRB-

posteroanterior

view

-RRB-

confirms

the

occlusions

of

the

three

left

crural

arteries

-LRB-

arrows

-RRB-

due

to

thrombo-embolismsFig

dA

old

male

patient

who

had

a

history

of

deep

venous

thrombosis

with

intermittent

claudication

of

the

right

lower

extremity

-LRB-

a

and

b

-RRB-

Thin

MIP

image

shows

an

aneurysmatic

right

popliteal

artery

with

a

tight

stenosis

distally

-LRB-

c

-RRB-

VRT

and

volume

MIP

-LRB-

d

-RRB-

confirm

these

findings

and

show

patent

proximal

crural

arteries

Conclusion

Multi-detector

row

CT

angiography

-LRB-

MDCTA

-RRB-

is

an

outstanding

non-invasive

imaging

test

in

the

evaluation

of

patients

with

peripheral

arterial

disease

-LRB-

PAD

-RRB-

and

is

currently

the

modality

of

choice

in

patients

with

intermittent

claudication

The

technique

can

be

used

in

the

evaluation

of

patency

after

revascularization

procedures

and

in

acute

ischemia

MDCTA

has

been

shown

to

have

high

diagnostic

performance

and

reproducibility

in

evaluating

peripheral

arterial

disease

-LRB-

PAD

-RRB-

MDCTA

reduces

diagnostic

costs

and

provides

adequate

information

for

decision

making

The

most

important

drawback

is

the

limited

lumen

evaluation

of

extensive

calcified

arteries

MDCTA

appears

to

be

clinically

less

valuable

in

critical

limb

ischemia

because

of

extensive

crural

artery

calcifications

O O O B 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 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 O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O 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 O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O 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 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 O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O

human
peripheral vascular diseases
radiography
x-ray computed methods
reproducibility of results


Osteoma in the upper cervical spine with spinal cord compression Osteoma is a common benign tumor . It occurs dominantly at the skull bone . Outside skull osteoma is rare , and primary intra-canal osteoma is extremely rare . To the author 's knowledge , only 14 cases of osteomas of the spine had been reported , in which only seven cases were in English literature . The authors reported two rare cases of intra-canal osteoma of the upper cervical spine with cord compression . Included are pertinent history , physical examination , rontgenographic evaluation before and after operation , surgical interventions , pathological study , and outcome . The available literature is also reviewed . On systemic examination and rontgenographic study , these two cases were found to have bone tumor in the upper cervical canal . Surgical interventions were performed , one with an en bloc excision , the other with a subtotal excision . The pathological study demonstrated a diagnosis of osteoma . After a follow-up with 20 and 15 months , the clinical symptoms of both cases significantly improved . Introduction Osteomas are rare , slow growing lesions composed of compact bone that occur almost exclusively in the skull -LSB- 2 , 7 -RSB- , most often in the inner and outer table of the calvarium or in the bones of the face or mandible -LSB- 1 , 12 , 13 -RSB- . The prevalence of this disease amounting those who have had sinus radiographs has been estimated to be 0.42 % -LSB- 7 -RSB- . Although these lesions may cause sinusitis or exophthalmos when they arise from the wall of the nasal sinuses or the orbit , cranial osteomas often cause no symptoms and are discovered incidentally . Primary intra-canal osteomas are extremely rare . To the authors ' knowledge , at the time of writing , only 14 cases of osteomas of the spine had been reported , in which only seven cases were in the English literature -LSB- 4 -- 6 , 8 , 9 , 11 -RSB- . The purpose of this article is to report on two patients who presented with cervical intra-canal osteoma . Case report Case One A 56-year-old man had presented with paresis and weakness of his extremities after a hyperextension injury of the cervical spine in August 2002 . The man had been asymptomatic prior to the accident . Physical examination demonstrated limitation in neck rotation , and motor weakness of the extremities with strength 3/5 in upper extremities and 4/5 in lower extremities . He could eat with chopsticks to a limited degree . He could walk . However , he needed cane or aid on stairs . Hypoesthesia was present at the upper extremities , bilaterally . The biceps tendon reflex , patellar tendon reflex , and Achilles tendon reflex were hyperactive , and the Hoffman and Babinski reflex were positive bilaterally . Sustained ankle clonus was present , bilaterally . Neurological examination was consistent with upper neuron cell injury . The Japanese orthopedic association -LRB- JOA -RRB- score for cervical myelopathy was 11 . Preoperative imaging study demonstrated a cortical like solid lesion . The results were shown in Fig. 1a -- e. Fig. 1a Cervical A -- P view X-ray showed densification at left side at C2 -- 3 level . b Cervical lateral view X-ray showed high density at C2 -- 3 level , the facet joints between C2 \ C3 were obscure . c CT scan through the intervertebral foramen between C2 and C3 showed the tumor occupied more than 60 % canal and the vertebral shape changed , caused by the chronic pressure . d Three dimensions CT reconstruction showed the three-dimension relationship between the tumor and the cervical spinal canal . e Middle sagittal plane T1WI MRI showed the spinal cord was pressed by the tumor . The signal of the tumor was low . f The same plane as c after operation , showed the whole decompression of the spinal canal , part of the tumor , near the vertebral artery was left . g The same plane as e after operation , showed the whole decompression of the cord and spinal canal . h , i The pathological study showed that the lesion was composed of uniformly dense , compact , cortical-like mature lamellar bone . H : × 100 , I : × 400 We performed a leminectomy of C2 and C3 . In the operation , we found that the tumor was adhesive with the left side vertebral artery . To avoid the injury of the artery , part of the tumor , near the vertebral artery , was left . However the decompression of the spinal cord was enough -LRB- Fig. 1f -- g -RRB- . The pathological study showed that the lesion was composed of uniformly dense , compact , cortical-like , mature lamellar bone -LRB- Fig. 1h -- i -RRB- , and a diagnosis of osteoma was made . Two weeks after the operation , this patient 's clinical symptoms improved significantly . Then , with hard cervical brace protection , the patient was permitted to ambulate . He noted gradual improvement of strength in his upper extremity . Three months later , the brace was removed . Twenty months later , the muscle strength was 5/5 in all extremities . He could eat with chopsticks , but awkwardly . He could walk with no disability . No hypoesthesia was present . The patient 's JOA score increased from 11 to 16 -LRB- Table 1 -RRB- . Table 1JOA score of the two cases before and after therapyBefore therapyFollow-upCase 1Case 2Case 1Case 2Motor Upper extremity2133 Lower extremity2243Feeling Upper extremity1122 Trunk2222 Lower extremity2222Sphincter2233Total11101615 Case two A 49-year-old man had experienced paresis and weakness of his extremities after a weight-hit injury of the head in November 2002 . The man had been asymptomatic before the accident . Physical examination showed moderate motor weakness and hypoesthesia of the upper extremity , with strength 3/5 in upper extremities and 4/5 in lower extremities . He could eat with spoon but could not with chopsticks . He could walk . However , he needed a cane or aid on stairs . The feel of trunk and lower extremity is fair . The biceps , patellar , and Achilles tendon reflexes were hyperactive , and the Hoffman and Babinski reflexes were positive bilaterally . Ankle clonus was noted continuously on both sides . Preoperative imaging study demonstrated lamina fracture of C3 , traumatic instability of C3 -- 5 , and a cortical like solid lesion at the left side of C2 lamina . The results were shown in Fig. 2a -- c. Fig. 2a Cervical lateral view X-ray showed high density at C2 -- 3 level , the facet joints between C2 \ C3 were obscure , traumatic instability of C3 -- 5 . b CT scan through C2 showed the tumor at the left side of the lamina , occupied about 20 % canal , and the left side lamina of the C2 became thicker . c Sagittal plane T2WI MRI showed the spinal cord was pressed by the tumor . The signal of the tumor was low . d Three-dimension CT reconstructive image showed complete decompression We performed a laminectomy of C3 -- C4 and part of C2 , as well as internal fixation of C3 -- 5 , using pedicle screw system . The tumor was removed completely and the spinal cord was decompressed . The pathological study showed that the lesion was also composed of uniformly dense , compact , cortical-like , mature lamellar bone without nidus -LRB- not shown -RRB- . Lateral view X-ray after operation showed the reconstruction of the stability by the pedicle screw system and lamina decompression of C3 -- 4 and part of C2 . Three dimension CT reconstructive image showed complete decompression of the spinal cord -LRB- Fig. 2d -RRB- . A month after the operation , this patient 's clinical symptoms improved significantly . Then , with hard cervical brace protection , the patient was permitted to ambulate , and he noted gradual improvement of strength in his upper extremity also . Three months later , the brace was removed . After 15 months , the muscle strength was 4/5 in upper extremity and 5/5 in lower extremity . He could eat with chopsticks , but awkwardly . He could walk without cane or aid , but slowly . No hypoesthesia was present . The JOA score increased from 10 to 15 -LRB- Table 1 -RRB- . Discussion Congenital disease , rheumatoid arthritis , fracture and dislocation , and other systemic diseases can cause the compression of the upper cervical spinal cord -LSB- 14 -RSB- . However , osteoma is one of the rare reasons . Osteoma is defined by WHO as a benign lesion consisting of well differentiated mature bone tissue with a predominantly laminar structure , and showing very slow growth . Osteomas are bosselated , round to oval sessile tumors that project from the subperiosteal or endosteal surfaces of the cortex -LSB- 3 -RSB- . They are composed of a composite of woven and lamellar bone that is frequently deposited in a cortical pattern with haversian-like systems . Some variants contain a component of trabecular bone in which the intertrabecular spaces are filled with hematopoietic marrow -LSB- 10 -RSB- . Osteoma usually occurs in the skull . Only occasionally have these lesions been reported in extracranial locations -LRB- Table 2 -RRB- . In 1980 , Pecker et al. reported the first osteoma in cervical inter-vertebral foramen . They used a Lateral interscalenic approach to excise the lesion -LSB- 8 -RSB- . In 1986 , Lantsman reported six cases of osteoma in spine , but the article was in Russian , no more details could be reviewed -LSB- 4 -RSB- . In 1993 -LSB- 5 -RSB- and 1996 -LSB- 6 -RSB- Laus reported the same case in Italian and English . To excise the lesion , they performed an anterior prevascular extra oral approach . In 1996 -LSB- 9 -RSB- , Peyser reported 11 cases of extracranial osteoma , in which five were in spine , one in the cervical spine , two in the lumbar spine and two in the scrum spine . In 1998 -LSB- 11 -RSB- , Rengachary reported that another osteoma affected the cervical spine . Table 2Cases reported in the literatureReferencesArticle languageCase numberSite of the lesionRecurredRengachary -LSB- 11 -RSB- English1CervicalNoPeyser -LSB- 9 -RSB- English5Cervical -LRB- 1 -RRB- , lumbar -LRB- 2 -RRB- , sacrum -LRB- 2 -RRB- One pain recurredLaus -LSB- 6 -RSB- English1CervicalNoLaus -LSB- 5 -RSB- Italy1CervicalNoLantsman -LSB- 4 -RSB- Russian6SpineNoPecker -LSB- 8 -RSB- French1CervicalNoTotal14aaLaus M. reported the same case in English and Italy The diagnosis of intra-canal osteoma is still confusing . In Peyser 's series -LSB- 9 -RSB- , none of the cases had correct diagnosis before the operation . In our cases , the rontgenographic study before operation could give some clues , but the final diagnosis still depended on the pathological findings . Histologically , the reactive bone induced by infection and trauma may be similar with a true osteoma -LSB- 10 -RSB- . However the differential diagnosis can be made by the tumor 's site and pertinent history . Traumatic reactive bones are most frequently observed in relation to the femur , beneath the quadriceps , in relation to the adductor magnus -LRB- the so-called rider 's bone -RRB- or in relation to the medial collateral ligament of the knee joint . The condition is also not infrequent at the elbow , the exostosis forming in the intermuscular planes of the brachialis following dislocation . Injury leads to the formation of a subperiosteal hemorrhage , the periosteum being detached by muscular traction . If the periosteum remains intact , the hematoma may become absorbed ; but if the periosteal reapposition and the absorption of the blood clot are prevented , traumatic bone overgrowth may occur . However , this condition could not occur at the endosteum . In the case of infective reactive bones , an infection history of relevant site should be noted . The clinical features of osteoma in the spine may be confusing . Cranial osteomas often cause no symptoms and are discovered incidentally , although these lesions may cause sinusitis or exophthalmus when they arise from the wall of the nasal sinuses or the orbit . It would be expected that the symptoms of spinal osteoma would depend on the location of the lesion and its relationship with the peripheral tissue . As Rengachary -LSB- 11 -RSB- and Laus -LSB- 5 , 6 -RSB- reported , the symptom of the spinal osteoma was caused from spinal cord or nerve root pressure . However in Peyser 's series all but one of the patients was symptomatic and had dull , aching pain at the time of the initial presentation . In our series , the two cases had no symptom before the injuries . It may be because osteomas are benign and very slow-growing lesions . And the spinal cord and never roots may adapt to the chronic pressure . Since the lesions cause spinal canal stenosis , they can cause the spinal cord to be more easily damaged by minor injury . The growth potential of osteoma remains unclear , as we know the cranial osteomas grow very slowly . Peyser 's excellent work showed us the growth potential feature of the spinal osteoma -LSB- 9 -RSB- . In their series , one patient who had a juxtacortical osteoma of the cervical spine , showed no major change on serial CT scans performed twelve years apart . However , another patient 's sacral osteoma showed significant growth on serial radiographs performed 18 years apart . The method of surgical management of an osteoma depends on the growth feature of the tumor . Cranial osteoma does not need surgical excision if there are no symptoms . The aim of surgical management of spinal osteoma is decompression and stabilization if instability exists . Rengachary and Laus performed total excision of the lesion , with no tumor recurrences . Peyser performed three total and two subtotal excisions , in the case series of osteomas , none recurred . However in one of the patients , partial resection of an osteoma from the body of the fifth lumbar vertebra resulted in no relief of pain and necessitated an additional procedure to remove the remainder of the lesion . In our series , it was relatively easy to perform an en bloc excision in the second case . In the first case , in view of a patient 's age and risk of vertebral artery injuries , a subtotal excision was performed , also with satisfied short time outcome . However , the follow-up was not long enough to observe the recurrence . Conclusion The incidence of intra-canal osteomas is rare . It can cause upper cervical myeolopathy . The rontgenographic study before operation can give some clues , but the final diagnosis still depends on the pathological findings . Surgical treatment , either en bloc or subtotal excision of the lesion , may be effective .

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


The Use of Herbal Medicine in Alzheimer 's Disease -- A Systematic Review The treatments of choice in Alzheimer 's disease -LRB- AD -RRB- are cholinesterase inhibitors and NMDA-receptor antagonists , although doubts remain about the therapeutic effectiveness of these drugs . Herbal medicine products have been used in the treatment of Behavioral and Psychological Symptoms of Dementia -LRB- BPSD -RRB- but with various responses . The objective of this article was to review evidences from controlled studies in order to determine whether herbs can be useful in the treatment of cognitive disorders in the elderly . Randomized controlled studies assessing AD in individuals older than 65 years were identified through searches of MEDLINE , LILACS , Cochrane Library , dissertation Abstract -LRB- USA -RRB- , ADEAR -LRB- Alzheimer 's Disease Clinical Trials Database -RRB- , National Research Register , Current Controlled trials , Centerwatch Trials Database and PsychINFO Journal Articles . The search combined the terms Alzheimer disease , dementia , cognition disorders , Herbal , Phytotherapy . The crossover results were evaluated by the Jadad 's measurement scale . The systematic review identified two herbs and herbal formulations with therapeutic effects for the treatment of AD : Melissa officinalis , Salvia officinalis and Yi-Gan San and BDW -LRB- Ba Wei Di Huang Wan -RRB- . Ginkgo biloba was identified in a meta-analysis study . All five herbs are useful for cognitive impairment of AD . M. officinalis and Yi-Gan San are also useful in agitation , for they have sedative effects . These herbs and formulations have demonstrated good therapeutic effectiveness but these results need to be compared with those of traditional drugs . Further large multicenter studies should be conducted in order to test the cost-effectiveness of these herbs for AD and the impact in the control of cognitive deterioration . Introduction Alzheimer 's disease -LRB- AD -RRB- is characterized as a progressive neurodegenerative disorder and considered as prominent cause of dementia in the elderly . The main characteristics of this disease are difficulties in household handling routine and cognitive and emotional disturbance in the elderly . The treatment of AD is a clinical challenge . With the development of cholinesterase inhibitors and a N-methyl-d-aspartate antagonist -LRB- memantine -RRB- , good perspectives have emerged in controlling the symptoms of AD . Therapeutic decisions have to be guided by clinical studies and should consider the physiopathogenesis and epidemiology of the disease . The main objective of these clinical trials is to reduce the Behavioral and Psychological Symptoms of Dementia -LRB- BPSD -RRB- and to improve cognition and the functional activity status , thus reducing the impairment of instrumental activities of the daily living -LRB- IADLs -RRB- and to lower the institutionalization rates -LRB- nursing home placement -RRB- . Unfortunately , only a limited number of trials have dealt with this topic and with follow-up periods shorter than two years . In spite of the absence of sufficient therapeutic effectiveness in mild and moderate AD , these drugs are still considered as the first line of treatment for AD -LRB- 1 -RRB- . Studies of cost-effectiveness suggest that memantine -LRB- 2,3 -RRB- and donepezil -LRB- 4 -RRB- are useful in the reduction of institutionalized care and/or cognitive impairment in patients with AD . Recently , two clinical trials showed no improvement of the cognitive deficit -LRB- 5,6 -RRB- or reduction in the institutionalization rate -LRB- 6 -RRB- . Searching for alternatives , many herbal products have been tested and employed in the treatment of AD , but with different clinical responses -LRB- 7 -RRB- . The assessment of these drugs through randomized controlled trials should be useful to identify effective products in the treatment of AD . Methods Searching at MEDLINE -LRB- during April 2006 , PubMed -RRB- , LILACS -LRB- Latin American and Caribbean Health Science Literature : 40th edition , May 2001 , the last research was performed in April 2006 -RRB- ; Cochrane Library -LRB- issue 1 , 2006 -RRB- ; Dissertation Abstract -LRB- USA , during April 2006 -RRB- ; ADEAR -LRB- Alzheimer 's Disease Clinical Trials Database , until April 2006 -RRB- ; National Research Register -LRB- 1/2006 -RRB- ; Current Controlled trials -LRB- the last research was performed in October 2005 -RRB- ; PsychINFO Journal Articles -LRB- during the year of 2006 -RRB- ; relevant web sites ; and scanning of reference list of relevant articles . There were no language or publication restrictions . Search for keywords in MeSH -LRB- medical subject heading -LRB- MeSH -RRB- with the words ` Alzheimer disease , dementia , cognition disorders ' was performed first . In the second part , the keywords were ` Herbal ' and ` Phytotherapy ' . The crossover results of the two searches were evaluated by the Jadad 's measurement scale -LRB- 8 -RRB- . Inclusion criteria : Three investigators independently reviewed all of the articles found . The articles were selected using the criteria listed below : The studies should be randomized ; double-blind and controlled -LRB- with a control group and a treatment group -RRB- . Studies should establish methodological procedures in the crossover or be conducted at the same time . In the case of being crossover , a washout period of at least 7 days was required . Patients included in the researches had their diagnosis rated into three degrees as follows : mild , moderate and severe forms of AD , according to the criteria from the National Institute of Neurological and Communicative Disorders and Stroke -- AD and Related Disorders Association -LRB- NINCDS-ADRDA -RRB- -LRB- 9 -RRB- . The models used were as follows : Mini-mental beginning values between 10 and 26 -LRB- initial and mild group -RRB- or < 10 -LRB- initial group -RRB- . Clinical trials should last for at least 1 month -LRB- 4 weeks -RRB- . Detailed description of the herbal product used . Neuropsychiatry symptoms progression should be measured with numerical score using the Assessment Scale -LRB- ADAS-noncog , range of score , 0 -- 70 -RRB- , NPI -LRB- Neuropsychiatric Inventory , range of score 0 -- 120 -RRB- , Clinical Global impression of change or Behavioral rating scale for Geriatric patients . The final score should be quantified using a combination of ADL and IADL methodological procedures . Exclusion criteria : The herbal product has already been target of a quantified systematic review study . In this case , only the results of the studies will be considered . Jadad 's measurement scale : Methodological quality was assessed using a scale developed and validated by Jadad et al. -LRB- 8 -RRB- . This scale assesses the completeness of reporting using three items with a five points maximum score . If the allocation into groups is explicitly randomized , item 1 is scored . A bonus point is given if an adequate method to generate the random sequence is described . If there is an explicit statement that the study is double-blind Item 2 is scored . A bonus point is given if the method is described and adequate . Item 3 is scored if there is either an explicit statement that all patients included were also analyzed or if the number and reasons for dropouts in all groups are given separately . For being classified as adequately reported a trial should score at least three of five points , a cut-off point is recommended by the author of the scale -LRB- 10 -RRB- . All extraction and quality assessments were performed by at least two independent reviewers using standard forms developed for each review . Disagreements were documented and discussed with final decisions made by the principal reviewer . Results Two herbs and two herbal formulations were identified to have effectiveness in the treatment of cognitive disturbance of AD in the systematic review : Salvia officinalis -LRB- 11 -RRB- , Melissa officinalis -LRB- 12 -RRB- , and Yi-Gan San -LRB- 13 -RRB- and Ba Wei Di Huang Wan -LRB- BDW -RRB- -LRB- 14 -RRB- . The main characteristics of the study are described in Table 1 . Gingko biloba was previously identified in one meta-analysis -LRB- 15 -RRB- , and only the conclusions of the study will be considered . Another study will be conducted with huperzine A , a product derived from a Chinese herb Huperzia serrata , to evaluate the safety and efficacy in the treatment of AD in a multicenter randomized controlled trial of its effect on cognitive function -LRB- 16 -RRB- . The studies of Salvia -LRB- 11 -RRB- , Melissa -LRB- 12 -RRB- , Yi-Gan San -LRB- 13 -RRB- and BDW -LRB- 14 -RRB- have reached Jadad 's measurement scale of ≥ 3 . The researches had a follow up of 1 month -LRB- Yi-Gan San -RRB- -LRB- 13 -RRB- , 2 months -LRB- BDW -RRB- -LRB- 14 -RRB- and 4 months -LRB- Salvia and Melissa -RRB- -LRB- 11,12 -RRB- . All samples studied were composed of patients with initial mild symptoms judged as AD . Two studies compared herbal medicines and control samples , using intention to treat -LSB- Salvia -LRB- 11 -RRB- and Melissa -LRB- 12 -RRB- -RSB- . None of the studies evaluated the institutionalization rate or compared the active principle with the current therapies with Acetyl Cholinesterase Inhibitor or memantine . Discussion The results of this systematic review identified four studies with methodological quality assessing S. officinalis -LRB- 11 -RRB- , M. officinalis -LRB- 12 -RRB- , Yi-Gan San -LRB- 13 -RRB- and BDW -LRB- 14 -RRB- . The last two are composed of formulations with different phytoactive agents . These herbs and formulations presented efficiency in reducing the mild and moderate symptoms of AD . Gingko biloba presented statistically significant mild effectiveness in the treatment of cognitive deficit in AD . The meta-analysis study of Cochrane -LRB- 13 -RRB- concluded that additional controlled studies would be necessary in order to recognize cognitive improvement with the use of gingko . There is still need of a prospective study with an appropriate duration and representative sample to identify if G. biloba reduces the development of AD -LRB- 17 -RRB- . Another plant with a large application perspective is H. serrata , after multicenter trial confirmation underway -LRB- 16 -RRB- . Melissa and Yi-Gan San showed reduction in the cognitive deficits and a good sedative effect in patients with AD -LRB- 12,13 -RRB- . Previous clinical studies showed that the extract of M. officinalis reduces laboratory-induced stress -LRB- 18 -RRB- and might have benefits in mood improvement -LRB- 19 -- 21 -RRB- . The use of these herbs and formulations should be well tolerated , -LRB- 22 -RRB- and adverse effects have not yet been reported -LRB- 23 -RRB- . Further studies should be conducted to compare the current therapies for AD and the use of these herbal remedies in controlling the symptoms of AD . The action mechanisms of these herbs and formulations are not well known . It has been suggested that the chemical composition of the essential oil of the Melissa and Salvia leaf extracts are monoterpene aldehydes , polyphenol flavonoids -LRB- including rosmarinic acid -RRB- -LRB- 24 -RRB- and monoterpene glycosides -LRB- 25 -RRB- . All of these components have many observable effects in vitro , which include powerful anti-oxidative activity -LRB- 26,27 -RRB- and an affinity to nicotinic and muscarinic receptor in the human cerebral cortex -LRB- 28 -RRB- . This last mechanism is of special interest , as modulation of cholinergic systems should play a role in improving the cognitive function , especially in AD . Yi-Gan San and BDW are mixes of many herbal ingredients . Yi-Gan San is a mixture of 7 different dried plants , many of them -LRB- Unticariae sinensis and Angelicae root -RRB- with possible actions in the serotoninergic and gaba system . BDW consists of 8 herbs : Rehmannia glutinosa Libosh . var purpurea Makino , Cornus officinalis Sieb et Zucc -LRB- Cornaceae -RRB- , Dioscorea batatas Decne root -LRB- Dioscoreaceae -RRB- , Alisma orientale Juzep rhizome -LRB- Alimataccae -RRB- , Poria cocos Wolf , Paeonia suffruticosa Andr . -LRB- Paeoniaceae -RRB- , Cinnamomum cassia Blume -LRB- Lauraceae -RRB- and Aconitum carmichaeli Debx . -LRB- Ranunculaceae -RRB- . Studies have suggested that BDW enhances the choline acetyltransferase activity and increases the acetylcholine content of the frontal cortex in a murine model -LRB- 29,30 -RRB- . Major methodological limitations of the four studies are small size of samples and short-term duration . There is no description of the chemical composition and/or possible active principles of the different products employed in studies Involving Yi-Gan San -LRB- 13 -RRB- and BDW -LRB- 14 -RRB- formulation -LRB- Table 1 -RRB- . In the study with BDW -LRB- 13 -RRB- , Sepia sp. and face powder were used as placebo ; however , the way that the shellfish formulation was performed was not described . In the control group of the study using the Yi-Gan-San -LRB- 14 -RRB- formulation , 25 mg per day of tiapride hydrochloride were introduced . This drug is a substituted derivative with selective dopamine D2-receptor antagonist properties . This intervention -LRB- contamination -RRB- occurred in 44 % of the individuals and was responsible for the symptoms , among them dizziness . Generally , crude herbal drugs are natural products and their chemical composition depends on several factors such as geographic source of the plant material , climate in which it was grown , and time of harvest . Commercially available herbal medicinal products also vary in their content and concentration of chemical constituents from batch to batch and when products containing the same herbal ingredient are compared between manufacturers . Even when herbal products are standardized for content of known active or marker compounds to achieve more consistent pharmaceutical quality , variations in the concentrations of other constituents can be observed . The use of a protocol such as the Consolidated Standards of Reporting Trials -LRB- CONSORT -RRB- , composed of 22 items , will probably minimize the limitations of RTC with phytotherapic agents -LRB- 31 -RRB- . The use of herbal medicines in the treatment of AD should be compared with the pharmacological treatment currently in use . Such studies should include the identification of the active principle in order to improve the validation of the clinical trial . Further large-scale , multicenter studies are necessary to determine the effectiveness of these substances in the cognitive deterioration of AD . Until then , this review provides some evidence of the benefit of Melissa , Salvia , Yi-Gan San and BDW in the treatment of AD .

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 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 B 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 B 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 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 B 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 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 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 B O O B 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 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 O O O O O O O O O O O O O O O O O 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 O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O 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 O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O 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 O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O 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 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 O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O 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 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 O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O 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 O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O 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 O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O

cognitive impairment
dementia
elderly
herbs
systematic review

alzheimer's disease
randomized clinical trial