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Biomedical subjects

R W Parkey

Publications and source records attributed to R W Parkey.

At least 19 recordsLinked to original sources

A fully coupled binary biochemical reactive-diffusion model with analytic solution.

Coupled multicomponent biochemical reactive diffusion underlies a variety of biological signalling processes and pharmacokinetic applications, such as paracrine signalling involving "cocktails" comprised of growth promoter/inhibitor factors and proteases associated with tumor angiogenesis, invasion and metastasis, extravascular drug delivery, and polymeric controlled-release drug codelivery design. Here, we present a model and develop a new analytic solution to illustrate the spatiotemporal behavior associated with fully coupled binary biochemical reactive diffusion. The complete coupling renders the solution appreciably more complex in structure and behavior than solutions for unicomponent or partially coupled models. Concentration behavior is illustrated by the computational simulation of binary-species tumor angiogenesis factor reactive-diffusion in the extravascular tissue matrix. The computational results indicate that (a) steady-state concentration profiles are achieved within 1 h of a change in factor production; (b) in the steady state, the spatial profiles of the two components tend to be similar; (c) exceedingly steep concentration gradients, involving several orders-of-magnitude differences in concentration over a few tenths of a millimeter, can occur in the vicinity of boundary sources due to inter-species reaction; (d) the concentration profiles of the two species differ from unicomponent predictions due to the simultaneous mass interchange between the two species. The analytic solution predictions are also used to provide a first-ever validation of a time-dependent, binary-component Crank-Nicholson numerical solution. The ability to quantitatively model interacting and often strongly varying concentration levels as a function of time and position can serve as a powerful complementary tool to experimental analyses for assessing disease state and interventional pharmacological efficacy, especially when the spatial scales on which in vivo behavior occurs taxes the limits of imaging capabilities.

Angiogenesis Inducing Agents↗

Bone phenotype of the aromatase deficient mouse.

Estrogens are important for normal bone growth and metabolism. The mechanisms are incompletely understood. Thus, we have undertaken characterization of the skeletal phenotype of aromatase (ArKO) deficient mice. No abnormalities have been noted in skeletal patterning in newborns. Adult ArKO mice show decreased femur length and decreased peak Bone Mineral Density (BMD) with accelerated bone loss by 7 months of age in females. Magnetic resonance microscopy (MR) and microCT (microCT) imaging disclosed decreased cancellous connectivity and reduced cancellous bone volume in ArKO females. Bone formation rate (BFR) is increased in ArKO females and decreased in ArKO males. Estradiol therapy reverses these changes. This anabolic effect of estradiol in the male skeleton is supported by 18-F- Positron Emission Tomography (PET) imaging, which clearly demonstrates decreased spinal uptake, but marked increase after estradiol therapy. Serum IGF-1 levels are high in young female ArKO mice but low in young ArKO males. The reduced BMD in ArKO females, despite the presence of elevated serum IGF 1, suggests that other mechanism(s) are operative. There is increased B-cell lymphopoiesis in adult female ArKO bone marrow cells. These results show that ArKO mice show the effects of estrogen deficiency on bone growth, mass, metabolism, microarchitecture and the hematopoietic microenvironment.

Animals↗

SPECT electronic collimation resolution enhancement using chi-square minimization.

An electronic collimation technique is developed which utilizes the chi-square goodness-of-fit measure to filter scattered gammas incident upon a medical imaging detector. In this data mining technique, Compton kinematic expressions are used as the chi-square fitting templates for measured energy-deposition data involving multiple-interaction scatter sequences. Fit optimization is conducted using the Davidon variable metric minimization algorithm to simultaneously determine the best-fit gamma scatter angles and their associated uncertainties, with the uncertainty associated with the first scatter angle corresponding to the angular resolution precision for the source. The methodology requires no knowledge of materials and geometry. This pattern recognition application enhances the ability to select those gammas that will provide the best resolution for input to reconstruction software. Illustrative computational results are presented for a conceptual truncated-ellipsoid polystyrene position-sensitive fibre head-detector Monte Carlo model using a triple Compton scatter gamma sequence assessment for a 99mTc point source. A filtration rate of 94.3% is obtained, resulting in an estimated sensitivity approximately three orders of magnitude greater than a high-resolution mechanically collimated device. The technique improves the nominal single-scatter angular resolution by up to approximately 24 per cent as compared with the conventional analytic electronic collimation measure.

Algorithms↗

Analytic treatment of resolution precision in electronically collimated SPECT imaging involving multiple-interaction gamma rays.

The widely applied single-interaction analytic expression characterizing the energy resolution component of the angular resolution precision for an electronically collimated point source is extended to include multiple-interaction Compton scatter sequences as well as sequences terminated by photoelectric absorption. The analytic formulation is developed using the statistical variance of the mean for components comprising composite, multivariate resolution precision estimators. It is demonstrated that enhanced resolution precision in the incident interaction scatter angle is attained when use is made of information from multiple interactions. An improvement in the resolution precision of up to approximately 40% is observed for triple Compton scatter. Comparison of the analytic estimates with Monte Carlo/chi-square results shows good agreement.

Chi-Square Distribution↗

Submaximal delayed-onset muscle soreness: correlations between MR imaging findings and clinical measures.

PURPOSE: To assess correlations between muscle edema on magnetic resonance (MR) images and clinical indexes of muscle injury in delayed-onset muscle soreness (DOMS) produced by submaximal exercise protocols. MATERIALS AND METHODS: Sixteen subjects performed 36 elbow flexions ("biceps curls") at one of two submaximal workloads that emphasized eccentric contractions. Changes in MR imaging findings, plasma levels of creatine kinase, and pain scores were correlated. RESULTS: Both exercise protocols produced DOMS in all subjects. The best correlation was between change in creatine kinase level and volume of muscle edema on MR images, regardless of the workload. Correlations tended to be better with the easier exercise protocol. CONCLUSION: Whereas many previous studies of DOMS focused on intense exercise protocols to ensure positive results, the present investigation showed that submaximal workloads are adequate to produce DOMS and that correlations between conventionally measured indexes of injury may be enhanced at lighter exercise intensities.

Adult↗

Quantitative MR imaging of the heart.

MR imaging cardiac quantitation is accurate, highly reproducible, and feasible using equipment available in most hospitals. For determination of myocardial mass, evaluation of RV function, and quantitative measurements of flow in the great vessels and peripheral vasculature, MR imaging is the reference method. Availability of methods for rapid scanning and analysis will lead to increased use of cardiac MR imaging in quantifying cardiac function.

Heart↗

Measurement of absolute epicardial coronary artery flow and flow reserve with breath-hold cine phase-contrast magnetic resonance imaging.

BACKGROUND: Noninvasive measurement of absolute coronary arterial flow and coronary flow reserve would be of considerable use in the diagnosis and management of patients with coronary artery disease. Phase-contrast magnetic resonance imaging (MRI) has been used to measure flow in a variety of vessels. The goal of the present study was to determine if MRI measurements of coronary artery flow in a single breath-hold can be used to determine flow reserve and the severity of pericardial stenosis. METHODS AND RESULTS: In eight mongrel dogs, a closed chest model of partial left anterior descending coronary artery (LAD) occlusion was created. Coronary flows in the left circumflex artery (LCx) and LAD were measured at rest and during adenosine infusion using velocity-encoded, breath-hold MRI and perivascular ultrasound (US) flowmeters. MRI measurements of absolute coronary flow and coronary flow reserve were highly correlated with US (r = .96 and .94, respectively). Flow reserve measured in the constricted LAD was significantly lower than that in the unconstricted LCx by both US (P = .002) and MRI (P = .011). CONCLUSIONS: MRI measurements of coronary flow and flow reserve were in good agreement with US measurements. In addition, MRI measurements of coronary flow reserve successfully discriminated stenotic from normal vessels. These results indicate that MRI is a useful method for the noninvasive assessment of coronary flow and stenosis.

Adenosine↗

High-voltage electric injury: assessment of muscle viability with MR imaging and Tc-99m pyrophosphate scintigraphy.

PURPOSE: To evaluate use of magnetic resonance (MR) imaging and technetium-99m pyrophosphate (PYP) scintigraphy in preoperative assessment of muscle viability after high-voltage electric injury. MATERIALS AND METHODS: Twelve injured limbs were studied. Immediate, equilibrium, and delayed Tc-99m PYP scintigrams and gadolinium-enhanced and unenhanced MR images were obtained. Imaging results were compared with clinical findings. RESULTS: Scintigraphy demonstrated nonperfusion in four limbs that were subsequently amputated, but MR imaging had poor sensitivity in nonperfused regions owing to lack of edema. Tc-99m PYP uptake increased at transition zones between normal and nonperfused regions. MR imaging allowed further characterization of these zones by demonstrating edema as enhancing (perfused) or nonenhancing (nonperfused). In all nonamputated limbs, edema showed enhancement. CONCLUSION: In high-voltage electric injury, gadolinium-enhanced MR imaging appears able to demonstrate zones of potential viability within radionuclide-avid tissue but has poor perfusion sensitivity when used alone.

Amputation, Surgical↗

Synthesis and evaluation of a new class of technetium-99m monocationic radiotracers from dithienyldiazalkanes.

Monocationic 99mTc complexes, [99mTcO2 (THEN)]+ and [99mTcO2(THPN)]+ derived from a new class of N2S2 chelators diethienyldiazalkanes, namely 1,6-di(2-thienyl)-2,5-diazahexane (THEN) and 1,7-di- (2-thienyl)-4,4-dimethyl-2,6-diazaheptane (THPN), have been synthesized using Sn(II) tartrate reduction of [99mTc]pertechnetate at pH 9 and extraction of the complexes as ion pairs with trifluoromethane sulfonate anion (CF3SO3-) in high radiochemical yield (approximately 90%). Radiochemical analysis of the 99mTc complexes using chromatography (Whatman Cellulose CEL300 DEAE anion exchange strip, MEK) and paper chromatography (Whatman I, acetone) revealed high radiochemical purity (> 90%). High octanol-saline partition coefficients (> 37) of [99mTcO2(THEN)]+ and [99mTcO2(THPN)]+ indicated a lipophilic nature of the complexes. Relative stability of the 99mTc complex was high as measured by DTPA challenge studies. Biodistribution of [99mTcO2(THEN)]+ and [99mTcO2(THPN)]+ in rats at 15 min post-injection showed heart-to-blood activity ratios of 0.26 and 0.46, respectively, with rapid blood clearance. Further studies involving the variation of substituents on the basic core structure of this new class of 99mTc complexes may provide radiotracers suitable for myocardial imaging.

Animals↗

Pulmonary embolism: comparison of MR images with radionuclide and angiographic studies.

PURPOSE: To assess the accuracy and potential of magnetic resonance (MR) imaging in evaluation of patients in whom pulmonary embolism is suspected. MATERIALS AND METHODS: Blinded, prospective interpretations of multiphasic, cardiac-gated spin-echo MR images were compared with retrospective chart review in 86 patients in whom pulmonary embolism was suspected. In 64 patients, the presence or absence of pulmonary emboli was established with x-ray angiography (n = 34) or ventilation-perfusion (V-P) scans and concurrent clinical impression (n = 30). RESULTS: In the subgroup with angiographic proof, MR imaging had a sensitivity of 90%, specificity of 77%, positive predictive value of 86%, and negative predictive value of 83%. In 21 patients with intermediate probability of pulmonary embolism on V-P scans and angiograms, MR images enabled diagnosis of pulmonary embolism in 12 of 12 patients (sensitivity, 100%) and absence of pulmonary embolism in seven of nine patients (specificity, 78%). CONCLUSION: MR imaging reliably depicts large and medium-size pulmonary emboli, regardless of infiltrates or effusion; hence, it may clarify findings on V-P scans that show intermediate probability of pulmonary embolism or are at variance with the clinical impression.

Adult↗

Lumbar muscle usage in chronic low back pain. Magnetic resonance image evaluation.

Methods for detecting recruitment patterns of the lumbar muscles during exercise in patients with chronic low back pain are limited. This article discusses the use of magnetic resonance imaging with Roman chair extension exercise to examine lumbar muscle usage in five normal volunteers, five chronic low back pain patients without surgery, and five chronic low back pain patients with surgery. Changes in signal intensities of psoas, multifidus, and longissimus/iliocostalis with graded exercise were measured at three lumbar disc levels. At rest, there was a difference between multifidus and longissimus/iliocostalis signal intensity in chronic low back pain subjects without surgery (P = 0.0162) and in chronic low back pain subjects with surgery (P = 0.0036), but not in normal subjects. At peak exercise, there was a difference in signal intensities between multifidus and longissimus/iliocostalis in all groups (normal volunteers, P = 0.0069; chronic low back pain patients without surgery, P = 0.0125; chronic low back pain patients with surgery, P = 0.0060). The exercise response was attenuated in chronic low back pain patients with surgery. Thus, MRI demonstrates static and dynamic differences in lumbar paraspinal musculature in chronic low back pain subjects compared to normal subjects.

Exercise↗

Denervated human skeletal muscle: MR imaging evaluation.

Because determination of neurologic integrity after severe limb trauma is crucial in patient care, the authors assessed magnetic resonance (MR) imaging as a tool to map denervated motor units of skeletal muscle in patients with traumatic peripheral neuropathy. Denervation was confirmed in 22 patients with use of electromyography, surgery, or both. MR imaging was performed with moderately T1- and T2-weighted spin-echo and short-tau inversion-recovery (STIR) sequences. MR imaging was unreliable in depicting acute denervation. Muscles of patients with subacute denervation had prolonged T1 and T2, which contributed to conspicuous hyperintensity on STIR images. Chronically denervated muscles showed marked atrophy, variable changes on STIR images, and conspicuous fatty infiltration on T1-weighted images. Normal variants in motor unit anatomy were seen in denervated muscle volumes outside the expected distribution of the injured nerve. MR imaging is promising for the noninvasive mapping and monitoring of denervated muscle in subacute and chronic phases of peripheral neuropathy.

Extremities↗

Synthesis and evaluation of technetium-99m monocationic mixed ligand complexes of phenyl substituted/condensed tetradentate Schiff's bases and trimethylphosphine.

Tc-99m monocationic mixed ligand complexes of phenyl substituted/condensed Schiff's bases, N,N'-ethylene-bis-(benzoylacetone imine) (Lb) or N,N'-ethylene-bis-(salicylaldehyde imine) (Lc) or N,N'-ethylene-bis-(2-hydroxyacetophenone imine) (Ld) and trimethylphosphine were synthesized to determine the influence of the presence of a phenyl group in these tracers on their heart uptake in rats. A new formulation procedure using aq. beta-hydroxypropylcyclodextrin (HPB) solution was developed for intravenous administration of nonpolar 99mTc complexes. Comparison of biodistribution data for the reference 99mTc complex from N,N'-ethylene-bis-(acetylacetone imine) and trimethylphosphine using HPB formulation and alternate formulation (0.9% saline) showed the same results. Biodistribution of the title 99mTc complexes, [99mTc Lb (PMe3)2]+, [99mTc Lc (PMe3)2]+ and [99mTc Ld (PMe3)2]+ showed heart-to-blood activity ratios of 1.7, 2.1 and 1.7, respectively, at 15 min post-injection in rats.

2-Hydroxypropyl-beta-cyclodextrin↗

Finger-specific flexor recruitment in humans: depiction by exercise-enhanced MRI.

To evaluate the spatial distribution of human forearm musculature stressed by finger-specific exercise, magnetic resonance imaging was performed in conjunction with exercise protocols designed to separately stress the flexor digitorum superficialis and flexor digitorum profundus. These muscles were shown to consist of subvolumes selectively recruited by flexion of the individual fingers. Knowledge of the finger-specific regions of muscle recruitment during finger flexion could improve sampling accuracy in electromyography, biopsy, magnetic resonance spectroscopy, and invasive vascular sampling studies of hand exercise.

Adult↗

Regional cardiac adrenergic function using I-123 meta-iodobenzylguanidine tomographic imaging after acute myocardial infarction.

The effect of acute myocardial infarction (AMI) on regional cardiac adrenergic function was studied in 27 patients mean +/- standard deviation 10 +/- 4 days after AMI. Regional adrenergic function was evaluated noninvasively with I-123 meta-iodobenzylguanidine (MIBG) using a dedicated 3-detector tomograph. Four hours after its administration, there was reduced MIBG uptake in the region of infarction, 0.38 +/- 0.31 counts/pixel/mCi x 103 compared with 0.60 +/- 0.30 counts/pixel/mCi x 103 and 0.92 +/- 0.35 counts/pixel/mCi x 103 in the zones bordering and distant from the infarct area, respectively, p less than 0.001. In all patients, the area of reduced MIBG uptake after 4 hours was more extensive that the associated thallium-201 perfusion defect with defect scores of 52 +/- 22 and 23 +/- 18%, respectively, p less than 0.001. After anterior wall AMI, the 4-hour MIBG defect score was 70 +/- 13% and the degree of mismatch between myocardial perfusion and MIBG uptake was 30 +/- 9% compared with 39 +/- 17 and 21 +/- 17% after inferior AMI, p less than 0.001 and p = 0.016, respectively. The 4-hour MIBG defect score correlated inversely with the predischarge left ventricular ejection fraction, r = -0.73, p less than 0.001. Patients with ventricular arrhythmia of greater than or equal to 1 ventricular premature complexes per hour, paired ventricular premature complexes or ventricular tachycardia detected during the late hospital phase had higher 4-hour MIBG defect scores, 62.5 +/- 15.0%, than patients with no detectable complex ventricular ectopic activity and a ventricular premature complex frequency of less than 1 per hour, 44.6 +/- 23.4%, p = 0.036.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Iodobenzylguanidine↗

Automated localization and identification of lower spinal anatomy in magnetic resonance images.

Clinical interpretation of the subtle changes present in MR images in the setting of disease currently relies on subjective image analysis. Image evaluation could potentially be improved by computerized segmentation and precise quantification of the image anatomy. However, this cannot be automated unless reliable navigation within an image is established, capable of compensating for unpredictable factors such as anatomical variability, positioning of an image plane in the body, and variable image characteristics. Focusing on the lower spinal region, this paper explores the presence of image- and anatomy-invariant features which facilitate automated, unconstrained identification, and localization of basic lower spine anatomy.

Algorithms↗