|
1
|
Jung D, Heiss R, Kramer V, Thoma OM, Regensburger AP, Rascher W, Uder M, Neurath MF, Knieling F, Waldner MJ. Contrast-Enhanced µCT for Visualizing and Evaluating Murine Intestinal Inflammation. Am J Cancer Res 2018; 8:6357-6366. [PMID: 30613304 PMCID: PMC6299705 DOI: 10.7150/thno.26013] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2018] [Accepted: 10/14/2018] [Indexed: 12/11/2022] Open
Abstract
Rationale: To develop a simple and fast protocol for the assessment of acute and chronic experimental intestinal inflammation using contrast-enhanced µCT. Methods: For the imaging studies, an acute 2% and 3% dextran sodium sulfate (n = 15, female, 8-12 weeks) and a chronic adoptive transfer colitis model (n = 10, female, 8-9 weeks) were established over 9 days or 6 weeks, respectively. Throughout the experiments, longitudinal measurement of murine intestinal wall thickness and time dependent perfusion was performed on a small animal µCT system (90 kV, 160 μA, FOV: 60 mm, scan time: 17 s, image size: 512x512, layer thickness: 118 µm) between 0.5 and 30 min after intravenous bolus injection of an iodine contrast agent. Weight development, small animal endoscopy, and histological ex vivo analysis were compared to contrast-enhanced µCT imaging findings. Results: Murine intestinal wall thickness was significantly increased in inflamed colons of acute colitis at day 9 in comparison to pre-inflamed state. Perfusion analysis revealed a late contrast enhancement in acute inflamed colons and the renal medulla at day 9 compared to control mice. An increasing intestinal wall thickness was monitored 3, 5 and 6 weeks after on-set of chronic colitis in comparison to controls. A good correlation with endoscopic (r = 0.75, p < 0.0001) and histologic degree of inflammation (r = 0.83, p = 0.04) was found. Conclusion: Contrast-enhanced µCT is a simple and fast method to assess acute intestinal inflammation and to monitor disease progression in experimental models of chronic colitis. According to our findings, one single contrast-enhanced µCT-scan is a valid non-invasive modality to quantify the degree of inflammation in the entire digestive tract in murine inflammatory models.
Collapse
|
|
2
|
Zappa M, Doblas S, Cazals-Hatem D, Milliat F, Lavigne J, Daniel F, Jallane A, Garteiser P, Vilgrain V, Ogier-Denis E, Van Beers BE. Quantitative MRI in murine radiation-induced rectocolitis: comparison with histopathological inflammation score. NMR IN BIOMEDICINE 2018; 31:e3897. [PMID: 29405471 DOI: 10.1002/nbm.3897] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/16/2017] [Revised: 12/17/2017] [Accepted: 12/26/2017] [Indexed: 06/07/2023]
Abstract
Murine radiation-induced rectocolitis is considered to be a relevant animal model of gastrointestinal inflammation. The purpose of our study was to compare quantitative MRI and histopathological features in this gastrointestinal inflammation model. Radiation rectocolitis was induced by localized single-dose radiation (27 Gy) in Sprague-Dawley rats. T2 -weighted, T1 -weighted and diffusion-weighted MRI was performed at 7 T in 16 rats between 2 and 4 weeks after irradiation and in 10 control rats. Rats were sacrificed and the histopathological inflammation score of the colorectal samples was assessed. The irradiated rats showed significant increase in colorectal wall thickness (2.1 ± 0.3 mm versus 0.8 ± 0.3 mm in control rats, P < 0.0001), normalized T2 signal intensity (4 ± 0.8 versus 2 ± 0.4 AU, P < 0.0001), normalized T1 signal intensity (1.4 ± 0.1 versus 1.1 ± 0.2 AU, P = 0.0009) and apparent and pure diffusion coefficients (ADC and D) (2.06 × 10-3 ± 0.34 versus 1.51 × 10-3 ± 0.23 mm2 /s, P = 0.0004, and 1.97 × 10-3 ± 0.43 mm2 /s versus 1.48 × 10-3 ± 0.29 mm2 /s, P = 0.008, respectively). Colorectal wall thickness (r = 0.84, P < 0.0001), normalized T2 signal intensity (r = 0.85, P < 0.0001) and ADC (r = 0.80, P < 0.0001) were strongly correlated with the histopathological inflammation score, whereas normalized T1 signal intensity and D were moderately correlated (r = 0.64, P = 0.0006, and r = 0.65, P = 0.0003, respectively). High-field MRI features of single-dose radiation-induced rectocolitis in rats differ significantly from those of control rats. Quantitative MRI characteristics, especially wall thickness, normalized T2 signal intensity, ADC and D, are potential markers of the histopathological inflammation score.
Collapse
Affiliation(s)
- Magaly Zappa
- Hôpitaux Universitaires Beaujon, Radiology, Université Paris VII, Clichy, France
- Laboratory of Imaging Biomarkers, Center of Research on Inflammation, UMR 1149, INSERM, University Paris-Diderot, Paris, France
| | - Sabrina Doblas
- Laboratory of Imaging Biomarkers, Center of Research on Inflammation, UMR 1149, INSERM, University Paris-Diderot, Paris, France
| | - Dominique Cazals-Hatem
- Hopital Beaujon, Pathology, Université Paris VII, Clichy, France
- Laboratory of Intestinal Inflammation, Center of Research on Inflammation, UMR 1149, INSERM, University Paris Diderot, Paris, France
| | - Fabien Milliat
- Institute for Radiological Protection and Nuclear Safety (IRSN), Research Laboratory in Radiobiology and Radiopathology, Fontenay-aux-Roses, France
| | - Jérémy Lavigne
- Institute for Radiological Protection and Nuclear Safety (IRSN), Research Laboratory in Radiobiology and Radiopathology, Fontenay-aux-Roses, France
| | - Fanny Daniel
- Laboratory of Intestinal Inflammation, Center of Research on Inflammation, UMR 1149, INSERM, University Paris Diderot, Paris, France
| | - Abelhak Jallane
- Laboratory of Intestinal Inflammation, Center of Research on Inflammation, UMR 1149, INSERM, University Paris Diderot, Paris, France
| | - Philippe Garteiser
- Laboratory of Imaging Biomarkers, Center of Research on Inflammation, UMR 1149, INSERM, University Paris-Diderot, Paris, France
| | - Valérie Vilgrain
- Hôpitaux Universitaires Beaujon, Radiology, Université Paris VII, Clichy, France
- Laboratory of Imaging Biomarkers, Center of Research on Inflammation, UMR 1149, INSERM, University Paris-Diderot, Paris, France
| | - Eric Ogier-Denis
- Laboratory of Intestinal Inflammation, Center of Research on Inflammation, UMR 1149, INSERM, University Paris Diderot, Paris, France
| | - Bernard E Van Beers
- Hôpitaux Universitaires Beaujon, Radiology, Université Paris VII, Clichy, France
- Laboratory of Imaging Biomarkers, Center of Research on Inflammation, UMR 1149, INSERM, University Paris-Diderot, Paris, France
| |
Collapse
|
|
3
|
Brückner M, Lenz P, Mücke MM, Gohar F, Willeke P, Domagk D, Bettenworth D. Diagnostic imaging advances in murine models of colitis. World J Gastroenterol 2016; 22:996-1007. [PMID: 26811642 PMCID: PMC4716050 DOI: 10.3748/wjg.v22.i3.996] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2015] [Revised: 09/09/2015] [Accepted: 11/13/2015] [Indexed: 02/06/2023] Open
Abstract
Inflammatory bowel diseases (IBD) such as Crohn’s disease and ulcerative colitis are chronic-remittent inflammatory disorders of the gastrointestinal tract still evoking challenging clinical diagnostic and therapeutic situations. Murine models of experimental colitis are a vital component of research into human IBD concerning questions of its complex pathogenesis or the evaluation of potential new drugs. To monitor the course of colitis, to the present day, classical parameters like histological tissue alterations or analysis of mucosal cytokine/chemokine expression often require euthanasia of animals. Recent advances mean revolutionary non-invasive imaging techniques for in vivo murine colitis diagnostics are increasingly available. These novel and emerging imaging techniques not only allow direct visualization of intestinal inflammation, but also enable molecular imaging and targeting of specific alterations of the inflamed murine mucosa. For the first time, in vivo imaging techniques allow for longitudinal examinations and evaluation of intra-individual therapeutic response. This review discusses the latest developments in the different fields of ultrasound, molecularly targeted contrast agent ultrasound, fluorescence endoscopy, confocal laser endomicroscopy as well as tomographic imaging with magnetic resonance imaging, computed tomography and fluorescence-mediated tomography, discussing their individual limitations and potential future diagnostic applications in the management of human patients with IBD.
Collapse
|
|
4
|
Abstract
BACKGROUND Traditional techniques analyzing mouse colitis are invasive, laborious, or indirect. Development of in vivo imaging techniques for specific colitis processes would be useful for monitoring disease progression and/or treatment effectiveness. The aim was to evaluate the applicability of the chemiluminescent probe L-012, which detects reactive oxygen and nitrogen species, for in vivo colitis imaging. METHODS Two genetic colitis mouse models were used; K8 knockout (K8(-/-)) mice, which develop early colitis and the nonobese diabetic mice, which develop a transient subclinical colitis. Dextran sulphate sodium was used as a chemical colitis model. Mice were anesthetized, injected intraperitoneally with L-012, imaged, and quantified for chemiluminescent signal in the abdominal region using an IVIS camera system. RESULTS K8(-/-) and nonobese diabetic mice showed increased L-012-mediated chemiluminescence from the abdominal region compared with control mice. L-012 signals correlated with the colitis phenotype assessed by histology and myeloperoxidase staining. Although L-012 chemiluminescence enabled detection of dextran sulphate sodium-induced colitis at an earlier time point compared with traditional methods, large mouse-to-mouse variations were noted. In situ and ex vivo L-012 imaging as well as [18F]FDG-PET imaging of K8(-/-) mice confirmed that the in vivo signals originated from the distal colon. L-012 in vivo imaging showed a wide variation in reactive oxygen and nitrogen species in young mice, irrespective of K8 genotype. In aging mice L-012 signals were consistently higher in K8(-/-) as compared to K8(+/+) mice. CONCLUSIONS In vivo imaging using L-012 is a useful, simple, and cost-effective tool to study the level and longitudinal progression of genetic and possibly chemical murine colitis.
Collapse
|
|
5
|
Acetylsalicylic Acid reduces the severity of dextran sodium sulfate-induced colitis and increases the formation of anti-inflammatory lipid mediators. BIOMED RESEARCH INTERNATIONAL 2013; 2013:748160. [PMID: 24083240 PMCID: PMC3780524 DOI: 10.1155/2013/748160] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/18/2013] [Accepted: 07/19/2013] [Indexed: 12/16/2022]
Abstract
The role of non-steroidal anti-inflammatory drugs in inflammatory bowel disease is controversial, as they have been implicated in disease aggravation. Different from other cyclooxygenase inhibitors, acetylsalicylic acid (ASA) enhances the formation of anti-inflammatory and proresolution lipoxins derived from arachidonic acid as well as resolvins from omega-3 polyunsaturated fatty acids such as docosahexaenoic acid (DHA). In this study, we examined the effect of ASA on murine dextran sodium sulfate colitis. A mouse magnetic resonance imaging (MRI) protocol and post mortem assessment were used to assess disease severity, and lipid metabolites were measured using liquid chromatography-coupled tandem mass spectrometry. Decreased colitis activity was demonstrated by phenotype and MRI assessment in mice treated with ASA, and confirmed in postmortem analysis. Analysis of lipid mediators showed sustained formation of lipoxin A4 and an increase of DHA-derived 17-hydroxydocosahexaenoic acid (17-HDHA) after treatment with ASA. Furthermore, in vitro experiments in RAW264.7 murine macrophages demonstrated significantly increased phagocytosis activity after incubation with 17-HDHA, supporting its proresolution effect. These results show a protective effect of ASA in a murine colitis model and could give a rationale for a careful reassessment of ASA therapy in patients with inflammatory bowel disease and particularly ulcerative colitis, possibly combined with DHA supplementation.
Collapse
|
|
6
|
Wathen CA, Foje N, van Avermaete T, Miramontes B, Chapaman SE, Sasser TA, Kannan R, Gerstler S, Leevy WM. In vivo X-ray computed tomographic imaging of soft tissue with native, intravenous, or oral contrast. SENSORS (BASEL, SWITZERLAND) 2013; 13:6957-80. [PMID: 23711461 PMCID: PMC3715264 DOI: 10.3390/s130606957] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/27/2013] [Revised: 05/16/2013] [Accepted: 05/23/2013] [Indexed: 02/07/2023]
Abstract
X-ray Computed Tomography (CT) is one of the most commonly utilized anatomical imaging modalities for both research and clinical purposes. CT combines high-resolution, three-dimensional data with relatively fast acquisition to provide a solid platform for non-invasive human or specimen imaging. The primary limitation of CT is its inability to distinguish many soft tissues based on native contrast. While bone has high contrast within a CT image due to its material density from calcium phosphate, soft tissue is less dense and many are homogenous in density. This presents a challenge in distinguishing one type of soft tissue from another. A couple exceptions include the lungs as well as fat, both of which have unique densities owing to the presence of air or bulk hydrocarbons, respectively. In order to facilitate X-ray CT imaging of other structures, a range of contrast agents have been developed to selectively identify and visualize the anatomical properties of individual tissues. Most agents incorporate atoms like iodine, gold, or barium because of their ability to absorb X-rays, and thus impart contrast to a given organ system. Here we review the strategies available to visualize lung, fat, brain, kidney, liver, spleen, vasculature, gastrointestinal tract, and liver tissues of living mice using either innate contrast, or commercial injectable or ingestible agents with selective perfusion. Further, we demonstrate how each of these approaches will facilitate the non-invasive, longitudinal, in vivo imaging of pre-clinical disease models at each anatomical site.
Collapse
Affiliation(s)
- Connor A. Wathen
- Department of Biological Sciences, 100 Galvin Life Sciences Center, University of Notre Dame, Notre Dame, IN 46556, USA; E-Mail:
| | - Nathan Foje
- Department of Chemistry and Biochemistry, 236 Nieuwland Science Hall, University of Notre Dame, Notre Dame, IN 46556, USA; E-Mails: (N.F.); (T.V.A.); (B.M.); (T.A.S.)
| | - Tony van Avermaete
- Department of Chemistry and Biochemistry, 236 Nieuwland Science Hall, University of Notre Dame, Notre Dame, IN 46556, USA; E-Mails: (N.F.); (T.V.A.); (B.M.); (T.A.S.)
- Penn High School, 55900 Bittersweet Road, Mishawaka, IN 46545, USA
| | - Bernadette Miramontes
- Department of Chemistry and Biochemistry, 236 Nieuwland Science Hall, University of Notre Dame, Notre Dame, IN 46556, USA; E-Mails: (N.F.); (T.V.A.); (B.M.); (T.A.S.)
- Penn High School, 55900 Bittersweet Road, Mishawaka, IN 46545, USA
| | - Sarah E. Chapaman
- Notre Dame Integrated Imaging Facility, Notre Dame, IN 46556, USA; E-Mail:
| | - Todd A. Sasser
- Department of Chemistry and Biochemistry, 236 Nieuwland Science Hall, University of Notre Dame, Notre Dame, IN 46556, USA; E-Mails: (N.F.); (T.V.A.); (B.M.); (T.A.S.)
- Bruker-Biospin Corporation, 4 Research Drive, Woodbridge, CT 06525, USA
| | - Raghuraman Kannan
- Department of Radiology, University of Missouri, Columbia, MO 65212, USA; E-Mail:
| | - Steven Gerstler
- Saint Joseph Regional Medical Center, Mishawaka, IN 46545, USA; E-Mail:
| | - W. Matthew Leevy
- Department of Biological Sciences, 100 Galvin Life Sciences Center, University of Notre Dame, Notre Dame, IN 46556, USA; E-Mail:
- Notre Dame Integrated Imaging Facility, Notre Dame, IN 46556, USA; E-Mail:
- Harper Cancer Research Institute, A200 Harper Hall, Notre Dame, IN 46530, USA
| |
Collapse
|
|
7
|
Heylen M, Deleye S, De Man JG, Ruyssers NE, Vermeulen W, Stroobants S, Pelckmans PA, Moreels TG, Staelens S, De Winter BY. Colonoscopy and µPET/CT are valid techniques to monitor inflammation in the adoptive transfer colitis model in mice. Inflamm Bowel Dis 2013; 19:967-976. [PMID: 23407045 DOI: 10.1097/mib.0b013e3182802c7c] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
Abstract
BACKGROUND Preclinical in vivo research on inflammatory bowel diseases requires proper animal models and techniques allowing longitudinal monitoring of colonic inflammation without the need to kill animals. We evaluated colonoscopy and μ-positron emission tomography/computed tomography (μPET/CT) as monitoring tools in a model for chronic colitis in mice. METHODS Colitis was induced by adoptive transfer of CD4(+)CD25(-)CD62L(+) T cells in immunocompromised severe combined immunodeficient mice. Three study protocols were designed. In study 1, colonoscopy and µPET/CT were performed once, 4 weeks after transfer. In study 2 and study 3, colitis was sequentially followed up through colonoscopy (study 2) or colonoscopy plus µPET/CT (study 3). Each study included postmortem evaluation of colonic inflammation (macroscopy, microscopy, and myeloperoxidase activity). RESULTS In study 1, both colonoscopy and µPET/CT detected colitis 4 weeks after transfer. Study 2 showed a gradual increase in colonoscopic score from week 2 (1.4 ± 0.6) to week 8 (6.0 ± 1.1). In study 3, colitis was detected 2 weeks after transfer by µPET/CT (2.0 ± 0.4) but not by colonoscopy, whereas both techniques detected inflammation 4 and 6 weeks after transfer. Colonoscopy correlated with µPET/CT (r = 0.812, 0.884, and 0.781, respectively) and with postmortem analyses in all 3 studies. CONCLUSIONS Adoptive transfer of CD4(+)CD25(-)CD62L(+) T cells in severe combined immunodeficient mice results in a moderate chronic colitis. Evolution of colitis could be monitored over time by both colonoscopy and µPET/CT. µPET/CT seems to detect inflammation at an earlier time point than colonoscopy. Both techniques represent reliable and safe methods without the need to kill animals.
Collapse
Affiliation(s)
- Marthe Heylen
- Laboratory of Experimental Medicine and Pediatrics, Division of Gastroenterology, University of Antwerp, Antwerp, Belgium
| | | | | | | | | | | | | | | | | | | |
Collapse
|
|
8
|
Abdelrahman MA, Marston G, Hull MA, Markham AF, Jones PF, Evans JA, Coletta PL. High-frequency ultrasound for in vivo measurement of colon wall thickness in mice. ULTRASOUND IN MEDICINE & BIOLOGY 2012; 38:432-442. [PMID: 22266235 DOI: 10.1016/j.ultrasmedbio.2011.12.011] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/06/2011] [Revised: 12/06/2011] [Accepted: 12/08/2011] [Indexed: 05/31/2023]
Abstract
Mouse models are becoming increasingly important in the study of molecular mechanisms of colorectal disease and in the development of novel therapeutics. To enhance this phase of preclinical research, cost-effective, easy to use noninvasive imaging is required to detect and monitor changes in the colon wall associated with disease pathology. This study investigated the feasibility of using 40-MHz (high frequency) B-mode ultrasound (HF-US) to image the normal mouse colon and measure its thickness in vivo by establishing a robust imaging protocol and conducting a blinded comparison of colon wall thickness (CWT) measurement between and within operators. The in vivo and ex vivo appearance of mouse colon under HF-US revealed distinct patterns. Colon wall thickness was reproducibly and accurately measured using HF-US compared with histology measurement. The technique was more sensitive in detecting changes in CWT in distal than proximal colon as it showed the highest level of inter- and intraoperator reproducibility. Using the protocol described, it is possible to detect changes in thickness of 0.09 mm and 0.25 mm in distal and proximal colon, respectively. In conclusion, HF-US provides an easy to use and noninvasive method to perform anatomical investigations of mouse colon and to monitor changes in CWT.
Collapse
Affiliation(s)
- Mostafa A Abdelrahman
- Leeds Institute of Molecular Medicine, University of Leeds, St. James's University Hospital, Leeds United Kingdom
| | | | | | | | | | | | | |
Collapse
|
|
9
|
Boll H, Bag S, Nölte IS, Wilhelm T, Kramer M, Groden C, Böcker U, Brockmann MA. Double-contrast micro-CT colonoscopy in live mice. Int J Colorectal Dis 2011; 26:721-7. [PMID: 21437593 DOI: 10.1007/s00384-011-1181-0] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 03/03/2011] [Indexed: 02/04/2023]
Abstract
PURPOSE Models of colon cancer in small rodents are of particular interest as they most closely simulate the development and growth of colonic cancer in humans. Micro-computed tomography has been used for detection of polyps in murine models of colon cancer. The study was performed to evaluate whether a novel high-speed continuous-rotation, single-breath-hold scanning protocol in combination with double-contrasting of the colon can be successfully applied for colonoscopy of live mice at acquisition times of 40 s. METHODS C57BL/6JApcMin/+ mice were intubated and ventilated. After double-contrasting the colon with barium and air, mice underwent continuous rotation micro-CT (mean resolution 41 × 41 × 53 μm) during a single-breath-hold period of 40 s. Sensitivity to detect colon polyps by four blinded radiologists was analysed. Number and location of polyps were verified in the excised colon. Radiation dose was measured using a thermoluminescence dosimeter placed within the distal colon. RESULTS In six of seven mice, a total of 12 polyps were detected in the explanted colon (one mouse without polyps). One tumor (8.3%) was located in the proximal third, seven tumors (58.1%) and four tumors (33.2%) were located in the middle and in the distal third of the colon, respectively. Mean tumor volume was 6.5 ± 3.6 mm(3). Sensitivity to detect colon polyps was 0.85 ± 0.1. Mean radiation dose was 0.241 ± 0.002 Gy. CONCLUSION Using a high-speed continuous rotation micro-CT protocol, double-contrast single-breath-hold colonoscopy in mice is feasible and yields sufficient contrast to visualize the proximal colonic folds and to detect colonic polyps in vivo.
Collapse
Affiliation(s)
- Hanne Boll
- Department of Neuroradiology Medical Faculty Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany
| | | | | | | | | | | | | | | |
Collapse
|
|
10
|
Abstract
Animal models of human diseases are increasingly available and are invaluable for studies of organ pathophysiology. Megacolon, abnormal dilatation of the colon not caused by mechanical obstruction, involves the destruction of the autonomic nervous system innervating the colon. Animal models of megacolon include mouse models of Chagas disease and Hirschprung's disease. Small animal imaging has become an important research tool and recent advances in preclinical imaging modalities have enhanced the information content available from longitudinal studies of animal models of human diseases. While numerous applications of imaging technologies have been reported to study the brain and heart of mouse models, fewer studies of the gastrointestinal system have been undertaken due to technical limitations caused by peristaltic and respiratory motion. Various imaging modalities relevant to study of the gastrointestinal tract of intact live animals are reviewed herein.
Collapse
Affiliation(s)
- Linda A Jelicks
- Department of Physiology & Biophysics, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA
| |
Collapse
|
|
11
|
Magnetic resonance imaging of experimental inflammatory bowel disease: quantitative and qualitative analyses with histopathologic correlation in a rat model using the ultrasmall iron oxide SHU 555 C. Invest Radiol 2009; 44:23-30. [PMID: 18836385 DOI: 10.1097/rli.0b013e3181899025] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVES To quantitatively and qualitatively characterize the MR findings of inflammatory bowel disease in a rat model after i.v. injection of the reticuloendothelial system cell specific ultrasmall iron oxide SHU 555 C. MATERIALS AND METHODS Colitis was induced in 15 rats using dinitrobenzene sulfonic acid instillation. Five rats served as controls. T1- and T2-weighted spin-echo- and T2*-weighted gradient-echo-sequences were acquired at 2.4 Tesla before and immediately, 15, 45, 60, and 90 minutes, and 24 hours after i.v.-injection of SHU 555 C (0.1 mmol Fe/kg). MR images were evaluated quantitatively regarding thickness and signal-to-noise ratio (SNR) of the bowel wall and qualitatively regarding overall bowel wall signal intensity and the occurrence of bowel wall ulcerations. MR findings were correlated to histology. RESULTS The inflamed bowel wall was significantly thicker than the noninflamed bowel wall and 90 minutes after contrast injection it showed a significant reduction of SNR in T1- (94 +/- 27 vs. 61 +/- 29; P < 0.01), T2- (67 +/- 26 vs. 28 +/- 17; P < 0.05), and T2*- (92 +/- 57 vs. 10 +/- 7; P < 0.05) weighted images as compared with unenhanced images. At 24 hours, the respective SNR values remained significantly reduced. The signal loss was homogeneous in 12 and focal in 3 of the 15 rats with colitis. Nine rats showed colonic wall ulcerations. In all but one animal (missed focal ulceration) MR findings correlated to the histologic findings. CONCLUSIONS SHU 555 C leads to a significant signal intensity loss of the inflamed bowel wall in T1-, T2- and T2*-weighted images. SHU 555 C enhanced MRI findings correlate well with histologic findings.
Collapse
|
|
12
|
Soldan M, Schanaider A, Madi K, Zaltman C, Machado JC. In vitro ultrasound biomicroscopic imaging of colitis in rats. JOURNAL OF ULTRASOUND IN MEDICINE : OFFICIAL JOURNAL OF THE AMERICAN INSTITUTE OF ULTRASOUND IN MEDICINE 2009; 28:463-469. [PMID: 19321674 DOI: 10.7863/jum.2009.28.4.463] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/27/2023]
Abstract
OBJECTIVE The purpose of this study was to show the feasibility of 50-MHz ultrasound biomicroscopy (UBM) to image the rat colon. METHODS B-mode images were obtained from ex vivo colon samples (n = 4) collected from Rattus norvegicus (Berkenhout, 1769) rats, with 2,4,6-trinitrobenzene sulfonic acid-induced colitis in 3 of them. Left colon rectangular fragments (5 x 5 mm) were obtained after necropsy, and UBM images were acquired with the samples immersed in saline at 37 degrees C. All layers of the normal intestinal wall were analyzed according to their thickness and the presence of uneven bowel mucosa (ulcers). The folds and layers detected by UBM were correlated with histopathologic analysis. RESULTS The 4 layers of the normal colon were identified on the UBM images: the mucosa (hyperechoic), muscularis mucosae (hypoechoic), submucosa (hyperechoic), and muscularis externa (hypoechoic). On 2 UBM images, superficial ulcers were detected, approximately 0.5 mm in size, with intestinal involvement limited to the mucosa. The histopathologic analysis verified enlargement of submucosa layers due to an edema associated with sub-mucosa leukocyte infiltration. On 1 UBM image, it was possible to detect a deep ulcer, which was confirmed by the light microscopic analysis. CONCLUSIONS An ultrasound imaging system was scaled and optimized to visualize the rat colon. Ultrasound biomicroscopy provided axial and lateral resolutions close to 25 and 45 mum, respectively, and adequate penetration depth to visualize the whole thickness of an inflamed colon. The system identified the colon layers and was able to detect mural changes and superficial ulcers on the order of 500 mum.
Collapse
Affiliation(s)
- Mônica Soldan
- Division of Gastroenterology, Clementino Fraga Filho University Hospital, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
| | | | | | | | | |
Collapse
|