Near-infrared fluorescence imaging and histology confirm anomalous edematous signal distribution detected in the rat lung by MRI after allergen challenge.
OBJECTIVE
To address the issue concerning the predominant location, on the left anatomic side, of edematous signals detected by magnetic resonance imaging (MRI) in the lungs of actively sensitized rats following intratracheal (IT) allergen challenge.


METHODS
Near-infrared fluorescence (NIRF) imaging was used to detect the lobular distribution in the lungs of normal rats of an IT instilled fluorescent dye, Cy5.5. Actively sensitized Brown Norway rats were examined by MRI 24 hours after IT administration of ovalbumin. The perivascular edema was quantified by histology in the different lobes of lungs removed from the same animals immediately after the MRI acquisitions.


RESULTS
An uneven distribution of Cy5.5 was found, predominantly on the left lobe, paralleling the localized development of allergic pulmonary inflammation in the left lobe detected as edematous signal by MRI and confirmed by histology. The patterns of the distributions of the dye between and within the lobes were very similar to those of perivascular edema assessed histologically.


CONCLUSIONS
The data indicate a relationship between the molecular deposition of the dye detected by NIRF in the lungs and the distribution of allergen eliciting the development of pulmonary inflammation in actively rats. The combination of MRI with NIRF imaging may provide important information in preclinical pharmacologic research in the area of airway diseases. While MRI is able to address the effects of compounds on the inflammatory response in models of airways diseases, NIRF imaging may provide important insights on drug distribution and interaction in the lung, being thus suited for molecular imaging studies.
Tigani
Bruno
B
Novartis Institutes for BioMedical Research, Discovery Technologies, Basel, Switzerland.
Gremlich
Hans-Ulrich
HU
Cannet
Catherine
C
Zurbruegg
Stefan
S
Quintana
Harry Karmouty
HK
Beckmann
Nicolau
N
D000485:Allergens; D000818:Animals; D001706:Biopsy; D002232:Carbocyanines; D005456:Fluorescent Dyes; D007091:Image Processing, Computer-Assisted; D008168:Lung / Q000473:pathology*; D008279:Magnetic Resonance Imaging; D008297:Male; D010047:Ovalbumin; D011654:Pulmonary Edema / Q000175:diagnosis* / Q000209:etiology / Q000473:pathology; D051381:Rats; D011914:Rats, Inbred BN; D012130:Respiratory Hypersensitivity / Q000150:complications*
D000485:Allergens; C098793:CY5.5 cyanine dye; D002232:Carbocyanines; D005456:Fluorescent Dyes; D010047:Ovalbumin