Tumor imaging with a macromolecular paramagnetic contrast agent: gadopentetate dimeglumine-polylysine.

RATIONALE AND OBJECTIVES: We evaluated magnetic resonance (MR) contrast enhancement of tumor tissue following injection of the macromolecular conjugate, gadopentetate dimeglumine-polylysine. METHODS: T1-weighted MR imaging scans were performed on female Fisher-344 rats with subcutaneously implanted mammary adenocarcinoma tumors. Following the baseline scan, gadopentetate dimeglumine-polylysine or gadopentetate dimeglumine was injected at a dose of 0.1 mmol gadolinium per kilogram. RESULTS: Gadopentetate dimeglumine-polylysine injection resulted in a maximum enhancement of tumor contrast of 310 +/- 60% (n = 7). Tumor tissue remained enhanced and well defined for several days after gadopentetate dimeglumine-polylysine injection. Gadopentetate dimeglumine injection at the same dose resulted in a 70 +/- 25% (n = 4) maximal tumor enhancement and a corresponding 25 +/- 4% muscle enhancement. CONCLUSION: Gadopentetate dimeglumine-polylysine provides higher, more sustained tumor contrast than does gadopentetate dimeglumine for the same dosage of gadolinium.

Noninvasive measurement of renal hemodynamic functions using gadolinium enhanced magnetic resonance imaging.

A technique for the assessment of single kidney hemodynamic functions utilizing a novel MR pulse sequence in conjunction with MR contrast material administration is described. Renal extraction fraction (EF) is derived by measuring the concentration of the incoming contrast agent in the renal artery and the outgoing concentration in the renal vein. The glomerular filtration rate (GFR) can then be determined by the product of EF and renal plasma flow. A modified inversion recovery MR pulse sequence is used to measure the T1 of moving blood. This pulse sequence uses a spatially nonselective inversion pulse. A series of small flip angle detection pulses are then used to monitor the recovery of longitudinal spin magnetization in an image plane intersecting the renal vessels. The recovery rate is measured in each vessel and the T1 of blood determined. These T1 measurements are then used to determine the ratio of contrast concentration in the renal arteries and veins. Blood flow measurements can be obtained simultaneously with T1 measurements by inserting flow-encoding magnetic field gradients into the pulse sequence. Preliminary results in human volunteers suggest the feasibility of noninvasively determining hemodynamic functions with magnetic resonance.

Transduction of membrane tension by the ion channel alamethicin.

Mechanoelectrical transduction in biological cells is generally attributed to tension-sensitive ion channels, but their mechanisms and physiology remain controversial due to the elusiveness of the channel proteins and potential cytoskeletal interactions. Our discovery of membrane tension sensitivity in ion channels formed by the protein alamethicin reconstituted into pure lipid membranes has demonstrated two simple physical mechanisms of cytoskeleton-independent transduction. Single channel analysis has shown that membrane tension energizes mechanical work for changes of conductance state equal to tension times the associated increase in membrane area. Results show a approximately 40 A2 increase in pore area and transfer of an 80-A2 polypeptide into the membrane. Both mechanisms may be implicated in mechanical signal transduction by cells.

Lipid-glass adhesion in giga-sealed patch-clamped membranes.

Adhesion between patch-clamped lipid membranes and glass micropipettes is measured by high contrast video imaging of the mechanical response to the application of suction pressure across the patch. The free patch of membrane reversibly alters both its contact angle and radius of curvature on pressure changes. The assumption that an adhesive force between the membrane and the pipette can sustain normal tension up to a maximum Ta at the edge of the free patch accounts for the observed mechanical responses. When the normal component of the pressure-induced membrane tension exceeds Ta membrane at the contact point between the free patch and the lipid-glass interface is pulled away from the pipette wall, resulting in a decreased radius of curvature for the patch and an increased contact angle. Measurements of the membrane radius of curvature as a function of the suction pressure and pipette radius determine line adhesion tensions Ta which range from 0.5 to 4.0 dyn/cm. Similar behavior of patch-clamped cell membranes implies similar adhesion mechanics.