Introduction to Biophotonics for Medical Applications

Summarized by:Name: AGNES Purwidyantri

Student ID No: D0228005

Biophotonics is the science of generating and harnessing light (photons) to image,

detect and manipulate biological materials

What is Biophotonics?

Optical Manipulation

TransfectionThe transfer of exogenous DNA into a cell

Femtosecond Laser Mediated Cell

Membrane Poration

Photoporation: the use of light to permeabilise cells. First inspired

from a Tirlapur and Konig, Nature 2002:

Used a near-infrared, femtosecond-pulsed laser beam (λ

800 nm) from an 80-MHz titanium–sapphire laser, with a mean power of 50–100 mW and

tightly focused using a high-numerical-aperture objective

Linear Fluorescence Microscopy

Introduction to Optical Coherence Tomography (OCT)

OPTICAL BIOPSY: The in situ imaging of tissue microstructure with a

resolution approaching that of histology, but without the need for tissue excision and processing

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Optical Coherence TomographyThree-dimensional imaging technique with

ultrahigh spatial resolution even in highly scattering media

Based on measurements of the reflected light from tissue discontinuitiese.g. the epidermis-dermis junction.

Based on interferometryinvolves interference between the reflected

light and the reference beam.

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OCT vs. standard imaging

1 mm 1 cm 10 cm

Penetration depth (log)

1 mm

10 mm

100 mm

1 mm

Resolution (log)

OCTConfocalmicroscopy

Ultrasound

Standardclinical

Highfrequency

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OCT in non-invasive diagnosticsOphthalmology

diagnosing retinal diseases.

Dermatologyskin diseases,early detection of skin

cancers.Cardio-vascular diseases

vulnerable plaque detection.

Endoscopy (fiber-optic devices)gastrology,…

Functional imagingDoppler OCT,spectroscopic OCT,optical properties,PS-OCT.

• Guided surgery– delicate procedures– brain surgery,

knee surgery, …

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The OCT setup

Broadbandsource

Detector

Fiber-opticbeamsplitte

r

TissueScanningreference mirror

Computer

Amplifier Bandpass filter

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Interference

- 6 - 4 - 2 0 2 4 6Dl@lD1

1.5

2

2.5

3

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ytisnetni

- 6 - 4 - 2 0 2 4 6Dl@lD1

1.5

2

2.5

3

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Michelson interferometer

light source

Detector

Coherent source

Partially coherent source

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Construction of image

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Normal Eye

Nominal width of scan: 2.8 mm

250 micronsHumphrey

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UHR-OCT versus commercial OCT

mm

mm

W. Drexler et al., “Ultrahigh-resolution ophthalmic optical coherencetomography”, Nature Medicine 7, 502-507 (2001)

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System perspective

OCT imaging engine• Resolution• Reference delay scanning• Doppler/polarization/spectroscopy• Detection• Frequency domain

Light sources• Superluminescent diodes• Semiconductor amplifiers• Femtosecond lasers• …

Beam delivery and probes• Hand-held probe• Catheter• Ophthalmoscope• Microscope

Image & signal processing• Motion reduction• Speckle reduction• Image enhancement• Rendering algorithms• …

Computer control• Drive system• Real-time display• Data management

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Choosing the light sourceFour primary considerations

wavelength,bandwidth,power (in a single-transverse-mode),stability;

portability, ease-of-use, etc.

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Choose light source – wavelength

Light propagation (Monte Carlo simulation)

Incident light

Ballistic component

“Snake” component

Diffuse reflectance

Absorption

Diffuse transmittance

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Ultra-high resolution OCTBroad bandwidth sources

solid-state lasers,sub-5 fs pulse;

Ti:Al2O3 (Spectral bandwidth: 350 nm demonstrated),other lasers/wavelengths available or needed.Special interferometers and fiber optics

support for broad spectral range,dispersion balanced,

current system used for OCT: 260 nm bandwidth, ~1.5µm resolution.

Chromatically corrected opticsaberrations can decrease resolution and SNR.Broad bandwidth detectors and electronics

dual balance detection, low noise circuitry necessary.

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Scanning devicesPiezo or motorized scanning devices

ideal for both longitudinal and lateral scanning.Galvanic mirrorsResonance scannersHelical mirrors

longitudinal scanning.Fiber stretcher

longitudinal scanning.

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RSOD (Rapid Scanning Optical Delay line) setup

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RSOD in the lab

Peter E. Andersen, Optics and Plasma Research Department

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Clinically adapted systems

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BCC II

LayersThinning of

layers

L. K. Jensen, MSc thesis (in Danish), 2003 [data obtained atLund Medical Laser Centre, courtesy K. Svanberg].

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OCT: Figures-of-merit – summaryDynamic range

100 dB (or better).Resolution (typical)

1-10 micrometers.Penetration depth

depending on wavelength/tissue,1-2 mm (typically) for

1300 nm in skin tissue.

Axial and lateral resolutions are decoupledimportant for

applications.

Pixel density is related to spatial resolution and image acquisition timeNz=2*Lz/dz,Nx=2*Lx/dx,image acq. time:

T=Nx*fs,scan velocity: vs=Lz*fs.

Image acquisitionseconds or less,real-time OCT.

Clinical adaptationinterfaced to standard

equipment,fiber-optic devices,endoscopes.

Thank You