First-pass renal perfusion imaging using MS-325, an albumin-targeted MRI contrast agent.

RATIONALE AND OBJECTIVES: MR angiography is proving to be a useful clinical study for the diagnosis of vascular disorders of renal arteries. However, its utility in terms of stenosis characterization is still limited. Renal perfusion could provide supplemental information that could allow for a comprehensive evaluation of renal artery stenosis by MR imaging. METHODS: MS-325 is a small-molecule blood pool agent that reversibly binds with serum albumin and hence leads to higher relaxivity and longer residence times in the blood. In this study, the authors evaluated the use of MS-325 to perform first-pass perfusion imaging and contrast-enhanced MR angiography in the characterization of renal artery stenosis in an animal model. RESULTS: Quantitative perfusion estimates were obtained in the renal cortex (258 +/- 19.8 mL/min/100 g) and are comparable to microsphere measurements (198 +/- 12.2 mL/min/100 g), given the practical constraints. Based on these measurements, perfusion showed minimal changes even when the diameter reductions reached 75%. CONCLUSIONS: MS-325 could provide quantitative perfusion estimates that when combined with MR angiography may lead to comprehensive evaluation of renal artery stenosis.

Controlled delivery of Gd-containing liposomes to lymph nodes: surface modification may enhance MRI contrast properties.

Surface modification of liposomes containing Gd-diethylenetriaminepentaacetyl-phosphatidylethanolamine (Gd-DTPA-PE) as an amphiphilic paramagnetic label influences their contrast properties as MRI agents. Liposomes with the mean diameter ca. 220 nm and 10% mol content of Gd-DTPA-PE were modified with dextran (molecular weight 6 kDa) or polyethyleneglycol (PEG, molecular weight 5 kDa). The preparations obtained were used for MR visualization of axillary and subscapular lymph nodes after SC injection into rabbit's paw. Dextran-modified liposomes were found to have limited or no effect on lymph node/muscle MR signal intensity ratio during the first 2 h after the administration when compared to nonmodified plain liposomes, whereas the liposomes modified with PEG demonstrated a 3-3.5-fold enhancement of lymph node signal. However, the partial biodistribution studies with the 111In-labeled liposomes revealed that PEG-modified vesicles accumulated in the axillary lymph node at half the amount comparing with nonmodified and dextran-modified liposomes. The phenomenon found might be explained by noticeably increased relaxivity of PEG-modified Gd-liposomes.

Time-lapse quantitative computed tomography lymphography: assessing lymphatic function in vivo.

RATIONALE AND OBJECTIVES: Immobility and massage produce different local limb lymph flow rates. We studied their influence on accumulation of radiopaque nanoparticulates in regional lymph nodes of normal rabbits. METHODS: Quantitative lymphography at 10-min intervals was used to follow the transport of subcutaneous (s.c.) nanoparticulates produced from insoluble esters of diatrizoic acid. In one design, both hindpaws received 0.5 ml of nanoparticulate s.c., and one hindpaw was massaged. In a second design, one hindpaw was injected and massaged while imaging the popliteal, presacral, and paraaortic nodes every 10 min. RESULTS: Gentle massage rapidly increased popliteal node accumulation in comparison with the immobile limb. On the massaged side, mean Hounsfield (HU) units, maximum Hounsfield units, and calculated iodine were significantly greater at 10 min and all subsequent times. In the node transfer experiments, it took 12, 30, and 45 min, respectively, to obtain 100-HU mean attenuation; 200-HU maximum attenuation thresholds were achieved at 20, 47, and 69 min, respectively. CONCLUSION: Quantitative computed tomography lymphography reflects local lymph physiology. Gentle massage of the s.c. injection site is a powerful lymphotropic stimulus.

Redistribution of renal blood flow after SWL evaluated by Gd-DTPA-enhanced magnetic resonance imaging.

Extracorporeal shockwave lithotripsy (SWL) is currently accepted as an effective noninvasive treatment for a wide variety of urinary tract calculi. However, the bioeffects of high-energy shockwaves on renal parenchyma have yet to be fully elucidated. The objective of this study was to measure the acute changes in regional renal hemodynamics associated with SWL utilizing dynamic gadolinium-DTPA-enhanced magnetic resonance imaging (MRI). Seven patients who underwent SWL for renal calculi had an MRI study within 4 hours after the treatment. To assess renal hemodynamics, a bolus of Gd DTPA (0.03 mmol/kg) was administered, and dynamic contrast enhanced images was obtained. Regions of interest (ROI) were defined over the cortex and medulla to obtain signal intensity-v-time curves. The contralateral kidney in each patient was used as the control. The initial slope of the contrast-enhanced signal intensity-v-time curve was used as a measure of the perfusion index (PI). In six patients, perfusion imaging showed a consistent trend of decreased cortical flow (29+/-8%) and a concomitant increase in medullary flow (34+/-14%) in the region of the kidney that was targeted with SWL in six patients (86%). This study shows that renal hemodynamics are modified by SWL. We hypothesize that this change represents a shunting of flow from cortex to medulla in an attempt to prevent ischemia of the medulla.

MR image time-intensity relations in spleen and kidney: a comparative study of GdDTPA, albumin-(GdDTPA), and Gd2O3 colloid.

Magnetic resonance images were performed using a gradient recalled echo sequence with acquisition of images every 30 s in anesthetized rats before and after intravenous bolus injections of 100 microns/kg GdDTPA, 60 microns/kg albumin-(GdDTPA), and 60 microns/kg Gd2O3 colloid. All three agents caused significant enhancement of the renal cortex, and even greater enhancement of the spleen. GdDTPA showed an early peak at 11 s followed by a wash-out as blood concentrations fell, whereas albumin-(GdDTPA) and Gd2O3 showed sustained tissue enhancement. The enhancement in each organ was equivalent for albumin-(GdDTPA) and Gd2O3 which stay intravascular; but 30% less for GdDTPA which enters the interstitial space. In addition GdDTPA showed an initial enhancement of the renal medulla but then a subsequent loss of signal, whereas albumin-(GdDTPA) resulted in a greater enhancement of the medulla as compared to the cortex. We conclude that time-intensity studies of local tissue response to MR indicators reflect tissue physiological parameters such as perfusion, blood volume, and concentrating ability in a semiquantitative manner.

Measurement of renal transit of gadopentetate dimeglumine with echo-planar MR imaging.

Times of peak gadolinium concentration ([Gd]) after intravenous (IV) and left ventricular (LV) bolus injection of gadopentetate dimeglumine were determined in renal cortex and medulla in normal rabbits and in rabbits after saline load (overhydration) or hemorrhage (dehydration). Magnetic resonance images were obtained with echo-planar inversion-recovery sequences, and signal intensity-versus-time curves in cortical and medullary regions of interest were converted to [Gd]-versus-time curves. Cortical perfusion measured with microspheres demonstrated that the three physiologic states were significantly different. There were three separate [Gd] peaks in both the cortex and medulla as the bolus moved from one anatomic compartment to the next. The first cortical peak occurred sooner after LV than after IV bolus injection (P < .05) and later in dehydrated than in normal and overhydrated rabbits (P < .05). The first medullary peak always followed the first cortical peak by about 6-10 seconds and mirrored the cortical patterns. The second and third cortical peaks were consistent with proximal and distal tubular transit. These peaks similarly showed faster response to LV than IV injection and were delayed by hemorrhage. The authors conclude that quantitative physiologic information can be obtained with dynamic contrast-enhanced MR imaging of the kidney.