Determinants of renal shape in chronic kidney disease patients.

BACKGROUND: The determinants of renal shape are not well established. The purpose of this study was to investigate the relationship between the renal shape, as measured by ultrasound, and the clinical characteristics in chronic kidney disease (CKD) patients. METHODS: The study included 121 CKD patients who had undergone kidney biopsy. The renal shape was defined by: (1) the renal shape index: renal length/(renal width + renal thickness) and (2) the renal width/length. IgA nephritis patients (excluding patients with diabetes), comprised the largest subgroup (n = 49) and were analyzed separately. RESULTS: The correlation analyses and two-sample Student's t test results showed that age, eGFR, BMI, cortex volume fraction measured by MRI (cortex volume/renal volume), percentage of global sclerosis, weight, sex, hypertension and diabetes were significantly correlated with the renal shape in both kidneys. In a stepwise multiple linear regression analysis, old age and high BMI were independently associated with plump kidney. As for the left renal shape index, low cortex volume fraction was also independently associated with plump kidney. In the IgA nephritis patient subgroup, the cortex volume fraction was the most significant factor contributing to the left renal shape index (r = 0.50, p < 0.01) and the width/length (r = -0.47, p < 0.01). CONCLUSION: Age and BMI were stronger determinants of renal shape than renal function in CKD patients. The left renal cortex volume fraction was also an independent determinant and a more important factor in IgA nephritis patients.

Quantitative 17O imaging towards oxygen consumption study in tumor bearing mice at 7 T.

(17)O magnetic resonance imaging (MRI) using a conventional pulse sequence was explored as a method of quantitative imaging towards regional oxygen consumption rate measurement for tumor evaluation in mice. At 7 T, fast imaging with steady state (FISP) was the best among gradient echo, fast spin echo and FISP for the purpose. The distribution of natural abundance H2(17)O in mice was visualized under spatial resolution of 2.5 × 2.5mm(2) by FISP in 10 min. The signal intensity by FISP showed a linear relationship with (17)O quantity both in phantom and mice. Following the injection of 5% (17)O enriched saline, (17)O re-distribution was monitored in temporal resolution down to 5 sec with an image quality sufficient to distinguish each organ. The image of labeled water produced from inhaled (17)O2 gas was also obtained. The present method provides quantitative (17)O images under sufficient temporal and spatial resolution for the evaluation of oxygen consumption rate in each organ. Experiments using various model compounds of R-OH type clarified that the signal contribution of body constituents other than water in the present in vivo(17)O FISP image was negligible.

Predicting the outcome of chronic kidney disease by the estimated nephron number: the rationale and design of PRONEP, a prospective, multicenter, observational cohort study.

BACKGROUND: The nephron number is thought to be associated with the outcome of chronic kidney disease (CKD). If the nephron number can be estimated in the clinical setting, it could become a strong tool to predict renal outcome. This study was designed to estimate the nephron number in CKD patients and to establish a method to predict the outcome by using the estimated nephron number. METHODS/DESIGN: The hypothesis of this study is that the estimated nephron number can predict the outcome of a CKD patient. This will be a multicenter, prospective (minimum 3 and maximum 5 years follow-up) study. The subjects will comprise CKD patients aged over 14 years who have undergone a kidney biopsy. From January 2011 to March 2013, we will recruit 600 CKD patients from 10 hospitals belonging to the National Hospital Organization of Japan. The primary parameter for assessment is the composite of total mortality, renal death, cerebro-cardiovascular events, and a 50% reduction in the eGFR. The secondary parameter is the rate of eGFR decline per year. The nephron number will be estimated by the glomerular density in biopsy specimens and the renal cortex volume. This study includes one sub-cohort study to establish the equation to calculate the renal cortex volume. Enrollment will be performed at the time of the kidney biopsy, and the data will consist of a medical interview, ultrasound for measurement of the kidney size, blood or urine test, and the pathological findings of the kidney biopsy. Patients will continue to have medical consultations and receive examinations and/or treatment as usual. The data from the patients will be collected once a year after the kidney biopsy until March 2016. All data using this study are easily obtained in routine clinical practice. DISCUSSION: This study includes the first trials to estimate the renal cortex volume and nephron number in the general clinical setting. Furthermore, this is the first prospective study to examine whether the nephron number predicts the outcome of CKD patients. The results from this study should provide powerful new tools for nephrologists in routine clinical practice. TRIAL REGISTRATION: UMIN-Clinical Trial Registration, UMIN000004784.

Role of glucose metabolism and cellularity for tumor malignancy evaluation using FDG-PET/CT and MRI.

OBJECTIVE: Standardized uptake value (SUV) is affected by many factors. In that respect, the brain reference index (BRI: regions of interest of tumor/regions of interest of cerebellum) is one of the quantitative approaches to eliminate the variety of factors that affect SUV. MRI pulse sequence findings can also provide information about tissue cellularity. This information is useful for evaluating the malignancy of lesions. We evaluated the role of glucose metabolism and cellularity for the diagnosis of pancreatic tumor malignancy. METHOD: We performed a radionuclide 2-(18)F-fluoro-2-deoxyglucose ((18)F-FDG) uptake analysis and a signal intensity analysis using MRI on 16 presurgery patients with either proven or suspected pancreatic cancer. The tumor glucose metabolism was evaluated with SUV and BRI in an FDG-PET study. Tumor cellularity was determined with the MRI factors, apparent diffusion coefficient (ADC), T2 value and tumor to nontumor ratio of proton density. We compared these results with the pathological findings. RESULTS: SUV (= 0.855), BRI ( =0.875), and ADC ( =0.830) showed a larger the area under the curve than T2 value (= 0.582) and tumor to nontumor ratio of proton density ( = 0.786) according to the receiver operating characteristics analysis, and we therefore considered that these three factors were better indexes for the diagnosis of tumor malignancy. SUV and BRI had a high specificity. In contrast, ADC had a high sensitivity. CONCLUSION: The glucose metabolism with PET/CT and cellularity with MRI are different indexes for the diagnosis of tumor malignancy. Both provide necessary information for making an accurate diagnosis. Using both types of information may therefore help in obtaining a highly accurate diagnosis.

ADC value and diffusion tensor imaging of prostate cancer: changes in carbon-ion radiotherapy.

PURPOSE: To assess the apparent diffusion coefficient (ADC) value and diffusion tensor image (DTI) including fractional anisotropy (FA) of the noncancerous prostate and prostate cancer before and after carbon-ion radiotherapy (CIRT). MATERIALS AND METHODS: Nine patients with biopsy-proven prostate cancer underwent 1.5T magnetic resonance (MR) examinations. One patient with benign prostatic hypertrophy and one healthy volunteer were also examined as references. The changes in ADC values and DTI of the entire prostate calculated from b-values of 0 and 700 (s/mm(2)) were estimated between before and after CIRT. RESULTS: ADC values of prostate cancer significantly increased after CIRT by paired t-test (P < 0.01) but those of noncancerous inner gland (IG) and peripheral zone (PZ) showed no significant change. By analysis of variance, significant differences in ADC values were observed among prostate cancer and noncancerous IG and PZ before CIRT (P < 0.05). After CIRT, those significant differences had disappeared. FAs showed no significant differences in any comparisons. DTI showed changes in the direction of the main axis of the tensor in prostate cancer after CIRT. CONCLUSION: There were changes in ADC and DTI in prostate cancer after CIRT. They may be useful for monitoring prostatic structural changes under radiotherapy.

Negative correlation between brain glutathione level and negative symptoms in schizophrenia: a 3T 1H-MRS study.

BACKGROUND: Glutathione (GSH), a major intracellular antioxidant, plays a role in NMDA receptor-mediated neurotransmission, which is involved in the pathophysiology of schizophrenia. In the present study, we aimed to investigate whether GSH levels are altered in the posterior medial frontal cortex of schizophrenic patients. Furthermore, we examined correlations between GSH levels and clinical variables in patients. METHODS AND FINDINGS: Twenty schizophrenia patients and 16 age- and gender-matched normal controls were enrolled to examine the levels of GSH in the posterior medial frontal cortex by using 3T SIGNA EXCITE (1)H-MRS with the spectral editing technique, MEGA-PRESS. Clinical variables of patients were assessed by the Global Assessment of Functioning (GAF), Scale for the Assessment of Negative Symptoms (SANS), Brief Psychiatric Rating Scale (BPRS), Drug-Induced Extra-Pyramidal Symptoms Scale (DIEPSS), and five cognitive performance tests (Word Fluency Test, Stroop Test, Trail Making Test, Wisconsin Card Sorting Test and Digit Span Distractibility Test). Levels of GSH in the posterior medial frontal cortex of schizophrenic patients were not different from those of normal controls. However, we found a significant negative correlation between GSH levels and the severity of negative symptoms (SANS total score and negative symptom subscore on BPRS) in patients. There were no correlations between brain GSH levels and scores on any cognitive performance test except Trail Making Test part A. CONCLUSION: These results suggest that GSH levels in the posterior medial frontal cortex may be related to negative symptoms in schizophrenic patients. Therefore, agents that increase GSH levels in the brain could be potential therapeutic drugs for negative symptoms in schizophrenia.

Delayed gadolinium-enhanced MR to determine glycosaminoglycan concentration in reparative cartilage after autologous chondrocyte implantation: preliminary results.

PURPOSE: To prospectively evaluate delayed gadolinium-enhanced magnetic resonance (MR) imaging of cartilage for assessment of glycosaminoglycan (GAG) concentration in reparative cartilage after autologous chondrocyte implantation (ACI). MATERIALS AND METHODS: The study was approved by the ethics review committee of the National Institute of Radiological Sciences, and informed consent was obtained from all patients. The study group comprised nine knees of nine patients (six male, three female; mean age at ACI, 21.2 years +/- 7.5 [standard deviation]; age range, 13-35 years) who had undergone ACI and second-look arthroscopy with biopsy. MR imaging was performed at 1.5 T before and after intravenous injection of anionic gadopentetate dimeglumine. The precontrast R1 (R1(pre)), postcontrast R1 (R1(post)), and difference between R1(pre) and R1(post) (DeltaR1) were measured in reparative cartilage and normal cartilage. GAG concentrations in cartilage biopsy specimens were measured by using high-performance liquid chromatography. To evaluate delayed gadolinium-enhanced MR imaging of cartilage for assessment of GAG concentration, the authors defined the relative R1(pre), relative R1(post), and relative DeltaR1 (ie, R1(pre), R1(post), or DeltaR1, respectively, in reparative cartilage divided by that in normal cartilage) and the relative GAG concentration (ie, GAG concentration in reparative cartilage divided by that in normal cartilage). They then examined the relationships between relative R1(pre), relative R1(post), relative DeltaR1, and relative GAG by using correlation analysis. RESULTS: A significant correlation between relative DeltaR1 and relative GAG concentration (r = 0.818, P < .05) was observed. However, no significant correlation between relative R1(pre) and relative GAG concentration (r = 0.010, P = .983) or between relative R1(post) and relative GAG concentration (r = 0.660, P = .106) was observed. CONCLUSION: Study results indicate that pre- and postcontrast imaging is necessary for delayed gadolinium-enhanced MR imaging evaluation of reparative cartilage after ACI.

Development of high-radiation-sensitive polymer gel for magnetic resonance imaging in three-dimensional dosimetry.

We developed a high radiation sensitive polymer gel by modifying the amounts of the gel components and the temperature for the gel preparation. We evaluated its relaxation time linearity against dose and compared the measured dose distribution with the calculated one. For the relaxation time-dose linearity, irradiations were carried out with a linear accelerator using 6 MV photons and doses ranging from 0-5.0 Gy. The relationship between dose and R(2) value (reciprocal of T(2) relaxation time) was measured and it had good linearity over a wide range (0.3-5 Gy). The measured dose distributions were in good agreement with calculated ones. Since the present gel has higher sensitivity and it is synthesized more easily at lower cost than conventional polymer gels, we expect to see improved three-dimensional (3D) dosimetry using it.

Time course evaluation of reparative cartilage with MR imaging after autologous chondrocyte implantation.

The aim of this study was to evaluate the qualitative change in reparative cartilage after autologous chondrocyte implantation (ACI). Ten knees of 10 patients were studied. The signal intensities of reparative and normal cartilage were evaluated by fat-suppressed three-dimensional spoiled-gradient recalled (FS 3D-SPGR) MR imaging. The signal intensity (SI) index (signal intensity of reparative cartilage divided by that of normal cartilage) was defined and the change in SI index was investigated. Histological and biochemical evaluation was done at the second look arthroscopy. The SI index was at its lowest level immediately after ACI and increased with time to 9 months thereafter. After 9-12 months, the SI index settled to almost level and was maintained at that value for at least 2-3 years postoperatively. The average of the SI indexes after 12 months to the last examination was 74.2 +/- 4.6 (range 64.2-82.8), which means signal intensity of reparative cartilage was maintained at a value lower than that of normal cartilage. The total ICRS score was 11.6 +/- 2.3 points (mean +/- SD). The GAG concentration was 107.9 +/- 17.0 microg/mg (mean +/- SD) in normal cartilage and 65.9 +/- 9.4 microg/mg in reparative cartilage. The quality of reparative cartilage as hyaline cartilage was inferior to that of normal cartilage. In the present study, the time course change in the SI index indicates that the major maturation process of implanted chondrocytes neared completion in 9-12 months. Minor changes, such as matrix remodeling with reorganization of the collagen fibers in reparative cartilage, may continue, but an almost identical condition seemed to be maintained during the first 2-3 years of follow-up. SI index does not always reflect all properties of reparative cartilage but may be a useful parameter for noninvasive evaluation.

Phosphorous-31 magnetic resonance spectroscopy of cervical cancer using transvaginal surface coil.

We developed a new transvaginal coil tuned for phosphorous-31 and measured its magnetic resonance spectroscopy ((31)P MRS) of uterine cervical cancer. In a 50-year-old woman with uterine cervical cancer (International Federation of Gynecology and Obstetrics [FIGO] stage IIIb), (31)P MRS with the new coil clearly differentiated the low intensity of phosphocreatinine (PCr) and high intensity of phosphomonoester (PME) in tumor from those in muscle. Results suggests that this method will be useful for assessing uterine cervical cancer.

Histologic characteristics of normal perivascular spaces along the optic tract: new pathogenetic mechanism for edema in tumors in the pituitary region.

BACKGROUND AND PURPOSE: Perivascular (PV) spaces are known to distend and cause edema along the optic tract (OT) in pituitary-region tumors. Interstitial fluid may be retained in PV spaces when tumors block their drainage outlets to subarachnoid spaces. However, these spaces and their outlets have not been anatomically elucidated. Our purpose was to evaluate how often large PV spaces are present along the OT and demonstrate their superficial communication points to adjacent subarachnoid spaces. METHODS: We examined serial histologic sections of 10 hemispheric blocks obtained from cadavers without cerebral abnormality. RESULTS: Large PV spaces, 0.5-1.5 mm in maximum height, were always present along the middle portion of the OT. Perforation points of the largest spaces were noted at the medial sulcus of the OT in seven hemispheres and through the OT in three. CONCLUSION: Large PV spaces are present along the middle portion of the OT. Their communication point to adjacent subarachnoid spaces was histologically demonstrated. The locations and variations of the outlet of large PV spaces explain the clinical features of edemas; these findings anatomically support the hypothesis that blockage of the outlets to subarachnoid spaces may play a role in distending the PV spaces and in causing edema in pituitary-region tumors. Only MR imaging has revealed this change; further pathologic investigations are awaited.

Changes in the pharmacokinetics of Gd-DTPA in experimental tumors after charged particle radiation: comparison with gamma-ray radiation.

We performed dynamic MRI to reveal the characteristic gadopentetate dimeglumine (Gd-DTPA) uptake in carbon-ion irradiated tumor and compare it with photon irradiation. Fibrosarcomas in C3H mice legs were irradiated with either 16 Gy of carbon ions (74 keV/mm) or an equivalent dose (30 Gy) of Cs-137 gamma-rays. Dynamic MRI was performed 1 or 6 days after irradiation when the tumors showed an initial growth delay or incipient regrowth, respectively. The enhancement pattern was visualized by mapping the maximum enhanced time (Tmax), relative signal intensity maximum (SImax), and time delay of starting enhancement (Td). Significantly larger Tmax and Td values were observed in the tumors 1 day after carbon-ion irradiation than in the nonradiated tumors (No-R) and tumors 1 day after gamma-ray irradiation. Among the selected pixels in the tumors 6 days after carbon irradiation, 77% had Tmax values of less than 120 sec, significantly more than in the No-R group. The Tmax maps for the tumors irradiated with gamma-rays showed a similar tendency to the carbon-irradiated ones, and only a significant difference was obtained between tumors 1 and 6 days after irradiation. Tmax and Td in the carbon-ion irradiated tumors were different from those in the gamma-ray-irradiated tumors. These treatment-specific kinetics may be useful in predicting the therapeutic efficacy of carbon-ion treatment.