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This study aimed to assess the suitability of hyperpolarized 129 Xe (HPXe) MRI for noninvasive longitudinal evaluation of pulmonary function in preclinical lung cancer models. A mouse model of lung cancer (LC) was induced in 5 mice by intraperitoneal injection of urethane, while a negative-control (NC) mice ( N  = 5) was prepared by injection of saline solution. Longitudinal HPXe MRI was performed over a 5-month period to monitor lung ventilation and gas exchange. The treatment efficacy of ethyl pyruvate (EP), an anti-inflammatory drug, to the mouse LC model was monitored using HPXe MRI by commencing administration of EP pre (early-phase) and 1-month post (late-phase) injection of urethane ( N  = 5 mice for each group). Gas-exchange function in LC mice was significantly reduced at 1-month after urethane injection compared with NC mice administered with saline ( P < 0.01). Thereafter, it remained consistently lower than that of the NC group for the full 5-month measurement period. In contrast, the ventilation function of the LC model mice was not significantly different to that of the NC mice. Histological analysis revealed alveolar epithelial hyperplasia in LC mice alveoli at 1 month after urethane injection, and adenoma was confirmed 3 months after the injection. The early- and late-phase EP interventions were found to improve HPXe MRI metrics (reduced at 1 month postinjection of urethane) and significantly inhibit tumor growth. These results suggest that HPXe MRI gas-exchange metrics can be used to quantitatively assess changes in the precancerous lesion microenvironment and to evaluate therapeutic efficacy in cancer. Thus, HPXe MRI can be utilized to noninvasively monitor pulmonary pathology during LC progression and can visualize functional changes during therapy., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Atsuomi Kimura et al.)

Three-dimensional (3D) representation of a tumor with respect to its size, shape, location, and boundaries is still a challenge in photoacoustic (PA) imaging using artificial contrast agents as probes. We carried out PA imaging of tumors in mice using 800RS-PMPC, which was obtained by coupling of 800RS, a near-infrared cyanine dye, with PMPC, a highly selective tumor-targeting methacrylate polymer having phosphorylcholine side chains, as a probe. The conjugate 800RS-PMPC forms compact nanoparticles (d DLS  = 14.3 nm), retains the biocompatibility of the parent polymer (PMPC) and exhibits unprecedented PA performance. When applied to mice bearing a 6 × 3 × 3 mm 3 tumor buried 6 mm beneath the skin, the probe 800RS-PMPC selectively accumulates in the tumor and emits PA signals that are strong enough to be unambiguously distinguished from noise signals of endogenous blood/hemoglobin. The PA image thus obtained under high-threshold conditions allows 3D characterization of the tumor in terms of its size, shape, location, and boundaries.

Purpose: To evaluate the usefulness of high-temporal-resolution dynamic contrast-enhanced (DCE) MRI and quantitative pharmacokinetic analysis to differentiate the normal-appearing pituitary gland from a pituitary macroadenoma., Materials and Methods: Twenty-seven patients with macroadenomas underwent preoperative DCE-MRI with a temporal resolution of 5 s using compressed sensing to obtain pharmacokinetic parameters. Two independent observers localized the normal-appearing pituitary gland on post-contrast T1-weighted images before and after referring to the corresponding K trans maps. Agreements between the localizations and intraoperative findings were evaluated using the kappa statistics. The Mann-Whitney U test was used to compare the pharmacokinetic parameters of the normal-appearing pituitary gland and adenoma., Results: For both observers, the agreement between the MRI-based localization and the intraoperative findings increased after referring to the K trans maps (observer 1, 0.930-1; observer 2, 0.636-0.855). The normal-appearing pituitary gland had significantly higher K trans [/min] (1.50 ± 0.80 vs 0.58 ± 0.49, P < 0.0001), k ep [/min] (3.19 ± 1.29 vs 2.15 ± 1.18, P = 0.0049), and v e (0.43 ± 0.15 vs 0.25 ± 0.17, P = 0.0003) than adenoma., Conclusion: High-temporal-resolution DCE-MRI and quantitative pharmacokinetic analysis help accurately localize the normal-appearing pituitary gland in patients with macroadenomas. The normal-appearing pituitary gland was characterized by higher K trans , k ep , and v e than macroadenoma. Dynamic contrast-enhanced MRI with high-temporal-resolution using compressed sensing was used for quantitative pharmacokinetic analysis of pituitary macroadenomas. An observer study, the use of K trans maps improved accuracy in localizing the normal-appearing pituitary gland. As compared to an adenoma, the normal-appearing pituitary gland had significantly higher K trans , k ep , and v e values.

Purpose: Identifying plaque components such as intraplaque hemorrhage, lipid rich necrosis, and calcification is important to evaluate vulnerability of carotid atherosclerotic plaque; however, conventional vessel wall MR imaging may fail to discriminate plaque components. We aimed to evaluate the components of plaques using quantitative susceptibility mapping (QSM), a newly developed post-processing technique to provide voxel-based quantitative susceptibilities., Methods: Seven patients scheduled for carotid endarterectomy were enrolled. Magnitude and phase images of five-echo 3D fast low angle shot (FLASH) were obtained using a 3T MRI, and QSM was calculated from the phase images. Conventional carotid vessel wall images (black-blood T 1 -weighted images [T 1 WI], T 2 -weighted images [T 2 WI], proton-density weighted images [PDWI], and time-of-flight images [TOF]) were also obtained. Pathological findings including intraplaque hemorrhage, calcification, and lipid rich necrosis at the thickest plaque section were correlated with relative susceptibility values with respect to the sternocleidomastoid muscle on QSM. On conventional vessel wall images, the contrast-noise ratio (CNR) between the three components and sternocleidomastoid muscle was measured respectively. Wilcoxon signed-rank test analyses were performed to assess the relative susceptibility values and CNR., Results: Pathologically, lipid rich necrosis was proved in all of seven cases, and intraplaque hemorrhage in five of seven cases. Mean relative susceptibility value of hemorrhage was higher than lipid rich necrosis unexceptionally (P = 0.0313). There were no significant differences between CNR of hemorrhage and lipid rich necrosis on all sequences. In all six cases with plaque calcification, susceptibility value of calcification was significantly lower than lipid rich necrosis unexceptionally (P = 0.0156). There were significant differences between CNRs of lipid rich necrosis and calcification on T 1 WI, PDWI, TOF (P < 0.05)., Conclusion: QSM of carotid plaque would provide a novel quantitative MRI contrast that enables reliable differentiation among intraplaque hemorrhage, lipid rich necrosis, and calcification, and be useful to identify vulnerable plaques.

Dynamic contrast-enhanced MRI may yield variable longitudinal-relaxation time (T1) values depending on the precision of the fat-suppression (FS) technique. This study aimed to investigate the influences of FS methods on T1 value measurements on phantoms containing test tubes filled with mixtures of five volumes of fat, six amounts of contrast agent, and water. Volumetric interpolated images were obtained using several FS methods and flip angles. T1 maps were created based on the variable flip angle approach. The T1 values of water obtained by point-resolved single-voxel spectroscopy (SVS) were used as reference values. Notably, FS methods were shown to have substantial effects on the measurement of T1 values. Among the tested FS methods, the Dixon (water) method produced T1 values most similar to SVS, which can be considered as a reference value for clinical practice.

Differences in the volumes of artifacts caused by variously shaped titanium objects on magnetic resonance imaging (MRI) were evaluated. Spherical-, square cubic-, and regular tetrahedron-shaped isotropic, and elongated spherical-, elongated cubic-, and elongated tetrahedron-shaped anisotropic objects, with identical volumes, were prepared. Samples were placed on a nickel-doped agarose gel phantom and covered with nickel-nitrate hexahydrate solution. Three-Tesla MR images were obtained using turbo spin echo and gradient echo sequences. Areas with ±30% of the signal intensity of the standard background value were considered artifacts. Sample volumes were deducted from these volumes to calculate the total artifact volumes. Isotropic samples had similar artifact volumes. For anisotropic samples, the artifact volume increased in proportion with the normalized projection area. MRI artifact size can be reduced by high anisotropic designs, and by positioning the long axis of the metal device as parallel as possible to the magnetic field axis.

Purpose: High Mobility Group Box1 (HMGB1), which is one of the damage-associated molecular pattern molecules relating to various inflammatory diseases, has gained interest as a therapeutic target because of its involvement in wound healing processes. In the present study, we investigated HMGB1 as a potential therapeutic target in a model of lung fibrosis using a preclinical hyperpolarized 129 Xe (HPXe) MRI system., Methods: Lung injury was induced by intra-peritoneal injection of bleomycin (BLM) in 19 mice. Three weeks post-injection (when fibrosis was confirmed histologically), administration of ethyl pyruvate (EP) and alogliptin (ALG), which are down- and up-regulators of HMGB1, respectively, was commenced in six and seven of the 19 mice, respectively, and continued for a further 3 weeks. A separate sham-instilled group was formed of five mice, which were administered with saline for 6 weeks. Over the second 3-week period, the effects of disease progression and pharmacological therapy in the four groups of mice were monitored by HPXe MRI metrics of fractional ventilation and gas-exchange function., Results: Gas-exchange function in BLM mice was significantly reduced after 3 weeks of BLM challenge compared to sham-instilled mice (P < 0.05). Ethyl pyruvate was found to improve HPXe MRI metrics of both ventilation and gas exchange, and repair tissue damage (assessed histologically), to a similar level as sham-instilled mice (P < 0.05), whilst ALG treatment caused no significant improvement of pulmonary function., Conclusion: This study demonstrates the down-regulator of HMGB1, EP, as a potential therapeutic agent for pulmonary fibrosis, as assessed by a non-invasive HPXe MRI protocol.

Recent advances in imaging technology have enabled us to obtain more detailed images of the human fetus in a nondestructive and noninvasive manner. Through detailed images, elaborate three-dimensional (3D) models of the developing brain can be reconstructed. The segmentation of the developing brain has been determined by serial sections. Therefore, in this study, we attempted to develop a 3D model of the fetal brain using magnetic resonance image (MRI). MR images from 19 specimens (11 embryonic specimens and eight fetal specimens from 5.2 to 225 mm in crown rump length) were used to reconstruct 3D models of regionalized developing brains. From this analysis, we succeeded in registering a maximum of nine landmarks on MR images and reconstructing 19 sequential models of the regionalized developing brain. To confirm the validity of the landmarks, we also compared our results with three serial sections from the Kyoto Collection; the same morphological characteristics were observed on both serial sections and MRI. The morphological minutiae could be found on MR images, and regionalized models of the developing brain could be reconstructed. These results will be useful for clinical diagnosis of living fetuses in utero., (© 2017 Japanese Teratology Society.)

Objectives: Disturbance of the development of the nasal septum in the early prenatal period causes congenital facial anomalies characterized by a flat nose and defects of the anterior nasal spine (ANS), such as Binder phenotype. The present research aimed to assess the development of the nasal septum and the ANS with growth in the early prenatal period., Methods: Magnetic resonance images were obtained from 56 specimens. Mid-sagittal images were analyzed by using geometric morphometrics for the development of the nasal septum, and angle analysis was performed for the development of the ANS. Additionally, we calculated and visualized the ontogenetic allometry of the nasal septum., Results: Our results showed that the nasal septum changed shape in the anteroposterior direction in smaller specimens, while it maintained an almost isometric shape in larger specimens. Furthermore, mathematical evidence revealed that the maturation periods of the shapes of the ANS and the nasal septum were around 12 and 14 weeks of gestation, respectively., Conclusion: The anteroposterior development of the nasal septum is specific until 14 weeks of gestation, and it is important for nasal protrusion and the development of the ANS. Therefore, the disturbance of such development could induce low nasal deformity, including Binder phenotype. © 2017 John Wiley & Sons, Ltd., (© 2017 John Wiley & Sons, Ltd.)

Purpose: The purpose of this work was to investigate disease progression and treatment response in a murine model of chronic obstructive pulmonary disease (COPD) using a preclinical hyperpolarized 129 Xe (HPXe) magnetic resonance imaging (MRI) strategy., Methods: COPD phenotypes were induced in 32 mice by 10 weeks of exposure to cigarette smoke (CS) and lipopolysaccharide (LPS). Efficacy of ethyl pyruvate (EP), an anti-inflammatory drug, was investigated by administering EP to 16 of the 32 mice after 6 weeks of CS and LPS exposure. HPXe MRI was performed to monitor changes in pulmonary function during disease progression and pharmacological therapy., Results: HPXe metrics of fractional ventilation and gas-exchange function were significantly reduced after 6 weeks of CS and LPS exposure compared to sham-instilled mice administered with saline (P < 0.05). After this observation, EP administration was started in 16 of the 32 mice and continued for 4 weeks. EP was found to improve HPXe MRI metrics to a similar level as in sham-instilled mice (P < 0.01). Histological analysis showed significant alveolar tissue destruction in the COPD group, but relatively normal alveolar structure in the EP and sham-instilled groups., Conclusion: This study demonstrates the potential efficacy of EP for COPD therapy, as assessed by a noninvasive, translatable 129 Xe MRI procedure. Magn Reson Med 78:721-729, 2017. © 2016 International Society for Magnetic Resonance in Medicine., (© 2016 International Society for Magnetic Resonance in Medicine.)

Zr-Ag composites were fabricated to decrease the magnetic susceptibility by compensating for the magnetic susceptibility of their components. The Zr-Ag composites with a different Zr-Ag ratio were swaged, and their magnetic susceptibility, artifact volume, and mechanical properties were evaluated by magnetic balance, three-dimensional (3-D) artifact rendering, and a tensile test, respectively. These properties were correlated with the volume fraction of Ag using the linear rule of mixture. We successfully obtained the swaged Zr-Ag composites up to the reduction ratio of 96% for Zr-4, 16, 36, 64Ag and 86% for Zr-81Ag. However, the volume fraction of Ag after swaging tended to be lower than that before swaging, especially for Ag-rich Zr-Ag composites. The magnetic susceptibility of the composites linearly decreased with the increasing volume fraction of Ag. No artifact could be estimated with the Ag volume fraction in the range from 93.7% to 95.4% in three conditions. Young's modulus, ultimate tensile strength (UTS), and 0.2% yield strength of Zr-Ag composites showed slightly lower values compared to the estimated values using a linear rule of mixture. The decrease in magnetic susceptibility of Zr and Ag by alloying or combining would contribute to the decrease of the Ag fraction, leading to the improvement of mechanical properties., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

The use of a quenching gas, isobutene, with a low vapor pressure was investigated to enhance the utility of hyperpolarized (129) Xe (HP Xe) MRI. Xenon mixed with isobutene was hyperpolarized using a home-built apparatus for continuously producing HP Xe. The isobutene was then readily liquefied and separated almost totally by continuous condensation at about 173 K, because the vapor pressure of isobutene (0.247 kPa) is much lower than that of Xe (157 kPa). Finally, the neat Xe gas was continuously delivered to mice by spontaneous inhalation. The HP Xe MRI was enhanced twofold in polarization level and threefold in signal intensity when isobutene was adopted as the quenching gas instead of N2 . The usefulness of the HP Xe MRI was verified by application to pulmonary functional imaging of spontaneously breathing mice, where the parameters of fractional ventilation (ra ) and gas exchange (fD ) were evaluated, aiming at future extension to preclinical studies. This is the first application of isobutene as a quenching gas for HP Xe MRI., (Copyright © 2016 John Wiley & Sons, Ltd.)

Recently, we developed novel chiral dendrimer-triamine-coordinated Gd-MRI contrast agents (Gd-MRI CAs), which showed longitudinal relaxivity (r₁) values about four times higher than that of clinically used Gd-DTPA (Magnevist(®), Bayer). In our continuing study of pharmacokinetic differences derived from both the chirality and generation of Gd-MRI CAs, we found that the ability of chiral dendrimer Gd-MRI CAs to circulate within the body can be directly evaluated by in vitro MRI (7 T). In this study, the association constants (K(a)) of chiral dendrimer Gd-MRI CAs to bovine serum albumin (BSA), measured and calculated with a quartz crystal microbalance (QCM) in vitro, were found to be an extremely easy means for evaluating the body-circulation ability of chiral dendrimer Gd-MRI CAs. The K(a) values of S-isomeric dendrimer Gd-MRI CAs were generally greater than those of R-isomeric dendrimer Gd-MRI CAs, which is consistent with the results of our previous MRI study in vivo.

Polymers are concentration-amplified with respect to the monomeric units. We show here that a phosphorylcholine polymer enriched with (13)C/(15)N at the methyl groups is self-traceable by multiple-resonance (heteronuclear-correlation) NMR in tumor-bearing mice inoculated with the mouse rectal cancer cell line (colon 26). Preliminary measurements indicated that the present polymeric nanoprobe was satisfactorily distinguished from lipids and detectable with far sub-micromolar spectroscopic and far sub-millimolar imaging sensitivities. Detailed ex vivo and in vivo studies for the tumor-bearing mice administered the probe with a mean molecular weight of 63,000 and a mean size of 13 nm, revealed the following: (1) this probe accumulates in the tumor highly selectively (besides renal excretion) and efficiently (up to 30% of the injected dose), (2) the tumor can thus be clearly in vivo imaged, the lowest clearly imageable dose of the probe being 100 mg/kg or 2.0 mg/20-g mouse, and (3) the competition between renal excretion and tumor accumulation is size-controlled; that is, the larger (higher molecular-weight) and smaller (lower molecular-weight) portions of the probe undergo tumor accumulation and renal excretion, respectively. The observed size dependence suggests that the efficient tumor-targeting of the present probe is stimulated primarily by the so-called enhanced permeability and retention (EPR) effect, that is, size-allowed invasion of the probe into the tumor tissue via defective vascular wall. Self-traceable polymers thus open an important area of magnetic resonance imaging (MRI) of tumors and may provide a highly potential tool to visualize various delivery/localization processes using synthetic polymers.

The feasibility of ventilation imaging with hyperpolarized (HP) (129) Xe MRI has been investigated for quantitative and regional assessment of ventilation in spontaneously breathing mice. The multiple breath ventilation imaging technique was modified to the protocol of spontaneous inhalation of HP (129) Xe delivered continuously from a (129) Xe polarizer. A series of (129) Xe ventilation images was obtained by varying the number of breaths before the (129) Xe lung imaging. The fractional ventilation, r, was successfully evaluated for spontaneously breathing mice. An attempt was made to detect ventilation dysfunction in the emphysematous mouse lung induced by intratracheal administration of porcine pancreatic elastase (PPE). As a result, the distribution of fractional ventilation could be visualized by the r map. Significant dysfunction of ventilation was quantitatively identified in the PPE-treated group. The whole-lung r value of 0.34 ± 0.01 for control mice (N = 4) was significantly reduced, to 0.25 ± 0.07, in PPE-treated mice (N = 4) (p = 0.038). This study is the first application of multiple breath ventilation imaging to spontaneously breathing mice, and shows that this methodology is sensitive to differences in the pulmonary ventilation. This methodology is expected to improve simplicity as well as noninvasiveness when assessing regional ventilation in small rodents., (Copyright © 2014 John Wiley & Sons, Ltd.)

Objective: This study was carried out to describe the clinical and magnetic resonance imaging (MRI) findings of patients with intermittent closed lock (ICL) of the temporomandibular joint (TMJ)., Study Design: This retrospective study included 58 joints with ICL and 526 joints without ICL as controls. We compared the MRI findings between the patients with and without ICL and investigated clinical and MRI finding of ICL patients. We divided ICL patients into 2 groups based on the treatment efficacy: effective and ineffective., Results: There were significant differences in the prevalence of disk deformity between the joints with and without ICL. Masticatory muscle pain was observed in 41.7% of the effective group and in 80% of the ineffective group, respectively., Conclusions: These results suggest that there is a relationship among the onset of ICL and disk deformation. Masticatory musclepain was significantly observed in the ineffective group., (Copyright © 2014 Elsevier Inc. All rights reserved.)

High-sensitivity nuclear magnetic resonance (NMR) of gaseous atoms realized by using a hyperpolarization technique is an attractive research tool used in a wide range of areas, such as physics, chemistry, material science and biomedical imaging. One of the most promising applications of this technology is the use as a noninvasive diagnostic tool for pulmonary diseases, where hyperpolarized (HP) noble gases, (3)He and (129)Xe, play a role as gaseous (i.e. inhalable) contrast agents of magnetic resonance imaging (MRI). During the last two decades, lung MRI with HP gases has become widely applicable from mouse to human. In this review we present a brief overview of recent progress made by our group in the development of HP (129)Xe MR measurements, while focusing on the methodology for probing pulmonary dysfunctions in mice.

Animal disease models are pivotal in investigating the pathogenesis of emphysema and developing novel drugs, but the modalities to evaluate murine emphysema models have been of limited validity and sensitivity. In this study, we evaluated hyperpolarized (129)Xe magnetic resonance imaging (MRI) and micro-computed tomography (micro-CT) compared with traditional methods, such as plethysmography and histology. Elastase-treated mice and adiponectin knockout mice were used as murine emphysema models to evaluate these modalities. Three weeks after elastase administration, significant and heterogeneous emphysema was evaluated according to the mean linear intercept and plethysmography parameters. Notably, the distribution of low-density areas, as examined by micro-CT, correlated with the mean linear intercept and plethysmography parameters in whole lungs. These correlations were also observed in regional areas. Furthermore, we introduced hyperpolarized (129)Xe MRI, which can evaluate gas exchange between the alveoli and blood during spontaneous breathing. Parameters of gas exchange (fD) and alveolar size (Vs/Va) were significantly decreased in elastase-treated mice, and moderately correlated with the plethysmography parameters. Of importance, we could detect a decrease of the fD value in low-density areas with micro-CT, suggesting that gas exchange decreased in emphysematous lesions. Likewise, these parameters (fD and Vs/Va) were also decreased in adiponectin knockout mice, which exhibit emphysema with a homogeneous distribution. We demonstrated the feasibility of (129)Xe MRI and micro-CT in combination with traditional modalities. These noninvasive modalities provide complementary data that can be used for repeated estimations of regional gas exchange and lung morphology.

Susceptibility artifacts generated in magnetic resonance (MR) images were quantitatively evaluated for various metals using a three-dimensional (3-D) artifact rendering to demonstrate the correlation between magnetic susceptibility and artifact volume. Ten metals (stainless steel, Co-Cr alloy, Nb, Ti, Zr, Mo, Al, Sn, Cu and Ag) were prepared, and their magnetic susceptibilities measured using a magnetic balance. Each metal was embedded in a Ni-doped agarose gel phantom and the MR images of the metal-containing phantoms were taken using 1.5 and 3.0 T MR scanners under both fast spin echo and gradient echo conditions. 3-D renderings of the artifacts were constructed from the images and the artifact volumes were calculated for each metal. The artifact volumes of metals decreased with decreasing magnetic susceptibility, with the exception of Ag. Although Sn possesses the lowest absolute magnetic susceptibility (1.8×10(-6)), the artifact volume from Cu (-7.8×10(-6)) was smaller than that of Sn. This is because the magnetic susceptibility of Cu was close to that of the agarose gel phantom (-7.3×10(-6)). Since the difference in magnetic susceptibility between the agarose and Sn is close to that between the agarose and Ag (-17.5×10(-6)), their artifact volumes were almost the same, although they formed artifacts that were reversed in all three dimensions., (Copyright © 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

MRI of hyperpolarized (129)Xe dissolved in pulmonary tissues, and blood has the potential to offer a new tool for regional evaluation of pulmonary gas exchange and perfusion; however, the extremely short T2* and low magnetization density make it difficult to acquire the image. In this study, an ultrashort echo-time sequence was introduced, and its feasibility to quantitatively assess emphysema-like pulmonary tissue destruction by a combination of dissolved- and gas-phase (129)Xe lung MRI was investigated. The ultrashort echo-time has made it possible to acquire dissolved (129)Xe images with reasonably high spatial resolution of 0.625 × 0.625 mm(2) and to obtain T2* of 0.67 ± 0.30 ms in a spontaneously breathing mouse at 9.4 T. The regional dynamic alveolar gas uptake as well as subsequent transport by pulmonary blood flow was also visualized. The ratio of (129)Xe magnetization that diffused into the septa relative to the gas-phase magnetization F was regionally evaluated. The mean F value of elastase-treated mice was 2.28 ± 0.46%, which was significantly reduced from that of control mice 3.41 ± 0.48% (P = 0.0052). This reflects the reduced uptake efficiency due to alveolar tissue destruction and is correlated with the histologically derived alveolar surface-to-volume ratio., (Copyright © 2012 Wiley Periodicals, Inc.)

Purpose: The purpose of this study was to evaluate the feasibility and potential usefulness of unenhanced magnetic resonance (MR) hepatic portal perfusion using arterial spin labeling (ASL) among healthy volunteers and hepatocellular carcinoma patients., Materials and Methods: The five healthy volunteers underwent unenhanced MR perfusion with inversion time 2 (TI2) values at 500-ms intervals between 2,000 and 4,000 ms, and the 12 patients underwent unenhanced MR perfusion using ASL and computed tomography (CT) perfusion during superior mesenteric artery (SMA) portography. The regions of interest were placed in both the right and left lobes of the liver or both the right anterior and posterior segments of the liver and were placed over the tumor if a lesion was located within a particular perfusion study slice., Results: In the healthy volunteer study, perfusion rate in hepatic parenchyma showed a peak at the TI2 value of 3,000 ms (254.3 ml/min/100 g ± 58.3). In patients, a fair correlation was observed between CT and MR perfusion (r = 0.795, P < 0.01)., Conclusion: Our results demonstrate a significant fair correlation between unenhanced MR hepatic portal perfusion imaging using ASL and CT perfusion during SMA portography.

In many clinical imaging procedures using arrays of multiple receiver coils, a uniform sensitivity process is performed using the sensitivity distribution from the body coil. This causes the noise to be uneven, and background noise cannot be used when measuring the signal-to-noise ratio (SNR). The SNR of clinical images with sensitivity correction using arrays of multiple receiver coils sets the region of interest (ROI) in the region where the signal is uniform, and is limited to the identical ROI method where measurements are taken with noise from the identical region. When SNR is measured with the identical ROI method, uneven noise caused by sensitivity correction as well as the signal strength distribution within the ROI of the object is reflected in the noise. Therefore, evaluation must be performed in as localized a position as possible. Measurement error becomes small on images with higher resolution, and if ROI larger than 10×10 pixels can be set in a region of even signal, SNR measurement of clinical images with less underestimation may be possible.

In the present study, a balanced steady-state free precession pulse sequence combined with compressed sensing was applied to hyperpolarized (129) Xe lung imaging in spontaneously breathing mice. With the aid of fast imaging techniques, the temporal resolution was markedly improved in the resulting images. Using these protocols and respiratory gating, (129) Xe lung images in end-inspiratory and end-expiratory phases were obtained successfully. The application of these techniques for pulmonary functional imaging made it possible to simultaneously evaluate regional ventilation and gas exchange in the same animal. A comparative study between healthy and elastase-induced mouse models of emphysema showed abnormal ventilation as well as gas exchange in elastase-treated mice., (Copyright © 2011 John Wiley & Sons, Ltd.)

Purpose: We investigated the characteristics of hyperpolarized (HP) (129)Xe magnetic resonance (MR) imaging obtained from balanced steady-state free precession (SSFP) measurement of mouse lungs, especially under spontaneous breathing, and compared the results with those obtained using traditional spoiled gradient echo (SPGR) method, focusing on improved signal-to-noise ratio (SNR) and reduced total acquisition time., Methods: We calculated magnetization response of the HP (129)Xe gas for the balanced SSFP sequence under spontaneous breathing to derive optimal conditions for the imaging experiment. We then placed an anesthetized mouse in the magnet (9.4T) supplied with oxygen gas and a mixture of HP (129)Xe gas supplied from a continuous-flow hyperpolarizing system. We obtained an axial plane image of the lung through balanced SSFP and SPGR sequences, changing the various magnetic resonance (MR) imaging parameters, and measured the SNR of these images., Results: We demonstrated the clear dependence of image intensity on flip angle and number of shots. The SNR was higher in balanced SSFP than in SPGR and 2.3-fold higher compared at each maximum. In contrast, total acquisition time in balanced SSFP was shortened to about one-eighth that of SPGR using a one-shot acquisition mode., Conclusion: In HP (129)Xe MR imaging of the lung of a spontaneously breathing mouse, balanced SSFP sequence with multi-shot and centric order acquisition provides higher SNR in a shorter acquisition time than SPGR.

Pulmonary study using hyperpolarized (HP) (129)Xe gas as an imaging medium must focus on dissolved-phase signals to make the most of the characteristic affinity of xenon for biological tissues, including blood. However, the spectral pattern of these signals differs between mice and other animals, including rats, canines, and humans. Dissolved-phase study has been reported only scarcely in mice, so spectral assignment has been an important subject for HP (129)Xe magnetic resonance (MR) spectroscopy (MRS) and MR imaging for its wider application. We performed MRS, including magnetization transfer experiments, and MR imaging studies to confirm the origin of dissolved-phase signals of mice ex vivo and in vivo and obtained evidence to assign dissolved-phase signals at 192 ppm for epicardial fat, 196 ppm for lung parenchyma, and 200 ppm for blood. These results were the first to show the possibility of fast exchange of xenon between plasma and red blood cells.

Background: Para-aortic lymph node (PALN) metastasis is an important prognostic factor in patients with pancreatic cancer, but accurate preoperative diagnosis is difficult. The objective of this study was to assess the accuracy of diagnosis of PALN by computed tomography (CT), magnetic resonance imaging (MRI), and (18)F-fluorodeoxyglucose positron-emission tomography (FDG-PET)., Methods: From August 2005 to July 2008, 119 patients with invasive ductal adenocarcinoma of the pancreas were included in this study. PALNs with a longer diameter >10 mm on CT or MRI were suspected of being involved by metastasis, whereas FDG uptake exceeding that of the adjacent normal tissue was considered to be positive for metastasis on FDG-PET studies. The imaging findings were compared with the pathological diagnosis of PALN metastasis., Results: PALN dissection was performed in 71 patients (60.0%). Although histopathological examination revealed metastasis in 6 patients (8.5%), none of these patients was positive in any of the preoperative imaging studies. The longer diameter, the shorter diameter, the ratio of the two diameters, and the calculated lymph node volume showed no significant differences between patients with and without PALN metastasis., Conclusions: Preoperative detection of PALN metastasis in patients with pancreatic cancer is very difficult. Intraoperative histopathological examination of frozen sections is necessary if radical resection is contemplated.

This is a study on the analysis of hyperpolarized (HP) (129)Xe dynamics applied in the lung of a pathological model mouse under spontaneous respiration. A novel parameter k(1)k(2) - a product of the rate constant for Xe transfer from gas to dissolved phase (k(1)) and from dissolved to gas phase (k(2)) - was shown to be derived successfully from the analysis of the HP (129)Xe dynamic MR experiment in the mouse lung under spontaneous respiration with the aid of a selective pre-saturation technique. A comparative study using healthy mice and model mice induced with lung cancer (by injection of murine tumor B16BL6 melanoma) was performed and a significant difference was found in the k(1)k(2) values of the two groups, that is, 0.020+/-0.007s(-2) (n=4) for healthy mice and 0.032+/-0.04s(-2) (n=3) for lung cancer model mice (p=0.04). Thus, the parameter obtained by our proposed method is considered useful for detection of lung tumors., (Copyright (c) 2009 Elsevier Ireland Ltd. All rights reserved.)

Purpose: We investigated the feasibility of 3D hyperpolarized (HP) (129)Xe magnetic resonance (MR) imaging at an extremely low concentration of HP (129)Xe supplied from a continuous flow-type hyperpolarizing (CF-HP) system and established a standard procedure for measuring regional lung ventilation of small animals, such as the mouse, as a baseline for further studies., Materials and Methods: We performed 3D HP (129)Xe MR imaging of the lungs of 2 healthy and 2 emphysematous mice that were spontaneously breathing diluted HP (129)Xe (<1%). From the three 3D MR images acquired by varying the flip angle of the radiofrequency (RF) pulse, we calculated the time constant of regional recovery, tau'(rep), which represents the time required for HP (129)Xe magnetization to be replenished approximately 63% after destruction of hyperpolarization by RF saturation pulse. After calculating the tau'(rep) maps, we examined the validity of our method., Results: We used diluted xenon from the CF-HP system to acquire 3D HP (129)Xe MR images of the mouse lung that were undiminished under spontaneous respiration. The averaged tau'(rep) values were longer for the emphysematous lungs than for the healthy lungs, which reflected ventilation defects in the emphysematous lung., Conclusions: This procedure permitted us to estimate the regional lung ventilation for any arbitrarily set slice, and it will provide a standard for measuring regional lung ventilation as a baseline for further studies.

When measuring the signal-to-noise ratio (SNR) of an image the used parallel magnetic resonance imaging, it was confirmed that there was a problem in the application of past SNR measurement. With the method of measuring the noise from the background signal, SNR with parallel imaging was higher than that without parallel imaging. In the subtraction method (NEMA standard), which sets a wide region of interest, the white noise was not evaluated correctly although SNR was close to the theoretical value. We proposed two techniques because SNR in parallel imaging was not uniform according to inhomogeneity of the coil sensitivity distribution and geometry factor. Using the first method (subtraction mapping), two images were scanned with identical parameters. The SNR in each pixel divided the running mean (7 by 7 pixels in neighborhood) by standard deviation/radical2 in the same region of interest. Using the second (consecutive) method, more than fifty consecutive scans of the uniform phantom were obtained with identical scan parameters. Then the SNR was calculated from the ratio of mean signal intensity to the standard deviation in each pixel on a series of images. Moreover, geometry factors were calculated from SNRs with and without parallel imaging. The SNR and geometry factor using parallel imaging in the subtraction mapping method agreed with those of the consecutive method. Both methods make it possible to obtain a more detailed determination of SNR in parallel imaging and to calculate the geometry factor.

Purpose: To apply a continuous flow-type hyperpolarizing (CF-HP) system to lung imaging and investigate the feasibility of hyperpolarized (129)Xe MRI at a low xenon concentration., Materials and Methods: Under two conditions where a 3% or 70% xenon gas mixture was constantly supplied, gas- and dissolved-phase (129)Xe images and diffusion-weighted (129)Xe-gas images were obtained from the mouse lung. Signal-to-noise ratio (SNR) of the (129)Xe images and the apparent diffusion coefficient (ADC) of xenon were compared between the two gas mixtures., Results: The SNR of gas- and dissolved-phase images were 28.9 +/- 5.2 and 12.0 +/- 2.0, respectively, using the 70% xenon gas mixture, while they were 22.9 +/- 4.8 and 6.8 +/- 0.6, using the 3% mixture. The ADC of xenon using the 3% xenon gas mixture was approximately 1.5 times higher than that using the 70% one. These results indicated that the high ADC increases the apparent replenishment rate of gas-phase magnetization, thus resulting in a reduction of the SNR loss induced by diluting xenon with quenching gases., Conclusion: The CF-HP system is useful for lung imaging at an extremely low concentration of xenon, which enables one to fully restrain an anesthetic effect of xenon and to reduce consumption of xenon in a measurement., ((c) 2008 Wiley-Liss, Inc.)

Parallel magnetic resonance imaging (MRI) with arrays of receiver coils such as those of sensitivity encoding (SENSE) are being widely used. However, conventional methods of image signal-to-noise ratio (SNR) determination cannot be used for parallel MRI, and a novel method has been reported in JSRT. However, this method of SNR determination is for phantom images not for clinical images. Therefore, we researched accurate measurement of the image noise of parallel MRI reconstruction including the unfolding process and uniformity filters. The possibility of a subtraction method using clinical images and the accuracy of standard deviation (SD) of clinical images for optimum ROI were studied because it was not possible to use the air-signal method. The results indicated that the position of the ROI was selected for uniformity of signal intensity area and that the size of the ROI was about 50 pixels. However, under these conditions, the noise value of SNR was higher than that using the phantom-subtraction method. In addition, the tissue-subtraction method was useful when the two scanning images were in agreement.

Purpose: The purpose of this study was to acquire a hyperpolarized (HP) (3)He image of the mouse lung and to estimate 3He T1 in the lung from wash-out curve analysis under spontaneous respiration., Materials and Methods: We first tested the K-Rb hybrid method for the spin-exchange optical pumping (SEOP) of 3He using a home-built noble gas polarizer operated at atmospheric pressure and then applied it to MR imaging and spectroscopy of the mouse lung. The longitudinal relaxation time (T1) of 3He in the mouse lung was estimated under spontaneous respiration by exploiting a novel method in which SF6 gas at thermal equilibrium was utilized in combination with the HP 3He gas in the quantitative wash-out curve analysis. This method utilizes the difference in the profile of the wash-out curve of HP 3He and SF6 at thermal equilibrium. That is, the slope of the 3He wash-out curve in the semi-logarithmic plots is affected by 3 factors, including RF pulse angle, respiration, and T1, whereas the slope of the SF6 wash-out curve is only the function of respiratory term., Results: A 3He lung image was obtained successfully, and we were able to estimate successfully 3He T1 in the mouse lung under spontaneous respiration using a novel method; the estimated T1 value was 68+/-25 s, which was reasonable compared with the value calculated from the literature data measured during breath-hold., Conclusion: We succeeded in acquiring the first 3He image of mouse lung in vivo in this country, and our proposed method of estimating 3He T1 in the lung under spontaneous respiration is noninvasive and readily applied to animals and would be useful to evaluate the alveolar gas exchange function as well as oxygen partial pressure (pO2) in lungs of animals.

The magnetic resonance phase-contrast technique for the measurement of flow velocity and volume in true and false lumens was studied in six patients with chronic dissecting aneurysms. Phase-contrast images were obtained at a level perpendicular to the dissecting aneurysms of the descending aorta. As the maximum diameter of aneurysms increased, the ratio of the cross-sectional area of the false to the true lumen increased and the peak average velocity in the true lumen during systole was decreased. This technique proved invaluable for determining prognosis and operability for this condition.

Background: Myocardial tissue tagging with the use of magnetic resonance imaging allows noninvasive regional analysis of heart wall motion and deformation. However, any evaluation of the effect of disease or treatment requires a baseline reference of normal values and variation. We studied the two-dimensional motion of material points imaged within the left ventricular wall using spatial modulation of magnetization (SPAMM) in 12 normal human volunteers., Methods and Results: Five parallel short-axis and five parallel long-axis slices were acquired at five times during systole. SPAMM tags were generated at end diastole using a 7-mm grid. Intersection point data were analyzed for displacement, rotation, and torsion, and triangles of points were analyzed for local rotation and principal strains. Short-axis displacement was the least in the septum for all longitudinal levels (P < .001). Torsion about the long axis was uniform circumferentially because of the motion of the centroids used to reference the rotation. In the long-axis images, the base displaced longitudinally toward the apex, with the posterior wall moving farther than the anterior wall (13.4 +/- 2.2 versus 9.7 +/- 1.8 mm, P < .001) in this direction. The largest principal strain (maximum lengthening) was approximately radially oriented in both views. In the short-axis images, the minimum principal strain (maximum shortening) increased in magnitude toward the apex (P < .001) with little circumferential variation, except at midventricle, where the anterior wall showed greater contraction than the posterior wall (-0.21 +/- 0.03 versus -0.19 +/- 0.02, P < .02)., Conclusions: Consistent regional variations in deformation are seen in the normal human heart. Displacement and maximum shortening strains are well characterized with two-dimensional magnetic resonance tagging; however, higher-resolution images will be required to study transmural variations.

A 25-year-old Japanese woman had fever and general fatigue for 3 months. Examination revealed no abnormalities in her pulse or blood pressure. Gallium 67 scintigraphy demonstrated an abnormal uptake in the right supraclavicular and anterior chest regions. A plain computerized tomogram (CT) scan revealed ringed high densities in the ascending and descending aorta and the left common carotid artery, however, an enhanced CT scan showed only irregular aortic walls. Angiography gave a final diagnosis of Takayasu's disease. Magnetic resonance imaging (MRI) angiography also demonstrated complete occlusive stenosis of the left common carotid artery and right subclavian artery. Our case suggests the usefulness of gallium 67 scintigraphy, plain CT scan and MRI angiography in the active phase or early diagnosis of Takayasu's disease.

Magnetic resonance imaging (MRI) is a new noninvasive technique for visualization of the cardiovascular system, and is used to evaluate tissue characteristics, cardiac function and blood flow abnormalities, as well as to obtain morphological information. In this paper we presented results of clinical and laboratory research obtained using conventional spin echo MRI with regard to cardiovascular anatomy, tissue characterization and physiology. Furthermore, experience with two new techniques, cine-MRI and volume-selected MR spectroscopy, and their potential clinical usefulness in detecting cardiovascular diseases are documented.

To assess the usefulness of X-ray computed tomography (CT) and magnetic resonance imaging (MRI) in detecting and evaluating ischemic heart disease, conventional and enhanced CT were performed for 180 patients (150 with transmural infarction, 12 with subendocardial infarction, and 18 with angina pectoris). MRI examinations were performed for 38 patients (31 with transmural infarction, three with subendocardial infarction, and four with angina pectoris). With enhanced CT, two findings in the myocardium were direct evidence of myocardial infarction: 1. filling defects on the early scans, and 2. late enhancement of the myocardium on the delayed scans. The former were observed mainly at the sites of recent anterior myocardial infarction and the latter were seen in about half of the patients with recent and remote anterior myocardial infarctions. However, these findings were inadequately imaged in patients with inferoposterior infarction and subendocardial infarction. Among 137 patients with transmural infarction, enhanced CT revealed left ventricular aneurysms in 51 (37%) and ventricular thrombi in 26 (19%). ECG-gated MRI apparatus having a superconducting magnetic operating at 0.25 Tesla was used, and data for this study were collected using the single-slice spin echo technique. In eight of nine patients with acute myocardial infarction, gated MRI demonstrated the infarcted myocardium as regions of high signal intensity relative to that of the adjacent normal myocardium. Such a difference in MRI signal intensity was scarcely recognized in the chronic stage of myocardial infarction, but the indirect findings of infarction, such as regional wall thinning, wall motion disturbances, left ventricular aneurysms, and ventricular thrombi were easily detected using MRI. No characteristic finding was obtained by CT or MRI in patients with angina pectoris.

Blood flow images by magnetic resonance imaging (MRI) using a 0.25 T unit were evaluated for nine normal volunteers and 108 subjects with a variety of cardiovascular abnormalities. Using the non-gated short-spin echo (SE) technique, blood flow in the cardiovascular systems was not imaged in the normal volunteers. Using end-systolic and end-diastolic SE techniques for the normal subjects, blood flow in the cardiac chambers was not clearly imaged. Blood flow in the ascending aorta and aotric arch often did not appear in the gated SE images of the normal subjects. However, blood flow in the descending aorta was often observed in the gated SE images. Blood flow imaging was demonstrated by both non-gated and gated SE techniques in regions where blood flow was relatively slow; for example, in the left atrium of mitral stenosis, in an aortic aneurysm, in a false lumen of an aortic dissection, and in the left ventricle having old myocardial infarction. Using the non-gated inversion recovery (IR) technique, no blood flow was imaged in the cardiovascular system except in the left atrium of one case with mitral stenosis. Using the non-gated short SE technique, there was good correlation between the thrombus formation and the presence of blood flow images in the left atria of 17 patients with mitral stenosis, and in the aneurysmal portions of the aorta or in the false lumens of aortic dissection of 18 patients. It was suggested that mural thrombi in such diseases were related to the relatively slow blood flow. Blood flow imaging easily distinguished stagnant blood flow from mural thrombi using non-gated short SE, end-systolic SE, and IR techniques. Thus, blood flow imaging using MRI should become an important means of evaluating the cardiovascular system.

Focuses on a medical case involving patients with central diabetes insipidus who had abnormal findings on magnetic resonance imaging that were compatible with his syndrome. Disorders which produce lymphocytic infiltration of the pituitary gland; Characteristics inherent with patients afflicted with the different types of disorders.