Mary E. Girton

Gadolinium-DTPA Enhanced Dynamic MR Imaging in the Evaluation of Cisplatinum Nephrotoxicity

Gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA) enhanced dynamic magnetic resonance (MR) imaging was used to monitor the nephrotoxic effects of cis-platinum (cis-diamminedichloroplatinum; CDDP), a chemotherapeutic agent that produces damage in the proximal convoluted tubule. Ten New Zealand white rabbits (NZWs) were divided into two groups and were evaluated at two clinically relevant doses of CDDP. Group 1 (four NZWs) received CDDP intravenously at 125 mg/m2 over 1 h. Rabbits in Group 2 (six NZWs) were infused with CDDP at 40 mg/m2 each day for 5 consecutive days. Dynamic MR images were performed in the axial plane at 1.5 T using a gradient recalled acquisition in the steady state sequence with an echo time of 11 ms, a repetition time of 20 ms, and a flip angle of 10° after a bolus injection of Gd-DTPA 0.1 mmol/kg. Thirty-two sequential post Gd-DTPA images (5.12 s/image) were obtained over 2 min 45 s at a single location. All rabbits underwent baseline normal and serial post CDDP Gd-DTPA enhanced dynamic MR scans. Analysis of the alterations in the normal pattern of renal enhancement caused by CDDP was facilitated by using a stacked profile image and quantitative region of interest measurements of signal intensity. Normally, after the injection of Gd-DTPA, a dark band promptly appears in the outer cortex of the kidneys and migrates centripetally toward the papilla, reflecting the tubular concentration of Gd-DTPA. In Group 1 rabbits, nephrotoxicity due to CDDP was observed as early as 9 h after administration of the drug, with a complete disappearance of the dark band by 7 days. In Group 2 rabbits, the band disappeared gradually and reappeared 2–10 days after the completion of CDDP treatment, indicative of tubular damage and recovery with return of the concentrating ability of the kidney. These results illustrate the feasibility of using Gd-DTPA dynamic MR as a sensitive monitor of drug induced alterations of renal function.

Dynamic enhanced magnetic resonance imaging of testicular perfusion in the rat

Magnetic Resonance Imaging (MRI) has several theoretical advantages in the evaluation of spermatic cord torsion and testicular ischemia. The technique uses no ionizing radiation, has both excellent spatial and temporal resolution and, when used with an intravenous bolus of a paramagnetic contrast agent, provides a semiquantitative assessment of tissue perfusion and vascular injury. In clinical instances of testicular torsion, accurate estimates of tissue perfusion are desirable since testicular salvage is inversely related to the duration of torsion and the degree of tissue ischemia. Perfusion imaging of the rat testis was used as a model to demonstrate the potential use of MRI in the experimental and clinical analysis of disorders that affect blood flow to the testis.

Opening of Blood–ocular Barrier Demonstrated by Contrast-enhanced Mr Imaging

Opening of the blood-ocular barrier following infusion of hyperosmolar agents into the internal carotid artery has been demonstrated by gadolinium enhanced magnetic resonance (MR) imaging. In five rhesus monkeys the disruption of the barrier was shown as increased signal intensity within the aqueous and vitreous humors. These findings suggest a potential use of contrast-enhanced MR imaging for detecting and evaluating the ocular microangiopathy of diabetic and hypertensive retinopathy and other diseases.

Gadolinium cryptelates as MR contrast agents

Gadolinium cryptelates are complexes of a lanthanide metal ion with amino acids of macrocyclic polyamines. These compounds are water soluble and possess reduced relaxation properties similar to Gd diethylene triamine pentaacetic acid (DTPA). Three Gd cryptelates (Gd NOTA, DOTA, TETA) were evaluated. Gadolinium DOTA is the most stable Gd complex with a dissociation constant of 10(-28) and appears to have a greater serum stability than Gd DTPA. Gadolinium NOTA and Gd TETA have lower dissociation constants than Gd DTPA at 10(-17) and 10(-19). Gadolinium DOTA has tissue distribution properties similar to Gd DTPA, is rapidly excreted by the kidneys, and provides a high degree of contrast enhancement on magnetic resonance (MR) images, both systemically and within the CNS. Hence, Gd DOTA is an alternative water-soluble MR contrast agent to Gd DTPA.

Variability of ischemia during spermatic cord torsion in the rat

Testicular torsion affects prepubertal males and causes testicular infarction and subfertility. Animal models of spermatic cord torsion have been used in an attempt to study the mechanism of testicular injury from torsion. Although standardized animal models of torsion have been proposed, their reliability in producing testicular ischemia has not been documented. Dynamic enhanced magnetic resonance imaging (MRI) of the testis was used in a rat model with surgically induced, unilateral, 720 degrees torsion to quantify the severity of ischemia. Intravenous dysprosium diethylenetriaminepentaacetic acid-bis methylamide (Dy-DTPA-BMA) was injected as a bolus followed by serial dynamic Turbo GRASS images. Region of interest (ROI) measurements were obtained within the testicular parenchyma during contrast enhancement and washout. Perfusion abnormalities ranging from minimal delay in contrast enhancement in the torqued testicle to complete absence of intraparenchymal blood flow were documented with dynamic enhanced MRI. Reperfusion scans 1 hour after surgical reduction of torsion showed normalization of testicular blood flow in all animals. Dynamic enhanced MRI appears to be a useful method of documenting the perfusion deficit arising from torsion of the testis. Standard animal models of torsion produce inconsistent results because they do not reliably reproduce testicular ischemia. The ability of MRI to quantify perfusion abnormalities in the testis may provide additional information in the evaluation of human patients with symptoms of testicular torsion.

Gadopentetate Dimeglumine Clearance in Renal Insufficiency in Rabbits

The total body clearance of gadopentetate dimeglumine (Gd-DTPA) was evaluated in 17 normal rabbits and 11 rabbits with renal insufficiency induced by angioinfarction. Serial measurements of the serum spin lattice relaxation rate (1/T1) were compared with actual gadolinium concentrations as determined by mass spectroscopy. Gadopentetate dimeglumine concentrations measured by both mass spectroscopy and magnetic resonance (MR) relaxometry decreased by two logs in both normals and rabbits with renal impairment by 24 hours and were highly correlated with each other (r = .98). The estimated total body clearance of gadopentetate dimeglumine was 14.1 +/- 0.56 cc/minute for the normal animals and 3.78 +/- 0.19 cc/minute for the impaired rabbits. These results indicate that gadopentetate dimeglumine is excreted rapidly, usually within 24 hours, even in the presence of renal insufficiency.