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Biomedical subjects

R R Price

Publications and source records attributed to R R Price.

At least 19 recordsLinked to original sources

Role of noradrenergic hyperactivity in neonatal opiate abstinence.

Despite the existence of a well-defined abstinence syndrome in offspring of opiate-dependent mothers, the mechanisms involved in neonatal abstinence remain unclear. The goal of the present study was to determine the contribution of noradrenergic neurons in the opiate abstinence syndrome in neonatal rats (10 days old). First, the ability of the alpha 2-adrenergic agonist, clonidine to attenuate the symptoms of neonatal opiate abstinence precipitated by naloxone was determined. Secondly, the activity of noradrenergic neurons was determined by measuring postmortem levels of 3-methoxy-4-hydroxyphenylglycol (MHPG) in the hypothalamus, hippocampus and cortex in opiate-abstinent pups. Neonatal opiate abstinence was characterized by an increased incidence of wall climbing, tremors and mouthing. Acute treatment with morphine and naloxone in chronic saline-treated pups also produced the tremor, albeit less severe than in pups treated chronically with morphine. Clonidine (0.2 mg/kg) attenuated the expression of tremor and mouthing in neonates, but increased wall climbing. Clonidine elicited wall climbing in opiate-naive neonates. Treatment with morphine followed by naltrexone increased MHPG levels in all of the brain areas examined, irrespective of the chronic treatment, but naltrexone treatment elicited a larger increase in MHPG levels in pups treated chronically with morphine. Acute morphine treatment increased MHPG levels only in the hypothalamus. The results of the present study provide behavioral and neurochemical data supporting the hypothesis that noradrenergic hyperactivity plays a role in neonatal opiate abstinence.

Adrenergic alpha-Agonists

Use of magnetic resonance imaging and P-31 magnetic resonance spectroscopy to detect and quantify muscle dysfunction in the amyopathic and myopathic variants of dermatomyositis.

OBJECTIVE: To investigate the use of magnetic resonance imaging (MRI) and P-31 magnetic resonance spectroscopy (MRS) in characterizing the metabolic and functional status of muscles in patients with amyopathic dermatomyositis (DM) and to compare the findings with those in patients with classic myopathic DM. METHODS: Nine patients with amyopathic DM, 11 patients with myopathic DM, and 11 normal individuals were studied. MRI images of thigh muscles were obtained, and T1 and T2 relaxation times were calculated. Biochemical status was quantitated with P-31 MRS, by determining concentrations of phosphate metabolites during rest and exercise. RESULTS: Patients with amyopathic DM showed no muscle inflammation, and MRS data obtained during rest were normal. During exercise at 25% and 50% maximum voluntary contractile force, the MRS data revealed significant differences between amyopathic DM patients and control subjects indicating inefficient metabolism. In contrast, muscles of patients with myopathic DM showed inflammation and metabolic abnormalities even during rest. CONCLUSION: Metabolic deficiencies in patients with amyopathic DM were unmasked by exercise, suggesting that the 2 DM syndromes may share muscle abnormalities. MRI/MRS may be useful in diagnosis and optimization of treatment.

Adult

In vivo localized proton NMR spectroscopy of thiamine-deficient rat brain.

Thiamine deficiency (TD) in rats produces lesions similar to those found in humans suffering from Wernicke's encephalopathy, an organic mental disorder associated with alcoholism. Male Sprague-Dawley rats (n = 29) were deprived of thiamine via a regimen of thiamine-deficient chow and daily intraperitoneal injections of the thiamine antagonist pyrithiamine hydrobromide. Spectra were obtained by using the STEAM sequence. No significant change occurred in the ratio of Cr/NAA, while the ratio of Cho/NAA declined significantly (60 +/- 11%) on Day 14. Eleven rats received intraperitoneal injections of thiamine hydrochloride at the end of 12 days, and dose-dependent recovery in Cho/NAA was observed.

Alcohol Amnestic Disorder

The AAPM/RSNA physics tutorial for residents. Contrast mechanisms in gradient-echo imaging and an introduction to fast imaging.

The strengths of spin-echo sequences in clinical magnetic resonance imaging are its relative insensitivity to magnetic field inhomogeneities and its versatility; however, they require relatively long imaging times. Use of gradient-echo sequences largely circumvents the problem. A gradient echo is created by means of a gradient reversal following a single radio-frequency (RF) pulse, typically with a flip angle that is less than 90 degrees, compared with a spin-echo sequence, which requires at least two RF pulses, typically a 90 degree excitation pulse followed by a 180 degree refocusing pulse. The shortened repetition times (TRs) in gradient-echo sequences together with small flip angles enable maintaining adequate image signal-to-noise ratios while still achieving a short imaging time. Numerous gradient-echo sequences have been developed, with the most common being (a) fast low angle shot (FLASH), which uses small flip angles and short TRs; (b) gradient-recalled acquisition in the steady state and fast imaging with steady-state precession (GRASS/FISP); (c) magnetization-prepared rapid gradient echo (MP-RAGE); and (d) echo planar. The shorter imaging times made possible through gradient-echo sequences are used clinically to minimize patient motion artifacts and to allow isotropic three-dimensional imaging with acceptable imaging times.

Contrast Media

Quality of clinical MR images and the use of contrast agents.

Attempts to optimize the quality of magnetic resonance images must balance the competing needs for high spatial resolution, high signal-to-noise ratio, a large number of sections, and a reasonable imaging time. These factors, which determine the ultimate image quality, are affected by a number of variables, including the field of view, the matrix and pixel size, choice of repetition time and echo time, section thickness, and the number of signals averaged. The manner in which these variables interrelate and their effect on the ultimate image quality are important in order to craft the most appropriate examination for each individual patient. A second major effect on soft-tissue contrast is the use of paramagnetic agents. The spectrum of utility of these agents within the central nervous system and the body is increasing. A large number of new agents are also being investigated, primarily for use outside the central nervous system.

Contrast Media

Magnetic resonance imaging and P-31 magnetic resonance spectroscopy provide unique quantitative data useful in the longitudinal management of patients with dermatomyositis.

OBJECTIVE: To evaluate the utility of magnetic resonance imaging (MRI) and P-31 magnetic resonance spectroscopy (MRS) in the longitudinal management of patients with dermatomyositis (DM). METHODS: The study group consisted of 11 patients, including 3 children, all of whom had a clinical diagnosis of DM. A control group of 8 subjects was studied simultaneously. MRI included images as well as calculations of T1 and T2 relaxation times. The P-31 MRS protocol evaluated metabolic status (i.e., inorganic phosphate/phosphocreatine ratios and phosphocreatine and ATP levels) during rest, exercise, and recovery. RESULTS: T2-weighted images of the thigh muscles showed inflammation even when serum creatine phosphokinase levels were in the normal range. Metabolic abnormalities, which were accentuated with exercise, were found in 10 patients. In some individuals, bioenergetic defects preceded other changes and persisted after resolution of inflammation. In general, clinical impressions correlated with MRI/MRS data. CONCLUSION: MRI and MRS provide unique data which are quantitative and which cannot be obtained from routine laboratory tests. These MR evaluations appear to be of value in assessing the status of DM patients during treatment with steroids and immunosuppressive drugs.

Adolescent

Attenuation of monochromatic X-rays by normal and abnormal breast tissues.

RATIONALE AND OBJECTIVES: A prior study indicated that differences in the x-ray linear attenuation coefficients of cancerous and normal breast tissues tend to increase as the energy of the incident beam decreases. The authors investigated x-ray energies down to 20 keV. In the current study, the linear attenuation coefficients for normal and selected cancerous breast tissues within the energy range of 14 to 18 keV were determined. METHODS: Fifty breast biopsy specimens consisting of a mixture of breast malignancies, normal tissues, fat specimens, and tumors grown in rats were used. X-ray linear attenuation coefficients were measured for each sample within the energy range of 14.15 to 18 keV, using monoenergetic x-rays from beamline X-19A at the National Synchrotron Light Source at Brookhaven National Laboratory. Each sample was measured at 130 different energies starting at 14.15 keV with step sizes of 0.030 keV. Correlation of the measured attenuation coefficients for cellular makeup was performed. RESULTS: The mean of linear attenuation coefficients for samples classified as "cancers" was 10.9% higher than the mean of samples classified as "normal" breast tissues and was 66.5% higher than the mean of samples classified as normal breast fat. CONCLUSIONS: Differences in the linear attenuation coefficients of monochromatic x-rays between 14.15 and 18 keV do exist between normal and cancerous tissues, but there is some degree of overlap.

Biopsy

Magnetic resonance perfusion/diffusion imaging of the excised dog kidney.

RATIONALE AND OBJECTIVES: The authors developed a model of tissue capillary beds applicable to perfusion/diffusion imaging with magnetic resonance imaging (MRI). The model consists of a formalin-fixed excised dog kidney attached to a variable speed pump. With this system, it is possible to perfuse the kidney at selected rates. METHODS: Using the intravoxel incoherent motion model (IVIM), the apparent diffusion coefficient (ADC), diffusion coefficient (D), and perfusion fraction (f) were computed for a region of interest (ROI) in the renal cortex and in the medulla of seven kidneys, one of which was injected with a vasodilator before fixation. ADC and D values were computed for both cortex and medulla. These values were normalized to zero flow and plotted against renal perfusion. The perfusion fraction f was expressed in percent and was not normalized to zero flow. RESULTS: Normalized ADC and f were correlated with tissue perfusion rates using the Spearman rank-sum test (n = 18, rs greater than 0.5, P less than or equal to .02 for the standard preparation in both cortex and medulla), whereas normalized D (rs much less than 0.5) was uncorrelated for both preparations in cortex and medulla. CONCLUSIONS: The isolated perfused dog kidney is a useful model of tissue capillary beds for perfusion imaging technique development. The perfusion/diffusion-related parameters ADC and f increase as flow increases in the tissues, whereas D does not.

Animals

Magnetic resonance angiography techniques.

After a radio frequency pulse, the decay of the magnetic resonance (MR) signal is described by two relaxation processes, T1 and T2. T1 describes the rate at which the magnetization realigns itself along the external magnetic field direction (ML), and T2 describes the rate of decay of the magnetization component along the transverse axis (MT). Magnetic resonance angiography (MRA) sequences have been developed that encode flow as changes in the apparent T1 or T2 of the moving blood relative to stationary tissues. MRA sequences typically use either time-of-flight (TOF) techniques to encode T1 or phase-contrast techniques to encode T2. TOF techniques encode flow as an apparent T1 shortening through the wash-in of fully relaxed blood from outside the image volume. The shorter T1 produces an enhancement of vascular structures relative to stationary tissues. TOF methods may use either sequential two-dimensional, three-dimensional, or multi-slab three-dimensional imaging sequences to produce a three-dimensional MRA data set. Phase-contrast methods use additional magnetic field gradients to encode flow as shifts in the phase of MT. Both TOF and phase-contrast methods use maximum intensity projection (MIP) images displayed in a cine format to aid in the visualization of three-dimensional vascular structures.

Animals

Magnetic resonance diffusion/perfusion phantom experiments.

Recently, several models for determining microcirculatory parameters using magnetic resonance imaging have been proposed. These include the intravoxel incoherent motion (IVIM) model, the intravoxel coherent motion (IVCM) model, and various tracer models. In order to evaluate these models before extension into physiological systems, phantom studies were used to assess model assumptions, measurement uncertainties, and sensitivity to changes in perfusion. Emphasis is placed on the IVIM model, but the techniques discussed could be extended to evaluation of other models as well. An overview of considerations in pulse sequence development, phantom design, and data interpretation is presented for a variety of phantoms ranging in complexity from stationary volumes of fluid and mechanically pumped phantoms to isolated animal kidneys and finally to an in vivo animal model.

Animals

Renal artery stenosis: in vivo perfusion MR imaging.

The intravoxel incoherent motion (IVIM) model of perfusion and diffusion imaging was applied to an in vivo canine model of unilateral renal artery stenosis and was compared with relative renal blood flow determination with radioactive microspheres. The percentage relative renal blood flow as determined with radioactive microspheres correlated closely with the percentage apparent diffusion coefficient. If this method can be adapted to human imaging, it may provide a noninvasive means for detecting renal artery stenosis.

Animals

Near-monochromatic X-ray beams produced by the free electron laser and Compton backscatter.

The intense photon output of a free electron laser may be made to collide with its own high energy electron beam to create nearly monochromatic x-rays using Compton backscatter techniques. These x-rays can be used for imaging and non-imaging diagnostic and therapeutic experiments. The initial configuration of the Vanderbilt Medical Free Electron Laser (Sierra Laser Systems, Sunnyvale, CA) produces intense x-rays up to 17.9 keV, although higher energies are easily attainable through the use of frequency doubling methods, alteration of the energy of the electron beam and coupling to conventional laser inputs.

Electrons

Gadolinium-enhanced MR angiography.

Experience in three patients (one each with meningioma, pineal tumor, and prominent jugular bulb) illustrates that magnetic resonance (MR) angiography can benefit from the administration of gadolinium diethylenetriaminepentaacetic acid. Data were acquired with a three-dimensional velocity-compensated (fast imaging with steady-state precession) sequence. MR angiograms were obtained with a ray projection algorithm by using maximum intensity values. Portions of the vascular anatomy--particularly venous structures and smaller arteries--were better portrayed on the postcontrast than on the precontrast angiograms. Enhancing lesions were also seen on the projection images. Enhancement of dura and extracranial tissues (sinus and nasal mucosa) can obscure vascular detail.

Adult

Dermatomyositis: correlative MR imaging and P-31 MR spectroscopy for quantitative characterization of inflammatory disease.

Magnetic resonance (MR) imaging and phosphorus-31 MR spectroscopy were used to examine four patients with dermatomyositis and five control subjects. T2-weighted images of the thigh muscles of patients showed increased signal intensity, with focal and inhomogeneous involvement predominantly in the vastus lateralis and secondarily in the vastus intermedius and vastus medialis. T1 and T2 values of the vastus lateralis in patients were significantly higher than those of the control subjects. T1 values of the rectus femoris and biceps femoris with more generalized inflammation were moderately elevated but still significantly higher than those of the control subjects. P-31 MR spectra of the quadriceps muscles were obtained during rest, during exercise at two graded levels, and in recovery. Concentrations of adenosine triphosphate and phosphocreatine (PCr) in the diseased muscles were 30% below normal values, and the inorganic phosphate/PCr ratios were increased in the patients' muscles at rest and throughout exercise. The T1 and T2 values as well as the P-31 metabolite data correlated with symptoms and clinical assessment.

Adult

AUR memorial award--1988. MRI enhancement of perfused tissues using chromium labeled red blood cells as an intravascular contrast agent.

It has been demonstrated that chromium (Cr) labeling significantly decreases the relaxation times of packed red blood cells (RBCs). In this study, the spin-lattice relaxation time (T1) of human red cells was shortened from 836 ms to 29 ms and the spin-spin relaxation time (T2) shortened from 134 ms to 18 ms, when the cells were labeled at a Cr incubation concentration of 50 mM. Labeling of canine cells at 50 mM resulted in a T1 of 36 ms and a T2 of 26 ms. A labeling concentration of 10 mM produced similar relaxation enhancement, with uptake of 47% of the available Cr, and was determined to be optimal. The enhancement of longitudinal and transverse relaxation rates (1/T1,-1/T2) per amount of hemoglobin-bound Cr are 6.9 s-1 mM-1 and 9.8 s-1 mM-1 respectively, different from those of a pure Cr+3 solution. Labeling cells at 10 mM decreased the survival half-time in vivo from 16.6 days to 4.7 days in dogs. No difference in red cell survival was found with the use of hetero-transfusion versus auto-transfusion of labeled RBCs. Significant shortening of the T1 (912 ms to 266 ms, P = .03) and T2 (90 ms to 70 ms, P = .006) of spleen and the T1 (764 ms to 282 ms, P = .005) and the T2 (128 ms to 86 ms, P = .005) of liver occurred when 10% of the RBC mass of dogs was exchanged with Cr labeled cells. Liver and spleen spin density changes (P greater than 0.23) and muscle spin density and relaxation changes (P greater than 0.4) were insignificant. The in vivo T1 of a canine spleen which had been infarcted did not change following transfusion with labeled cells, where the T1 of liver did shorten. We believe this preliminary study suggests that Cr labeled red cells may have the potential to become an intravascular magnetic resonance imaging contrast agent.

Animals