Optoacoustic Characterization of Postprandial Intestinal Blood Flow

Inflammatory Bowel Diseases Clinical Trial

— NEPOMUC  

Official title:

Noninvasive Characterization of Postprandial Intestinal Blood Flow Using Multispectral Optoacoustic Tomography

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05160077
• Other study ID #: 346_21 B
• Status: Completed
• Phase: N/A
• Start date: November 23, 2021
• Est. completion date: January 15, 2022

Study information

• Verified date: November 2021
• Source: University of Erlangen-Nürnberg Medical School
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Inflammatory activities in the gastrointestinal tract are accompanied by an increase in blood flow in the intestinal wall layers of the respective organs. Also in chronic inflammatory bowel diseases, the release of vasoactive inflammatory mediators leads to vasodilation and consecutive increase of blood flow in the bowel wall. So far, these changes in blood flow can be detected by power Doppler sonography without being part of routine clinical diagnostics. Another promising option for non-invasive measurement of blood flow in the intestinal wall is Multispectral Optoacoustic Tomography (MSOT). Previous studies have shown that MSOT can be used to quantitatively measure hemoglobin in the bowel wall and thus provide information on blood flow and inflammatory activity in the intestines of patients with Crohn's disease. This is currently being further investigated in a pivotal study (Euphoria, H2020) and could lead to the possibility of non-invasive assessment of disease activity in inflammatory bowel disease (IBD) in the future. The regional blood flow in the intestinal wall and the distribution of gastrointestinal blood flow are also subject to strong postprandial changes. During absorption of food components, blood flow increases sequentially in the respective sections of the gastrointestinal tract, leading to postprandial hyperemia. Because postprandial hyperemia is particularly regulated locally by the presence of dietary components, there is a relationship between the sequential increase in blood flow in the intestinal wall and the peristaltic transport of chyme through the gastrointestinal tract. Postprandial hyperemia could also lead to an increase in the optoacoustic hemoglobin signal of the intestinal wall and thus have an impact on the assessment of inflammatory activity in IBD using MSOT. Additionally, MSOT allows the identification of non-absorbable exogenous chromophores, such as indocyanine green (ICG), which could allow co-localization of the chyme in the intestinal lumen after oral application of ICG. This pilot study investigates whether postprandial blood flow changes can be quantitatively measured using MSOT and whether these changes occur simultaneously with the gastrointestinal passage of the chyme as measured by the ICG signal in the intestinal lumen.

Description:

The gastrointestinal tract essentially fulfills two major functions: digestion and absorption of food, and physical and immunological barrier against environmental influences. These basic functions are critically dependent on splanchnic blood flow at both the macrovascular and microvascular levels. In particular, advances in vascular biology have revealed a central and intricate role of blood circulation in inflammatory bowel disease (IBD). Until now, changes in blood flow have been used as surrogate markers for altered inflammatory activity in the intestine, e.g., by Doppler sonographic detection. Multispectral Optoacoustic Tomograph (MSOT) allows for non-invasive, quantitative imaging of the molecular composition of target tissues. In MSOT, similar to conventional sonography, a transducer is placed on the skin but energy is delivered to the tissue by means of laser light in the near infrared spectrum instead of ultrasound waves. This leads to a constant alternation of minimal expansions and contractions (thermoelastic expansion) of individual tissue components or molecules. The resulting ultrasound waves can subsequently be detected by the same examination unit. Previous studies have shown that quantitative determination of hemoglobin can provide information on blood flow and inflammatory activity in the intestine of adult patients with Crohn's disease. In particular, the distinction between the activity levels of the disease (remission/low/moderate/high) is promising for saving invasive measures in the future when evaluating the progression of the disease. In addition to inflammatory processes, food intake also causes fluctuations in regional blood flow in the gastrointestinal tract. This manifests as postprandial hyperemia, which occurs sequentially in the different sections of the gastrointestinal tract from oral to aboral. The time course of postprandial hyperemia in the different sections of the gastrointestinal tract has been scientifically investigated in many studies. While an increase in blood flow in the stomach and duodenum can be detected after 30-60 minutes, it takes much longer for postprandial hyperemia to be detected in the areas used to measure inflammatory activity with MSOT in IBD such as the terminal ileum and sigmoid colon. An increase in blood flow in the ileum can be measured after 120 minutes at the earliest, and the arrival of chyme in the colon and the accompanying local increase in blood flow occur after approximately 240-300 minutes. It is unclear whether this postprandial hyperemia can lead to a change and potential increase in the optoacoustic hemoglobin signal of the intestinal wall, resulting in falsely high MSOT signals in the determination of inflammatory activity. This study investigates influences of a standardized dietary on the MSOT signal of the intestinal wall using a longitudinal design. Optoacoustic signals will be compared between subjects in fasting and postprandial states. Because the postprandial increase in intestinal blood flow is predominantly a result of the local presence of chyme in the intestine, a simultaneous determination of intestinal transit of chyme during MSOT measurement would be helpful to validate whether postprandial changes in MSOT signals are attributable to hyperemia in the corresponding bowel segment. Besides imaging of hemoglobin, MSOT enables the detection of exogenous chromophores (i.e. dyes). In this study, the oral administration of the nonabsorbable dye indocyanine green (ICG) will be used for noninvasive identification of the chyme. The combination of exogenous and endogenous chromophores thus allows accurate co-localization and registration of intestinal wall blood flow patterns and chyme transit. This information enables accurate anatomical mapping of interfering influences on the determination of hemoglobin using MSOT.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: January 15, 2022
• Est. primary completion date: January 15, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age over 18 years
• Written declaration of consent Exclusion Criteria:

Generally valid:

• Pregnancy
• Nursing mothers
• Tattoo in the field of investigation
• Subcutaneous fat tissue over 3 cm
• Chronic or acute diseases of the gastrointestinal tract or symptoms suggestive of such a disease
• Diseases requiring acute treatment
• Lack of written consent

ICG related:

• Known hypersensitivity to ICG, sodium iodide or iodine
• Hyperthyroidism, focal or diffuse thyroid autonomy
• Treatment with radioactive iodine for the diagnostic examination of thyroid function within two weeks before or after the study
• Restricted renal function
• Intake of the following drugs: Beta-blockers, anticonvulsants, cyclopropane, bisulphite compounds, haloperidol, heroin, meperidine, metamizole, methadone, morphine, nitrofurantoin, opium alkaloids, phenobarbital, phenylbutazone, probenecid, rifamycin, any injection containing sodium bisulphite.

Related Conditions & MeSH terms

• Digestive System Disease
• Digestive System Diseases
• Gastrointestinal Diseases
• Inflammatory Bowel Diseases

Intervention

Diagnostic Test:
• Multispectral optoacoustic tomography (MSOT)
MSOT Acuity Echo, iThera medical, Munich

Locations

Country	Name	City	State
Germany	University Hospital Erlangen	Erlangen	Bavaria

Sponsors (1)

Lead Sponsor	Collaborator
University of Erlangen-Nürnberg Medical School

Country where clinical trial is conducted

Germany, 

References & Publications (13)

Bennink R, Peeters M, Van den Maegdenbergh V, Geypens B, Rutgeerts P, De Roo M, Mortelmans L. Evaluation of small-bowel transit for solid and liquid test meal in healthy men and women. Eur J Nucl Med. 1999 Dec;26(12):1560-6. — View Citation

Calabrese E, Maaser C, Zorzi F, Kannengiesser K, Hanauer SB, Bruining DH, Iacucci M, Maconi G, Novak KL, Panaccione R, Strobel D, Wilson SR, Watanabe M, Pallone F, Ghosh S. Bowel Ultrasonography in the Management of Crohn's Disease. A Review with Recommendations of an International Panel of Experts. Inflamm Bowel Dis. 2016 May;22(5):1168-83. doi: 10.1097/MIB.0000000000000706. Review. — View Citation

Camilleri M, Colemont LJ, Phillips SF, Brown ML, Thomforde GM, Chapman N, Zinsmeister AR. Human gastric emptying and colonic filling of solids characterized by a new method. Am J Physiol. 1989 Aug;257(2 Pt 1):G284-90. — View Citation

Deban L, Correale C, Vetrano S, Malesci A, Danese S. Multiple pathogenic roles of microvasculature in inflammatory bowel disease: a Jack of all trades. Am J Pathol. 2008 Jun;172(6):1457-66. doi: 10.2353/ajpath.2008.070593. Epub 2008 May 5. Review. — View Citation

Goertz RS, Egger C, Neurath MF, Strobel D. Impact of food intake, ultrasound transducer, breathing maneuvers and body position on acoustic radiation force impulse (ARFI) elastometry of the liver. Ultraschall Med. 2012 Aug;33(4):380-5. Epub 2012 Jun 21. — View Citation

Knieling F, Neufert C, Hartmann A, Claussen J, Urich A, Egger C, Vetter M, Fischer S, Pfeifer L, Hagel A, Kielisch C, Görtz RS, Wildner D, Engel M, Röther J, Uter W, Siebler J, Atreya R, Rascher W, Strobel D, Neurath MF, Waldner MJ. Multispectral Optoacoustic Tomography for Assessment of Crohn's Disease Activity. N Engl J Med. 2017 Mar 30;376(13):1292-1294. doi: 10.1056/NEJMc1612455. — View Citation

Kvietys PR. The Gastrointestinal Circulation. San Rafael (CA): Morgan & Claypool Life Sciences; 2010. — View Citation

Matheson PJ, Wilson MA, Garrison RN. Regulation of intestinal blood flow. J Surg Res. 2000 Sep;93(1):182-96. Review. — View Citation

Ntziachristos V, Razansky D. Molecular imaging by means of multispectral optoacoustic tomography (MSOT). Chem Rev. 2010 May 12;110(5):2783-94. doi: 10.1021/cr9002566. Review. — View Citation

Regensburger AP, Brown E, Krönke G, Waldner MJ, Knieling F. Optoacoustic Imaging in Inflammation. Biomedicines. 2021 Apr 28;9(5). pii: 483. doi: 10.3390/biomedicines9050483. Review. — View Citation

Sou S, Matsui T, Yao T, Naito M, Yorioka M, Beppu T, Nagahama T, Futami K. Differentiating enterocutaneous fistulae from suture abscesses complicating Crohn's disease using oral administration of indocyanine green. J Gastroenterol Hepatol. 2006 Dec;21(12):1850-3. — View Citation

Waldner MJ, Knieling F, Egger C, Morscher S, Claussen J, Vetter M, Kielisch C, Fischer S, Pfeifer L, Hagel A, Goertz RS, Wildner D, Atreya R, Strobel D, Neurath MF. Multispectral Optoacoustic Tomography in Crohn's Disease: Noninvasive Imaging of Disease Activity. Gastroenterology. 2016 Aug;151(2):238-40. doi: 10.1053/j.gastro.2016.05.047. Epub 2016 Jun 3. — View Citation

Weber J, Beard PC, Bohndiek SE. Contrast agents for molecular photoacoustic imaging. Nat Methods. 2016 Jul 28;13(8):639-50. doi: 10.1038/nmeth.3929. Review. — View Citation

* Note: There are 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change of the quantitative de-/oxygenated hemoglobin signal (in arbitrary units)	Change of the quantitative de-/oxygenated hemoglobin signal in the wall of the gastrointestinal tract (gastric antrum, terminal ileum, transverse colon, and sigmoid colon) over a postprandial time of 7 hours.	every 60 minutes over 8 hours on each of the three examination days
Secondary	Change of the qualitative and quantitative ICG signal (in arbitrary units)	Change of the qualitative and quantitative ICG signal (in arbitrary units) in the lume of the gastrointestinal tract (gastric antrum, terminal ileum, transverse colon, and sigmoid colon) over a postprandial time of 7 hours.	every 60 minutes over 8 hours on on the third examination day
Secondary	Change of the quantitative single wavelengths signal (in arbitrary units)	Change of the quantitative single wavelengths signal (in arbitrary units) in the wall of the gastrointestinal tract (gastric antrum, terminal ileum, transverse colon, and sigmoid colon) over a postprandial time of 7 hours.	every 60 minutes over 8 hours on each of the three examination days
Secondary	Change of the optoacoustic spectrum (in arbitrary units, normalized)	Change of the optoacoustic spectrum (in arbitrary units, normalized) in the wall of the gastrointestinal tract (gastric antrum, terminal ileum, transverse colon, and sigmoid colon) over a postprandial time of 7 hours.	every 60 minutes over 8 hours on each of the three examination days
Secondary	Change of Blood flow in the big splanchnic arteries.	Change of Blood flow in the coeliac trunk, superior mesenteric artery, inferior mesenteric artery measured by Doppler sonography over a postprandial time of 7 hours.	every 60 minutes over 8 hours on each of the three examination days
Secondary	Change of Resistance Index in the big splanchnic arteries.	Change of Resistance Index in the coeliac trunk, superior mesenteric artery, inferior mesenteric artery measured by Doppler sonography over a postprandial time of 7 hours.	every 60 minutes over 8 hours on each of the three examination days
Secondary	Change of Pulsatility Index in the big splanchnic arteries.	Change of Pulsatility Index in the coeliac trunk, superior mesenteric artery, inferior mesenteric artery measured by Doppler sonography over a postprandial time of 7 hours.	every 60 minutes over 8 hours on each of the three examination days
Secondary	Change of peak systolic velocity in the big splanchnic arteries.	Change of peak systolic velocity in the coeliac trunk, superior mesenteric artery, inferior mesenteric artery measured by Doppler sonography over a postprandial time of 7 hours.	every 60 minutes over 8 hours on each of the three examination days
Secondary	Change of end diastolic velocity in the big splanchnic arteries.	Change of end diastolic velocity in the coeliac trunk, superior mesenteric artery, inferior mesenteric artery measured by Doppler sonography over a postprandial time of 7 hours.	every 60 minutes over 8 hours on each of the three examination days