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 encapsulated polymeric nanoparticles is presented here. The methodology potentially allows diagnosis of motility disease in gastrointestinal tract and the 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 anatomical coregistration using low energy x-ray imaging. High resolution x-ray images were obtained using phosphor screen positioned at the same optical plane producing the anatomical overlay, providing context for molecular signal translocation. Effects of pharmacological drugs that either slow the motility, or drugs involved in compartmentalization of the noninvasive optical nanoparticle signals will be discussed.

Optical Probe- Characterization

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

120 min 210 min

10 min 16 min 20 min 34 min

A B C D

E F

NIRF Imaging of GI Tract

Time Lapse Imaging

Image X-ray, NIRF EX:730, and EM 790E0

Optical Probesby

gavage

Time Lapse Imaging

Image NIRF EX:730, and EM 790

Rectal Deliveryof

KODAK X-Sight 761 Nanospheres

NIRF Imaging of lower GI. Time lapse images- Montage of images between 0-180 min. Images were obtained in the identical positions and similar signal contrast. f-stop 2.8, no binning.

KODAK in-Vivo Image Station FX 4000MM

KODAK X-Sight 761 Nanospheres was delivered by gavage. Planar images obtained using KODAK in-Vivo Multispectral FX system at the two precise rotational positions are shown here. The prolonged retention of the optical signal in the gastric environment was determined- ~95% intensity of the optical probe was observed after 180 min (from comparision of A and C). EX: 720 EM;790, 30 sec exp, 2X2 binning..

A B C

NIRF Imaging of Lower GI

Imaging of Drug Induced Gastric Motility

Proton Pump Inhibitors

Loperamide

A B C D

10 min 180 min

Sennosides

Imaging of KODAK X-Sight 761 Nanospheres together with drugs a, omeprazole, a proton pump inhibitor, b,loperamide, anti diarrheal, and c, sennosides, over the counter laxative. The NIRF image showing gastric motility (compare distribution of signal in “c” from “a and b”) was taken after 15 min of the delivery of the admixtures by gavage using KODAK in-Vivo Multispectral FX system . F-stop 2.8, no binning.

ConclusionsTime Lapse Imaging (min)

0 20 40 60 80 100 120

Net

Inte

nsi

ty (

a.u

)

0.0

2.0e+5

4.0e+5

6.0e+5

8.0e+5

1.0e+6

1.2e+6

1.4e+6 Motility in the lower GIAs plotted from net intensities obtained at a particular point (ROI) within the rectal delivery area of the KODAK X- Sight 761 Nanospheres (see above).

• Dye encapsulated polymeric nanoparticles, KODAK X-Sight 761 Nanospheres maintain integrity in the acidic gastric environment and are a strong candidate for translatable NIRF gastrointestinal imaging contrast agents. These agents report favorably the physiological and drug induced GI motility at both the upper and lower GI tract.

Motility

"Molecular Imaging - Wisdom To See For Maladies To Flee"Dr. Rao V. L. Papineni

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.