Katsusuke Kyotani

Compensatory glutamine metabolism promotes glioblastoma resistance to mTOR inhibitor treatment

The mechanistic target of rapamycin (mTOR) is hyperactivated in many types of cancer, rendering it a compelling drug target; however, the impact of mTOR inhibition on metabolic reprogramming in cancer is incompletely understood. Here, by integrating metabolic and functional studies in glioblastoma multiforme (GBM) cell lines, preclinical models, and clinical samples, we demonstrate that the compensatory upregulation of glutamine metabolism promotes resistance to mTOR kinase inhibitors. Metabolomic studies in GBM cells revealed that glutaminase (GLS) and glutamate levels are elevated following mTOR kinase inhibitor treatment. Moreover, these mTOR inhibitor-dependent metabolic alterations were confirmed in a GBM xenograft model. Expression of GLS following mTOR inhibitor treatment promoted GBM survival in an α-ketoglutarate-dependent (αKG-dependent) manner. Combined genetic and/or pharmacological inhibition of mTOR kinase and GLS resulted in massive synergistic tumor cell death and growth inhibition in tumor-bearing mice. These results highlight a critical role for compensatory glutamine metabolism in promoting mTOR inhibitor resistance and suggest that rational combination therapy has the potential to suppress resistance.

Triexponential function analysis of diffusion‐weighted MRI for diagnosing prostate cancer

To evaluate more detailed information noninvasively through on diffusion and perfusion in prostate cancer (PCa) using triexponential analysis of diffusion‐weighted imaging (DWI).

Pancreatic fat content assessed by 1H magnetic resonance spectroscopy is correlated with insulin resistance, but not with insulin secretion, in Japanese individuals with normal glucose tolerance

Whereas some clinical studies have shown that excessive fat accumulation in the pancreas is associated with impairment of insulin secretion, others have not found such an association. 1H magnetic resonance spectroscopy allows quantitative fat analysis in various tissues including the pancreas. The pathological relevance of pancreatic fat content (PFC) in Japanese individuals remains unclear, however.

Dynamic Blood Oxygen Level-dependent MR Imaging of Muscle: Comparison of Postocclusive Reactive Hyperemia in Young Smokers and Nonsmokers.

PURPOSE The role of early stage functional assessment of muscle blood flow response (MFR) by dynamic muscle blood oxygen level-dependent (BOLD) magnetic resonance (MR) imaging is unknown. We investigated the effect of smoking on vascular function according to MFR derived from dynamic muscle BOLD MR imaging during postocclusive reactive hyperemia in young smokers and nonsmokers. METHODS Sixteen healthy male volunteers (8 smokers, 8 nonsmokers; mean age, 30.4 ± 4.6 years) underwent BOLD MR imaging of the left calf muscle. During reactive hyperemia provoked by a cuff-compression technique, we measured muscle BOLD (mB) using a 3-tesla single-shot multi-echo gradient-echo echo-planar imaging sequence. The 2 key mB variables in the reactive hyperemic phase that we studied were times to half hyperemic peak (T(1/2peak)) and peak (TTP), each measured from cuff deflation. We used the Welch test to assess differences in these between smokers and nonsmokers. RESULTS T(1/2peak) and TTP were significantly longer in smokers (P < 0.05) in reactive hyperemia. T(1/2peak) was 13.8 ± 5.4 s in smokers and 7.6 ± 1.5 s in nonsmokers, and TTP was 67.5 ± 18.8 s in smokers and 45.4 ± 7.1 s in nonsmokers. CONCLUSION Dynamic BOLD MR imaging of calf muscle during postocclusive reactive hyperemia demonstrated statistically significant differences in T(1/2peak) and TTP between young smokers and nonsmokers, indicating the presence of early stage smoking-related deterioration in MFR.

Radiofrequency-shielding Effect of a Titanium Mesh Implanted for Cranioplasty

PURPOSE After cranioplasty with a titanium mesh, radiofrequency (RF)-shielding images appear during magnetic resonance (MR) imaging. To clarify their influence, we evaluated the effect of mesh position, phase-encoding direction, and type of coil employed. MATERIALS AND METHODS On a 1.5-tesla MR imager, we placed a titanium mesh board (100 × 100 × 0.8 mm) on the surface of a cubic phantom to mimic a human brain and used a quadrature coil and an 8-channel neurovascular coil to measure nonuniformity, signal decay ratio, and the B1 map. RESULTS Nonuniformity was 6.7 times higher at the quadrature head coil and 1.6 times higher at the neurovascular coil when the mesh was on the phantoms right side or anterior to it than when it was on its superior end or absent. The profile of the signal decay ratio increased by 1.9% mm(-1) from 0 to 40 mm from the mesh side to the base value at the quadrature head coil when the mesh was on the phantoms right side and 0.9% mm(-1) from 0 to 80 mm at the neurovascular coil when the mesh was on the phantoms right side or anterior to it. The quadrature head coil showed greater incline of the profile when the mesh was on the right in coronal and axial views and no notable change in the profile in coronal and sagittal views when the mesh was on the superior end. In the B1 map, the flip angle was lower when the mesh was nearer. CONCLUSION The response to the RF-shielding effect from a titanium mesh depends on the location of the mesh and the RF coil used but not on the phase-encoding direction.

Influence of arm position and respiration technique during liver examinations on the detectability of mammary lesions

During liver computed tomography (CT), scanning is performed with the raised arm position and an inhalation technique. However, for liver magnetic resonance imaging (MRI), the arms are placed at the sides of the body and an exhalation technique is used. This study was aimed at evaluating the effect that the patient’s arm position and respiration technique had on the ability to detect mammary glands in the scan range to discover unexpected mammary lesions during the liver MRI examination. Liver MRI and CT images were compared for 337 female patients. More than half of the mammary glands were included in 97.3% of MRI, but in 4.7% of CT. No mammary lesions were found during CT, whereas seven were found during MRI. The mammary lesions are more likely to be detected when the patient places her arms at the sides of the body and uses the exhalation technique during liver MRI.

Assessment of the Quality of Breast MR Imaging Using the Modified Dixon Method and Frequency-Selective Fat Suppression: A Phantom Study

To obtain objective and concrete data by physically assessing the quality of breast magnetic resonance images based on the fat-suppression effect by the modified Dixon method (mDixon) and frequency-selective fat suppression (e-Thrive) using an original lipid-content breast phantom that could easily reveal the influence of non-uniform fat suppression in breast magnetic resonance imaging. The fat-suppression uniformity was approximately seven times superior when using mDixon compared with when using e-Thrive. mDixon appears to have a significant advantage.

Comparison of dosimetric parameters in the treatment planning of magnetic resonance imaging–based intracavitary image-guided adaptive brachytherapy with and without optimization using the central shielding technique

Abstract This study aimed to compare dosimetric parameters between non-optimized and optimized treatment planning (NOP and OP, respectively) of magnetic resonance imaging (MRI) –based intracavitary (IC) image-guided adaptive brachytherapy (IGABT) using the central shielding (CS) technique for cervical cancer. Fifty-three patients treated with external beam radiotherapy using CS and MRI-based IGABT with the IC approach alone were evaluated. The total high-risk clinical target volume (HR-CTV) D90 was aimed at >70 Gy equivalent dose in 2 Gy fractions (EQD2). In the small HR-CTV group (≤30 cm3), the mean D90s for NOP/OP were 98.6/80.7 Gy. In the large (30.1–40 cm3) and extensive (>40 cm3) HR-CTV groups, the mean D90s were 81.9/77.5 and 71.1/73.6 Gy, respectively. The mean D2cc values for organs at risks (OARs) in OP were acceptable in all groups, despite the high bladder D2cc in the NOP. The correlation between HR-CTV at first brachytherapy (BT) and NOP D90 was stronger than that between HR-CTV at first BT and OP D90. The targeted HR-CTV D90 and dose constraints of D2cc for OARs were both achieved in 16 NOP/47 OP patients for the bladder, 39/50 for the rectum, and 47/50 for the sigmoid colon (P < 0.001, P = 0.007, and P = 0.34, respectively). For small tumors, the role of optimization was to reduce the D2cc for OARs while maintaining the targeted D90. However, optimization was of limited value for extensive tumors. Methods of optimization in IGABT with CS for cervical cancer should be standardized while considering its effectiveness and limitations.

The lesion characteristics assessed by LGE‐MRI after the cryoballoon ablation and conventional radiofrequency ablation

Rhythm outcomes after the pulmonary vein isolation (PVI) using the cryoballoon (CB) are reported to be excellent. However, the lesions after CB ablation have not been well discussed. We sought to characterize and compare the lesion formation after CB ablation with that after radiofrequency (RF) ablation.