The prevalence of both parkinsonian signs and Parkinson's disease (PD) per se increases with age.... more The prevalence of both parkinsonian signs and Parkinson's disease (PD) per se increases with age. Although the pathophysiology of PD has been studied extensively, less is known about the functional changes taking place in the basal ganglia circuitry with age. To specifically address this issue, 3 groups of rhesus macaques were studied: normal middle-aged animals (used as controls), middle-aged animals with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)einduced parkinsonism, and aged animals (>20 years old) with declines in motor function. All animals underwent the same behavioral and pharmacologic magnetic resonance imaging (phMRI) procedures to measure changes in basal ganglia function in response to dopaminergic drug challenges consisting of apomorphine administration followed by either a D1 (SCH23390) or a D2 (raclopride) receptor antagonist. Significant functional changes were predominantly seen in the external segment of the globus pallidus (GPe) in aged animals and in the striatum (caudate nucleus and putamen) in MPTP-lesioned animals. Despite significant differences seen in the putamen and GPe between MPTP-lesioned versus aged animals, a similar response profile to dopaminergic stimulations was found between these 2 groups in the internal segment of the GP. In contrast, the pharmacologic responses seen in the control animals were much milder compared with the other 2 groups in all the examined areas. Our phMRI findings in MPTP-lesioned parkinsonian and aged animals suggest that changes in basal ganglia function in the elderly may differ from those seen in parkinsonian patients and that phMRI could be used to distinguish PD from other age-associated functional alterations in the brain.
There is a great need for the development of noninvasive, highly sensitive, and widely available ... more There is a great need for the development of noninvasive, highly sensitive, and widely available imaging methods that can potentially be used to longitudinally monitor treatment of Parkinson's disease (PD). Here we report the monitoring of GDNF-induced functional changes of the basal ganglia in hemiparkinsonian monkeys via pharmacological MRI measuring the blood oxygenation level-dependent (BOLD) response to a direct dopamine agonist (apomorphine, APO). After testing BOLD responsiveness to APO in their normal state, two additional scans were taken with the same dose of APO stimulation after induced parkinsonism. Then all animals were chronically treated with GDNF for 18 weeks by a programmable pump and catheter system. The catheter was surgically implanted into the right putamen and connected to the pump via flexible polyurethane tubing, phMRI scans were taken at both 6 and 18 weeks while they received 22.5 microg of GDNF per day. In addition, behavioral changes were monitored t...
In this work, the three-dimensional velocity and concentration fields on both the blood and dialy... more In this work, the three-dimensional velocity and concentration fields on both the blood and dialysate sides in an artificial kidney were simulated, taking into account the effects of the flow profiles induced by the inlet and outlet geometrical structures and the interaction between the flows of blood and dialysate. First, magnetic resonance imaging experiments were performed to validate the mathematical model. Second, the effects of the flow profiles induced by the blood and dialysate inlet and outlet geometrical structures on mass transfer were theoretically investigated. Third, the clearance of toxins was compared with the clearance value calculated by a simple model that is based on the ideal flow profiles on both the blood and dialysate sides. Our results show that as the blood flow rate increases, the flow field on the blood side becomes less uniform; however, as the dialysate flow rate increases, the flow field on the dialysate side becomes more uniform. The effect of the inl...
Speed of visual word recognition is an important variable affecting linguistic competence. Althou... more Speed of visual word recognition is an important variable affecting linguistic competence. Although speed of visual word recognition varies widely between individuals, the neural basis of reaction time (RT) differences is poorly understood. Recently, a magnetic resonance technique called diffusion tensor imaging (DTI) has been shown to provide information about white matter (WM) microstructure in vivo. Here, we used DTI to explore whether visual word recognition RT correlates with regional fractional anisotropy (FA) values in the WM of healthy young adults. Participants completed a speeded lexical decision task that involved visual input, linguistic processes, and a motor response output. Results indicated that lexical decision RT was correlated negatively with FA in WM of inferior parietal and frontal language regions rather than in WM of visual or motor regions. Voxels within the inferior parietal and frontal correlation clusters were composed primarily of DTI-based tracts oriented in the anterior-posterior orientation at or near the superior longitudinal fasciculus (SLF) and likely including other smaller association fibers. These results provide new microstructural evidence demonstrating that speed of lexical decision is associated with the degree to which portions of frontal and parietal WM are directionally oriented.
New imaging techniques are needed to longitudinally monitor the development, progression and trea... more New imaging techniques are needed to longitudinally monitor the development, progression and treatment of Parkinson's disease. The present study was designed to test whether the blood oxygenation leveldependent (BOLD) response to dopaminergic stimulation as measured by pharmacological MRI (phMRI) correlated to specific histological and behavioral features of the parkinsonian state. Nine adult rhesus monkeys were rendered hemiparkinsonian by intracarotid administration of MPTP. Three months after MPTP treatment, the trained, MRI-adapted awake animals were scanned with a phMRI technique while being administered a presynaptic (D-amphetamine) or postsynaptic (apomorphine) dopamine stimulating agents. The primary findings were (1) the putamen and substantia nigra (SN) but not the caudate nucleus displayed significant BOLD responses to these dopaminergic drugs; (2) a significant relationship was found between amphetamine-evoked activation and the number of surviving dopamine neurons in the SN, which was also correlated with bradykinesia; and (3) inverse relationships were seen in response to apomorphine and amphetamine stimulation between the MPTP-lesioned and unlesioned putamen and SN. The results suggest that phMRI may prove useful for longitudinally monitoring the progression and treatment of PD.
We constructed a device to compress small samples of articular cartilage while the samples were i... more We constructed a device to compress small samples of articular cartilage while the samples were imaged in a 1.5 T imager. With the use of a piezoelectric piston, the device compressed 1-cm-diameter cylindrical samples of articular cartilage (200 microm) at a rate of 2 Hz. Simultaneously, we imaged the samples with a displacement-sensitive stimulated-echo acquisition mode (STEAM) sequence. We validated the technique using tissue that mimicked silicone samples. We compared the results from the same cartilage samples before and after they were degraded by digestion in trypsin. The extent of degradation was visualized from T(1)-weighted images of the samples after they were soaked in 0.5 mmolar of GdDTPA. The resulting elastographic images show compression and differential strain in directions both parallel and perpendicular to the surface of the cartilage. The static elastographic images that depict compression made before digestion and after 5 and 15 hr of trypsin digestion show that the elastic modulus of the samples decreased with a spatial variation consistent with the enzymatic digestion as revealed by the T(1) images. We believe this technique will be useful in studies of the mechanical properties of articular cartilage and other tissues, and may in the future be extended to the clinical setting.
Magnetic particulates have been shown to be powerful transverse relaxation enhancers and are unde... more Magnetic particulates have been shown to be powerful transverse relaxation enhancers and are under consideration as an MR contrast agent for the detection of liver and spleen lesions. This work describes the magnetic properties of a commercially available magnetic particulate and a Monte Carlo simulation of the effect of these particles on the transverse relaxation rates of water protons for spin-echo experiments. From the simultations, empirical relations were developed to describe the dependence of the enhancement on particle size, and concentration as well as the diffusion constant of water and the pulse spacing of a Carr-Purcell-Meiboom-Gill pulse sequence used to measure the transverse relaxation time. The simulations are shown to agree with measurements of relaxation rates in agar samples containing the magnetic particulates.
Advances in imaging and computerized analyses have enabled three-dimensional bone motion in the t... more Advances in imaging and computerized analyses have enabled three-dimensional bone motion in the treated clubfoot to be measured precisely. Three-dimensional translations and rotations of the talus, calcaneus, navicular, and cuboid of surgically treated clubfeet were less in magnitude and sometimes different in direction (or without motion in a specific plane) compared with the contralateral normal feet. Surgical techniques used for clubfoot treatment do not restore normal hindfoot bone motion when examined with high-resolution magnetic resonance imaging, computer reconstruction, and image analysis techniques. These data advance the knowledge of hindfoot bone motion and establish a new and quantitative objective.
Functional magnetic resonance imaging (fMRI) is increasingly used in non-human primate research. ... more Functional magnetic resonance imaging (fMRI) is increasingly used in non-human primate research. In the present study, we adapt the familiarization-novelty preference (FNP) procedure used in human infant research to examine visual behavior in alert, unanaesthetized rhesus monkeys that were acclimated to the fMRI environment, but did not undergo behavioral training. In keeping with the typical FNP paradigm, we recorded eye movements (looking time and number of fixations) while monkeys viewed a series of four identical pictures (familiarization phase) followed by two different pictures (novelty phase). Number of fixations and looking time both increased during the novelty phase, thereby demonstrating visual discrimination of the new from the old picture. Importantly, discrimination did not occur on catch trials in which six identical pictures were presented. Moreover, brain activation in the amygdala was more strongly associated with the novelty phase than with the familiarization phase. In addition, magnitude of brain activation in the amygdala was correlated with the behavioral effect of visual discrimination. These findings demonstrate the feasibility of using eye movements as an index of visual discrimination in untrained monkeys during fMRI scanning. This methodological approach helps to extend the repertoire of research tools for fMRI in non-human primates.
Knowledge of hind foot bone motion is important for understanding gait as well as various foot pa... more Knowledge of hind foot bone motion is important for understanding gait as well as various foot pathologies, but the three-dimensional (3D) motion of these bones remains incompletely understood. The purpose of this study was to quantify the motion of the talus, calcaneus, navicular, and cuboid in normal adult feet during open chain quasi-static uniplanar plantar flexion motion. Magnetic resonance images of the right feet of six normal young adult males were taken from which 3D virtual models were made of each hind foot bone. The 3D motion of these models was analyzed. Each hind foot bone rotated in the same plane about half as much as the foot (mean 0.54 degrees of bone rotation per degree of foot motion, range 0.40-0.73 degrees per degree of foot motion as measured relative to the fixed tibia). Talar motion was primarily uniaxial, but the calcaneus, navicular, and cuboid bones exhibited biplanar (sometimes triplanar) translation in addition to biaxial rotation. Net translational motions of these bones averaged 0.39 mm of bone translation per degree of foot motion (range 0.06-0.62 mm per degree of foot motion). These data reflect the functional anatomy of the foot, extend the findings of prior studies, provide a standard for comparison to patients with congenital or acquired foot deformities, and establish an objective reference for quantitatively assessing the efficacy of various hind foot therapies.
We used an innovative, nonintrusive MRI technique called the two-dimensional (2D) Phase-Contrast ... more We used an innovative, nonintrusive MRI technique called the two-dimensional (2D) Phase-Contrast (2DPC) velocity-imaging technique to investigate the effect of flow baffles on the dialysate-side flow distribution in two different hollow-fiber hemodialyzers (A and B); each with flow rates between 200 and 1000 mL/min (3.33 x 10(-6) and 1.67 x 10(-5) m3/s). Our experimental results show that (1) the dialysate-side flow distribution was nonuniform with channeling flow occurred at the peripheral cross section of these hollow-fiber hemodialyzers, and (2) the existing designs of flow baffles failed to promote uniform dialysate-side flow distribution for all flow rates studies.
To design nanoparticles containing accessible gadolinium atoms (Gd-NPs) as a contrast agent for m... more To design nanoparticles containing accessible gadolinium atoms (Gd-NPs) as a contrast agent for magnetic resonance imaging of tumors. Nanoparticles containing phospholipid-chelates (phosphoethanolamine diethylenetriaminepentaacetate) and DSPE-PEG (MW5000) were prepared from Brij 78 and stearyl alcohol using the nanotemplate engineering approach. After addition of GdCl3, the presence of gadolinium on the surface of nanoparticles was quantified using inductively coupled plasma atomic emission spectroscopy. The in vitro relaxivities of the Gd-NPs in phosphate buffered saline were assessed at 4.7 T. The conditional binding constants of nanoparticle formulations were determined spectrophotometrically by competitive titration. Transmetallation kinetics of Gd from nanoparticles with Cu2+ and Zn2+ as the competing ions was measured in acetate buffer. The biodistribution profiles, pharmacokinetics, and contrast enhancement in tumor region was studied after administration of Gd-NPs to nude mice bearing A549 lung carcinoma xenografts. Gd-NPs with an average diameter of 138 nm possessing surface chelating functions were prepared from GRAS (generally regarded as safe) materials. The longitudinal relaxivity (r1) and transverse relaxivity (r2) of Gd-NPs in 10% fetal bovine serum at 4.7 T were 7.1 (+/-0.2) and 13.0 (+/-0.7) 1/mM/s, respectively. These pegylated Gd-NPs had enhanced relaxivities and exhibited particle size stability, sufficient binding affinity, and kinetic inertness under physiologic conditions. The contrast enhancement in tumors was demonstrated 40, 120, and 360 minutes after intravenous injection of Gd-NPs at a dose of 0.1 mmol Gd/kg. The Gd plasma concentration of Gd-NPs over a period of 24 hours fit a two-compartmental model with Cl sys = 0.89 mL/h and MRT = 5.93 h. The amount of Gd that accumulated in the tumor region was consistent with the estimated value obtained by T1 measurements using MR imaging. Pegylated nanoparticles composed of biocompatible, biodegradable materials and possessing accessible Gd ions on their surface induce relaxivities in the bulk water signal and accumulated sufficiently in tumors, demonstrating their utility as potential magnetic resonance imaging tumor contrast enhancement agents.
Kinetic modeling, based on the fundamental principle of mass balance, is one of the most widely u... more Kinetic modeling, based on the fundamental principle of mass balance, is one of the most widely used analytic methods to study the biological system. It provides a powerful tool to conceptualize clinical problems requiring further understanding. Several precise mathematical equations can be derived to describe the evolution of a biological system, and each model parameter is defined rigorously. Therefore, the relative importance of each parameter can be both quantitatively and qualitatively evaluated. The goal of kinetic modeling in hemodialysis (HD) is to help physicians understand the uremic syndrome more clearly and allow them to provide adequate dialytic therapy to patients. Solely by empirical observation and clinical judgment, it is very difficult, if not impossible, to determine the adequate dose of dialysis therapy, which depends on many factors, such as patient size, generation rate of endogenous toxins, residual renal function, dialyzer clearance, frequency, and treatment time (1).
The accuracy of cine phase-contrast magnetic resonance (MR) imaging for motion analysis was evalu... more The accuracy of cine phase-contrast magnetic resonance (MR) imaging for motion analysis was evaluated. By using a rotating phantom and postprocessing algorithm for phase tracking, errors arising during data acquisition were identified and compensation methods were developed. A spatially varying background phase offset in the velocity images was found to be due to eddy current-induced fields. The magnitude of the offset was in the range of 0–20 cm/sec, which is of the same order of magnitude as cardiac contractile velocities. Background offset is thus an important source of error in tracking cardiac motion. Study of different tracking algorithms revealed the need for an integration scheme using motion terms higher than velocity. Also, considerable improvement in the accuracy and stability of the predicted trajectories was obtained by averaging the trajectories proceeding both forward and backward in time from the starting point. With the algorithm developed, the motion of the phantom was tracked through a complete rotation of the phantom to an accuracy of 2 pixels.
Conventional T2-weighted spin-echo magnetic resonance imaging of the knee requires a long TR. Fas... more Conventional T2-weighted spin-echo magnetic resonance imaging of the knee requires a long TR. Fast spin-echo (FSE) imaging can improve acquisition efficiency severalfold by collecting multiple lines of k space for each TR. Compromises in resolution, section coverage, and contrast inevitably result. The authors examined the compromises encountered in FSE imaging of the knee and discuss the variations in image contrast and resolution due to choices of sequence parameters. For short TR/TE knee imaging, FSE does not appear to offer any advantages, since the increased collection efficiency for one section reduces the available number of sections, so that the total imaging time for a given number of sections remains constant relative to conventional spin-echo imaging. For T2-weighted images, considerable time can be saved and comparable quality images can be obtained. This saved time can be usefully spent on increasing both the resolution of the image and its signal-to-noise ratio, while still reducing total acquisition time by a factor of two. The preferred FSE T2-weighted images were acquired with a TR of 4,500 msec, TE of 120 msec, and eight echoes. The available number of sections is compromised, and the sequence remains sensitive to flow artifacts; however, the FSE sequence appears to be promising for knee imaging.
We have developed an algorithm to estimate and display the spatial distribution of the thickness ... more We have developed an algorithm to estimate and display the spatial distribution of the thickness of articular cartilage in human knees. We used a simulation to derive the most appropriate formula for estimating thickness in digital images. The algorithm was tested by imaging a thickness phantom and comparing the results with the known dimensions of the phantom. The results demonstrated that the maximum error encountered in estimating thickness is one pixel while the average error is 0.4 pixels. We imaged a human knee on a cadaver in two separate sessions and used the two image sets to derive thickness maps of the patellar articular cartilage. The thickness maps generated independently from these image sets were very similar, indicating the reliability of the method in deriving accurate thickness estimates. J. Magn. Reson. Imaging 2001;13:120-126.
Functional imaging of the non-human primate brain in awake animals is now feasible because of rec... more Functional imaging of the non-human primate brain in awake animals is now feasible because of recent methodological advances. Here we detail our procedures for conducting functional MRI (fMRI) studies in rhesus monkeys. Our emphasis has been on analyzing drug-evoked responses within and across test groups, meaning that techniques have had to be developed for training and testing relatively large groups of animals. Group size is important as unbiased estimates are best derived from analyzing responses in multiple animals with replicate scans per animal due to partial volume errors in evaluating small brain regions and motion artifacts during scanning. While the procedures presented here were developed for mapping responses obtained from stimulating dopaminergic systems, much of the methodology is generally applicable for non-human primate fMRI studies and addresses specific problems encountered in imaging awake animals. These are (1) adapting animals to an MRI environment, (2) minimizing head movements, (3) reducing ambient scanning noise levels, and (4) developing multivariate methods of image data analysis suitable for eliciting the dynamic brain response while (5) detecting and deleting outlying observations due to motion artifacts. Procedures are demonstrated for first pre-processing and analyzing responses in a voxel-based approach in a single animal and then proceeding to analyze responses across animals and replicate scans for regions of interest. Collectively, the procedures described provide an approach for fMRI mapping of elicited responses using conventional 1.5T MR scanners.
The prevalence of both parkinsonian signs and Parkinson's disease (PD) per se increases with age.... more The prevalence of both parkinsonian signs and Parkinson's disease (PD) per se increases with age. Although the pathophysiology of PD has been studied extensively, less is known about the functional changes taking place in the basal ganglia circuitry with age. To specifically address this issue, 3 groups of rhesus macaques were studied: normal middle-aged animals (used as controls), middle-aged animals with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)einduced parkinsonism, and aged animals (>20 years old) with declines in motor function. All animals underwent the same behavioral and pharmacologic magnetic resonance imaging (phMRI) procedures to measure changes in basal ganglia function in response to dopaminergic drug challenges consisting of apomorphine administration followed by either a D1 (SCH23390) or a D2 (raclopride) receptor antagonist. Significant functional changes were predominantly seen in the external segment of the globus pallidus (GPe) in aged animals and in the striatum (caudate nucleus and putamen) in MPTP-lesioned animals. Despite significant differences seen in the putamen and GPe between MPTP-lesioned versus aged animals, a similar response profile to dopaminergic stimulations was found between these 2 groups in the internal segment of the GP. In contrast, the pharmacologic responses seen in the control animals were much milder compared with the other 2 groups in all the examined areas. Our phMRI findings in MPTP-lesioned parkinsonian and aged animals suggest that changes in basal ganglia function in the elderly may differ from those seen in parkinsonian patients and that phMRI could be used to distinguish PD from other age-associated functional alterations in the brain.
There is a great need for the development of noninvasive, highly sensitive, and widely available ... more There is a great need for the development of noninvasive, highly sensitive, and widely available imaging methods that can potentially be used to longitudinally monitor treatment of Parkinson's disease (PD). Here we report the monitoring of GDNF-induced functional changes of the basal ganglia in hemiparkinsonian monkeys via pharmacological MRI measuring the blood oxygenation level-dependent (BOLD) response to a direct dopamine agonist (apomorphine, APO). After testing BOLD responsiveness to APO in their normal state, two additional scans were taken with the same dose of APO stimulation after induced parkinsonism. Then all animals were chronically treated with GDNF for 18 weeks by a programmable pump and catheter system. The catheter was surgically implanted into the right putamen and connected to the pump via flexible polyurethane tubing, phMRI scans were taken at both 6 and 18 weeks while they received 22.5 microg of GDNF per day. In addition, behavioral changes were monitored t...
In this work, the three-dimensional velocity and concentration fields on both the blood and dialy... more In this work, the three-dimensional velocity and concentration fields on both the blood and dialysate sides in an artificial kidney were simulated, taking into account the effects of the flow profiles induced by the inlet and outlet geometrical structures and the interaction between the flows of blood and dialysate. First, magnetic resonance imaging experiments were performed to validate the mathematical model. Second, the effects of the flow profiles induced by the blood and dialysate inlet and outlet geometrical structures on mass transfer were theoretically investigated. Third, the clearance of toxins was compared with the clearance value calculated by a simple model that is based on the ideal flow profiles on both the blood and dialysate sides. Our results show that as the blood flow rate increases, the flow field on the blood side becomes less uniform; however, as the dialysate flow rate increases, the flow field on the dialysate side becomes more uniform. The effect of the inl...
Speed of visual word recognition is an important variable affecting linguistic competence. Althou... more Speed of visual word recognition is an important variable affecting linguistic competence. Although speed of visual word recognition varies widely between individuals, the neural basis of reaction time (RT) differences is poorly understood. Recently, a magnetic resonance technique called diffusion tensor imaging (DTI) has been shown to provide information about white matter (WM) microstructure in vivo. Here, we used DTI to explore whether visual word recognition RT correlates with regional fractional anisotropy (FA) values in the WM of healthy young adults. Participants completed a speeded lexical decision task that involved visual input, linguistic processes, and a motor response output. Results indicated that lexical decision RT was correlated negatively with FA in WM of inferior parietal and frontal language regions rather than in WM of visual or motor regions. Voxels within the inferior parietal and frontal correlation clusters were composed primarily of DTI-based tracts oriented in the anterior-posterior orientation at or near the superior longitudinal fasciculus (SLF) and likely including other smaller association fibers. These results provide new microstructural evidence demonstrating that speed of lexical decision is associated with the degree to which portions of frontal and parietal WM are directionally oriented.
New imaging techniques are needed to longitudinally monitor the development, progression and trea... more New imaging techniques are needed to longitudinally monitor the development, progression and treatment of Parkinson's disease. The present study was designed to test whether the blood oxygenation leveldependent (BOLD) response to dopaminergic stimulation as measured by pharmacological MRI (phMRI) correlated to specific histological and behavioral features of the parkinsonian state. Nine adult rhesus monkeys were rendered hemiparkinsonian by intracarotid administration of MPTP. Three months after MPTP treatment, the trained, MRI-adapted awake animals were scanned with a phMRI technique while being administered a presynaptic (D-amphetamine) or postsynaptic (apomorphine) dopamine stimulating agents. The primary findings were (1) the putamen and substantia nigra (SN) but not the caudate nucleus displayed significant BOLD responses to these dopaminergic drugs; (2) a significant relationship was found between amphetamine-evoked activation and the number of surviving dopamine neurons in the SN, which was also correlated with bradykinesia; and (3) inverse relationships were seen in response to apomorphine and amphetamine stimulation between the MPTP-lesioned and unlesioned putamen and SN. The results suggest that phMRI may prove useful for longitudinally monitoring the progression and treatment of PD.
We constructed a device to compress small samples of articular cartilage while the samples were i... more We constructed a device to compress small samples of articular cartilage while the samples were imaged in a 1.5 T imager. With the use of a piezoelectric piston, the device compressed 1-cm-diameter cylindrical samples of articular cartilage (200 microm) at a rate of 2 Hz. Simultaneously, we imaged the samples with a displacement-sensitive stimulated-echo acquisition mode (STEAM) sequence. We validated the technique using tissue that mimicked silicone samples. We compared the results from the same cartilage samples before and after they were degraded by digestion in trypsin. The extent of degradation was visualized from T(1)-weighted images of the samples after they were soaked in 0.5 mmolar of GdDTPA. The resulting elastographic images show compression and differential strain in directions both parallel and perpendicular to the surface of the cartilage. The static elastographic images that depict compression made before digestion and after 5 and 15 hr of trypsin digestion show that the elastic modulus of the samples decreased with a spatial variation consistent with the enzymatic digestion as revealed by the T(1) images. We believe this technique will be useful in studies of the mechanical properties of articular cartilage and other tissues, and may in the future be extended to the clinical setting.
Magnetic particulates have been shown to be powerful transverse relaxation enhancers and are unde... more Magnetic particulates have been shown to be powerful transverse relaxation enhancers and are under consideration as an MR contrast agent for the detection of liver and spleen lesions. This work describes the magnetic properties of a commercially available magnetic particulate and a Monte Carlo simulation of the effect of these particles on the transverse relaxation rates of water protons for spin-echo experiments. From the simultations, empirical relations were developed to describe the dependence of the enhancement on particle size, and concentration as well as the diffusion constant of water and the pulse spacing of a Carr-Purcell-Meiboom-Gill pulse sequence used to measure the transverse relaxation time. The simulations are shown to agree with measurements of relaxation rates in agar samples containing the magnetic particulates.
Advances in imaging and computerized analyses have enabled three-dimensional bone motion in the t... more Advances in imaging and computerized analyses have enabled three-dimensional bone motion in the treated clubfoot to be measured precisely. Three-dimensional translations and rotations of the talus, calcaneus, navicular, and cuboid of surgically treated clubfeet were less in magnitude and sometimes different in direction (or without motion in a specific plane) compared with the contralateral normal feet. Surgical techniques used for clubfoot treatment do not restore normal hindfoot bone motion when examined with high-resolution magnetic resonance imaging, computer reconstruction, and image analysis techniques. These data advance the knowledge of hindfoot bone motion and establish a new and quantitative objective.
Functional magnetic resonance imaging (fMRI) is increasingly used in non-human primate research. ... more Functional magnetic resonance imaging (fMRI) is increasingly used in non-human primate research. In the present study, we adapt the familiarization-novelty preference (FNP) procedure used in human infant research to examine visual behavior in alert, unanaesthetized rhesus monkeys that were acclimated to the fMRI environment, but did not undergo behavioral training. In keeping with the typical FNP paradigm, we recorded eye movements (looking time and number of fixations) while monkeys viewed a series of four identical pictures (familiarization phase) followed by two different pictures (novelty phase). Number of fixations and looking time both increased during the novelty phase, thereby demonstrating visual discrimination of the new from the old picture. Importantly, discrimination did not occur on catch trials in which six identical pictures were presented. Moreover, brain activation in the amygdala was more strongly associated with the novelty phase than with the familiarization phase. In addition, magnitude of brain activation in the amygdala was correlated with the behavioral effect of visual discrimination. These findings demonstrate the feasibility of using eye movements as an index of visual discrimination in untrained monkeys during fMRI scanning. This methodological approach helps to extend the repertoire of research tools for fMRI in non-human primates.
Knowledge of hind foot bone motion is important for understanding gait as well as various foot pa... more Knowledge of hind foot bone motion is important for understanding gait as well as various foot pathologies, but the three-dimensional (3D) motion of these bones remains incompletely understood. The purpose of this study was to quantify the motion of the talus, calcaneus, navicular, and cuboid in normal adult feet during open chain quasi-static uniplanar plantar flexion motion. Magnetic resonance images of the right feet of six normal young adult males were taken from which 3D virtual models were made of each hind foot bone. The 3D motion of these models was analyzed. Each hind foot bone rotated in the same plane about half as much as the foot (mean 0.54 degrees of bone rotation per degree of foot motion, range 0.40-0.73 degrees per degree of foot motion as measured relative to the fixed tibia). Talar motion was primarily uniaxial, but the calcaneus, navicular, and cuboid bones exhibited biplanar (sometimes triplanar) translation in addition to biaxial rotation. Net translational motions of these bones averaged 0.39 mm of bone translation per degree of foot motion (range 0.06-0.62 mm per degree of foot motion). These data reflect the functional anatomy of the foot, extend the findings of prior studies, provide a standard for comparison to patients with congenital or acquired foot deformities, and establish an objective reference for quantitatively assessing the efficacy of various hind foot therapies.
We used an innovative, nonintrusive MRI technique called the two-dimensional (2D) Phase-Contrast ... more We used an innovative, nonintrusive MRI technique called the two-dimensional (2D) Phase-Contrast (2DPC) velocity-imaging technique to investigate the effect of flow baffles on the dialysate-side flow distribution in two different hollow-fiber hemodialyzers (A and B); each with flow rates between 200 and 1000 mL/min (3.33 x 10(-6) and 1.67 x 10(-5) m3/s). Our experimental results show that (1) the dialysate-side flow distribution was nonuniform with channeling flow occurred at the peripheral cross section of these hollow-fiber hemodialyzers, and (2) the existing designs of flow baffles failed to promote uniform dialysate-side flow distribution for all flow rates studies.
To design nanoparticles containing accessible gadolinium atoms (Gd-NPs) as a contrast agent for m... more To design nanoparticles containing accessible gadolinium atoms (Gd-NPs) as a contrast agent for magnetic resonance imaging of tumors. Nanoparticles containing phospholipid-chelates (phosphoethanolamine diethylenetriaminepentaacetate) and DSPE-PEG (MW5000) were prepared from Brij 78 and stearyl alcohol using the nanotemplate engineering approach. After addition of GdCl3, the presence of gadolinium on the surface of nanoparticles was quantified using inductively coupled plasma atomic emission spectroscopy. The in vitro relaxivities of the Gd-NPs in phosphate buffered saline were assessed at 4.7 T. The conditional binding constants of nanoparticle formulations were determined spectrophotometrically by competitive titration. Transmetallation kinetics of Gd from nanoparticles with Cu2+ and Zn2+ as the competing ions was measured in acetate buffer. The biodistribution profiles, pharmacokinetics, and contrast enhancement in tumor region was studied after administration of Gd-NPs to nude mice bearing A549 lung carcinoma xenografts. Gd-NPs with an average diameter of 138 nm possessing surface chelating functions were prepared from GRAS (generally regarded as safe) materials. The longitudinal relaxivity (r1) and transverse relaxivity (r2) of Gd-NPs in 10% fetal bovine serum at 4.7 T were 7.1 (+/-0.2) and 13.0 (+/-0.7) 1/mM/s, respectively. These pegylated Gd-NPs had enhanced relaxivities and exhibited particle size stability, sufficient binding affinity, and kinetic inertness under physiologic conditions. The contrast enhancement in tumors was demonstrated 40, 120, and 360 minutes after intravenous injection of Gd-NPs at a dose of 0.1 mmol Gd/kg. The Gd plasma concentration of Gd-NPs over a period of 24 hours fit a two-compartmental model with Cl sys = 0.89 mL/h and MRT = 5.93 h. The amount of Gd that accumulated in the tumor region was consistent with the estimated value obtained by T1 measurements using MR imaging. Pegylated nanoparticles composed of biocompatible, biodegradable materials and possessing accessible Gd ions on their surface induce relaxivities in the bulk water signal and accumulated sufficiently in tumors, demonstrating their utility as potential magnetic resonance imaging tumor contrast enhancement agents.
Kinetic modeling, based on the fundamental principle of mass balance, is one of the most widely u... more Kinetic modeling, based on the fundamental principle of mass balance, is one of the most widely used analytic methods to study the biological system. It provides a powerful tool to conceptualize clinical problems requiring further understanding. Several precise mathematical equations can be derived to describe the evolution of a biological system, and each model parameter is defined rigorously. Therefore, the relative importance of each parameter can be both quantitatively and qualitatively evaluated. The goal of kinetic modeling in hemodialysis (HD) is to help physicians understand the uremic syndrome more clearly and allow them to provide adequate dialytic therapy to patients. Solely by empirical observation and clinical judgment, it is very difficult, if not impossible, to determine the adequate dose of dialysis therapy, which depends on many factors, such as patient size, generation rate of endogenous toxins, residual renal function, dialyzer clearance, frequency, and treatment time (1).
The accuracy of cine phase-contrast magnetic resonance (MR) imaging for motion analysis was evalu... more The accuracy of cine phase-contrast magnetic resonance (MR) imaging for motion analysis was evaluated. By using a rotating phantom and postprocessing algorithm for phase tracking, errors arising during data acquisition were identified and compensation methods were developed. A spatially varying background phase offset in the velocity images was found to be due to eddy current-induced fields. The magnitude of the offset was in the range of 0–20 cm/sec, which is of the same order of magnitude as cardiac contractile velocities. Background offset is thus an important source of error in tracking cardiac motion. Study of different tracking algorithms revealed the need for an integration scheme using motion terms higher than velocity. Also, considerable improvement in the accuracy and stability of the predicted trajectories was obtained by averaging the trajectories proceeding both forward and backward in time from the starting point. With the algorithm developed, the motion of the phantom was tracked through a complete rotation of the phantom to an accuracy of 2 pixels.
Conventional T2-weighted spin-echo magnetic resonance imaging of the knee requires a long TR. Fas... more Conventional T2-weighted spin-echo magnetic resonance imaging of the knee requires a long TR. Fast spin-echo (FSE) imaging can improve acquisition efficiency severalfold by collecting multiple lines of k space for each TR. Compromises in resolution, section coverage, and contrast inevitably result. The authors examined the compromises encountered in FSE imaging of the knee and discuss the variations in image contrast and resolution due to choices of sequence parameters. For short TR/TE knee imaging, FSE does not appear to offer any advantages, since the increased collection efficiency for one section reduces the available number of sections, so that the total imaging time for a given number of sections remains constant relative to conventional spin-echo imaging. For T2-weighted images, considerable time can be saved and comparable quality images can be obtained. This saved time can be usefully spent on increasing both the resolution of the image and its signal-to-noise ratio, while still reducing total acquisition time by a factor of two. The preferred FSE T2-weighted images were acquired with a TR of 4,500 msec, TE of 120 msec, and eight echoes. The available number of sections is compromised, and the sequence remains sensitive to flow artifacts; however, the FSE sequence appears to be promising for knee imaging.
We have developed an algorithm to estimate and display the spatial distribution of the thickness ... more We have developed an algorithm to estimate and display the spatial distribution of the thickness of articular cartilage in human knees. We used a simulation to derive the most appropriate formula for estimating thickness in digital images. The algorithm was tested by imaging a thickness phantom and comparing the results with the known dimensions of the phantom. The results demonstrated that the maximum error encountered in estimating thickness is one pixel while the average error is 0.4 pixels. We imaged a human knee on a cadaver in two separate sessions and used the two image sets to derive thickness maps of the patellar articular cartilage. The thickness maps generated independently from these image sets were very similar, indicating the reliability of the method in deriving accurate thickness estimates. J. Magn. Reson. Imaging 2001;13:120-126.
Functional imaging of the non-human primate brain in awake animals is now feasible because of rec... more Functional imaging of the non-human primate brain in awake animals is now feasible because of recent methodological advances. Here we detail our procedures for conducting functional MRI (fMRI) studies in rhesus monkeys. Our emphasis has been on analyzing drug-evoked responses within and across test groups, meaning that techniques have had to be developed for training and testing relatively large groups of animals. Group size is important as unbiased estimates are best derived from analyzing responses in multiple animals with replicate scans per animal due to partial volume errors in evaluating small brain regions and motion artifacts during scanning. While the procedures presented here were developed for mapping responses obtained from stimulating dopaminergic systems, much of the methodology is generally applicable for non-human primate fMRI studies and addresses specific problems encountered in imaging awake animals. These are (1) adapting animals to an MRI environment, (2) minimizing head movements, (3) reducing ambient scanning noise levels, and (4) developing multivariate methods of image data analysis suitable for eliciting the dynamic brain response while (5) detecting and deleting outlying observations due to motion artifacts. Procedures are demonstrated for first pre-processing and analyzing responses in a voxel-based approach in a single animal and then proceeding to analyze responses across animals and replicate scans for regions of interest. Collectively, the procedures described provide an approach for fMRI mapping of elicited responses using conventional 1.5T MR scanners.
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Papers by Peter Hardy