Jonathan K. Riek

Reproducibility of hepatic fat fraction measurement by magnetic resonance imaging

To evaluate the reproducibility of magnetic resonance imaging (MRI)‐determined hepatic fat fraction (%) across imaging sites with different magnet types and field strength. Reproducibility among MRI platforms is unclear, even though evaluating hepatic fat fractions (FFs) using MRI‐based methods is accurate against MR spectroscopy.

Pre-Treatment Whole Blood Gene Expression Is Associated with 14-Week Response Assessed by Dynamic Contrast Enhanced Magnetic Resonance Imaging in Infliximab-Treated Rheumatoid Arthritis Patients

Approximately 30% of rheumatoid arthritis patients achieve inadequate response to anti-TNF biologics. Attempts to identify molecular biomarkers predicting response have met with mixed success. This may be attributable, in part, to the variable and subjective disease assessment endpoints with large placebo effects typically used to classify patient response. Sixty-one patients with active RA despite methotrexate treatment, and with MRI-documented synovitis, were randomized to receive infliximab or placebo. Blood was collected at baseline and genome-wide transcription in whole blood was measured using microarrays. The primary endpoint in this study was determined by measuring the transfer rate constant (Ktrans) of a gadolinium-based contrast agent from plasma to synovium using MRI. Secondary endpoints included repeated clinical assessments with DAS28(CRP), and assessments of osteitis and synovitis by the RAMRIS method. Infliximab showed greater decrease from baseline in DCE-MRI Ktrans of wrist and MCP at all visits compared with placebo (P<0.001). Statistical analysis was performed to identify genes associated with treatment-specific 14-week change in Ktrans. The 256 genes identified were used to derive a gene signature score by averaging their log expression within each patient. The resulting score correlated with improvement of Ktrans in infliximab-treated patients and with deterioration of Ktrans in placebo-treated subjects. Poor responders showed high expression of activated B-cell genes whereas good responders exhibited a gene expression pattern consistent with mobilization of neutrophils and monocytes and high levels of reticulated platelets. This gene signature was significantly associated with clinical response in two previously published whole blood gene expression studies using anti-TNF therapies. These data provide support for the hypothesis that anti-TNF inadequate responders comprise a distinct molecular subtype of RA characterized by differences in pre-treatment blood mRNA expression. They also highlight the importance of placebo controls and robust, objective endpoints in biomarker discovery. Trial Registration: ClinicalTrials.gov NCT01313520

Advanced MR techniques in multicenter clinical trials.

MRI has had a place in the clinical trials process for more than 20 years. However, for much of that time MRI has been used primarily for subjective interpretation and relatively straightforward structural measurements. More advanced MR techniques have been considered too difficult to implement consistently across multiple sites in a single trial—this despite the fact that these techniques often provide the best window into the direct effects of targeted therapeutics. As an example, numerous compounds are currently under development whose principle effect is to temporarily or permanently alter tumor microvasculature. Changes induced by these compounds typically manifest as reductions in blood flow and vascular permeability within tumors. These changes can be measured directly using dynamic contrast‐enhanced MRI. Early studies using this technique were limited to single centers, limiting both the overall size of the studies and the rate at which they were able to accrue patients. Recent efforts, however, have demonstrated that with sufficient attention to protocol design, imaging site selection and training, and analysis standardization, it is possible to obtain consistent and high quality results using even relatively complex acquisition protocols. This article will briefly review both the benefits and the drawbacks of including advanced MR techniques in clinical trial protocols. It will then review in detail the challenges presented by the need to deploy these techniques both to large research institutions and to community imaging centers which may have little or no familiarity with them at the outset of the trial. J. Magn. Reson. Imaging 2013;37:761–769.

Image-intensifier-based volume tomographic angiography imaging system: geometric distortion correction

An image intensifier-based rotational volume tomographic angiography imaging system has been constructed. The system consists of an x-ray tube and an image intensifier that are separately mounted on a gantry. This system uses an image intensifier coupled to a TV camera as a 2D detector so that a set of 2D projections can be acquired for a direct 3D reconstruction. Although an image intensifier offers good detection quantum efficiency and possibly results in a better low contrast resolution than a fluorescent screen, it introduces two types of distortion: S distortion and pincushion distortion. To obtain accurate reconstructions, these distortions must be corrected prior to 3D reconstruction. Techniques for the correction of these distortions have been developed. These techniques were tested using experimental data acquired with the image intensifier-based volume tomographic angiography imaging system. The results indicate that the distortion correction techniques work well.

A method for fully automated measurement of neurological structures in MRI

A method for fully automating the measurement of various neurological structures in MRI is presented. This technique uses an atlas-based trained maximum likelihood classifier. The classifier requires a map of prior probabilities, which is obtained by registering a large number of previously classified data sets to the atlas and calculating the resulting probability that each represented tissue type or structure will appear at each voxel in the data set. Classification is then carried out using the standard maximum likelihood discriminant function, assuming normal statistics. The results of this classification process can be used in three ways, depending on the type of structure that is being detected or measured. In the most straightforward case, measurement of a normal neural sub-structure such as the hippocampus, the results of the classifier provide a localization point for the initiation of a deformable template model, which is then optimized with respect to the original data. The detection and measurement of abnormal structures, such as white matter lesions in multiple sclerosis patients, requires a slightly different approach. Lesions are detected through the application of a spectral matched filter to areas identified by the classifier as white matter. Finally, detection of unknown abnormalities can be accomplished through anomaly detection.

Effect of Z-motion in the phase of the K-space MRI data and identification of periodic Z-motion kernels

In 2-D spin-echo magnetic resonance imaging, patient motion perpendicular to the selected slice (out-of-plane motion) is difficult to detect. A novel method for detecting sinusoidal motion without using any special pulse sequences is proposed. Once the motion is detected, the artifacts arising from different sources may be substantially reduced, leading to better and more efficient diagnosis.<<ETX>>

Modeling data acquisition and the effects of patient motion in magnetic resonance imaging

In this paper, we present a comprehensive model for MR data acquisition in the presence of patient motion to provide a better understanding as to the source of motion artifacts. This model identifies and quantifies various sources of motion artifacts in 2-D Fourier imaging. We verify our model by comparing the results predicted by the model with actual MR images of phantoms subjected to motion with controlled parameters. We expect that the knowledge of the sources of artifacts will lead to new and better methods of compensating for them.

Modeling and correction of artifacts due to z-motion in 2-D MRI

In 2D Fourier magnetic resonance imaging (MRI), patient motion, including respiratory, cardiac, and involuntary motion, plays a significant role in degradation of the image quality. The in-plane motion (x-y motion) results only in phase distortions in the raw (Fourier domain) MRI data, which can be easily corrected once the motion kernel is known. However, the effect of motion in the slice-selection direction (z-motion) has not yet been completely analyzed due to its significantly more complex nature. The authors propose a novel model to represent the effect of z-motion in the data acquisition process, and then develop two postprocessing methods for the correction of z-motion artifacts provided that the z-motion kernel is known. The model takes the form of a multi-input single-output, shift-variant system. Thus, the inversion of this system is treated by using some nonlinear methods such as the projection onto convex sets (POCS) technique and a Monte Carlo method.<<ETX>>

Reconstruction of a Three-Dimensional Volume from a Motion-Corrupted Two-Dimensional Data Set in Magnetic Resonance Imaging

Patient motion plays an important role in the degradation of image quality in magnetic resonance imaging (MRI), in that ghost-like artifacts are produced in the final image that may obscure important features. The motion can be respiratory, cardiac, can involve blood flow, and can be voluntary or involuntary. The motion in the plane of the slice to be imaged introduces phase errors in the MRI signal that can be removed if the motion is known. Motion perpendicular to the slice, however, is more complicated because different structures move into and out of the slice. In this paper we present a model to connect the 3-D source to the final 2-D MRI data set, assuming that the source has a known, arbitrary motion in the direction perpendicular to the slice. We then discuss two different techniques to reconstruct the 3-D volume swept out by the slice during the data acquisition. Reconstructions are presented to demonstrate that 3-D information can indeed be extracted from the corrupted 2-D data set.

Correction of image-phase aberrations in MRI with applications

This paper presents a quick and efficient way to detect and correct the linear and constant image-phase terms associated with MR images. We show that this correction provides us with the knowledge of the exact location of the DC term in k-space, which proves to be useful in the detection of x and y motion parameters. In addition, by displaying the real positive part of the image after the proposed correction, we can reduce background noise, motion artifacts and flow artifacts. Examples, analyses and results are provided to demonstrate the usefulness of the proposed detection and correction method.