Changes In Relaxation Rate Research Articles

Unfolding of Alanine-Based Peptides Using Electron Spin Resonance Distance Measurements

We describe a scheme for tagging an alanine-based peptide with a Cu(II) and a nitroxide to measure unfolding transitions. The enhancement in longitudinal relaxation rate of the nitroxide due to the presence of Cu(II) was measured at physiological temperatures by pulsed electron spin resonance (ESR). The change in relaxation rate provided the average interspin distance between the Cu(II) and the nitroxide. Control experiments on a proline-based peptide verify the robustness of the method. The change in interspin distances with temperature for the alanine-based peptide is in accord with the change in helicity measured by circular dichroism. The data provide an opportunity to examine the unfolding process in polyalanine peptides. The distance in the folded state is in concordance with molecular dynamics. However, the ESR experiment measures an average distance of 17 A in the unfolded state, whereas molecular dynamics indicates a distance of 42 A if the unfolded geometry was a polyproline type II helix. Therefore, ESR demonstrates that the unfolded state of this alanine-based peptide is not an ideal extended polyproline type II helix.

Loss of strength in Ni3Al at elevated temperatures

Stress decrease above the stress peak temperature (750 K) is studied in ⟨123⟩ single crystals of Ni3(Al, 3 at.% Hf ). Two thermally activated deformation mechanisms are evidenced on the basis of stress relaxation and strain rate change experiments. From 500 to 1070 K, the continuity of the activation volume/temperature curves reveals a single mechanism of activation enthalpy 3.8 eV/atom and volume 90 b 3 at 810 K with an athermal stress of 330 MPa. Over the very same temperature interval, impurity or solute diffusion towards dislocation cores is evidenced through serrated yielding, peculiar shapes of stress–strain curves while changing the rate of straining and stress relaxation experiments. This complicates the identification of the deformation mechanism, which is likely connected with cube glide. From 1070 to 1270 K, the high-temperature mechanism has an activation enthalpy and volume of 4.8 eV/atom and 20 b 3, respectively, at 1250 K.

In vivo quantification of delayed gadolinium enhancement in the nucleus pulposus of human intervertebral disc

To quantify the delayed contrast agent enhancement in the nucleus pulposus of the intervertebral disc by means by T1 relaxation time measurements, and to correlate the enhancement with visual grading of disc degeneration. Diffusion of nutrients through the endplate is a key factor in tissue viability in the intervertebral disc. It can be simulated in vivo using magnetic resonance imaging (MRI) by measuring delayed gadolinium (Gd) enhancement of the disc. Twenty male volunteers underwent a lumbar spine examination at 1.5T. T2-weighted sagittal images were used to score disc degeneration. T1 relaxation times were measured before and 90 minutes after intravenous administration of Gd-DTPA-BMA by applying a series of sagittal single-slice inversion-recovery fast spin-echo (IR-FSE) scans. A total of 93 discs were analyzed. A statistically significant decrease in the T1 relaxation time of the nucleus pulposus was observed as a result of contrast-agent intake. The percentage change in the T1 relaxation rate for individual discs was up to 126%. A positive trend was observed between the change in the T1 relaxation rate and the grading of disc degeneration. Quantification of delayed enhancement of the intervertebral disc may provide a new means of studying alterations in degenerative disc disease (DDD) that explain the variation in diffusion into the intervertebral disc.

Acquisition of MR perfusion images and contrast-enhanced MR angiography in acute ischaemic stroke patients: which procedure should be done first?

Multimodal MRI for acute ischaemic stroke usually includes perfusion imaging (PI) and contrast-enhanced neck MR angiography (CE-MRA), as well as diffusion-weighted imaging and T2* weighted imaging. Because both PI and CE-MRA require the infusion of contrast medium, the likelihood exists that one study may conflict with the other due to the accumulation of previously injected contrast medium. The purpose of this study is to determine the appropriate order of PI and CE-MRA in this multimodal MRI protocol for evaluation of acute ischaemic stroke. We studied 35 patients with acute ischaemic stroke in the unilateral middle cerebral artery territory. 17 patients underwent CE-MRA following PI (group A) and 18 patients underwent PI following CE-MRA (group B). For qualitative analysis of the CE-MRA and colour-coded maps of the PI, two independent observers graded the image quality. Interobserver agreement was assessed using kappa statistics, and we assessed the statistical differences of imaging quality between groups A and B using the Mann-Whitney U-test). For the quantitative analysis of PI, two parameters--the maximum change in the transverse relaxation rate (DeltaR2(max)) and the relative signal drop (DeltaS/S(0))--were calculated from the time-signal intensity curve of an unaffected middle cerebral artery territory, and we compared the differences in the parameters of group A and B (t-test). Interobserver agreements for CE-MRA and PI were good. In the qualitative analysis of CE-MRA and PI, no significant difference was observed between groups A and B. In the quantitative analysis of PI, there were no relevant differences in DeltaR2(max) and DeltaS/S(0) between the two groups. In simultaneous CE-MRA and PI, there was no deterioration of diagnostic imaging quality with regard to the order of the two post-contrast sequences. They can be performed according to the preference of each institution.

In vivo quantification of regional myocardial blood flow: Validity of the fast‐exchange approximation for intravascular T1 contrast agent and long inversion time

In the present study we investigated the effects of water exchange between intra- and extravascular compartments on absolute quantification of regional myocardial blood flow (rMBF) using a saturation-recovery sequence with a rather long inversion time (TI, 176 ms) and a T1-shortening intravascular contrast agent (CMD-A2-Gd-DOTA). Data were acquired in normal and ischemically injured pigs, with radiolabeled microsphere flow measurements used as the gold standard. Five water exchange rates (fast, 6 Hz, 3 Hz, 1 Hz, and no exchange) were tested. The results demonstrate that the fast-exchange approximation may be appropriate for rMBF quantification using the described experimental setting. Relaxation rate change (DeltaR1) analysis improved the accuracy of the analysis of rMBF compared to the MR signal. In conclusion, the current protocol could provide sufficient accuracy for estimating rMBF assuming fast exchange and a linear relationship between signal and tissue concentration when quantification of precontrast T1 is not an option.

Activity of the Vascular-Disrupting Agent 5,6-Dimethylxanthenone-4-Acetic Acid against Human Head and Neck Carcinoma Xenografts

Head and neck squamous cell carcinomas (HNSCC) constitute a majority of the tumors of the upper aerodigestive tract and continue to present a significant therapeutic challenge. To explore the potential of vascular-targeted therapy in HNSCC, we investigated the antivascular, antitumor activity of the potent vascular-disrupting agent (VDA) 5,6-dimethylxanthenone-4-acetic acid (DMXAA) against two HNSCC xenografts with markedly different morphologic and vascular characteristics. Athymic nude mice bearing subcutaneous FaDu (human pharyngeal squamous cell carcinoma) and A253 (human submaxillary gland epidermoid carcinoma) tumors were administered a single dose of DMXAA (30 mg/kg, i.p). Changes in vascular function were evaluated 24 hours after treatment using contrast-enhanced magnetic resonance imaging (MRI) and immunohistochemistry (CD31). Signal enhancement (E) and change in longitudinal relaxation rates (ΔR1) were calculated to measure alterations in vascular perfusion. MRI showed a 78% and 49% reduction in vascular perfusion in FaDu and A253 xenografts, respectively. CD31-immunostaining of tumor sections revealed three-fold (FaDu) and two-fold (A253) reductions in microvessel density (MVD) 24 hours after treatment. DMXAA was equally effective against both xenograffs, with significant tumor growth inhibition observed 30 days after treatment. These results indicate that DMXAA may be beneficial in the management of HNSCC, alone or in combination with other treatments.

Source of nonlinearity in echo‐time‐dependent BOLD fMRI

Stimulation-induced changes in transverse relaxation rates can provide important insight into underlying physiological changes in blood oxygenation level-dependent (BOLD) contrast. It is often assumed that BOLD fractional signal change (DeltaS/S) is linearly dependent on echo time (TE). This relationship was evaluated at 9.4 T during visual stimulation in cats with gradient-echo (GE) and spin-echo (SE) echo-planar imaging (EPI). The TE dependence of GE DeltaS/S is close to linear in both the parenchyma and large vessel area at the cortical surface for TEs of 6-20 ms. However, this dependence is nonlinear for SE studies in the TE range of 16-70 ms unless a diffusion-weighting of b = 200 s/mm(2) is applied. This behavior is not caused by inflow effects, T(2)* decay during data acquisition in SE-EPI, or extravascular spin density changes. Our results are explained by a two-compartment model in which the extravascular contribution to DeltaS/S vs. TE is linear, while the intravascular contribution can be nonlinear depending on the magnetic field strength and TE. At 9.4 T, the large-vessel IV signal can be minimized by using long TE and/or moderate diffusion weighting. Thus, stimulation-induced relaxation rate changes should be carefully determined, and their physiological meanings should be interpreted with caution.

Influence of Human Serum Albumin on Longitudinal and Transverse Relaxation Rates (R1 and R2) of Magnetic Resonance Contrast Agents

Exogenous magnetic resonance (MR) contrast media (CM) are used to improve detection and delineation of physiological and pathologic structures. Temporary binding between CM and proteins such as human serum albumin (HSA) may alter the relaxation-enhancing properties of specific contrast agents. In this study, the presence and strength of HSA interaction with different CM was investigated. Three contrast agents were chosen: Gd-DTPA, Gd-BT-DO3A, and Gd-BOPTA, each of which is known to have a different protein interaction. Samples were prepared using 7 different HSA concentrations, all at a constant CM concentration of 0.5 mmol/L. The relaxation rates, R1 and R2, of each sample were measured at 1.5 T. Virtual docking studies were performed to estimate the number of high affinity-binding sites of Gd-BOPTA and the surface of the HSA dimer. Gd-BOPTA caused the greatest increase in R1 and R2, which followed an exponential dependency with increasing HSA concentration. Between the range of 0 and 7 g/dL of HSA, Gd-DTPA and Gd-BT-DO3A showed a relative change in both relaxation rates of approximately 13% and 22% for R1 and 26% and 30% for R2, respectively. In contrast, Gd-BOPTA demonstrated a relative increase of approximately 108% and 363% for R1 and R2, respectively. Changes of HSA concentration within physiological range (3.5-5.5 g/dL) resulted in an increase of R1 and R2 of approximately 40% when using Gd-BOPTA. The docking study revealed that approximately 10 small hydrophobic pockets exist on the HSA surface where the aromatic tail of Gd-BOPTA can fit in and a stronger noncovalent binding can occur compared with Gd-DTPA and Gd-BT-DO3A. Relaxation rates of Gd-BOPTA showed a strong dependency on HSA. In contrast, Gd-DTPA and Gd-BT-DO3A demonstrated little or no relevant dependency. On the basis of these results, the influence of serum protein concentration should be considered in both research studies and in clinical use.

Advances in Clinical 3-Tesla Neuroimaging

Three-tesla magnetic resonance (MR) imaging represents one of the major forefronts of diagnostic neuroradiology today. Heat deposition, changes in T1 relaxation rates, susceptibility differences, and greater inherent sensitivity to motion artifacts represent challenges to clinical implementation. However, the situation appears remarkably similar to that encountered almost 15 years ago as the field of MR transitioned from 0.3-0.6 T to 1.5 T units. Current-generation 3 T MR units already provide markedly improved imaging of the brain as compared with 1.5 T units. This is illustrated in the article that follows, together with many of the advanced techniques now available and in the pipeline to deal with the difficulties inherent at 3 T.

Quantitative study of changes in oxidative metabolism during visual stimulation using absolute relaxation rates

In the context of quantitative functional MRI (fMRI), deoxyhemoglobin (dHb) content is the essential physiological parameter for calibrating the blood oxygenation level-dependent (BOLD) signal. In studies on humans, the baseline dHb content or its equivalent has been evaluated indirectly by means of carbon dioxide breathing as a physiological reference condition. In this study with normal volunteers, quantitative mapping of baseline dHb content was performed in a direct manner by measuring the reversible contribution of the effective transverse relaxation rate. The BOLD signal change in the visual cortex during 8 Hz flicker visual stimulation was calibrated based on the quantitative map of baseline dHb content. The calibrated relaxation rate change that represents the stimulation-induced fractional change of dHb content decreased by 14% within the activated visual cortex. Simultaneous measurement of cerebral blood flow (CBF) with BOLD showed an increase of 59%. From the calibrated relaxation rate and CBF changes, the cerebral metabolic rate of oxygen (CMRO2) was calculated to increase by 19-28% within the activated visual cortex. The ratio of the CBF increase to the CMRO2 increase was 2-3:1, which agreed well with results of similar quantitative fMRI studies for humans. The method proposed here for quantitative evaluation of the BOLD signal may be applicable not only to fMRI for normal human subjects, but also to physiologically altered or diseased states, because it requires no physiological perturbation.

Differential Contribution of Troponin I Phosphorylation Sites to the Endothelin-modulated Contractile Response

Cardiac troponin I is a phosphorylation target for endothelin-activated protein kinase C. Earlier work in cardiac myocytes expressing nonphosphorylatable slow skeletal troponin I provided evidence that protein kinase C-mediated cardiac troponin I phosphorylation accelerates relaxation. However, replacement with the slow skeletal isoform also alters the myofilament pH response and the Ca2+ transient, which could influence endothelin-mediated relaxation. Here, differences in the Ca2+ transient could not explain the divergent relaxation response to endothelin in myocytes expressing cardiac versus slow skeletal troponin I nor could activation of Na+/H+ exchange. Three separate clusters within cardiac troponin I are phosphorylated by protein kinase C, and we set out to determine the contribution of the Thr144 and Ser23/Ser24 clusters to the endothelin-mediated contractile response. Myocyte replacement with a cardiac troponin I containing a Thr144 substituted with the Pro residue found in slow skeletal troponin I resulted in prolonged relaxation in response to acute endothelin compared with control myocytes. Ser23/Ser24 also is a target for protein kinase C phosphorylation of purified cardiac troponin I, and although this cluster was not acutely phosphorylated in intact myocytes, significant phosphorylation developed within 1 h after adding endothelin. Replacement of Ser23/Ser24 with Ala indicated that this cluster contributes significantly to relaxation during more prolonged endothelin stimulation. Overall, results with these mutants provide evidence that Thr144 plays an important role in the acute acceleration of relaxation, whereas Ser23/Ser24 contributes to relaxation during more prolonged activation of protein kinase C by endothelin.

Magnetic Resonance Imaging Visualization of Hyaluronidase in Ovarian Carcinoma

Hyaluronan, a high molecular weight, negatively charged polysaccharide, is a major constituent of the extracellular matrix. High molecular weight hyaluronan is antiangiogenic, but its degradation by hyaluronidase generates proangiogenic breakdown products. Thus, by expression of hyaluronidase, cancer cells can tilt the angiogenic balance of their microenvironment. Indeed, hyaluronidase-mediated breakdown of hyaluronan correlates with aggressiveness and invasiveness of ovarian cancer metastasis and with tumor angiogenesis. The goal of this work was to develop a novel smart contrast material for detection of hyaluronidase activity by magnetic resonance imaging (MRI). Gadolinium-diethylenetriaminepentaacetic acid (GdDTPA) covalently linked to hyaluronan on the surface of agarose beads showed attenuated relaxivity. Hyaluronidase, either purified from bovine testes or secreted by ES-2 and OVCAR-3 human epithelial ovarian carcinoma cells, activated the hyaluronan-GdDTPA-beads by rapidly altering the R1 and R2 relaxation rates. The change in relaxation rates was consistent with the different levels of biologically active hyaluronidase secreted by those cells. Hyaluronan-GdDTPA-beads were further used for demonstration of MRI detection of hyaluronidase activity in the proximity of s.c. ES-2 ovarian carcinoma tumors in nude mice. Thus, hyaluronan-GdDTPA-beads could allow noninvasive molecular imaging of hyaluronidase-mediated tilt of the peritumor angiogenic balance.

Preliminary dose response study of a gel dosimeter using 2-Hydroxyethyl Methacrylate (HEMA)

In this work we present a gel dosimeter based on 2-Hydroxyethyl Methacrylate (HEMA). The gel dosimeter is manufactured in normal atmospheric oxygen (normoxic) and undergoes a measurable change after irradiation. The gel is shown to provide a signal to noise ratio of up to at least 35 and have a linear change in transverse relaxation rate up to 70 Gy when measured with magnetic resonance imaging.

A study of the NMR relaxation mechanisms of ABCl 3 ( A=Rb, Cs, B=Cd, Mn) single crystals with the electric quadrupole and the electric magnetic types

The 87Rb and 133Cs spin-lattice relaxation rates of RbCdCl 3 and CsCdCl 3 single crystals grown using the slow evaporation method were measured over the temperature range 160–400 K. The changes in the 87Rb spin-lattice relaxation rate near 340, 363, and 395 K correspond to phase transitions of the RbCdCl 3 crystal. The jump in T 1 −1 at 395 K is due to a shortening in the c-direction as a result of a phase transition from a cubic to a tetragonal structure. We suggest that the cubic Rb environment is favored above 395 K due to the fast motions and soft modes, which cause relaxation and average out the quadrupolar splittings. The temperature dependence of the relaxation rate below 340 K in RbCdCl 3 can be represented by T 1 - 1 = α T 2 and is thus in accordance with a Raman process. The 133Cs nuclei in the CsCdCl 3 crystal produce only one resonance line, which indicates that the local structure around the Cs atoms is cubic. The temperature dependence of the relaxation rate of the Cs nuclei can also be described with the quadratic equation T 1 - 1 = α T 2 . In the case of the RbCdCl 3 and CsCdCl 3 crystals, which are of electric quadrupolar type, their relaxations proceed via Raman processes, whereas in RbMnCl 3 and CsMnCl 3 crystals, which are of magnetic relaxation type, the relaxations proceed via single phonon processes. Therefore, the relaxation mechanisms of these different types of ABCl 3 crystals (quadrupolar and magnetic) are completely different NMR behavior.

Nuclear-magnetic-resonance interaction mechanism in Rb2CoCl4 single crystals with the electric magnetic type

The Rb87 spin-lattice relaxation time of Rb2CoCl4 single crystals grown using the slow evaporation method was measured using nuclear magnetic resonance. The recovery trace for the central line of Rb87 with dominant magnetic relaxation cannot be represented with a single exponential function, but can be represented with a linear combination of two exponential functions. The change in the Rb87 spin-lattice relaxation rate near Tc1 corresponds to the ferroelectric to incommensurate phase transition. There is a weak anomalous contribution to T1, and this seems to be the only detectable influence of a structural phase transition. The temperature dependence of T1−1 near Ti is more or less continuous and is not affected by the normal-incommensurate phase transition. For T>Ti, the spin-lattice relaxation rate is governed by molecular motion as described by the Bloembergen-Purcell-Pound theory. This behavior is different to that found for Rb in Rb2ZnCl4. The phase-transition temperatures of the Rb2CoCl4 and Rb2ZnCl4 single crystals are quite similar, but their phase-transition mechanisms are different. The nuclear-magnetic-resonance (NMR) interaction mechanism in Rb2ZnCl4 is well known to be of the electric quadrupolar type whereas in Rb2CoCl4 it is of magnetic origin. Therefore a completely different NMR behavior is obtained in the two crystals.

Relaxation of atomic polarization in paraffin-coated cesium vapor cells

The relaxation of atomic polarization in buffer-gas-free, paraffin-coated cesium vapor cells is studied using a variation on Franzen's technique of ``relaxation in the dark'' [Franzen, Phys. Rev. {\bf 115}, 850 (1959)]. In the present experiment, narrow-band, circularly polarized pump light, resonant with the Cs D2 transition, orients atoms along a longitudinal magnetic field, and time-dependent optical rotation of linearly polarized probe light is measured to determine the relaxation rates of the atomic orientation of a particular hyperfine level. The change in relaxation rates during light-induced atomic desorption (LIAD) is studied. No significant change in the spin relaxation rate during LIAD is found beyond that expected from the faster rate of spin-exchange collisions due to the increase in Cs density.

304 Detection of Vascular Expression of E-Selectin in Vivo by Mr Imaging

Background: We aimed to develop a contrast agent suitable for targeting to E-selectin expressed on activated vascular endothelium in an in vivo model of inflammation and detection by magnetic resonance (MR) imaging.Methods: Anti-murine E-selectin F(ab')2 monoclonal antibody (mAb) (MES-1) was conjugated with ultrasmall superparamagnetic iron oxide nanoparticles (USPIO). Flow cytometry, PERL staining for iron, and MR imaging were performed using CHO cells expressing mouse E-selectin (CHO-E) to detect binding of the conjugate in vitro, and a mouse model of contact hypersensitivity to oxazolone in the ear was used to investigate the in vivo characteristics of the MES-1-USPIO, with serial imaging being performed using an Oxford/Varian 9.4T MR imaging system with a custom receive-only coil. Tissue sections were stained to define the distribution of E-selectin expression and the localisation of the MES-1-USPIO conjugate.Results: The MES-1-USPIO was shown to bind to CHO-E in vitro. Following injection of MES-1-USPIO in vivo, distinct changes in the R2 relaxation rate (1/T2) characteristics could be detected in inflamed ears compared to controls. Histological analysis confirmed the vascular endothelial distribution of the MES-1-USPIO.Conclusions: E-selectin expression in vivo can be selectively and directly imaged non-invasively with magnetic resonance. This molecular imaging tool has the potential to be useful for the diagnosis and monitoring of early or occult inflammation, and may provide an attractive alternative to established clinical investigations such as the use of radiolabelled leukocytes. In addition, such an agent may have value in the investigation of some solid tumours and metastases, either by targeting tumour-associated neovasculature or tumour cells expressing E-selectin.

Improved quantitative dynamic regional oxygen‐enhanced pulmonary imaging using image registration

Oxygen-enhanced MR imaging has been demonstrated in a number of recent studies as a potential method to visualize regional ventilation in the lung. A quantitative pixel-by-pixel analysis is hampered by motion and volume change due to breathing. In this study, image registration via active shape modeling is shown to produce significant improvements in the regional analysis of both static and dynamic oxygen-enhanced pulmonary MRI for five normal volunteers. The method enables the calculation of regional change in relaxation rate between breathing air and 100% oxygen, which is proportional to the change in regional oxygen concentration, and regional oxygen wash-in and wash-out time constants. Registration-corrected mapping of these parameters is likely to provide improved information in the regional assessment of a range of lung diseases.

Routine clinical brain MRI sequences for use at 3.0 Tesla

To establish image parameters for some routine clinical brain MRI pulse sequences at 3.0 T with the goal of maintaining, as much as possible, the well-characterized 1.5-T image contrast characteristics for daily clinical diagnosis, while benefiting from the increased signal to noise at higher field. A total of 10 healthy subjects were scanned on 1.5-T and 3.0-T systems for T(1) and T(2) relaxation time measurements of major gray and white matter structures. The relaxation times were subsequently used to determine 3.0-T acquisition parameters for spin-echo (SE), T(1)-weighted, fast spin echo (FSE) or turbo spin echo (TSE), T(2)-weighted, and fluid-attenuated inversion recovery (FLAIR) pulse sequences that give image characteristics comparable to 1.5 T, to facilitate routine clinical diagnostics. Application of the routine clinical sequences was performed in 10 subjects, five normal subjects and five patients with various pathologies. T(1) and T(2) relaxation times were, respectively, 14% to 30% longer and 12% to 19% shorter at 3.0 T when compared to the values at 1.5 T, depending on the region evaluated. When using appropriate parameters, routine clinical images acquired at 3.0 T showed similar image characteristics to those obtained at 1.5 T, but with higher signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR), which can be used to reduce the number of averages and scan times. Recommended imaging parameters for these sequences are provided. When parameters are adjusted for changes in relaxation rates, routine clinical scans at 3.0 T can provide similar image appearance as 1.5 T, but with superior image quality and/or increased speed.

A simple model of entropy relaxation for explaining effective activation energy behavior below the glass transition temperature

Strong changes in relaxation rates observed at the glass transition region are frequently explained in terms of a physical singularity of the molecular motions. We show that the unexpected trends and values for activation energy and preexponential factor of the relaxation time tau, obtained at the glass transition from the analysis of the thermally stimulated current signal, result from the use of the Arrhenius law for treating the experimental data obtained in nonstationary experimental conditions. We then demonstrate that a simple model of structural relaxation based on a time dependent configurational entropy and Adam-Gibbs relaxation time is sufficient to explain the experimental behavior, without invoking a kinetic singularity at the glass transition region. The pronounced variation of the effective activation energy appears as a dynamic signature of entropy relaxation that governs the change of relaxation time in nonstationary conditions. A connection is demonstrated between the peak of apparent activation energy measured in nonequilibrium dielectric techniques, with the overshoot of the dynamic specific heat that is obtained in calorimetry techniques.