Brain Structures in a Human Embryo Imaged with MR Microscopy.

PURPOSE: To delineate brain microstructures in human embryos during the formation of the various major primordia by MR microscopy, with different contrasts appropriate for each target. METHODS: We focused mainly on the internal structures in the cerebral cortex and the accessory nerves of the brain. To find appropriate sequence parameters, we measured nuclear magnetic resonance (NMR) parameters and created kernel density plots of T1 and T2 values. We performed T1-weighted gradient echo imaging with parameters similar to those used in the previous studies. We performed T2*-weighted gradient echo imaging to delineate the target structures with the appropriate sequence parameters according to the NMR parameter and flip angle measurements. We also performed high-resolution imaging with both T1- and T2*-weighted sequences. RESULTS: T1, T2, and T2* values of the target tissues were positively correlated and shorter than those of the surrounding tissues. In T1-weighted images with a voxel size of (30 µm)3 and (20 µm)3, various organs and tissues and the agarose gel were differentiated as in previous studies, and the structure of approximately 40 µm in size was depicted, but the detailed structures within the cerebral cortex and the accessory nerves were not delineated. In T2*-weighted images with a voxel size of (30 µm)3, the layered structure within the cerebral cortex and the accessory nerves were clearly visualized. Overall, T1-weighted images provided more information than T2*-weighted images, but important internal brain structures of interest were visible only in T2*-weighted images. Therefore, it is essential to perform MR microscopy with different contrasts. CONCLUSION: We have visualized brain structures in a human embryo that had not previously been delineated by MR microscopy. We discussed pulse sequences appropriate for the structures of interest. This methodology would provide a way to visualize crucial embryological information about the anatomical structure of human embryos.

Histological Properties of a Chemically Fixed Human Embryo Visualized with Quantitative Susceptibility Mapping.

A chemically fixed Carnegie stage 23 (approximately 56 days of gestation) human embryo specimen was imaged using 3D spin-echo and gradient-echo sequences in a static magnetic field strength of 4.74T, and a quantitative susceptibility map was calculated using the 3D gradient-echo image. The acquired 3D microscopic images (90 µm cube voxel size) clarified the relationship between R2 (transverse relaxation rate), R2* (apparent transverse relaxation rate), and magnetic susceptibility in the heart, liver, kidney, and spinal cord. The results suggested that the R2* and magnetic susceptibility in each tissue were probably due to paramagnetic iron ions originating from erythrocytes. The large R2* (~130 s-1) and magnetic susceptibility (~0.122 ppm) in the liver were attributed to its hemopoietic function. A large magnetic susceptibility (~0.116 ppm) was also observed in the spinal cord, but we conclude that more detailed future studies are needed.

Amelioration of Tumor-promoting Microenvironment via Vascular Remodeling and CAF Suppression Using E7130: Biomarker Analysis by Multimodal Imaging Modalities.

E7130 is a novel anticancer agent created from total synthetic study of the natural compound norhalichondrin B. In addition to inhibiting microtubule dynamics, E7130 also ameliorates tumor-promoting aspects of the tumor microenvironment (TME) by suppressing cancer-associated fibroblasts (CAF) and promoting remodeling of tumor vasculature. Here, we demonstrate TME amelioration by E7130 using multi-imaging modalities, including multiplexed mass cytometry [cytometry by time-of-flight (CyTOF)] analysis, multiplex IHC analysis, and MRI. Experimental solid tumors characterized by large numbers of CAFs in TME were treated with E7130. E7130 suppressed LAP-TGFß1 production, a precursor of TGFß1, in CAFs but not in cancer cells; an effect that was accompanied by a reduction of circulating TGFß1 in plasma. To our best knowledge, this is the first report to show a reduction of TGFß1 production in TME. Furthermore, multiplex IHC analysis revealed reduced cellularity and increased TUNEL-positive apoptotic cells in E7130-treated xenografts. Increased microvessel density (MVD) and collagen IV (Col IV), an extracellular matrix (ECM) component associated with endothelial cells, were also observed in the TME, and plasma Col IV levels were also increased by E7130 treatment. MRI revealed increased accumulation of a contrast agent in xenografts. Moreover, diffusion-weighted MRI after E7130 treatment indicated reduction of tumor cellularity and interstitial fluid pressure. Overall, our findings strongly support the mechanism of action that E7130 alters the TME in therapeutically beneficial ways. Importantly, from a translational perspective, our data demonstrated MRI as a noninvasive biomarker to detect TME amelioration by E7130, supported by consistent changes in plasma biomarkers.

High-resolution MRI for human embryos with isotropic 10 µm resolution at 9.4 T.

Magnetic resonance (MR) microscopy of human embryos has contributed significantly to the development of human embryology. Higher-resolution MR microscopy will have obvious benefits, for example, in visualizing small structures that are blurred or lost in lower-resolution images, providing detailed information on the development and growth of various organs, and improving the accuracy of MR volumetry. However, high-resolution MR microscopy has yet to be realized because of many technical challenges. In this study, therefore, we have performed high-resolution MR microscopy for human embryos with isotropic resolutions of (12 µm)3 at full sampling and (10 µm)3 at compressed sensing, which far exceeds the resolution of previous embryonic MR studies. The hardware and the pulse sequence were improved to achieve higher spatial resolution. Line profile, signal-to-noise ratio, and histogram analysis using phantom images were performed to verify that the resolution and the voxel size were identical. Comparison with optical microscopy images of embryo specimens at the same developmental stage was performed to confirm that the microstructures were well delineated. Our results show that imaging at this high resolution effectively depicts the microstructures of human embryos. This technology is the cornerstone for constructing an unprecedented high-quality atlas that will contribute to the development of human embryology.

Numerical and Clinical Evaluation of the Robustness of Open-source Networks for Parallel MR Imaging Reconstruction.

PURPOSE: Deep neural networks (DNNs) for MRI reconstruction often require large datasets for training. Still, in clinical settings, the domains of datasets are diverse, and how robust DNNs are to domain differences between training and testing datasets has been an open question. Here, we numerically and clinically evaluate the generalization of the reconstruction networks across various domains under clinically practical conditions and provide practical guidance on what points to consider when selecting models for clinical application. METHODS: We compare the reconstruction performance between four network models: U-Net, the deep cascade of convolutional neural networks (DC-CNNs), Hybrid Cascade, and variational network (VarNet). We used the public multicoil dataset fastMRI for training and testing and performed a single-domain test, where the domains of the dataset used for training and testing were the same, and cross-domain tests, where the source and target domains were different. We conducted a single-domain test (Experiment 1) and cross-domain tests (Experiments 2-4), focusing on six factors (the number of images, sampling pattern, acceleration factor, noise level, contrast, and anatomical structure) both numerically and clinically. RESULTS: U-Net had lower performance than the three model-based networks and was less robust to domain shifts between training and testing datasets. VarNet had the highest performance and robustness among the three model-based networks, followed by Hybrid Cascade and DC-CNN. Especially, VarNet showed high performance even with a limited number of training images (200 images/10 cases). U-Net was more robust to domain shifts concerning noise level than the other model-based networks. Hybrid Cascade showed slightly better performance and robustness than DC-CNN, except for robustness to noise-level domain shifts. The results of the clinical evaluations generally agreed with the results of the quantitative metrics. CONCLUSION: In this study, we numerically and clinically evaluated the robustness of the publicly available networks using the multicoil data. Therefore, this study provided practical guidance for clinical applications.

Development of an Add-on 23Na-MRI Radiofrequency Platform for a 1H-MRI System Using a Crossband Repeater: Proof-of-concept.

23Na-MRI provides information on Na+ content, and its application in the medical field has been highly anticipated. However, for existing clinical 1H-MRI systems, its implementation requires an additional broadband RF transmitter, dedicated transceivers, and RF coils for Na+ imaging. However, a standard medical MRI system cannot often be modified to perform 23Na imaging. We have developed an add-on crossband RF repeater system that enables 23Na-MRI simply by inserting it into the magnet bore of an existing 1H MRI. The three axis gradient fields controlled by the 1H-MRI system were directly used for 23Na imaging without any deformation. A crossband repeater is a common technique used for amateur radio. This concept was proven by a saline solution phantom and in vivo mouse experiments. This add-on RF platform is applicable to medical 1H MRI systems and can enhance the application of 23Na-MRI in clinical usage.

Development of a Car-mounted Mobile MR Imaging System for Diagnosis of Sports-related Wrist Injury.

Portable MRI scanners, in which a permanent magnet with a low magnetic field is mounted on a small car, have enabled the performance of MRI examinations in various remote environments. Here, we have modified the portable MRI system to enable the early diagnosis of wrist sports injuries among tennis players. A RF probe specifically designed for the human wrist was developed, and a power supply scheme using a small generator was introduced. The portable MRI system was located at a tennis school and imaging of the wrists of junior tennis players was performed. To demonstrate clinical feasibility, image quality was assessed by a radiologist and clinical evaluations were performed. In most cases, the image quality was sufficient for diagnosis, and triangular fibrocartilage complex damage could be detected. The results indicated that the modified portable MRI system could be applied for an early diagnosis of wrist injuries.

Use of a Small Car-Mounted Magnetic Resonance Imaging System for On-Field Screening for Osteochondritis Dissecans of the Humeral Capitellum.

Mobile magnetic resonance imaging (MRI) using a car is a recent advancement in imaging technology. Specifically, a car-mounted mobile MRI system is expected to be used for medical check-ups; however, this is still in the research stage. This study demonstrated the practicality of a small car-mounted mobile MRI in on-field screening for osteochondritis dissecans (OCD) of the humeral capitellum. In the primary check-up, we screened the throwing elbows of 151 young baseball players using mobile MRI and ultrasonography. We definitively diagnosed OCD at the secondary check-up using X-ray photography and computed tomography or MRI. We investigated the sensitivity and specificity of mobile MRI and ultrasonography for OCD. Six patients were diagnosed with OCD. The sensitivity was 83.3% for mobile MRI and 66.7% for ultrasonography, with specificity of 99.3% vs. 100%, respectively. One patient was detected using ultrasonography but was missed by mobile MRI due to poor imaging quality at the first medical check-up. Following this false-negative case, we replaced a damaged radio frequency coil to improve the image quality, and the mobile MRI could detect all subsequent OCD cases. Two patients were diagnosed by mobile MRI only; ultrasonography missed cases lacking subchondral bone irregularity, such as a healing case, and an early-stage case. Mobile MRI could screen for OCD from the very early stages through the healing process and is therefore a practical tool for on-field screening.

New Cluster Analysis Method for Quantitative Dynamic Contrast-Enhanced MRI Assessing Tumor Heterogeneity Induced by a Tumor-Microenvironmental Ameliorator (E7130) Treatment to a Breast Cancer Mouse Model.

BACKGROUND: Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) can provide insight into tumor perfusion. However, a method that can quantitatively measure the intra-tumor distribution of tumor voxel clusters with a distinct range of Ktrans and ve values remains insufficiently explored. HYPOTHESIS: Two-dimensional cluster analysis may quantify the distribution of a tumor voxel subregion with a distinct range of Ktrans and ve values in human breast cancer xenografts. STUDY TYPE: Prospective longitudinal study. ANIMAL MODEL: Twenty-two female athymic nude mice with MCF-7 xenograft, treated with E7130, a tumor-microenvironmental ameliorator, or saline. FIELD STRENGTH/SEQUENCE: 9.4 Tesla, turbo rapid acquisition with relaxation enhancement, and spoiled gradient-echo sequences. ASSESSMENT: We performed two-dimensional k-means clustering to identify tumor voxel clusters with a distinct range of Ktrans and ve values on Days 0, 2, and 5 after treatment, calculated the ratio of the number of tumor voxels in each cluster to the total number of tumor voxels, and measured the normalized distances defined as the ratio of the distance between each tumor voxel and the nearest tumor margin to a tumor radius. STATISTICAL TESTS: Unpaired t-tests, Dunnett's multiple comparison tests, and Chi-squared test were used. RESULTS: The largest and second largest clusters constituted 44.4% and 27.5% of all tumor voxels with cluster centroid values of Ktrans at 0.040 min-1 and 0.116 min-1 , and ve at 0.131 and 0.201, respectively. At baseline (Day 0), the average normalized distances for the largest and second largest clusters were 0.33 and 0.24, respectively. E7130-treated group showed the normalized distance of the initial largest cluster decreasing to 0.25, while that of the second largest cluster increasing to 0.31. Saline-treated group showed no change. DATA CONCLUSION: A two-dimensional cluster analysis might quantify the spatial distribution of a tumor subregion with a distinct range of Ktrans and ve values. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 1.

Implementation of the QRAPMASTER data analysis using dictionary matching and quantitative evaluation of the magnetization transfer effect.

PURPOSE: To clarify the magnetization transfer (MT) effect on T1 and T2 values obtained with the QRAPMASTER sequence. METHODS: A phantom consisting of MnCl2 aqueous solution with various proton relaxation times and a chicken breast sample was imaged with the QRAPMASTER sequence and a multislice multiple spin-echo (MSMSE) sequence that was the basis of the QRAPMASTER sequence using a 1.5 T MRI system. T1 values were calculated by data matching using the dictionary dataset created by a Bloch image simulation of the QRAPMASTER sequence. T2 values were calculated by data matching using the dictionary dataset created by a Bloch image simulation of the MSMSE sequence. The MT effect on the images acquired with the QRAPMASTER and MSMSE sequences was calculated by numerically solving Bloch equations using a two-pool model. RESULTS: The linearity and accuracy of the regression lines between the T1 values measured by the QRAPMASTER sequence and those measured by the standard method excluding the T1 values of the chicken breast sample was excellent (R = 0.9969-0.9986, slope = 1.0065-1.016) for consecutive four slices including the central slice. The linearity of the regression lines for the T2 values of all samples was good (R = 0.963-0.985) for the four slices. The accuracy of the regression line was not good (slope = 0.674-0.758), which was mainly due to the effect of eddy currents. The large deviation of the T1 values of the chicken breast sample from the regression line was semi-quantitatively reproduced by the Bloch simulation for the two-pool model. CONCLUSION: This study demonstrated that the T1 value of a biological sample obtained by the QRAPMASTER sequence was shortened by the MT effect.

Bloch Simulation of a Three-point Dixon Experiment Using a Four-dimensional Numerical Phantom.

A 4D numerical phantom, which is defined in the 3D spatial axes and the resonance frequency axis, is indispensable for Bloch simulations of biological tissues with complex distribution of materials. In this study, a 4D numerical phantom was created using MR image datasets of a biological sample containing water and fat, and the Bloch simulations were performed using the 4D numerical phantom. As a result, 3D images of the sample containing water and fat were successfully reproduced, which demonstrated the usefulness of the concept of the 4D numerical phantom.

Development of a method for the Bloch image simulation of biological tissues.

PURPOSE: The purpose of this study is to develop a method for the Bloch image simulation of biological tissues including various chemical components and T2* distribution. METHODS: The nuclear spins in the object material were modeled as a spectral intensity function Sr→ω defined by superposition of Lorentz functions with various central precession frequencies and the half width of 1/(πT2'), where 1/T2' is a relaxation rate attributable to microscopic field inhomogeneity in a voxel. Four-dimensional numerical phantoms were created to simulate Sr→ω and used for MRI simulations of the phantoms containing water and fat protons. Single slice multiple (16) gradient-echo sequences (ΔTE = 2.2 and 1.384 ms) were used for experiments at 1.5 T and 3 T and MRI simulations to evaluate the validity of the approach. RESULTS: Experimentally measured image intensities of the multiple gradient-echo imaging sequences were well reproduced by the MRI simulations. The correlation coefficients between the experimentally measured image intensities and those numerically simulated were 0.9895 to 0.9992 for the 4-component phantom at 1.5 T and 0.9580 to 0.9996 for the 7-component phantom at 3 T. CONCLUSION: T2* and chemical shift effects were successfully implemented in the MRI simulator (BlochSolver). Because this approach can be applied to other MRI simulators, the method developed in this study is useful for MRI simulation of biological tissues containing water and fat protons.

SET/TAF1 forms a distance-dependent feedback loop with Aurora B and Bub1 as a tension sensor at centromeres.

During mitosis, spatiotemporal regulation of phosphorylation at the kinetochore is essential for accurate chromosome alignment and proper chromosome segregation. Aurora B kinase phosphorylates kinetochore substrates to correct improper kinetochore-microtubule (KT-MT) attachments, whereas tension across the centromeres inactivates Aurora B kinase, and PP2A phosphatase dephosphorylates the kinetochore proteins to stabilize the attachments. However, the molecular entity of the tension sensing mechanism remains elusive. In a previous report, we showed that centromeric SET/TAF1 on Sgo2 up-regulates Aurora B kinase activity via PP2A inhibition in prometaphase. Here we show that Aurora B and Bub1 at the centromere/kinetochore regulate both kinase activities one another in an inter-kinetochore distance-dependent manner, indicating a positive feedback loop. We further show that the centromeric pool of SET on Sgo2 depends on Bub1 kinase activity, and the centromeric localization of SET decreases in a distance-dependent manner, thereby inactivating Aurora B in metaphase. Consistently, ectopic targeting of SET to the kinetochores during metaphase hyperactivates Aurora B via PP2A inhibition, and thereby rescues the feedback loop. Thus, we propose that SET, Aurora B and Bub1 form a distance-dependent positive feedback loop, which spatiotemporally may act as a tension sensor at centromeres.

Dynamics of xylem and phloem sap flow in an outdoor zelkova tree visualized by magnetic resonance imaging.

Xylem and phloem sap flows in an intact, young Japanese zelkova tree (Zelkova serrata (Thunb.) Makino) growing outdoors were measured using magnetic resonance imaging (MRI). Two propagator-based sequences were developed for q-space imaging: pulse field gradient (PFG) with spin echo (PFG-SE) and stimulated echo (PFG-STE), which were used for xylem and phloem flow measurements, respectively. The data evaluation methods were improved to image fast xylem flow and slow phloem flow. Measurements were taken every 2-3 h for several consecutive days in August 2016, and diurnal changes in xylem and phloem sap flows in a cross-section of the trunk were quantified at a resolution of 1 mm2. During the day, apparent xylem flow volume exhibited a typical diurnal pattern following a vapor pressure deficit. The velocity mapping of xylem sap flow across the trunk cross section revealed that the greatest flow volume was found in current-year earlywood that had differentiated in April-May. The combined xylem flow in the 1- and 2-year-old annual rings also contributed to one-third of total sap flow. In the phloem, downward sap flow did not exhibit diurnal changes. This novel application of MRI in visualization of xylem and phloem sap flow by MRI is a promising tool for in vivo study of water transport in mature trees.

Relationship between Li+ diffusion and ion conduction for single-crystal and powder garnet-type electrolytes studied by 7Li PGSE NMR spectroscopy.

Ion-conducting garnets are important candidates for use in all-solid Li batteries and numerous materials have been synthesized with high ionic conductivities. For understanding ion conduction mechanisms, knowledge on Li+ diffusion behaviour is essential. The proposed nano-scale lithium pathways are composed of tortuous and narrow Li+ channels. The pulsed gradient spin-echo (PGSE) NMR method provides time-dependent 7Li diffusion on the micrometre space. For powder samples, collision-diffraction echo-attenuation plots were observed in a short observation time, which had not been fully explained. The diffraction patterns were reduced or disappeared for single-crystal garnet samples of Li6.5La3Zr1.5Ta0.5O12 (LLZO-Ta) and Li6.5La3Zr1.5Nb0.5O12 (LLZO-Nb). The inner morphology and grain boundaries affect importantly the collision-diffraction behaviours which is inherent to powder samples. The 7Li diffusion observed by PGSE-NMR depends on the observation time (Δ) and the pulsed field gradient (PFG) strength (g) in both powder and single-crystal samples, and the anomalous effects were reduced in the single-crystal samples. The scattered Li diffusion constants converged to a unique value (DLi) with a long Δ and a large g, which is eventually the smallest value. The DLi activation energy was close to that of the ionic conductivity (σ). The DLi values are plotted versus the σ values measured for four powder and two single-crystal garnet samples. Assuming the Nernst-Einstein (NE) relation which was derived for isolated ions in solution, the carrier numbers (NNE) were estimated from the experimental values of DLi and σ. The NNE values of metal-containing garnets were large (<1023 cm-3) and insensitive to temperature. They were larger than Li atomic numbers in cm3 calculated from the density, molecular formula and Avogadro number for LLZOs except for cubic LLZO (Li7La3Zr2O12, NNE∼ 1020 cm-3).

Aurora B kinase activity is regulated by SET/TAF1 on Sgo2 at the inner centromere.

The accurate regulation of phosphorylation at the kinetochore is essential for establishing chromosome bi-orientation. Phosphorylation of kinetochore proteins by the Aurora B kinase destabilizes improper kinetochore-microtubule attachments, whereas the phosphatase PP2A has a counteracting role. Imbalanced phosphoregulation leads to error-prone chromosome segregation and aneuploidy, a hallmark of cancer cells. However, little is known about the molecular events that control the balance of phosphorylation at the kinetochore. Here, we show that localization of SET/TAF1, an oncogene product, to centromeres maintains Aurora B kinase activity by inhibiting PP2A, thereby correcting erroneous kinetochore-microtubule attachment. SET localizes at the inner centromere by interacting directly with shugoshin 2, with SET levels declining at increased distances between kinetochore pairs, leading to establishment of chromosome bi-orientation. Moreover, SET overexpression induces chromosomal instability by disrupting kinetochore-microtubule attachment. Thus, our findings reveal the novel role of SET in fine-tuning the phosphorylation level at the kinetochore by balancing the activities of Aurora B and PP2A.

Development of a small car-mounted magnetic resonance imaging system for human elbows using a 0.2 T permanent magnet.

Portable magnetic resonance imaging (MRI) scanners can provide opportunities for mobile operation in many environments including disease screening and primary care suites. Here, we develop a new, compact transportable MRI system for imaging small joints of the extremities using a 0.2 T, 200 kg permanent magnet. The whole system, including the magnet, gradient coils, RF probes, and MRI consoles (80 kg in weight) was installed in a standard-size minivan-style vehicle. The use of the open-geometry magnet enables easy patient positioning within the limited space of the vehicle. We show that our portable MRI system provides clinically relevant images of screening for elbow injuries induced by overuse of overhand throwing. This transportable system is deployable during sport events or in environments with poor access to MRI systems, and could be applicable for mass screening, early diagnosis, and case finding.

Toward understanding the anomalous Li diffusion in inorganic solid electrolytes by studying a single-crystal garnet of LLZO-Ta by pulsed-gradient spin-echo nuclear magnetic resonance spectroscopy.

Li diffusion was observed by 7Li nuclear magnetic resonance (NMR) spectroscopy in three single-crystal samples of LLZO-Ta (Li6.5La3Zr1.5Ta0.5O12) grown by the floating zone melting method as well as a crushed sample in this study. Previously, the pulsed-gradient spin-echo 7Li NMR method was applied to Li+ diffusion measurements in inorganic solid electrolyte powder samples. Anomalous Li+ diffusion behaviors were observed such as dependence of the observing time (Δ) and pulsed-field-gradient strength (g), and the diffusive-diffraction patterns in short Δ in the echo-attenuation plots. In the powder samples, it is uncertain that the Li ions diffuse in the bulk within grain, across grains, or both. To date, the origins of the anomalous Li+ diffusion have not yet been clearly understood. From models of atomic-level lithium pathways, the micrometer-space diffusion channels are assumed to be narrow with curvatures. In contrast to the powder samples, a single crystal is supposed to be uniform without grain boundaries and the Li ions in single-crystal samples can diffuse in the bulk with negligible effects from the surface. The single-crystal samples are expected to give us proper answers. We found that the 7Li echo-attenuation plots of the single-crystal samples showed anomalous phenomena in dependence on Δ and g with much reduced manners. We found that the phenomena are inherent characteristics of Li+ diffusion in inorganic solid electrolytes. From the aspects of Li+ carrier numbers, the fast divergent Li+ diffusion constants, observed at short Δ with small g, contribute importantly to the electrochemical high ionic conduction measured by impedance spectroscopy.

Diffusion-weighting Caused by Spoiler Gradients in the Fast Imaging with Steady-state Precession Sequence May Lead to Inaccurate T2 Measurements in MR Fingerprinting.

Magnetic resonance fingerprinting (MRF) is a promising framework that allows the quantification of multiple magnetic resonance parameters with a single scan. MRF using fast imaging with steady-state precession (MRF-FISP) has robustness to off-resonance artifacts and has many applications in inhomogeneous fields. However, the spoiler gradient used in MRF-FISP is sensitive to diffusion motion, and may lead to quantification errors when the spoiler moment increases. In this study, we examined the effect of the diffusion weighting in MRF-FISP caused by spoiler gradients. The T2 relaxation times were greatly underestimated when large spoiler moments were used. The T2 underestimation was prominent for tissues with large values of T2 and diffusion coefficients. The T2 bias was almost independent of the apparent diffusion coefficient (ADC) and T2 values when the ADC map was measured and incorporated into the matching process. These results reveal that the T2 underestimation resulted from the diffusion weighting caused by the spoiler gradients.