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Biomedical subjects

K R Burnett

Publications and source records attributed to K R Burnett.

At least 19 recordsLinked to original sources

Ferrioxamine as a magnetic resonance contrast agent. Preclinical studies and phase I and II human clinical trials.

The preclinical and clinical trial experience with ferrioxamine (S-FDF; Salutar, Inc.) as a contrast agent for magnetic resonance imaging (MRI) is summarized. The results in 44 patients or subjects show that the drug is safe and well tolerated when given intravenously. In certain conditions, early results show that the use of this contrast agent provides more information than can be obtained with MRI alone.

Adult↗

Dynamic display of the temporomandibular joint meniscus by using "fast-scan" MR imaging.

In order to display temporomandibular joint (TMJ) images as a dynamic or motion study, a protocol was developed to obtain MR images of the TMJ in multiple phases of opening by using the "fast-scanning" capabilities of the GE Signa MR scanner. To facilitate this procedure a prototype device was also developed to passively open the patient's mouth from resting (closed) to fully open in user-defined increments (minimum 1 mm). MR imaging (surface coil) was carried out at each successive station using the GRASS, pulse-sequence data base of the GE Signa system operating at 1.5 T. Image-acquisition parameters were optimized in studies of cadavers and volunteers to obtain the clearest delineation of the TMJ meniscus and to determine any potential tradeoffs between total imaging time per slice (image quality), patient tolerance, and other practical considerations. For viewing, the images were sequentially placed in the video memory of the operating console and displayed in a back-and-forth-closed cine loop or "movie" mode at variable (operator-selectable) speeds. The dynamic sequences in four individuals were compared with static open- and closed-mouth views obtained with routine pulse sequences. Any single image from the dynamic display lacked the high resolution of the routine static images because of technical limitations of the pulse-sequence data base. However, in the movie mode the pertinent joint structures (such as meniscus and condyle) were clearly delineated, as were several of the important muscles of mastication. The anterior motion (translation) of the meniscus during jaw opening is particularly evident and suggests great potential for functional evaluation. These results show the feasibility of dynamic TMJ imaging with MR. The added information of the cine display potentially complements the routine static images and may prove extremely valuable in the assessment of TMJ dysfunction.

Cartilage, Articular↗

Intravenous digital subtraction angiography (DSA) of hemodialysis access fistulae.

Hemodialysis access fistulae or grafts are subject to a variety of complications, including thrombosis, stenoses, and aneurysm or pseudoaneurysm formation. The usual radiologic methods to evaluate these problems consist of retrograde venous angiography or standard femoral or brachial arteriography. Both are invasive, and may traumatize the artery or graft. Six patients with internal blood access were studied using digital subtraction angiography; five using a central venous injection and one with direct graft injection. Preliminary results indicate that intravenous digital subtraction angiography (IV-DSA) can depict the anatomy of access fistula with adequate spatial resolution. Pathologic entities (stenoses, aneurysms) can be demonstrated, as well as other findings of uncertain clinical significance (kinks and webs). In addition, hemodynamic data can be inferred from the near-physiologic sequence of vessel opacification. Methods are in development that will allow determination of absolute blood flow in pertinent vessels via IV-DSA. There were no complications in this small series, and all examinations were performed on outpatients utilizing standard technique.

Adult↗

Magnetic field dependence of proton relaxation rates in tissue with added Mn2+: rabbit liver and kidney.

Since contrast in magnetic resonance imaging (MRI) is so sensitive to the magnetic relaxation rates of tissue protons, the use of paramagnetic ions to alter contrast in a tissue-specific fashion is an alluring prospect. The influence of these ions on the proton relaxation rates in homogeneous solutions is known to vary dramatically according to whether the ions are present as hydrated aquoions, in solute chelate, or immobilized in macromolecules. In tissue, there is the additional complication of access of water to the ions. In the present study, Mn2+ ions were introduced into rabbits both orally and intravenously in various chemical complexes. Accumulation of these ions in rabbit liver is demonstrated here, qualitatively, by MRI. The quantitation of the change in relaxation rates is investigated in excised samples of liver and kidney by study of the magnetic field dependence (dispersion) of the relaxation rates of the protons (NMRD profiles) of tissue water. Results are presented for several sets of experiments, including dose-response data for weakly chelated Mn2+ and time-response data for free and complexed Mn2+. The general findings are that, for liver, the response (the increment in the NMRD profile) is relatively rapid (less than 2 m); that it is relatively independent of how, or in what form, the Mn2+ is introduced; that it persists for several hours (at least); and that it saturates with increasing body load of Mn2+. Moreover, from the form of the NMRD profiles of liver, it is clear that the Mn2+ ions are bound irrotationally, perhaps to cell membrane, and, when introduced in chelated form, can become separated even from strongly associated chelate complexes. For kidney, the results are qualitatively similar, though different in detail.

Animals↗

Gadolinium oxide: a protoype agent for contrast enhanced imaging of the liver and spleen with magnetic resonance.

Gd2O3 particles (less than 2 microns) in suspension were evaluated as a potential contrast agent for liver-spleen imaging with magnetic resonance. The agent was administered IV to rabbits in doses ranging from 10 to 120 mumol/kg and the tissues removed after sacrifice for in vitro T1 and T2 analysis. The temporal response was determined in liver and spleen samples of rabbits given a fixed dose (60 mumol/kg) and sacrificed at intervals from 15 min to 60 hr later. Documentation of the subanatomic location of Gd2O3 particles in tissue was accomplished by electron microscopy and x-ray dispersion microanalysis. T1 weighted images were obtained at 0.12T on a prototype resistive scanner. The liver, spleen, and lung relaxation times are very responsive to Gd2O3 IV and the effect is dose related. A peak effect is observed between 3-7 hr after injection and relaxation times may normalize by 60 hr. By electron microscopic and x-ray analysis, Gd2O3 is most prominently found in the hepatic and splenic sinusoids. The images show marked enhancement of liver and splenic tissues, aiding in the clear delineation of these tissues from neighboring structures.

Animals↗

Contrast enhancement of spontaneous animal CNS tumors with gadolinium DTPA: a correlation of MRI with x-ray CT.

A visual comparison was made between both pre-contrast and post-contrast x-ray computerized tomographic images (X-CT) and magnetic resonance tomographic images (MRI) of spontaneous CNS tumors in three animals. The contrast agents, HypaqueR-76 (X-CT) and Gadolinium DTPA (MRI), were administered as an intravenous bolus injection. The parameters for comparison of pre- and post-contrast features included: lesion discrimination, demarcation, and intensity and pattern of enhancement. Necropsy specimens were included to correlate the anatomic fidelity of scan appearances for each modality and to establish a final diagnosis. There was good visual correlation of the lesion site with both X-CT and MRI. The intensity of lesion enhancement with the contrast reagents was similar for each modality but there were subtle differences in the pattern of enhancement. Overall, MRI in conjunction with the contrast agent Gadolinium DTPA, was as good or better at delineating the presence and extent of CNS tumors than contrast enhanced X-CT. Contrast agents may be necessary to provide increased lesion detectability and delineation when imaging with magnetic resonance.

Adenoma↗

NMR in vitro measurements: a quality control study of the RADX table-top spectrometer.

A series of experiments was performed to evaluate the accuracy and reproducibility of relaxation values obtained by two RADX table-top spectrometers operating at 5 MHz (R5) and 10 MHz (R10) respectively. The output (T1, T2, and proton content) of each machine was compared (for tissue specimens and paramagnetic solutions) to reference spectrometers. In the range of tissue T1's, R5 overestimates T1 by approx. 10% and R10 underestimates by approx. 23%. For tissue specimens, the T2 output of both machines is within 3% of the reference facility. Proton content values correlate well with the % wet weight of tissues (y = .46x + 24, r = .85) but accuracy deteriorates badly if tissue T1 greater than 400 msec or T2 greater than 300 msec. The output of both machines is accurate and reproducible within 5% over the range of tissue relaxation values (biological fluids excluded).

Animals↗

The oral administration of MnCl2: a potential alternative to IV injection for tissue contrast enhancement in magnetic resonance imaging.

Mn+2 (as MnCl2) was administered to rabbits intravenously and orally (a route of administration which based upon our previous experiments in rats promises to give selective hepatobiliary enhancement with less systemic toxicity). Nuclear magnetic relaxation dispersion or T1 (NMRD) was performed on selected tissues (heart, liver, kidney, serum, and bile) in both animal groups to examine possible qualitative and semiquantitative differences in T1 relaxation at equivalent sacrifice times. One animal was given an oral dose of MnCl2 (620 micromoles/kg) and imaged sequentially (T1 weighted sequence, .12T) for 30 minutes. The NMRD curves for organ tissues show an increase in relaxation efficacy in the 10-20MHz range characteristic of Mn-macromolecular complexes and are similar irrespective of the route of administration. The lack of increased relaxation enhancement for bile in this frequency range reflects cleavage of this complex upon excretion. Decreased overall relaxation in the liver is observed when oral Mn+2 is compared to IV Mn+2 due to the small fraction of administered dose that is absorbed. However, the images document a significant increase in the intensity of liver signal after the oral dose. We suspect this dose may ultimately be adjusted downward to give selective hepatobiliary effects.

Administration, Oral↗

Proton relaxation enhancement in tissue due to ingested manganese chloride: time course and dose response in the rat.

MnCl2, a potential NMR contrast agent, was force fed by cannula to 27 fasted rats in an attempt to establish the efficacy of this route of administration. The animals were sacrificed and the relaxation times (T1 and T2) of liver, spleen, kidney, heart, and skeletal muscle were determined in vitro. One group of rats was subject to a range of doses (8.3-333.3 mg/kg) and sacrificed at 90 minutes. Another group received a single large dose (500 mg/kg) with animals sacrificed at intervals from 15-225 minutes. The single large dose caused a rapid and prolonged reduction in liver T1 (-93% of normal) and to a lesser degree affected the other organs. The dose response data shows that liver T1 is also affected at significantly lower dosages than the other tissues tested. These results suggest the oral route as a possible alternative to IV Mn+2. Further studies with inorganic and organic manganese are indicated.

Animals↗