Synergistic defect in 60S ribosomal subunit assembly caused by a mutation of Rrs1p, a ribosomal protein L11-binding protein, and 3′-extension of 5S rRNA in Saccharomyces cerevisiae

Rrs1p, a ribosomal protein L11-binding protein, has an essential role in biogenesis of 60S ribosomal subunits. We obtained conditionally synthetic lethal allele with the rrs1-5 mutation and determined that the mutation is in REX1, which encodes an exonuclease. The highly conserved leucine at 305 was substituted with tryptophan in rex1-1. The rex1-1 allele resulted in 3′-extended 5S rRNA. Polysome analysis revealed that rex1-1 and rrs1-5 caused a synergistic defect in the assembly of 60S ribosomal subunits. In vivo and in vitro binding assays indicate that Rrs1p interacts with the ribosomal protein L5–5S rRNA complex. The rrs1-5 mutation weakens the interaction between Rrs1p with both L5 and L11. These data suggest that the assembly of L5–5S rRNA on 60S ribosomal subunits coordinates with assembly of L11 via Rrs1p

Neurite imaging reveals microstructural variations in human cerebral cortical gray matter

We present distinct patterns of neurite distribution in the human cerebral cortex using diffusion magnetic resonance imaging (MRI). We analyzed both high-resolution structural (T1w and T2w images) and diffusion MRI data in 505 subjects from the Human Connectome Project. Neurite distributions were evaluated using the neurite orientation dispersion and density imaging (NODDI) model, optimized for gray matter, and mapped onto the cortical surface using a method weighted towards the cortical mid-thickness to reduce partial volume effects. The estimated neurite density was high in both somatosensory and motor areas, early visual and auditory areas, and middle temporal area (MT), showing a strikingly similar distribution to myelin maps estimated from the T1w/T2w ratio. The estimated neurite orientation dispersion was particularly high in early sensory areas, which are known for dense tangential fibers and are classified as granular cortex by classical anatomists. Spatial gradients of these cortical neurite properties revealed transitions that colocalize with some areal boundaries in a recent multi-modal parcellation of the human cerebral cortex, providing mutually supportive evidence. Our findings indicate that analyzing the cortical gray matter neurite morphology using diffusion MRI and NODDI provides valuable information regarding cortical microstructure that is related to but complementary to myeloarchitecture

Diffusion tensor model links to neurite orientation dispersion and density imaging at high b-value in cerebral cortical gray matter

Diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) are widely used models to infer microstructural features in the brain from diffusion-weighted MRI. Several studies have recently applied both models to increase sensitivity to biological changes, however, it remains uncertain how these measures are associated. Here we show that cortical distributions of DTI and NODDI are associated depending on the choice of b-value, a factor reflecting strength of diffusion weighting gradient. We analyzed a combination of high, intermediate and low b-value data of multi-shell diffusion-weighted MRI (dMRI) in healthy 456 subjects of the Human Connectome Project using NODDI, DTI and a mathematical conversion from DTI to NODDI. Cortical distributions of DTI and DTI-derived NODDI metrics were remarkably associated with those in NODDI, particularly when applied highly diffusion-weighted data (b-value = 3000 sec/mm2). This was supported by simulation analysis, which revealed that DTI-derived parameters with lower b-value datasets suffered from errors due to heterogeneity of cerebrospinal fluid fraction and partial volume. These findings suggest that high b-value DTI redundantly parallels with NODDI-based cortical neurite measures, but the conventional low b-value DTI is hard to reasonably characterize cortical microarchitecture

Age-dependent plasticity in the superior temporal sulcus in deaf humans: a functional MRI study

BACKGROUND: Sign-language comprehension activates the auditory cortex in deaf subjects. It is not known whether this functional plasticity in the temporal cortex is age dependent. We conducted functional magnetic-resonance imaging in six deaf signers who lost their hearing before the age of 2 years, five deaf signers who were >5 years of age at the time of hearing loss and six signers with normal hearing. The task was sentence comprehension in Japanese sign language. RESULTS: The sign-comprehension tasks activated the planum temporale of both early- and late-deaf subjects, but not that of hearing signers. In early-deaf subjects, the middle superior temporal sulcus was more prominently activated than in late-deaf subjects. CONCLUSIONS: As the middle superior temporal sulcus is known to respond selectively to human voices, our findings suggest that this subregion of the auditory-association cortex, when deprived of its proper input, might make a functional shift from human voice processing to visual processing in an age-dependent manner

Quantitative and qualitative evaluation of sequential PET/MRI using a newly developed mobile PET system for brain imaging

[Purpose]To evaluate the clinical feasibility of a newly developed mobile PET system with MR-compatibility (flexible PET; fxPET), compared with conventional PET (cPET)/CT for brain imaging.[Methods]Twenty-one patients underwent cPET/CT with subsequent fxPET/MRI using 18F-FDG. As qualitative evaluation, we visually rated image quality of MR and PET images using a four-point scoring system. We evaluated overall image quality for MR, while we evaluated overall image quality, sharpness and lesion contrast. As quantitative evaluation, we compared registration accuracy between two modalities [(fxPET and MRI) and (cPET and CT)] measuring spatial coordinates. We also examined the accuracy of regional 18F-FDG uptake.[Results]All acquired images were of diagnostic quality and the number of detected lesions did not differ significantly between fxPET/MR and cPET/CT. Mean misregistration was significantly larger with fxPET/MRI than with cPET/CT. SUVmax and SUVmean for fxPET and cPET showed high correlations in the lesions (R = 0.84, 0.79; P < 0.001, P = 0.002, respectively). In normal structures, we also showed high correlations of SUVmax (R = 0.85, 0.87; P < 0.001, P < 0.001, respectively) and SUVmean (R = 0.83, 0.87; P < 0.001, P < 0.001, respectively) in bilateral caudate nuclei and a moderate correlation of SUVmax (R = 0.65) and SUVmean (R = 0.63) in vermis.[Conclusions]The fxPET/MRI system showed image quality within the diagnostic range, registration accuracy below 3 mm and regional 18F-FDG uptake highly correlated with that of cPET/CT

Grading Meningioma : A Comparative Study of Thallium-SPECT and FDG-PET

The purpose was to compare capability of fluorine-18 fluorodeoxyglucose (FDG)-PET and thallium-201 (Tl)-SPECT for grading meningioma. This retrospective study was conducted as a case-control study under approval by the institutional review board. In the hospital information system, 67 patients (22 men and 45 women) who had both FDG-PET and Tl-SPECT preoperative examinations were found with histopathologic diagnosis of meningioma. The maximum FDG uptake values of the tumors were measured, and they were standardized to the whole body (SUVmax) and normalized as gray matter ratio (SUVRmax). Mean and maximum Tl uptake ratios (TURmean and TURmax, respectively) of the tumors were measured and normalized as ratios to those of the contralateral normal brain. Receiver-operating characteristic curve analyses of the 4 indexes were conducted for differentiation between low- and high-grade meningiomas, and areas under the curves (AUCs) were compared. Correlation coefficients were calculated between these indexes and Ki-67. Fifty-six meningiomas were classified as grade I (low grade), and 11 were grade II or III (high grade). In all 4 indexes, a significant difference was observed between low- and high-grade meningiomas (P<0.05). AUCs were 0.817 (SUVmax), 0.781 (SUVRmax), 0.810 (TURmean), and 0.831 (TURmax), and no significant difference was observed among the indexes. Their sensitivity and specificity were 72.7% to 90.9% and 71.4% to 87.5%, respectively. Correlation of the 4 indexes to Ki-67 was statistically significant, but coefficients were relatively low (0.273-0.355). Tl-SPECT, which can be used at hospitals without a cyclotron or an FDG distribution network, has high diagnostic capability of meningioma grades comparable to FDG-PET

Brain MRI with Quantitative Susceptibility Mapping: Relationship to CT Attenuation Values

[Background]: Quantitative susceptibility mapping (QSM) is used to differentiate between calcification and iron deposits. Few studies have examined the relationship between CT attenuation values and magnetic susceptibility in such materials. Purpose: To assess the relationship among metal concentration, CT attenuation values, and magnetic susceptibility in paramagnetic and diamagnetic phantoms, and the relationship between CT attenuation values and susceptibility in brain structures that have paramagnetic or diamagnetic properties. [Materials and Methods]: In this retrospective study, CT and MRI with QSM were performed in gadolinium and calcium phantoms, patients, and healthy volunteers between June 2016 and September 2017. In the phantom study, we evaluated correlations among metal concentration, CT attenuation values, and susceptibility. In the human study, Pearson and Spearman correlations were performed to assess the relationship between CT attenuation values and susceptibility in regions of interest placed in the globus pallidus (GP), putamen, caudate nucleus, substantia nigra, red nucleus, dentate nucleus, choroid plexus, and hemorrhagic and calcified lesions. [Results]: Eighty-four patients (mean age, 64.8 years 6 19.6; 49 women) and 20 healthy volunteers (mean age, 72.0 years 6 7.6; 11 men) were evaluated. In the phantoms, strong linear correlations were identified between gadolinium concentration and CT and MRI QSM values (R2 = 0.95 and 0.99, respectively; P , .001 for both) and between calcium concentration and CT and MRI QSM values (R2 = 0.89 [P = .005] and R2 = 0.98 [P , .001], respectively). In human studies, positive correlations between CT attenuation values and susceptibility were observed in the GP (R2 = 0.52, P , .001) and in hemorrhagic lesions (R2 = 0.38, P , .001), and negative correlations were found in the choroid plexus (R2 = 0.53, P , .001) and in calcified lesions (R2 = 0.38, P = .009). [Conclusion]: CT attenuation values showed a positive correlation with susceptibility in the globus pallidus and hemorrhagic lesions and negative correlation in the choroid plexus and calcified lesions

Neuromelanin‐Sensitive Magnetic Resonance Imaging Using DANTE Pulse

BACKGROUND: Neuromelanin-sensitive magnetic resonance imaging techniques have been developed but currently require relatively long scan times. The aim of this study was to assess the ability of black-blood delay alternating with nutation for tailored excitation-prepared T1-weighted variable flip angle turbo spin echo (DANTE T1-SPACE), which provides relatively high resolution with a short scan time, to visualize neuromelanin in the substantia nigra pars compacta (SNpc). METHODS: Participants comprised 49 healthy controls and 25 patients with Parkinson's disease (PD). Contrast ratios of SNpc and hyperintense SNpc areas, which show pixels brighter than thresholds, were assessed between DANTE T1-SPACE and T1-SPACE in healthy controls. To evaluate the diagnostic ability of DANTE T1-SPACE, the contrast ratios and hyperintense areas were compared between healthy and PD groups, and receiver operating characteristic analyses were performed. We also compared areas under the curve (AUCs) between DANTE T1-SPACE and the previously reported gradient echo neuromelanin (GRE-NM) imaging. Each analysis was performed using original images in native space and images transformed into Montreal Neurological Institute space. Values of P < 0.05 were considered significant. RESULTS: DANTE T1-SPACE showed significantly higher contrast ratios and larger hyperintense areas than T1-SPACE. On DANTE T1-SPACE, healthy controls showed significantly higher contrast ratios and larger hyperintense areas than patients with PD. Hyperintense areas in native space analysis achieved the best AUC (0.94). DANTE T1-SPACE showed AUCs as high as those of GRE-NM. CONCLUSIONS: DANTE T1-SPACE successfully visualized neuromelanin of the SNpc and showed potential for evaluating PD. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society

Two-Minute Quantitative Susceptibility Mapping From Three-Dimensional Echo-Planar Imaging: Accuracy, Reliability, and Detection Performance in Patients With Cerebral Microbleeds

Objectives: The aim of this study was to assess the accuracy, reliability, and cerebral microbleed (CMB) detection performance of 2-minute quantitative susceptibility mapping (QSM) from 3-dimensional echo-planar imaging (3D-EPI). Materials and Methods: Gadolinium phantom study was conducted using 3D-EPI, single–echo time (TE), and multi-TE gradient-recalled echo (GRE) sequences on two 3-T magnetic resonance (MR) scanners to assess the accuracy between measured and theoretical susceptibility values. The institutional review board approved this prospective study, and 40 healthy volunteers were enrolled with written consent between April 2018 and October 2019. Each underwent 3D-EPI, single-TE, and multi-TE GRE sequences consecutively on one 3-T MR scanner, and QSMs were calculated to assess the reliability of 3D-EPI QSM. Intraclass correlation coefficient (ICC), linear regression, and Bland-Altman plots were calculated. Patients with CMB who underwent both 3D-EPI and GRE QSM scans were retrospectively enrolled. Two radiologists evaluated images independently, and Cohen κ coefficients were calculated to compare CMB detection performance. Results: Phantom study showed excellent validity of 3D-EPI QSM on both MR scanners: Skyra, R2 = 0.996, P < 0.001, ICC = 0.997, mean difference, −2 ppb (95% confidence interval [CI], −45 to 40 ppb); Prisma, R2 = 0.992, P < 0.001, ICC = 0.988, mean difference, 15 ppb (95% CI, −67 to 97 ppb). A human study of 40 healthy volunteers (59 ± 13 years, 25 women) showed excellent reliability with 3D-EPI QSM for both single-TE and multi-TE GRE (R2 = 0.981, P < 0.001, ICC = 0.988; R2 = 0.983, P < 0.001, ICC = 0.990, respectively), supported by a Bland-Altman mean difference of 4 ppb (95% CI, −15 to 23 ppb) for single-TE GRE and 3 ppb (95% CI, −15 to 20 ppb) for multi-TE GRE. The CMB detection performance evaluation from 38 patients (51 ± 20 years, 20 women) showed almost perfect agreement between 3D-EPI and GRE QSM for both raters (κ = 0.923 and 0.942, P < 0.001). Conclusions: Faster QSM from 3D-EPI demonstrated excellent accuracy, reliability, and CMB detection performance