Reproducibility of T1ρ and T2 quantification in a multi-vendor multi-site study.

OBJECTIVE: To evaluate the multi-vendor multi-site reproducibility of two-dimensional (2D) multi-echo spin-echo (MESE) T2 mapping (product sequences); and to evaluate the longitudinal reproducibility of three-dimensional (3D) magnetization-prepared angle-modulated partitioned k-space spoiled gradient echo snapshots (MAPSS) T1ρ and T2 mapping (research sequences), and 2D MESE T2 mapping, separated by 6 months, in a multi-vendor multi-site setting. METHODS: Phantoms and volunteers (n = 5 from each site, n = 20 in total) were scanned on four 3 T magnetic resonance (MR) systems from four sites and three vendors (Siemens, General Electric, and Phillips). Two traveling volunteers (3 knees) scanned at all 4 sites at baseline and 6-month follow-up. Data was transferred to one site for centralized processing. Coefficients of variation (CVs) were calculated to evaluate reproducibility. RESULTS: For baseline 2D MESE T2 measures, average CV were 0.37-2.45% (intra-site) and 5.96% (inter-site) for phantoms, and 3.15-8.49% (intra-site) and 14.16% (inter-site) for volunteers. For longitudinal phantom data, intra-site CVs were 1.42-3.48% for 3D MAPSS T1ρ, 1.77-3.56% for 3D MAPSS T2, and 1.02-2.54% for 2D MESE T2. For the longitudinal volunteer data, the intra-site CVs were 2.60-4.86% for 3D MAPSS T1ρ, 3.33-7.25% for 3D MAPSS T2, and 3.11-8.77% for 2D MESE T2. CONCLUSION: This study demonstrated excellent intra-site reproducibility of 2D MESE T2 imaging, while its inter-site variation was slightly higher than 3D MAPSS T2 imaging (10.06% as previously reported). This study also showed excellent reproducibility of longitudinal T1ρ and T2 cartilage quantification, in a multi-vendor multi-site setting for both product 2D MESE T2 and 3D MAPSS T1p/T2 research sequences.

Multi-vendor multi-site T1ρ and T2 quantification of knee cartilage.

OBJECTIVE: To develop 3D T1ρ and T2 imaging based on the same sequence structure on MR systems from multiple vendors, and to evaluate intra-site repeatability and inter-site inter-vendor reproducibility of T1ρ and T2 measurements of knee cartilage. METHODS: 3D magnetization-prepared angle-modulated partitioned k-space spoiled gradient echo snapshots (3D MAPSS) were implemented on MR systems from Siemens, GE and Philips. Phantom and human subject data were collected at four sites using 3T MR systems from the three vendors with harmonized protocols. Phantom data were collected by means of different positioning of the coil. Volunteers were scanned and rescanned after repositioning. Two traveling volunteers were scanned at all sites. Data were transferred to one site for centralized processing. RESULTS: Intra-site average coefficient of variations (CVs) ranged from 1.09% to 3.05% for T1ρ and 1.78-3.30% for T2 in phantoms, and 1.60-3.93% for T1ρ and 1.44-4.08% for T2 in volunteers. Inter-site average CVs were 5.23% and 6.45% for MAPSS T1ρ and T2, respectively in phantoms, and 8.14% and 10.06% for MAPSS T1ρ and T2, respectively, In volunteers. CONCLUSION: This study showed promising results of multi-site, multi-vendor reproducibility of T1ρ and T2 values in knee cartilage. These quantitative measures may be applied in large-scale multi-site, multi-vendor trials with controlled sequence structure and scan parameters and centralized data processing.

A modified equivalent annulus model for the hollow fiber hemodialyzer.

Experimental approaches to optimize hollow fiber hemodialyzer design are expensive and time-consuming. Computer modeling is an effective way to study mass transfer in the hemodialyzer because a substantial reduction in experimental time and cost can be achieved. This paper presents a two-dimensional modified "equivalent annulus" model, which employs Navier-Stokes (N-S) equations to describe blood and dialysate flow, and Kedem-Katchalsky (K-K) equations to calculate transmembrane flow. N-S equations and K-K equations must be coupled together in the process of computing. The corresponding experiments were designed to validate this model, and experimental results agreed well with numerical results. The distribution of velocity, pressure and solute concentration were investigated in detail, presenting a clear insight into dialyzer mass transfer. This model can be applied to help optimize hemodialyzer design.

Measuring the thickness of articular cartilage from MR images.

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.

Recombinant Semliki forest virus infects and kills human prostate cancer cell lines and prostatic duct epithelial cells ex vivo.

Semliki Forest Virus (SFV) is a broad host range RNA virus capable of high-level recombinant protein expression and apoptosis induction in many cell types. We have successfully used a recombinant, replication deficient SFV vector to express the LacZ marker gene product in seven human prostate cell lines, as well as in human prostate tissue explants. Flow cytometry revealed that 40-60% of PPC-1 prostate cancer cells died 24-72 h after infection with SFV-LacZ virus. Most human prostate cancer cell lines expressed high levels of recombinant protein. Infection of human prostate tissue ex vivo led to similarly high expression levels but the recombinant beta-galactosidase was confined to duct epithelial cells. Infection of cell and tissue cultures resulted in detachment of adherent cells from the culture surface and detachment of epithelial cells from the basement membrane of tissue. Our results indicate that SFV may be useful in targeting recombinant protein expression and apoptosis to prostatic duct epithelial cells.

Characterization of the calcaneal fat pad in diabetic and non-diabetic patients using magnetic resonance imaging.

It is well known that diabetic patients have a high incidence of foot ulceration. The purpose of this study was to determine whether magnetic resonance (MR) imaging can detect changes in the composition of the calcaneal fat pad in diabetic feet. MR data were collected in vitro from amputated specimens (eight from diabetic patients and eight from non-diabetic patients) as well as in vivo from age-matched diabetic and control subjects (four subjects each group.) Three types of images were acquired: spin lattice (T1), spin-spin (T2), and magnetization transfer (MT). The in vitro results showed statistically significant differences in the T1, T2, and MT parameters between the two disease groups. The same trends were shown in the study of live subjects but the differences were not statistically significant. The differences are believed to arise from changes in the composition of the tissues as a result of the progression of diabetes.

Chronic ethanol exposure and withdrawal influence NMDA receptor subunit and splice variant mRNA expression in the rat cerebral cortex.

Chronic ethanol exposure and subsequent withdrawal are known to change NMDA receptor activity. This study examined the effects of chronic ethanol administration and withdrawal on the expression of several NMDA receptor subunit and splice variant mRNAs in the rat cerebral cortex. Ethanol dependence was induced by ethanol vapour exposure. To delineate between seizure-induced changes in expression during withdrawal and those due to withdrawal per se, another group of naive rats was treated with pentylenetetrazol (PTZ) injection (30 mg/kg, i.p.). RNA samples from the cortices of chronically treated and withdrawing animals were compared to those from pair-fed controls. Changes in NMDA receptor mRNA expression were determined using ribonuclease protection assays targetting the NR2A, -2B, -2C and NR1-pan subunits as well as the three alternatively spliced NR1 inserts (NR1-pan describes all the known NR1 splice variants generated from the 5' insert and the two 3' inserts). The ratio of NR1 mRNA incorporating the 5' insert vs. that lacking it was decreased during ethanol exposure and up to 48 h after withdrawal. NR2B mRNA expression was elevated during exposure, but returned to control levels 18 h after withdrawal. Levels of NR2A, NR2C, NR1-pan and both 3' NR1 insert mRNAs from the ethanol-treated groups did not alter compared with the pair-fed control group. No changes in the level of any NMDA receptor subunit mRNA was detected in the PTZ-treated animals. These data support the hypothesis that changes in NMDA receptor subunit composition may underlie a neuronal adaptation to the chronic ethanol-inhibition and may therefore be important in the precipitation of withdrawal hyperactivity.

Fat suppressed MRI of articular cartilage with a spatial-spectral excitation pulse.

We developed a three-dimensional, gradient-recalled-echo imaging technique that incorporates a short-duration spatial-spectral excitation pulse from the family of binomial pulses. Binomial pulses of different orders were tested on phantoms and on normal volunteers to find the composite pulse that produced in the shortest duration the most reliable fat suppression. Composite pulses employing unipolar slice-selective gradients with explicit rewinder gradients between each radio-frequency (RF) pulse were compared with composite RF pulses employing alternating-polarity, slice-select gradients. The advantage of the sequences using the unipolar gradients is improved fat suppression. Images of the knees of volunteers produced with the composite RF pulse have contrast between fat and articular cartilage equivalent to that on images created by the gradient-recalled-echo imaging technique employing a conventional chemsat pulse. The optimum RF pulse consisted of three amplitude- and phase-modulated pulses combined with unipolar slice-select gradients.

Measurement of magnetic resonance T2 for physiological experiments.

The proton transverse relaxation time (T2) of human skeletal muscles has been increasingly used in magnetic resonance imaging experiments to examine muscle physiology and neuromuscular control. However, little attention has been paid to the experimental factors affecting the accuracy or sensitivity of the T2 measurement. We have explored theoretically and experimentally the structure of several magnetic resonance pulse sequences for measuring T2 of the first dorsal interosseous muscle and found that a multiecho imaging technique using non-slice-selective refocusing pulses (MENSS) produces more accurate T2 estimates than multiecho slice-selective (MESS) imaging methods that are commonly used. Using either technique we acquired four 5-mm-thick transverse images of the first dorsal interosseous muscle with a spatial resolution of 0.6 mm within 5 min. The T2 measured by the MENSS method was closer to the true T2 than was the T2 estimated by the MESS method. After a given amount of exercise, the MENSS technique revealed an average 28 +/- 10% increase in T2 compared with a 13 +/- 3% increase measured with an equivalent MESS technique. We conclude that the MENSS method is a more accurate and sensitive procedure for studying neuromuscular physiology compared with the more commonly used MESS method.

Task-dependent effect of limb immobilization on the fatigability of the elbow flexor muscles in humans.

Because short-term limb immobilization produces selective adaptations in the neuromuscular system that probably interact with the task-dependent expression of muscle fatigue, the purpose of this study was to determine the effects of limb immobilization on the ability of human subjects to sustain isometric contractions at low and moderate submaximal forces. Four weeks of elbow joint immobilization caused a substantial decrease in the daily activity of biceps brachii during immobilization, a significant reduction in the cross-sectional area and volume of the elbow flexor muscles as measured by magnetic resonance imaging, and a decline in the maximum voluntary contraction (MVC) activation and force of the elbow flexor muscles. Immobilization had a task-dependent effect on muscle fatigue with a substantially increased endurance time (reduced fatigability) at a low force (20% MVC) and no statistical effect at a moderate force (65% MVC). Despite atrophy of the elbow flexor muscles due to the immobilization, the twitch force elicited in biceps brachii by electrical stimulation was greater after immobilization. The selective improvement of fatigue resistance for the low-force contraction and the absence of a change in the time course of the twitch suggests that the immobilization-induced adaptations included an improved efficacy of some excitation-contraction processes and underscored the major role of these mechanisms in determining the endurance time for low-force, long-duration contractions.

Plasma concentrations of bupivacaine following single needle lumbar sympathectomy using two volumes of 0.25% bupivacaine plain solution.

Plasma bupivacaine concentrations were measured in 10 patients after lumbar sympathectomy using 10 ml or 20 ml of 0.25% bupivacaine plain solution. A single needle technique was employed, positioned at the L3 level. Mean peak concentrations were greater in the larger volume group and were statistically significant at 20, 30, 60, 90 and 120 min. Plasma bupivacaine levels peaked earlier in the smaller volume group. Some patients in the larger volume group still had plasma bupivacaine levels at or near peak values at 120 min. No patient approached toxic plasma levels of bupivacaine.

Intervertebral disks on MR images: variation in signal intensity with the disk-to-magnetic field orientation.

PURPOSE: To demonstrate and quantitate the magic angle effect in the intervertebral disk. MATERIALS AND METHODS: Magnetic resonance (MR) images of a lumbar intervertebral disk in a healthy volunteer were obtained with MR images with horizontal and vertical magnetic fields. Thin-section spin-echo images of an excised intervertebral disk were obtained with a horizontal field machine at orientations with respect to the main magnetic field between +90 degrees and -90 degrees. T1 and T2 were measured independently in this disk at two orientations. RESULTS: Images of the in vivo disk demonstrated a variation in the signal intensity of the anulus fibrosus that was different for the two MR units. The images obtained in the excised intervertebral disk demonstrated a signal intensity variation with disk orientation that was most pronounced in the anterior portion of the anulus. Relaxation time measurements showed the signal intensity reduction to arise from a reduction in T2 with oblique orientations. CONCLUSION: The observed signal intensity variation with disk orientation arises from an anisotropy in T2 caused by the restriction of water associated with collagen in the anulus. The magic angle effect in intervertebral disks will be observed with vertical magnetic field MR imagers.

Long-term use of subarachnoid clonidine for analgesia in refractory reflex sympathetic dystrophy. Case report.

BACKGROUND AND OBJECTIVES: A case is presented of intractable reflex sympathetic dystrophy resistant to all other types of treatment. METHODS: Twice daily subarachnoid clonidine was used to manage the symptoms via an implanted drug delivery system. RESULTS: The patient has successfully administered his own subarachnoid clonidine for over 18 months with no signs of tolerance or toxicity. CONCLUSIONS: Continuous subarachnoid clonidine may offer a solution to the management of some cases of intractable reflex sympathetic dystrophy.

Flumazenil: an unreliable antagonist in baclofen overdose.

We report a case of inadvertent overdose of baclofen given intrathecally resulting in coma. This was unresponsive to flumazenil and required supportive intensive therapy. With the increasing use of baclofen intrathecally for spasticity and its wide interpatient dose variability, there is a need to find a safe antagonist to baclofen for routine medical use.

Optimization of a dual echo in the steady state (DESS) free-precession sequence for imaging cartilage.

Three-dimensional (3D) MR imaging of the knee is useful to detect cartilage abnormalities, although the tissue contrast in 3D gradient-recalled echo (GRE) sequences such as gradient-recalled acquisition in the steady state (GRASS) or fast low-angle shot (FLASH) is poor. T2 contrast can be added to a GRASS sequence by combining the signals from the first and second gradient echoes, which form immediately after and immediately before each radio frequency (RF) pulse in a 3D GRE sequence. We have optimized a 3D dual echo in the steady state (DESS) sequence, which produces one averaged image from the two echoes, for use in the detection of articular cartilage abnormalities. In the optimization process, we examined the imaging parameters of flip angle (alpha), repetition time (TR), echo time (TE), and bandwidth to maximize the contrast between cartilage and joint fluid. A theoretical simulation of the sequence was confirmed with experiments conducted on phantoms with known T1 and T2. On the basis of theoretical predictions and experiments using healthy volunteers, we determined that an optimized sequence with a bandwidth of 98 Hz per pixel, TR of 30 msec, a TE of 7.1 msec, and an alpha of 60 degrees produced the highest contrast between cartilage and fluid within a defined acquisition time of 6 minutes. Additional contrast was obtained by filtering the second-echo image to eliminate noise before adding it to the first-echo image.

Validation of cine phase-contrast MR imaging for motion analysis.

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.

Separation of fat and water in fast spin-echo MR imaging with the three-point Dixon technique.

A method for suppressing fat in fast spin-echo imaging with the three-point Dixon technique is described. The method differs from the three-point Dixon method used in conventional spin-echo imaging in that the readout gradient instead of a radio-frequency pulse is shifted. This method preserves the Carr-Purcell-Meiboom-Gill nature of the fast spin-echo sequence and hence is less sensitive to magnetic field inhomogeneities and resonance frequency mistuning. As in the original three-point Dixon technique used in conventional spin-echo imaging, three acquisitions are required to estimate the field inhomogeneity and completely separate fat and water. The extra time required is not excessive considering that the fast spin-echo method is frequently applied with multiple signal acquisition. Also, this technique achieves an expected signal-to-noise ratio comparable to 2.67 signal acquisitions, which is approximately 94% of the signal-to-noise ratio obtained with three signal acquisitions. The method is demonstrated with applications to phantoms and a human volunteer.