Transverse Relaxation Rate Research Articles

Multimodal assessment of white matter tracts in amyotrophic lateral sclerosis.

Several quantitative magnetic resonance imaging (MRI) techniques have been proposed to investigate microstructural tissue changes in amyotrophic lateral sclerosis (ALS) including diffusion tensor imaging (DTI), magnetization transfer imaging, and R2* mapping. Here, in this study, we compared these techniques with regard to their capability for detecting ALS related white matter (WM) changes in the brain and their association with clinical findings. We examined 27 ALS patients and 35 age-matched healthy controls. MRI was performed at 3T, after which we analyzed the diffusion properties, the magnetization transfer ratio (MTR), and the effective transversal relaxation rate R2* in 18 WM tracts that were obtained by a fully automated segmentation technique. ALS patients, especially with a bulbar onset, showed a bilateral increase in radial and mean diffusivity, as well as a reduction in fractional anisotropy of the corticospinal tract (CST), and diffusion changes in the parietal and temporal superior longitudinal fasciculus. A reduction of the MTR was found in both CSTs and an R2* reduction was seen only in the left CST. Tract-specific diffusion properties were not related to clinical status in a cross-sectional manner but demonstrated some association with disease progression over three subsequent months. DTI reveals more widespread WM tissue changes than MTR and R2*. These changes are not restricted to the CST, but affect also other WM tracts (especially in patients with bulbar onset), and are associated with the short term course of the disease.

Joint non-uniform sampling of all incremented time delays for quicker acquisition in protein relaxation studies

NMR relaxometry plays crucial role in studies of protein dynamics. The measurement of longitudinal and transverse relaxation rates of ^{15}N is the main source of information on backbone motions. However, even the most basic approach exploiting a series of ^{15}N HSQC spectra can require several hours of measurement time. Standard non-uniform sampling (NUS), i.e. random under-sampling of indirect time domain, typically cannot reduce this by more than 2–4times due to relatively low “compressibility” of these spectra. In this paper we propose an extension of NUS to relaxation delays. The two-dimensional space of t_1/t_{relax} is sampled in a way similar to NUS of t_1/t_2 domain in 3D spectra. The signal is also processed in a way similar to that known from 3D NUS spectra i.e. using one of the most popular compressed sensing algorithms, iterative soft thresholding. The 2D Fourier transform matrix is replaced with mixed inverse Laplace-Fourier transform matrix. The peak positions in resulting 3D spectrum are characterized by two frequency coordinates and relaxation rate and thus no additional fitting of exponential curves is required. The method is tested on three globular proteins, providing satisfactory results in a time corresponding to acquisition of two conventional ^{15}N HSQC spectra.

Multimodal MEMPRAGE, FLAIR, and [Formula: see text] Segmentation to Resolve Dura and Vessels from Cortical Gray Matter.

While widely in use in automated segmentation approaches for the detection of group differences or of changes associated with continuous predictors in gray matter volume, T1-weighted images are known to represent dura and cortical vessels with signal intensities similar to those of gray matter. By considering multiple signal sources at once, multimodal segmentation approaches may be able to resolve these different tissue classes and address this potential confound. We explored here the simultaneous use of FLAIR and apparent transverse relaxation rates (a signal related to relaxation maps and having similar contrast) with T1-weighted images. Relative to T1-weighted images alone, multimodal segmentation had marked positive effects on 1. the separation of gray matter from dura, 2. the exclusion of vessels from the gray matter compartment, and 3. the contrast with extracerebral connective tissue. While obtainable together with the T1-weighted images without increasing scanning times, apparent transverse relaxation rates were less effective than added FLAIR images in providing the above mentioned advantages. FLAIR images also improved the detection of cortical matter in areas prone to susceptibility artifacts in standard MPRAGE T1-weighted images, while the addition of transverse relaxation maps exacerbated the effect of these artifacts on segmentation. Our results confirm that standard MPRAGE segmentation may overestimate gray matter volume by wrongly assigning vessels and dura to this compartment and show that multimodal approaches may greatly improve the specificity of cortical segmentation. Since multimodal segmentation is easily implemented, these benefits are immediately available to studies focusing on translational applications of structural imaging.

Water Proton NMR: A Tool for Protein Aggregation Characterization.

Formulation stability is a critical attribute of any protein-based biopharmaceutical drug due to a protein's inherent tendency to aggregate. Advanced analytical techniques currently used for characterization of protein aggregates are prone to a number of limitations and usually require additional manipulations with the sample, such as dilution, separation, labeling, and use of special cuvettes. In the present work, we compared conventional techniques for the analysis of protein aggregates with a novel approach that employs the water proton transverse relaxation rate R2(1H2O). We explored differences in the sensitivity of conventional techniques, size-exclusion chromatography (SEC), microflow imaging (MFI), and dynamic light scattering (DLS), and water NMR (wNMR) toward the presence of monoclonal antibody aggregates generated by different stresses. We demonstrate that wNMR outperformed SEC, DLS, and MFI in that it was most consistently sensitive to increases in both soluble and insoluble aggregates, including subvisible particles. The simplicity of wNMR, its sensitivity, and possibility of noninvasive measurements are unique advantages that would permit its application for more efficient and higher throughput optimization of protein formulations.

Can transverse relaxation rates in deep gray matter be approximated from functional and T2-weighted FLAIR scans for relative brain iron quantification?

Alterations in iron concentration in certain deep gray matter regions are known to occur in aging and several clinical conditions. In vivo measurements of R2∗ transverse relaxation rates and quantitative susceptibility mapping (QSM) have been shown to be strongly correlated with iron concentration in tissue, but their calculation requires the acquisition of a multi-echo gradient recalled echo sequence (MGRE). In the current study, we examined the feasibility of approximating R2∗ rates using metrics derived from fMRI-EPI and T2-weighted FLAIR images, which are widely available. In a sample of 40 healthy subjects, we obtained these metrics (vEPI and vFLAIR), as well as R2∗ rates and QSM estimates, and found significant correlations between vEPI and vFLAIR and R2∗ rates in several subcortical gray matter regions known to accumulate iron, but not in a control corticospinal white matter region. These relationships were preserved after referencing vEPI and vFLAIR with respect to the values in the control region. Effect sizes (above 0.5 for some of the regions, particularly the largest ones) were calculated and put in relation to those of the correlation between QSM and R2∗ rates. We propose that the metrics described here may be applied, possibly in a retrospective fashion, to analyze datasets with available EPI or T2-weighted FLAIR scans (and lacking a MGRE sequence), to devise new hypotheses regarding links between iron concentration in brain tissue and other variables of interest.

Myelin Detection Using Rapid Quantitative MR Imaging Correlated to Macroscopically Registered Luxol Fast Blue-Stained Brain Specimens.

Myelin detection is of great value in monitoring diseases such as multiple sclerosis and dementia. However, most MR imaging methods to measure myelin are challenging for routine clinical use. Recently, a novel method was published, in which the presence of myelin is inferred by using its effect on the intra- and extracellular water relaxation rates and proton density, observable by rapid quantitative MR imaging. The purpose of this work was to validate this method further on the brains of 12 fresh, intact cadavers. The 12 brains were scanned with a quantification sequence to determine the longitudinal and transverse relaxation rates and proton density as input for the myelin estimations. Subsequently, the brains were excised at postmortem examination, and brain slices were stained with Luxol fast blue to verify the presence of myelin. The optical density values of photographs of the stained brain slices were registered with the MR images and correlated with the myelin estimation performed by quantitative MR imaging. A correlation was found between the 2 methods with a mean Spearman ρ for all subjects of 0.74 ± 0.11. Linear regression showed a mean intercept of 1.50% ± 2.84% and a mean slope of 4.37% ± 1.73%/%. A lower correlation was found for the separate longitudinal relaxation rates and proton density (ρ = 0.63 ± 0.12 and -0.73 ± 0.09, respectively). For transverse relaxation rates, the ρ was very low (0.11 ± 0.28). The observed correlation supports the validity of myelin measurement by using the MR imaging quantification method.

"One-for-All"-Type, Biodegradable Prussian Blue/Manganese Dioxide Hybrid Nanocrystal for Trimodal Imaging-Guided Photothermal Therapy and Oxygen Regulation of Breast Cancer.

Multimodal imaging-guided diagnosis and therapy has been highlighted in the area of theranostic nanomaterials. To provide more suitable theranostic candidates, Prussian blue (PB)/manganese dioxide (MnO2) hybrid nanoparticles (PBMn) smaller than 50 nm are prepared by a one-pot method. MnO2, which is reduced from KMnO4, not only controls the particle size, the optical properties, and the transverse relaxation rate (r2) of PB but also enhances the catalysis efficacy of PB to H2O2 for oxygen generation. PBMn can serve as a photoacoustic imaging (PAI) and longitudinal relaxation (T1) mode magnetic resonance imaging contrast agent (14 times and 1.8 times of the saline-treated group, respectively). Injection of PBMn can regulate the oxygen partial pressure of the tumor tissue from 2.1 ± 0.2 to 9.3 ± 0.4 kPa and rearrange the ratio of oxygenated hemoglobin and deoxygenate hemoglobin inside the tumor, which favor the enhancement of the diamagnetic T2-weighted imaging (T2WI) signal intensity (two times that of the saline-treated group). Furthermore, PBMn-mediated PTT can efficiently inhibit the growth of the MCF-7 tumor in vitro and in vivo. PBMn can serve as a PAI/T1/T2 trimodal contrast agent and in imaging-guided PTT, as well as in the oxygen regulation of the exografted breast cancer.

Precise measurement of magnetic field gradients from free spin precession signals of 3He and 129Xe magnetometers

We report on precise measurements of magnetic field gradients extracted from transverse relaxation rates of precessing spin samples. The experimental approach is based on the free precession of gaseous, nuclear spin polarized $^3$He and $^{129}$Xe atoms in a spherical cell inside a magnetic guiding field of about 400 nT using LT$_C$ SQUIDs as low-noise magnetic flux detectors. The transverse relaxation rates of both spin species are simultaneously monitored as magnetic field gradients are varied. For transverse relaxation times reaching 100 h, the residual longitudinal field gradient across the spin sample could be deduced to be$|\vec{\nabla}B_z|=(5.6 \pm 0.4)$ pT/cm. The method takes advantage of the high signal-to-noise ratio with which the decaying spin precession signal can be monitored that finally leads to the exceptional accuracy to determine magnetic field gradients at the sub pT/cm scale.

Combined Diffusion Tensor Imaging and Apparent Transverse Relaxation Rate Differentiate Parkinson Disease and Atypical Parkinsonism.

Both diffusion tensor imaging and the apparent transverse relaxation rate have shown promise in differentiating Parkinson disease from atypical parkinsonism (particularly multiple system atrophy and progressive supranuclear palsy). The objective of the study was to assess the ability of DTI, the apparent transverse relaxation rate, and their combination for differentiating Parkinson disease, multiple system atrophy, progressive supranuclear palsy, and controls. A total of 106 subjects (36 controls, 35 patients with Parkinson disease, 16 with multiple system atrophy, and 19 with progressive supranuclear palsy) were included. DTI and the apparent transverse relaxation rate measures from the striatal, midbrain, limbic, and cerebellar regions were obtained and compared among groups. The discrimination performance of DTI and the apparent transverse relaxation rate among groups was assessed by using Elastic-Net machine learning and receiver operating characteristic curve analysis. Compared with controls, patients with Parkinson disease showed significant apparent transverse relaxation rate differences in the red nucleus. Compared to those with Parkinson disease, patients with both multiple system atrophy and progressive supranuclear palsy showed more widespread changes, extending from the midbrain to striatal and cerebellar structures. The pattern of changes, however, was different between the 2 groups. For instance, patients with multiple system atrophy showed decreased fractional anisotropy and an increased apparent transverse relaxation rate in the subthalamic nucleus, whereas patients with progressive supranuclear palsy showed an increased mean diffusivity in the hippocampus. Combined, DTI and the apparent transverse relaxation rate were significantly better than DTI or the apparent transverse relaxation rate alone in separating controls from those with Parkinson disease/multiple system atrophy/progressive supranuclear palsy; controls from those with Parkinson disease; those with Parkinson disease from those with multiple system atrophy/progressive supranuclear palsy; and those with Parkinson disease from those with multiple system atrophy; but not those with Parkinson disease from those with progressive supranuclear palsy, or those with multiple system atrophy from those with progressive supranuclear palsy. DTI and the apparent transverse relaxation rate provide different but complementary information for different parkinsonisms. Combined DTI and apparent transverse relaxation rate may be a superior marker for the differential diagnosis of parkinsonisms.

MR imaging differentiation of Fe2+ and Fe3+ based on relaxation and magnetic susceptibility properties.

The aim of this study is to evaluate the MR imaging behavior of ferrous (Fe2+) and ferric (Fe3+) iron ions in order to develop a noninvasive technique to quantitatively differentiate between both forms of iron. MRI was performed at 3T in a phantom consisting of 21 samples with different concentrations of ferrous and ferric chloride solutions (between 0 and 10mmol/L). A multi-echo spoiled gradient-echo pulse sequence with eight echoes was used for both T 2* and quantitative susceptibility measurements. The transverse relaxation rate, R 2*=1/T 2*, was determined by nonlinear exponential fitting based on the mean signals in each sample. The susceptibilities, χ, of the samples were calculated after phase unwrapping and background field removal by fitting the spatial convolution of a unit dipole response to the measured internal field map. Relaxation rate changes, ΔR 2*(c Fe), and susceptibility changes, Δχ(c Fe), their linear slopes, as well as the ratios ΔR 2*(c Fe)/Δχ(c Fe) were determined for all concentrations. The linear slopes of the relaxation rate were (12.5±0.4)s-1/(mmol/L) for Fe3+ and (0.77±0.09)s-1/(mmol/L) for Fe2+ (significantly different, z test P<0.0001). The linear slopes of the susceptibility were (0.088±0.003)ppm/(mmol/L) for Fe3+ and (0.079±0.006)ppm/(mmol/L) for Fe2+. The individual ratios ΔR 2*/Δχ were greater than 40s-1/ppm for all samples with ferric solution and lower than 20s-1/ppm for all but one of the samples with ferrous solution. Ferrous and ferric iron ions show significantly different relaxation behaviors in MRI but similar susceptibility patterns. These properties can be used to differentiate ferrous and ferric samples.

Benchmarking transverse spin relaxation based oxygenation measurements in the brain during hypercapnia and hypoxia

To simultaneously assess reproducibility of three MRI transverse relaxation parameters ( R2', R2*, and R2 ) for brain tissue oxygenation mapping and to assess changes in these parameters with inhalation of gases that increase and decrease oxygenation, to identify the most sensitive parameter for imaging brain oxygenation. Forty-eight healthy subjects (25 male, ages 35 ± 8 years) were scanned at 3.0 Tesla, each with one of four gases (mildly and strongly hypercapnic and hypoxic) administered in a challenge paradigm, using a gas delivery setup designed for patient use. Cerebral blood flow mapping with arterial spin labeling, and simultaneous R2', R2*, and R2 mapping with gradient-echo sampling of free induction decay and echo (GESFIDE) were performed. Reproducibility in air and gas-induced changes were evaluated using nonparametric analysis with correction for multiple comparisons. Our gas delivery setup achieved stable gas challenges as shown by physiological monitoring. Test-retest variability of R2', R2*, and R2 were found to be 0.24 s-1 (8.6% of mean), 0.24 s-1 (1.3% of mean), and 0.15 s-1 (1.0% of mean), respectively. Strong hypoxia produced the most conclusive oxygenation-driven relaxation change, inducing increases in R2' (25 ± 13%, P = 0.03), R2* (5 ± 2%, P = 0.02), and R2 (2 ± 2%, NS). We benchmarked the intra-scan test-retest variability in GESFIDE-based transverse relaxation rate mapping. Using a reliable framework for gas challenge paradigms, we recommend strong hypoxia for validating oxygenation mapping methods, and the use of tissue R2' change, instead of R2* or R2 , as a metric for studying brain tissue oxygenation using transverse relaxation methods. 1 Technical Efficacy: Stage 1 J. MAGN. RESON. IMAGING 2017;46:704-714.

Progressive iron accumulation across multiple sclerosis phenotypes revealed by sparse classification of deep gray matter.

To create an automated framework for localized analysis of deep gray matter (DGM) iron accumulation and demyelination using sparse classification by combining quantitative susceptibility (QS) and transverse relaxation rate (R2*) maps, for evaluation of DGM in multiple sclerosis (MS) phenotypes relative to healthy controls. R2*/QS maps were computed using a 4.7T 10-echo gradient echo acquisition from 16 clinically isolated syndrome (CIS), 41 relapsing-remitting (RR), 40 secondary-progressive (SP), 13 primary-progressive (PP) MS patients, and 75 controls. Sparse classification for R2*/QS maps of segmented caudate nucleus (CN), putamen (PU), thalamus (TH), and globus pallidus (GP) structures produced localized maps of iron/myelin in MS patients relative to controls. Paired t-tests, with age as a covariate, were used to test for statistical significance (P ≤ 0.05). In addition to DGM structures found significantly different in patients compared to controls using whole region analysis, singular sparse analysis found significant results in RRMS PU R2* (P = 0.03), TH R2* (P = 0.04), CN QS (P = 0.04); in SPMS CN R2* (P = 0.04), GP R2* (P = 0.05); and in PPMS CN R2* (P = 0.04), TH QS (P = 0.04). All sparse regions were found to conform to an iron accumulation pattern of changes in R2*/QS, while none conformed to demyelination. Intersection of sparse R2*/QS regions also resulted in RRMS CN R2* becoming significant, while RRMS R2* TH and PPMS QS TH becoming insignificant. Common iron-associated volumes in MS patients and their effect size progressively increased with advanced phenotypes. A localized technique for identifying sparse regions indicative of iron or myelin in the DGM was developed. Progressive iron accumulation with advanced MS phenotypes was demonstrated, as indicated by iron-associated sparsity and effect size. 1 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2017;46:1464-1473.

Ultraslow fluctuations in the pseudogap states ofHgBa2CaCu2O6+δ

We report the transverse relaxation rates 1/$T_2$'s of the $^{63}$Cu nuclear spin-echo envelope for double-layer high-$T_c$ cuprate superconductors HgBa$_{2}$CaCu$_{2}$O$_{6+d}$ from underdoped to overdoped. The relaxation rate 1/$T_{2L}$ of the exponential function (Lorentzian component) shows a peak at 220$-$240 K in the underdoped ($T_c$ = 103 K) and the optimally doped ($T_c$ = 127 K) samples but no peak in the overdoped ($T_c$ = 93 K) sample. The enhancement in 1/$T_{2L}$ suggests development of the zero frequency components of local field fluctuations. Ultraslow fluctuations are hidden in the pseudogap states.

Bone quantitative susceptibility mapping using a chemical species-specific R2* signal model with ultrashort and conventional echo data.

To develop quantitative susceptibility mapping (QSM) of bone using an ultrashort echo time (UTE) gradient echo (GRE) sequence for signal acquisition and a bone-specific effective transverse relaxation rate ( R2*) to model water-fat MR signals for field mapping. Three-dimensional radial UTE data (echo times ≥ 40 μs) was acquired on a 3 Tesla scanner and fitted with a bone-specific signal model to map the chemical species and susceptibility field. Experiments were performed ex vivo on a porcine hoof and in vivo on healthy human subjects (n = 7). For water-fat separation, a bone-specific model assigning R2* decay mostly to water was compared with the standard models that assigned the same decay for both fat and water. In the ex vivo experiment, bone QSM was correlated with CT. Compared with standard models, the bone-specific R2* method significantly reduced errors in the fat fraction within the cortical bone in all tested data sets, leading to reduced artifacts in QSM. Good correlation was found between bone CT and QSM values in the porcine hoof (R2 = 0.77). Bone QSM was successfully generated in all subjects. The QSM of bone is feasible using UTE with a conventional echo time GRE acquisition and a bone-specific R2* signal model. Magn Reson Med 79:121-128, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Cognitive Implications of Deep Gray Matter Iron in Multiple Sclerosis.

Deep gray matter iron accumulation is increasingly recognized in association with multiple sclerosis and can be measured in vivo with MR imaging. The cognitive implications of this pathology are not well-understood, especially vis-à-vis deep gray matter atrophy. Our aim was to investigate the relationships between cognition and deep gray matter iron in MS by using 2 MR imaging-based iron-susceptibility measures. Forty patients with multiple sclerosis (relapsing-remitting, n = 16; progressive, n = 24) and 27 healthy controls were imaged at 4.7T by using the transverse relaxation rate and quantitative susceptibility mapping. The transverse relaxation rate and quantitative susceptibility mapping values and volumes (atrophy) of the caudate, putamen, globus pallidus, and thalamus were determined by multiatlas segmentation. Cognition was assessed with the Brief Repeatable Battery of Neuropsychological Tests. Relationships between cognition and deep gray matter iron were examined by hierarchic regressions. Compared with controls, patients showed reduced memory (P < .001) and processing speed (P = .02) and smaller putamen (P < .001), globus pallidus (P = .002), and thalamic volumes (P < .001). Quantitative susceptibility mapping values were increased in patients compared with controls in the putamen (P = .003) and globus pallidus (P = .003). In patients only, thalamus (P < .001) and putamen (P = .04) volumes were related to cognitive performance. After we controlled for volume effects, quantitative susceptibility mapping values in the globus pallidus (P = .03; trend for transverse relaxation rate, P = .10) were still related to cognition. Quantitative susceptibility mapping was more sensitive compared with the transverse relaxation rate in detecting deep gray matter iron accumulation in the current multiple sclerosis cohort. Atrophy and iron accumulation in deep gray matter both have negative but separable relationships to cognition in multiple sclerosis.

A macrocyclic 19F-MR based probe for Mn2 + sensing

We report a novel fluorinated aza-macrocycle that affords a linear increase in longitudinal and transverse 19F NMR relaxation rates between 100μM to 1mM Mn2+ concentrations. The linear response which is unaffected in the presence of other biologically relevant metal ions and 19F-MR phantom images of macrocycle solutions in presence of Mn2+ indicate the potential applicability of the probe as a 19F-MR based Mn2+ sensor.

Quantitative ultrashort echo time imaging for assessment of massive iron overload at 1.5 and 3 Tesla.

Hepatic iron content (HIC) quantification via transverse relaxation rate (R2*)-MRI using multi-gradient echo (mGRE) imaging is compromised toward high HIC or at higher fields due to the rapid signal decay. Our study aims at presenting an optimized 2D ultrashort echo time (UTE) sequence for R2* quantification to overcome these limitations. Two-dimensional UTE imaging was realized via half-pulse excitation and radial center-out sampling. The sequence includes chemically selective saturation pulses to reduce streaking artifacts from subcutaneous fat, and spatial saturation (sSAT) bands to suppress out-of-slice signals. The sequence employs interleaved multi-echo readout trains to achieve dense temporal sampling of rapid signal decays. Evaluation was done at 1.5 Tesla (T) and 3T in phantoms, and clinical applicability was demonstrated in five patients with biopsy-confirmed massively high HIC levels (>25 mg Fe/g dry weight liver tissue). In phantoms, the sSAT pulses were found to remove out-of-slice contamination, and R2* results were in excellent agreement to reference mGRE R2* results (slope of linear regression: 1.02/1.00 for 1.5/3T). UTE-based R2* quantification in patients with massive iron overload proved successful at both field strengths and was consistent with biopsy HIC values. The UTE sequence provides a means to measure R2* in patients with massive iron overload, both at 1.5T and 3T. Magn Reson Med 78:1839-1851, 2017. © 2017 Wiley Periodicals, Inc.

Nonlinear detection of secondary isotopic chemical shifts in NMR through spin noise

The detection of minor species in the presence of large amounts of similar main components remains a key challenge in analytical chemistry, for instance, to obtain isotopic fingerprints. As an alternative to the classical NMR scheme based on coherent excitation and detection, here we introduce an approach based on spin-noise detection. Chemical shifts and transverse relaxation rates are determined using only the detection circuit. Thanks to a nonlinear effect in mixtures with small chemical shift dispersion, small signals on top of a larger one can be observed with increased sensitivity as bumps on a dip; the latter being the signature of the main magnetization. Experimental observations are underpinned by an analytical theory: the coupling between the magnetization and the coil provides an amplified detection capability of both small static magnetic field inhomogeneities and small NMR signals. This is illustrated by two-bond 12C/13C isotopic measurements.

Numerical Analysis of the Magnetization Behavior in Magnetic Resonance Imaging in the Presence of Multiple Chemical Exchange Pools

The purpose of this study was to demonstrate a simple and fast method for solving the time-dependent Bloch-McConnell equations describing the behavior of magnetization in magnetic resonance imaging (MRI) in the presence of multiple chemical exchange pools. First, the time-dependent Bloch- McConnell equations were reduced to a homogeneous linear differential equation, and then a simple equation was derived to solve it using a matrix operation and Kronecker tensor product. From these solutions, the longitudinal relaxation rate (R1ρ) and transverse relaxation rate in the rotating frame (R2ρ) and Z-spectra were obtained. As illustrative examples, the numerical solutions for linear and star-type three-pool chemical exchange models and linear, star- type, and kite-type four-pool chemical exchange models were presented. The effects of saturation time (ST) and radiofrequency irradiation power (ω1) on the chemical exchange saturation transfer (CEST) effect in these models were also investigated. Although R1ρ and R2ρ were not affected by the ST, the CEST effect observed in the Z-spectra increased and saturated with increasing ST. When ω1 was varied, the CEST effect increased with increasing ω1 in R1ρ, R2ρ, and Z-spectra. When ω1 was large, however, the spillover effect due to the direct saturation of bulk water protons also increased, suggesting that these parameters must be determined in consideration of both the CEST and spillover effects. Our method will be useful for analyzing the complex CEST contrast mechanism and for investigating the optimal conditions for CEST MRI in the presence of multiple chemical exchange pools.

Detection of Acute Tubular Necrosis Using Blood Oxygenation Level-Dependent (BOLD) MRI

Background/Aims: To date, there is no imaging technique to assess tubular function in vivo. Blood oxygen level-dependent magnetic resonance imaging (BOLD MRI) measures tissue oxygenation based on the transverse relaxation rate (R2*). The present study investigates whether BOLD MRI can assess tubular function using a tubule-specific pharmacological maneuver. Methods: Cross sectional study with 28 participants including 9 subjects with ATN-induced acute kidney injury (AKI), 9 healthy controls, and 10 subjects with nephron sparing tumor resection (NSS) with clamping of the renal artery serving as a model of ischemia/reperfusion (I/R)-induced subclinical ATN (median clamping time 15 min, no significant decrease of eGFR, p=0.14). BOLD MRI was performed before and 5, 7, and 10 min after intravenous administration of 40 mg furosemide. Results: Urinary neutrophil gelatinase-associated lipocalin was significantly higher in ATN-induced AKI and NSS subjects than in healthy controls (p=0.03 and p=0.01, respectively). Before administration of furosemide, absolute medullary R2*, cortical R2*, and medullary/cortical R2* ratio did not significantly differ between ATN-induced AKI vs. healthy controls and between NSS-I/R vs. contralateral healthy kidneys (p>0.05 each). Furosemide led to a significant decrease in the medullary and cortical R2* of healthy subjects and NSS contralateral kidneys (p<0.05 each), whereas there was no significant change of R2* in ATN-induced AKI and the NSS-I/R kidneys (p>0.05 each). Conclusion: BOLD-MRI is able to detect even mild tubular injury but necessitates a tubule-specific pharmacological maneuver, e.g. blocking the Na⁺-K⁺-2Cl^- transporter by furosemide.