Accurate and precise measurement of blood-retinal barrier breakdown using dynamic Gd-DTPA MRI.
Dynamic T1-weighted magnetic resonance imaging (MRI) after the injection of Gd-DTPA is a promising method for investigating breakdown of the blood-retinal barrier (BRB). Previously, the authors demonstrated that in a T1-weighted image, the initial rate of change in the vitreous water MRI signal as gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA) enters the vitreous space strongly correlated with the extent of BRB breakdown. Here, a practical approach to measuring a more relevant physiologic parameter is presented: the permeability surface area product (PS). The theory is a development of earlier work used in investigating the breakdown of the blood-brain barrier. The accuracy and precision of this approach was investigated in rabbits pretreated with sodium iodate (30 mg/kg intravenously). The MRI-derived PS normalized to the area of leaky retina (5.65 +/- 0.25 x 10(-4) cm/min, mean +/- standard error of the mean; n = 6) was compared to a similarly normalized PS calculated using a classical physiologic method (4.12 +/- 0.73 x 10(-4) cm/min; n = 6). Good agreement between the two methods was found (P = 0.09). This result demonstrates that the MRI-derived PS is an accurate and precise measure of BRB breakdown under these conditions. The mathematical model of Gd-DTPA distribution in vivo also is validated. Based on these results, several potential sources of error are discussed, including the effect of back-flow of Gd-DTPA from the vitreous space to the plasma, the underlying vascular patency, and MRI slice selection.
Berkowitz
B A
BA
National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina.
Tofts
P S
PS
Sen
H A
HA
Ando
N
N
de Juan
E
E
D000818:Animals; D001813:Blood-Retinal Barrier; D002463:Cell Membrane Permeability; D003287:Contrast Media; D005260:Female; D005682:Gadolinium; D019786:Gadolinium DTPA; D007452:Iodates; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008433:Mathematics; D009942:Organometallic Compounds; D004369:Pentetic Acid; D011817:Rabbits; D015203:Reproducibility of Results; D012164:Retinal Diseases / Q000175:diagnosis* / Q000378:metabolism; D014822:Vitreous Body / Q000378:metabolism
D003287:Contrast Media; D007452:Iodates; D009942:Organometallic Compounds; D004369:Pentetic Acid; D005682:Gadolinium; D019786:Gadolinium DTPA; C032285:sodium iodate