1  David  Levitz,  PhD  –  Ariel  Beery,  MPA/MA    

Introduction to multimodal imaging An introduction to MobileOCT’s proprietary method, combining high resolution structural, polarization difference, and spectral imaging modalities

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We believe the only cure is early screening

We  can  save  more  lives  in  the  ba1le  against  cancer,  if  only  we  catch  cancer  earlier.    Our  proprietary  technology  can  augment  any  digital  camera  to  provide  clinicians  with  revoluConary  access  to  informaCon  about  Cssue  microstructure  and  composiCon,  including  biomarkers,  so  they  can  beGer  idenCfy  and  characterize  cancers.    

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More is more

•  Current  clinical  imaging  techniques  relies  primarily  on  bright-­‐field  imaging  

•  Tissue  is  not  uniform  –    it  contains  mulCple  layers  and  components  

•  No  single  mode  of  imaging  can  quickly  and  reliably  achieve  high  sensi7vity  and  specificity  

•  By  combining  the  strengths  of  mulCple  imaging  modaliCes,  we  can  provide  the  clinician  with  a  more  complete  picture  of  the  Cssue  

Freckle,  before  and  aPer  PDI:    

Standard  Image   PolarizaCon  Difference  Image  

Malignant  Basel  Cell  Carcinoma  

Standard  Image   PolarizaCon  Difference  Image  

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MobileOCT’s Multimodal Technology

MobileOCT’s  proprietary  technology  does  this  by  using:    •  High  resolu:on  bright-­‐field  imaging  to  provide  the  ‘standard  view’  that  clinicians  are  used  to  working  with  

•  Polariza:on  difference  imaging  (PDI)  to  provide  informaCon  about  the  micro-­‐structural  paGerns  in  the  superficial  layer  of  the  Cssue  

•  Spectral  imaging  to  provide  the  clinician  with  informaCon  about  the  composiCon  of  Cssue  (water,  oxy-­‐  and  deoxy-­‐hemoglobin),  including  some  biomarkers  

MobileOCT’s  adaptor  in  blue,  on  a  Welch  Allyn  video  colposcope  

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Why multimodal is so important:

15%  returns  from  the  surface,  mainly  as  glare  

•  Image  seen  is  formed  by  light  returning  from  different  layers  of  Cssue,  containing  someCmes  conflicCng  informaCon.  

•   To  beGer  analyze  a  sample,  MobileOCT  analyzes  each  element  separately.    

4%  returns  from  the  superficial  layer  (where  most  cancers  form)  

~80%  of  the  light  returns  from  the  deeper  dermis  (or  stroma),  where  informaCon  on  certain  biomarkers  is  found  

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Mode 1: bright-field imaging, the standard

MobileOCT’s  technology  can  be  mounted  on  any  digital  camera,  enabling  the  same  high  resoluCon  images  physicians  are  used  to  seeing    

Stratum    Corneum  

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Mode 2: Polarization Difference Imaging(PDI)

1.  Linearly  polarized  light  is  sent  into  the  sample  (            )  

2.  Light  returning  from  superficial  layer  maintains  polarizaCon  

3.  Light  returning  from  deeper  layer  is  diffuse,  with  its  polarizaCon  evenly  split  between  the  PAR  (          )  and  ORTH  (      )  orientaCons  

4.  We  isolate  the  superficial  layer  with  the  following  equaCon:  

Camera/Sensor  

PDI  =  PAR  –  ORTH    

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Why PDI works: examples from skin

Freckle:  

Malignant  basal  cell  carcinoma  

Standard   PDI  

N.  squamous  cell  carcinoma  

The  freckle,  a  surface  feature,  does  not  impact  the  superficial  layer  

The  disrupCon  occurring  amongst  the  basal  cells  is  hidden  when  observing  the  sample  under  even  high  resoluCon  imaging    

The  faded  area  observed  in  the  high  resoluCon  image  ‘pops  out’  when  PDI  is  applied,  because  one  can  now  observe  the  distrupCon  in  the  superficial  layer  

Jacques et al, J Biomed Opt 2002  

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Mode 3: multi-spectral imaging

•  All  the  wavelengths  of  light  are  analyzed  together,  to  quanCfy  biomarker  content  in  dermis  (stroma)  

•  Tissue  chromophores  are  known  a  priori  (i.e:  Water,  oxy-­‐  and  deoxy-­‐hemoglobin,  melanin,  bilirubin)  

•  The  quanCfied  makeup  of  the  deep  layer  provides  more  details  on  the  structural  changes  visualized  with  PDI  

Tsumra et al., internal paper, Chiba University, Liu et al., Applied Optics, 46, 8328-8334 (2007) Jacques et al Biomed Opt Express (2011)  

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Better Together

•  Each  mode  has  its  own  inherent  strengths  and  challenges  

•  MobileOCT’s  technology  enables  the  clinician  to  view  each  mode  separately,  and  soon  will  enable  viewing  a  composite  of  all  three  models  

•  By  increasing  the  power  available  to  clinicians,  MobileOCT  hopes  to  help  find  cancer,  sooner.