1. NeO2
A Depth-Resolved Near
Infrared Oximeter to
Diagnose Necrotizing
Enterocolitis
Capstone Group J
Nikhil Kalluri, Kritika Iyer, Josh Woo, Samantha St. Germain, Kevin Chang
2. Clinical
Motivation
Highest
incident rate of
all disorders
affecting
neonates
50% Mortality
Rate
1,330
deaths/year in
the US alone
Over $1
billion/year in
hospital costs
(US)
If NEC is diagnosed earlier
in the progression of the
disease, many lives will be
saved!
3. Necrotizing Enterocolitis
Intestine in normal,
healthy neonate
Intestine in neonate
with NEC
Stage I
•Bloody stools
•distension
Stage II
•Metabolic
acidosis
•Intestinal dilation
Stage III
•Hypertension
•Gut ischemia
•Intestinal rupture
5. Depth-Resolved Near-Infrared Spectroscopy (NIRS)
• Measures oxygen saturation levels
• Tissue-specific oxygen measurements
• Benefits: Depth-resolved, high-resolution, detects NEC
at its onset (Stage I)
Our Novel
Approach
Our goal is to use this technology as a quantitative approach to
detect NEC at earlier stages by identifying lower oxygen levels,
which are directly indicative of tissue ischemia. We want to
revolutionize the diagnostic modalities used to detect NEC, and aim
to have our device serve as the gold standard for diagnosis.
7. Overview of Our Device
7
• Two rows of 10 LEDs
• LEDs fired sequentially; photons migrate from LED source, into
the tissue, then to a photodetector on the surface of the skin
• Distance between a particular LED and the photodetector
corresponds to a specific tissue depth
8. Overview of Our Device Cont.
8
• Target species of the probe is hemoglobin (Hb)
• -Oxy and deoxy Hb distinguishable at 660 nm and 880 nm
• Signals give measurements of HbO2 and Hb at various depths in
intestines
• - ratio of oxy to deoxy Hb will differentiate between healthy
and diseased tissue.
9. 65% of original light intensity (Io) will be absorbed by the photodetector.
Photon Path Monte Carlo Simulations
9
660 nm
IN
660 nm
OUT
log(Absorbancezr)(J/cm3) log(Absorbancezr)(J/cm3)
Ski
n
Intestine
Blood
Intestine
Ski
n
Blood
log(Fluencezr)( J/cm2)log(Fluencezr)( J/cm2)
Ski
n
Intestine
Blood
Intestine
Ski
n
Blood
10. Photon Path Monte Carlo Simulations
10
56% of original light intensity (Io) will be absorbed by the PD
di= 4 mm, ds= 2 mm
Intestine
Skin
Blood
log(Absorbancezr)(J/cm3) log(Absorbancezr)(J/cm3)
Skin
Intestine
Blood
log(Fluencezr)( J/cm2)log(Fluencezr)( J/cm2)
Skin
Intestine
Blood
Intestine
Skin
Blood
880 nm
IN 880 nm
OUT
17. Gel Experiments - Protocol
Prepare gelatin
solution
Reagent
measurement
Allow gelatin to
set
in vitro
phantom test
18. Gel Experiments - Tests
1
8,12,20 wt %
gelatin
control: no dye
660 filter: red dye
2
Spatial resolution
Red and control
in 1 cm
horizontal layers
3
Depth resolution
Red and control
in 2 mm vertical
layers
19. Gel Experiments - Set up
12% Gelatin
No dye
12% Gelatin
Red dye
2 mm vertical
layers
1 cm horizontal
layers
8% Gelatin
No dye
20% Gelatin
No dye
21. Gel Experiments - Results
0
0.5
1
1.5
2
2.5
3
3.5
4
4.5
5
1 2 3 4 5 6
Voltage(V)
LED Number
12% Gelatin without Red Dye
N=10
0
1
2
3
4
5
6
1 2 3 4 5 6
Voltage(V) LED Number
12% Gelatin with Red Dye
660nm
880nm
N=10
22. Gel Experiments - Results
0
1
2
1 2 3 4 5 6
VoltageRatio
LED number
Voltage Ratios for Depth
Resolution
0
1
2
1 2 3 4 5 6
VoltageRatio
LED number
Voltage Ratios of Spatial
ResolutionOne-tailed student’s t-test
p << 0.05
(p = 1.35E-5)
One-tailed student’s t-test
p > .05
(p = 0.061 and p = 0.051)
N=10
N=10
23. Animal Experiments - Protocol
Baby pig, 8 lb
Survey abdominal region
in methodical fashion
1 2
4 3
28. Special Thanks
This work was supported by funding from the University of California, Los
Angeles (UCLA) Department of Bioengineering. We would like to thank the
following mentors for their guidance in this project:
Dr. Warren Grundfest
Dr. George Saddik
Dr. Stephanie Seidlits
Dr. Dino Di Carlo
Dr. James Dunn
Raghav Gupta
Ashkan Maccabi
Theodore Kee
Arshia Ehsanipour
Nhan Huynh
Jaime De Anda.
30. Bashkatov, AN., EA Genina, and VV Tuchin. "Optical Properties Of Skin, Subcutaneous, And Muscle Tissues: A Review." Journal of Innovative Optical Health
Sciences 04.1 (2011): 9-38.
Ding, Huafeng, et al. “Refractive Indices of Human Skin Tissues at Eight Wavelengths and Estimated Dispersion Relations between 300 and 1600nm.”
Physics in Medicine and Biology 51 (2006): 1479-1489.
Wei, Hua-Jing, et al. “Optical properties of human normal small intestine tissue determined by Kubelka-Munk method in vitro.” World Journal of
Gastroenterology 9.9 (2003): 2067-2072.
Kostic, Marko. Development and Testing of a Portable Multi-Channel Depth-Resolved Near Infrared Spectroscopy System for Lower Leg Tissue Oxygenation
Monitoring. Thesis, University of California, Los Angeles. 2013.
Prahl, Scott. "Tabulated Molar Extinction Coefficient for Hemoglobin in Water." OMLC. Mar. 1998. Web.
Chiou, Y.b., and U. Blume-Peytavi. "Stratum Corneum Maturation." Journal of Vascular Research: Skin Pharmacology and Physiology 17.2 (2004): 57-66.
Haber, H. P., and M. Stern. "Intestinal Ultrasonography in Children and Young Adults: Bowel Wall Thickness Is Age Dependent." Journal of Ultrasound in
Medicine 19.5 (2000): 315-21.
Cook, Jason R., Richard R. Bouchard, and Stanislav Y. Emelianov. "Tissue mimicking phantoms for photoacoustic and ultrasonic imaging." Biomedical Optics
Express 2.11 (2011): 3193-3206.
"FDA Approves Use of UCLA-created Wearable Device to Address Gastrointestinal Disorders." EE. Web. 29 Jan. 2016.
Gephart, Sheila M. et al.,“Necrotizing Enterocolitis Risk,” Adv Neonatal Care. 2012 April ; 12(2): 77–89.
References
31. References Cont.
Umberger, Erin. “NEC Society to Host First U.S. NEC Conference, Made Possible by PCORI Engagement Award.” NEC Society. Web. 25 Jan. 2016.
Neu, Josef. Walker, Allan W, “Necrotizing Enterocolitis,” N Engl J Med 2011;364:255-64.
Schnabl, K. L. et al., “Necrotizing enterocolitis: A multifactorial disease with no cure.” World Journal of Gastroenterology 2008 Apr 14; 14(14) 2142-2161.
Srinivasan, PS Brandler, MD, D’Souza, A. “Necrotizing Enterocolitis.” Clin Perinatol 35 (2008) 251–272.
Hsueh, Wei, et al. "Neonatal necrotizing enterocolitis: clinical considerations and pathogenetic concepts." Pediatric and Developmental Pathology 6.1
(2003): 6-23.
Oh, S, et al. "Monitoring Technologies in the Neonatal Intensive Care Unit: Implications for the Detection of Necrotizing Enterocolitis." Journal of
Perinatology 30.11 (2010): 701-08.
Staryszak, J, et al. “Usefulness of ultrasound examinations in the diagnostics of necrotizing enterocolitis.” Polish Journal of Radiology 80 (2015): 1-9.
Gay, Andre N. et al., “Near-infrared spectroscopy measurement of abdominal tissue oxygenation is a useful indicator of intestinal blood flow and
necrotizing enterocolitis in premature piglets.” Journal of Pediatric Surgery (2011) 46, 1034 - 1040.
Wang, Lihong, Steven L. Jacques, and Liqiong Zheng. "MCML—Monte Carlo Modeling of Light Transport in Multi-layered Tissues." Computer Methods
and Programs in Biomedicine 47.2 (1995): 131-46.