Search

Purpose To develop an in-plane simultaneous multisegment (IP-SMS) imaging technique using a 2D-RF pulse and to demonstrate its ability to achieve high spatial resolution in EPI while reducing image distortion. Methods The proposed IP-SMS technique takes advantage of periodic replicates of the excitation profile of a 2D-RF pulse to simultaneously excite multiple segments within a slice. These segments were acquired over a reduced FOV and separated using a joint GRAPPA reconstruction by leveraging virtual coils that combined the physical coil sensitivity and 2D-RF pulse spatial response. Two excitations were used with complementary spatial response profiles to adequately cover a full FOV, producing a full-FOV image that had the benefits of reduced FOV with high spatial resolution and reduced distortion. The IP-SMS technique was implemented in a diffusion-weighted single-shot EPI sequence. Experimental demonstrations were performed on a phantom and healthy human brain. Results In the phantom experiment, IP-SMS enabled a four-fold acceleration using an eight-channel coil without causing residual aliasing artifacts. In the human brain experiment, diffusion-weighted images with high in-plane resolution (1 × 1 mm2 ) and substantially reduced image distortion were obtained in all imaging planes in comparison with a commercial diffusion-weighted EPI sequence. The capability of IP-SMS for contiguous whole-brain coverage was also demonstrated. Conclusion The proposed IP-SMS technique can realize the benefits of reduced-FOV imaging while achieving a full-FOV coverage with good image quality and time efficiency.

To evaluate the feasibility of high b-value diffusion-weighted imaging (DWI) for distinguishing non-muscle-invasive bladder cancer (NMIBC) from muscle-invasive bladder cancer (MIBC) and low- from high-grade bladder urothelial carcinoma using a fractional-order calculus (FROC) model as well as a combination of FROC DWI and bi-parametric Vesical Imaging-Reporting and Data System (VI-RADS). Fifty-eight participants with bladder urothelial carcinoma were included in this IRB-approved prospective study. Diffusion-weighted images, acquired with 16 b-values (0–3600 s/mm2), were analyzed using the FROC model. Three FROC parameters, D, β, and μ, were used for delineating NMIBC from MIBC and for tumor grading. A receiver operating characteristic (ROC) analysis was performed based on the individual FROC parameters and their combinations, followed by comparisons with apparent diffusion coefficient (ADC) and bi-parametric VI-RADS based on T2-weighted images and DWI. D and μ were significantly lower in the MIBC group than in the NMIBC group (p = 0.001 for each), and D, β, and μ all exhibited significantly lower values in the high- than in the low-grade tumors (p ≤ 0.011). The combination of D, β, and μ produced the highest specificity (85%), accuracy (78%), and the area under the ROC curve (AUC, 0.782) for distinguishing NMIBC and MIBC, and the best sensitivity (89%), specificity (86%), accuracy (88%), and AUC (0.892) for tumor grading, all of which outperformed the ADC. The combination of FROC parameters with bi-parametric VI-RADS improved the AUC from 0.859 to 0.931. High b-value DWI with a FROC model is useful in distinguishing NMIBC from MIBC and grading bladder tumors. • Diffusion parameters derived from a FROC diffusion model may differentiate NMIBC from MIBC and low- from high-grade bladder urothelial carcinomas. • Under the condition of a moderate sample size, higher AUCs were achieved by the FROC parameters D (0.842) and μ (0.857) than ADC (0.804) for bladder tumor grading with p ≤ 0.046. • The combination of the three diffusion parameters from the FROC model can improve the specificity over ADC (85% versus 67%, p = 0.031) for distinguishing NMIBC and MIBC and enhance the performance of bi-parametric VI-RADS.

During the ongoing COVID-19 pandemic, an artifact with hyperintense signal was observed on the brain images of a number of patients or research subjects, particularly those with heavy body weight and/or increased respiratory rate. The artifact was primarily seen on 3D or 2D sagittal or coronal T2-weighted images, although it occasionally also appeared in the axial plane. It manifested as a bright spot or a cluster of bright spots at similar locations, superior or lateral superior to the skull. This artifact was found to be caused by condensed water droplet(s) in the head coil as a consequence of the altered moisture flow pattern associated with each exhalation due to the mask on the patient. We call this artifact condensation artifact. Several strategies have been proposed to prevent or resolve the artifact. LEVEL OF EVIDENCE: 5 TECHNICAL EFFICACY: Stage 1.

BACKGROUND Visualization of aortic valve dynamics is important in diagnosing valvular diseases but is challenging to perform with magnetic resonance imaging (MRI) due to the limited temporal resolution. PURPOSE To develop an MRI technique with sub-millisecond temporal resolution and demonstrate its application in visualizing rapid aortic valve opening and closing in human subjects in comparison with echocardiography and conventional MRI techniques. STUDY TYPE Prospective. POPULATION Twelve healthy subjects. FIELD STRENGTH/SEQUENCE 3 T; gradient-echo-train-based sub-millisecond periodic event encoded imaging (get-SPEEDI) and balanced steady-state free precession (bSSFP). ASSESSMENT Images were acquired using get-SPEEDI with a temporal resolution of 0.6 msec. get-SPEEDI was triggered by an electrocardiogram so that each echo in the gradient echo train corresponded to an image at a specific time point, providing a time-resolved characterization of aortic valve dynamics. For comparison, bSSFP was also employed with 12 msec and 24 msec temporal resolutions, respectively. The durations of the aortic valve rapid opening (Tro ), rapid closing (Trc ), and the maximal aortic valve area (AVA) normalized to height were measured with all three temporal resolutions. M-mode echocardiograms with a temporal resolution of 0.8 msec were obtained for further comparison. STATISTICAL TEST Parameters were compared between the three sequences, together with the echocardiography results, with a Mann-Whitney U test. RESULTS Significantly shorter Tro (mean ± SD: 27.5 ± 6.7 msec) and Trc (43.8 ± 11.6 msec) and larger maximal AVA/height (2.01 ± 0.29 cm2 /m) were measured with get-SPEEDI compared to either bSSFP sequence (Tro of 56.3 ± 18.8 and 63.8 ± 20.2 msec; Trc of 68.2 ± 16.6 and 72.8 ± 18.2 msec; maximal AVA/height of 1.63 ± 0.28 and 1.65 ± 0.32 cm2 /m for 12 msec and 24 msec temporal resolutions, respectively, P

Objective. To investigate quantitative imaging markers based on parameters from two diffusion-weighted imaging (DWI) models, continuous-time random-walk (CTRW) and intravoxel incoherent motion (IVIM) models, for characterizing malignant and benign breast lesions by using a machine learning algorithm. Approach. With IRB approval, 40 women with histologically confirmed breast lesions (16 benign, 24 malignant) underwent DWI with 11 b-values (50 to 3000 s/mm2) at 3T. Three CTRW parameters, D m , α, and β and three IVIM parameters D diff, D perf, and f were estimated from the lesions. A histogram was generated and histogram features of skewness, variance, mean, median, interquartile range; and the value of the 10%, 25% and 75% quantiles were extracted for each parameter from the regions-of-interest. Iterative feature selection was performed using the Boruta algorithm that uses the Benjamin Hochberg False Discover Rate to first determine significant features and then to apply the Bonferroni correction to further control for false positives across multiple comparisons during the iterative procedure. Predictive performance of the significant features was evaluated using Support Vector Machine, Random Forest, Naïve Bayes, Gradient Boosted Classifier (GB), Decision Trees, AdaBoost and Gaussian Process machine learning classifiers. Main Results. The 75% quantile, and median of D m ; 75% quantile of f; mean, median, and skewness of β; kurtosis of D perf; and 75% quantile of D diff were the most significant features. The GB differentiated malignant and benign lesions with an accuracy of 0.833, an area-under-the-curve of 0.942, and an F1 score of 0.87 providing the best statistical performance (p-value < 0.05) compared to the other classifiers. Significance. Our study has demonstrated that GB with a set of histogram features from the CTRW and IVIM model parameters can effectively differentiate malignant and benign breast lesions.

Purpose To demonstrate an MRI technique-Submillisecond Periodic Event Encoded Dynamic Imaging (SPEEDI)-for capturing cyclic dynamic events with submillisecond temporal resolution. Methods The SPEEDI technique is based on an FID or an echo signal in which each time point in the signal is used to sample a distinct k-space raster, followed by repeated FIDs or echoes to produce the remaining k-space data in each k-space raster. All acquisitions are synchronized with a cyclic event, resulting in a set of time-resolved images of the cyclic event with a temporal resolution determined by the dwell time. In SPEEDI, spatial encoding is accomplished by phase encoding. The SPEEDI technique was demonstrated in two experiments at 3 T to (1) visualize fast-changing electric currents that mimicked the waveform of an action potential, and (2) characterize rapidly decaying eddy currents in an MRI system, with a temporal resolution of 0.2 ms and 0.4 ms, respectively. In both experiments, compressed sensing was incorporated to reduce the scan times. Phase difference maps related to the dynamics of electric currents or eddy currents were then obtained. Results In the first experiment, time-resolved phase maps resulting from the action potential-mimicking current waveform were successfully obtained and agreed well with theoretical calculations (normalized RMS error = 0.07). In the second experiment, spatially resolved eddy current phase maps revealed time constants (27.1 ± 0.2 ms, 41.1 ± 3.5 ms, and 34.8 ± 0.7 ms) that matched well with those obtained from an established method using point sources (26.4 ms, 41.2 ms and 34.8 ms). For both experiments, phase maps from fully sampled and compressed-sensing-accelerated k-space data exhibited a high structural similarity (> 0.8) despite a two-fold to three-fold acceleration. Conclusions We have illustrated that SPEEDI can provide submillisecond temporal resolution. This capability will likely lead to future exploration of ultrafast, cyclic biomedical processes using MRI.

Objective. This study aimed at developing a simultaneous multi-segment (SMSeg) imaging technique using a two-dimensional (2D) RF pulse in conjunction with echo planar imaging (EPI) to image multiple focal regions. Approach. The SMSeg technique leveraged periodic replicates of the excitation profile of a 2D RF pulse to simultaneously excite multiple focal regions at different locations. These locations were controlled by rotating and scaling transmit k-space trajectories. The resulting multiple isolated focal regions were projected into a composite ‘slice’ for display. GRAPPA-based parallel imaging was incorporated into SMSeg by taking advantage of coil sensitivity variations in both the phase-encoded and slice-selection directions. The SMSeg technique was implemented at 3 T in a single-shot gradient-echo EPI sequence and demonstrated in a phantom and human brains for both anatomic imaging and functional imaging. Main results. In both the phantom and the human brain, SMSeg images from three focal regions were simultaneously acquired. SMSeg imaging enabled up to a six-fold acceleration in parallel imaging without causing appreciable residual aliasing artifacts when compared with a conventional gradient-echo EPI sequence with the same acceleration factor. In the functional imaging experiment, BOLD activations associated with a visuomotor task were simultaneously detected in two non-coplanar segments (each with a size of 240 × 30 mm2), corresponding to visual and motor cortices, respectively. Significance. Our study has demonstrated that SMSeg imaging can be a viable method for studying multiple focal regions simultaneously.

We aim to quantify the benefits of cooperation between humanitarian relief agencies in terms of stocking decisions. We consider two agencies that stock the same type of relief item at different locations prone to individual disaster risks and agree to transship the shortage amount from available stocks in case of a disaster. We incorporate the disaster risk to the Newsvendor model by conditioning the stock quantity decisions on the event that a major disaster occurs within the lifetime of the stocked relief item. We optimize the stock quantity for each agency in response to the other's quantity and compute a Nash Equilibrium solution numerically. We apply this game theoretic approach to the case of earthquake preparedness in Istanbul to optimize the stocking decisions of an agency for shelter units in cooperation with another agency. We investigate the characteristics of the solutions under various parameter settings and identify cases in which cooperation may be beneficial to one or both of the agencies.

Purpose To investigate the role of neutrophil extracellular traps (NETs) and NET-associated proteins in the pathogenesis of oGVHD and whether dismantling of NETs with heparin reduces those changes. Methods Ocular surface washings from oGVHD patients and healthy subjects were analyzed. Isolated peripheral blood human neutrophils were stimulated to generate NETs and heparinized NETs. We performed in vitro experiments using cell lines (corneal epithelial, conjunctival fibroblast, meibomian gland (MG) epithelial and T cells), and in vivo experiments using murine models, and compared the effects of NETs, heparinized NETs, NET-associated proteins and neutralizing antibodies to NET-associated proteins. Results Neutrophils, exfoliated epithelial cells, NETs and NET-associated proteins (extracellular DNA, Neutrophil Elastase, Myeloperoxidase, Oncostatin M (OSM), Neutrophil gelatinase-associated lipocalin (NGAL) and LIGHT/TNFSF14) are present in ocular surface washings (OSW) and mucocellular aggregates (MCA). Eyes with high number of neutrophils in OSW have more severe signs and symptoms of oGVHD. NETs (and OSM) cause epitheliopathy in murine corneas. NETs (and LIGHT/TNFSF14) increase proliferation of T cells. NETs (and NGAL) inhibit proliferation and differentiation of MG epithelial cells. NETs enhance proliferation and myofibroblast transformation of conjunctival fibroblasts. Sub-anticoagulant dose Heparin (100 IU/mL) dismantles NETs and reduces epithelial, fibroblast, T cell and MG cell changes induced by NETs. Conclusion NETs and NET-associated proteins contribute to the pathological changes of oGVHD (corneal epitheliopathy, conjunctival cicatrization, ocular surface inflammation and meibomian gland disease). Our data points to the potential of NET-associated proteins (OSM or LIGHT/TNFSF14) to serve as biomarkers and NET-dismantling biologics (heparin eye drops) as treatment for oGVHD.

Background Motor symptoms in Parkinson disease (PD) have exhibited lateral asymmetry, suggesting asymmetric neuronal loss in the substantia nigra (SN). Diffusion MRI may be able to help confirm tissue microstructural alterations in the substantia nigra to probe for the presence of asymmetry. Purpose To investigate lateral asymmetry in the SN of patients with PD by using diffusion MRI with both Gaussian and non-Gaussian models. Materials and Methods In this cross-sectional study conducted from March 2015 to March 2017, 27 participants with PD and 27 age-matched healthy control (HC) participants, all right handed, underwent MRI at 3.0 T. High-spatial-resolution diffusion images were acquired with a reduced field of view by using seven b values up to 3000 sec/mm2. A continuous-time random-walk (CTRW) non-Gaussian diffusion model was used to produce anomalous diffusion coefficient (Dm) and temporal (α) and spatial (β) diffusion heterogeneity indexes followed by a Gaussian diffusion model to yield an apparent diffusion coefficient (ADC). Individual or linear combinations of diffusion parameters in the SN were unilaterally and bilaterally compared between the PD and HC groups. Results In the bilateral comparison between the PD and HC groups, differences were observed in β (0.67 ± 0.06 [standard deviation] vs 0.64 ± 0.04, respectively; P = .016), ADC (0.48 μm2/msec ± 0.08 vs 0.53 μm2/msec ± 0.06, respectively; P = .03), and the combination of CTRW parameters (P = .02). In the unilateral comparison, differences were observed in all diffusion parameters on the left SN (P .20). In a receiver operating characteristic (ROC) analysis to delineate left SN abnormality in PD, the combination of Dm, α, and β produced the best sensitivity (sensitivity, 0.78); the combination of Dm and β produced the best specificity (specificity, 0.85); and the combination of α and β produced the largest area under the ROC curve (area under the ROC curve, 0.73). Conclusion These results suggest that quantitative diffusion MRI is sensitive to brain tissue changes in participants with Parkinson disease and provide evidence of substantia nigra lateral asymmetry in this disease. © RSNA, 2019 Online supplemental material is available for this article.

OBJECTIVES: To investigate factors associated with residual sleepiness in patients who were highly adherent to continuous positive airway pressure (CPAP). Nocturnal inactivity, comorbidities, concomitant medications, and, in particular, white matter (WM) differences using diffusion magnetic resonance imaging (MRI) were explored using a continuous-time random-walk (CTRW) model. METHODS: Twenty-seven male patients (30–55 years of age) with obstructive sleep apnea (OSA) received CPAP as the only treatment (CPAP ≥ 6hr./night) for at least 30 days. Based on the Psychomotor Vigilance Task (PVT) results, participants were divided into a non-sleepy group (lapses ≤ 5; n = 18) and a sleepy group (lapses > 5; n = 9). Mean nocturnal inactivity (sleep proxy) was measured using actigraphy for one week. Diffusion-weighted imaging (DWI) with high b-values, as well as diffusion tensor imaging (DTI), was performed on a 3 Tesla MRI scanner. The DWI dataset was analyzed using the CTRW model that yielded three parameters: temporal diffusion heterogeneity α, spatial diffusion heterogeneity β, and an anomalous diffusion coefficient D(m). The differences in α, β, D(m), and the combination of α and β between the two groups were investigated by a whole-brain analysis using tract-based spatial statistics (TBSS), followed by a regional analysis on individual fiber tracts using a standard parcellation template. Results from the CTRW model were compared with those obtained from DTI. The three CTRW parameters were also correlated with the clinical assessment scores, Epworth Sleepiness Scale (ESS), PVT lapses, and PVT mean reaction time (MRT) in specific fiber tracts. RESULTS: There were no differences between groups in mean sleep duration, comorbidities, and the number or type of medications, including alerting and sedating medications. In the whole-brain DWI analysis, the sleepy group showed higher α (17.27% of the WM voxels) and D(m) (17.14%) when compared to the non-sleepy group (P < 0.05), whereas no significant difference in β was observed. In the regional fiber analysis, the sleepy and non-sleepy groups showed significant differences in α, β, or their combinations in a total of twelve fiber tracts, whereas similar differences were not observed in DTI parameters, when age was used as a covariate. Additionally, moderate to strong correlations between the CTRW parameters (α, β, or D(m)) and the sleepiness assessment scores (ESS, PVT lapses, or PVT MRT) were observed in specific fiber tracts (|R| = 0.448–0.654, P = 0.0003–0.019). CONCLUSIONS: The observed differences in the CTRW parameters between the two groups indicate that WM alterations can be a possible mechanism to explain reversible versus residual sleepiness observed in OSA patients with identical high level of CPAP use. The moderate to strong correlations between the CTRW parameters and the clinical scores suggest the possibility of developing objective and quantitative imaging markers to complement clinical assessment of OSA patients.

To evaluate the feasibility of high b-value diffusion-weighted imaging (DWI) for distinguishing non-muscle-invasive bladder cancer (NMIBC) from muscle-invasive bladder cancer (MIBC) and low- from high-grade bladder urothelial carcinoma using a fractional-order calculus (FROC) model as well as a combination of FROC DWI and bi-parametric Vesical Imaging-Reporting and Data System (VI-RADS).Fifty-eight participants with bladder urothelial carcinoma were included in this IRB-approved prospective study. Diffusion-weighted images, acquired with 16 b-values (0-3600 s/mmD and μ were significantly lower in the MIBC group than in the NMIBC group (p = 0.001 for each), and D, β, and μ all exhibited significantly lower values in the high- than in the low-grade tumors (p ≤ 0.011). The combination of D, β, and μ produced the highest specificity (85%), accuracy (78%), and the area under the ROC curve (AUC, 0.782) for distinguishing NMIBC and MIBC, and the best sensitivity (89%), specificity (86%), accuracy (88%), and AUC (0.892) for tumor grading, all of which outperformed the ADC. The combination of FROC parameters with bi-parametric VI-RADS improved the AUC from 0.859 to 0.931.High b-value DWI with a FROC model is useful in distinguishing NMIBC from MIBC and grading bladder tumors.• Diffusion parameters derived from a FROC diffusion model may differentiate NMIBC from MIBC and low- from high-grade bladder urothelial carcinomas. • Under the condition of a moderate sample size, higher AUCs were achieved by the FROC parameters D (0.842) and μ (0.857) than ADC (0.804) for bladder tumor grading with p ≤ 0.046. • The combination of the three diffusion parameters from the FROC model can improve the specificity over ADC (85% versus 67%, p = 0.031) for distinguishing NMIBC and MIBC and enhance the performance of bi-parametric VI-RADS.

Applications of fractional calculus in magnetic resonance imaging (MRI) have increased over the last twenty years. From the mathematical, computational, and biophysical perspectives, fractional calculus provides new tools for describing the complexity of biological tissues (cells, organelles, membranes and macromolecules). Specifically, fractional order models capture molecular dynamics (transport, rotation, and vibration) by incorporating power law con-volution kernels into the time and space derivatives appearing in the equations that govern nuclear magnetic resonance (NMR) phenomena. Hence, it is natural to expect fractional calculus models of relaxation and diffusion to be applied to problems in NMR and MRI. Early studies considered the fractal dimensions of multi-scale materials in the non-linear growth of the mean squared displacement, assumed power-law decays of the spectral density, and suggested stretched exponential signal relaxation to describe non-Gaussian behavior. Subsequently, fractional order generalization of the Bloch, and Bloch-Torrey equations were developed to characterize NMR (and MRI) relaxation and diffusion. However, even for simple geometries, analytical solutions of fractional order equations in time and space are difficult to obtain, and predictions of the corresponding changes in image contrast are not always possible. Currently, a multifaceted approach using coarse graining, simulation, and accelerated computation is being developed to identify ‘imaging’ biomarkers of disease. This review surveys the principal fractional order models used to describe NMR and MRI phenomena, identifies connections and limitations, and finally points to future applications of the approach.

To evaluate the performance of a fractional order calculus (FROC) diffusion model for imaging-based assessment of Lauren classification in gastric adenocarcinoma. In this study, 43 patients (15 females, 28 males) with gastric adenocarcinoma underwent MRI at 1.5 T. According to pathology-based Lauren classification, 10 patients had diffuse-type, 20 had intestinal-type, and 13 had mixed-type lesions. The diffuse and mixed types were combined as diffuse-and-mixed type to be differentiated from the intestinal type using diffusion MRI. Diffusion-weighted images were acquired by using eleven b-values (0–2000 s/mm2). Three FROC model parameters comprising diffusion coefficient D, intravoxel diffusion heterogeneity β, and a microstructural quantity μ, together with a conventional apparent diffusion coefficient (ADC), were estimated. The mean parameter values in the tumour were computed by using a percentile histogram analysis. Individual or linear combinations of the mean parameters in the tumour were used to differentiate the diffuse-and-mixed type from the intestinal type using descriptive statistics and receiver operating characteristic (ROC) analyses. Significant differences were observed between diffuse-and-mixed-type and intestinal-type lesions in D (0.99 ± 0.20 μm2/ms vs. 1.11 ± 0.23 μm2/ms; p = 0.036), β (0.37 ± 0.08 vs. 0.43 ± 0.11; p = 0.043), μ (7.92 ± 2.79 μm vs. 9.87 ± 1.52 μm; p = 0.038), and ADC (0.81 ± 0.34 μm2/ms vs. 0.96 ± 0.19 μm2/ms; p = 0.033). Among the individual parameters, μ produced the largest area under the ROC curve (0.739). The combinations of (D, β, μ) and (β and μ) produced the best overall performance with a sensitivity of 0.739, specificity of 0.750, accuracy of 0.744, and area under the curve of 0.793 (95% confidence interval: 0.657–0.929). Diffusion MRI with the FROC model holds promise for non-invasive assessment of Lauren classification for gastric adenocarcinoma. • High b-value diffusion MRI with a FROC model that is sensitive to tissue microstructures can differentiate the diffuse-and-mixed type from intestinal type of gastric adenocarcinoma. • The combination of FROC parameters produced the best result for distinguishing the diffuse-and-mixed type from the intestinal type with an area under the receiver operating characteristic curve of 0.793. • The FROC model parameters, individually or conjointly, hold promise for repeated, non-invasive evaluations of gastric adenocarcinoma at various time points throughout disease progression or regression to complement conventional Lauren classification.

The purpose of this study is to investigate the feasibility of using a continuous-time random-walk (CTRW) diffusion model, together with a quartile histogram analysis, for assessing glioma malignancy by probing tissue heterogeneity as well as cellularity. In this prospective study, 91 patients (40 females, 51 males) with histopathologically proven gliomas underwent MRI at 3 T. The cohort included 42 grade II (GrII), 19 grade III (GrIII) and 29 grade IV (GrIV) gliomas. Echo-planar diffusion-weighted imaging was conducted using 17 b-values (0-4000 s/mm2 ). Three CTRW model parameters, including an anomalous diffusion coefficient Dm , and two parameters related to temporal and spatial diffusion heterogeneity α and β, respectively, were obtained. The mean parameter values within the tumor regions of interest (ROIs) were computed by utilizing the first quartile of the histograms as well as the full ROI for comparison. A Bonferroni-Holm-corrected Mann-Whitney U-test was used for the group comparisons. Individual and combinations of the CTRW parameters were evaluated for the characterization of gliomas with a receiver operating characteristic analysis. All first-quartile mean CTRW parameters yielded significant differences (p-values < 0.05) between pair-wise comparisons of GrII (Dm : 1.14 ± 0.37 μm2 /ms; α: 0.904 ± 0.03, β: 0.913 ± 0.06), GrIII (Dm : 0.88 ± 0.21 μm2 /ms; α: 0.888 ± 0.01, β: 0.857 ± 0.06) and GrIV gliomas (Dm : 0.73 ± 0.22 μm2 /ms; α: 0.878 ± 0.01; β: 0.791 ± 0.07). The highest sensitivity, specificity, accuracy and area-under-the-curve of using the combinations of the first-quartile parameters were 84.2%, 78.5%, 75.4% and 0.76 for GrII and GrIII classification; 86.2%, 89.4%, 75% and 0.76 for GrIII and GrIV classification; and 86.2%, 85.7%, 84.5% and 0.90 for GrII and GrIV classification, respectively. Quartile-based analysis produced higher accuracy and area-under-the-curve than the full ROI-based analysis in all classifications. The CTRW diffusion model, together with a quartile-based histogram analysis, offers a new way for probing tumor structural heterogeneity at a subvoxel level, and has potential for in vivo assessment of glioma malignancy to complement histopathology.

Recent studies of cancer somatic mutation profiles seek to identify mutations for targeted therapy in personalized medicine. Analysis of profiles, however, is not trivial, as each profile is heterogeneous and there are multiple confounding factors that influence the cause-and-effect relationships between cancer genes such as cancer (sub)type, biological processes, total number of mutations, and non-linear mutation interactions. Moreover, cancer is biologically redundant, i.e., distinct mutations can result in the alteration of similar biological processes, so it is important to identify all possible combinatorial sets of mutations for effective patient treatment. To model this phenomena, we propose the correlated zero-inflated negative binomial process to infer the inherent structure of somatic mutation profiles through latent representations. This stochastic process takes into account different, yet correlated, co-occurring mutations using profile-specific negative binomial dispersion parameters that are mixed with a correlated beta-Bernoulli process and a probability parameter to model profile heterogeneity. These model parameters are inferred by iterative optimization via amortized and stochastic variational inference using the Pan Cancer dataset from The Cancer Genomic Archive (TCGA). By examining the the latent space, we identify biologically relevant correlations between somatic mutations.

It has been increasingly reported that in biological tissues diffusion-weighted MRI signal attenuation deviates from mono-exponential decay, especially at high b-values. A number of diffusion models have been proposed to characterize this non-Gaussian diffusion behavior. One of these models is the continuous-time random-walk (CTRW) model, which introduces two new parameters: a fractional order time derivative α and a fractional order spatial derivative β. These new parameters have been linked to intravoxel diffusion heterogeneities in time and space, respectively, and are believed to depend on diffusion times. Studies on this time dependency are limited, largely because the diffusion time cannot vary over a board range in a conventional spin-echo echo-planar imaging sequence due to the accompanying T2 decays. In this study, we investigated the time-dependency of the CTRW model in Sephadex gel phantoms across a broad diffusion time range by employing oscillating-gradient spin-echo, pulsed-gradient spin-echo, and pulsed-gradient stimulated echo sequences. We also performed Monte Carlo simulations to help understand our experimental results. It was observed that the diffusion process fell into the Gaussian regime at extremely short diffusion times whereas it exhibited a strong time dependency in the CTRW parameters at longer diffusion times.

OBJECTIVE: The goal of this work is to study the changes in white matter integrity in R6/2, a well-established animal model of Huntington’s disease (HD) that are captured by ex vivo diffusion imaging (DTI) using a high field MRI (17.6 T). MATERIALS AND METHODS: DTI and continuous time random walk (CTRW) models were used to fit changes in the diffusion-weighted signal intensity in the corpus callosum of controls and in R6/2 mice. RESULTS: A significant 13% decrease in fractional anisotropy, a 7% increase in axial diffusion, and a 33% increase in radial diffusion were observed between R6/2 and control mice. No change was observed in the CTRW beta parameter, but a significant decrease in the alpha parameter (− 21%) was measured. Histological analysis of the corpus callosum showed a decrease in axonal organization, myelin alterations, and astrogliosis. Electron microscopy studies demonstrated ultrastructural changes in degenerating axons, such as an increase in tortuosity in the R6/2 mice. CONCLUSIONS: DTI and CTRW diffusion models display quantitative changes associated with the microstructural alterations observed in the corpus callosum of the R6/2 mice. The observed increase in the diffusivity and decrease in the alpha CTRW parameter providing support for the use of these diffusion models for non-invasive detection of white matter alterations in HD.

Purpose To investigate white matter (WM) structural alterations using diffusion tensor imaging (DTI) in obstructive sleep apnea (OSA) patients, with or without residual sleepiness, following adherent continuous positive airway pressure (CPAP) treatment. Possible quantitative relationships were explored between the DTI metrics and two clinical assessments of somnolence. Materials and Methods Twenty-nine male patients (30–55 years old) with a confirmed diagnosis of OSA were recruited. The patients were treated with CPAP therapy only. The Psychomotor Vigilance Task (PVT) and Epworth Sleepiness Scale (ESS) were performed after CPAP treatment and additionally administered at the time of the magnetic resonance imaging (MRI) scan. Based on the PVT results, the patients were divided into a nonsleepy group (lapses ≤5) and a sleepy group (lapses >5). DTI was performed at 3T, followed by an analysis using tract-based spatial statistics (TBSS) to investigate the differences in fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (λ1), and radial diffusivity (λ23) between the two groups. Results A higher MD (P 0.17). The alterations in FA or MD of individual fiber tracts occurred mainly in the internal/external capsule, corona radiata, corpus callosum, and sagittal stratum regions. The FA and MD values correlated with the PVT and ESS assessments from all patients (R ≥ 0.517, P < 0.05). Conclusion Global and regional WM alterations, as revealed by DTI, can be a possible mechanism to explain why OSA patients with high levels of CPAP use can have differing responses to treatment. Compromised myelin sheath, indicated by increased radial diffusivity, can be involved in the underlying WM changes. Evidence level: 1 J. MAGN. RESON. IMAGING 2017;45:1371–1378

BACKGROUND AND PURPOSE: Imaging-based tumor grading is highly desirable but faces challenges in sensitivity, specificity, and diagnostic accuracy. A recently proposed diffusion imaging method by using a fractional order calculus model offers a set of new parameters to probe not only the diffusion process itself but also intravoxel tissue structures, providing new opportunities for noninvasive tumor grading. This study aimed to demonstrate the feasibility of using the fractional order calculus model to differentiate low- from high-grade gliomas in adult patients and illustrate its improved performance over a conventional diffusion imaging method using ADC (or D ). MATERIALS AND METHODS: Fifty-four adult patients (18–70 years of age) with histology-proved gliomas were enrolled and divided into low-grade ( n = 24) and high-grade ( n = 30) groups. Multi-b-value diffusion MR imaging was performed with 17 b-values (0–4000 s/mm 2 ) and was analyzed by using a fractional order calculus model. Mean values and SDs of 3 fractional order calculus parameters ( D , β, and μ) were calculated from the normal contralateral thalamus (as a control) and the tumors, respectively. On the basis of these values, the low- and high-grade glioma groups were compared by using a Mann-Whitney U test. Receiver operating characteristic analysis was performed to assess the performance of individual parameters and the combination of multiple parameters for low- versus high-grade differentiation. RESULTS: Each of the 3 fractional order calculus parameters exhibited a statistically higher value ( P ≤ .011) in the low-grade than in the high-grade gliomas, whereas there was no difference in the normal contralateral thalamus ( P ≥ .706). The receiver operating characteristic analysis showed that β (area under the curve = 0.853) produced a higher area under the curve than D (0.781) or μ (0.703) and offered a sensitivity of 87.5%, specificity of 76.7%, and diagnostic accuracy of 82.1%. CONCLUSIONS: The study demonstrated the feasibility of using a non-Gaussian fractional order calculus diffusion model to differentiate low- and high-grade gliomas. While all 3 fractional order calculus parameters showed statistically significant differences between the 2 groups, β exhibited a better performance than the other 2 parameters, including ADC (or D ).

BACKGROUND AND PURPOSE: The limitations inherent in the current methods of diagnosing mild cognitive impairment have constrained the use of early therapeutic interventions to delay the progression of mild cognitive impairment to dementia. This study evaluated whether quantifying enlarged perivascular spaces observed on MR imaging can help differentiate those with mild cognitive impairment from cognitively healthy controls and, thus, have an application in the diagnosis of mild cognitive impairment. MATERIALS AND METHODS: We automated the identification of enlarged perivascular spaces in brain MR Images using a custom quantitative program designed with Matlab. We then quantified the densities of enlarged perivascular spaces for patients with mild cognitive impairment (n = 14) and age-matched cognitively healthy controls (n = 15) and compared them to determine whether the density of enlarged perivascular spaces can serve as an imaging surrogate for mild cognitive impairment diagnosis. RESULTS: Quantified as a percentage of volume fraction (v/v%), densities of enlarged perivascular spaces were calculated to be 2.82 ± 0.40 v/v% for controls and 4.17 ± 0.57 v/v% for the mild cognitive impairment group in the subcortical brain (P CONCLUSIONS: The density of enlarged perivascular spaces was found to be significantly higher in those with mild cognitive impairment compared with age-matched healthy control subjects. The density of enlarged perivascular spaces, therefore, may be a useful imaging biomarker for the diagnosis of mild cognitive impairment.

Purpose To demonstrate that a continuous-time random-walk (CTRW) diffusion model can improve diagnostic accuracy of differentiating low- and high-grade pediatric brain tumors. Methods Fifty-four children with histopathologically confirmed brain tumors underwent diffusion MRI scans at 3Twith 12 b-values (0-4000 s/mm2). The diffusion imageswere fit to a simplified CTRW model to extract anomalous diffusion coefficient, Dm, and temporal and spatial heterogeneity parameters, α and β, respectively. Using histopathology results as reference, a k-means clustering algorithm and a receiver operating characteristic (ROC) analysis were employed to determine the sensitivity, specificity, and diagnostic accuracy of the CTRW parameters in differentiating tumor grades. Results Significant differences between the low- and high-grade tumors were observed in the CTRW parameters (p-values

The purpose of this study was to develop an analytical expression for a fractional motion (FM) diffusion model to characterize diffusion-induced signal attenuation in a twice-refocused spin-echo (TRSE) sequence that is resilient to eddy currents, and to demonstrate its applicability to human brain imaging in vivo. Based on the FM theory, which provides a unified statistical description for Langevin motions, the diffusion-weighted (DW) MR signal was measured with a TRSE sequence that balances the concomitant gradients. The analytical expression was fitted to a set of DW images acquired with 14 b-values (0-4000 s/mm2 ) from a total of 10 healthy human subjects at 3 T, yielding three FM parameter maps based on anomalous diffusion coefficient Dφ, ψ , diffusion increment variance φ, and diffusion correlation ψ, respectively. These parameters were used to characterize different brain regions in gray matter (GM), white matter (WM), and cerebrospinal fluid. The analytical expression for the TRSE-based FM model accurately described diffusion signal attenuation in healthy brain tissues at high b-values. TRSE's robustness against eddy currents was illustrated by comparing results from an expression for a conventional Stejskal-Tanner sequence. The TRSE-based FM model also produced consistent GM-WM contrast (p < 0.01) across all brain regions studied, whereas the consistency was not observed with the Stejskal-Tanner-based FM model. This new analytical expression is expected to enable further investigations to probe tissue structures by exploiting anomalous diffusion properties without being hindered by eddy-current perturbations at high b-values.

Nontask functional magnetic resonance imaging (fMRI) has become one of the most popular noninvasive areas of brain mapping research for neuroscientists. In nontask fMRI, various sources of “noise” corrupt the measured blood oxygenation level-dependent signal. Many studies have aimed to attenuate the noise in reconstructed voxel measurements through spatial and temporal processing operations. While these solutions make the data more “appealing,” many commonly used processing operations induce artificial correlations in the acquired data. As such, it becomes increasingly more difficult to derive the true underlying covariance structure once the data have been processed. As the goal of nontask fMRI studies is to determine, utilize, and analyze the true covariance structure of acquired data, such processing can lead to inaccurate and misleading conclusions drawn from the data if they are unaccounted for in the final connectivity analysis. In this article, we develop a framework that represents the spatiotemporal processing and reconstruction operations as linear operators, providing a means of precisely quantifying the correlations induced or modified by such processing rather than by performing lengthy Monte Carlo simulations. A framework of this kind allows one to appropriately model the statistical properties of the processed data, optimize the data processing pipeline, characterize excessive processing, and draw more accurate functional connectivity conclusions.

Relaxation parameter estimation and brain activation detection are two main areas of study in magnetic resonance imaging (MRI) and functional magnetic resonance imaging (fMRI). Relaxation parameters can be used to distinguish voxels containing different types of tissue whereas activation determines voxels that are associated with neuronal activity. In fMRI, the standard practice has been to discard the first scans to avoid magnetic saturation effects. However, these first images have important information on the MR relaxivities for the type of tissue contained in voxels, which could provide pathological tissue discrimination. It is also well-known that the voxels located in gray matter (GM) contain neurons that are to be active while the subject is performing a task. As such, GM MR relaxivities can be incorporated into a statistical model in order to better detect brain activation. Moreover, although the MR magnetization physically depends on tissue and imaging parameters in a nonlinear fashion, a linear model is what is conventionally used in fMRI activation studies. In this study, we develop a statistical fMRI model for Differential T2(*) ConTrast Incorporating T1 and T2(*) of GM, so-called DeTeCT-ING Model, that considers the physical magnetization equation to model MR magnetization; uses complex-valued time courses to estimate T1 and T2(*) for each voxel; then incorporates gray matter MR relaxivities into the statistical model in order to better detect brain activation, all from a single pulse sequence by utilizing the first scans.

The acquisition of sub-sampled data from an array of receiver coils has become a common means of reducing data acquisition time in MRI. Of the various techniques used in parallel MRI, SENSitivity Encoding (SENSE) is one of the most common, making use of a complex-valued weighted least squares estimation to unfold the aliased images. It was recently shown in Bruce et al. [Magn. Reson. Imag. 29(2011):1267–1287] that when the SENSE model is represented in terms of a real-valued isomorphism, it assumes a skew-symmetric covariance between receiver coils, as well as an identity covariance structure between voxels. In this manuscript, we show that not only is the skew-symmetric coil covariance unlike that of real data, but the estimated covariance structure between voxels over a time series of experimental data is not an identity matrix. As such, a new model, entitled SENSE-ITIVE, is described with both revised coil and voxel covariance structures. Both the SENSE and SENSE-ITIVE models are represented in terms of real-valued isomorphisms, allowing for a statistical analysis of reconstructed voxel means, variances, and correlations resulting from the use of different coil and voxel covariance structures used in the reconstruction processes to be conducted. It is shown through both theoretical and experimental illustrations that the miss-specification of the coil and voxel covariance structures in the SENSE model results in a lower standard deviation in each voxel of the reconstructed images, and thus an artificial increase in SNR, compared to the standard deviation and SNR of the SENSE-ITIVE model where both the coil and voxel covariances are appropriately accounted for. It is also shown that there are differences in the correlations induced by the reconstruction operations of both models, and consequently there are differences in the correlations estimated throughout the course of reconstructed time series. These differences in correlations could result in meaningful differences in interpretation of results.

Patients with type 2 diabetes mellitus have considerably higher risk of developing cognitive impairment and dementia. WM changes in these patients have been reported. Our aim was to demonstrate that gradual and continuous WM change and the associated cognitive decline in patients with type 2 diabetes mellitus can be captured by DTI parameters, which can be used to complement neuropsychological test scores in identifying patients with type 2 diabetes mellitus with and without mild cognitive impairment.Forty-two patients with type 2 diabetes mellitus, divided into a group with mild cognitive impairment (n = 20) and a group with normal cognition (n = 22), were enrolled with age-, sex-, and education-matched healthy controls (n = 26). 3T DTI followed by Tract-Based Spatial Statistics analysis was used to investigate the differences in fractional anisotropy, mean diffusivity, axial diffusivity (λ1), and radial diffusivity (λ23) among the groups. A receiver operating characteristic analysis assessed the performance of DTI parameters for separating the 2 groups with type 2 diabetes mellitus.The whole-brain Tract-Based Spatial Statistics analysis revealed that 7.3% and 24.9% of the WM exhibited decreased fractional anisotropy and increased mean diffusivity (P.05), respectively, between the diabetes mellitus with mild cognitive impairment and the diabetes mellitus with normal cognition groups, while considerably larger WM regions showed fractional anisotropy (36.6%) and mean diffusivity (58.8%) changes between the diabetes mellitus with mild cognitive impairment and the healthy control groups. These changes were caused primarily by an elevated radial diffusivity observed in the patients with diabetes mellitus with mild cognitive impairment. Radial diffusivity also exhibited subtle but statistically significant changes between the diabetes mellitus with normal cognition and the healthy control groups. Analyses on individual fiber tracts showed pronounced fractional anisotropy reduction and mean diffusivity elevation in regions related to cognitive functions. The receiver operating characteristic analysis on the right cingulum (hippocampus) showed that fractional anisotropy produced a larger area under the curve (0.832) than mean diffusivity (0.753) for separating mild cognitive impairment from normal cognition among patients with type 2 diabetes mellitus. When fractional anisotropy was combined with mean diffusivity, the area under the curve was further improved to 0.857.DTI parameters can show a substantial difference between patients with type 2 diabetes mellitus with and without mild cognitive impairment, suggesting their potential use as an imaging marker for detecting cognitive decline in patients with type 2 diabetes mellitus. More important, DTI parameters may capture gradual and continuous WM changes that can be associated with early stages of cognitive decline in patients with type 2 diabetes mellitus before they can be diagnosed clinically by using conventional neuropsychological tests.

To develop a mathematical model that incorporates the magnetic resonance relaxivities into the image reconstruction process in a single step.In magnetic resonance imaging, the complex-valued measurements of the acquired signal at each point in frequency space are expressed as a Fourier transformation of the proton spin density weighted by Fourier encoding anomalies: T2(⁎), T1, and a phase determined by magnetic field inhomogeneity (∆B) according to the MR signal equation. Such anomalies alter the expected symmetry and the signal strength of the k-space observations, resulting in images distorted by image warping, blurring, and loss in image intensity. Although T1 on tissue relaxation time provides valuable quantitative information on tissue characteristics, the T1 recovery term is typically neglected by assuming a long repetition time. In this study, the linear framework presented in the work of Rowe et al., 2007, and of Nencka et al., 2009 is extended to develop a Fourier reconstruction operation in terms of a real-valued isomorphism that incorporates the effects of T2(⁎), ∆B, and T1. This framework provides a way to precisely quantify the statistical properties of the corrected image-space data by offering a linear relationship between the observed frequency space measurements and reconstructed corrected image-space measurements. The model is illustrated both on theoretical data generated by considering T2(⁎), T1, and/or ∆B effects, and on experimentally acquired fMRI data by focusing on the incorporation of T1. A comparison is also made between the activation statistics computed from the reconstructed data with and without the incorporation of T1 effects.Accounting for T1 effects in image reconstruction is shown to recover image contrast that exists prior to T1 equilibrium. The incorporation of T1 is also shown to induce negligible correlation in reconstructed images and preserve functional activations.With the use of the proposed method, the effects of T2(⁎) and ∆B can be corrected, and T1 can be incorporated into the time series image-space data during image reconstruction in a single step. Incorporation of T1 provides improved tissue segmentation over the course of time series and therefore can improve the precision of motion correction and image registration.

Objectives To demonstrate the feasibility of a novel fractional motion (FM) diffusion model for distinguishing low- versus high-grade pediatric brain tumors; and to investigate its possible advantage over apparent diffusion coefficient (ADC) and/or a previously reported continuous-time random-walk (CTRW) diffusion model. Materials and methods With approval from the institutional review board and written informed consents from the legal guardians of all participating patients, this study involved 70 children with histopathologically-proven brain tumors (30 low-grade and 40 high-grade). Multi-b-value diffusion images were acquired and analyzed using the FM, CTRW, and mono-exponential diffusion models. The FM parameters, Dfm, φ, ψ (non-Gaussian diffusion statistical measures), and the CTRW parameters, Dm, α, β (non-Gaussian temporal and spatial diffusion heterogeneity measures) were compared between the low- and high-grade tumor groups by using a Mann-Whitney-Wilcoxon U test. The performance of the FM model for differentiating between low- and high-grade tumors was evaluated and compared with that of the CTRW and the mono-exponential models using a receiver operating characteristic (ROC) analysis. Results The FM parameters were significantly lower (p, Highlights • The fractional motion (FM) diffusion model was applied to pediatric brain tumors. • The FM model parameters can be sensitive to tissue microstructures. • The FM model outperforms the mono-exponential diffusion model. • The FM model performs similarly to the continuous-time random-walk (CTRW) model. • Our results challenge those from recent biophysics studies in cell cultures.