Op

tica

l C

oh

ere

nce

To

mo

gra

ph

y (

OC

T)

(1)

OC

Tper

form

scr

oss

-sec

tional

imag

ing

by

mea

suri

ng

the

bac

ksca

tter

edlig

ht

from

sam

ple

s.

•T

he

inte

rfer

om

etri

c bio

psy

allo

ws

hig

h-s

pee

d v

isual

izat

ion o

f ti

ssue

wit

h h

igh s

pat

ial re

solu

tion.

•R

eal-ti

me

imag

ing w

ith h

igh r

esolu

tion c

an b

e im

ple

men

ted.

•T

he

fiber

-bas

ed d

esig

n is

com

pac

t an

d p

ort

able

and a

llow

s in

tegra

tion w

ith c

athet

er/e

ndosc

ope.

•N

o n

eed t

o u

se f

luore

scen

t st

ains

or

tags.

Adva

nta

ges

•H

igh r

esolu

tion

•G

reat

pro

bin

g d

epth

( <

2 c

m f

or

eye,

1-2

mm

for

smal

l blo

od v

esse

ls)

•R

elat

ive

sim

plic

ity,

low

har

dw

are

cost

Op

tica

l C

oh

ere

nce

To

mo

gra

ph

y (

OC

T)

(2)

Op

tica

l C

oh

ere

nce

To

mo

gra

ph

y (

OC

T)

(3)

sr

EE

dE

EE

EI

sr

sr

d

rE

sE

Op

tica

l C

oh

ere

nce

To

mo

gra

ph

y (

OC

T)

(4)

sr

EE

Gt

Et

EE

EE

EI

sr

sr

sr

rE

sE

Op

tica

l C

oh

ere

nce

To

mo

gra

ph

y (

OC

T)

(5)

Issu

es invo

lved

in t

he

des

ign o

f th

e O

CT

sys

tem

Op

tica

l C

oh

ere

nce

To

mo

gra

ph

y (

OC

T)

(6)

Op

tica

l C

oh

ere

nce

To

mo

gra

ph

y (

OC

T)

(7)

OC

T im

age

and

his

tolo

gic

al

sect

ion f

rom

a

hea

vily

cal

cifi

ed

hum

an a

ort

a

Bio

imag

ing

: op

tica

l d

iffu

sio

n t

om

og

rap

hy

Light

pas

sing

thro

ugh

ahig

hly

scat

teri

ng

med

ium

mea

sure

d

Unkn

ow

nab

sorp

tion

and/o

rdif

fusi

on

cross

-sec

tion

of

mat

eria

ldet

erm

ined

KM

mea

sure

men

tsper

form

edw

ith

Kso

urc

esan

dM

det

ecto

rs

Tim

e-dom

ain

mea

sure

sdel

ayof

light

puls

eat

det

ecto

r.

Freq

uen

cyd

om

ain

mea

sure

sam

plit

ude/

phas

eof

modula

ted

light

enve

lope.

Als

okn

ow

nas

dif

fuse

opti

cal

tom

ogra

phy

or

photo

n

mig

rati

on

Dete

rmin

ati

on

of

ph

oto

n p

ath

s in

a t

issu

e

ct

Ds

a

as

: ab

sorp

tion c

oef

fici

ent

: photo

n f

lux

c

: s

pee

d o

f lig

ht

in t

he

med

ium

: sc

atte

ring c

oef

fici

ent

Da

s:

dif

fusi

on c

onst

ant

hig

h s

catt

erin

glo

w a

bso

rpti

on

Dif

fusi

on

ap

pro

xim

ati

on

the

in-v

ivo

chara

cter

izati

on a

nd m

easu

rem

ent

of

bio

logic

al

pro

cess

es o

n t

he

cellu

lar

and m

ole

cula

rle

vel th

rough t

he

use

of

imagin

g d

evic

es”

--D

.J.

Wagen

aar

PET

Biolu

min

esce

nce

im

agin

gFl

uore

scen

ce

imag

ing

Rep

ort

er G

ene

Nat

ura

l bio

logic

al

mole

cule

slu

cife

rase

GFP

Label

sPo

sitr

on-

emit

ting iso

topes

(1

5O

, 1

1C

)lu

cife

rin

Light

illum

inat

ion

Imag

ing T

ools

Scin

tilla

tor

crys

tal

+ P

MT

CC

D,

PMT

CC

D,

PMT

Mo

lecu

lar

imag

ing

From

GE

-Am

ersh

am p

rese

ntat

ion

Mo

lecu

lar

imag

ing

In s

itu

real-ti

me d

ete

ctio

n i

s p

oss

ible

.•

Volu

met

ric

spec

trosc

opy:

M

easu

re t

he

opti

cal pro

per

ties

of

each

voxel

at

eac

h s

pec

tral

w

avel

ength

•Fl

uore

scen

t ag

ents

: U

se n

ear

IR

or

visi

ble

flu

ore

scen

t tr

acer

s to

en

han

ce c

ontr

ast

•Fl

uore

scen

t lif

e-ti

me

imag

ing:

Tim

e-dec

ay p

roper

ties

of

fluore

scen

t si

gnal

pro

vide

info

rmat

ion

•Fu

nct

ional

im

agin

g:

Mea

sure

dyn

amic

pro

per

ties

of

trac

er

upta

ke f

or

applic

atio

ns

such

as

phar

mac

oki

net

ics

•M

ole

cula

r im

agin

g:

Dev

elop

fluore

scen

t tr

acer

s th

at a

re

des

igned

to p

robe

spec

ific

m

ole

cula

r pro

per

ties

and t

arget

par

ticu

lar

tiss

ues

(e.

g., t

um

ors

)

•Sa

fety

: N

o r

adio

acti

ve e

xposu

re

•Po

rtab

le:

Does

not

requir

e la

rge

mag

net

or

gam

ma

cam

era

•Fa

st:

Can

pote

nti

ally

ach

ieve

hig

h f

ram

e ra

tes

com

par

ed t

o

PET

or

MR

I

•In

expen

sive

: does

not

requir

e co

her

ent

light

•Sp

atia

l re

solu

tion

–N

eeds

to b

e hig

h e

nough t

o

separ

ate

tiss

ues

of

inte

rest

–D

oes

not

hav

e re

solu

tion o

f C

T o

r M

RI

–Se

ems

reas

onab

le t

o e

xpec

t 1m

m r

esolu

tion 1-1

0 c

m

dep

th

Op

tica

l to

mo

gra

ph

y

Bio

-im

ag

ing

: Near-

Infr

are

d S

pect

rosc

op

y (

NIR

S),

a.k

.a.,

In-v

ivo

Dif

fuse

Op

tica

l Im

ag

ing

(1

)

•M

ole

cula

r im

agin

g

•D

iffu

se (

NIR

) im

agin

g (

tom

ogra

phy)

-Br

ain

Stra

hle

r, B

iol.

Psyc

h., 2

002

Bio

-im

ag

ing

: Near-

Infr

are

d S

pect

rosc

op

y (

NIR

S),

a.k

.a.,

In-v

ivo

Dif

fuse

Op

tica

l Im

ag

ing

(2

)

•D

iffu

se (

NIR

) im

agin

g (

tom

ogra

phy)

-T

issu

e-

Cas

e R

evie

w (

CW

): Inva

sive

Duct

al C

arci

nom

a (P

N6

01

5)

Dep

th:

1.8

53

.85

4.8

5 c

m

X-r

ay

78

0 n

m

83

0 n

m

Mo

nte

Carl

o s

imu

lati

on

Tiss

ue M

ediu

m

?

inou

t

Dif

fusi

on t

heo

ryM

onte

Car

lo

g=0.9

g=0.5

g=0 (

isotr

opic

)

Dif

fusi

on

theo

ry

Monte

Car

lo

sim

ula

tion

Bio

-im

ag

ing

: Near-

Infr

are

d S

pect

rosc

op

y (

NIR

S),

a.k

.a.,

In-v

ivo

Dif

fuse

Op

tica

l Im

ag

ing

(3

)

htt

p:/

/ww

w.x

enogen

.com

CW

•si

mple

st a

ppro

aches

usi

ng C

CD

•no f

luore

scen

ce lif

etim

e in

fo

Xen

og

en

: C

W b

iolu

min

esc

en

ce i

mag

ing

Xen

og

en

: C

W b

iolu

min

esc

en

ce i

mag

ing

KO

DA

K I

mag

e S

tati

on

20

00

MM

: C

W

Sim

ilar

to P

ET/C

T

Com

bin

atio

n o

f C

T a

nd

bio

lum

ines

cence

Abso

rpti

on a

nd

scat

teri

ng f

rom

es

tim

ated

CT

num

ber

s

Not

accu

rate

way

of

com

bin

ing t

he

two

Bio

lum

inesc

en

ce /

CT

G. W

an

g (

U. Io

wa)

Flu

ore

scen

ce m

ole

cula

r to

mo

gra

ph

y

V. N

tzia

chri

sto

s, R

. W

eis

sled

er

(MG

H)

Flu

ore

scen

ce m

ole

cula

r to

mo

gra

ph

y

V. N

tzia

chri

sto

s, R

. W

eis

sled

er

(MG

H)

•M

odula

tes

light

amplit

ude

usi

ng R

F so

urc

e at

fre

quen

cy f

.

•M

easu

res

mag

nit

ude

and p

has

e of

opti

cal det

ecto

r's

signal

.

•Sc

atte

ring a

nd a

bso

rpti

on c

han

ge

mag

nit

ude

and p

has

e of

det

ecte

d s

ignal

.

•Ea

ch m

easu

rem

ent

is a

com

ple

x n

um

ber

.

•Sp

ecia

l ca

se:

If f

= 0

, th

is is

know

n a

s co

nti

nuous

wav

e (C

W)

mea

sure

men

t.

Op

tica

l to

mo

gra

ph

y: f

req

uen

cy-d

om

ain

ap

pro

ach

es

Fre

qu

en

cy-d

om

ain

ap

pro

ach

es

Fre

qu

en

cy-d

om

ain

im

ple

men

tati

on

Fre

qu

en

cy-d

om

ain

im

ple

men

tati

on

Sevic

k-M

ura

ca, T

exas

A&

M

Fre

qu

en

cy-d

om

ain

im

ple

men

tati

on

Sevic

k-M

ura

ca, T

exas

A&

M

Short

puls

e of

light

is u

sed a

s an

opti

cal so

urc

e.Li

ght

trav

els

to d

etec

tor

along d

iffe

rent

pat

hs

due

to s

catt

erin

g.

Syst

em m

easu

res

tim

e dom

ain r

esponse

, s(

t),

at o

pti

cal det

ecto

rs.

The

syst

em c

an d

o t

he

fluore

scen

ce lif

etim

e im

agin

g.

Op

tica

l to

mo

gra

ph

y: t

ime-d

om

ain

ap

pro

ach

es

ct

Ds

a

Tim

e dom

ain

•Ball

isti

c p

ho

ton

s: c

oher

entl

y sc

atte

red lig

ht

that

pro

pag

ates

in t

he

forw

ard d

irec

tion,

trav

els

the

short

est

pat

h,

and c

arri

es m

axim

um

in

form

atio

n o

n t

he

inte

rnal

str

uct

ure

of

the

tiss

ue.

•Sn

ake

photo

ns:

port

ions

of

light

that

sca

tter

in w

iggly

tra

ject

ori

es,

still

in

the

forw

ard d

irec

tion.

Tim

e-del

ayed

wit

h r

espec

t to

bal

listi

c photo

ns,

yet

st

ill c

arry

info

rmat

ion o

n t

he

scat

teri

ng m

ediu

m.

•D

iffu

se p

ho

ton

s: m

ost

port

ions

of

the

light

bea

m t

hat

under

go m

ult

iple

sc

atte

ring,

trav

el long d

ista

nce

s w

ithin

med

ium

, an

d c

arry

lit

tle

info

rmat

ion o

n t

he

tiss

ue.

To b

e dis

crim

inat

ed a

gai

nst

.

Op

tica

l to

mo

gra

ph

y: t

ime-d

om

ain

ap

pro

ach

es

GE

Amer

sham

Tim

e-d

om

ain

: GE/A

RT

Exp

lore

Op

tix

Bio

-im

ag

ing

: Near-

Infr

are

d S

pect

rosc

op

y (

NIR

S),

a.k

.a.,

In-v

ivo

Dif

fuse

Op

tica

l Im

ag

ing

(6

)

Basi

c co

nce

pt

of

fluore

scen

t ta

ggin

g

Fluoro

phore

pro

vides

enhan

ced c

ontr

ast

Wit

h t

arget

ed d

eliv

ery

: si

te-s

pec

ific

im

agin

g (

e.g.

tum

ors

)Fl

uoro

phore

abso

rbs

ener

gy

at e

xci

tati

on w

avel

ength

, x

Fluoro

phore

re-

emit

s at

em

issi

on w

avel

ength

, m

Flu

ore

scen

ce-b

ase

d o

pti

cal

dif

fusi

on

to

mo

gra

ph

y

Op

tica

l to

mo

gra

ph

y: c

om

pari

son

* Fr

equen

cy d

om

ain: sa

me

char

acte

rist

ics

as t

ime

dom

ain

Near-

field

vs.

far-

field

Seo

ul A

rts

Cen

ter

Near-

field

an

d f

ar-

field

im

ag

ing

Bio

-im

ag

ing

: Near-

Fie

ld S

can

nin

g O

pti

cal

Mic

rosc

op

y (

NSO

M o

r SN

OM

)

•C

om

bin

atio

n o

f a

subw

avel

ength

ap

ertu

re t

o illu

min

ate

an o

bje

ct w

ith

a det

ecto

r ve

ry c

lose

to t

he

sam

ple

ac

com

plis

hes

hig

h r

esolu

tion b

y non-d

iffr

acti

on lim

ited

pro

cess

.

•U

se o

f a

subw

avel

ength

aper

ture

is

achie

ved b

y a

taper

ed o

pti

cal fi

ber

w

ith a

tip

rad

ius

< 1

00

nm

.

•Im

port

ant

to k

eep t

he

opti

cal pro

be

at a

const

ant

dis

tance

fro

m t

he

sam

ple

surf

ace.

Ph

oto

aco

ust

ic t

om

og

rap

hy (

PA

T)

Ph

oto

aco

ust

ic t

om

og

rap

hy (

PA

T)

Hz

mm

μmμm

Mvx

/s

Ph

oto

aco

ust

ic t

om

og

rap

hy (

PA

T)

in v

ivo