imaging inside the human body ggy with light ggy with light
TRANSCRIPT
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
U n i v e r s i t y o f P e n n s y l v a n i a
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
U n i v e r s i t y o f P e n n s y l v a n i a
The Dream.The Dream.The Dream.The Dream.
from: Star Trek
U n i v e r s i t y o f P e n n s y l v a n i a
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
U n i v e r s i t y o f P e n n s y l v a n i a
inexpensive ...
Why is this hard?Why is this hard?Why is this hard?Why is this hard?
I i W t I i Milk?
U n i v e r s i t y o f P e n n s y l v a n i a
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
U n i v e r s i t y o f P e n n s y l v a n i a
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
U n i v e r s i t y o f P e n n s y l v a n i a
"Random" Walk
Random Walks and DiffusionRandom Walks and DiffusionRandom Walks and DiffusionRandom Walks and Diffusion
U n i v e r s i t y o f P e n n s y l v a n i a
Example: Random Walks from Example: Random Walks from pPhiladelphia’s City Hall
pPhiladelphia’s City Hall
U n i v e r s i t y o f P e n n s y l v a n i a
Example: Random Walks from Example: Random Walks from pPhiladelphia’s City Hall
pPhiladelphia’s City Hall
U n i v e r s i t y o f P e n n s y l v a n i a
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!
U n i v e r s i t y o f P e n n s y l v a n i a
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
U n i v e r s i t y o f P e n n s y l v a n i a
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
U n i v e r s i t y o f P e n n s y l v a n i a
SpectroscopySpectroscopySpectroscopySpectroscopy
Total Hemoglobin Concentration = [HbO2] + [Hb] = THCTotal Hemoglobin Concentration [HbO2] + [Hb] THCTissue Oxygen Saturation = [HbO2] / THC = StO2
U n i v e r s i t y o f P e n n s y l v a n i a
Spectral Fingerprints enable determination of tissue composition.
ImagingImagingImagingImaging
U n i v e r s i t y o f P e n n s y l v a n i a
Tomography of Tissue PhantomTomography of Tissue PhantomTomography of Tissue PhantomTomography of Tissue Phantom
U n i v e r s i t y o f P e n n s y l v a n i a
Reconstructed ImagesReconstructed ImagesReconstructed ImagesReconstructed Images
T L tt “DOT” d “PENN” 1 f f
U n i v e r s i t y o f P e n n s y l v a n i a
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)
U n i v e r s i t y o f P e n n s y l v a n i a
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
U n i v e r s i t y o f P e n n s y l v a n i a
- Average Blood Flow Density- Brownian Dynamics
Circulatory Circulatory ySystem
ySystem
Images from Human
U n i v e r s i t y o f P e n n s y l v a n i a
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
U n i v e r s i t y o f P e n n s y l v a n i a
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
U n i v e r s i t y o f P e n n s y l v a n i a
• 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)
U n i v e r s i t y o f P e n n s y l v a n i a
Imaging & MonitoringImaging & MonitoringImaging & MonitoringImaging & MonitoringTomography Approach Hand-held Approach
U n i v e r s i t y o f P e n n s y l v a n i a
Functional Activation In BrainFunctional Activation In BrainFunctional Activation In BrainFunctional Activation In Brain
U n i v e r s i t y o f P e n n s y l v a n i a
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
U n i v e r s i t y o f P e n n s y l v a n i a
CMRO2 Rate of Cerebral Oxygen Metabolism
Motor Stimulus: OpticalMotor Stimulus: OpticalMotor Stimulus: OpticalMotor Stimulus: Optical
U n i v e r s i t y o f P e n n s y l v a n i a
Motor Stimulus: OpticalMotor Stimulus: OpticalMotor Stimulus: OpticalMotor Stimulus: Optical
U n i v e r s i t y o f P e n n s y l v a n i a
Opportunity: Other Techniques are InvasiveOpportunity: Other Techniques are Invasivepp y qpp y q
U n i v e r s i t y o f P e n n s y l v a n i a
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
U n i v e r s i t y o f P e n n s y l v a n i a
Acute Ischemic Stroke Study ProtocolAcute Ischemic Stroke Study Protocolyy
U n i v e r s i t y o f P e n n s y l v a n i a
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
U n i v e r s i t y o f P e n n s y l v a n i a
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
U n i v e r s i t y o f P e n n s y l v a n i a
Paradoxical ResponseParadoxical Response
Diffuse Optical Tomography of BreastDiffuse Optical Tomography of Breastp g p yp g p y
U n i v e r s i t y o f P e n n s y l v a n i a
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
U n i v e r s i t y o f P e n n s y l v a n i a
• Therapy Monitoring
Parallel-Plane DOT InstrumentParallel-Plane DOT InstrumentParallel Plane DOT InstrumentParallel Plane DOT Instrument
U n i v e r s i t y o f P e n n s y l v a n i a
DOT image: 3DDOT image: 3DDOT image: 3DDOT image: 3D
U n i v e r s i t y o f P e n n s y l v a n i a
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
U n i v e r s i t y o f P e n n s y l v a n i a
• 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
U n i v e r s i t y o f P e n n s y l v a n i a
• 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
U n i v e r s i t y o f P e n n s y l v a n i a
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)
U n i v e r s i t y o f P e n n s y l v a n i a