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OBJECTIVE - Currently, approximately 60-70% of patients with unilateral temporal lobe epilepsy (TLE) remain seizure-free 3 years after surgery. The goal of this work was to develop a presurgical connectivity-based biomarker to identify those patients who will have an unfavorable seizure outcome 1-year postsurgery.
METHODS - Resting-state functional and diffusion-weighted 3T magnetic resonance imaging (MRI) was acquired from 22 unilateral (15 right, 7 left) patients with TLE and 35 healthy controls. A seizure propagation network was identified including ipsilateral (to seizure focus) and contralateral hippocampus, thalamus, and insula, with bilateral midcingulate and precuneus. Between each pair of regions, functional connectivity based on correlations of low frequency functional MRI signals, and structural connectivity based on streamline density of diffusion MRI data were computed and transformed to metrics related to healthy controls of the same age.
RESULTS - A consistent connectivity pattern representing the network expected in patients with seizure-free outcome was identified using eight patients who were seizure-free at 1-year postsurgery. The hypothesis that increased similarity to the model would be associated with better seizure outcome was tested in 14 other patients (Engel class IA, seizure-free: n = 5; Engel class IB-II, favorable: n = 4; Engel class III-IV, unfavorable: n = 5) using two similarity metrics: Pearson correlation and Euclidean distance. The seizure-free connectivity model successfully separated all the patients with unfavorable outcome from the seizure-free and favorable outcome patients (p = 0.0005, two-tailed Fisher's exact test) through the combination of the two similarity metrics with 100% accuracy. No other clinical and demographic predictors were successful in this regard.
SIGNIFICANCE - This work introduces a methodologic framework to assess individual patients, and demonstrates the ability to use network connectivity as a potential clinical tool for epilepsy surgery outcome prediction after more comprehensive validation.
Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.
Dopamine function is broadly implicated in multiple neuropsychiatric conditions believed to have a genetic basis. Although a few positron emission tomography (PET) studies have investigated the impact of single-nucleotide polymorphisms (SNPs) in the dopamine D2 receptor gene (DRD2) on D2/3 receptor availability (binding potential, BP), these studies have often been limited by small sample size. Furthermore, the most commonly studied SNP in D2/3 BP (Taq1A) is not located in the DRD2 gene itself, suggesting that its linkage with other DRD2 SNPs may explain previous PET findings. Here, in the largest PET genetic study to date (n=84), we tested for effects of the C957T and -141C Ins/Del SNPs (located within DRD2) as well as Taq1A on BP of the high-affinity D2 receptor tracer F-Fallypride. In a whole-brain voxelwise analysis, we found a positive linear effect of C957T T allele status on striatal BP bilaterally. The multilocus genetic scores containing C957T and one or both of the other SNPs produced qualitatively similar striatal results to C957T alone. The number of C957T T alleles predicted BP in anatomically defined putamen and ventral striatum (but not caudate) regions of interest, suggesting some regional specificity of effects in the striatum. By contrast, no significant effects arose in cortical regions. Taken together, our data support the critical role of C957T in striatal D2/3 receptor availability. This work has implications for a number of psychiatric conditions in which dopamine signaling and variation in C957T status have been implicated, including schizophrenia and substance use disorders.
Chemical exchange saturation transfer (CEST) imaging of fast exchanging amine protons at 3 ppm offset from the water resonant frequency is of practical interest, but quantification of fast exchanging pools by CEST is challenging. To effectively saturate fast exchanging protons, high irradiation powers need to be applied, but these may cause significant direct water saturation as well as non-specific semi-solid magnetization transfer (MT) effects, and thus decrease the specificity of the measured signal. In addition, the CEST signal may depend on the water longitudinal relaxation time (T ), which likely varies between tissues and with pathology, further reducing specificity. Previously, an analysis of the asymmetry of saturation effects (MTR ) has been commonly used to quantify fast exchanging amine CEST signals. However, our results show that MTR is greatly affected by the above factors, as well as asymmetric MT and nuclear Overhauser enhancement (NOE) effects. Here, we instead applied a relatively more specific inverse analysis method, named AREX (apparent exchange-dependent relaxation), that has previously been applied only to slow and intermediate exchanging solutes. Numerical simulations and controlled phantom experiments show that, although MTR depends on T and semi-solid content, AREX acquired in steady state does not, which suggests that AREX is more specific than MTR . By combining with a fitting approach instead of using the asymmetric analysis to obtain reference signals, AREX can also avoid contaminations from asymmetric MT and NOE effects. Animal experiments show that these two quantification methods produce differing contrasts between tumors and contralateral normal tissues in rat brain tumor models, suggesting that conventional MTR applied in vivo may be influenced by variations in T , semi-solid content, or NOE effect. Thus, the use of MTR may lead to misinterpretation, while AREX with corrections for competing effects likely enhances the specificity and accuracy of quantification to fast exchanging pools.
Copyright © 2017 John Wiley & Sons, Ltd.
Accurate quantification of chemical exchange saturation transfer (CEST) effects, including dipole-dipole mediated relayed nuclear Overhauser enhancement (rNOE) saturation transfer, is important for applications and studies of molecular concentration and transfer rate (and thereby pH or temperature). Although several quantification methods, such as Lorentzian difference (LD) analysis, multiple-pool Lorentzian fits, and the three-point method, have been extensively used in several preclinical and clinical applications, the accuracy of these methods has not been evaluated. Here we simulated multiple-pool Z spectra containing the pools that contribute to the main CEST and rNOE saturation transfer signals in the brain, numerically fit them using the different methods, and then compared their derived CEST metrics with the known solute concentrations and exchange rates. Our results show that the LD analysis overestimates contributions from amide proton transfer (APT) and intermediate exchanging amine protons; the three-point method significantly underestimates both APT and rNOE saturation transfer at -3.5 ppm (NOE(-3.5)). The multiple-pool Lorentzian fit is more accurate than the other two methods, but only at lower irradiation powers (≤1 μT at 9.4 T) within the range of our simulations. At higher irradiation powers, this method is also inaccurate because of the presence of a fast exchanging CEST signal that has a non-Lorentzian lineshape. Quantitative parameters derived from in vivo images of rodent brain tumor obtained using an irradiation power of 1 μT were also compared. Our results demonstrate that all three quantification methods show similar contrasts between tumor and contralateral normal tissue for both APT and the NOE(-3.5). However, the quantified values of the three methods are significantly different. Our work provides insight into the fitting accuracy obtainable in a complex tissue model and provides guidelines for evaluating other newly developed quantification methods.
Copyright © 2017 John Wiley & Sons, Ltd.
Studies have shown that tumor angiogenesis is an essential process for tumor growth, proliferation and metastasis. Also, tumor angiogenesis is an important prognostic factor of clear cell renal cell carcinoma (ccRCC), as well as a factor in guiding treatment with antiangiogenic agents. Here, we attempted to find the associations between tumor angiogenesis and radiomic imaging features from PET/MRI. Specifically, sparse canonical correlation analysis was conducted on 3 feature datasets (i.e., radiomic imaging features, tumor microvascular density (MVD), and vascular endothelial growth factor (VEGF) expression) from 9 patients with primary ccRCC. In order to overcome the potential bias of intratumoral heterogeneity of angiogenesis, this study investigated the relationship between regional expressions of angiogenesis and VEGF, and localized radiomic features from different parts within the tumors. Our study highlighted the significant strong correlations between radiomic features and MVD, and also demonstrated that the spatiotemporal features extracted from DCE-MRI provided stronger radiomic correlation to MVD than the textural features extracted from Dixon sequences and FDG PET. Furthermore, PET/MRI, which takes advantage of the combined functional and structural information, had higher radiomics correlation to MVD than solely utilizing PET or MRI alone.
PURPOSE - MRI of cortical bone has the potential to offer new information about fracture risk. Current methods are typically performed with 3D acquisitions, which suffer from long scan times and are generally limited to extremities. This work proposes using 2D UTE with half pulses for quantitatively mapping bound and pore water in cortical bone.
METHODS - Half-pulse 2D UTE methods were implemented on a 3T Philips Achieva scanner using an optimized slice-select gradient waveform, with preparation pulses to selectively image bound or pore water. The 2D methods were quantitatively compared with previously implemented 3D methods in the tibia in five volunteers.
RESULTS - The mean difference between bound and pore water concentration acquired from 3D and 2D sequences was 0.6 and 0.9 mol H/L (3 and 12%, respectively). While 2D pore water methods tended to slightly overestimate concentrations relative to 3D methods, differences were less than scan-rescan uncertainty and expected differences between healthy and fracture-prone bones.
CONCLUSION - Quantitative bound and pore water concentration mapping in cortical bone can be accelerated by 2 orders of magnitude using 2D protocols with optimized half-pulse excitation. Magn Reson Med 77:945-950, 2017. © 2017 International Society for Magnetic Resonance in Medicine.
© 2017 International Society for Magnetic Resonance in Medicine.
Total intracranial volume (TICV) is an essential covariate in brain volumetric analyses. The prevalent brain imaging software packages provide automatic TICV estimates. FreeSurfer and FSL estimate TICV using a scaling factor while SPM12 accumulates probabilities of brain tissues. None of the three provide explicit skull/CSF boundary (SCB) since it is challenging to distinguish these dark structures in a T1-weighted image. However, explicit SCB not only leads to a natural way of obtaining TICV (i.e., counting voxels inside the skull) but also allows sub-definition of TICV, for example, the posterior fossa volume (PFV). In this article, they proposed to use multi-atlas label fusion to obtain TICV and PFV simultaneously. The main contributions are: (1) TICV and PFV are simultaneously obtained with explicit SCB from a single T1-weighted image. (2) TICV and PFV labels are added to the widely used BrainCOLOR atlases. (3) Detailed mathematical derivation of non-local spatial STAPLE (NLSS) label fusion is presented. As the skull is clearly distinguished in CT images, we use a semi-manual procedure to obtain atlases with TICV and PFV labels using 20 subjects who both have a MR and CT scan. The proposed method provides simultaneous TICV and PFV estimation while achieving more accurate TICV estimation compared with FreeSurfer, FSL, SPM12, and the previously proposed STAPLE based approach. The newly developed TICV and PFV labels for the OASIS BrainCOLOR atlases provide acceptable performance, which enables simultaneous TICV and PFV estimation during whole brain segmentation. The NLSS method and the new atlases have been made freely available. Hum Brain Mapp 38:599-616, 2017. © 2016 Wiley Periodicals, Inc.
© 2016 Wiley Periodicals, Inc.
Automated software improves the accuracy and reliability of blood velocity, vessel diameter, blood flow, and shear rate ultrasound measurements, but existing software offers limited flexibility to customize and validate analyses. We developed FloWave.US-open-source software to automate ultrasound blood flow analysis-and demonstrated the validity of its blood velocity (aggregate relative error, 4.32%) and vessel diameter (0.31%) measures with a skeletal muscle ultrasound flow phantom. Compared with a commercial, manual analysis software program, FloWave.US produced equivalent in vivo cardiac cycle time-averaged mean (TAMean) velocities at rest and following a 10-s muscle contraction (mean bias <1 pixel for both conditions). Automated analysis of ultrasound blood flow data was 9.8 times faster than the manual method. Finally, a case study of a lower extremity muscle contraction experiment highlighted the ability of FloWave.US to measure small fluctuations in TAMean velocity, vessel diameter, and mean blood flow at specific time points in the cardiac cycle. In summary, the collective features of our newly designed software-accuracy, reliability, reduced processing time, cost-effectiveness, and flexibility-offer advantages over existing proprietary options. Further, public distribution of FloWave.US allows researchers to easily access and customize code to adapt ultrasound blood flow analysis to a variety of vascular physiology applications.
Copyright © 2016 the American Physiological Society.
PURPOSE - A temporal diffusion MRI spectroscopy based approach has been developed to quantify cancer cell size and density in vivo.
METHODS - A novel imaging microstructural parameters using limited spectrally edited diffusion (IMPULSED) method selects a specific limited diffusion spectral window for an accurate quantification of cell sizes ranging from 10 to 20 μm in common solid tumors. In practice, it is achieved by a combination of a single long diffusion time pulsed gradient spin echo (PGSE) and three low-frequency oscillating gradient spin echo (OGSE) acquisitions. To validate our approach, hematoxylin and eosin staining and immunostaining of cell membranes, in concert with whole slide imaging, were used to visualize nuclei and cell boundaries, and hence, enabled accurate estimates of cell size and cellularity.
RESULTS - Based on a two compartment model (incorporating intra- and extracellular spaces), accurate estimates of cell sizes were obtained in vivo for three types of human colon cancers. The IMPULSED-derived apparent cellularities showed a stronger correlation (r = 0.81; P < 0.0001) with histology-derived cellularities than conventional ADCs (r = -0.69; P < 0.03).
CONCLUSION - The IMPULSED approach samples a specific region of temporal diffusion spectra with enhanced sensitivity to length scales of 10-20 μm, and enables measurements of cell sizes and cellularities in solid tumors in vivo. Magn Reson Med 78:156-164, 2017. © 2016 International Society for Magnetic Resonance in Medicine.
© 2016 International Society for Magnetic Resonance in Medicine.
The induced current elimination (ICE) method has been previously applied to decouple monopole coil arrays in ultrahigh field MRI. However, the method creates low B spots near the decoupling elements. In this study, we aim to improve the performance of ICE-decoupled monopole array in human head imaging at 7 Tesla. Eight-channel ICE-decoupled monopole arrays were optimized by varying the position of the decoupling elements. A series of numerical studies were performed using the co-simulation method. In simulation, decoupling performance, quality (Q-) values and transmit field (B) were comparatively investigated. In addition, we constructed an optimized ICE-decoupled monopole array and compared its performance with the unoptimized array. The simulation results showed that a good trade-off between decoupling and B loss can be obtained when decoupling elements were moved 2.5-cm away from coil elements. This was validated by in-vivo MR imaging using the constructed array. Compared with the unoptimized ICE decoupled monopole array, the optimized array had a more homogeneous transmit field and no dark spots or signal cancellations in the MR images.
Copyright © 2016 Elsevier Inc. All rights reserved.