Amanda K. W. Buck

Multi‐parametric MRI characterization of healthy human thigh muscles at 3.0 T – relaxation, magnetization transfer, fat/water, and diffusion tensor imaging

Muscle diseases commonly have clinical presentations of inflammation, fat infiltration, fibrosis, and atrophy. However, the results of existing laboratory tests and clinical presentations are not well correlated. Advanced quantitative MRI techniques may allow the assessment of myo‐pathological changes in a sensitive and objective manner. To progress towards this goal, an array of quantitative MRI protocols was implemented for human thigh muscles; their reproducibility was assessed; and the statistical relationships among parameters were determined. These quantitative methods included fat/water imaging, multiple spin‐echo T2 imaging (with and without fat signal suppression, FS), selective inversion recovery for T1 and quantitative magnetization transfer (qMT) imaging (with and without FS), and diffusion tensor imaging. Data were acquired at 3.0 T from nine healthy subjects. To assess the repeatability of each method, the subjects were re‐imaged an average of 35 days later. Pre‐testing lifestyle restrictions were applied to standardize physiological conditions across scans. Strong between‐day intra‐class correlations were observed in all quantitative indices except for the macromolecular‐to‐free water pool size ratio (PSR) with FS, a metric derived from qMT data. Two‐way analysis of variance revealed no significant between‐day differences in the mean values for any parameter estimate. The repeatability was further assessed with Bland–Altman plots, and low repeatability coefficients were obtained for all parameters. Among‐muscle differences in the quantitative MRI indices and inter‐class correlations among the parameters were identified. There were inverse relationships between fractional anisotropy (FA) and the second eigenvalue, the third eigenvalue, and the standard deviation of the first eigenvector. The FA was positively related to the PSR, while the other diffusion indices were inversely related to the PSR. These findings support the use of these T1, T2, fat/water, and DTI protocols for characterizing skeletal muscle using MRI. Moreover, the data support the existence of a common biophysical mechanism, water content, as a source of variation in these parameters. Copyright

Skeletal muscle diffusion tensor-MRI fiber tracking : Rationale, data acquisition and analysis methods, applications and future directions

The mechanical functions of muscles involve the generation of force and the actuation of movement by shortening or lengthening under load. These functions are influenced, in part, by the internal arrangement of muscle fibers with respect to the muscles mechanical line of action. This property is known as muscle architecture. In this review, we describe the use of diffusion tensor (DT)‐MRI muscle fiber tracking for the study of muscle architecture. In the first section, the importance of skeletal muscle architecture to function is discussed. In addition, traditional and complementary methods for the assessment of muscle architecture (brightness‐mode ultrasound imaging and cadaver analysis) are presented. Next, DT‐MRI is introduced and the structural basis for the reduced and anisotropic diffusion of water in muscle is discussed. The third section discusses issues related to the acquisition of skeletal muscle DT‐MRI data and presents recommendations for optimal strategies. The fourth section discusses methods for the pre‐processing of DT‐MRI data, the available approaches for the calculation of the diffusion tensor and the seeding and propagating of fiber tracts, and the analysis of the tracking results to measure structural properties pertinent to muscle biomechanics. Lastly, examples are presented of how DT‐MRI fiber tracking has been used to provide new insights into how muscles function, and important future research directions are highlighted. Copyright

First Implantation of Silicon Nanopore Membrane Hemofilters.

An implantable hemofilter for the treatment of kidney failure depends critically on the transport characteristics of the membrane and the biocompatibility of the membrane, cartridge, and blood conduits. A novel membrane with slit-shaped pores optimizes the trade-off between permeability and selectivity, enabling implanted therapy. Sustained (3–8) day function of an implanted parallel-plate hemofilter with minimal anticoagulation was achieved by considering biocompatibility at the subnanometer scale of chemical interactions and the millimeter scale of blood fluid dynamics. A total of 400 nm-thick polysilicon flat sheet membranes with 5–8 nm × 2 micron slit-shaped pores were surface-modified with polyethylene glycol. Hemofilter cartridge geometries were refined based on computational fluid dynamics models of blood flow. In an uncontrolled pilot study, silicon filters were implanted in six class A dogs. Cartridges were connected to the cardiovascular system by anastamoses to the aorta and inferior vena cava and filtrate was drained to collection pouches positioned in the peritoneum. Pain medicine and acetylsalicylic acid were administered twice daily until the hemofilters were harvested on postoperative days 3 (n = 2), 4 (n = 2), 5 (n = 1), and 8 (n = 1). No hemofilters were thrombosed. Animals treated for 5 and 8 days had microscopic fractures in the silicon nanopore membranes and 20–50 ml of transudative (albumin sieving coefficient &thgr;alb ~ 0.5 – 0.7) fluid in the collection pouches at the time of explant. Shorter experimental durations (3–4 days) resulted in filtration volumes similar to predictions based on mean arterial pressures and membrane hydraulic permeability and (&thgr;alb ~ 0.2 – 0.3), similar to preimplantation measurements. In conclusion, a detailed mechanistic and materials science attention to blood–material interactions allows implanted hemofilters to resist thrombosis. Additional testing is needed to determine optimal membrane characteristics and identify limiting factors in long-term implantation.

Matching of postcontraction perfusion to oxygen consumption across submaximal contraction intensities in exercising humans

Studying the magnitude and kinetics of blood flow, oxygen extraction, and oxygen consumption at exercise onset and during the recovery from exercise can lead to insights into both the normal control of metabolism and blood flow and the disturbances to these processes in metabolic and cardiovascular diseases. The purpose of this study was to examine the on- and off-kinetics for oxygen delivery, extraction, and consumption as functions of submaximal contraction intensity. Eight healthy subjects performed four 1-min isometric dorsiflexion contractions, with two at 20% MVC and two at 40% MVC. During one contraction at each intensity, relative perfusion changes were measured by using arterial spin labeling, and the deoxyhemoglobin percentage (%HHb) was estimated using the spin- and gradient-echo sequence and a previously published empirical calibration. For the whole group, the mean perfusion did not increase during contraction. The %HHb increased from ∼28 to 38% during contractions of each intensity, with kinetics well described by an exponential function and mean response times (MRTs) of 22.7 and 21.6 s for 20 and 40% MVC, respectively. Following contraction, perfusion increased ∼2.5-fold. The %HHb, oxygen consumption, and perfusion returned to precontraction levels with MRTs of 27.5, 46.4, and 50.0 s, respectively (20% MVC), and 29.2, 75.3, and 86.0 s, respectively (40% MVC). These data demonstrate in human subjects the varied recovery rates of perfusion and oxygen consumption, along with the similar rates of %HHb recovery, across these exercise intensities.

Development of a high resolution MRI intracranial atherosclerosis imaging phantom

Background and purpose Currently, there is neither a standard protocol for vessel wall MR imaging of intracranial atherosclerotic disease (ICAD) nor a gold standard phantom to compare MR sequences. In this study, a plaque phantom is developed and characterized that provides a platform for establishing a uniform imaging approach for ICAD. Materials and methods A patient specific injection mold was 3D printed to construct a geometrically accurate ICAD phantom. Polyvinyl alcohol hydrogel was infused into the core shell mold to form the stenotic artery. The ICAD phantom incorporated materials mimicking a stenotic vessel and plaque components, including fibrous cap and lipid core. Two phantoms were scanned using high resolution cone beam CT and compared with four different 3 T MRI systems across eight different sites over a period of 18 months. Inter-phantom variability was assessed by lumen dimensions and contrast to noise ratio (CNR). Results Quantitative evaluation of the minimum lumen radius in the stenosis showed that the radius was on average 0.80 mm (95% CI 0.77 to 0.82 mm) in model 1 and 0.77 mm (95% CI 0.74 to 0.81 mm) in model 2. The highest CNRs were observed for comparisons between lipid and vessel wall. To evaluate manufacturing reproducibility, the CNR variability between the two models had an average absolute difference of 4.31 (95% CI 3.82 to 5.78). Variation in CNR between the images from the same scanner separated by 7 months was 2.5–6.2, showing reproducible phantom durability. Conclusions A plaque phantom composed of a stenotic vessel wall and plaque components was successfully constructed for multicenter high resolution MRI standardization.

Quantitative Magnetic Resonance Imaging of Skeletal Muscle Disease.

Quantitative magnetic resonance imaging (qMRI) describes the development and use of MRI to quantify physical, chemical, and/or biological properties of living systems. Neuromuscular diseases often exhibit a temporally varying, spatially heterogeneous, and multi-faceted pathology. The goal of this protocol is to characterize this pathology using qMRI methods. The MRI acquisition protocol begins with localizer images (used to locate the position of the body and tissue of interest within the MRI system), quality control measurements of relevant magnetic field distributions, and structural imaging for general anatomical characterization. The qMRI portion of the protocol includes measurements of the longitudinal and transverse relaxation time constants (T1 and T2, respectively). Also acquired are diffusion-tensor MRI data, in which water diffusivity is measured and used to infer pathological processes such as edema. Quantitative magnetization transfer imaging is used to characterize the relative tissue content of macromolecular and free water protons. Lastly, fat-water MRI methods are used to characterize fibro-adipose tissue replacement of muscle. In addition to describing the data acquisition and analysis procedures, this paper also discusses the potential problems associated with these methods, the analysis and interpretation of the data, MRI safety, and strategies for artifact reduction and protocol optimization.

Anisotropic Smoothing Improves DT-MRI-Based Muscle Fiber Tractography

Purpose To assess the effect of anisotropic smoothing on fiber tracking measures, including pennation angle, fiber tract length, and fiber tract number in the medial gastrocnemius (MG) muscle in healthy subjects using diffusion-weighted magnetic resonance imaging (DW-MRI). Materials and Methods 3T DW-MRI data were used for muscle fiber tractography in the MG of healthy subjects. Anisotropic smoothing was applied at three levels (5%, 10%, 15%), and pennation angle, tract length, fiber tract number, fractional anisotropy, and principal eigenvector orientation were quantified for each smoothing level. Results Fiber tract length increased with pre-fiber tracking smoothing, and local heterogeneities in fiber direction were reduced. However, pennation angle was not affected by smoothing. Conclusion Modest anisotropic smoothing (10%) improved fiber-tracking results, while preserving structural features.

Original article submission: Platelet stress accumulation analysis to predict thrombogenicity of an artificial kidney

An implantable artificial kidney using a hemofilter constructed from an array of silicon membranes to provide ultrafiltration requires a suitable blood flow path to ensure stable operation in vivo. Two types of flow paths distributing blood to the array of membranes were evaluated: parallel and serpentine. Computational fluid dynamics (CFD) simulations were used to guide the development of the blood flow paths. Pressure data from animal tests were used to obtain pulsatile flow conditions imposed in the transient simulations. A key consideration for stable operation in vivo is limiting platelet stress accumulation to avoid platelet activation and thrombus formation. Platelet stress exposure was evaluated by CFD particle tracking methods through the devices to provide distributions of platelet stress accumulation. The distributions of stress accumulation over the duration of a platelet lifetime for each device revealed that stress accumulation for the serpentine flow path exceeded levels expected to cause platelet activation while the accumulated stress for the parallel flow path was below expected activation levels.