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Page 1: Biomedical Imaging II

BMI II SS06 – Class 6 “OT Instrum.” Slide 1

Biomedical Imaging IIBiomedical Imaging II

Class 6 – Optical Tomography II: Instrumentation

03/13/06

Page 2: Biomedical Imaging II

BMI II SS06 – Class 6 “OT Instrum.” Slide 2

Measurement principleMeasurement principle

Measure optical intensity migrating from small irradiation spot (source, S) to detector (D) position

“Scan” object to obtain measurements for many S-D pairs

Light propagation is scatter-dominated Signals are obtained under any angle

Signal is strongest near source (backscattered)

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BMI II SS06 – Class 6 “OT Instrum.” Slide 3

DOT characteristics summaryDOT characteristics summary

Functional imaging method

Sensitive to hemoglobin oxygenation states (contrast mechanism)

Low spatial resolution (~mm - ~cm)

Excellent temporal resolution (~ms), capability of studying hemodynamics

DOT assesses tissue function rather than providing an accurate image of anatomical features.

Examples: breast cancer, functional brain imaging

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BMI II SS06 – Class 6 “OT Instrum.” Slide 4

Continuous Wave (C.W.) MeasurementsContinuous Wave (C.W.) Measurements

Simplest form of OT: lowest spatial resolution, “easy” implementation, greatest penetration

Measuring transmission of constant light intensity (DC)

Simple, least expensive technology most S-D pairs

High “frame rates” possible

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BMI II SS06 – Class 6 “OT Instrum.” Slide 5

Example: Optical brain imagingExample: Optical brain imaging

“Partial view” or back reflection geometry

Scalp

Bone

Cortex

CSF

2-3 cm

Source / Detector 1

Detector 2

Detector 3

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BMI II SS06 – Class 6 “OT Instrum.” Slide 6

Time-Resolved MeasurementsTime-Resolved Measurements

Measuring the arrival time/temporal spread of short pulses (<ns) due to scattering & absorption (narrowing the “banana”)

Expensive, delicate hardware (single-photon counters, fast lasers, optical reflections, delays…)

Long acquisition times (low frame rates)

Potentially better spatial resolution than DC measurements

t

I

t0 t

I

t0

Prompt or ballistic Photons (t = d/c)

d

“Snake” Photons

Diffuse Photons

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BMI II SS06 – Class 6 “OT Instrum.” Slide 7

Frequency-Domain MeasurementsFrequency-Domain Measurements

Propagation of photon density waves (PDW): PDW = 9 cm, cPDW = 0.06 c (*

Measure PDW modulation (or amplitude) and phase delay

RF equipment (100MHz-1GHz)

Wave strongly damped, challenging measurement

t

I

t0

t

I

t0

t

I

t0Photon density waves

t

I

t0

Phase

Modulation

(* f = 200 MHz, μa = 0.1 cm-1, μs’ = 10 cm-1 n = 1.37

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BMI II SS06 – Class 6 “OT Instrum.” Slide 8

Principle components of a DOT system Principle components of a DOT system

Target

Lightsource

Delivery

Sourcescan

Detector

Detectorscan

DAQstorage

Timing,control

Collection

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BMI II SS06 – Class 6 “OT Instrum.” Slide 9

Multi-detector implementationMulti-detector implementation

Scanning of single detector (only used in lab setups):

• Safes hardware components, cost

• Long acquisition times

Parallel multi-detector acquisition

• No “time skew”

• Stable setup

• Added hardware

Mixed approach (Scanning limited number of detectors)

• Feasible for “static imaging”

• Used in TR, FD methods because of expensive detection hardware

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BMI II SS06 – Class 6 “OT Instrum.” Slide 10

Multi-source position implementationMulti-source position implementation

Time-division multiplexing : One source position is illuminated at one time for the duration of the detection (~10-100 ms).

Time skew between sources

Switching mechanism necessary:

• Optical switch (challenges: isolation, stability, size)

• Electronic switching of multiple sources (multiple laser sources & drivers – cost, complexity)

Frequency encoding: All sources are on at the same time.

Intensity modulation at different frequencies allows electronic separation of the signals originating from different sources.

No time skew

Reduced dynamic range

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BMI II SS06 – Class 6 “OT Instrum.” Slide 11

Dynamic rangeDynamic range

Ratio of largest to smallest “useable” signal (saturation limit noise limit)

Typically 1:104 (80 dB) for detection electronics

Signal falls of rapidly (~ factor 10 per cm distance on surface)

Determines the maximum tissue volume that can be probed

With second sourceOne source

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BMI II SS06 – Class 6 “OT Instrum.” Slide 12

Solution: Detector gain switchingSolution: Detector gain switching

I1

12 10

II

13 100

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14 1,000

II

15 10,000

II

S1

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0 1

0 1

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S2

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BMI II SS06 – Class 6 “OT Instrum.” Slide 13

Semiconductors ISemiconductors I

Energy levels in solids have band structure :

Thermal excitation creates intrinsic carriers (electron-hole pairs): ni = np 1.51010 cm-1 (Si at room temperature, kT = 0.025 eV)

Photoelectric excitation possible for

g gh E hc E

Valence band

Conduction band

Ele

ctro

n en

erg

y

Bound electrons

Free electrons

Eg < 5 eV for insulatorEg 1 eV for semiconductorEg = 0 eV for metals

+

-

22 3

gE

kTi in p T e

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BMI II SS06 – Class 6 “OT Instrum.” Slide 14

Semiconductors IISemiconductors II

Doping with impurities increases number of free carriers (~ typ. by factor of 107) according to Ea,d 0.045 < kT

Donor: Pentavalent impurity (e.g., P) provides excess e- n-type semiconductor

Acceptor: Trivalent impurity (e.g., B) “captures” e- creates additional holes p -type semiconductor

Internal photoelectric effect:

Donor doped: n-type

Acceptor doped: n-type

, ,a d a dh E hc E

Ed

Ea

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BMI II SS06 – Class 6 “OT Instrum.” Slide 15

Diode junction of p-type and n-type semiconductors:

1. Diffusion of carriers potential across junction (n-type is left positively charged, p-type is left negatively charged)

2. Recombination at junction region of depletion of free carriers high resistance voltage drop

3. Carriers generated within diffusion length of the depletion region are separated by potential slope

4. Photoelectric current Ip produced by

photodiode (proportional to irradiation intensity)

Photodiodes (PD)Photodiodes (PD)

+ --

- - -

- --

- --

-++

+ ++

+ ++

++

+p n

Diffusion lengthNegative

net chargePositive

net charge

Anode CathodeIp

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BMI II SS06 – Class 6 “OT Instrum.” Slide 16

Photodiode OperationPhotodiode Operation

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BMI II SS06 – Class 6 “OT Instrum.” Slide 17

Photodiode (Transimpedance) AmplifierPhotodiode (Transimpedance) Amplifier

Converts photocurrent to voltage according to:

Bandwidth:

Highly linear

“Photovoltaic Mode”

out PD fV I R

3

1

2dbf

fRC

PD

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BMI II SS06 – Class 6 “OT Instrum.” Slide 18

PD characteristicsPD characteristics

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BMI II SS06 – Class 6 “OT Instrum.” Slide 19

Photomultiplier tubes (PMT)Photomultiplier tubes (PMT)

External photoelectric effect converts light intensity into current of free electron

Cascade of secondary electron emission / multiplication

Signal amplification G = N typ. ~106 (N: no. of dynodes, : gain per dynode ~4)

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BMI II SS06 – Class 6 “OT Instrum.” Slide 20

PMT spectral sensitivityPMT spectral sensitivity

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BMI II SS06 – Class 6 “OT Instrum.” Slide 21

Avalanche PhotodiodesAvalanche Photodiodes

Reverse biased with high voltage (~100V)

Internal 10-1000× amplification through avalanche effect

Gain temperature sensitive -> requires cooling/regulation

Available in ready-to-use modules

Pricey

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BMI II SS06 – Class 6 “OT Instrum.” Slide 22

Comparison PD vs. PMTComparison PD vs. PMT

Property PD PMT

Sensitivity 10-12 W 10-15 - 10-16 W

Active area ~ mm2 ~ cm2

Speed MHz - GHz (small area) ~ GHz

Dynamic range >109 <105

Size Small (mm) Medium to large (~cm)

Power supply Low voltage High voltage (~0.1-1 kV)

Ruggedness Very good Limited

Cost Cheap – moderate (~$10) Expensive (~$100)

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BMI II SS06 – Class 6 “OT Instrum.” Slide 23

Light sources ILight sources I

Near infrared range (600-900 nm)

Power ~1-100 mW: Signal quality vs. exposure limit (~ mW/mm2)

Laser diodes (semiconductor lasers): Most widely used

+ Small

+ Inexpensive (o.k…. ~$10 - $1000)

+ High efficiency, easy-to-operate

+ RF modulation possible

+ ps-pulsed systems available

(Poor beam quality)

Discrete wavelengths (760, 785, 800, 810, 830,.. nm)

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BMI II SS06 – Class 6 “OT Instrum.” Slide 24

Semiconductor-based light sourcesSemiconductor-based light sources

“Forward bias” causes reduction of potential wall diode in conducting mode

Electrons and holes recombine in depletion layer, carriers are replenished by current source

Emitting of recombination radiation light emitting diode

For special diode geometries and reflecting end faces, laser action can be achieved laser diode

+ --

- - -

- --

- --

-+ +

+ ++

+ ++

++

+p n

+

-- - -- ---

--

--

+ ++ +

++ ++ ++ + + + +

-

+ +

LED

LD

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BMI II SS06 – Class 6 “OT Instrum.” Slide 25

Types of laser diodesTypes of laser diodes

“Butterfly”

“HHL”

“TO3”

“C-mount”

“5-mm can /9-mm can:”Low / mid-power (mW-100 mW)

Hi-power (~W)

Hi-power (~W)

“Fiber pigtail”

Telco app.

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BMI II SS06 – Class 6 “OT Instrum.” Slide 26

Laser diode driversLaser diode drivers

Laser diodes require a controlled current source

LD are highly sensitive to ESD, short pulses, and all kinds of electromagnetic interference

Line filters

Power on ramping

Off shorting

LD require cooling and often temperature control to stabilize the output power Thermoelectric cooling (TEC) elements

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BMI II SS06 – Class 6 “OT Instrum.” Slide 27

Light sources IILight sources II

Solid state lasers: Optically active crystals (TiSa)

+ Short pulses (< ps, time-resolved systems)

+ Good beam profile

Bulky (requires pump laser)

Expensive

Difficult to operate

Non-laser sources: light emitting diodes (LED)

Broad wavelength range

Diffuse emitter

Power ~ 10mW

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BMI II SS06 – Class 6 “OT Instrum.” Slide 28

Snells’ law:

Total internal reflection for > c when going from n1 to n2 < n1:

Fiber components:

Core (n1)

Cladding (n2)Coating (mechanical stab.)

n1 > n2 “guided modes”

Light propagation in optical fibers ILight propagation in optical fibers I

01

0 1

sin

sin

n

n

0

1

2

1

sin c

na

n

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BMI II SS06 – Class 6 “OT Instrum.” Slide 29

Light propagation in optical fibers IILight propagation in optical fibers II

Acceptance angle a: Maximum incoupling angle ai resulting in guided transmission:

“Numerical Aperture” NA = sin a

Divergence angle: Maximum exiting angle ad (ai ad aa)

2 21 2

0

1sin a n n

n

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BMI II SS06 – Class 6 “OT Instrum.” Slide 30

Properties of some optical materialsProperties of some optical materials

Important interfaces

Various fiber materials

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BMI II SS06 – Class 6 “OT Instrum.” Slide 31

Fiber modesFiber modes

Different modes of optical propagation = different spatial intensity patterns

Number of possible modes depending on core radius, refractive indices

Multimode (MM) fibers

large core > 50 m

Higher efficiency

Higher power

(Cheaper)

Single-mode (SM) fibers

small core < 10 m

Better beam quality

No pulse shape

distortion (Telecom apps)

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BMI II SS06 – Class 6 “OT Instrum.” Slide 32

Intensity profile for MM fibersIntensity profile for MM fibers

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BMI II SS06 – Class 6 “OT Instrum.” Slide 33

Fiber transmission lossesFiber transmission losses

Absorption losses

Bending losses

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BMI II SS06 – Class 6 “OT Instrum.” Slide 34

Coupling light into optical fibersCoupling light into optical fibers

Focusing optics must provide:

Focus spot size s core diameter

Beam convergence angle acceptance angle

Mechanical alignment:

Focus on fiber core front face (x-y-z)

Beam perpendicular to front face (-)

Fiber face cut, polished

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BMI II SS06 – Class 6 “OT Instrum.” Slide 35

DYNOT system (best DOT imager around!!!)DYNOT system (best DOT imager around!!!)

referencesignals

Target

LD 1

Incouplingoptics

MDU

Source fiber bundles

Collecting fiberbundles

Laser current

DPS 1

Laserdiodes

Fiberpigtails

Motor controller

Beamsplitter

LD 2

Laser controller

Mirror

DPS 2

PCI busData acquisition

board

Measuringhead

OTDM

LDD + TECD

LDD + TECD

f 1 f 1

f 2 f 2

Personalcomputer

Bifurcatedfibers

Referencesignals

1

2

3

4

5

6

7

8

910

11

12

13

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BMI II SS06 – Class 6 “OT Instrum.” Slide 36

Fiber OpticsFiber Optics

Deliver light to/from tissue

Bifurcated design ( co-located S/D pairs)

Source fiber bundle

Detector fiber bundle

Probing end

Reinforced jacketing

Soft jacket

Bifurcation

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BMI II SS06 – Class 6 “OT Instrum.” Slide 37

Laser DiodesLaser Diodes

Laser Diodes

780 nm

830 nm

“Fiber pigtails” = opt. output

Electrical connectors

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BMI II SS06 – Class 6 “OT Instrum.” Slide 38

Laser ControllerLaser Controller

Commercial Newport 8000 Laser diode and temperature controller

Thorlabs Inc. OEM laser driver

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BMI II SS06 – Class 6 “OT Instrum.” Slide 39

Fast Multi-Channel Optical SwitchFast Multi-Channel Optical Switch

Multi-wavelength

32 fibers

~70 Hz switch speed = 2Hz frame rate @ 30 sources

fiber pigtails

incoupling unit

circular fiber array

DC servomotor

beam-splitter cube

focusing optics

rotating mirror

source fiber bundles

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BMI II SS06 – Class 6 “OT Instrum.” Slide 40

Commercial fiber-optic switchCommercial fiber-optic switch

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BMI II SS06 – Class 6 “OT Instrum.” Slide 41

Multi-Channel Detector Multi-Channel Detector

Gain switching

32 Parallel detection channels

Electronic wavelength separation

Gain Setting of detector determines its sensitivity

Gain (TTL) S/H

Out @

Out @

Ref. f2

PTIA

PTIA

PGA

PGA

Lock-in@ f2

Lock-in@ f2

S/HS/HLock-in@ f1

Lock-in @ f1

SiPD

1 1000

S/HS/H

1 1000

Ref. f1

Page 42: Biomedical Imaging II

BMI II SS06 – Class 6 “OT Instrum.” Slide 42

The DYNOT (DYnamic Near-infrared OT) InstrumentThe DYNOT (DYnamic Near-infrared OT) Instrument

7

3

4

5

1

2

9

8

1

2

3

4

5

5

6

6

1 – power supply, 2 – motor controller, 3 – detector, 4 – laser controller, 5 – host PC w/ monitor, 6 – fiber optics, 7 – optical switch, 8 – optics shielding cover, 9 – laser diodes

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BMI II SS06 – Class 6 “OT Instrum.” Slide 43

HelmetHelmetHelmet kit can be configured depending on application

Probes individually spring loaded

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BMI II SS06 – Class 6 “OT Instrum.” Slide 44

Measurement GeometriesMeasurement Geometries

1. Unilateral temporal arrangement (motor cortex)

2. Distributed Arrangement (frontal, temporal, parietal)

3. Installing / adjusting the optical probes

4. Complete 56 arrangement 30 sources 30 detectors = 900 data channels

1

2

3 4

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BMI II SS06 – Class 6 “OT Instrum.” Slide 45

Baby HelmetBaby Helmet

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BMI II SS06 – Class 6 “OT Instrum.” Slide 46

Dual Breast Measurement HeadDual Breast Measurement Head

Patient in prone position

Simultaneous dynamic bilateral breast imaging

Fiber protrusion individually adjusted (manually; pneumatic possible)

Measuring cup positions individually adjusted

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BMI II SS06 – Class 6 “OT Instrum.” Slide 47

Highly Flexible 2×-Breast SetupHighly Flexible 2×-Breast Setup

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BMI II SS06 – Class 6 “OT Instrum.” Slide 48

Adjusting MechanismAdjusting Mechanism

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BMI II SS06 – Class 6 “OT Instrum.” Slide 49

Probe PlacementProbe Placement

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BMI II SS06 – Class 6 “OT Instrum.” Slide 50

Optical Fibers

Animal Imaging StudiesAnimal Imaging Studies