Capturing fast relaxing spins with SWIFT adiabatic rotating frame spin-lattice relaxation (T1ρ) mapping.

Rotating frame spin-lattice relaxation, with the characteristic time constant T1ρ, provides a means to access motion-restricted (slow) spin dynamics in MRI. As a result of their restricted motion, these spins are sometimes characterized by a short transverse relaxation time constant T2 and thus can be difficult to detect directly with conventional image acquisition techniques. Here, we introduce an approach for three-dimensional adiabatic T1ρ mapping based on a magnetization-prepared sweep imaging with Fourier transformation (MP-SWIFT) sequence, which captures signal from almost all water spin populations, including the extremely fast relaxing pool. A semi-analytical procedure for T1ρ mapping is described. Experiments on phantoms and musculoskeletal tissue specimens (tendon, articular and epiphyseal cartilages) were performed at 9.4 T for both the MP-SWIFT and fast spin echo (FSE) read outs. In the phantom with liquids having fast molecular tumbling and a single-valued T1ρ time constant, the measured T1ρ values obtained with MP-SWIFT and FSE were similar. Conversely, in normal musculoskeletal tissues, T1ρ values measured with MP-SWIFT were much shorter than the values obtained with FSE. Studies of biological tissue specimens demonstrated that T1ρ-weighted SWIFT provides higher contrast between normal and diseased tissues relative to conventional acquisitions. Adiabatic T1ρ mapping with SWIFT readout captures contributions from the otherwise undetected fast relaxing spins, allowing more informative T1ρ measurements of normal and diseased states.

Endoscopic carpal tunnel release in Jamaica--seven years experience.

OBJECTIVE: To assess the patient profile and outcome of treatment, by endoscopic release, of patients with carpal tunnel syndrome. METHODS: A descriptive study was done using data from two sets of patients who had endoscopic carpal tunnel release in Jamaica from 2004 to 2006 and 2006 to 2010. The medical records of patients who had a diagnosis of carpal tunnel syndrome using symptoms, clinical signs and confirmation by nerve conduction test were reviewed. The data were analysed using SPSS and Micosoft Excel. RESULTS: A total of 68 patients with 75 cases of carpal tunnel syndrome were done. Fifty-two (76%) of these patients were females and about 50% were older than 41 years old. There were 61 (90%) unilateral cases. Of these, the majority of cases affected the right hand. All patients had improvement in symptoms after one week, required minimal analgesic use, had good compliance with rehabilitation and returned to work after about two weeks. There were three cases of pilar tenderness, two cases of transient paraesthesia in the index finger which resolved after three weeks. There were three failed cases from the first series which had to be converted to open carpal tunnel release. The complication rate was 6.7%. No serious complications occurred in the second series and all were treated successfully without interventional surgery. The rate of conversion to open release was 4%. CONCLUSION: Carpal tunnel affects mostly middle aged females and when treatment is done by endoscopic release, there is a fast resolution of symptoms and early return to work.

Regional differences in MRI detection of amyloid plaques in AD transgenic mouse brain.

Our laboratory and others have reported the ability to detect individual Alzheimer's disease (AD) amyloid plaques in transgenic mouse brain in vivo by magnetic resonance imaging (MRI). Since amyloid plaques contain iron, most MRI studies attempting to detect plaques in AD transgenic mouse brain have employed techniques that exploit the paramagnetic effect of iron and have had mixed results. In the present study, using five-way anatomic spatial coregistration of MR images with three different histological techniques, properties of amyloid plaques in AD transgenic mouse brain were revealed that may explain their variable visibility in gradient- and spin-echo MR images. The results demonstrate differences in the visibility of plaques in the cortex and hippocampus, compared to plaques in the thalamus, by the different MRI sequences. All plaques were equally detectable by T(2)SE, while only thalamic plaques were reliably detectable by T(2)*GE pulse sequences. Histology revealed that cortical/hippocampal plaques have low levels of iron while thalamic plaques have very high levels. However, the paramagnetic effect of iron does not appear to be the sole factor leading to the rapid decay of transverse magnetization (short T(2)) in cortical/hippocampal plaques. Accordingly, MRI methods that rely less on iron magnetic susceptibility effect may be more successful for eventual human AD plaque MR imaging, particularly since human AD plaques more closely resemble the cortical and hippocampal plaques of AD transgenic mice than thalamic plaques.

Feasibility of single-voxel MRS measurement of apparent diffusion coefficient of water in breast tumors.

We report initial results with single voxel spectroscopy (SVS) using diffusion weighting and localization by adiabatic selective refocusing (LASER) in breast tumors to measure the apparent diffusion coefficient of water (ADCw). This is a quick (30 s) and relatively easy method to implement compared with image-based diffusion measurements, and is insensitive to lipid signal contamination. The ADCw and concentration of total choline containing compounds [tCho] were evaluated for associations with each other and final pathologic diagnosis in 25 subjects. The average (+/- SD) ADCw in benign and malignant lesions was 1.96 +/- 0.47 mm(2)/s and 1.26 +/- 0.29 x 10(-3) mm(2)/s, respectively, P< 0.001. Receiver operating characteristic curve analysis showed an area under the curve of 0.92. Analysis of the single voxel (SV) ADCw and [tCho] showed significant correlation with a R(2) of 0.56, P< 0.001. Compared with more commonly used image-based methods of measuring water ADC, SV-ADCw is faster, more robust, insensitive to fat, and potentially easier to implement on standard clinical systems.

MR imaging contrast enhancement based on intermolecular zero quantum coherences.

A new method for magnetic resonance imaging (MRI) based on the detection of relatively strong signal from intermolecular zero-quantum coherences (iZQCs) is reported. Such a signal would not be observable in the conventional framework of magnetic resonance; it originates in long-range dipolar couplings (10 micrometers to 1 millimeter) that are traditionally ignored. Unlike conventional MRI, where image contrast is based on variations in spin density and relaxation times (often with injected contrast agents), contrast with iZQC images comes from variations in the susceptibility over a distance dictated by gradient strength. Phantom and in vivo (rat brain) data confirm that iZQC images give contrast enhancement. This contrast might be useful in the detection of small tumors, in that susceptibility correlates with oxygen concentration and in functional MRI.

Platelet concentrates produced from whole blood using the Atreus processing system.

BACKGROUND: The Atreus 2C+ system automates whole blood (WB) processing into a red cell concentrate, plasma and buffy coat (BC) suitable for platelet concentrate (PC) manufacture. This study compared the quality of PC made from BC using the Atreus, with those made by a manual method. STUDY DESIGN AND METHODS: WB was collected into Atreus disposables or standard bottom and top processing packs and held without active cooling for 26 h at 22 +/- 2 degrees C before processing, either with the Atreus, or using a centrifuge and press. BC were rested for 3 h and then 4 BC were pooled with one unit of plasma, mixed, centrifuged and pressed to make a pooled PC. The PC were analysed for quality markers to day 9 of storage. RESULTS: Platelet quality was good in both Atreus 2C+ derived PC and control units throughout storage. Metabolic markers (pH, ATP and HSR) and activation markers (CD62P, sCD62P, annexin V binding, microparticles, GP IIb/IIIa) did not differ between the Atreus and control units. Atreus-derived PC had significantly lower platelet yields (302 +/- 59 x 10(9) platelets/unit; mean +/- standard deviation, n = 8) than control PC (411 +/- 76 x 10(9) platelets/unit; P < 0.01), but met the UK guidelines for platelet yield. CONCLUSION: From these in vitro data, PC produced from buffy coats prepared using the Atreus appear suitable for clinical use, and WB may be held at ambient temperature overnight without the use of active cooling devices. Optimizing the secondary processing conditions to handle Atreus 2C+ derived BC may increase the platelet yield.

Bioenergetic abnormalities associated with severe left ventricular hypertrophy.

Transmurally localized 31P-nuclear magnetic resonance spectroscopy (NMR) was used to study the effect of severe pressure overload left ventricular hypertrophy (LVH) on myocardial high energy phosphate content. Studies were performed on 8 normal dogs and 12 dogs with severe left ventricular hypertrophy produced by banding the ascending aorta at 8 wk of age. Spatially localized 31P-NMR spectroscopy provided measurements of the transmural distribution of myocardial ATP, phosphocreatine (CP), and inorganic phosphate (Pi); spectra were calibrated from measurements of ATP content in myocardial biopsies using HPLC. Blood flow was measured with microspheres. In hypertrophied hearts during basal conditions, ATP was decreased by 42%, CP by 58%, and the CP/ATP ratio by 32% in comparison with normal. Increasing myocardial blood flow with adenosine did not correct these abnormalities, indicating that they were not the result of persistent hypoperfusion. Atrial pacing at 200 and 240 beats per min caused no change in high energy phosphate content in normal hearts but resulted in further CP depletion with Pi accumulation in the inner left ventricular layers of the hypertrophied hearts. These changes were correlated with redistribution of blood flow away from the subendocardium in LVH hearts. These findings demonstrate that high energy phosphate levels and the CP/ATP ratio are significantly decreased in severe LVH. These abnormalities are proportional to the degree of hypertrophy but are not the result of persistent abnormalities of myocardial perfusion. In contrast, depletion of CP and accumulation of Pi during tachycardia in LVH are closely related to the pacing-induced perfusion abnormalities and likely reflect subendocardial ischemia.

Lactate turnover in rat glioma measured by in vivo nuclear magnetic resonance spectroscopy.

Elevated tissue lactate concentrations typically found in tumors can be measured by in vivo nuclear magnetic resonance (NMR) spectroscopy. In this study, lactate turnover in rat C6 glioma was determined from in vivo 1H NMR measurements of [3-13C]lactate buildup during steady-state hyperglycemia with [1-13C]glucose. With this tumor model, a narrow range of values was observed for the first-order rate constant that describes lactate efflux, k2 = 0.043 +/- 0.007 (n = 12) SD min-1. For individual animals, the standard error in k2 was small (< 18%), which indicated that the NMR data fit the kinetic model well. Lactate measurements before and after infusing [1-13C]glucose showed that the majority of the tumor lactate pool was metabolically active. Signals from 13C-labeled glutamate in tumors were at least 10-fold smaller than the [3-13C]lactate signal, whereas spectra of the contralateral hemispheres revealed the expected labeling of [4-13C]glutamate, as well as [2-13C] and [3-13C]glutamate, which indicates that label cycled through the tricarboxylic acid cycle in the brain tissue. Lack of significant 13C labeling of glutamate was consistent with low respiratory metabolism in this glioma. It is concluded that lactate in rat C6 glioma is actively turning over and that the kinetics of lactate efflux can be quantified noninvasively by 1H NMR detection of 13C label. This noninvasive NMR approach may offer a valuable tool to help evaluate tumor growth and metabolic responsiveness to therapies.

Applications of magnetic resonance in model systems: tumor biology and physiology.

A solid tumor presents a unique challenge as a system in which the dynamics of the relationship between vascularization, the physiological environment and metabolism are continually changing with growth and following treatment. Magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) studies have demonstrated quantifiable linkages between the physiological environment, angiogenesis, vascularization and metabolism of tumors. The dynamics between these parameters continually change with tumor aggressiveness, tumor growth and during therapy and each of these can be monitored longitudinally, quantitatively and non-invasively with MRI and MRS. An important aspect of MRI and MRS studies is that techniques and findings are easily translated between systems. Hence, pre-clinical studies using cultured cells or experimental animals have a high connectivity to potential clinical utility. In the following review, leaders in the field of MR studies of basic tumor physiology using pre-clinical models have contributed individual sections according to their expertise and outlook. The following review is a cogent and timely overview of the current capabilities and state-of-the-art of MRI and MRS as applied to experimental cancers. A companion review deals with the application of MR methods to anticancer therapy.

Spatial assessment of the dynamics of lactate formation in focal ischemic rat brain.

Early identification of the potentially salvageable penumbra is critical for the determination of therapeutic intervention strategies in acute focal cerebral ischemia. This study differentiates the ischemic penumbra from the core on the basis of the dynamics of lactate formation. This was tested in a rat model of focal cerebral ischemia by infusion of [1-13C]-glucose, using lactate-edited magnetic resonance spectroscopic imaging techniques. The authors detected essentially no enrichment of lactate with 13C-label from the infused 13C-glucose in the ischemic core. However, in borderzone areas, 13C was incorporated into lactate, which could point toward compromised but potentially viable tissue. The authors' findings suggest that this combination of 13C-glucose infusion with the proposed magnetic resonance methods may aid in differentiating the penumbra from the core in cerebral ischemia.

3-D FLASH imaging using a single surface coil and a new adiabatic pulse, BIR-4.

A new adiabatic pulse, which can induce uniform and arbitrary flip angles despite the presence of transmitter coil magnetic field (B1) inhomogeneities, is employed for 3-D fast imaging using a single surface coil for pulse transmission and signal detection. Computer calculations and phantom, rat, and human surface coil imaging experiments demonstrate the utility of this adiabatic pulse for T1-weighted imaging with a transmitter coil which generates a highly inhomogeneous B1 field profile.

Release of protein from axons during rapid axonal transport: an in vitro preparation.

An in vitro system from the frog was used to study fast axonal transport and determine if transported protein is released from the axons. This preparation included the eighth and ninth dorsal root ganglia with their roots, sciatic nerve and gastrocnemius muscle. The preparation was placed in three-compartment chamber with each compartment separated by a silicone grease barrier. The dorsal root ganglia were incubated in [14C]leucine for 5 h in compartment A. The labeled protein was transported down the axon from compartment A to compartment B. The sciatic nerve in compartment B was superfused with frog Ringer. This solution was collected in hourly samples and dialyzed to remove unincoprorated leucine before counting. Incubating the ganglia in 100 microng/ml cycloheximide in frog Ringer blocked the release of labeled protein from the axon. Superfusing compartment B with solution containing 100 microng/ml cycloheximide inhibited axonal and Schwann cell protein synthesis, but did not block the release of labeled protein. It was concluded that the labeled protein released into the superfusing solution was synthesized in the ganglia and transported to the axon before release. SDS acrylamide gels were used to separate the labeled proteins. Sectioning the gels in 2 mm slices and determining the radioactivity showed that 80-85% of the counts were contained in two fast moving bands.

Demyelinating and myelination-inhibiting factors induced by chloroform-methanol insoluble proteins of myelin.

A host of proteins was seen when the chloroform-methanol insoluble protein (CMIP) fraction of bovine brain myelin was transferred from polyacrylamide gels to cellulose nitrate sheets. Inoculation of rabbits with the CMIP fraction generated a number of antibodies which were demonstrated by the immunoblot technique. These antisera against CMIP contained antibodies which induced demyelination and inhibited myelin formation in central nervous system cultures. The demyelinating factor was specific for centrally myelinated fibers, and did not demyelinate peripherally myelinated axons.

Antisera to an axolemma-enriched fraction inhibit neurite outgrowth and destroy axons in vitro.

Antisera prepared to an axolemma-enriched fraction derived from rat brain inhibited neurite outgrowth and destroyed mature axons in spinal cord-dorsal root ganglia cultures. Similar antibody-mediated anti-axon effects may be important in some diseases of the human nervous system.

The return of the frequency sweep: designing adiabatic pulses for contemporary NMR.

Frequency-modulated (FM) pulses that function according to adiabatic principles are becoming increasingly popular in many areas of NMR. Often adiabatic pulses can extend experimental capabilities and minimize annoying experimental imperfections. Here, adiabatic principles and some of the current methods used to create these pulses are considered. The classical adiabatic rapid passage, which is a fundamental element upon which all adiabatic pulses and sequences are based, is analyzed using vector models in different rotating frames of reference. Two methods to optimize adiabaticity are described, and ways to tailor modulation functions to best satisfy specific experimental needs are demonstrated. Finally, adiabatic plane rotation pulses and frequency-selective multiple spin-echo sequences are considered.

Asymmetric adiabatic pulses for NH selection.

Many types of NMR experiments demand the use of frequency-selective pulses to invert magnetization within discrete frequency limits. For certain experiments, only one side of the inversion band must be sharply demarcated, in which case this transition bandwidth can be narrowed when using an asymmetric adiabatic full passage. In the present study, a highly efficient asymmetric adiabatic full passage was created from a combination of two adiabatic half passages which used different modulation functions (HS12 and tanh/tan). Each adiabatic half passage occupied a different amount of time in the total pulse and performed one-half of the inversion. On one side, HS12 produced a sharp transition between inverted and noninverted states which was approximately 2.5 times narrower than the transition bandwidth afforded by a symmetric hyperbolic secant pulse of equal length. On the other side of the narrow transition band, the tanh/tan pulse achieved broadband inversion. These asymmetric pulses were applied to select NH groups immediately adjacent to the water signal in water-flip-back HSQC experiments using a double spin echo for the reverse INEPT step.

Fast broadband inversion by adiabatic pulses.

Despite the advantages of compensation for resonance offset and B1 inhomogeneity, adiabatic pulses are not yet in general use in high-resolution NMR, often because of the conception that these pulses require longer time or increased power to perform. We show that adiabatic pulses with tangential frequency sweeps and other frequency-modulation functions can be optimized to accomplish 13C and 1H broadband inversion using pulse lengths of 192 and 64 micro(s), respectively, at B1 strengths available with modern high-resolution probes.

Resolution improvements in in vivo 1H NMR spectra with increased magnetic field strength.

The measurement of cerebral metabolites using highly homologous localization techniques and similar shimming methods was performed in the human brain at 1.5 and 4 T as well as in the dog and rat brain at 9.4 T. In rat brain, improved resolution was achieved by shimming all first- and second-order shim coils using a fully adiabatic FASTMAP sequence. The spectra showed a clear improvement in spectral resolution for all metabolite resonances with increased field strength. Changes in cerebral glutamine content were clearly observed at 4 T compared to 1.5 T in patients with hepatic encephalopathy. At 9.4 T, glutamine H4 at 2.46 ppm was fully resolved from glutamate H4 at 2.37 ppm, as was the potential resonance from gamma-amino-butyric acid at 2.30 ppm and N-acetyl-aspartyl-glutamate at 2.05 ppm. Singlet linewidths were found to be as low as 6 Hz (0.015 ppm) at 9.4 T, indicating a substantial decrease in ppm linewidth with field strength. Furthermore, the methylene peak of creatine was partially resolved from phosphocreatine, indicating a close to 1:1 relationship in gray matter. We conclude that increasing the magnetic field strength increases spectral resolution also for 1H NMR, which can lead to more than linear sensitivity gains.

Measurement of human brain lithium in vivo by MR spectroscopy.

PURPOSE: To quantify lithium in the human brain. METHODS: A 7Li MR spectroscopy method was developed with special features for high precision including: a) sampling a large cerebral volume to maximize the signal-to-noise ratio; b) adiabatic excitation pulses to ensure uniform spin mutation; c) morphometric analysis of the MR images of the sampled cerebrum; d) a mathematical model derived from empirical data to correct for receiver inhomogeneity effects; and e) a long interpulse delay, to eliminate errors arising from uncertain T1 values. RESULTS: A theoretical precision of 5.2% and an accuracy of better than 7.2% in someone with a brain lithium level of 1.0 mEq per liter of cerebral volume and precision and accuracy of 6.8 and 8.6%, respectively, in someone with 0.5 mEq/L brain lithium was calculated. This level of precision was surpassed in phantoms and patients. Brain lithium in 10 patients treated with lithium carbonate varied from 0.52 to 0.87 mEq/L (mean = 0.58 mEq/L; SD = 0.17 mEq/L). Brain-to-serum lithium ratios varied from 0.50 to 0.97 mEq/L (mean = 0.77 mEq/L; SD = 0.14 mEq/L). Substantial variation in brain lithium was observed in patients with similar serum lithium. CONCLUSIONS: A highly reliable method to quantify human brain lithium by 7Li MR spectroscopy has been implemented. Unexpected variability in brain versus serum levels of lithium was detected in patients with bipolar disease.

Effects of continuous localized infusion of granulocyte-macrophage colony-stimulating factor and inoculations of irradiated glioma cells on tumor regression.

OBJECT: Glioblastoma multiforme (GBM) is a malignant tumor of the central nervous system that directly suppresses immunological defenses in vitro and in vivo. The authors used the peripheral delivery of continuously infused granulocyte-macrophage colony-stimulating factor (GM-CSF) in the presence of irradiated tumor antigens as a tumor-specific stimulant to dendritic cells to initiate an immune response to GBM in rats. METHODS: The 9L gliosarcoma tumors were established in the flanks of syngeneic Fischer 344 rats. Osmotic minipumps implanted in the animals' contralateral flanks continuously delivered recombinant GM-CSF (0, 0.1, 1, or 10 ng/day) for 28 days. Irradiated gliosarcoma cells were intermittently injected at the site of the GM-CSF infusion. Animals in the saline control group (0 ng/day GM-CSF) died on Day 59 with average tumor volumes greater than 30,000 mm3. This control group was significantly different from the GM-CSF-treated animals, which all survived with average tumor volumes that peaked on Day 23 and later regressed completely. Tumor growth as well as peak tumor volumes (5833+/-2284 mm3, 3294+/-1632 mm3, and 1979+/-1142 mm3 for 0.1, 1, and 10 ng/day GM-CSF, respectively) in the different treatment groups reflected a significant dose-response relationship with the GM-CSF concentrations. All animals treated with GM-CSF and irradiated cells were resistant to additional challenges of peripheral and intracerebral gliosarcoma, even when they were inoculated 8 months after initial immunotherapy. The colocalization of GM-CSF and inactivated tumor antigens was required to stimulate immunoprotection. To test the efficacy of a peripherally administered immunological therapy on intracerebral brain tumors the authors transplanted 10(6) gliosarcoma cells into the striatum of treated and control animals. Subcutaneous pumps that released GM-CSF (10 ng/day) and irradiated gliosarcoma cells were placed in the treated animals. The control animals all died within 31 days after intracerebral tumor implantation. In contrast, 40% of the animals receiving GM-CSF-irradiated cell vaccinations survived beyond 300 days. These long-term survivors showed no evidence of gliosarcoma at the injection site on evaluation by magnetic resonance imaging. CONCLUSIONS: These results suggest that the continuous localized delivery of subcutaneous GM-CSF in conjunction with inactivated tumor antigens can initiate a systemic response that leads to the regression of distant peripheral and intracerebral tumors. The success of this treatment illustrates the feasibility of tumor-specific peripheral immunological stimulation after tumor resection to prevent the recurrence of malignant brain tumors.