M. Muge Karaman

Differentiating low- and high-grade pediatric brain tumors using a continuous-time random-walk diffusion model at high b-values

To demonstrate that a continuous‐time random‐walk (CTRW) diffusion model can improve diagnostic accuracy of differentiating low‐ and high‐grade pediatric brain tumors.

A statistical examination of SENSE image reconstruction via an isomorphism representation.

In magnetic resonance imaging, the parallel acquisition of subsampled spatial frequencies from an array of multiple receiver coils has become a common means of reducing data acquisition time. SENSitivity Encoding (SENSE) is a popular parallel image reconstruction model that uses a complex-valued least squares estimation process to unfold aliased images. In this article, the linear mathematical framework derived in Rowe et al. [J Neurosci Meth 159 (2007) 361-369] is built upon to perform image reconstruction with subsampled data acquired from multiple receiver coils, where the SENSE model is represented as a real-valued isomorphism. A statistical analysis is performed of the various image reconstruction operators utilized in the SENSE model, with an emphasis placed on the effects of each operator on voxel means, variances and correlations. It is shown that, despite the attractiveness of models that unfold the aliased images from subsampled data, there is an artificial correlation induced between reconstructed voxels from the different folds of aliased images. As such, the mathematical framework outlined in this manuscript could be further developed to provide a means of accounting for this unavoidable correlation induced by image reconstruction operators.

A Diffusion Tensor Imaging Study on White Matter Abnormalities in Patients with Type 2 Diabetes Using Tract-Based Spatial Statistics

BACKGROUND AND PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Differentiation of Low- and High-Grade Gliomas Using High b-Value Diffusion Imaging with a Non-Gaussian Diffusion Model

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/mm2) 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).

A fractional motion diffusion model for grading pediatric brain tumors

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 < 0.0001) in the high-grade (Dfm: 0.81 ± 0.26, φ: 1.40 ± 0.10, ψ: 0.42 ± 0.11) than in the low-grade (Dfm: 1.52 ± 0.52, φ: 1.64 ± 0.13, ψ: 0.67 ± 0.13) tumor groups. The ROC analysis showed that the FM parameters offered better specificity (88% versus 73%), sensitivity (90% versus 82%), accuracy (88% versus 78%), and area under the curve (AUC, 93% versus 80%) in discriminating tumor malignancy compared to the conventional ADC. The performance of the FM model was similar to that of the CTRW model. Conclusions Similar to the CTRW model, the FM model can improve differentiation between low- and high-grade pediatric brain tumors over ADC.

The SENSE-Isomorphism Theoretical Image Voxel Estimation (SENSE-ITIVE) model for reconstruction and observing statistical properties of reconstruction operators

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.

Brain white matter changes in CPAP-treated obstructive sleep apnea patients with residual sleepiness

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.

A statistical fMRI model for differential T2* contrast incorporating T1 and T2* of gray matter

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.

A fractional motion diffusion model for a twice-refocused spin-echo pulse sequence

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. TRSEs 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.

Capturing complexity of the diffusion-weighted MR signal decay

Diffusion-weighted MRI (dMRI) is a key component of clinical radiology. When analyzing diffusion-weighted images, radiologists often seek to infer microscopic tissue structure through measurements of the diffusion coefficient, D0 (mm2/s). This multi-scale problem is framed by the creation of diffusion models of signal decay based on physical laws, histological structure, and biophysical constraints. The purpose of this paper is to simplify the model building process by focusing on the observed decay in the effective diffusion coefficient as a function of diffusion weighting (b-value), D(b), that is often observed in complex biological tissues. We call this approach the varying diffusion curvature (VDC) model. Since this is a heuristic model, the exact functional form of this decay is not important, so here we examine a simple exponential function, D(b) = D0exp(-bD1), where D0 and D1 capture aspects of hindered and restricted diffusion, respectively. As an example of the potential of the VDC model, we applied it to dMRI data collected from normal and diseased human brain tissue using Stejskal-Tanner diffusion gradient pulses. In order to illustrate the connection between D0 and D1 and the sub-voxel structure we also analyzed dMRI data from families of Sephadex beads selected with increasing tortuosity. Finally, we applied the VDC model to dMRI simulations of nested muscle fiber phantoms whose permeability, atrophy, and fiber size distribution could be changed. These results demonstrate that the VDC model is sensitive to sub-voxel tissue structure and composition (porosity, tortuosity, and permeability), hence can capture tissue complexity in a manner that could be easily applied in clinical dMRI.