Diffuse Optics:fundamentail y Tissue Applications

Diffuse Optics: Fundamentals
& Tissue Applications

Arjun G. Yodh
Department of Physics & Astronomy
University of Pennsylvania
Acknowledgement: NIH, ARMY

Outline
Brief Introduction/Motivation
Light Transport
Single Scattering
Multiple Scattering (Linear Transport & Diffusion Equations)
Solutions (Homogeneous Turbid Media)
Solutions (Simple Heterogeneous Turbid Media)
Image Reconstruction
Temporal Fluctuations: Diffuse Correlation Transport
Biomedical Motivations Revisited

Background on Hemodynamics
Oxygen Metabolism
Validation of the Techniques

In-Vivo Biomedical Applications (recent)
Breast
Brain
Cancer Therapy Monitoring
Summary/Future/Acknowledgements
The Dream.
from: Star Trek

from: Minority Report
In-Vivo Optical Biopsy

Near Infrared Light
Penetrates Tissue
Sensitivity to Tissue
Physiology
Unique Contrasts are
Complementary to Other
Medical Diagnostics
Non-invasive, safe,
rapid, portable,
continuous,
inexpensive ...
Imaging & Monitoring
Clinical Scenarios
Stroke detection and monitoring

Cancer Imaging and Diagnosis
Cancer Therapy monitoring
Mitochondial diseases
Epilepsy
Brain Activation
Muscle Activation
(Peripheral Vascular Disease)
Outline
Light Transport
Single Scattering

Oxygen Metabolism

Breast
Brain
Light Transport
E0, I0
How are photons lost from the

incident light beam?
Absorption (linear response)

L
I0
It = I 0 e
-aL
a = Absorption Coefficient
a = [Absorber Concentration] ()
Extinction
Coefficient
Light
Wavelength
Absorption Information
L
I0
It = I0 e -aL
What molecules are present?

(Hemoglobin, water, lipids, )
What are their concentrations?
What is their local environment?
(spectral shifts & broadening)
Scattering (single scattering limit)
Is ( )
I0
It = I 0 e
-sL
s = Scattering Coefficient
s = [Scatterer Concentration]s ()
Scattering
Cross-section
Light
Wavelength
Scattering (single scattering limit)

Is ()
I0
It = I0 e -sL
L
d () = Differential Scattering Cross-section

s = d () d
Is () = d () I0
1
(g = anisotropy factor =
s
d () cos () d) = cos () )
s = reduced scattering coefficient = s (1-g)

(s)-1 = photon random walk step length
Scattering Information
Is ()
I0
It = I0 e -sL
L
What are the scatterers?

(particles, organelles, cells, cell-networks)
What are scatterer concentrations?

What is their local environment?
(surrounding fluids)
Scattering: Temporal Fluctuations
time
What is moving?
(organelles, red blood cells, )
How much is moving, how fast &
what is the manner of motion?
(Blood flow)
Traditional Optical Techniques
Rigorous
Tested
I0
It = I 0 e
L
-(s + a ) L
Outline
Light Transport
Single Scattering

Oxygen Metabolism

Breast
Brain
Problem of Tissue: Multiple Scattering
Linear Transport Theory

= Radiance [W/(cm2 sr)]
Power/Area-Angle at
traveling in direction
L ~ E*(r,t) E(r,t)
Radiance is balanced in each
small volume of medium.
Transport
Transport Theory:
Theory: Convective
Convective Time
Time Derivative
Derivative
dr
Transport
Transport Theory:
Theory: Microscopic
Microscopic Sources
Sources &
& Sinks
Sinks
dr
Absorption &
Scattering Losses
t = a + s
Radiance
Scattered into
Sources
Linear Transport Equation

dr
t = a + s
Photon Fluence Rate & Flux
Fluence rate (W/cm2)
Flux (W/cm2)
PNN Approximation
Fluence & Flux in PNN Approximation
Radiance in the P11 Approximation (N=1)
Substitute P1 form of L into the linear transport equation.
Photon Diffusion Equation
Photon Diffusion Equation: Assumptions

Scattering length much smaller
than absorption length
Fluence rate much greater than
Flux (radiance is largely isotropic)
Isotropic sources
(breaks down close to fiber sources)
( << s )
Photon Diffusion Equation: Assumptions

(s)-1 ~ 0.01 - 0.1 mm
OK for Tissues
(s)-1 ~ 1 mm
(a)-1 ~ 2 - 10 cm
(s) ~ 300 MHz

Scattering (on average)
Independent of Incident Direction.

Tissue Measurements are NOT Precision
Measurements.
Outline
Light Transport
Single Scattering

Oxygen Metabolism

Breast
Brain
Ideal Solutions
Infinite
homogeneous
turbid media
Point sources
Frequency Domain: Diffuse

Photon Density Waves*
*first suggested by Enrico Gratton

Frequency Domain: Point

Sources & Greens Functions
If
,
= Greens Function Solution.
for arbitrary source distribution

Frequency Domain: Point

Sources & Greens Functions
Point Source at the Origin in Infinite Homogeneous Media

Diffuse Photon Density Waves
Frequency Dispersion
Diffusive Wave Optics
Boas, Oleary, Chance, Yodh. Physical Review E, 47(5) 1993.

Oleary, Boas, Chance, Yodh. Physical Review Letters, 69 1992.
Time Domain Solution
Time Resolved Reflectance and Transmittance for The Noninvasive

Measurement of Tissue Optical-Properties, Patterson, MS, Chance, B,
Wilson, BC, Applied Optics 28, 1989
What has been gained?

Can separate scattering from
absorption.
Can measure absorption in turbid
media.
Can measure scattering (photon
random walk step) in turbid media.
What about heterogeneous media?

Outline
Light Transport
Single Scattering

Oxygen Metabolism

Breast
Brain
Boundary Conditions: Semi-infinite Media
e.g. Air-Tissue Boundary

Fiber Source Changed to Displaced Point Source
(lt ~ (s)-1 )
Boundary Conditions: Semi-infinite Media
R() is a Fresnel Coefficient

Semi-infinite
Semi-infinite Media:
Media: Partial-flux
Partial-flux Boundary
Boundary Condition
Condition
Reff depends on indices of refraction (easily calculated)

Ls approximately (s)-1
Extrapolated Zero-boundary Condition
Solutions: Semi-infinite Medium
Method of images
Solutions: Semi-infinite Medium
Danen, R.M., Wang, Y., Li, X.D., Thayer, W.S., and Yodh, A.G., Photochemistry and Photobiology. 67, 33-40 (1998)
Solutions: Slab Medium
Spectroscopy:
Spectroscopy: Absorption
Absorption Coefficients
Coefficients vs.
vs.
Total Hemoglobin Concentration = [HbO2] + [Hb] = THC

THC =
Tissue Oxygen Saturation = [HbO2] / THC = StO2
Outline
Light Transport
Single Scattering

Oxygen Metabolism

Breast
Brain
Arridge SR, Optical tomography in medical imaging, Inverse Problems 15, R41-R93, 1999
= D0 + D
(Born)
(Rytov)
Basic Scattering Theory (Example)
D = 0
Greens Function
>>
, Incident wave, Greens function ~

,
Inverting the Data

Discretize the Integral
Inverting the Data (one-step)
[] = W [a]
(Set of linear equations)
[a] = W []
-1
Principles of Computerized Tomographic Imaging by Avinash C. Kak, Malcolm Slaney

Inverting the Data (iteratively)
3D Image Reconstruction
Finite difference forward calculation, parallel processor implementation.
Culver, J.P., Choe, R., Holboke, M.J., Zubkov, L., Durduran, T., Slemp, A., Ntziachristos,
V., Pattanayak, D.N., Chance, B., and Yodh, A.G., Medical Physics 30, 235-247 (2003)
Outline
Light Transport
Single Scattering

Oxygen Metabolism

Breast
Brain
(Single) Dynamic Light Scattering
s
Correlation Transport Equation

~ E*(r,t+) E(r,t)
B. J. Ackerson, R. L. Dougherty, N. M. Reguigui, and U.Nobbman, "Correlation transfer: application of radiative transfer
solution methods to photon correlation problems," J. Thermophys. Heat Transfer 6, 577588 (1992).
R. L. Dougherty, B. J. Ackerson, N. M. Reguigui, F. Dorri-Nowkoorani, and U. Nobbmann, "Correlation transfer:
development and application," J. Quant. Spectrosc. Radiat. Transfer. 52, 713727 (1994).
P11 Approximation (Again)
Correlation Diffusion Equation

D. A. Boas, L. E. Campbell, and A. G. Yodh, Phys. Rev. Lett. 75, 18551858 (1995).
is Light Diffusion Coefficient.
= fraction of scatterers that move.
Differential Form of Diffusing-Wave Spectroscopy (DWS)

G. Maret and P. E. Wolf, Z. Phys. B 65, 409413 (1987); D. J. Pine, D. A. Weitz,
P. M. Chaikin, and E. Herbolzheimer, Phys. Rev. Lett. 60, 11341137 (1988).
Remainder Analysis Formally Same

as Photon Diffusion Equation
Solutions ~
)2
(k0
Diffuse Correlation Imaging &

Spectroscopy
Measurements of Blood Flow
Blood Flow Index (BFI)

gives r2 ()
r2 () ~ Db
Db = BFI
= fraction of scatterers moving
Db = effective diffusion constant
rBFI = relative blood flow change
Outline
Light Transport
Single Scattering

Oxygen Metabolism

Breast
Brain
Sensitivity to Tissue Physiology

1. Absorption Variations [a()]
- Access to tissue chromophore concentrations
- Hemoglobin Concentration (Hb), Blood Volume
- Blood Oxygen Saturation (HbO2/[Hb + HbO2])
- Water, Lipids
2. Exogenous Contrast Agents
- Absorption Contrast, Drugs, [a()]
- Fluorescence [c], lifetime
- Uptake & Clearance [a()], [c(t)]
3. Scattering Variations [s,()]
- Organelle Concentrations (mitochondria,)
- Background fluids, n(,t).
4. Motions of Scatterers [r2()], , BFI
- Average Blood Flow Density
- Brownian Dynamics
Circulatory
System
Images from Human

Physiology by Vander,
Sherman and Luciano,
Chapter 13.
Circulatory System
At any given time, some of the
Hemoglobin carried in the red
blood cells is oxygenated (HbO2)
and some is deoxygenated (Hb).
Images from Human

Physiology by Vander,
Sherman and Luciano,
Chapter 13.
Oxygen Exchange
98% of Oxygen in Blood is
bound reversibly to hemoglobin.
O2 (dissolved gas) + Hb HbO2

Blood Volume/Concentration: [Hb] + [HbO2]
Blood Oxygen Saturation (SO2): [HbO2] / ([Hb] + [HbO2] )
Hypoxia:
Hypoxia: Deficiency
Deficiency of
of Oxygen
Oxygen at
at Tissue
Tissue Level
Level
O2 IN
O2 OUT
Tissues
Arterioles
Venules
O2 OUT
(Metabolism)
Arterial Oxygen too low.

Blood flow too slow (ischemic hypoxia).
Local Tissue metabolism too large.
Clinical Scenarios (revisited)
Stroke detection and monitoring

Cancer Imaging and Diagnosis
Cancer Therapy monitoring
Mitochondial diseases
Epilepsy
Brain Activation
Muscle Activation
(Peripheral Vascular Disease)
[Hb] , [HbO2] , THC, StO2 , BFI , rBFI

Cerebral Oxygen Metabolism: CMRO22
from DOS/NIRS
from DCS
Outline
Light Transport
Single Scattering

Oxygen Metabolism

Breast
Brain
DOS: Oxyhemoglobin Dissociation Curve

Mouse erythrocytes in tissue
phantom over the course of
phantom deoxygenation.
Wang, H.-W., Putt, M.E., Emanuele, M.J., Shin, D.E.,

Glatstein, E., Yodh, A.G., and Busch, T.M.,
Treatment-induced changes in tumor oxygenation
predict photodynamic therapy outcome. Cancer
Research 64, 7553-7561 (2004)
Diffuse optics get oxygen saturation (SO2).

Oxygen electrodes get pO2.
Validation of DCS
DCS has been validated:
against ASL-MRI
against Xenon-CT
against Transcranial Doppler Ultrasound
against Color Doppler Ultrasound
against Fluorescent Microspheres
against Laser Doppler
by comparison to Literature
in Phantoms
Validating DCS Across Spatial Scales in Brain
DCS vs Laser Doppler: Rat Brain (3cm)
Hypocapnia by
Hyperventilation.
(Flow decreases
during activation
period.)
Live vs Dead Piglet (25 cm)
Chao Zhou, Stephanie A. Eucker, Turgut Durduran, Guoqiang Yu, Jill Ralston, Stuart H.
Friess, Rebecca N. Ichord, Susan S. Margulies, and Arjun G. Yodh. Journal of Biomedical
Optics, 14(3):034015, 2009.
DCS vs Fluorescent Microspheres:

Neonatal Piglet Brain (25 cm)
Flow decrease
measured versus
time after ~200
Radian/sec
rotational head
injury to mimic
traumatic brain
injury in babies.
Hypercapnia (Whole Brain Response)
Two-layer model
Hypercapnia (Scalp Response)
Small (if any) scalp flow change detected during measurement!

DCS Validation with Xenon-CT
with Kofke, Levine, Grady, Detre, Greenberg

Example Patient
DCS vs Xenon-CT: Bed-Side Comparison
Good correlation, good agreement

with Kofke, Levine, Grady, Detre, Greenberg
Outline
Light Transport
Single Scattering

Oxygen Metabolism

Breast
Brain
Diffuse Optical Tomography of Breast
Regine Choe, Soren D. Konecky, Alper Corlu, Kijoon Lee, Turgut Durduran, David R. Busch, Saurav Pathak, Brian J. Czerniecki,
Julia Tchou, Douglas L. Fraker, Angela DeMichele, Britton Chance, Simon R. Arridge, Martin Schweiger, Joseph P. Culver,
Mitchell D. Schnall, Mary E. Putt, Mark A. Rosen, and Arjun G. Yodh, Journal of Biomedical Optics, 14(2):024020, 2009.
Potential niches for DOT in Breast Cancer
Parallel-Plane DOT Instrument
Culver, Choe, Holboke, Zubkov, Durduran, Slemp, Ntziachristos, Chance, Yodh, Medical Physics 30 2003
3D Diffuse Optical Tomography
Invasive Ductal Carcinoma
53-year-old post-menopausal female, 2.2 cm invasive ductal carcinoma

Cyst & Invasive Ductal Carcinoma
47-year-old pre-menopausal female, 6 cm cyst & 1.3 cm invasive ductal carcinoma

Example: Malignant vs Benign

Malignant: Invasive Ductal Carcinoma
MRI axial slice
rTHC
rStO 2
rTHC
rStO 2
Optical Index
Region of Interest
Benign: Fibroadenoma
MRI axial slice
Optical Index
Region of Interest
Tumor/Normal Endogenous Contrast (N=51)
(A) Benign,
(B) Malignant measured before core biopsy, (C) Malignant measured after core biopsy
Outline
Light Transport
Single Scattering

Oxygen Metabolism

Breast
Brain
Functional Activation In Brain
Functional Activation In Brain
THC = Total Hemoglobin Concentration

StO2 = Blood Oxygen Saturation
rBF = Relative Blood Flow
CMRO2 = Rate of Cerebral Oxygen Metabolism
Motor Stimulus: Optical
Motor Stimulus: Optical
Durduran, T., Yu, G., Burnett, M.G., Detre,

J.A., Greenberg, J.H., Wang, J., Zhou, C.,
and Yodh, A.G., Diffuse optical
measurement of blood flow, blood
oxygenation and metabolism in human
brain during sensorimotor cortex activation.
Optics Letters 29, 1766-1768 (2004).
Population Average (n=5)
Durduran, Yu, Burnett, Detre, Greenberg, Wang, Zhou, Yodh, Optics Letters, 2004
Clinic: Relevant Cerebral Physiology

MAP
ICP
CPP = MAP - ICP

Cerebral Blood Flow Autoregulation
CPP = MAP - ICP

Intracranial Pressure (ICP) Monitoring
Other CBF Monitoring Schemes

Xenon CT
Arterial-Spin-Labeled MRI (ASL-MRI)
Transcranial Doppler Ultrasound (TCD)
Opportunities for Optics

Continuous CBF monitoring at the
bedside.
Direct measurement of Tissue
Microvasculature.
Combine with NIRS/DOS to get
cerebral metabolism.
Acute Ischemic Stroke Study Protocol
Turgut Durduran, Chao Zhou, Brian L. Edlow,

Guoqiang Yu, Regine Choe, Meeri N. Kim, Brett L.
Cucchiara, Mary E. Putt, Qaisar Shah, Scott E. Kasner,
Joel H. Greenberg, Arjun G. Yodh, and John A. Detre,
Opt. Express, 17(5):3884-3902, 2009.
Cerebral
Cerebral Blood
Blood Flow
Flow vs.
vs. Head
Head of
of Bed
Bed Angle:
Angle:
Healthy
Healthy Subjects
Subjects vs.
vs. Stroke
Stroke Patients
Patients
Common Response
Injured hemisphere doesnt autoregulate.
Cerebral
Cerebral Blood
Blood Flow
Flow vs.
vs. Head
Head of
of Bed
Bed Angle:
Angle:
Healthy
Healthy Subjects
Subjects vs.
vs. Stroke
Stroke Patients
Patients
Paradoxical Response
Injured hemisphere doesnt autoregulate.
Results
HOB position was found to be a significant factor in both
hemispheres (healthy and stroke groups).
HOB was a stronger factor in the infarcted area which also
showed a larger variation (stroke group).
Paradoxical Response (25% of stroke group): the maximal
CBF occurred at an elevated angle. Therefore, standard clinical
practice of HOB flat might not be optimal for all stroke
patients.
Turgut Durduran, Chao Zhou, Brian L. Edlow, Guoqiang Yu, Regine Choe, Meeri N. Kim, Brett L. Cucchiara, Mary E. Putt,
Qaisar Shah, Scott E. Kasner, Joel H. Greenberg, Arjun G. Yodh, and John A. Detre, Opt. Express, 17(5):3884-3902, 2009.
Outline
Light Transport
Single Scattering

Oxygen Metabolism

Breast
Brain
Tumor Therapy Monitoring
Neoadjuvant chemotherapy
Choe, Corlu, Lee, Durduran, Konecky, Grosicka-Koptyra, Arridge, Czerniecki,

Fraker, DeMichele, Chance, Rosen, Yodh, Medical Physics, 32, 2005.
Photodynamic Therapy
Injection of
photosensi tizer
Tumor
Illuminated
by light
Laser
Single t
S1
Intersystem
Crossing
Excited
Trip let
T1
c
n
e
Type I
O2
1O
n
tio
rp
Photoactiva ted
drug
induced
Type I I
s
b
A
3O
single t
oxygen
c
s
re
o
lu
F
destroys
2
tum or
Diffuse
Diffuse Optical
Optical Measurements
Measurements of
of Tumor
Tumor
Response
Response Before,
Before, During
During &
& After
After PDT
PDT
Measurement Protocol
Radiation-Induced Fibrosarcoma (RIF) mice tumors

Control group = light (135J/cm2 at 75 mW/cm2)
Treated group = light + Photofrin (5 mg/Kg)
Treatment efficacy
Days after PDT for tumor growth to a volume of 400 mm3
(starting volume ~100 mm3)
Before/After PDT
Significant decreases in blood flow and oxygen saturation

Responses During PDT
Large slope Poor treatment efficacy

Yu, Durduran, Zhou, Wang, Putt, Saunders, Sehgal, Glatstein, Yodh, Busch,
Clinical Cancer Research 11, (2005)
Oxygenation Response Just After PDT
(n = 12)
Low relative - SO2 immediately after PDT Poor treatment efficacy

Wang, Putt, Emanuele, Shin, Glatstein, Yodh, Busch, Cancer Research 64, (2004)
Summary/Future
Diffuse Optics Probes Physiology of
Deep Tissues.
Breast Tumors, Brain, Head & Neck

Tumors, Muscle ...
Animal Model Research (Pre-clinical)
Summary/Future
Image Reconstruction (large data sets)
Image/Data Processing
(composite indices, automated segmentation)
Flow plus Oxygen gives Metabolism

Contrast Agents (fluorescence)
Multi-modal Imaging & Diagnosis
Near Surface (skin)
Dosimetry
Microscopic Origins of Signals
(molecular, tissue level)
Identify New Applications
Collaborators
PhD Students & Post-docs
Baker, Wes
Ban, Han Yong
Buckley, Erin
Busch, David
Kim, Meeri
Xing, Xiaoman
Choe, Regine
Durduran, Turgut
Patak, Saurav
Boas, David
Cheung, Cecil
Cheung,Rex
Corlu, Alper
Culver, Joseph
Danen, Robert
Fisher, Jonathan A. N.
Giammarco, Joe
Gonatas, Dinos
Holboke, Monica
Intes, Xavier
Konecky, Sore
Lee, Kijoon
Li, Xingde
Liu, Hanli
Meglinsky, Igor
Ntziachristos, Vasilis
O'Leary, Maureen
Ripoll, Jorge
Slemp, Alison
Solonenko, Michael
Sunar, Ulas
Vulcan, Teodor
Wang, Hsing-Wen
Yu, Guoqiang
Zhou, Chao
Zubkov, Leonid
Senior Collaborators
Simon Arridge, University College London, UK
Larry Campbell, Hobart & Williams College
Mark Burnett, University of Pennsylvania
Theresa Busch, University of Pennsylvania
Britton Chance, University of Pennsylvania
Brian Czerniecki, University of Pennsylvania
Angela DeMichele, University of Pennsylvania
John Detre, University of Pennsylvania
Jared Finlay, University of Pennsylvania (HUP)
Tom Floyd, University of Pennsylvania
Doug Fraker, University of Pennsylvania
Joe Friedberg, University of Pennsylvania
Eli Glatstein, University of Pennsylvania
Joel Greenberg, University of Pennsylvania
Steve Hahn, University of Pennsylvania
Daniel Licht, Children's Hospital of Philadelphia (CHOP)
Chandrakala (Kala) Menon, University of Pennsylvania

Emile Mohler III, University of Pennsylvania
Shoko Nioka, Johnson Foundation, Penn/HUP
Deva Pattanayak, Vishay Intertechnology Inc.
Mary Putt, University of Pennsylvania
Harry Quon, University of Pennsylvania
Nimi Ramanujam, Duke University
Robert (Bob) Rogers, University of Delaware
Mark Rosen, University of Pennsylvania
Mitch Schnall, University of Pennsylvania
Martin Schwieger, University College London, UK
Chandra (Sandy) Sehgal, University of Pennsylvania
Bruce Tromberg, University of California at Irvine
Qing Zhu, University of Connecticut
Tim Zhu, University of Pennsylvania

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Diffuse Optics: Fundamentals

& Tissue Applications

Acknowledgement: NIH, ARMY

Biomedical Motivations Revisited

Validation of the Techniques

from: Star Trek

In-Vivo Optical Biopsy

Imaging & Monitoring

Stroke detection and monitoring

Biomedical Motivations Revisited

Validation of the Techniques

How are photons lost from the

Absorption (linear response)

What molecules are present?

Scattering (single scattering limit)

Scattering (single scattering limit)

d () = Differential Scattering Cross-section

s = reduced scattering coefficient = s (1-g)

What are the scatterers?

What are scatterer concentrations?

Scattering: Temporal Fluctuations

Traditional Optical Techniques

Biomedical Motivations Revisited

Validation of the Techniques

Problem of Tissue: Multiple Scattering

Linear Transport Theory

Linear Transport Equation

Photon Fluence Rate & Flux

Fluence rate (W/cm2)

Fluence & Flux in PNN Approximation

Radiance in the P11 Approximation (N=1)

Substitute P1 form of L into the linear transport equation.

Photon Diffusion Equation

Photon Diffusion Equation: Assumptions

Photon Diffusion Equation: Assumptions

(s) ~ 300 MHz

Independent of Incident Direction.

Biomedical Motivations Revisited

Validation of the Techniques

Frequency Domain: Diffuse

*first suggested by Enrico Gratton

Frequency Domain: Point

for arbitrary source distribution

Frequency Domain: Point

Point Source at the Origin in Infinite Homogeneous Media

Diffusive Wave Optics

Boas, Oleary, Chance, Yodh. Physical Review E, 47(5) 1993.

Time Domain Solution

Time Resolved Reflectance and Transmittance for The Noninvasive

What has been gained?

What about heterogeneous media?

Biomedical Motivations Revisited

Validation of the Techniques

Boundary Conditions: Semi-infinite Media

e.g. Air-Tissue Boundary

Boundary Conditions: Semi-infinite Media

R() is a Fresnel Coefficient

Reff depends on indices of refraction (easily calculated)

Extrapolated Zero-boundary Condition

Solutions: Semi-infinite Medium

Solutions: Semi-infinite Medium

Solutions: Slab Medium