1

PhotoOncology

Brian C WilsonOntario Cancer Institute/University of Toronto

bringing light to lifebringing light to life

LLaboratory for aboratory for AApplied pplied BBiophotonics iophotonics University Health Network, TorontoUniversity Health Network, Toronto

bringing light to lifebringing light to life

LLaboratory for aboratory for AApplied pplied BBiophotonics iophotonics University Health Network, TorontoUniversity Health Network, Toronto

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OPTICAL IMAGING & SPECTROSCOPY OPTICAL THERAPIES

OPTICAL DIAGNOSTICSMEDICAL DEVICES

www.uhnres.utoronto.ca/biophotonics

Observations

Idea

Project

Impact

Parenchymal tissue density is a breast cancer risk indicator

Boyd NF, et al. CEBP 1998;7:1133-1144.

Asymmetry in optical spectra indicative for presence of cancer

Egan RL et al. Acta Radiologica 1988;29:497-503.

Optical Transillumination Breast Spectroscopy (TIBS) may be able to quantify breast cancer risk.

Prototype engineeringPatient recruitment for cross section proof of principle study. Understand spectra

Low Density

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Establish predictive value for different applications: Investigation and Clinical

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Longitudinal monitoring study

Diet study in adolescent girls

TIBS correlation to cancer risk

Research tool: Evaluate lifestyle and

environmental effects in young women

Clinical tool: Identify women at risk early in live and permit feedback during

Risk reduction intervention

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OUTLINE• Photodynamic Therapy

- specific clinical example: prostate cancer- other applications/concepts

• Fluorescence Image-Guided Surgery- Brain, prostate,…

• GI Endoscopy- Fluorescence- Raman- DOCT- future trends

Focus: clinical realities/challenges in photo-oncology

PDT is the use of drugs (photosensitizers) activated by light to produce specific biological effects,

usually mediated by oxygen

Inject( inactive)photosensitzer

Destroy/modifytarget

Activate with non-thermal light

Target tissues/cells takeup photosensitzer

photosensitizer

light

oxygen

Excited singlet-stateoxygen

Biological effects

• cellular (necrosis, apoptosis)• vascular• immunologic

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• solid tumors*• dysplasias*• papillomas• rheumatoid arthritis• age related macular degeneration*• actinic keratosis*• cosmesis• psoriasis• endometrial ablation• localized infection: bacterial, fungal• prophylaxis of arterial restenosis

* Approved indications

Skin-BCC*

Lung*Esophagus*

Bladder*Head & Neck

BrainOcular melanomaOvarianProstateRenal CellCervix*PancreasBone

#↓

*Photofrin{mTHPC

*ALA*BPD

Current Clinical Status

Current projects

TOOKAD

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Vasoconstriction

Bloodstasis

Vascularpermeability

ThrombusFormation &

Vascularocclusion

VasoconstrictionVasoconstriction

BloodstasisBloodstasis

Vascularpermeability

Vascularpermeability

ThrombusFormation &

Vascularocclusion

ThrombusFormation &

Vascularocclusion

O2

O2

O2

Lipidperoxidation

ECresponseTo VTPT

Tumornecrosis

Lipidperoxidation

ECresponseTo VTPT

Tumornecrosis

cytotoxicROS

Light

cytotoxicROS

LightLightLight

Photoconsumptionof O2 and blooddeoxygenation

Photoconsumptionof O2 and blooddeoxygenation

Damageprogression

Damageprogression

Damageprogression

Damageprogression

Tumor

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Tookad Phase I/II Plasma conc. in the 5 drug groups (0.1, 0.25, 0.5, 1 and 2mg/kg)

Illumination

Injection

PDT for (recurrent) prostate cancer using vascular-targeted PS

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Studies in Dog Normal Prostate

2-day post-PDT

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BeyondProstate

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NotDetectable

Minimal damage to: - urethra- rectum, bladder- nerve bundle- ± radiation

Chen et al, Photochem. Photobiol.76:88-95,2002Zheng et al, Rad. Res. 161: 723-731, 2004

SKIN PHOTOSENSITIZATION STUDIESpre-clinical and clinical

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Weersink et al, Photochem. Photobiol. 81:106-113, 2004.

PS-,UV+ PS+, UV-

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Treatment Planning

‘Moderate’ plan.79.0% peripheral prostate treated

‘Moderate’ plan.79.0% peripheral prostate treated

‘Conservative’ plan.47.2% peripheral prostate treated

‘Conservative’ plan.47.2% peripheral prostate treated

‘Aggressive’ plan.91.3% peripheral prostate treated

‘Aggressive’ plan.91.3% peripheral prostate treated

Light Delivery

ProstateUrethra

Rectum

Hydrodissection

Light Dosimetry Unit

Laptop for Display and Collection

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Treatment Time (min)

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ence

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Prostate d=5mm Urethra d=10mmHydrodissection Rectum

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Light Dosimetry Unit

Laptop for Display and Collection

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Prostate d=5mm Urethra d=10mmHydrodissection Rectum

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Prostate d=5mm Urethra d=10mmHydrodissection Rectum

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Rectum

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Light Dosimetry Unit

Laptop for Display and Collection

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Treatment Time (min)

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Prostate d=5mm Urethra d=10mmHydrodissection Rectum

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Light Dosimetry Unit

Laptop for Display and Collection

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Treatment Time (min)

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ence

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Prostate d=5mm Urethra d=10mmHydrodissection Rectum

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Prostate d=5mm Urethra d=10mmHydrodissection Rectum

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Monitoring

∇D(x)∇φ(x) - µa(x)φ(x) =0 ∇D(x)∇φ(x) - µa(x)φ(x) =0

Tissue optical properties

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PDT dose>necrosisthreshold

PDT dose<< necrosisthreshold

PDT dose<< necrosisthreshold

bladder

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8/14 biopsy-proven complete responses in Rx-recurrencepts. receiving the highest light doses

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Clinical reality: intra- and inter-pt. heterogeneity

• Inadequate light delivery?inaccurate treatment planningerrors in fiber placement/delivered energy density

• Non-uniform PS, O2?• Variable tissue sensitivity?

Treatment reconstruction

T1-weighted MRI, post gadolinium injection4. Calculation of delivered dose

1. Target tracing on T2 MRI

2. Necrosis tracing

3. Placement of source fibres

Trans-rectal US

Dosimetry: light

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Light Dose Accuracy

Avg. prediction error: ±44%,

⇒ 1.4/-2.3 mmerror in predicting the light dose contour position.

How to cover complex volume of prostate withuniform cylindrically-diffusing fibers?

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L.. Vesselov et al, Applied Optics 2005/Walsh Medical, ON

bare

coated

bare

coated

Excimer laser: 248 nm, 4 J cm-2, 10 nsec, 150 pulses

Beam expanding and imaging optics

Amplitude Mask, micro machinedin 100µm Copperfolie

Ge doped, 100 µm diameter MMoptical fibre

Setup to write Type II Bragg gratings into GE-doped multimode optical fibres.

Excimer laser: 248 nm, 4 J cm-2, 10 nsec, 150 pulses

Beam expanding and imaging optics

Amplitude Mask, micro machinedin 100µm Copperfolie

Ge doped, 100 µm diameter MMoptical fibre

Setup to write Type II Bragg gratings into GE-doped multimode optical fibres.

Potential Solution (from telecom):fiber Bragg gratings

Aq=94%of ideal

Pq =0.97% of ideal

L=80mm, Tr=2% blockedLq=96%, +12% -8%, STDEV=6%,

Azimuthal Emission

Polar Emission

Axial Emission

Aq=94%of ideal

Pq =0.97% of ideal

L=80mm, Tr=2% blockedLq=96%, +12% -8%, STDEV=6%,

Azimuthal Emission

Polar Emission

Axial Emission

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Inverse treatment plan to calculate outputpower profile along the length of anintra-urethral fiber to give fixed lightfluence at the prostate boundary (radialsymmetry)→ design Bragg grating, build fiber

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Dosimetry: photosensitizer

Whole Blood Whole Blood Absorption SpectroscopyAbsorption Spectroscopy

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photoactive

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350 400 450 500 550 600 650 700 750 800 850 900wavelength (nm)

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in solution

white light source

spectrometerscattering material

Bloodsampleholder

optical fibers

white light source

spectrometerscattering material

Bloodsampleholder

optical fibers

Diffuse Transmittance SpectroscopyDiffuse Transmittance Spectroscopy

ProstateSource(Halogen lamp)

Detector(Spectrometer)

ProstateSource(Halogen lamp)

Detector(Spectrometer)

Net

OD

(760

nm

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Pre-Infusion

Net

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(760

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Pre-InfusionPre-Infusion

start of treatmentstart of treatment

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biological effectT1

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1O2

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NIR phosphorescencespectroscopy in situOption?

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Dosimetry: tissue oxygenation

Weersink et al, J. Photochem. Photobiol. \:211-222, 2005

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HbHbO2TOOKADProstateSource

(Halogen lamp)

Detector(Spectrometer)

ProstateSource(Halogen lamp)

Detector(Spectrometer)

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Planned Studies

• Retreatment in Rx recurrences

• Phase IIb/III in Rx recurrences: ‘aggressive’ TPs

• Phase I/II in Primary: ?tissue sensitivity altered

• MRI-guided focal irradiation

• pre-clinical studies: ±hyper/hypo-thermiawater-soluble PSeffect of hormone treatment

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A-A+

androgen treatment increases cell survival following Tookad-PDT

*

**

* P<0.05

PDT- other planned/ongoing work

Metronomic PDT: very low drug and light dose rates overextended times (brain, skin)

New applications epilepsy, bone growth, infections

Therapeutic ‘beacons’ enzyme and/or mRNA hybridizationactivated

2-photon PDT for age-related macular degeneration

Nanoparticle-based Qdot-based 2-photon

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mPDT-brain tumors

Tumor cell specificapoptosis in brain

Acute-dose PDT

-6 -4 -2 0 2 4 6 8 10

Pre-ALA

within normal

slight risk

pronounced risk

Post- ALA

severe health risk

1000mg/kg/d

500100

ALA drinking (days)

Mor

b idi

t y s c

ore

Bisland et al, Photochem.Photobiol. 80:2-30, 2004

PDT of spinal metastases

Burch et al, J. Orthoped. Res, 23: 995-1003, 2005; J. Biomed Opt 10:2005Siwerdsen et al, Med. Phys. 32: 241-254, 2005

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PDT of osteomyelitis

Bisland et al, Photochem. Photobiol. Sci. 5: 31-38, 2006

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PDT- Molecular Beacons

Singlet oxygen generation

Chen et al, JACS 126:11450-51, 2004

OUTLINE• Photodynamic Therapy

- specific clinical example: prostate cancer- other applications/concepts

• Fluorescence Image-Guided Surgery- Brain, prostate,…

• GI Endoscopy- Fluorescence- Raman- DOCT- future trends

Focus: clinical realities/challenges in photo-oncology

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• Lacroix et al JNS 2001

– 4.2 months survival advantage for malignant brain tumor resection of >98% compared with <98% [416 cases]

ALA

↓

PpIX

↓

heme

Fe

ALA

↓

PpIX

↓

heme

Fe

Can fluorescence imaging provide clearer visualizationof residual tumor?

-autofluorescence-drug-induced (e.g. PDT sensitizer)

Fluorescence-Guided Resection: brain tumor

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400 nmblue light

500 ~ 750 nmfluorescence

fluorescenceCCD imaging

Patent pending

multiple spectralwindows:400nm: blue500nm: green550nm: yellow630nm: red720nm: near IR

0.5 m

“Point & Shoot” Fluorescence system•Multi-channel fluorescence (+ WL) imaging•Point fluorescence emission spectroscopy‘Point & Shoot’ fluorescence camera/spectrometer

Yang et al, Lasers Surg. Med. 32: 224-232, 2003

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Bogaards et l, Lasers Surg. Med. 35: 181-190, 2004

0.01

0.1

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Res

idua

l tum

or (%

)

WLR WLR+FGR0.0

Completeness of tumor resection:

WLR 68% ± 38%WLR+FGR 98% ± 3.5%

1. White light images2. Fluorescence images3. Fluorescent Point Spectroscopy4. Tissue Biopsy

White light normal areasWhite light tumor areasFluorescence – ve areasFluorescence + ve areas

~ 50% tumor resectionTime point A: Bulk tumor measurements

Pre-op CT scanALA administration

1. White light images2. Fluorescence images3. Fluorescent Point Spectroscopy4. Tissue Biopsy

White light normal areasWhite light tumor areasFluorescence – ve areasFluorescence + ve areas

~ 50% tumor resectionTime point A: Bulk tumor measurements

Pre-op CT scanALA administration

Maximum tumor resection [white light]Time point B: Tumor bed measurements

1. White light images2. Fluorescence images3. Fluorescent Point Spectroscopy4. Tissue Biopsy5. OTS localization

White light normal areasWhite light tumor areasFluorescence – ve areasFluorescence + ve areas

Procedure End

Maximum tumor resection [white light]Time point B: Tumor bed measurements

1. White light images2. Fluorescence images3. Fluorescent Point Spectroscopy4. Tissue Biopsy5. OTS localization

White light normal areasWhite light tumor areasFluorescence – ve areasFluorescence + ve areas

Procedure End

Clinical trial(multi-center)

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Fluorescence Image-Guidance at Prostatectomy

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FGR- future trends

Time-resolved imaging/spectroscopy

Targeted fluorescent contrast, including NP

Multispectral imaging

Combination with , e.g MRINP

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Soltesz EG et al, 2005

Rat 9L glioma model

Qdot580 + CD44GFP filter set

WL

Qdot-MAb for fluorescence-guided tumor resection

Background Autofluorescence subtracted

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OUTLINE• Photodynamic Therapy

- specific clinical example: prostate cancer- other applications/concepts

• Fluorescence Image-Guided Surgery- Brain, prostate,…

• GI Endoscopy- Fluorescence- Raman- DOCT- future trends

Focus: clinical realities/challenges in photo-oncology

Endoscopic

Imaging:White-lightFluorescence

Camera ‘pill’

OCT

Point Spectroscopy:-Raman-ESS-fluorescence

• most solid tumors (excl. skin) arise asthin lesions on the lining of hollow organs(lung, GI tract, cervix, bladder,…)

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Detect lesions early

Detect lesions that are occult to white light endoscopy

Differentiate benign and (pre)malignant lesions

Conventional White Light Endoscopy

Clinical Challenges

Autofluorescence imaging (bronchoscopy) Dr. S. Lam,BCCA

Fluorescence endoscopy

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Xillix Tech.

OncoLIFE system

White-light mode autofluorescence mode (Fgreen/Rred)

Colonto distinguish hyperplastic (benign)and adenomatous polyps

&to detect flat adenomas

?

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TYPE OF LESION

WL WL+FL

Adenomatous Polyp 69/120 (57.5%) 97/120 (80.8%) Hyperplastic Polyp 34/55 (61.8%) 40/55 (72.7%)

Zanati et al, in prepper-lesion sensitivity

Examples of adenomatous polyps missed by WL (left) but detected by FL (right) colonoscopy

Examples of True Negative lesions seen on fluorescence

fold

Hyperplasticpolyp

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Fluo

resc

ence

Inte

nsity

(a.u

.)

Wavelength (nm)

400 500 600 800700

Normal colon

Hyperplastic polyp

Dysplastic polyp

Adenocarcinoma

In vivo autofluorescence emission spectra-colon

Tytgat et al, Gastrointest. Endosc. 53: 642-650, 2001

Fluorescence microscopy to investigate underlyingtissue changes that cause the fluorescence

Normal Crypt Adenomatous crypt

base

opening

Base 2

normal benign adenomatous

DaCosta et al, J. Clin. Path. 58:766-774, 2005

tissuebiopsy

human primaryculture

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Autofluorescence endoscopy: colon

- improved sensitivity and specificity for hyperplastic vs adenomatous polyps (provisional)

- ability to detect flat adenomas (?sensitivity)

- understanding of tissue changes in polyps

- definite sensitivity/specificity trial in progress

main GI endoscopic challenges:

Esophagusto detect dysplasia in Barrett’s Esophagus

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Normal Squamous -

Dysplasia -

Gastric Metaplasia -

Intestinal Metaplasia -

Normal Squamous -

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Gastric Metaplasia -

Intestinal Metaplasia -

White Light Endoscopy

Hypothesis: Barrett’s Esophagus

Normal Squamous -

Gastric Metaplasia -

Intestinal Metaplasia -

Dysplasia -

Normal Squamous -

Gastric Metaplasia -

Intestinal Metaplasia -

Dysplasia -

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Average spectra Individual spectra

Autofluorescence spectra in esophagus (blue excitation)

Statistically-significant differences on average but huge pt-to-pt variations

Surface EpitheliumDeep Mucosal Glands Surface EpitheliumDeep Mucosal Glands

LS

LS

LS

→ no quantitative differencesin the intrinsic autofluorescence between BE and dysplasia

Differences seen in vivo likely dueto altered morphology/attenuation

Kara M et al, Am. J. Gastroenter.., in press

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White light endoscopy LIFE

BEBE

SE

SE

Problem: high red autofluorescence in non-dysplastic BE

Alternatives: find optimal LIFE parameters (λex,λem)use targeted fluorescence contrast agentRaman spectroscopyOptical Coherence TomographyConfocal endoscopy,…

ALA

↓

PpIX

↓

heme

Fe

ALA

↓

PpIX

↓

heme

Fe

skin

1 hr

3 hr

6 hr

2 mg/kg 10 mg/kg 30 mg/kg

Barrett’s Esophagus

1 hr

3 hr

6 hr

2 mg/kg 10 mg/kg 30 mg/kg

Barrett’s Esophagus

ALA in Barrett’s Esophagus - 2mg/kg at 6 hours

also highly variableuse targeted “contrast agent”

30

Challenges:

• Identify effective Ab* (high target specificity and affinity, available, human-compatible,….)

*or peptides, antisense,..

• Optimum fluorophore(s): especially for multiplexedimaging

• In vivo imaging instrumentation with correct spectral-spatial-temporal response

Goblet cells

Glands

Cell division of Surface cells

Normal Lining Barrett’s esophagus With low-grade dysplasia

With high-grade dysplasia

Invasive carcinoma

Biomarkers for differentiating benign vs. malignant ?

Villin EGFr CEA MUC1 MUC4 MUC5AC

Human colon tumor

DaCosta et al, Digest. Endosc. 15: 153-173, 2003

e.g. Ab-F* conjugate

Diode Laser

Imaging Stage

ComputerMonitor

CCD Camera

Optical Fiber Lens

Fluorescence Emission

Filter

Diode Laser

Imaging Stage

ComputerMonitor

CCD Camera

Optical Fiber Lens

Fluorescence Emission

Filter

31

Review: Michalet et al., Science 307:538 – 544, 2005

Potential advantages:

• Broad excitation spectra• Narrow, size-dependent emission spectra• Low photobleaching• High brightness

Challenges:

• cost• toxicity• bioconjugation• biodistribution

32

• QD670 + Anti-Villin Mab: topical application

λ3λ2

λ1

λ2

λ3

+

+

+

Mab1

Mab2

Mab3

e.g. Mab1 specific to dysplasia+carcinoma

Mab2 specific to low-grade dysplasia

Mab3 specific to high-grade dysplasia

"Cocktail" injection

λ1

λ2

λ3

Hyperspectral Imaging

λ3λ3λ2λ2

λ1λ1

λ2λ2

λ3λ3

+

+

+

Mab1

Mab2

Mab3

e.g. Mab1 specific to dysplasia+carcinoma

Mab2 specific to low-grade dysplasia

Mab3 specific to high-grade dysplasia

"Cocktail" injection

λ1λ1

λ2λ2

λ3λ3

Hyperspectral Imaging

λ3λ2

λ1

λ2

λ3

+

+

+

Mab1

Mab2

Mab3

e.g. Mab1 specific to dysplasia+carcinoma

Mab2 specific to low-grade dysplasia

Mab3 specific to high-grade dysplasia

"Cocktail" injection

λ1

λ2

λ3

Hyperspectral Imaging

λ3λ3λ2λ2

λ1λ1

λ2λ2

λ3λ3

+

+

+

Mab1

Mab2

Mab3

e.g. Mab1 specific to dysplasia+carcinoma

Mab2 specific to low-grade dysplasia

Mab3 specific to high-grade dysplasia

"Cocktail" injection

λ1λ1

λ2λ2

λ3λ3

Hyperspectral Imaging

0.5 cmMouse model for colorectal CaCell line – LS174T (human adenoCa)Exc 470 nm, Em LP500 nm

QD710

QD550

QD570AF

Multiplexed QDots-Fluorescence

0.5 cmMouse model for colorectal CaCell line – LS174T (human adenoCa)Exc 470 nm, Em LP500 nm

QD710

QD550

QD570AF

Multiplexed QDots-Fluorescence

(simulated multiplexing)3 mm

1 mm

Ab1-Qdgreen Ab2-Qdred

BE model

topical application

33

In Vivo 3QDot-Monoclonal Antibody “Cocktail” Targeted Imaging in an LS174T Colon Adenocarcinoma Mouse Xenograft Model

(QD560+CEA, QD580+EGFr, QD700+CC49)

No tumor localization!

Non-Specific Accumulation

Need to get surface chemistry right - for adequate tumor uptake and- to minimize toxicity

-major challenge

Organic layer

-C=OOH-C=OOH

-C=OOH-C=OOH

-C=OOH-C=OOH

-C=OOH-C=OOH

CdSe

ZnS

-C=OOH-C=OOH

-C=OOH-C=OOH

-C=OOH-C=OOH

-C=OOH-C=OOH

-C=OOH-C=OOH

-C=OOH-C=OOH

-C=OOH-C=OOH

Monoclonal

Antibody

Liver SpleenKidney

34

HOW TO ENHANCE DYSPLASIA DETECTION?

WHITE LIGHT ENDOSCOPY with Random Biopsies

CHROMOENDOSCOPY

•REGULAR

•MAGNIFICATION

FLUORESCENCE

• POINT SPECTROSCOPY

• IMAGING

• AUTO OR WITH FLUOROPHORE(S)

• CONFOCAL

• ENDOCYTOSCOPY

• (Doppler) OPTICAL COHERENCE TOMOGRAPHY

NARROW BAND IMAGING

• RAMAN

SPECTROSCOPY

Optical biopsy- many clinical studies of different optical modalities

(fluorescence, Raman, elastic scattering,….)

35

LaserLaser

SampleSample

Spectrograph/CCDSpectrograph/CCDLaserLaser

SampleSample

Spectrograph/CCDSpectrograph/CCD

Visionex probe

M. Shim et al, J. Raman Spectr 28:131-42, 1997Appl Spectr 53: 619-27, 1999Photochem Photobiol 72:146-50,2000

• 65 patients (59 males)• Mean age = 65 (range 35-88)• Mean Barrett’s length = 6 cm (range 3-15)• # of spectra/biopsies = 233

– Excluded = 41

– Analyzed = 192

Gastric-type mucosaSignificant reactive changes

112 IM54 LGD26 HGD/early ACA

Clinical Trial: Barrett’s esophagus

36

Linear Discriminant Analysis on

Principal Component Scores(with leave-one-out cross-validation)

-4 -3 -2 -1 0 1 2 3 4 5 6-4

-3

-2

-1

0

1

2

3

Discriminant Function 1

Dis

crim

inan

tFun

ctio

n 2

IM

LGD/IND

HGD

Histological Diagnosis

Spectral Diagnosis

Sensitivity = 88%Specificity = 89%Accuracy = 89%

IM/LGD

IM/LGD HGD/ACA

HGD/ACA

147

2319

3

Differentiating ‘high-risk’ from ‘low-risk’ Barrett’s

WongKeeSong et al, Proc. SPIE 5692: 2005

37

optical analogue of high-frequency ultrasound ….cross-sectional subsurface imaging using interferometry.

low-coherenceCW optical source

referencemirror

detector

tissue

beamsplitter

coherence length

low-coherenceCW optical source

referencemirror

detector

tissue

beamsplitter

coherence length

coherence length

Source

Demodulator

Detector

Sample

Scanningreference

mirror

Computer

50/50 coupler

10 µm

• 10 µm resolution• up to 32 frames per sec• best flow sensitivity:

~ 0.02 mm/sec~ 0.02 mm diameter

• typical flow sensitivity:~ 0.1 mm/sec~ 0.05 mm diameter

flow sensitivitywhen

frame rate

Yang VXD et al, Rev Sci Instr 74: 437-440, 2003; Optics Express, 11: 794-809, 2003.

38

0.5 mm

Rat esophagus mucosa

0.5 mm

smmm

lpep

mpimpe

me

e.g. esophagus

39

Barrett’s Adeno-Ca

Conventional OCTConventional OCT

Measures interference in the time domain- One point at a time

Sensitivity ?

∆z • PowerImaging Speed

Frequency DomainFrequency Domain

Fourier Transform

k(t) zz

High Speed Esophageal Imaging

SM LP SE

3.0 cm3.0 cm

2.0 cm

Brouma & Tearney, MGH

40

FUTURE?

integrated, multidimensional

imaging/spectroscopy

(ultra) structural(e.g. OCT

Confocal, LSS)

Functional(e.g. DOCT)

Gene expression(e.g. Ab-F*)

Biochemical(e.g. Raman)

Multimodal Optical DiagnosisMultimodal Optical DiagnosisAccuracy of Spectroscopic Classification Accuracy of Spectroscopic Classification

(%)(%)

GeorgakoudiGeorgakoudi et al: Gastroenterology 120:1620, 2001et al: Gastroenterology 120:1620, 2001CP1110893-39

Fluorescence 100 97 79 88

Reflectance 86 100 79 88

LSS 100 91 93 96

Combination 100 100 93 100

FluorescenceFluorescence 100100 9797 7979 8888

ReflectanceReflectance 8686 100100 7979 8888

LSSLSS 100100 9191 9393 9696

CombinationCombination 100100 100100 9393 100100

Sens Spec Sens SpecSensSens SpecSpec SensSens SpecSpec

HGD vsNDB/LGDHGD HGD vsvs

NDB/LGDNDB/LGDLGD/HGD vs

NDBLGD/HGD LGD/HGD vsvs

NDBNDB

Tools or Toys ?

41

National Cancer Institute of CanadaNational Cancer Institute (US) Canadian Institutes of Health ResearchOntario Research & Development Challenge FundPhotonics Research OntarioCanadian Institute for Photonic InnovationsCanadian Foundation for Innovation

Princess Margaret Hospital FoundationSt Michael’s Hospital Foundation

DUSA Pharmaceuticals, NYAxcan, QuebecXillix Technologies Corp, BCNegma-Lerads, FranceQLT Inc, BC

CollaboratorsUHN Biophotonics Faculty and Students

National Cancer Institute of CanadaNational Cancer Institute (US) Canadian Institutes of Health ResearchOntario Research & Development Challenge FundPhotonics Research OntarioCanadian Institute for Photonic InnovationsCanadian Foundation for Innovation

Princess Margaret Hospital FoundationSt Michael’s Hospital Foundation

DUSA Pharmaceuticals, NYAxcan, QuebecXillix Technologies Corp, BCNegma-Lerads, FranceQLT Inc, BC

CollaboratorsUHN Biophotonics Faculty and Students