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Biomedical Imaging by Near Infrared Light

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Biomedical Imaging by Near Infrared Light Powered By Docstoc
					Biomedical Imaging by
  Near Infrared Light
            Dr. Ronald Xu
          Assistant Professor
     Biomedical Engineering Center

            270 Bevis Hall
               688-3635
           xu.202@osu.edu

             Feb. 16, 2005
                Outline
 Light tissue interaction
 Near Infrared imaging of tissue
  oxygen saturation and
  hemoglobin concentration
 Breast cancer diagnosis by near
  infrared light
 Conclusions and future work
How Photons Interact with Biological Tissue

                      Scattered and reflected




       s       s’
                           Scattered and
                            absorbed



                       mal, msl, g
                    Scattered and transmitted
Scattering is Caused by Tissue Ultrastructure




                 (http://omlc.ogi.edu)
Absorption is Caused by Multiple Chromophores
                                         In NIR Region, Hb and HbO are
                                             Major Sensitive Absorber

                                 4000
                                                                  - Deoxy-hemoglobin
                                                                                                  HbO m a 1   HbO m a 2
                                                                                                   l2    l       l1    l
                                                                                         Hb   l1 l 2
                                                                                                 Hb HbO   Hb2 HbO 
                                 3500
                                                                                                                 l   l1
extinct coeff (cm-1/mol/liter)




                                                                  - Oxy-hemoglobin
                                 3000
                                                                                                    Hb m a 2   Hb m a 1
                                                                                                     l1 l         l2 l
                                                                                         HbO   l1 l 2
                                                                                                  Hb HbO   Hb2 HbO 
                                 2500      l1 = 690nm                                                             l   l1

                                 2000

                                 1500
                                                                      l2 = 830nm             [ HbT ]  [ Hb ]  [ HbO ]
                                                                                                    [ HbO ]
                                 1000                                                        SO2 
                                                                                                     [ HbT ]
                                 500


                                   650      700          750       800        850      900

                                                        wavelength (nm)
          What Near Infrared Light
              Can Measure?
   Absorption measurement
       Tissue hemoglobin concentration
       Tissue oxygen saturation
       Cytochrome-c-oxidase concentration
       Melanin concentration
       Bilirubin, water, glucose, …
   Scattering measurement
       Lipid concentration
       Cell nucleus size
       Cell membrane refractive index change
       …
        Why Tissue Oximetry?
   Tissue oxygenation and hemoglobin
    concentration are sensitive indicators of
    viability and tissue health.
   Many diseases have specific effects on
    tissue oxygen and blood supply: stroke,
    vascular diseases, cancers, …
   Non-invasive, real time, local measurement
    of tissue O2 and HbT is not commercially
    available
  Why Near Infrared? Pros and Cons
Compared with Other Imaging Modalities
    Advantages:
        Deep penetration into biological tissue
        Non-invasive
        Non-radioactive
        Real time functional imaging
        Portable
        Low cost
        Tissue physiological parameters
        Potential of molecular sensitivity

    Disadvantages:
        Low spatial and depth resolution
        Hard to quantify
     Near Infrared Diffuse Optical
     Imaging: Problem Definition
   Find embedded tissue heterogeneity
                       o
   By solving: OD  ln  f ( St O2B , H bt B , St O2 , H bt T )
                                                    T

                       i
                                   i                    o
                          source              detector

          StO2B, HbtB



                                          StO2T
                                          HbtT
Diffuse Approximation for Photon
  Migration in Biological Tissue
 Radiative transfer equation:
            
     1 I (r , t , es )                                         
                        es  I (r , t , es )  ( m a  m s ) I (r , t , es )
     c      t
                    '                           
      m s  f (es , es )I (r , t , es )d 2es ' q(r , t , es )
            4
 Time dependent diffuse equation:
           
     1  (r , t )                                            
                      k (r ) (r , t )  m a (r , t )  q0 (r , t )
     c t
                                                     
     Where:         (r , t )   I (r , t , es )d 2es
                        4
Simplified diffusion model for Continuous Wave (CW) illumination:
                                                
      m a (r )    k (r ) (r )  q0 (r )
        Major Assumptions for
       CW Diffuse Approximation

 Regard photons as particles
 Neglect interference and polarization
  properties.
 Highly turbid media (scattering >> absorption)
 Steady state
 Dipole Sources and Extrapolated Boundary
    for Semi-Infinite Homogenous Media
                                                                     s’                                           z  2 ze  z0

                                                                                                                  z e  2 /( 3m s ' )
Negative source is
introduced to meet BC                                                                                             z0  1 / m s '
                                                                      s
Extrapolated boundary
where fluence rate is 0


Isotropic source at one
transport length

                                 i                         i                    
                 o               exp( meff r  rs )             exp( meff rs '  r )
                          4D r  rs                       4D rs '  r
         Farrell, T.J., M.S. Patterson, et al., A diffusion theory model of spatially resolved, steady-state diffuse reflectance for the
         noninvasive determination of tissue optical properties in vivo. Medical Physics, 1992. 19(4): p. 879-888.
             Image Reconstruction for Tissue with
                  Embedded Heterogeneity
         S                                      +                          Assume an absorption perturbation ma
                                                                        -5                                  
                                                                     x 10      ma (r )  ma (r )  ma (r )
                                                                                          0

                                                                     14
                                                                              Result in optical perturbation 
                                                                      12                                   
                                                                               (r , rs )  0 (r , rs )  (r , rs )
                                                                      10
                                                                                and ma are correlated (Born approx)
                                                                                                                        
                                                                      8        (r , rs )    G( r 'r )ma (r ' )0 (r ' , rs ) / Dd 3r '
                               N                                      6        Numerical expression of above eq.
                W m            i     i
                                          a
                                                                      4
                           i 1                                               (rsm , rdm )     W11  W1n      ma ,1 
                                                                                                                       
                                                                      2                              
                                                                              (r , r )        W                      
                                                                                  sm dm  m ,1    m1  Wmn  m,n  ma ,n  n ,1
                  
W  G (ri  rs )G (rd  ri )
        S                             S                                 S                            S                
(         exp(  meff r  rs )        exp(  meff rs '  r ))  (       exp(  meff r  rd )        exp(  meff r  rd ' )
     4D r  rs                     4D rs '  r                        4D r  rd                     4D r 'rd '
A Portable Near Infrared Imager
  for Breast Cancer Diagnosis




Cheng, X., X. Xu, et al., Optical imaging system with direct image
reconstruction, US patent, 09/778,617, 2001.
 Breast Cancer Diagnosis by Near
Infrared Imaging: Basic Hypothesis

   [HbT] of cancerous tissues is higher
    than the surrounding normal tissues
    (vascularization).
   SO2 of cancerous tissues is lower
    than the surrounding normal tissues
    (metabolism).
Preliminary Clinical Trial at BeiJing Cancer Institute
                                D[SO2]% vs. D[Hbt]%
                                                         120%

                                                         100%
                      cancer(fine_needle aspiration)
                                                         80%

                                                         60%
     D[Hbt]%




               cancer (see active cell hyperplasia)
                                                          40%
                                            cancer (5X6cm2)
                                                         20%
                       cancer (typical symptoms)
                                                           0%
           -25%      -20%     -15%      -10%       -5%       0%       5%       10%
                                                         -20%

                                                         -40%
               fibroadenoma                                     fibroadenoma
                                                         -60%
                                               D[SO2]%

     Cheng, X., X. Xu, et al., A novel optical scanning system for breast cancer imaging.
     Proc. SPIE, 2001. 4244: p. 468-473.j
Pilot Clinical Study at Massachusetts General Hospital




   Cheng, X., J.-m. Mao, et al., Breast Cancer Detection by Mapping Hemoglobin Concentration
   and Oxygen Saturation. Applied Optics, 2003. 42(31): p. 6412-6421.
Near Infrared/Ultrasound Dual Modal Imaging
         for Breast Cancer Diagnosis

Near infrared Imaging:
-Low depth resolution
-Limited spatial resolution
-High chemical sensitivity
-Low cost                                                        Hybrid Imaging:
                                                                 -High depth resolution
                                Portable near
                                                                 -High spatial resolution
                               infrared imager
                                                                 -High chemical sensitivity
                                                                 -Low cost
                                                                 -Real time
Ultrasound Imaging:                                Image co-
-High depth resolution                            registration
-High spatial resolution                            marker
-No chemical sensitivity
-Low cost

                                   Portable
                              ultrasound imager
                    Future Work
   Technology development
       Algorithm development: 3D image reconstruction for layered
        tissues and tissues with embedded heterogeneity
       Hybrid imaging combining multiple modalities for improved
        contrast and spatial/ depth resolution.
   Clinical applications
       Breast cancer diagnosis, therapeutical assessment and
        image guided surgery
       Miniature near infrared/ultrasound sensor for brain
        functional study
       Other clinical opportunities: sports medicine, ophthalmology,
        neonatalogy, cardiology, OB/GYN, …
Biomedical Imaging by
  Near Infrared Light
            Dr. Ronald Xu
          Assistant Professor
     Biomedical Engineering Center

            270 Bevis Hall
               688-3635
           xu.202@osu.edu

             Feb. 16, 2005
More Hypothesis: normal and cancerous tissues
   response differently to external pressure
   •   Normal tissue
         External pressure will reduce the difference in
         [HbT] distribution. Regions with higher [HbT]
         tend to loss blood with a larger rate than regions
         with lower [HbT].

   •   Cancerous tissue
         External pressure will increase the difference in
         [HbT] distribution. Cancer tissues tend to loss
         blood with a lower rate than the surrounding
         normal tissues.
 Handheld probe with load cell for pressure study

                       Rubber cushion
Compressive
load cell

Linear
                               2
bearings

Probe body
                                Probe
                                 Tissue
                                house



      Cheng, X. and X. Xu, Study of the pressure effect in near infrared spectroscopy. Proc.
      SPIE, 2003. 4955: p. 397-406.
 Pressure Regulated Imaging for
Normal Breast and Nipple Tissues
         [SO2] before   Dynamic imaging
                         of [HbT] during        Pressure profile and
         compression                            corresponding Hbt change
                          compression

                                           55
                        90




Nipple

                        70                 25




                        88                 28



Normal
Breast
                        78
                                            8
Benchtop test on a tumor simulating phantom
2D Imaging on Tumor
 Simulating Phantom
2D [Hbt] projection as tumor moves
from bottom (-0.65”) up (-0.15”).




2D [SO2] projection as tumor is
gradually deoxygenated




2D [Hbt] mapping as tumor moves
horizontally at a step of 1mm
A Blood Circulation System for Benchtop
     Validation of Tissue Oximeter



                                                     Computer
                         Roller
                         pump              Tissue
               Water                      Oximeter
               bath                        Probe
                              PH meter
                              PO2 meter
               N2

               O2
                       Membrane        Blood
               CO2     Oxygenator     Phantom
                                        Full Range Continuous
                                         De-oxygenation Test
                        100
                                                                                          Full range
                                                       Full oxygenation                    oxygenation test
                                                       ([SO2]>98%)
Oxygen Saturation (%)




                        80                                                                 was performed on
                                                                                           liquid phantom
                        60                                                                 (blood: ~6%, lipid:
                                                                                           1%).
                        40                                                                Continuous de-
                                                                                           oxygenation over 4
                        20                                                                 hours after fully
                                                                                           oxygenated.
                         0           Full de-oxygenation                                  Total sampling
                                     ([SO2]<10%)                                           points over 4000.
                        -20
                           0   500     1000   1500    2000   2500   3000   3500   4000

                                                     Sample No.
                                                                  Stepped [SO2] Test: Compared
                                                                 with Gold Standard Gas Analyzer
Tissue Oximeter Measurements of SO2 vs. OSM Measurement
Oxygen Saturation Measured by Photonify Probe (%)




                                                    100
                                                                                                            •   [SO2] test on a 25% diluted
                                                     90                                                         blood phantom.
                                                     80


                                                     70
                                                                                                            •   Flow rates of N2/ O2/ CO2
                                                                                                                were adjusted for:
                                                     60                                                         1)maintaining PH level,
                                                                                                                2)stabilizing [SO2]/ [PO2]
                                                     50
                                                                                                                @different levels.
                                                     40


                                                     30
                                                                                                            •   The resulting correlation
                                                                                                                coefficient between oximeter
                                                     20                                                         reading and gold standard
                                                                                                                reading is 0.9883
                                                     10


                                                      0
                                                          0        20      40       60      80        100
                                                              Oxygen Saturation Measured by OSM3(%)
                                                   Linearity and Sensitivity
                                                   for [Hbt] measurement

                                     0.122
                                       0.45                                                             [Hbt] test was
                                                                                                         performed on a
NIR Measurement of [Hbt] ((g/dL) )
NIR Measurement of [Hbt] g/dL




                                        0.4
                                     0.121                 Measurement
                                                                                                         liquid blood
                                       0.35                Least square fit                              phantom with 1%
                                      0.12
                                                                                                         starting lipid%.
                                        0.3      0.015% change in
                                     0.119                                                              Linear correlation
                                                 blood concentration
                                       0.25                                                              coefficient: > 0.96
                                     0.118
                                        0.2                                                             Sensitivity up to
                                     0.117                                                               0.02% of blood
                                       0.15
                                                                                                         volume change,
                                     0.116
                                        0.1

                                     0.115
                                       0.05
                                            0
                                          0.76   0.5
                                                 0.77     0.78 1.5
                                                          1      0.79 2 0.82.5 0.81
                                                                                  3       3.5
                                                                                        0.82      4
                                                                                                0.83
                                                        Blood Concentration Vol%
                                                        Blood Concentration ((Vol% ))
          Technology Validation on an
          Isolated Animal Limb Model




              Arterial
              port
   Extra-                       2
corporeal        Area of major       4
                 vessels and tubes
  blood                              3
circulation                    1         Tissue
                                         oximeterp
              Venous                     robes
              port
                                         Full Range De-oxygenation
                                             Test on Limb Model
                                  Continuous de-oxygenation captured by probe #3
                         90

                         80
                                          Corresponding to 99.7%
                                          arterial blood oxygenation
Tissue Oxygenation (%)




                         70

                         60

                         50

                         40                                     Corresponding to 4.0%
                                                                arterial blood oxygenation
                         30

                         20

                         10

                          0
                              0     1    2     3     4      5       6      7     8      9    10

                                                   Time (minutes)
                         Stepped [SO2] Test on
                              Limb Model
                                       [SO2] Correlation Test on Probe #3                    Oxygenation and
Tissue Oximeter Measurement (%)

                                  80                                                          pH level were
                                                                                              controlled by
                                  70
                                                                                              N2/O2/CO2 flow
                                  60                                                          rates
                                  50
                                                                                             Blood was drawn
                                                                                              from both arterial
                                  40                                                          and venous ports
                                  30
                                                                                              for gold standard
                                                                                              measurement
                                  20
                                                                                             Regression slope:
                                  10                                                          0.715
                                  0
                                                                                             Regression
                                   0   10   20   30   40   50   60   70   80   90   100       intercept: 6.908
                                             OSM Measurement (%)                             Correlation
                                                                                              Coefficient: 0.996
                                                      Stepped [Hbt] Test on
                                                          Limb Model
Tissue [Hbt] captured by probe #3 (g/dL)



Correlation between tissue [Hbt] and blood [Hbt]                                        Blood [Hbt] level was
                                           0.36                                          controlled by injecting
                                                                                         saline into the circuit.
                                           0.34                                         Blood was drawn from
                                           0.32                                          both arterial and venous
                                           0.3
                                                                                         ports for gas analyzer
                                                                                         measurement.
                                           0.28                                         Tissue [Hbt] is measured
                                           0.26                                         Regression slope: 0.0312
                                           0.24                                         Regression intercept: -
                                                                                         0.0061
                                           0.22
                                                                                        Correlation Coefficient:
                                           0.2                                           0.9986
                                           0.18
                                           0.16
                                                  5   6   7   8   9   10   11   12
                                              Blood [Hbt] Measured by OSM3 (g/dL)

				
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