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Non-Invasive Near Infrared Fluorescence Imaging of Gastrointestinal Transit and Gastric Motility.

Rao V. L. Papineni*#, William Mclaughlin#, Tao Ji#, John Harder#, and Ramesh Koka4.
#Carestream Health, Inc. 4Gastroenterology Associates of SW Florida
*E.Mail: rao.papineni1@carestreamhealth.com

Near infrared fluorescence imaging (NIRF) of


murine gastrointestinal (GI) tract Imaging by dye NIRF Imaging of GI Tract
encapsulated polymeric nanoparticles is presented
here. The methodology potentially allows diagnosis
of motility disease in gastrointestinal tract and the A B C D
possibilities of image guided interventions of both the
upper and lower GI tract. Further, one can monitor
the effectiveness of intestinal motility disease
treatment. A commercially available multimodal
imaging system KODAK in-Vivo Multispectral FX
system or KODAK in-Vivo Image Station FX
4000MM were used for the NIRF imaging of mice
subjected to treatment with commercially available
dye encapsulated KODAK X-sight 761 nanosphere.
These particles were delivered by gavage or
intraperitoneal injections or delivered rectally. Time-
lapse fluorescence images were obtained with
10 min 16 min 20 min 34 min
anatomical coregistration using low energy x-ray
imaging. High resolution x-ray images were
obtained using phosphor screen positioned at the E0
Image X-ray, NIRF EX:730, and EM 790
same optical plane producing the anatomical overlay, E F Optical Probes
by
providing context for molecular signal translocation. gavage Time Lapse Imaging
Effects of pharmacological drugs that either slow the
motility, or drugs involved in compartmentalization
of the noninvasive optical nanoparticle signals will be
discussed. NIRF Imaging using KODAK X-Sight 761
Nanospheres. Time lapse images- shown are
representative images in the same positions and
identical signal contrast (A-D, above). Images E and F
obtained at different time points. The inset E0 is
contrasted for signal intensity to show the features of
the intestines. 1 min exp; f-stop 2.8, no binning.
KODAK in-Vivo Image Station FX 4000MM
Optical Probe- Characterization
120 min 210 min

A B C D

NIRF Imaging of Lower GI

10 min 180 min


KODAK X-Sight 761 Nanospheres was delivered by
gavage. Planar images obtained using KODAK in-Vivo
Multispectral FX system at the two precise rotational Image NIRF EX:730, and EM 790 NIRF Imaging of lower GI. Time lapse images-
positions are shown here. The prolonged retention of the Montage of images between 0-180 min. Images
optical signal in the gastric environment was determined- Rectal Delivery were obtained in the identical positions and similar
~95% intensity of the optical probe was observed after 180 of signal contrast. f-stop 2.8, no binning.
min (from comparision of A and C). EX: 720 EM;790, 30 KODAK X-Sight 761 Time Lapse Imaging
sec exp, 2X2 binning.. Nanospheres KODAK in-Vivo Image Station FX 4000MM

Imaging of Drug Induced Gastric Motility 1.4e+6 Motility in the lower GI


Net Intensity (a.u)

Sennosides 1.2e+6 As plotted from net


intensities obtained at a
1.0e+6
particular point (ROI)
8.0e+5 within the rectal delivery
A B C area of the KODAK X-
Loperamide 6.0e+5
Sight 761 Nanospheres
4.0e+5
(see above).
Proton Pump 2.0e+5 Motility
Inhibitors
0.0
0 20 40 60 80 100 120
Time Lapse Imaging (min)

Imaging of KODAK X-Sight 761 Nanospheres together Conclusions


with drugs a, omeprazole, a proton pump inhibitor, • Dye encapsulated polymeric nanoparticles, KODAK X-Sight 761
b,loperamide, anti diarrheal, and c, sennosides, over the Nanospheres maintain integrity in the acidic gastric environment
counter laxative. The NIRF image showing gastric motility
and are a strong candidate for translatable NIRF gastrointestinal
(compare distribution of signal in “c” from “a and b”) was
taken after 15 min of the delivery of the admixtures by imaging contrast agents. These agents report favorably the
gavage using KODAK in-Vivo Multispectral FX system . physiological and drug induced GI motility at both the upper and
F-stop 2.8, no binning. lower GI tract.

Carestream is a trademark of Carestream Health, Inc. The Kodak trademark is used under license from Kodak. Carestream Molecular Imaging is a division of Carestream
Health, Inc. Although the Carestream In-Vivo Multispectral Imaging System FX can be used for in vivo and in vitro molecular imaging of materials, researchers should be aware
that the methods of preparing and viewing the materials for molecular imaging may be subject to various patent rights.
"Molecular Imaging - Wisdom To See For Maladies To Flee"
Dr. Rao V. L. Papineni

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