Effect of the Relationship between Respiratory Interval and Temporal Resolution on Image Quality in Free-breathing Abdominal MR Imaging.

PURPOSE: To evaluate how the relationship between respiratory interval (RI) and temporal resolution (TR) impacts image quality in free-breathing abdominal MRI (FB-aMRI) using golden-angle radial sparse parallel (GRASP). METHODS: Ten healthy volunteers (25.9 ± 2.5 years, four women) underwent 2 mins free-breathing fat-suppression T1-weighted imaging using GRASP at RIs of 3 and 5s (RI3 and RI5, respectively) and retrospectively reconstructed at TR of 1.8, 2.9, 4.8, and 7.7s (TR1.8, TR2.9, TR4.8, and TR7.7, respectively) in each patient. The standard deviation (SD) under the diaphragm was measured using SD maps showing the discrepancy for each horizontal section at all TRs. Two radiologists evaluated image quality (visualization of the right hepatic vein at the confluence of the inferior vena cava, posterior segment branch of portal vein, pancreas, left kidney, and artifacts) at all TRs using a 5-point scale. RESULTS: The SD was significantly higher at TR1.8 compared to TR4.8 (P < 0.01) and TR7.7 (P < 0.001), as well as at TR2.9 compared to TR7.7 (P < 0.01) for both RIs. The SD between TR4.8 and TR7.7 did not differ for both RIs. For all visual assessment metrics, the TR1.8 scores were significantly lower than the TR4.8 and TR7.7 scores for both RIs. The pancreas and left kidney scores at TR2.9 were significantly lower than those at TR7.7 (P < 0.05) for RI5. Additionally, the left kidney score at TR1.8 was lower than that at TR2.9 (P < 0.05) for RI3. All scores at TR2.9, TR4.8, and TR7.7 were similar for RI3, while those at TR4.8 and TR7.7 were similar for RI5. CONCLUSION: Prolonging the TRs compared to RIs enhances image quality in FB-aMRI using GRASP.

Clinical, imaging, and molecular features of radiation-induced glioblastomas developing more than 20 years after radiation therapy for intracranial germinomatous germ cell tumor: illustrative cases.

BACKGROUND: Germinomatous germ cell tumor is highly sensitive to chemoradiotherapy; patients are expected to survive for decades. Many radiation-induced malignant gliomas (RIMGs) occur >10 years after radiotherapy. Standard therapy for RIMGs has not been established because of the lesion's rarity, the patient's shorter survival period, and the risk of radiation necrosis by repeat radiation. OBSERVATIONS: Two patients, a 32-year-old man and a 50-year-old man, developed glioblastomas more than 20 years after radiation monotherapy for germinoma with or without mature teratoma. The first patient showed a tumor in the left frontotemporal region with disseminated lesions and died 2 months after partial resection of the tumor without responding to the chemotherapy with temozolomide and bevacizumab. Methylation classifier analysis classified the pathology as closest to diffuse pediatric-type high-grade glioma, Rtk1 subtype. The second patient showed a tumor mass in the brainstem and left cerebellar peduncle, which worsened progressively during chemotherapy with temozolomide and bevacizumab. The tumor transiently responded to stereotactic radiotherapy with the CyberKnife. However, the patient died of RIMG recurrence-related aspiration pneumonia 11 months after the biopsy. Methylation classifier analysis classified the pathology as closest to infratentorial pilocytic astrocytoma. LESSONS: Chemoradiotherapy may improve the survival of patients with RIMGs. Furthermore, molecular features may influence the clinical, locoregional, and pathological features of RIMG.

Usefulness of Breath-Hold Fat-Suppressed T2-Weighted Images With Deep Learning-Based Reconstruction of the Liver: Comparison to Conventional Free-Breathing Turbo Spin Echo.

OBJECTIVES: The aim of this study was to evaluate the usefulness of breath-hold turbo spin echo with deep learning-based reconstruction (BH-DL-TSE) in acquiring fat-suppressed T2-weighted images (FS-T2WI) of the liver by comparing this method with conventional free-breathing turbo spin echo (FB-TSE) and breath-hold half Fourier single-shot turbo spin echo with deep learning-based reconstruction (BH-DL-HASTE). MATERIALS AND METHODS: The study cohort comprised 111 patients with suspected liver disease who underwent 3 T magnetic resonance imaging. Fifty-eight focal solid liver lesions ≥10 mm were also evaluated. Three sets of FS-T2WI were acquired using FB-TSE, prototypical BH-DL-TSE, and prototypical BH-DL-HASTE, respectively. In the qualitative analysis, 2 radiologists evaluated the image quality using a 5-point scale. In the quantitative analysis, we calculated the lesion-to-liver signal intensity ratio (LEL-SIR). Friedman test and Dunn multiple comparison test were performed to assess differences among 3 types of FS-T2WI with respect to image quality and LEL-SIR. RESULTS: The mean acquisition time was 4 minutes and 43 seconds ± 1 minute and 21 seconds (95% confidence interval, 4 minutes and 28 seconds to 4 minutes and 58 seconds) for FB-TSE, 40 seconds for BH-DL-TSE, and 20 seconds for BH-DL-HASTE. In the qualitative analysis, BH-DL-HASTE resulted in the fewest respiratory motion artifacts ( P < 0.0001). BH-DL-TSE and FB-TSE exhibited significantly less motion-related signal loss and clearer intrahepatic vessels than BH-DL-HASTE ( P < 0.0001). Regarding the edge sharpness of the left lobe, BH-DL-HASTE scored the highest ( P < 0.0001), and BH-DL-TSE scored higher than FB-TSE ( P = 0.0290). There were no significant differences among 3 types of FS-T2WI with respect to the edge sharpness of the right lobe ( P = 0.1290), lesion conspicuity ( P = 0.5292), and LEL-SIR ( P = 0.6026). CONCLUSIONS: BH-DL-TSE provides a shorter acquisition time and comparable or better image quality than FB-TSE, and could replace FB-TSE in acquiring FS-T2WI of the liver. BH-DL-TSE and BH-DL-HASTE have their own advantages and may be used complementarily.

Time to enhancement of breast lesions and normal breast parenchyma in light of menopausal status and menstrual cycle for ultrafast dynamic contrast-enhanced MRI using compressed sensing.

PURPOSE: To assess the dependency of the Time to enhancement (TTE) of breast lesions and normal breast parenchyma from menopausal status and menstrual cycle using ultrafast compressed sensing (CS) -accelerated dynamic contrast-enhanced (DCE) MRI. METHODS: This institutional review board approved retrospective study included 89 breast cancers, 22 benign lesions and 131 normal breast parenchymal foci. A prototypical ultrafast DCE sequence obtained 30 phases with 2.9 s temporal resolution. Mean and median TTE of all breast cancers, benign lesions and normal breast parenchymal foci were assessed. we also assessed whether there were any differences in TTE regarding the menopausal status and menstrual cycle. RESULTS: The TTE of breast cancer was significantly shorter than that of benign lesions and normal breast parenchymal foci in both the premenopausal status (5.8 vs. 8.7 and 8.7 s, respectively) (p = 0.0028 and < 0.0001, respectively) and postmenopausal status (5.8 vs. 11.6 and 11.6 s, respectively) (p < 0.0001 in both). The TTE of parenchymal foci in the premenopausal status was significantly shorter than that in the postmenopausal status (p = 0.0025). Although the TTE interval between cancer and parenchymal foci in premenopausal status is shorter than that in postmenopausal status, the AUCs in the pre- and postmenopausal status for differentiating breast cancer and parenchymal foci were comparable with using different cutoff TTE values. There were no differences in TTE regarding the menstrual cycle. CONCLUSIONS: The TTE derived from ultrafast CS-accelerated DCE MRI was useful to differentiate breast cancer from benign lesions and normal breast parenchymal foci in both pre- and postmenopausal status.

Optimal Temporal Resolution to Achieve Good Image Quality and Perform Pharmacokinetic Analysis in Free-breathing Dynamic Contrast-enhanced MR Imaging of the Pancreas.

PURPOSE: The optimal temporal resolution for free-breathing dynamic contrast-enhanced MRI (FBDCE-MRI) of the pancreas has not been determined. This study aimed to evaluate the appropriate temporal resolution to achieve good image quality and to perform pharmacokinetic analysis in FBDCE-MRI of the pancreas using golden-angle radial sparse parallel (GRASP). METHODS: Sixteen participants (53 ± 15 years, eight females) undergoing FBDCE-MRI were included in this prospective study. Images were retrospectively reconstructed at four temporal resolutions (1.8, 3.0, 4.8, and 7.8s). Two radiologists (5 years of experience) evaluated the image quality of each reconstructed image by assessing the visualization of the celiac artery (CEA), the common hepatic artery, the splenic artery, each area of the pancreas, and artifacts using a 5-point scale. Using Tissue-4D, pharmacokinetic parameters were calculated for each area in the reconstructed images at each temporal resolution for 16 examinations, excluding two with errors in the pharmacokinetic modeling analysis. Friedman and Bonferroni tests were used for analysis. A P value < 0.05 was considered statistically significant. RESULTS: During vascular assessment, only scores for the CEA at 7.8s were significantly lower than the other temporal resolutions. Scores of all pancreatic regions and artifacts were significantly lower at 1.8s than at 4.8s and 7.8s. In the pharmacokinetic analysis, all volume transfer coefficients (Ktrans), rate constants (Kep), and the initial area under the concentration curve (iAUC) in the pancreatic head and tail were significantly lower at 4.8s and 7.8s than at 1.8s. iAUC in the pancreatic body and extracellular extravascular volume fraction (Ve) in the pancreatic head were significantly lower at 7.8s than at 1.8s. CONCLUSION: A temporal resolution of 3.0s is appropriate to achieve image quality and perform pharmacokinetic analysis in FBDCE-MRI of the pancreas using GRASP.

Reduced-dose WBRT combined with SRS for 1-4 brain metastases aiming at minimizing neurocognitive function deterioration without compromising brain tumor control.

Background and purpose: To minimize cognitive decline without increasing brain tumor recurrence (BTR) by reduced-dose whole-brain radiotherapy (RD-WBRT) (25 Gy, 10 fractions) + stereotactic radiosurgery (SRS) in patients with ≤ 4 brain metastases. Materials and methods: Eligible patients with ≤ 4 brain metastases on contrast-enhanced MRI and Karnofsky Performance Status ≥ 70. The primary endpoint was the non-inferiority of BTR at distant sites in the brain (BTR-distant)-free survival at 6 months compared to that of the standard dose (SD)-WBRT (30 Gy, 10 fractions) + SRS arm in a randomized clinical trial (JROSG99-1) of SRS with/without SD-WBRT. Secondary endpoints included BTR at any brain sites (BTR-all) and neurocognitive function assessed by a six-test standardized battery. Results: Forty patients from seven institutions were enrolled (median age 69 years). The primary tumor site was a lung in 28 patients; 20 patients had a solitary brain metastasis. The median survival time was 19.0 months (95 %CI: 13.8 %-27.5 %). The BTR-distant-free survival at 6 months was 76.9 % (59.5 %-87.7 %), which is comparable to that of historical control although predetermined non-inferiority (>71 %) could not be confirmed (p = 0.16). The cumulative incidence of BTR-all at 6 months accounting for the competing risk of death was 23.0 % (11.4-37.1), which was not worse than that of historical control (p = 0.774). The frequency of the cumulative incidence of persistent cognitive decline at 6 months was 48.6 % under the [>2.0 SD in ≥ 1 test] definition. Conclusions: RD-WBRT may yield comparable intracranial tumor control when combined with SRS, and may reduce the risk of neurocognitive decline compared to that after SD-WBRT.

The impact of target positioning error and tumor size on radiobiological parameters in robotic stereotactic radiosurgery for metastatic brain tumors.

This study aimed to evaluate the effect of target positioning error (TPE) on radiobiological parameters, such as tumor control probability (TCP) and normal tissue complication probability (NTCP), in stereotactic radiosurgery (SRS) for metastatic brain tumors of different sizes using CyberKnife. The reference SRS plans were created using the circular cone of the CyberKnife for each spherical gross tumor volume (GTV) with diameters (φ) of 5, 7.5, 10, 15, and 20 mm, contoured on computed tomography images of the head phantom. Subsequently, plans involving TPE were created by shifting the beam center by 0.1-2.0 mm in three dimensions relative to the reference plans using the same beam arrangements. Conformity index (CI), generalized equivalent uniform dose (gEUD)-based TCP, and NTCP of estimated brain necrosis were evaluated for each plan. When the gEUD parameter "a" was set to - 10, the CI and TCP for the reference plan at the φ5-mm GTV were 0.90 and 80.8%, respectively. The corresponding values for plans involving TPE of 0.5-mm, 1.0-mm, and 2.0-mm were 0.62 and 77.4%, 0.40 and 62.9%, and 0.12 and 7.2%, respectively. In contrast, the NTCP for all GTVs were the same. The TCP for the plans involving a TPE of 2-mm was 7.2% and 68.8% at the φ5-mm and φ20-mm GTV, respectively. The TPEs corresponding to a TCP reduction rate of 3% at the φ5-mm and φ20-mm GTV were 0.41 and 0.99 mm, respectively. TPE had a significant effect on TCP in SRS for metastatic brain tumors using CyberKnife, particularly for small GTVs.

Radiobiological evaluation considering the treatment time with stereotactic radiosurgery for brain metastases.

Objective: We evaluated the radiobiological effect of the irradiation time with the interruption time of stereotactic radiosurgery (SRS) using CyberKnife® (CK) systemfor brain metastases. Methods: We used the DICOM data and irradiation log file of the 10 patients with brain metastases from non-small-cell lung cancer (NSCLC) who underwent brain SRS. We defined the treatment time as the sum of the dose-delivery time and the interruption time during irradiations, and we used a microdosimetric kinetic model (MKM) to evaluate the radiobiological effects of the treatment time. The biological parameters, i.e. α0, ß0, and the DNA repair constant rate (a + c), were acquired from NCI-H460 cell for the MKM. We calculated the radiobiological dose for the gross tumor volume (GTVbio) to evaluate the treatment time's effect compared with no treatment time as a reference. The D95 (%) and the Radiation Therapy Oncology Group conformity index (RCI) and Paddick conformity index (PCI) were calculated as dosimetric indices. We used several DNA repair constant rates (a + c) (0.46, 1.0, and 2.0) to assess the radiobiological effect by varying the DNA repair date (a + c) values. Results: The mean values of D95 (%), RCI, and PCI for GTVbio were 98.8%, 0.90, and 0.80, respectively, and decreased with increasing treatment time. The mean values of D95 (%), RCI, and PCI of GTVbio at 2.0 (a+c) value were 94.9%, 0.71, and 0.49, respectively. Conclusion: The radiobiological effect of the treatment time on tumors was accurately evaluated with brain SRS using CK. Advances in knowledge: There has been no published investigation of the radiobiological impact of the longer treatment time with multiple interruptions of SRS using a CK on the target dose distribution in a comparison with the use of a linac. Radiobiological dose assessment that takes into account treatment time in the physical dose in this study may allow more accurate dose assessment in SRS for metastatic brain tumors using CK.

Protein Modification at Tyrosine with Iminoxyl Radicals.

Post-translational modifications (PTMs) of proteins are a biological mechanism for reversibly controlling protein function. Synthetic protein modifications (SPMs) at specific canonical amino acids can mimic PTMs. However, reversible SPMs at hydrophobic amino acid residues in proteins are especially limited. Here, we report a tyrosine (Tyr)-selective SPM utilizing persistent iminoxyl radicals, which are readily generated from sterically hindered oximes via single-electron oxidation. The reactivity of iminoxyl radicals with Tyr was dependent on the steric and electronic demands of oximes; isopropyl methyl piperidinium oxime 1f formed stable adducts, whereas the reaction of tert-butyl methyl piperidinium oxime 1o was reversible. The difference in reversibility between 1f and 1o, differentiated only by one methyl group, is due to the stability of iminoxyl radicals, which is partly dictated by the bond dissociation energy of oxime O-H groups. The Tyr-selective modifications with 1f and 1o proceeded under physiologically relevant, mild conditions. Specifically, the stable Tyr-modification with 1f introduced functional small molecules, including an azobenzene photoswitch, to proteins. Moreover, masking critical Tyr residues by SPM with 1o, and subsequent deconjugation triggered by the treatment with a thiol, enabled on-demand control of protein functions. We applied this reversible Tyr modification with 1o to alter an enzymatic activity and the binding affinity of a monoclonal antibody with an antigen upon modification/deconjugation. The on-demand ON/OFF switch of protein functions through Tyr-selective and reversible covalent-bond formation will provide unique opportunities in biological research and therapeutics.

High-resolution three-dimensional T1-weighted hepatobiliary MR cholangiography using Gd-EOB-DTPA for assessment of biliary tree anatomy: Parallel imaging versus compressed sensing.

PURPOSE: To compare the quality of images obtained by T1-weighted hepatobiliary MR cholangiography using Gd-EOB-DTPA with 1-mm isovoxel acquisition and compressed sensing (T1-MRCCS) or parallel imaging (T1-MRCPI) for assessment of biliary tree anatomy. METHOD: We prospectively reviewed T1-MRCCS, T1-MRCPI, and respiratory-triggered 3D T2-weighted MR cholangiography (T2-MRC) images in 58 patients. Two radiologists independently assessed the three sets of images and scored the biliary tree visualization and overall image quality in all cases using a 5-point Likert scale. The resulting scores were compared among T1-MRCCS, T1-MRCPI, and T2-MRC images using a Friedman test followed by a Scheffe test. The inter-reader agreement in scoring was assessed using κ statistics. RESULTS: The image quality scores for the gallbladder on both T1-MRCCS and T1-MRCPI were significantly lower than those on T2-MRC (p < 0.01) for both readers. Meanwhile, the image quality scores for the right and left hepatic ducts and the anterior and posterior branches of the right hepatic duct on both T1-MRCCS and T1-MRCPI were significantly higher than those on T2-MRC (p < 0.05) for both readers. For Reader 2, the overall image quality scores on T1-MRCCS and T1-MRCPI were both significantly higher than those on T2-MRC (p < 0.05). There were no significant differences between the image quality scores on T1-MRCCS and T1-MRCPI for visualization of each bile duct (p < 0.05). CONCLUSIONS: There may be no significant difference in quality between T1-MRCCS images and T1-MRCPI images for assessment of biliary tree anatomy, and both types of images may be better than T2-MRC images, although clinical indication is limited compared with T2-MRC.

Detecting Mild Lower-limb Skeletal Muscle Fatigue with Stimulated-echo q-space Imaging.

The feasibility of detecting mild exercise-related muscle fatigue via stimulated echo (STE) and q-space imaging (qsi) was evaluated. The right calves of seven healthy volunteers were subjected to mild exercise loading, and qsi was generated using spin echo (Δ: 45.6 ms) and three different STE (Δ: 114, 214, and 414 ms) acquisitions. We concluded that qsi with an increased STE diffusion time can detect mild fatigue in the gastrocnemius muscle.

Intracranial Distribution of Intravenously Administered Gadolinium-based Contrast Agent over a Period of 24 Hours: Evaluation with 3D-real IR Imaging and MR Fingerprinting.

PURPOSE: To evaluate the feasibility for the detection of slight contrast effects after intravenous administration of single dose gadolinium-based contrast agent (IV-SD-GBCA), the time course of the GBCA distribution up to 24 h was examined in various fluid spaces and brain parenchyma using 3D-real IR imaging and MR fingerprinting (MRF). METHODS: Twenty-four patients with a suspicion of endolymphatic hydrops were scanned at pre-administration and at 10 min, 4 and 24 h post-IV-SD-GBCA. 3D-real IR images and MRF at the level of the internal auditory canal were obtained. The signal intensity on the 3D-real IR image of the cerebrospinal fluid (CSF) in the cerebellopontine angle cistern (CPA), Sylvian fissure (Syl), lateral ventricle (LV), and cochlear perilymph (CPL) was measured. The T1 and T2 values of cerebellar gray (GM) and white matter (WM) were measured using MRF. Each averaged value at the various time points was compared using an analysis of variance. RESULTS: The signal intensity on the 3D-real IR image in each CSF region peaked at 4 h, and was decreased significantly by 24 h (P< 0.05). All patients had a maximum signal intensity at 4 h in the CPA, and Syl. The mean CPL signal intensity peaked at 4 h and decreased significantly by 24 h (P < 0.05). All patients but two had a maximum signal intensity at 4 h. Regarding the T1 value in the cerebellar WM and GM, the T1 value at 10 min post-IV-GBCA was significantly decreased compared to the pre-contrast scan, but no significant difference was observed at the other time points. There was no significant change in T2 in the gray or white matter at any of the time points. CONCLUSION: Time course of GBCA after IV-SD-GBCA could be evaluated by 3D-real IR imaging in CSF spaces and in the brain by MRF.

Efficacy and Safety of the Radiotherapy for Liver Cancer: Assessment of Local Controllability and its Role in Multidisciplinary Therapy.

This study investigated the efficacy and safety of radiotherapy as part of multidisciplinary therapy for advanced hepatocellular carcinoma (HCC). Clinical data of 49 HCC patients treated with radiotherapy were assessed retrospectively. The efficacy of radiotherapy was assessed by progression-free survival, disease control rate, and overall survival. Safety was assessed by symptoms and hematological assay, and changes in hepatic reserve function were determined by Child-Pugh score and albumin-bilirubin (ALBI) score. Forty patients underwent curative radiotherapy, and nine patients with portal vein tumor thrombus (PVTT) underwent palliative radiotherapy as part of multidisciplinary therapy. Local disease control for curative therapy was 80.0% and stereotactic body radiotherapy was 86.7% which was greater than that of conventional radiotherapy (60.0%). Patients with PVTT had a median observation period of 651 days and 75% three-year survival when treated with multitherapy, including radiotherapy for palliative intent, transcatheter arterial chemoembolization, and administration of molecular targeted agents. No adverse events higher than grade 3 and no changes in the Child-Pugh score and ALBI score were seen. Radiotherapy is safe and effective for HCC treatment and can be a part of multidisciplinary therapy.

Diurnal variation in the glycogen content of the human liver using 13 C MRS.

Glycogen in tissues functions not only as carbohydrate reserves, but also as molecular sensors capable of activating signaling pathways in response to physical activity. While glycogen in the skeletal muscles is mainly a local energy substrate, glycogen in the liver serves as a glucose reserve to maintain normal blood glucose levels in the body, even during the sleep state. The aim of this study is to compare the diurnal variation of glycogen in the muscle and liver of human subjects under normal conditions. The glycogen content was measured in the muscle and liver of 10 young, healthy, male volunteers using 13 C MRS, a non-invasive technique. The subjects remained sedentary, and glycogen concentration was measured six times daily. Experimental meals were provided to achieve individual energy balance, estimated according to the energy requirement guideline for patients from Japan. The largest variation in muscle glycogen compared with 1 h after supper (20:00 on Day 1) was 3.1 ± 8.2 mmol/L (16:00 on Day 2). In the liver, however, the glycogen content decreased by 80.6 ± 40.4 mmol/L through the overnight fasting period (07:00 on Day 2). This study demonstrated that the glycogen content in the liver was significantly lower in the morning, while the glycogen content in the calf muscles underwent minimal diurnal variation. The overnight fast is a characteristic daily condition, in which liver glycogen content is low, whereas muscle glycogen content is relatively unaffected.

Impacts of interactions between ADH1B and ALDH2 genotypes on alcohol flushing, alcohol reeking on the day after drinking, and age distribution in Japanese alcohol-dependent men.

OBJECTIVE: This study sought to evaluate the impacts of interactions between the alcohol dehydrogenase-1B (rs1229984) genotype and the aldehyde dehydrogenase-2 (rs671) genotype on alcohol flushing, alcohol reeking on the day after drinking, and the age distribution in alcohol-dependent patients. METHODS: The study subjects were 4107 Japanese alcohol-dependent men who underwent alcohol dehydrogenase-1B and aldehyde dehydrogenase-2 genotyping: 4051 patients were asked about their current or former tendency to experience facial flushing after drinking a glass of beer, and 969 patients were asked about whether they had ever been told that they reeked of alcohol more than 12 hours after they had stopped drinking. RESULTS: Current, former, and never flushing were reported in 3.5, 14.9, and 81.5%, respectively, of the subject, and alcohol reeking after more than 12 hours in 36.1% of the subjects. The fast-metabolizing ADH1B*2(+) genotype (*1/*2 or *2/*2) and the inactive ALDH2*2(+) genotype (*1/*2 or *2/*2) affected the multivariate odds ratios for current or former flushing [odds ratio, 95% confidence interval = 2.27 (1.79-2.86) and 23.0 (18.6-28.5), respectively, vs. *2(-) genotype] and for alcohol reeking [0.39 (0.29-0.52) and 1.56 (1.09-2.25), respectively, vs. *2(-) genotype]. An age-dependent decrease in the ADH1B*2(-) and ALDH2*2(-) combination from 32.3% in the 30-39-year age group to 12.5% in the 70-79-year age group and an age-dependent increase in the ADH1B*2(+) and ALDH2*2(-) combination from 52.5% in the 30-39-year age group to 70.5% in the 70-79-year age group were observed (P < 0.0001 for trend). The frequencies of the ADH1B*2(-) and ALDH2*2(+) combination (4.7-6.2%) and the ADH1B*2(+) and ALDH2*2(+) combination (8.9-12.0%) did not change markedly with increasing age. CONCLUSION: Interactions between the alcohol dehydrogenase-1B and aldehyde dehydrogenase-2 genotypes modified alcohol flushing, alcohol reeking on the day after drinking, and the age distribution. These findings support the protective roles of the ADH1B*2(+) and ALDH2*2(+) genotypes against the development of alcohol dependence.

The neurocognitive function change criteria after whole-brain radiation therapy for brain metastasis, in reference to health-related quality of life changes: a prospective observation study.

BACKGROUND: We sought to construct the optimal neurocognitive function (NCF) change criteria sensitive to health-related quality of life (HR-QOL) in patients who have undergone whole-brain radiation therapy (WBRT) for brain metastasis. METHODS: We categorized the patients by the changes of NCF into groups of improvement versus deterioration if at least one domain showed changes that exceeded the cut-off while other domains remained stable. The remaining patients were categorized as stable, and the patients who showed both significant improvement and deterioration were categorized as 'both.' We examined the clinical meaning of NCF changes using the cut-off values 1.0, 1.5, and 2.0 SD based on the percentage of patients whose HR-QOL changes were ≥ 10 points. RESULTS: Baseline, 4-month and 8-month data were available in 78, 41 (compliance; 85%), and 29 (81%) patients, respectively. At 4 months, improvement/stable/deterioration/both was seen in 15%/12%/41%/32% of the patients when 1.0 SD was used; 19%/22%/37%/22% with 1.5 SD, and 17%/37%/37%/9% with 2.0 SD. The HR-QOL scores on the QLQ-C30 functional scale were significantly worse in the deterioration group versus the others with 1.0 SD (p = 0.013) and 1.5 SD (p = 0.015). With 1.5 SD, the HR-QOL scores on the QLQ-BN20 was significantly better in the improvement group versus the others (p = 0.033). However, when 'both' was included in 'improvement' or 'deterioration,' no significant difference in HR-QOL was detected. CONCLUSIONS: The NCF cut-off of 1.5 SD and the exclusion of 'both' patients from the 'deterioration' and 'improvement' groups best reflects HR-QOL changes.

Induction of ADCC by a folic acid-mAb conjugate prepared by tryptophan-selective reaction toward folate-receptor-positive cancer cells.

We developed conjugates between monoclonal antibody (mAb) and folic acid (FA) by using a tryptophan (Trp)-selective reaction, which yields relatively homogenous products compared to conventional methods. The obtained mAb-FA conjugates showed significant cellular cytotoxicity toward folate receptor-expressing cancer cells, demonstrating that the conjugates retained the Fc region's original function.

Detection of IV-gadolinium Leakage from the Cortical Veins into the CSF Using MR Fingerprinting.

PURPOSE: It has been reported that leakage of intravenously administered gadolinium-based contrast agents (IV-GBCAs) into the cerebrospinal fluid (CSF) from the cortical veins even in healthy subjects can be detected using a highly sensitive pulse sequence such as heavily T2-weighted 3D fluid-attenuated inversion recovery and 3D-real inversion recovery (IR). The purpose of this study was to evaluate the feasibility of MR fingerprinting to detect GBCA leakage from the cortical veins after IV-GBCA. MATERIALS: Fourteen patients with suspected endolymphatic hydrops (EH) who received a single dose of IV-GBCA (39-79 years old) were included. The real IR images as well as MR fingerprinting images were obtained at 4 h after IV-GBCA. T1 and T2 values were obtained using MR fingerprinting and analyzed in ROIs covering intense GBCA leakage, and non-leakage areas of the CSF as determined on real IR images. The scan time for real IR imaging was 10 min and that for MR fingerprinting was 41 s. RESULTS: The mean T1 value of the ROI in the area of GBCA leakage was 2422 ± 261 ms and that in the non-leakage area was 3851 ± 235 ms (P < 0.01). There was no overlap between the T1 values in the area of GBCA leakage and those in the non-leakage area.The mean T2 value in the area of GBCA leakage was 319 ± 90 ms and that in the non-leakage area was 670 ± 166 ms (P < 0.01). There was some overlap between the T2 values in the area of GBCA leakage and those in the non-leakage area. CONCLUSION: Leaked GBCA from the cortical veins into the surrounding CSF can be detected using MR fingerprinting obtained in <1 min.

Comprehensive Evaluation of B1+-corrected FISP-based Magnetic Resonance Fingerprinting: Accuracy, Repeatability and Reproducibility of T1 and T2 Relaxation Times for ISMRM/NIST System Phantom and Volunteers.

PURPOSE: This study aimed to evaluate comprehensively; accuracy, repeatability and reproducibility of T1 and T2 relaxation times measured by magnetic resonance fingerprinting using B1+-corrected fast imaging with steady-state precession (FISP-MRF). METHODS: The International Society of Magnetic Resonance in Medicine/National Institute of Standards and Technology (ISMRM/NIST) phantom was scanned for 100 days, and six healthy volunteers for 5 days using a FISP-MRF prototype sequence. Accuracy was evaluated on the phantom by comparing relaxation times measured by FISP-MRF with the reference values provided by the phantom manufacturer. Daily repeatability was characterized as the coefficient of variation (CV) of the measurements over 100 days for the phantom and over 5 days for volunteers. In addition, the cross-scanner reproducibility was evaluated in volunteers. RESULTS: In the phantom study, T1 and T2 values from FISP-MRF showed a strong linear correlation with the reference values of the phantom (R2 = 0.9963 for T1; R2 = 0.9966 for T2). CVs were <1.0% for T1 values larger than 300 ms, and <3.0% for T2 values across a wide range. In the volunteer study, CVs for both T1 and T2 values were <5.0%, except for one subject. In addition, all T2 values estimated by FISP-MRF in vivo were lower than those measured with conventional mapping sequences reported in previous studies. The cross-scanner variation of T1 and T2 showed good agreement between two different scanners in the volunteers. CONCLUSION: B1+-corrected FISP-MRF showed an acceptable accuracy, repeatability and reproducibility in the phantom and volunteer studies.

Usefulness of breath-hold compressed sensing accelerated three-dimensional magnetic resonance cholangiopancreatography (MRCP) added to respiratory-gating conventional MRCP.

PURPOSE: To clarify the clinical usefulness of breath-hold compressed sensing three-dimensional magnetic resonance cholangiopancreatography (BH-MRCP) added to conventional respiratory-gating MRCP (RG-MRCP), we prospectively evaluated the image quality of BH-MRCP and compared it with that of RG-MRCP. We also evaluated to what extent the overall image quality was improved by adding BH-MRCP to RG-MRCP. MATERIALS AND METHODS: A total of 113 patients who underwent RG-MRCP and BH-MRCP at a 3-T MR unit were enrolled. We set a scan time of approximately 180 s for RG-MRCP and 20 s for BH-MRCP before examination, and measured actual scan time and assessed image quality using a 5-point scale (5, good; 1, poor). Image quality scores of 1, 2 and 3 were considered clinically inadequate. Image quality scores of RG-MRCP and BH-MRCP were compared. In addition, we compared "RG-MRCP alone" and "hybrid MRCP" (the best-scoring image was picked from RG-MRCP and BH-MRCP when the RG-MRCP score was clinically inadequate). RESULTS: The mean actual scan time of RG-MRCP/BH-MRCP was 191/20 s. The mean scores of RG-MRCP, BH-MRCP and hybrid MRCP were 3.67, 3.35 and 3.92, respectively. The score of hybrid MRCP was significantly better than that of RG-MRCP (P <  0.05). The image quality of RG-MRCP was clinically inadequate in 43/113 (38 %) cases and the inadequate image quality was improved to be clinically adequate in 13/43 (30 %) cases by adding BH-MRCP. CONCLUSION: BH-MRCP brings added value to RG-MRCP because an additional examination of BH-MRCP could compensate for the image deterioration of RG-MRCP caused by motion artifacts.