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Biomedical subjects

W H Perman

Publications and source records attributed to W H Perman.

At least 19 recordsLinked to original sources

Simultaneous MR acquisition of arterial and brain signal-time curves.

Regional cerebral blood flow (rCBF) provides important information about local neuronal functional and cerebrovascular status. Determination of rCBF requires sequential measurements of tracer concentration in arterial blood and brain tissue unless the tracer is trapped in the brain in proportion to rCBF. Since gadopentate dimeglumine is not trapped within brain tissue, we have developed the simultaneous dual FLASH pulse sequence (SDFLASH) which sequentially measures the MR signal change in both the internal carotid artery and brain parenchyma simultaneously during the passage of a bolus of paramagnetic contrast material.

Animals

Evaluation of two new gadolinium chelates as contrast agents for MRI.

Two new gadolinium chelates were investigated for potential use as tissue-specific contrast agents for magnetic resonance imaging. In vitro measurements of stability constants, octanol/water partition coefficients and relaxation times in solutions of water and human serum albumin (HSA) were performed with each new chelate and compared with gadolinium-diethylenetriamine pentaacetic acid, Gd(DTPA). Biodistribution studies and magnetic resonance imaging in rats were used to evaluate the new chelates in vivo. The stability constants (log K) of gadolinium-N,N''-bis(3-hydroxy-6-methyl-2- pyridylmethyl)diethylenetriamine-N,N',N''-triacetic acid, Gd(DTTA-HP), and gadolinium-1,7,13-triaza-4,10,16-trioxacyclooctadecane-N,N', N''-triacetic acid, Gd(TTCT), were determined to be 23.65 and 18.07, respectively. These can be compared to a literature value of 22.46 for Gd(DTPA). Octanol/water partition coefficients for both complexes showed they were more lipophilic than Gd(DTPA). Gd(DTTA-HP) exhibited a smaller relaxivity in water but a larger relaxivity in 4% HSA than Gd(DTPA). Gd(TTCT) exhibited a lower relaxivity than Gd(DTPA) in both water and 4% HSA. Both complexes showed similar biodistributions to Gd(DTPA) no carrier-added concentrations. Gd(DTTA-HP) had a greater percent change in signal intensity than Gd(DTPA) on T1-weighted spin-echo images in the heart, liver, and kidney. Percent change in signal intensity for Gd(TTCT) was lower than Gd(DTPA) in heart, liver, and kidney.

Acetates

Pressure-gated acquisition of cardiac MR images.

Electrocardiographically gated magnetic resonance (MR) image acquisition is not optimal for the quantification of in vivo cardiac deformation, because of the cycle-length dependence of cardiac mechanical events. The authors developed a method for acquisition of cardiac MR images gated to the first derivative of left-ventricular-developed pressure and used the method in a canine model. Application of this method may improve myocardial stress-strain analyses.

Animals

Regional myocardial stress distribution from magnetic resonance image-based mathematical models.

The instantaneous regional stress distribution within the myocardium, which cannot be directly measured, has been estimated using improved numerical methods and nonaxisymmetric biventricular geometry. To do this, we have employed computer-aided solid mathematical modeling to generate a three-dimensional representation for an ex vivo canine biventricular unit using magnetic resonance imaging. A two-dimensional transverse section was isolated from the solid mathematical model for regional stress analysis using p-version finite element analysis. Loading conditions and material property descriptions were taken from published reports. Analyses showed the maximum principal stresses to range from -1.76 X 10(5) to 8.52 X 10(5) dynes/cm2 during systolic loading, and from -3.85 X 10(4) to 1.13 X 10(5) dynes/cm2 during diastolic loading. This study demonstrates that magnetic resonance image-based solid mathematical biventricular models are suitable for regional stress analysis using p-version finite element analysis. p-Version finite element analysis using magnetic resonance image-based cardiac representations facilitates in vivo stress-strain analyses and may allow the clinical estimation of regional myocardial stress.

Animals

Liver imaging at 1.5 tesla: pulse sequence optimization based on improved measurement of tissue relaxation times.

In order to predict the most sensitive MR imaging sequence for detecting liver metastases at 1.5 T, in vivo measurements of T1 and T2 relaxation times and proton density were obtained using multipoint techniques. Based on these measurements, two-dimensional contrast contour plots were constructed demonstrating signal intensity contrast between hepatic lesions and surrounding liver parenchyma for different pulse sequences and pulse timing parameters. The data predict that inversion recovery spin echo (IRSE) imaging should yield the greatest contrast between liver metastases and liver parenchyma at 1.5 T, followed by short tau inversion recovery (STIR) and spin-echo (SE) pulse sequences. T2-weighted SE images provided greater liver/lesion contrast than T1-weighted SE pulse sequences. Calculated T1, T2, and proton density values of the spleen were similar to those of hepatic metastatic lesions, indicating that the signal intensity of the spleen may be used as an internal standard to predict the signal intensity of hepatic metastases on T1- and T2-weighted images at 1.5 T.

Adult

Brain surface cortical sulcal lengths: quantification with three-dimensional MR imaging.

The repeatability and accuracy of brain surface cortical sulcal length measurements obtained with three-dimensional (3D) reconstructions of volumetric, gradient-echo magnetic resonance (MR) images were tested. The brains of eight healthy adult volunteers and one cadaver were imaged in both the coronal and sagittal planes to yield a set of 128 1.5-2.0-mm-thick contiguous sections. 3D reconstructions of the brain cerebral cortical surfaces were obtained with computer software. Location and distance measurements of surface sulci were repeated on each reconstructed image. The same structures in the cadaver brain were independently measured with a 3D electromagnetic digitizer to validate the results of the 3D MR imaging method. All measurements from reconstructed images had high repeatability, and there were no statistically significant differences between measurement trials. The accuracy of measurements with 3D MR imaging was also good; the mean difference between digitizer and 3D MR measurements for sulcal lengths was 0.81 cm (average, 5.45-12.9 cm).

Adult

Separation of spin populations with gradient echoes as an aid in pulse sequence tuning.

Tuning of nuclear magnetic resonance pulse sequences with pulsed "crusher" gradients or phase cycling serves to remove unwanted spin populations from the data acquisition window. Verification that unwanted spin population are not detected is often determined by the absence of obvious artifacts in an image. This approach is unsatisfactory in some instances because signal contamination with unwanted spin populations may not be obvious. This is a particular concern with multiple-spin echo, volume-selective, and other multiple-pulse sequences. A solution to this problem is the separation of spin populations using gradient echoes, allowing the existence of unwanted populations to be easily observed separately. Tuning of a pulse sequence is straightforward when spin populations can be independently observed.

Humans

Rapid acquisition spin-echo (RASE) MR imaging: a new technique for reduction of artifacts and acquisition time.

The rapid acquisition spin-echo (RASE) technique combines a short repetition time, a short echo time, and a single excitation pulse sequence with half-Fourier data sampling. This allows for acquisition of 11 strongly T1-weighted sections during a single 23-second breath-holding period. Measurements obtained from volunteers and with phantoms reveal that RASE images have a lower signal-to-noise ratio and contrast-to-noise ratio than do conventional multiacquisition spin-echo (SE) images due to reduced data acquisition. However, liver-spleen contrast and spatial resolution are not affected. Moreover, contrast-to-artifact (C/A) measurements are 77% greater with RASE. When normalized for imaging time, all parameters are significantly higher with RASE, with a C/A per unit time that was 338% higher. Randomized, blinded review of RASE and SE sequences from 20 patients was conducted to evaluate qualitative performance. Excellent to good performances for phase-encoding artifact reduction, edge sharpness, and overall image quality were recorded for 89%, 88%, and 86% of RASE examinations, respectively, versus 41%, 59%, and 47% of conventional SE examinations, respectively. All results were statistically significant with P less than .001. RASE is an easily implemented imaging technique that utilizes widely available existing technology. Its major benefits relate to significant reduction in imaging time, elimination of respiratory artifacts, and the potential for performing dynamic contrast material-enhanced screening examinations.

Abdomen

A method for correctly setting the rf flip angle.

Currently the accepted method for setting the correct rf power levels to achieve 90 degrees and 180 degrees rf pulses for MR imaging is to peak the echo amplitude of a rf spin-echo sequence. The echo amplitude of this alpha-2 alpha pulse sequence is proportional to sin3 (alpha) and has a relatively broad maximum. Recently another method for setting the rf flip angle by maximizing the ratio of the stimulated echo to the primary echo amplitudes (in a 3 alpha sequence) demonstrated accuracy similar to that of the spin-echo method using a shorter repetition time. We present a new, more sensitive, and more accurate method for setting the correct rf power levels for 90 degrees and 180 degrees rf pulses. In this method, based upon the stimulated echo pulse sequence, we are able to accurately set the rf power to within +/- 0.1 dB by minimizing the signal amplitude of the third spin echo. This null method works for both selective and nonselective rf pulses of flip angle 90 degrees or 180 degrees, allowing the user to accurately adjust the relative amplitudes of the four rf pulse types within a single pulse sequence.

Calibration

Multiple short-echo (2.5-ms) quantitation of in vivo sodium T2 relaxation.

The MR behavior of the sodium-23 nucleus in vivo is a complex problem which has generated considerable interest over the last 20 years. Early studies on excised tissue samples revealed that the sodium nucleus exhibited a two-component T2 relaxation. This biexponential T2 relaxation was characterized by a short component with a T2 = 0.7-4.8 ms, and a long component with a T2 = 7.0-26.0 ms. We have developed a 3D pulse sequence capable of performing multiple Hahn echo in vivo sodium-23 imaging at echo times as short as 2.5 ms. This sequence obtains the shorter spin echo times by presaturating the spins outside of the desired imaging region, allowing the use of nonselective rf pulses. Using this sequence we have been able to quantify the long and short T2 components of normal brain tissue, vitreous humor of the eye, and a rabbit VX-2 carcinoma. We found that gray matter and white matter of normal brain have a monoexponential T2 relaxation with T2 = 17.6 +/- 2.4 ms. The vitreous humor T2 relaxation is also monoexponential with T2 = 56.8 +/- 2.1 ms. However, we find that some of the rabbit VX2 carcinomas exhibit a biexponential T2 decay with a short component of 3.3 +/- 4.6 ms and a long component of 22.0 +/- 9.0 ms.

Absorption

Projection flow imaging by bolus tracking using stimulated echoes.

Previous investigators have employed the concept of bolus tracking using either spin echoes or gradient echoes. In this paper we introduce two methods of bolus tracking using planar- and volume-selective stimulated echoes. The planar method employs a selective 90 degrees rf pulse which tags all spins in a particular plane. At a time tau 1 later, a nonselective 90 degrees rf pulse is employed, followed after a time tau 2, by another nonselective rf pulse. Only spins which experience all three rf pulses form a stimulated echo at time tau 1 after the third rf pulse. A balanced pair of flow-compensated dephasing (crusher) gradients further ensures that the stimulated echo is due only to the effect of all three rf pulses while minimizing flow dephasing. The first part of this gradient pair is applied after the initial rf pulse in the first tau 1 period to dephase the tagged spins. The second part of this gradient pair is applied after the third rf pulse to rephase the spins. Since the plane of the excited slice is orthogonal to the readout direction, flowing spins are imaged in an angiographic manner as they move away from the excited slice. A modification to this basic sequence excites only a small volume. In this manner, the suppression of stationary spins is effected by volume-selective excitation. In both the planar- and the volume-selective techniques, the excited spins undergo T1 and T2 relaxation during the tau 1 period but only T1 relaxation in the tau 2 period. In blood, where T1 is much greater than T2, keeping tau 1 as short as possible minimizes signal loss due to T2 dephasing. These methods demonstrate increased sensitivity compared to similar bolus tracking methods using either spin echoes or gradient echoes.

Blood Flow Velocity

Clinical and experimental sodium magnetic resonance imaging.

In conclusion, sodium MR imaging has potential for providing physiologic information relevant to cell mitosis, cell energy state, rCBV, and seizures. Considerable technical and experimental development is necessary, however, before sodium MRI becomes a routine examination in the clinical setting.

Brain Chemistry

Experimental and human brain neoplasms: detection with in vivo sodium MR imaging.

Elevations of intracellular sodium concentration have been observed in rapidly proliferating cells and malignant neoplasms. Sodium magnetic resonance (MR) imaging (with repetition times of 133 msec and echo times of 13, 26, 39, and 42 msec) was performed in ten patients and three dogs with central nervous system neoplasms. In all instances the neoplasms were associated with an increased sodium signal compared with that of normal brain. Unfortunately, the available echo times did not enable discrimination of intracellular sodium from extracellular sodium, which was present in high concentrations in adjacent vasogenic edema fluid. Further study is necessary to establish the utility of sodium MR imaging for the investigation of malignant neoplasms.

Animals

Magnetic resonance imaging of gadolinium-labeled monoclonal antibody polymers directed at human T lymphocytes implanted in canine brain.

Two different murine monoclonal anti-human T cell antibodies, that were coupled to gadolinium (Gd), bind specifically to human T lymphocyte cells implanted in canine brain. This binding was at a concentration of Gd sufficient to detect the implanted cells and to distinguish them from the surrounding brain tissue with magnetic resonance imaging (MRI) at a field strength of 1.5 Tesla. These Gd-labeled immunoglobulin preparations did not bind bovine T cells at a concentration sufficient to be detected on MRI. A protein solution containing the immunoglobulins (100 micrograms), gelatin (2 mg), and bovine serum albumin (2.5 mg) was reacted with the dianhydride of diethylenetriaminepentaacetic acid (DTPA); the DTPA serves as a metal chelator and as a protein crosslinking agent. The DTPA-protein complex was reacted with Gd chloride. There were approximately 10 DTPA residues per protein molecule in the modified protein mixture. Isolated human or bovine monocytes (approximately 12 million cells) were implanted in the brains of anesthetized dogs in a volume of 40 microliters. The blood-brain barrier was then disrupted by the intra-arterial injection of hyperosmotic mannitol, and the Gd-labeled antibodies were injected through a catheter placed at the branch of the internal and external carotid arteries. The brains were imaged 48 to 72 hours later. The MRI scans revealed a markedly decreased T1 relaxation time with a high signal intensity (TE = 25 msec, TR = 200 msec) related to the human T cell implants. There was no evidence of decreased T1 at the site of the bovine T cells. Neither control murine gamma globulin coupled to Gd-DTPA nor anti-human T cell antibodies uncoupled to Gd modified the MRI contrast of the human T cells in the brain.

Animals

Clinical and experimental vasogenic edema: in vivo sodium MR imaging. Work in progress.

To investigate the sodium magnetic resonance (MR) imaging characteristics of acute vasogenic edema, an experimental canine model was developed. Vasogenic edema was produced in the hemisphere of the dogs by the intraarterial infusion of hypertonic mannitol (25%). This solution opens the blood-brain barrier, allowing the influx of water, electrolytes, and proteins into the brain. The main advantage of this model over the established "cold injury" model is the lack of associated brain necrosis. Two patients with chronic vasogenic edema secondary to well-circumscribed meningiomas also underwent MR imaging. The sodium signal was markedly elevated in both clinical and experimental studies of vasogenic edema fluid compared with signal in healthy brain tissue. Extracellular sodium associated with vasogenic edema displayed MR imaging characteristics similar to that of sodium in serum. There was a trend toward a shortened T2 in edema fluid secondary to the presence of serum macromolecules.

Animals

Methodology of in vivo human sodium MR imaging at 1.5 T.

The methodology of sodium-23 (Na-23) imaging is reported in relationship to the physiological factors that determine the chemical environment of the Na-23 nucleus. Contrast resolution is given as a function of imaging time and spatial resolution. Data showing the optimal relaxation time for sodium imaging are given, and the linear quantitative relationship between sodium concentration and voxel intensity for our imaging system is confirmed. The major problem facing in vivo sodium imaging is the ability to differentiate intracellular sodium from extracellular sodium. The sodium in blood serum (extracellular) and packed red blood cells (intracellular) both exhibit biexponential T2 decay. These results indicate that T2 measurements alone will be insufficient for discriminating extracellular from intracellular sodium. Instead, other methods based on the underlying physiological properties of in vivo sodium imaging, such as the diffusion coefficient, will be necessary to truly separate extracellular from intracellular sodium.

Brain Neoplasms

Electrical conductivity in lipid bilayer membranes induced by pentachlorophenol.

Electrical conductivity induced in thin lipid bilayer membranes by pentachlorophenol has been studied. The membranes were formed from phosphatidyl choline, phosphatidyl ethanolamine, or phosphatidyl glycerol and various amounts of cholesterol. The position and the magnitude of the maximum of the conductivity vs. pH curve depend on the type of lipids and cholesterol content. At low pentachlorophenol concentrations and low pH the concentration dependence of conductivity is quadratic and becomes linear at higher pH. Above 10(-5) M of pentachlorophenol the concentration dependence of the membrane conductivity tends to saturate. Presence of pentachlorophenol enhances membrane transport of nonactin-K+ complex. Increase of cholesterol content increases pentachlorophenol induced conductivity in all membranes and shifts the conductivity toward lower pH. For phosphatidyl choline the largest rate of change of membrane conductivity with cholesterol occurs at 1:1 phospholipid to cholesterol molar ratio. Pentachlorophenol is found to be a class II uncoupler and the experimental results are consistent with the hypothesis that the membrane permeable species are dimers formed by combination of neutral and dissociated pentachlorophenol molecules. Several schemes of membrane conduction, including dimer formation in the aqueous phase as well as at the membrane-water interface have been considered. Arguments are given in favor of the formation of dimers within the membrane surface.

Electric Conductivity