PEG-poly(L-lysine)-based polymeric micelle MRI contrast agent: Feasibility study of a Gd-micelle contrast agent for MR lymphography.

PURPOSE: To investigate the feasibility of polymeric micelle of poly(ethyleneglycol) (PEG)-b-poly(L-lysine-DOTA) (Gd-micelle) as a contrast agent for magnetic resonance lymphography (MRL). MATERIALS AND METHODS: Twenty-four female BALB/c mice were randomly divided into four groups of six mice each. Among them, mice of two groups were injected of complete Freund's adjuvant to obtain inflamed lymph nodes. We subcutaneously injected 0.5 µmol Gd per mouse of Gd-micelle or gadofluorine P in the right rear footpad. Identical 3D T1 -weighted gradient-echo imaging (1T MRI system) were subsequently obtained to create time-intensity curves of the right popliteal, sacral, and lumbar-aortic lymph nodes and to measure the contrast ratios (CRs). The peak CR, area under the curve (AUC), and elimination half-life (T1/2 ) of CR of the popliteal lymph node were assessed by two-way factorial analysis of variance. We also performed a qualitative assessment of normal and inflamed lymph node at three timepoints. RESULTS: The mean peak CR of Gd-micelle was 2.64 and 1.89 for gadofluorine P in normal mice, and 3.48 and 2.73 in the inflamed lymph node. Statistically, peak CR was higher for Gd-micelle (P = 0.004). In addition, the AUC was larger (P < 0.001) and T1/2 was longer (P < 0.001) for Gd-micelle. In qualitative assessment, Gd-micelle demonstrated the same or higher scores in every lymph node, and demonstrated a higher score in lumbar-aortic lymph node of a 360-minute image (P = 0.006) and in inflamed lymph node of a 360-minute image (P = 0.009). CONCLUSION: Compared to gadofluorine P, Gd-micelle showed higher and more prolonged enhancement in MRL imaging in normal and inflamed lymph nodes. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2018;47:238-245.

Efficacy and feasibility of ambulatory treatment-based monthly nedaplatin plus S-1 in definitive or salvage concurrent chemoradiotherapy for early, advanced, and relapsed esophageal cancer.

BACKGROUND: Standard chemoradiotherapy (CRT) using cisplatin (CDDP) and 5-fluorouracil (5-FU) is an optional treatment for patients with stage II-III esophageal cancer. However, there are some demerits in this regimen because CDDP administration requires a large transfusion volume and 5-FU must be continuously infused over 24 h. Therefore, hospitalization is unavoidable. We collected retrospectively the data of definitive CRT with nedaplatin and S-1 as carried out in our institution. METHODS: Patients with early and advanced esophageal cancer and relapsed esophageal cancer after radical surgery were included. Nedaplatin 80 mg/m(2) was given on days 1 and 29, and S-1 80 mg/m(2) on days 1-14 and 29-42. No prophylactic treatment with granulocyte colony stimulating factor was administered. Patients received two courses of concurrent radiotherapy of more than 50 Gy with or without two additional courses as adjuvant therapy every 4 weeks. RESULTS: Between August 2011 and June 2015, 89 patients (age range, 44-86 years; K-PS 90-100, 81 %; squamous cell carcinoma histology, 97 %; definitive/salvage CRT, 75/25 %) were collected. Twenty-one (24 %) patients completed four cycles, and 94 % received two or more cycles. Grade 4 leukopenia, thrombocytopenia, and anemia occurred in 12, 7, and 10 % of the patients, respectively. Five patients developed febrile neutropenia. Grade 3 non-hematological toxicity included infection in 12 %, mucositis/esophagitis in 3 %, kidney in 3 %, and fatigue in 3 %. Sixty-four patients (72 %) received the prescribed full dose and full cycles of chemotherapy. A complete response was achieved in 76 patients (85 %). The 3-year overall survival rate was 54.4 % in definitive CRT and 39.8 % in salvage CRT, respectively. Sixty-two subjects (70 %) received treatment as outpatients. CONCLUSIONS: Nedaplatin and S-1 in combination with radiotherapy is feasible, and toxicity is tolerable. This treatment method has the potential to shorten hospitalization without impairing the efficacy of CRT.

The effects on gastric emptying and carbohydrate loading of an oral nutritional supplement and an oral rehydration solution: a crossover study with magnetic resonance imaging.

BACKGROUND: Preoperative administration of clear fluids by mouth has recently been endorsed as a way to improve postoperative outcomes. A carbohydrate-containing beverage supplemented with electrolytes or proteins may have additional benefits for patients' satisfaction. However, effects on gastric residual, nausea, and emesis and the effectiveness of these beverages for improving patients' hydration status have not been well defined. METHODS: We evaluated changes in gastric volume over time by magnetic resonance imaging, as well as blood glucose levels, before and after administration of 500 mL oral rehydration solution (ORS) containing 1.8% glucose and electrolytes in 10 healthy volunteers. The same volume of an oral nutritional supplement (ONS) containing 18% glucose and supplemental arginine (545 mOsm/kg) was given to the same population using a crossover design. RESULTS: The mean (median, 95% confidence interval) gastric fluid volume at 1 hour after oral ingestion was 55.0 (55.3, 39.0-70.9) mL in the ORS group, whereas 409.2 (410.9, 371.4-447.0) mL in the ONS group (P = 0.0002). The gastric fluid volume of all participants in the ORS group returned to <1 mL/kg at 90 minutes after ingestion, whereas none reached <1 mL/kg at 120 minutes in the ONS group. The ONS group showed a sustained increase in the blood glucose level after ingestion (P < 0.0001 to baseline at 30, 60, 120 minutes), while the ORS group showed an initial increase (P < 0.0001, P = 0.01, P = 0.205 at each time point). CONCLUSIONS: ORS supplemented with a small amount of glucose showed faster gastric emptying, which may make it suitable for preoperative administration. In contrast, ONS supplemented with arginine with a relatively low osmolality was associated with a longer time for gastric emptying, although it showed a sustained increase in blood glucose level.

Association between iron content and gray matter missegmentation with voxel-based morphometry in basal ganglia.

PURPOSE: To show an association between T2-weighted signal intensity (T2-SI) variation and missegmentation in the putamen of healthy adults, using 3.0-tesla magnetic resonance scanner and voxel-based morphomery (VBM). MATERIALS AND METHODS: Contiguous sagittal T1-weighted images and axial T2-weighted images of the brain were obtained from 1380 healthy participants using a 3.0 Tesla (T) MR scanner. After image preprocessing with Statistical Parametric Mapping 5, the association between T2-SI ratio (= A/B, where A is the mean of the T2-SI in the putamen, and B is that in the thalamus) variation and gray matter missegmentation was assessed using VBM. RESULTS: A significant positive correlation was revealed between T2-SI ratio and bilateral putamen volume on the gray matter images. In addition, we found a significant negative correlation between T2-SI ratio and bilateral putamen volume on the white matter images. We consider that these results show the influence of missegmentation. CONCLUSION: To the best of our knowledge, this is the first VBM study to demonstrate an association between T2-SI variation and gray matter missegmentation. These results indicate the possibility that VBM may be more affected by individual differences in iron content levels than by individual differences in tissue volumes if detected-regions with VBM contained substantial iron deposition.

Integrated lymphography using fluorescence imaging and magnetic resonance imaging in intact mice.

We assessed lymph drainage in living mice by an integrated imaging method using fluorescence imaging (FLI) and magnetic resonance imaging (MRI). Mice were subcutaneously injected with quantum dots and gadofluorine 8 into the right rear footpad. They were fixed on a transparent flat plate and underwent FLI and MRI successively. Small markers were attached to the mouse surface for spatial coregistration, and image fusion of FLIs and MRIs was performed. Two-dimensional fluorescence reflectance imaging was used for FLI. FLI and MRI provided generally consistent results and demonstrated lymphatic flow to the popliteal, sacral, and iliac lymph nodes in most mice and to the renal, inguinal, and lumbar-aortic lymph nodes in some mice. On the fusion images, the locations of the lymph nodes in the mouse trunk were in good agreement between FLI and MRI, indicating successful spatial registration even for the deep structures. The popliteal node tended to be visualized a little farther caudally in FLI than in MRI, presumably because the overlying tissues were thicker in the cranial portion. Integrated FLI/MRI lymphography with image fusion appears to be a useful tool for analysis of the murine lymphatic system.

A retrospective comparison of clinical outcomes and quality of life measures between definitive chemoradiation alone and radical surgery for clinical stage II-III esophageal carcinoma.

BACKGROUND: This retrospective study was conducted to compare the treatment and quality of life (QOL) results between radical surgery and definitive chemoradiotherapy (CRT) for stage II-III carcinoma of the esophagus. METHODS: Between 2000 and 2009, 128 consecutive patients were selected for this study in which 72 were treated with definitive CRT and 56 with radical surgery. QOL was assessed using Functional Assessment of Cancer Therapy-Esophagus for 51 patients who were free of disease at the time of survey. RESULTS: With a median follow-up period of 37.8 months with 66 survivors, the 4y-DFS in the surgery group were 36% in the CRT group and 51% in the surgery group (P = 0.0028). In the CRT group, the number of cases of the advanced age, T4 stage, and stage III was significantly larger than the surgery group. QOL assessments were completed at rates of 100% in the CRT group and 88% in the surgery group. Overall E Total score had a significant difference between arms (CRT > surgery, P = 0.045). CONCLUSIONS: CRT was inferior to surgery in survival but superior in QOL measures, although the CRT group had a larger number of patients with poorer prognostic factors.

Safety of using iodized oil in chemoembolization for liver tumors in patients with previous adverse reactions to iodinated contrast media.

PURPOSE: To evaluate the safety of using iodized oil in chemoembolization for liver tumors in patients with previous adverse reactions to iodinated contrast media. MATERIALS AND METHODS: Records were retrospectively reviewed for all patients with a history of an adverse reaction to iodinated contrast media who underwent angiography using gadolinium-based contrast media and/or carbon dioxide at our institution from January 1998 to September 2006. Patients who underwent chemoembolization or hepatic artery infusion for liver tumors using iodized oil were identified. RESULTS: There were 84 procedures with use of iodized oil performed in 36 patients. Mild adverse reactions potentially related to iodized oil were seen in two procedures (2.4%). There were no moderate or severe adverse reactions (0.0%). CONCLUSION: Iodized oil can be safely used in patients with previous adverse reactions to iodinated contrast media.

Tract-specific analysis of the superior occipitofrontal fasciculus in schizophrenia.

Diffusion tensor imaging has been highlighted as a non-invasive tool to explore neural connectivity in vivo. Several studies have suggested disorganization of the neural network (circuitry) including the thalamo-prefrontal connection in schizophrenia. Recent research using post-mortem brains showed that the superior occipitofrontal fasciculus (SOFF) fibers extended to the thalamus. We postulated that the SOFF has some relationship with the anatomical structural components of the thalamo-prefrontal circuitry. We quantitatively assessed the diffusion abnormalities of the SOFF using diffusion tensor tractography (DTT) in schizophrenia. Nineteen male patients with schizophrenia and 20 age-matched normal controls were studied. DTT of the SOFF (DTT-SOFF) was visualized using free software (dTV II/VOLUME-ONE), and we performed tract-specific measurement of the fractional anisotropy (FA), then calculated the apparent diffusion coefficient (ADC) of the DTT-SOFF. Tractography and tract-specific analysis of the SOFF were successfully performed in all subjects. All tracts appeared to be connecting the prefrontal area to the thalamus. The mean FA value of patients with schizophrenia [0.376 (S.D. 0.030)] was significantly lower than that of controls [0.432 (S.D. 0.032)], and the ADC value of patients with schizophrenia [0.771 (x10(-3) mm(2)/s) (S.D. 0.041)] was significantly higher than that of controls [0.726 (x10(-3) mm(2)/s) (S.D. 0.027)]. Our results suggest that the so-called SOFF may be a structural component connecting the prefrontal area to the thalamus and that it is deteriorated in schizophrenia.

Radiosensitization by hyperthermia in the chicken B-lymphocyte cell line DT40 and its derivatives lacking nonhomologous end joining and/or homologous recombination pathways of DNA double-strand break repair.

Hyperthermia has a radiosensitizing effect, which is one of the most important biological bases for its use in cancer therapy with radiation. Although the mechanism of this effect has not been clarified in molecular terms, possible involvement of either one or both of two major DNA double-strand break (DSB) repair pathways, i.e. nonhomologous end joining (NHEJ) and homologous recombination (HR), has been speculated. To test this possibility, we examined cells of the chicken B-lymphocyte cell line DT40 and its derivatives lacking NHEJ and/or HR: KU70(-/-), DNA-PKcs(-/-/-), RAD54(-/-) and KU70(-/-)/RAD54(-/-). Radiosensitization by hyperthermia could be seen in all of the mutants, including KU70(-/-)/RAD54(-/-), which lacked both NHEJ and HR. Therefore, radiosensitization by hyperthermia cannot be explained simply by its inhibitory effects, if any, on NHEJ and/or HR alone. However, in NHEJ-defective KU70(-/-) and DNA-PKcs(-/-/-), consisting of two subpopulations with distinct radiosensitivity, the radiosensitive subpopulation, which is considered to be cells in G(1) and early S, was not sensitized. Substantial sensitization was seen only in the radioresistant subpopulation, which is considered to be cells in late S and G(2), capable of repairing DSBs through HR. This observation did not exclude possible involvement of NHEJ in G(1) and early S phase and also suggested inhibitory effects of hyperthermia on HR. Thus partial contribution of NHEJ and HR in radiosensitization by hyperthermia, especially that depending on the cell cycle stage, remains to be considered.