Background. Amide proton transfer (APT) imaging is a novel molecular MRI technique to detect endogenous mobile proteins and peptides through chemical exchange saturation transfer. We prospectively assessed the usefulness of APT imaging in predicting the histological grade of adult diffuse gliomas. Methods. Thirty-six consecutive patients with histopathologically proven diffuse glioma (48.1+14.7 y old, 16 males and 20 females) were included in the study. APT MRI was conducted on a 3T clinical scanner and was obtained with 2 s saturation at 25 saturation frequency offsets v ¼ 26 to +6 ppm (step 0.5 ppm). dB 0 maps were acquired separately for a point-by-point dB 0 correction. APT signal intensity (SI) was defined as magnetization transfer asymmetry at 3.5 ppm: magnetization transfer ratio (MTR) asym ¼ (S [23.5 ppm] 2 S [+3.5 ppm])/S 0. Regions of interest were carefully placed by 2 neuroradiologists in solid parts within brain tumors. The APT SI was compared with World Health Organization grade, Ki-67 labeling index (LI), and cell density. Results. The mean APT SI values were 2.1+0.4% in grade II gliomas (n ¼ 8), 3.2+0.9% in grade III gliomas (n ¼ 10), and 4.1+1.0% in grade IV gliomas (n ¼ 18). Significant differences in APT intensity were observed between grades II and III (P , .05) and grades III and IV (P , .05), as well as between grades II and IV (P , .001). There were positive correlations between APT SI and Ki-67 LI (P ¼ .01, R ¼ 0.43) and between APT SI and cell density (P , .05, R ¼ 0.38). The gliomas with microscopic necrosis showed higher APT SI than those without necrosis (P , .001). Conclusions. APT imaging can predict the histopathological grades of adult diffuse gliomas.

Background/AimsBehavioral and psychological symptoms of dementia (BPSDs) negatively impact the prognosis of dementia patients and increase caregiver distress. The aims of this study were to clarify the differences of trajectories of 12 kinds of BPSDs by disease severity in four major dementias and to develop charts showing the frequency, severity, and associated caregiver distress (ACD) of BPSDs using the data of a Japan multicenter study (J-BIRD).MethodsWe gathered Neuropsychiatric Inventory (NPI) data of patients with Alzheimer’s disease (AD; n = 1091), dementia with Lewy bodies (DLB; n = 249), vascular dementia (VaD; n = 156), and frontotemporal lobar degeneration (FTLD; n = 102) collected during a 5-year period up to July 31, 2013 in seven centers for dementia in Japan. The NPI composite scores (frequency × severity) of 12 kinds of items were analyzed using a principal component analysis (PCA) in each dementia. The factor scores of the PCA were compared in each dementia by disease severity, which was determined with Clinical Dementia Rating (CDR).ResultsSignificant increases with higher CDR scores were observed in 1) two of the three factor scores which were loaded for all items except euphoria in AD, 2) two of the four factor scores for apathy, aberrant motor behavior (AMB), sleep disturbances, agitation, irritability, disinhibition, and euphoria in DLB, and 3) one of the four factor scores for apathy, depression, anxiety, and sleep disturbances in VaD. However, no increases were observed in any of the five factor scores in FTLD.ConclusionsAs dementia progresses, several BPSDs become more severe, including 1) apathy and sleep disturbances in AD, DLB, and VaD, 2) all of the BPSDs except euphoria in AD, 3) AMB, agitation, irritability, disinhibition, and euphoria in DLB, and 4) depression and anxiety in VaD. Trajectories of BPSDs in FTLD were unclear.

No abstract

In this report, we present the terminology, definition and classification of pregnancy induced hypertension (PIH) by the Japan Society for the Study of Hypertension in Pregnancy (JSSHP). PIH is classified as gestational hypertension (GH), preeclampsia (PE), superimposed preeclampsia (S-PE) or eclampsia (E). Subclassifications by symptoms (severity and gestational age at onset) are also shown. Hypertension Research In PregnancyKey words: definition, pregnancy induced hypertension, preeclampsia TerminologyIn 2004, "Toxemia of Pregnancy" was revised to "Pregnancy induced Hypertension (PIH)" in Japan. 1,2)Definition PIH is defined as hypertension (blood pressure ≥ 140/90 mmHg) with or without proteinuria ( ≥ 300 mg/24 hours) emerging after 20 weeks gestation, but resolving up to 12 weeks postpartum.1-10) PIH is also defined as new onset proteinuria ( ≥ 300 mg/24 hours) in hypertensive women who exhibit no proteinuria before 20 weeks gestation. Classification Gestational hypertension (GH)GH is diagnosed in women whose blood pressure reaches ≥ 140/90 mmHg for the first time during pregnancy (after 20 weeks gestation), but without proteinuria. Blood pressure normalizes by 12 weeks postpartum. Preeclampsia (PE)Hypertension (blood pressure ≥ 140 / 90 mmHg) accompanied with proteinuria exceeding 300 mg/24 hours emerges for the first time after 20 weeks gestation, but both symptoms normalize by 12 weeks postpartum. Superimposed preeclampsia (S-PE)Superimposed preeclampsia is diagnosed in the following three cases. (1) New onset proteinuria ( ≥ 300 mg/24 hours) in hypertensive women who exhibit no proteinuria before 20 weeks gestation. (2) Hypertension and proteinuria documented antecedent to pregnancy and/or detected before 20 weeks gestation, one or both of which progressing after 20 weeks gestation. (3) Renal disease with proteinuria documented antecedent to pregnancy and/or detected before 20 weeks gestation, which is accompanied with new onset hypertension after 20 weeks gestation. Eclampsia (E)Eclampsia is defined as the onset of convulsions in a woman with PIH that cannot be attributed to other causes. The seizures are generalized and may appear before, during, or after labor.Subclassification by symptoms *Severity* The severity of PIH is assessed by the extent of symptoms. Both blood pressure and proteinuria are dependable indicators of severity.

With the publication in 2015 of the consensus statement by the perfusion study group of the International Society for Magnetic Resonance in Medicine (ISMRM) and the EU-COST action ‘ASL in dementia’ on the implementation of arterial spin labelling MRI (ASL) in a clinical setting, the development of ASL can be considered to have become mature and ready for clinical prime-time. In this review article new developments and remaining issues will be discussed, especially focusing on quantification of ASL as well as on new technological developments of ASL for perfusion imaging and flow territory mapping. Uncertainty of the achieved labelling efficiency in pseudo-continuous ASL (pCASL) as well as the presence of arterial transit time artefacts, can be considered the main remaining challenges for the use of quantitative cerebral blood flow (CBF) values. New developments in ASL centre around time-efficient acquisition of dynamic ASL-images by means of time-encoded pCASL and diversification of information content, for example by combined 4D-angiography with perfusion imaging. Current vessel-encoded and super-selective pCASL-methodology have developed into easily applied flow-territory mapping methods providing relevant clinical information with highly similar information content as digital subtraction angiography (DSA), the current clinical standard. Both approaches seem therefore to be ready for clinical use.

Recently, non-Gaussian diŠusion-weighted imaging (DWI) techniques, including qspace imaging (QSI) and diŠusional kurtosis imaging (DKI), have emerged as advanced methods to evaluate tissue microstructure in vivo using water diŠusion. QSI and DKI have shown promising results in clinical applications, such as in the evaluation of brain tumors (e.g., grading gliomas), degenerative diseases (e.g., speciˆc diagnosis of Parkinson disease), demyelinating diseases (e.g., assessment of normal-appearing tissue of multiple sclerosis), and cerebrovascular diseases (e.g., assessment of the microstructural environment of fresh infarctions). Representative metrics in clinical use are the full width at half maximum, also known as the mean displacement of the probability density function curve, which is derived from QSI, and diŠusional kurtosis, which is derived from DKI. These new metrics may provide information on tissue structure in addition to that provided by conventional Gaussian DWI investigations that use the apparent diŠusion coe‹cient and fractional anisotropy, recognized indices for evaluating disease and normal development in the brain and spine. In some clinical situations, sensitivity for detecting pathological conditions is higher using QSI and DKI than conventional DWI and diŠusion tensor imaging (DTI) because DWI and DTI calculations are based on the assumption that water molecules follow a Gaussian distribution, whereas hindrance of the distribution of water molecules by complex and restricted structures in actual neural tissues produces distributions that are far from Gaussian. We review the technical aspects and clinical applications of QSI and DKI, focusing on clinical use and in vivo studies and highlighting diŠerences from conventional diŠusional metrics.

The CDKN2A and CDKN2B genes, encoding p16 and p15 respectively, are located on chromosome 9p21, a locus at which frequent homozygous and heterozygous deletions occur in many primary human tumors, including esophageal carcinoma. CDKN2A and CDKN2B inhibit cyclin dependent kinase 4 (CDK4) and CDK6 and control cellular proliferation by preventing entry into the S phase of the cell cycle. Their inactivation may contribute to uncontrolled growth in human cancer. We previously described CDKN2A exon 2 mutations in a pilot study of 43 esophageal cancers. In order to determine whether CDKN2A and CDKN2B are frequent targets of 9p21 deletion in esophageal carcinogenesis, we have now analyzed 60 primary esophageal cancers for mutations in both exons 1 and 2 of CDKN2A and CDKN2B by direct sequencing of PCR amplified genomic DNAs. In conjunction with our previously published data, we have identified a total of eight nucleic acid substitutions among 60 esophageal carcinomas; here, we describe one new CDKN2B nonsense mutation and one new silent CDKN2B mutation that occurred somatically. Taken together, these results suggest that intragenic mutations in CDKN2A and CDKN2B occur in esophageal cancer, but that they are infrequent events. In view of the known high frequency of loss of heterozygosity at the chromosome 9p21 locus in esophageal cancers, the current data suggest that intragenic mutation is not the predominant mode of inactivation of CDKN2A and CDKN2B or that other genes are targets of deletion at this locus in these cancers.

Parallel transmission-based APT imaging of brain tumors showed good reproducibility.