Viscoelastic power law parameters of in vivo human brain estimated by MR elastography.

The noninvasive imaging technique of magnetic resonance elastography (MRE) was used to estimate the power law behavior of the viscoelastic properties of the human brain in vivo. The mechanical properties for four volunteers are investigated using shear waves induced over a frequency range of 10-50Hz to produce a displacement field measured by magnetic resonance motion-encoding gradients. The average storage modulus (µR) reconstructed with non-linear inversion (NLI) increased from approximately 0.95 to 2.58kPa over the 10-50Hz span; the average loss modulus (µI) also increased from 0.29 to 1.25kPa over the range. These increases were modeled by independent power law (PL) relations for µR and µI returning whole brain, group mean exponent values of 0.88 and 1.07 respectively. Investigation of these exponents also showed distinctly different behavior in the region of the cerebral falx compared to other brain structures.

Suitability of poroelastic and viscoelastic mechanical models for high and low frequency MR elastography.

PURPOSE: Descriptions of the structure of brain tissue as a porous cellular matrix support application of a poroelastic (PE) mechanical model which includes both solid and fluid phases. However, the majority of brain magnetic resonance elastography (MRE) studies use a single phase viscoelastic (VE) model to describe brain tissue behavior, in part due to availability of relatively simple direct inversion strategies for mechanical property estimation. A notable exception is low frequency intrinsic actuation MRE, where PE mechanical properties are imaged with a nonlinear inversion algorithm. METHODS: This paper investigates the effect of model choice at each end of the spectrum of in vivo human brain actuation frequencies. Repeat MRE examinations of the brains of healthy volunteers were used to compare image quality and repeatability for each inversion model for both 50 Hz externally produced motion and ≈1 Hz intrinsic motions. Additionally, realistic simulated MRE data were generated with both VE and PE finite element solvers to investigate the effect of inappropriate model choice for ideal VE and PE materials. RESULTS: In vivo, MRE data revealed that VE inversions appear more representative of anatomical structure and quantitatively repeatable for 50 Hz induced motions, whereas PE inversion produces better results at 1 Hz. Reasonable VE approximations of PE materials can be derived by equating the equivalent wave velocities for the two models, provided that the timescale of fluid equilibration is not similar to the period of actuation. An approximation of the equilibration time for human brain reveals that this condition is violated at 1 Hz but not at 50 Hz. Additionally, simulation experiments when using the "wrong" model for the inversion demonstrated reasonable shear modulus reconstructions at 50 Hz, whereas cross-model inversions at 1 Hz were poor quality. Attenuation parameters were sensitive to changes in the forward model at both frequencies, however, no spatial information was recovered because the mechanisms of VE and PE attenuation are different. CONCLUSIONS: VE inversions are simpler with fewer unknown properties and may be sufficient to capture the mechanical behavior of PE brain tissue at higher actuation frequencies. However, accurate modeling of the fluid phase is required to produce useful mechanical property images at the lower frequencies of intrinsic brain motions.

Temperature of the magnetic nanoparticle microenvironment: estimation from relaxation times.

Accurate temperature measurements are essential to safe and effective thermal therapies for cancer and other diseases. However, conventional thermometry is challenging so using the heating agents themselves as probes allows for ideal local measurements. Here, we present a new noninvasive method for measuring the temperature of the microenvironment surrounding magnetic nanoparticles from the Brownian relaxation time of nanoparticles. Experimentally, the relaxation time can be determined from the nanoparticle magnetization induced by an alternating magnetic field at various applied frequencies. A previously described method for nanoparticle temperature estimation used a low frequency Langevin function description of magnetic dipoles and varied the excitation field amplitude to estimate the energy state distribution and the corresponding temperature. We show that the new method is more accurate than the previous method at higher applied field frequencies that push the system farther from equilibrium.

Multiresolution MR elastography using nonlinear inversion.

PURPOSE: Nonlinear inversion (NLI) in MR elastography requires discretization of the displacement field for a finite element (FE) solution of the "forward problem", and discretization of the unknown mechanical property field for the iterative solution of the "inverse problem". The resolution requirements for these two discretizations are different: the forward problem requires sufficient resolution of the displacement FE mesh to ensure convergence, whereas lowering the mechanical property resolution in the inverse problem stabilizes the mechanical property estimates in the presence of measurement noise. Previous NLI implementations use the same FE mesh to support the displacement and property fields, requiring a trade-off between the competing resolution requirements. METHODS: This work implements and evaluates multiresolution FE meshes for NLI elastography, allowing independent discretizations of the displacements and each mechanical property parameter to be estimated. The displacement resolution can then be selected to ensure mesh convergence, and the resolution of the property meshes can be independently manipulated to control the stability of the inversion. RESULTS: Phantom experiments indicate that eight nodes per wavelength (NPW) are sufficient for accurate mechanical property recovery, whereas mechanical property estimation from 50 Hz in vivo brain data stabilizes once the displacement resolution reaches 1.7 mm (approximately 19 NPW). Viscoelastic mechanical property estimates of in vivo brain tissue show that subsampling the loss modulus while holding the storage modulus resolution constant does not substantially alter the storage modulus images. Controlling the ratio of the number of measurements to unknown mechanical properties by subsampling the mechanical property distributions (relative to the data resolution) improves the repeatability of the property estimates, at a cost of modestly decreased spatial resolution. CONCLUSIONS: Multiresolution NLI elastography provides a more flexible framework for mechanical property estimation compared to previous single mesh implementations.

Subzone based magnetic resonance elastography using a Rayleigh damped material model.

PURPOSE: Recently, the attenuating behavior of soft tissue has been addressed in magnetic resonance elastography by the inclusion of a damping mechanism in the methods used to reconstruct the resulting mechanical property image. To date, this mechanism has been based on a viscoelastic model for material behavior. Rayleigh, or proportional, damping provides a more generalized model for elastic energy attenuation that uses two parameters to characterize contributions proportional to elastic and inertial forces. In the case of time-harmonic vibration, these two parameters lead to both the elastic modulus and the density being complex valued (as opposed to the case of pure viscoelasticity, where only the elastic modulus is complex valued). METHODS: This article presents a description of Rayleigh damping in the time-harmonic case, discussing the differences between this model and the viscoelastic damping models. In addition, the results from a subzone based Rayleigh damped elastography study of gelatin and tofu phantoms are discussed, along with preliminary results from in vivo breast data. RESULTS: Both the phantom and the tissue studies presented here indicate a change in the Rayleigh damping structure, described as Rayleigh composition, between different material types, with tofu and healthy tissue showing lower Rayleigh composition values than gelatin or cancerous tissue. CONCLUSIONS: It is possible that Rayleigh damping elastography and the concomitant Rayleigh composition images provide a mechanism for differentiating tissue structure in addition to measuring elastic stiffness and attenuation. Such information could be valuable in the use of Rayleigh damped magnetic resonance elastography as a diagnostic imaging tool.

An octahedral shear strain-based measure of SNR for 3D MR elastography.

A signal-to-noise ratio (SNR) measure based on the octahedral shear strain (the maximum shear strain in any plane for a 3D state of strain) is presented for magnetic resonance elastography (MRE), where motion-based SNR measures are commonly used. The shear strain, γ, is directly related to the shear modulus, µ, through the definition of shear stress, τ = µÎ³. Therefore, noise in the strain is the important factor in determining the quality of motion data, rather than the noise in the motion. Motion and strain SNR measures were found to be correlated for MRE of gelatin phantoms and the human breast. Analysis of the stiffness distributions of phantoms reconstructed from the measured motion data revealed a threshold for both strain and motion SNR where MRE stiffness estimates match independent mechanical testing. MRE of the feline brain showed significantly less correlation between the two SNR measures. The strain SNR measure had a threshold above which the reconstructed stiffness values were consistent between cases, whereas the motion SNR measure did not provide a useful threshold, primarily due to rigid body motion effects.

Effects of frequency- and direction-dependent elastic materials on linearly elastic MRE image reconstructions.

The mechanical model commonly used in magnetic resonance elastography (MRE) is linear elasticity. However, soft tissue may exhibit frequency- and direction-dependent (FDD) shear moduli in response to an induced excitation causing a purely linear elastic model to provide an inaccurate image reconstruction of its mechanical properties. The goal of this study was to characterize the effects of reconstructing FDD data using a linear elastic inversion (LEI) algorithm. Linear and FDD phantoms were manufactured and LEI images were obtained from time-harmonic MRE acquisitions with variations in frequency and driving signal amplitude. LEI responses to artificially imposed uniform phase shifts in the displacement data from both purely linear elastic and FDD phantoms were also evaluated. Of the variety of FDD phantoms considered, LEI appeared to tolerate viscoelastic data-model mismatch better than deviations caused by poroelastic and anisotropic mechanical properties in terms of visual image contrast. However, the estimated shear modulus values were substantially incorrect relative to independent mechanical measurements even in the successful viscoelastic cases and the variations in mean values with changes in experimental conditions associated with uniform phase shifts, driving signal frequency and amplitude were unpredictable. Overall, use of LEI to reconstruct data acquired in phantoms with FDD material properties provided biased results under the best conditions and significant artifacts in the worst cases. These findings suggest that the success with which LEI is applied to MRE data in tissue will depend on the underlying mechanical characteristics of the tissues and/or organs systems of clinical interest.

Time-harmonic magnetic resonance elastography of the normal feline brain.

Imaging of the mechanical properties of in vivo brain tissue could eventually lead to non-invasive diagnosis of hydrocephalus, Alzheimer's disease and other pathologies known to alter the intracranial environment. The purpose of this work is to (1) use time-harmonic magnetic resonance elastography (MRE) to estimate the mechanical property distribution of cerebral tissue in the normal feline brain and (2) compare the recovered properties of grey and white matter. Various in vivo and ex vivo brain tissue property measurement strategies have led to the highly variable results that have been reported in the literature. MR elastography is an imaging technique that can estimate mechanical properties of tissue non-invasively and in vivo. Data was acquired in 14 felines and elastic parameters were estimated using a globo-regional nonlinear image reconstruction algorithm. Results fell within the range of values reported in the literature and showed a mean shear modulus across the subject group of 7-8 kPa with all but one animal falling within 5-15 kPa. White matter was statistically stiffer (p<0.01) than grey matter by about 1 kPa on a per subject basis. To the best of our knowledge, the results reported represent the most extensive set of estimates in the in vivo brain which have been based on MRE acquisition of the three-dimensional displacement field coupled to volumetric shear modulus image reconstruction achieved through nonlinear parameter estimation. However, the inter-subject variation in mean shear modulus indicates the need for further study, including the possibility of applying more advanced models to estimate the relevant tissue mechanical properties from the data.

Magnetic resonance elastography using 3D gradient echo measurements of steady-state motion.

Magnetic resonance elastography (MRE) is an important new method used to measure the elasticity or stiffness of tissues in vivo. While there are many possible applications of MRE, breast cancer detection and classification is currently the most common. Several groups have been developing methods based on MR and ultrasound (US). MR or US is used to estimate the displacements produced by either quasi-static compression or dynamic vibration of the tissue. An important advantage of MRE is the possibility of measuring displacements accurately in all three directions. The central problem in most versions of MRE is recovering elasticity information from the measured displacements. In previous work, we have presented simulation results in two and three dimensions that were promising. In this article, accurate reconstructions of elasticity images from 3D, steady-state experimental data are reported. These results are significant because they demonstrate that the process is truly three-dimensional even for relatively simple geometries and phantoms. Further, they show that the integration of displacement data acquisition and elastic property reconstruction has been successfully achieved in the experimental setting. This process involves acquiring volumetric MR phase images with prescribed phase offsets between the induced mechanical motion and the motion-encoding gradients, converting this information into a corresponding 3D displacement field and estimating the concomitant 3D elastic property distribution through model-based image reconstruction. Fully 3D displacement fields and resulting elasticity images are presented for single and multiple inclusion gel phantoms.

Three-dimensional subzone-based reconstruction algorithm for MR elastography.

Accurate characterization of harmonic tissue motion for realistic tissue geometries and property distributions requires knowledge of the full three-dimensional displacement field because of the asymmetric nature of both the boundaries of the tissue domain and the location of internal mechanical heterogeneities. The implications of this for magnetic resonance elastography (MRE) are twofold. First, for MRE methods which require the measurement of a harmonic displacement field within the tissue region of interest, the presence of 3D motion effects reduces or eliminates the possibility that simpler, lower-dimensional motion field images will capture the true dynamics of the entire stimulated tissue. Second, MRE techniques that exploit model-based elastic property reconstruction methods will not be able to accurately match the observed displacements unless they are capable of accounting for 3D motion effects. These two factors are of key importance for MRE techniques based on linear elasticity models to reconstruct mechanical tissue property distributions in biological samples. This article demonstrates that 3D motion effects are present even in regular, symmetric phantom geometries and presents the development of a 3D reconstruction algorithm capable of discerning elastic property distributions in the presence of such effects. The algorithm allows for the accurate determination of tissue mechanical properties at resolutions equal to that of the MR displacement image in complex, asymmetric biological tissue geometries. Simulation studies in a realistic 3D breast geometry indicate that the process can accurately detect 1-cm diameter hard inclusions with 2.5x elasticity contrast to the surrounding tissue.

The outcome of pregnancy in Kell alloimmunisation.

OBJECTIVE: To assess management and outcome of pregnancies with anti-Kell in the West Midlands in the UK over 13 years. DESIGN: A retrospective review of casenotes. SETTING: A regional referral clinic for red cell alloimmune disease and fetal medicine unit at a university hospital. POPULATION: Sixty-five pregnancies were identified in 52 Kell-sensitised women with Kell positive partners from the records of the Birmingham Blood Transfusion Centre. METHODS: Information from the casenotes was entered on a database and comparisons were made using the SPSS for Windows statistics package. MAIN OUTCOME MEASURES: Mode of sensitisation, degree of fetal or neonatal anaemia, need for transfusion, gestation at delivery, birthweight and pregnancy outcome. RESULTS: Alloimmunisation was transfusion-related in 29 pregnancies and pregnancy-induced in 33. The cause could not be identified in three cases. There were 22 proven Kell positive fetuses, of which 18 were affected, in which alloimmunisation was pregnancy-related in 12 cases and transfusion-related in five. Antibody titres and amniotic fluid OD450 were not helpful in management. Severe or very severe disease occurred in 50% of the affected pregnancies (9/18). There was no difference in pregnancy outcome between transfusion or pregnancy induced sensitisation. CONCLUSIONS: Anti-Kell alloimmunisation is an uncommon cause of serious anaemia in a significant proportion of affected pregnancies. There appears to be no difference between that caused by pregnancy or transfusion. Estimation of fetal haemoglobin concentration by cordocentesis is recommended, as antibody titres and amniocentesis are not helpful.

Elasticity reconstruction from experimental MR displacement data: initial experience with an overlapping subzone finite element inversion process.

The determination of the elastic property distribution in heterogeneous gel samples with a finite element based reconstruction scheme is considered. The algorithm operates on small overlapping subzones of the total field to allow for a high degree of spatial discretization while maintaining computational tractability. By including a Maxwellian-type viscoelastic property in the model physics and optimizing the spatial distribution of this property in the same manner as elasticity, a Young's modulus image is obtained which reasonably reflects the true distribution within the gel. However, the image lacks the clarity and accuracy expected based on simulation experience. Preliminary investigations suggest that transient effects in the data are the cause of a significant mismatch between the inversion model, which assumes steady-state conditions, and the actual displacements as measured by a phase contrast MR technique.

Brain activation during working memory 1 month after mild traumatic brain injury: a functional MRI study.

OBJECTIVE: To assess patterns of regional brain activation in response to varying working memory loads shortly after mild traumatic brain injury (MTBI). BACKGROUND: Many individuals complain of memory difficulty shortly after MTBI. Memory performance in these individuals can be normal despite these complaints. METHODS: Brain activation patterns in response to a working memory task (auditory n-back) were assessed with functional MRI in 12 MTBI patients within 1 month of their injury and in 11 healthy control subjects. RESULTS: Brain activation patterns differed between MTBI patients and control subjects in response to increasing working memory processing loads. Maximum intensity projections of statistical parametric maps in control subjects showed bifrontal and biparietal activation in response to a low processing load, with little additional increase in activation associated with the high load task. MTBI patients showed some activation during the low processing load task but significantly increased activation during the high load condition, particularly in the right parietal and right dorsolateral frontal regions. Task performance did not differ significantly between groups. CONCLUSION: MTBI patients differed from control subjects in activation pattern of working memory circuitry in response to different processing loads, despite similar task performance. This suggests that injury-related changes in ability to activate or to modulate working memory processing resources may underlie some of the memory complaints after MTBI.

An overlapping subzone technique for MR-based elastic property reconstruction.

A finite element-based nonlinear inversion scheme for magnetic resonance (MR) elastography is detailed. The algorithm operates on small overlapping subzones of the total region of interest, processed in a hierarchical order as determined by progressive error minimization. This zoned approach allows for a high degree of spatial discretization, taking advantage of the data-rich environment afforded by the MR. The inversion technique is tested in simulation under high-noise conditions (15% random noise applied to the displacement data) with both complicated user-defined stiffness distributions and realistic tissue geometries obtained by thresholding MR image slices. In both cases the process has proved successful and has been capable of discerning small inclusions near 4 mm in diameter. Magn Reson Med 42:779-786, 1999.

Neuroanatomic substrates of semantic memory impairment in Alzheimer's disease: patterns of functional MRI activation.

Impairment in semantic processing occurs early in Alzheimer's disease (AD) and differential impact on subtypes of semantic relations have been reported, yet there is little data on the neuroanatomic basis of these deficits. Patients with mild AD and healthy controls underwent 3 functional MRI auditory stimulation tasks requiring semantic or phonological decisions (match-mismatch) about word pairs (category-exemplar, category-function, pseudoword). Patients showed a significant performance deficit only on the exemplar task. On voxel-based fMRI activation analyses, controls showed a clear activation focus in the left superior temporal gyrus for the phonological task; patients showed additional foci in the left dorsolateral prefrontal and bilateral cingulate areas. On the semantic tasks, predominant activation foci were seen in the inferior and middle frontal gyrus (left greater than right) in both groups but patients showed additional activation suggesting compensatory recruitment of locally expanded foci and remote regions, for example, right frontal activation during the exemplar task. Covariance analyses indicated that exemplar task performance was strongly related to signal increase in bilateral medial prefrontal cortex. The authors conclude that fMRI can reveal similarities and differences in functional neuroanatomical processing of semantic and phonological information in mild AD compared to healthy elderly, and can help to bridge cognitive and neural investigations of the integrity of semantic networks in AD.

Prenatal diagnosis of tuberous sclerosis with intracerebral signs at 14 weeks' gestation.

We report the ultrasound detection of cranial abnormalities at 14 weeks' gestation in a fetus subsequently confirmed as having tuberous sclerosis using DNA linkage analysis within the affected family. The presence of asymmetrical ventricular enlargement persisted antenatally. Magnetic resonance imaging at 26 weeks indicated the possibility of poor gyral formation consistent with a neuronal migration disorder. Cardiac rhabdomyomata were not visualized on ultrasound scan until 30 weeks' gestation. Postnatal cranial ultrasound confirmed the significant neuropathology which was manifested by severe developmental delay and intractable fits in the child. The potential benefits of earlier diagnosis of tuberous sclerosis by cranial imaging are discussed, although in this patient the routine booking scan resulted in a path of prenatal diagnosis being undertaken which had originally been declined. A mechanism is proposed to explain the variable expression of tuberous sclerosis within this family based on altered TSC2 activity affecting neuronal migration.

Pruritus in pregnancy and obstetric cholestasis.

Pruritus is often considered a common but minor symptom of pregnancy. However, pruritus caused by obstetric cholestasis is increasingly being recognized as a cause of so-called 'unexplained' stillbirths. This article reviews recent literature and outlines possible management strategies with the aim of reducing maternal morbidity and improving perinatal outcome.

Imaging equipment and techniques for optimal intraoperative imaging during endovascular interventions.

Because endovascular procedures represent an ever-increasing portion of many vascular surgery practices, many surgeons are faced with difficult choices. Endovascular procedures often require open surgery, and open surgical techniques increasingly require fluoroscopic imaging. Without good intraoperative imaging, endovascular procedures are difficult and endovascular aneurysm repair is impossible. How does one balance the need for optimal imaging without sacrificing the ability to safely perform open surgical procedures, especially in the early stages of a developing endovascular program? Strategies include the use of a portable c-arm and carbon fiber table in the operating room (OR), adding a fixed imaging platform to an OR, gaining access to an angiography suite that does not meet OR requirements, and modifying it into an interventional suite that does meet operating room standards. Once the optimal equipment and facilities have been chosen, other choices must be considered. Should a radiology technician be hired? Should an interventional radiologist be available to assist or be incorporated as a routine member of the team? How will typical operating room procedures and technique need to be altered in an effort to optimize intraoperative imaging for endovascular procedures? This article gives an overview of the many issues that arise as a vascular surgery practice evolves to incorporate complex endovascular procedures.

Intrahepatic cholestasis of pregnancy: prevalence and ethnic distribution.

We undertook a retrospective analysis of the prevalence of obstetric cholestasis in the population of the South Birmingham area in the various ethnic subgroups. A diagnosis of intrahepatic cholestasis of pregnancy was made on the basis of symptoms of generalised pruritus along with biochemical evidence of the condition, after ruling out other liver diseases. We found an overall prevalence of 0.7%, with an occurrence in the white population of 0.62%, compared to that in the Asians of Pakistani origin of 1.46%. In the Asians of Indian origin it was found to be 1.24%. The prevalence of obstetric cholestasis was significantly higher in the Pakistani and Indian subgroups compared to the whites.