In-vivo confocal real-time mini-microscopy in animal models of human inflammatory and neoplastic diseases.
OBJECTIVE
Although various improvements in tissue imaging modalities have recently been achieved, in-vivo molecular and subsurface imaging in the field of gastroenterology remains a technical challenge. In this study we evaluated a newly developed, handheld, miniaturized confocal laser microscopy probe for real-time in-vivo molecular and subsurface imaging in rodent models of human disease.


METHODS
The minimicroscope uses a 488-nm, single line laser for fluorophore excitation. The optical slice thickness is 7 microm, the lateral resolution 0.7 microm. The range of the z-axis is 0-250 microm below the tissue surface. Imaging was performed using different fluorescent staining protocols; 5-carboxyfluorescein-labeled octreotate was synthesized for targeted molecular imaging.


RESULTS
Cellular and subcellular details of the gastrointestinal tract could be visualized in vivo at high resolution. Confocal real-time microscopy allowed in-vivo identification of tumor vessels and liver metastases, as well as diagnosis of focal hepatic inflammation, necrosis, and associated perfusion anomalies. Somatostatin-receptor targeting permitted in-vivo molecular staining of AR42-J-induced carcinoma and pancreatic islet cells.


CONCLUSIONS
Confocal mini-microscopy allows rapid in-vivo molecular and subsurface imaging of normal and pathological tissue in the gastrointestinal tract at high resolution. Because this technology is applicable to humans, it might impact on future in-vivo microsocpic and molecular diagnosis of diseases such as cancer and inflammation.
Goetz
M
M
Medical Clinic I, University of Mainz, Mainz, Germany. mgoetz@mail.uni-mainz.de
Fottner
C
C
Schirrmacher
E
E
Delaney
P
P
Gregor
S
S
Schneider
C
C
Strand
D
D
Kanzler
S
S
Memadathil
B
B
Weyand
E
E
Holtmann
M
M
Schirrmacher
R
R
Weber
M M
MM
Anlauf
M
M
Klöppel
G
G
Vieth
M
M
Galle
P R
PR
Bartenstein
P
P
Neurath
M F
MF
Kiesslich
R
R
D000818:Animals; D004195:Disease Models, Animal; D004867:Equipment Design; D005260:Female; D005452:Fluoresceins; D005456:Fluorescent Dyes; D005770:Gastrointestinal Neoplasms / Q000473:pathology*; D007150:Immunohistochemistry; D007249:Inflammation / Q000473:pathology*; D007515:Islets of Langerhans / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018613:Microscopy, Confocal / Q000295:instrumentation* / Q000379:methods; D008904:Miniaturization; D015282:Octreotide; D010190:Pancreatic Neoplasms / Q000473:pathology; D017481:Receptors, Somatostatin
D005452:Fluoresceins; D005456:Fluorescent Dyes; D017481:Receptors, Somatostatin; C045132:4-carboxyfluorescein; D015282:Octreotide