Axon tracing in the adult rat optic nerve and tract after intravitreal injection of MnDPDP using a semiautomatic segmentation technique.
OBJECTIVE
To develop and validate an objective technique for 3D segmentation of manganese-enhanced MR images of the optic nerve/tract (ON) in adult rats to improve contrast-to-noise (CNR) calculations and use the technique to ascertain if manganese dipyridoxyl diphosphate (MnDPDP) gives sufficient Mn(2+) enhancement compared to MnCl(2) when used for functional imaging of the visual pathway.


METHODS
Intravitreous injection of the manganese-releasing MR contrast agent MnDPDP (30 nmol Mn(2+)) was performed to trace the ON in adult rats (n = 4). A positive control group of rats (n = 5) received a standard preparation of MnCl(2) (200 nmol Mn(2+)), while gadodiamide (1500 nmol Gd(3+)) was administered in negative control rats (n = 2). An objective technique for 3D segmentation of the enhanced ON was developed. CNR profiles along the ON were calculated by resampling the 3D image-volume in 2D planes perpendicular to the Mn(2+) enhanced ON in 0.2 mm steps, 4 mm along the segmented ON measured from the lamina cribrosa.


RESULTS
The ON was successfully segmented and CNR calculated accurately within 2 minutes in a representative 3D MR image volume. Intravitreal MnDPDP injection resulted in significant MRI contrast enhancement of the retina and ON after 12-24 hours similar to that of MnCl(2) injection.


CONCLUSIONS
3D semiautomated image segmentation and the use of MnDPDP can improve in vivo axon tracing based on MRI. Mn(2+) was found to be released from MnDPDP after intravitreal injection in sufficient amounts to obtain functional tracing of the adult rat primary visual pathway.
D000704:Analysis of Variance; D000818:Animals; D002712:Chlorides / Q000008:administration & dosage / Q000494:pharmacology; D003287:Contrast Media / Q000008:administration & dosage / Q000494:pharmacology*; D004492:Edetic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D005260:Female; D019786:Gadolinium DTPA / Q000008:administration & dosage / Q000494:pharmacology; D021621:Imaging, Three-Dimensional; D007267:Injections; D008279:Magnetic Resonance Imaging; D017895:Manganese Compounds / Q000008:administration & dosage / Q000494:pharmacology; D009900:Optic Nerve / Q000033:anatomy & histology*; D011732:Pyridoxal Phosphate / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D012044:Regression Analysis; D014018:Tissue Distribution; D014822:Vitreous Body
D002712:Chlorides; D003287:Contrast Media; D017895:Manganese Compounds; D011732:Pyridoxal Phosphate; C064925:gadodiamide; D004492:Edetic Acid; D019786:Gadolinium DTPA; C060076:N,N'-bis(pyridoxal-5-phosphate)ethylenediamine-N,N'-diacetic acid; C025340:manganese chloride