Apparent Relaxation Rate Research Articles

Ten-Fold Solvent Kinetic Isotope Effect for the Nonradiative Relaxation of the Aqueous Ferrate(VI) Ion.

Hypervalent iron intermediates have been invoked in the catalytic cycles of many metalloproteins, and thus, it is crucial to understand how the coupling between such species and their environment can impact their chemical and physical properties in such contexts. In this work, we take advantage of the solvent kinetic isotope effect (SKIE) to gain insight into the nonradiative deactivation of electronic excited states of the aqueous ferrate(VI) ion. We observe an exceptionally large SKIE of 9.7 for the nanosecond-scale relaxation of the lowest energy triplet ligand field state to the ground state. Proton inventory studies demonstrate that a single solvent O-H bond is coupled to the ion during deactivation, likely due to the sparse vibrational structure of ferrate(VI). Such a mechanism is consistent with that reported for the deactivation of f-f excited states of aqueous trivalent lanthanides, which exhibit comparably large SKIE values. This phenomenon is ascribed entirely to dissipation of energy into a higher overtone of a solvent acceptor mode, as any impact on the apparent relaxation rate due to a change in solvent viscosity is negligible.

Quantitative Blood Oxygenation Level Dependent Magnetic Resonance Imaging for Estimating Intra-renal Oxygen Availability Demonstrates Kidneys Are Hypoxemic in Human CKD

Kidney blood oxygenation level dependent (BOLD) magnetic resonance imaging (MRI) has shown great promise in evaluating relative oxygen availability. This method is quite efficacious in evaluating acute responses to physiological and pharmacologic maneuvers. Its outcome parameter, R2∗ is defined as the apparent spin-spin relaxation rate measured in the presence of magnetic susceptibility differences and it is measured using gradient echo MRI. Although associations between R2∗ and renal function decline have been described, it remains uncertain to what extent R2∗ is a true reflection of tissue oxygenation. This is primarily because of not taking into account the confounding factors, especially fractional blood volume (fBV) in tissue. This case-control study included 7 healthy controls and 6 patients with diabetes and chronic kidney disease (CKD). Using data before and after administration of ferumoxytol, a blood pool MRI contrast media, the fBVs in kidney cortex and medulla were measured. This pilot study independently measured fBV in kidney cortex (0.23 ± 0.03 vs. 0.17 ± 0.03) and medulla (0.36 ± 0.08 vs. 0.25 ± 0.03) in a small number of healthy controls (n= 7) versus CKD (n= 6). These were then combined with BOLD MRI measurements to estimate oxygen saturation of hemoglobin (StO2) (0.87 ± 0.03 vs. 0.72 ± 0.10 in cortex; 0.82 ± 0.05 vs. 0.72 ± 0.06 in medulla) and partial pressure of oxygen in blood (bloodPO2) (55.4 ± 6.5 vs. 38.4 ± 7.6 mmHg in cortex; 48.4 ± 6.2 vs. 38.1 ± 4.5 mmHg in medulla) in control versus CKD. The results for the first time demonstrate that cortex is normoxemic in controls and moderately hypoxemic in CKD. In the medulla, it is mildly hypoxemic in controls and moderately hypoxemic in CKD. Whereas fBV, StO2, and bloodPO2 were strongly associated with estimated glomerular filtration rate (eGFR), R2∗ was not. Our results support the feasibility of quantitatively assessing oxygen availability using noninvasive quantitative BOLD MRI that could be translated to the clinic.

Effectiveness of functional magnetic resonance imaging for early identification of chronic kidney disease: A systematic review and network meta-analysis

PurposeThe commonly used clinical indicators are not sensitive enough on detecting early chronic kidney disease (CKD), whether functional magnetic resonance imaging (fMRI) can be regarded as a new noninvasive method to identify early stages of CKD and even different stages remains unknown. We performed a network meta-analysis to explore the question. MethodsFive databases were searched to identify eligible articles from 2000 to 2022. The outcome indicators were imaging biomarkers of fMRI techniques, including apparent diffusion coefficient (ADC) by diffusion-weighted imaging (DWI), fractional anisotropy (FA) by diffusion tensor imaging (DTI), diffusion coefficient (D), pseudodiffusion coefficient (D*), and perfusion fraction (f) by intravoxel incoherent motion imaging (IVIM), and apparent relaxation rate (R2*) by blood oxygen level-dependent (BOLD). ResultsA total of 21 articles with 1472 patients were included for analysis. Cortical FA, f, and R2* values in CKD stages 1–2 were found statistically different with healthy controls (mean difference (MD), −0.03, 95% confidence interval (CI) −0.05, −0.01; MD, −0.04, 95% CI −0.06, −0.02; MD, 2.22, 95% CI 0.87, 3.57, respectively), and cortical ADC values were significantly different among different CKD stages (stages 3 and 1–2: MD, −0.15, 95% CI −0.23, −0.06; stages 4–5 and 3: MD −0.27, 95% CI −0.39, −0.14). ConclusionThe results indicated fMRI techniques had great efficacy in assessing early stages and different stages of CKD, among which DTI, IVIM, and BOLD exerted great superiority in differentiating early CKD patients from the general population, while DWI showed the advantage in distinguishing different CKD stages.

Developmental trajectory of magnetic susceptibility in the healthy rhesus macaque brain.

Quantitative susceptibility mapping (QSM) is used to quantify iron deposition in non-human primates in our study. Although QSM has many applications in detecting iron deposits in the human brain, including the distribution of iron deposits in specific brain regions, the change of iron deposition with aging, and the comparison of iron deposits between diseased groups and healthy controls, few studies have applied QSM to non-human primates, while most animal brain experiments focus on biochemical and anatomical results instead of non-invasive experiments. Additionally, brain imaging in children's research is difficult, but can be substituted using young rhesus monkeys, which are very similar to humans, as research animals. Therefore, understanding the relationship between iron deposition and age in rhesus macaques' brains can offer insights into both the developmental trajectory of magnetic susceptibility in the animal model and the correlated evidence in children's research. Twenty-three healthy rhesus macaque monkeys (23 ± 7.85 years, range 2-29 years) were included in this research. Seven regions of interest (ROIs-globus pallidus, substantia nigra, dentate nucleus, caudate nucleus, putamen, thalamus, red nucleus) have been analyzed in terms of QSM and R2 * (apparent relaxation rate). Susceptibility in most ROIs correlated significantly with the growth of age, similarly to the results for R2 *, but showed different trends in the thalamus and red nucleus, which may be caused by the different sensitivities of myelination and iron deposition in R2 * and QSM analysis. By assessing the correlation between iron content and age in healthy rhesus macaques' brains using QSM, we provide a piece of pilot information on normality for advanced animal disease models. Meanwhile, this study also could serve as the normative basis for further clinical studies using QSM for iron content quantification. Due to the comparison of the susceptibility on the same experimental objects, this research can also provide practical support for future research on characteristics for QSM and R2 *.

Comprehensive Assessment of Protein and Excipient Stability in Biopharmaceutical Formulations Using 1H NMR Spectroscopy.

Biopharmaceutical proteins are important drug therapies in the treatment of a range of diseases. Proteins, such as antibodies (Abs) and peptides, are prone to chemical and physical degradation, particularly at the high concentrations currently sought for subcutaneous injections, and so formulation conditions, including buffers and excipients, must be optimized to minimize such instabilities. Therefore, both the protein and small molecule content of biopharmaceutical formulations and their stability are critical to a treatment’s success. However, assessing all aspects of protein and small molecule stability currently requires a large number of analytical techniques, most of which involve sample dilution or other manipulations which may themselves distort sample behavior. Here, we demonstrate the application of 1H nuclear magnetic resonance (NMR) spectroscopy to study both protein and small molecule content and stability in situ in high-concentration (100 mg/mL) Ab formulations. We show that protein degradation (aggregation or fragmentation) can be detected as changes in 1D 1H NMR signal intensity, while apparent relaxation rates are specifically sensitive to Ab fragmentation. Simultaneously, relaxation-filtered spectra reveal the presence and degradation of small molecule components such as excipients, as well as changes in general solution properties, such as pH. 1H NMR spectroscopy can thus provide a holistic overview of biopharmaceutical formulation content and stability, providing a preliminary characterization of degradation and acting as a triaging step to guide further analytical techniques.

Real-time measurement of diffusion exchange rate in biological tissue

Diffusion exchange spectroscopy (DEXSY) provides a means to isolate the signal attenuation associated with exchange from other sources of signal loss. With the total diffusion weighting b1+b2=bs held constant, DEXSY signals acquired with b1=0 or b2=0 have no exchange weighting, while a DEXSY signal acquired with b1=b2 has maximal exchange weighting. The exchange rate can be estimated by fitting a diffusion exchange model to signals acquired with variable mixing times. Conventionally, acquired signals are normalized by a signal with b1=0 and b2=0 to remove the decay due to spin–lattice relaxation. Instead, division by a signal with equal bs but b1=0 or b2=0 reduces spin–lattice relaxation weighting of the apparent exchange rate (AXR). Furthermore, apparent diffusion-weighted R1 relaxation rates can be estimated from non-exchange-weighted DEXSY signals. Estimated R1 values are utilized to remove signal decay due to spin–lattice relaxation from exchange-weighted signals, permitting a more precise estimate of AXR with less data. Data reduction methods are proposed and tested with regards to statistical accuracy and precision of AXR estimates on simulated and experimental data. Simulations show that the methods are capable of accurately measuring the ground-truth exchange rate. The methods remain accurate even when the assumption that DEXSY signals attenuate with b is violated, as occurs for restricted diffusion. Experimental data was collected from fixed neonatal mouse spinal cord samples at 25 and 7°C using the strong static magnetic field gradient produced by a single-sided permanent magnet (i.e., an NMR MOUSE). The most rapid method for exchange measurements requires only five data points (an 80 s experiment as implemented) and achieves a similar level of accuracy and precision to the baseline method using 44 data points. This represents a significant improvement in acquisition speed, overcoming a barrier which has limited the use of DEXSY on living specimen.

EARLY ASSESSMENT OF RENAL TRANSPLANTS USING BOLD-MRI: PROMISING RESULTS.

Non-invasive evaluation of renal transplant function is essential to minimize and manage renal rejection. A computer-assisted diagnostic (CAD) system was developed to evaluate kidney function post-transplantation. The developed CAD system utilizes the amount of blood-oxygenation extracted from 3D (2D + time) blood oxygen level-dependent magnetic resonance imaging (BOLD-MRI) to estimate renal function. BOLD-MRI scans were acquired at five different echo-times (2, 7, 12, 17, and 22) ms from 15 transplant patients. The developed CAD system first segments kidneys using the level-sets method followed by estimation of the amount of deoxyhemoglobin, also known as apparent relaxation rate (R2*). These R2* estimates were used as discriminatory features (global features (mean R2*) and local features (pixel-wise R2*)) to train and test state-of-the-art machine learning classifiers to differentiate between non-rejection (NR) and acute renal rejection. Using a leave-one-out cross-validation approach along with an artificial neural network (ANN) classifier, the CAD system demonstrated 93.3% accuracy, 100% sensitivity, and 90% specificity in distinguishing AR from non-rejection . These preliminary results demonstrate the efficacy of the CAD system to detect renal allograft status non-invasively.

Resveratrol Protects Against Post-Contrast Acute Kidney Injury in Rabbits With Diabetic Nephropathy.

Resveratrol (Res) is a multi-functional polyphenol compound that has protective functions in acute kidney diseases. Here, we examined whether the resveratrol could ameliorate post-contrast acute kidney injury (PC–AKI) following diabetic nephropathy (DN), and explored any underlying mechanism(s) in vivo and in vitro. Twenty-four rabbits with DN were randomly divided into four groups: control (Cont), resveratrol (Res), iohexol (PC–AKI), and resveratrol plus iohexol (Res+PC–AKI) groups. Functional magnetic resonance imaging, renal histology, blood and urinary biomarkers, silent information regulator l (SIRT1), peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α), hypoxia-inducible transcription factor-1α (HIF-1α), and apoptosis-associated protein expression were assessed ex vivo. For in vitro experiments, renal tubular epithelial (HK-2) cells subjected to high glucose conditions were treated with resveratrol, Ex527, an SIRT1 inhibitor, or 2-methoxyestradiol (2-MeOE2), HIF-1α inhibitor, before treatment with iohexol. With regard to the rabbit model of acute renal injury in DN, compared to the PC–AKI group, the Res+PC–AKI group showed decreased levels of cystatin C and urinary neutrophil gelatinase-associated lipocalin, increased pure molecular diffusion (D) and the fraction of water flowing in capillaries (f), a decreased apparent relaxation rate (R2*), renal injury score and apoptosis rate, increased protein expression levels of SIRT1 and PGC-1α, and decreased levels of HIF-1α and apoptosis-associated protein. In addition, iohexol decreased HK-2 cell survival and increased the cell apoptosis rate; results were reversed after treating cells with resveratrol. Resveratrol reduced renal hypoxia, mitochondrial dysfunction and renal tubular cell apoptosis by activating SIRT1–PGC–1α–HIF-1α signaling pathways in PC–AKI with DN.

General mathematical formula for near equilibrium relaxation kinetics of basic enzyme reactions and its applications to find conformational selection steps

A general mathematical formula of basic enzyme reactions was derived with nearly no dependence on conditions nor assumptions on relaxation kinetic processes near equilibrium in a simple single-substrate-single-product enzyme reaction. The new formula gives precise relationships between the rate constants of the elementary reaction steps and the apparent relaxation rate constant, rather than the initial velocity that is generally used to determine enzymatic parameters according to the Michaelis–Menten theory. The present formula is shown to be complementary to the Michaelis–Menten formulae in a sense that the initial velocity and the relaxation rate constant data together could determine the enzyme–substrate dissociation constant KES, which has been usually conditionally approximated by the Michaelis constant KM within the framework of the Michaelis–Menten formulae. We also describe relaxation kinetics of enzyme reactions that include the conformational selection processes, in which only one enzymatic conformer among a conformational ensemble can bind with either the substrate or product. The present mathematical approaches, together with numerical computation analyses, suggested that the presence of conformational selection steps in enzymatic reactions can be experimentally detected simply by enzymatic assays with catalytic amounts of enzyme.

Chemical exchange saturation transfer MRI serves as predictor of early progression in glioblastoma patients.

PurposeTo prospectively investigate chemical exchange saturation transfer (CEST) MRI in glioblastoma patients as predictor of early tumor progression after first-line treatment.Experimental DesignTwenty previously untreated glioblastoma patients underwent CEST MRI employing a 7T whole-body scanner. Nuclear Overhauser effect (NOE) as well as amide proton transfer (APT) CEST signals were isolated using Lorentzian difference (LD) analysis and relaxation compensated by the apparent exchange-dependent relaxation rate (AREX) evaluation. Additionally, NOE-weighted asymmetric magnetic transfer ratio (MTRasym) and downfield-NOE-suppressed APT (dns-APT) were calculated. Patient response to consecutive treatment was determined according to the RANO criteria. Mean signal intensities of each contrast in the whole tumor area were compared between early-progressive and stable disease.ResultsPre-treatment tumor signal intensity differed significantly regarding responsiveness to first-line therapy in NOE-LD (p = 0.0001), NOE-weighted MTRasym (p = 0.0186) and dns-APT (p = 0.0328) contrasts. Hence, significant prediction of early progression was possible employing NOE-LD (AUC = 0.98, p = 0.0005), NOE-weighted MTRasym (AUC = 0.83, p = 0.0166) and dns-APT (AUC = 0.80, p = 0.0318). The NOE-LD provided the highest sensitivity (91%) and specificity (100%).ConclusionsCEST derived contrasts, particularly NOE-weighted imaging and dns-APT, yielded significant predictors of early progression after fist-line therapy in glioblastoma. Therefore, CEST MRI might be considered as non-invasive tool for customization of treatment in the future.

EPR-based oximetric imaging: a combination of single point-based spatial encoding and T1 weighting.

Spin-lattice relaxation rate (R1 )-based time-domain EPR oximetry is reported for in vivo applications using a paramagnetic probe, a trityl-based Oxo71. The R1 dependence of the trityl probe Oxo71 on partial oxygen pressure (pO2 ) was assessed using single-point imaging mode of spatial encoding combined with rapid repetition, similar to T1 -weighted MRI, for which R1 was determined from 22 repetition times ranging from 2.1 to 40.0 μs at 300 MHz. The pO2 maps of a phantom with 3 tubes containing 2 mM Oxo71 solutions equilibrated at 0%, 2%, and 5% oxygen were determined by R1 and apparent spin-spin relaxation rate ( R2*) simultaneously. The pO2 maps derived from R1 and R2* agreed with the known pO2 levels in the tubes of Oxo71. However, the histograms of pO2 revealed that R1 offers better pO2 resolution than R2* in low pO2 regions. The SDs of pixels at 2% pO2 (15.2 mmHg) were about 5 times lower in R1 -based estimation than R2*-based estimation (mean ± SD: 13.9 ± 1.77 mmHg and 18.3 ± 8.70 mmHg, respectively). The in vivo pO2 map obtained from R1 -based assessment displayed a homogeneous profile in low pO2 regions in tumor xenografts, consistent with previous reports on R2*-based oximetric imaging. The scan time to obtain the R1 map can be significantly reduced using 3 repetition times ranging from 4.0 to 12.0 μs. Using the single-point imaging modality, R1 -based oximetry imaging with useful spatial and oxygen resolutions for small animals was demonstrated.

Enhanced spectral profile in the study of Doppler-broadened Rydberg ensembles

Combination of the electromagnetically-induced-transparency (EIT) effect and Rydberg-state atoms has attracted great attention recently due to its potential application in the photon-photon interaction or qubit operation. In this work, we studied the Rydberg-EIT spectra with room-temperature 87Rb atoms. Spectroscopic data under various experimental parameters all showed that the contrast of EIT transparency as a function of the probe field intensity is initially enhanced, reaches a maximum value and then decays gradually. The contrast of spectral profile at the optimum probe field intensity is enhanced by 2–4 times as compared with that at weakest intensity. Moreover, the signal-to-noise ratio of the spectrum can potentially be improved by 1 to 2 orders of magnitude. We provided a theoretical model to explain this behavior and clarified its underlying mechanism. Our work overcomes the obstacle of weak signal in the Rydberg-EIT spectrum caused by an apparent relaxation rate of the Rydberg polariton and weak coupling transition strength, and provides the useful knowledge for the Rydberg-EIT study.

An analytical model which determines the apparent T1 for Modified Look-Locker Inversion Recovery – Analysis of the longitudinal relaxation under the influence of discontinuous balanced (classical MOLLI) and spoiled gradient echo readouts

Quantitative nuclear magnetic resonance imaging (MRI) shifts more and more into the focus of clinical research. Especially determination of relaxation times without/and with contrast agents becomes the foundation of tissue characterization, e.g. in cardiac MRI for myocardial fibrosis. Techniques which assess longitudinal relaxation times rely on repetitive application of readout modules, which are interrupted by free relaxation periods, e.g. the Modified Look-Locker Inversion Recovery = MOLLI sequence. These discontinuous sequences reveal an apparent relaxation time, and, by techniques extrapolated from continuous readout sequences, a putative real T1 is determined. What is missing is a rigorous analysis of the dependence of the apparent relaxation time on its real partner, readout sequence parameters and biological parameters as heart rate. This is provided in this paper for the discontinuous balanced steady state free precession (bSSFP) and spoiled gradient echo readouts. It turns out that the apparent longitudinal relaxation rate is the time average of the relaxation rates during the readout module, and free relaxation period. Knowing the heart rate our results vice versa allow to determine the real T1 from its measured apparent partner.

A theoretical framework for determining cerebral vascular function and heterogeneity from dynamic susceptibility contrast MRI

Mapping the complex heterogeneity of vascular tissue in the brain is important for understanding cerebrovascular disease. In this translational study, we build on previous work using vessel architectural imaging (VAI) and present a theoretical framework for determining cerebral vascular function and heterogeneity from dynamic susceptibility contrast magnetic resonance imaging (MRI). Our tissue model covers realistic structural architectures for vessel branching and orientations, as well as a range of hemodynamic scenarios for blood flow, capillary transit times and oxygenation. In a typical image voxel, our findings show that the apparent MRI relaxation rates are independent of the mean vessel orientation and that the vortex area, a VAI-based parameter, is determined by the relative oxygen saturation level and the vessel branching of the tissue. Finally, in both simulated and patient data, we show that the relative distributions of the vortex area parameter as a function of capillary transit times show unique characteristics in normal-appearing white and gray matter tissue, whereas tumour-voxels in comparison display a heterogeneous distribution. Collectively, our study presents a comprehensive framework that may serve as a roadmap for in vivo and per-voxel determination of vascular status and heterogeneity in cerebral tissue.

Blood Oxygenation Level-Dependent MRI to Assess Renal Oxygenation in Renal Diseases: Progresses and Challenges.

BOLD-MRI (blood oxygenation-level dependent magnetic resonance imaging) allows non-invasive measurement of renal tissue oxygenation in humans, without the need for contrast products. BOLD-MRI uses the fact that magnetic properties of hemoglobin depend of its oxygenated state:: the higher local deoxyhemoglobin, the higher the so called apparent relaxation rate R2* (sec−1), and the lower local tissue oxygen content. Several factors other than deoxyhemoglobin (such as hydration status, dietary sodium intake, and susceptibility effects) influence the BOLD signal, and need to be taken into account when interpreting results. The last 5 years have witnessed important improvements in the standardization of these factors, and the appearance of new, highly reproducible analysis techniques of BOLD-images, that are reviewed in this article. Using these new BOLD-MRI analysis techniques, it has recently been shown that persons suffering from chronic kidney diseases (CKD) have lower cortical oxygenation than normotensive controls, thus confirming the chronic hypoxia hypothesis. The acute alterations in R2* after the administration of furosemide are smaller in CKD, and represent an estimate of the oxygen-dependent tubular transport of sodium. BOLD-MRI-alone or in combination with other functional MRI methods- can be used to monitor the renal effects of drugs, and is increasingly used in the preclinical setting. The near future will tell whether or not BOLD-MRI represents a new tool to predict renal function decline an adverse renal outcome.

A comparison study between the saturation-recovery-T1 and CASL MRI methods for quantitative CBF imaging

The saturation-recovery (SR)-T1 MRI method for quantitatively imaging cerebral blood flow (CBF) change (ΔCBF) concurrently with the blood oxygenation level dependence (BOLD) alteration has been recently developed and validated by simultaneous measurement of relative CBF change using laser Doppler flowmetry (LDF) in rats at 9.4T. In this study, ΔCBF induced by mildly transient hypercapnia and measured by the SR-T1 MRI method was rigorously compared with an established perfusion MRI method—continuous arterial spin labeling (CASL) approach in normal and preclinical middle cerebral artery occlusion (MCAo) rat models. The results show an excellent agreement between ΔCBF values measured with these two imaging methods. Moreover, the intrinsic longitudinal relaxation rate (R1int) was experimentally determined in vivo in normal rat brains at 9.4T by comparing two independent measures of the apparent longitudinal relaxation rate (R1app) and CBF measured by the CSAL approach across a wide range of perfusion. In turn, the R1int constant can be employed to calculate the CBF value based on the R1app measurement in healthy brain. This comparison study validates the fundamental relationship for linking brain tissue water R1app and cerebral perfusion, demonstrates the feasibility of imaging and quantifying both CBF and its change using the SR-T1 MRI method in vivo.

Effects of magnetization transfer on T1 contrast in human brain white matter

MRI based on T1 relaxation contrast is increasingly being used to study brain morphology and myelination. Although it provides for excellent distinction between the major tissue types of gray matter, white matter, and CSF, reproducible quantification of T1 relaxation rates is difficult due to the complexity of the contrast mechanism and dependence on experimental details. In this work, we perform simulations and inversion-recovery MRI measurements at 3T and 7T to show that substantial measurement variability results from unintended and uncontrolled perturbation of the magnetization of MRI-invisible 1H protons of lipids and macromolecules. This results in bi-exponential relaxation, with a fast component whose relative contribution under practical conditions can reach 20%. This phenomenon can strongly affect apparent relaxation rates, affect contrast between tissue types, and result in contrast variations over the brain. Based on this novel understanding, ways are proposed to minimize this experimental variability and its effect on T1 contrast, quantification accuracy and reproducibility.

Feasibility of high-resolution one-dimensional relaxation imaging at low magnetic field using a single-sided NMR scanner applied to articular cartilage

Low field Nuclear Magnetic Resonance increases the contrast of the longitudinal relaxation rate in many biological tissues; one prominent example is hyaline articular cartilage. In order to take advantage of this increased contrast and to profile the depth-dependent variations, high resolution parameter measurements are carried out which can be of critical importance in an early diagnosis of cartilage diseases such as osteoarthritis. However, the maximum achievable spatial resolution of parameter profiles is limited by factors such as sensor geometry, sample curvature, and diffusion limitation. In this work, we report on high-resolution single-sided NMR scanner measurements with a commercial device, and quantify these limitations. The highest achievable spatial resolution on the used profiler, and the lateral dimension of the sensitive volume were determined. Since articular cartilage samples are usually bent, we also focus on averaging effects inside the horizontally aligned sensitive volume and their impact on the relaxation profiles. Taking these critical parameters into consideration, depth-dependent relaxation time profiles with the maximum achievable vertical resolution of 20μm are discussed, and are correlated with diffusion coefficient profiles in hyaline articular cartilage in order to reconstruct T2 maps from the diffusion-weighted CPMG decays of apparent relaxation rates.

High resolution NMR study of T1 magnetic relaxation dispersion. IV. Proton relaxation in amino acids and Met-enkephalin pentapeptide

Nuclear Magnetic Relaxation Dispersion (NMRD) of protons was studied in the pentapeptide Met-enkephalin and the amino acids, which constitute it. Experiments were run by using high-resolution Nuclear Magnetic Resonance (NMR) in combination with fast field-cycling, thus enabling measuring NMRD curves for all individual protons. As in earlier works, Papers I-III, pronounced effects of intramolecular scalar spin-spin interactions, J-couplings, on spin relaxation were found. Notably, at low fields J-couplings tend to equalize the apparent relaxation rates within networks of coupled protons. In Met-enkephalin, in contrast to the free amino acids, there is a sharp increase in the proton T1-relaxation times at high fields due to the changes in the regime of molecular motion. The experimental data are in good agreement with theory. From modelling the relaxation experiments we were able to determine motional correlation times of different residues in Met-enkephalin with atomic resolution. This allows us to draw conclusions about preferential conformation of the pentapeptide in solution, which is also in agreement with data from two-dimensional NMR experiments (rotating frame Overhauser effect spectroscopy). Altogether, our study demonstrates that high-resolution NMR studies of magnetic field-dependent relaxation allow one to probe molecular mobility in biomolecules with atomic resolution.

Assessment of Intrarenal Oxygenation in Renal Donor With Blood Oxygenation Level–dependent Magnetic Resonance Imaging

To examine change of the apparent relaxation rate R2* values in living kidney donors after uninephrectomy using blood oxygenation level-dependent magnetic resonance imaging. Between July 2011 and January 2012, 45 kidney donors were enrolled into this study. Blood oxygenation level-dependent magnetic resonance imaging scanning was performed before surgery, 3 and 7 days postoperatively. Participants were followed up for 1 year. The R2* values in medulla (mR2*) were significantly greater than that of cortex (cR2*), both in resected kidney and remaining one. cR2* values of the remaining kidney was 17.52 ± 1.36 s(-1) and then decrease significantly by 8.97% to 15.95 ± 1.14 s(-1) at 3 days (P <.001) and by 7.82% to 16.15 ± of 1.05 s(-1) at 7 days. No significant modification occurred in mR2* after surgery. Multivariate regression analysis showed that the decrease in cR2* values of the remaining kidney was positively associated with sex (r = 0.418), body surface area (r = 0.307), and preoperative cR2* values (r = 0.659). Comparing with glomerular filtration rate at 7 days, a further increment in the glomerular filtration rate was noted at 1 year in patients with cR2* values decrease of ≥ 10% at 1 week (62.63 ± 11.69 vs 56.97 ± 7.51 mL/min/1.73 m(2), P = .02) but not in the other patients (66.43 ± 10.89 vs 62.78 ± 13.74, P = .064). Kidney donation will induce early, profound oxygenation modification within the renal cortex of the remaining kidney. Donors with cR2* value decrease of ≥ 10% at 1 week have a more favorable renal function compensation at 1 year.