Imaging Inside the Human Body Imaging Inside the Human Body g g ywith Light

g g ywith Light

Arjun G. YodhUniversity of PennsylvaniaDepartment of Physics & AstronomyDepartment of Physics & Astronomy

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GoalsGoalsGoalsGoals

• Dreams• Red/Near-infrared Transmission Window• Why is this hard?• How does light travel in the body?• Random Walks / Diffusion Models• Spectroscopy, Imaging, Blood Flow Monitoring• Primer on Blood Dynamics• Examples

Breast Cancer Imaging, Stroke Monitoring

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The Dream.The Dream.The Dream.The Dream.

from: Star Trek

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from: Minority Report

from: Star Trek

Red/Near-infrared Transmission WindowRed/Near-infrared Transmission Window

• Near Infrared Light Penetrates TissuePenetrates Tissue

N i i f • Non-invasive, safe, rapid, portable, continuous, i i

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inexpensive ...

Why is this hard?Why is this hard?Why is this hard?Why is this hard?

I i W t I i Milk?

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Ice in Water Ice in Milk?

Why is this hard?Why is this hard?Why is this hard?Why is this hard?

Water Water + Little Milk MilkWater Water + Little Milk Milk

Light doesn’t get Absorbed, it Scatters

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Light doesn t get Absorbed, it Scatters

How does light travel in the body?How does light travel in the body?g yg y

"R d " W lk

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"Random" Walk

Random Walks and DiffusionRandom Walks and DiffusionRandom Walks and DiffusionRandom Walks and Diffusion

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Example: Random Walks from Example: Random Walks from pPhiladelphia’s City Hall

pPhiladelphia’s City Hall

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Example: Random Walks from Example: Random Walks from pPhiladelphia’s City Hall

pPhiladelphia’s City Hall

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Random Walk: QuantificationRandom Walk: QuantificationQQ

After N steps of length l, p g ,typical walker will be l√Nfrom starting point!

√N factor is THE fundamental

g p

√N acto s u da e tafeature of Random Walks

To travel distance 10l from starting point, require ~100 random steps of length l!

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require ~100 random steps of length l!

Random Walks / Diffusion ModelsRandom Walks / Diffusion Models

l* i l hl* scattering lengthla absorption length

Light concentration, (r, t), obeys a diffusion equation g ( ) y q

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What has been gained?What has been gained?What has been gained?What has been gained?

• Scattering separated from absorption.

• Absorption can be measured in turbid mediamedia.

• C b D Ti• Can probe Deep Tissues

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SpectroscopySpectroscopySpectroscopySpectroscopy

Total Hemoglobin Concentration = [HbO2] + [Hb] = THCTotal Hemoglobin Concentration [HbO2] + [Hb] THCTissue Oxygen Saturation = [HbO2] / THC = StO2

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Spectral Fingerprints enable determination of tissue composition.

ImagingImagingImagingImaging

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Tomography of Tissue PhantomTomography of Tissue PhantomTomography of Tissue PhantomTomography of Tissue Phantom

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Reconstructed ImagesReconstructed ImagesReconstructed ImagesReconstructed Images

T L tt “DOT” d “PENN” 1 f f

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Top: Letters “DOT” and “PENN” 1 cm from surfaces.Bottom: Letters “DOT” in center of tank.

Blood Flow Index (BFI)Blood Flow Index (BFI)Blood Flow Index (BFI)Blood Flow Index (BFI)

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Sensitivity to Tissue PhysiologySensitivity to Tissue Physiologyy y gyy y gy1. Absorption Variations

- Access to tissue composition.p- Hemoglobin Concentration- Blood Oxygen Saturation- Water, Lipids

2. Exogenous Contrast Agents- Absorption Contrast, Drugs,…- Fluorescenceuo esce ce- Uptake & Clearance

3. Scattering VariationsOrganelle Concentrations (mitochondria )- Organelle Concentrations (mitochondria,…)

- Background fluids.

4. Motions of ScatterersA Bl d Fl D it

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- Average Blood Flow Density- Brownian Dynamics

Circulatory Circulatory ySystem

ySystem

Images from Human

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Images from Human Physiology by Vander, Sherman and Luciano, Chapter 13.

Circulatory SystemCirculatory SystemCirculatory SystemCirculatory System

At any given time some of theAt any given time, some of the Hemoglobin carried in the red blood cells is oxygenated (HbO2) and some is deoxygenated (Hb).

Images from Human

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Images from Human Physiology by Vander, Sherman and Luciano, Chapter 13.

Oxygen ExchangeOxygen ExchangeOxygen ExchangeOxygen Exchange

O2 IN O2 OUT

Arterioles Venules

Tissues

O OUTO2 OUT(Metabolism)

Hypoxia: Deficiency of Oxygen at Tissue Level• Arterial Oxygen too low.• Blood flow too slow (ischemic hypoxia).

Hypoxia: Deficiency of Oxygen at Tissue Level

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• Local Tissue metabolism too large.

Clinical Scenarios for Light ProbesClinical Scenarios for Light Probesgg

S• Stroke detection and monitoring• Cancer Imaging and Diagnosis• Cancer Therapy monitoring• Mitochondial diseases• Brain Activation• Muscle Activation

(Peripheral Vascular Disease)

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Imaging & MonitoringImaging & MonitoringImaging & MonitoringImaging & MonitoringTomography Approach Hand-held Approach

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Functional Activation In BrainFunctional Activation In BrainFunctional Activation In BrainFunctional Activation In Brain

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from: Minority Report

Functional Activation In BrainFunctional Activation In BrainFunctional Activation In BrainFunctional Activation In Brain

THC = Total Hemoglobin ConcentrationStO2 = Blood Oxygen SaturationrBF = Relative Blood FlowCMRO2 = Rate of Cerebral Oxygen Metabolism

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CMRO2 Rate of Cerebral Oxygen Metabolism

Motor Stimulus: OpticalMotor Stimulus: OpticalMotor Stimulus: OpticalMotor Stimulus: Optical

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Motor Stimulus: OpticalMotor Stimulus: OpticalMotor Stimulus: OpticalMotor Stimulus: Optical

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Opportunity: Other Techniques are InvasiveOpportunity: Other Techniques are Invasivepp y qpp y q

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Opportunity: Direct Measurement of Blood Opportunity: Direct Measurement of Blood Flow in Deep Tissues is Not So EasyFlow in Deep Tissues is Not So Easy

MRI

Xenon-CT

DopplerUltrasound

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Acute Ischemic Stroke Study ProtocolAcute Ischemic Stroke Study Protocolyy

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Cerebral Blood Flow vs. Head of Bed Angle: Cerebral Blood Flow vs. Head of Bed Angle: gHealthy Subjects vs. Stroke Patients

gHealthy Subjects vs. Stroke Patients

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Common ResponseCommon Response

Cerebral Blood Flow vs. Head of Bed Angle: Cerebral Blood Flow vs. Head of Bed Angle: gHealthy Subjects vs. Stroke Patients

gHealthy Subjects vs. Stroke Patients

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Paradoxical ResponseParadoxical Response

Diffuse Optical Tomography of BreastDiffuse Optical Tomography of Breastp g p yp g p y

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Potential for DOT in Breast CancerPotential for DOT in Breast Cancer

• Non-invasive• Relatively portable, rapid and

inexpensivep• Complementary contrasts

(hemodynamics, water, lipid,(hemodynamics, water, lipid,contrast agents,…)

• Radiographically dense breasts• Radiographically dense breasts• Combine with other modalities

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• Therapy Monitoring

Parallel-Plane DOT InstrumentParallel-Plane DOT InstrumentParallel Plane DOT InstrumentParallel Plane DOT Instrument

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DOT image: 3DDOT image: 3DDOT image: 3DDOT image: 3D

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Invasive Ductal CarcinomaInvasive Ductal CarcinomaInvasive Ductal CarcinomaInvasive Ductal Carcinoma

rTHC – Hemoglobin rStO2 – Oxygen Sat. r′s – Scatteringg 2 yg s g

rHbO2 – Oxyhemoglobin rHb – Deoxyhemoglobin

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• 53-year-old post-menopausal female, 2.2 cm invasive ductal carcinoma

Cyst & Invasive Ductal CarcinomaCyst & Invasive Ductal Carcinomayy

rTHC – Hemoglobin rStO2 – Oxygen Sat. r′s – Scattering

rHbO2 – Oxyhemoglobin rHb – Deoxyhemoglobin

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• 47-year-old pre-menopausal female, 6 cm cyst & 1.3 cm invasive ductal carcinoma

Example: Malignant vs BenignExample: Malignant vs BenignExample: Malignant vs BenignExample: Malignant vs Benign

M li I i D l C iOptical IndexrTHC

Malignant: Invasive Ductal CarcinomaRegion of InterestrStO 2

MRI axial slice rTHC – Hemoglobin rStO2 – Oxygen Sat. r′s – Scattering

Region of Interest

Benign: FibroadenomaMRI axial slice rTHC Optical IndexrStO 2rTHC – Hemoglobin rStO2 – Oxygen Sat. r′s – Scattering

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Summary/FutureSummary/Future

• Diffuse Optics Probes Physiology of

Summary/FutureSummary/Future

• Diffuse Optics Probes Physiology of Deep Tissues.

• Breast Tumors, Brain, Head & Neck

Tumors Muscle Tumors, Muscle ...

• Animal Model Research (Pre-clinical)

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