Citations

Object The object of this study was to determine the potential of magnetic resonance elastography (MRE) to preoperatively assess the stiffness of meningiomas. Methods Thirteen patients with meningiomas underwent 3D brain MRE examination to measure stiffness in the tumor as well as in surrounding brain tissue. Blinded to the MRE results, neurosurgeons made a qualitative assessment of tumor stiffness at the time of resection. The ability of MRE to predict the surgical assessment of stiffness was tested using a Spearman rank correlation. Results One case was excluded due to a small tumor size. In the remaining 12 cases, both tumor stiffness alone (p = 0.023) and the ratio of tumor stiffness to surrounding brain tissue stiffness (p = 0.0032) significantly correlated with the surgeons' qualitative assessment of tumor stiffness. Results of the MRE examination provided a stronger correlation with the surgical assessment of stiffness compared with traditional T1- and T2-weighted imaging (p = 0.089), particularly when considering meningiomas of intermediate stiffness. Conclusions In this cohort, preoperative MRE predicted tumor consistency at the time of surgery. Tumor stiffness as measured using MRE outperformed conventional MRI because tumor appearance on T1- and T2-weighted images could only accurately predict the softest and hardest meningiomas.

Background and purposePrimary progressive apraxia of speech, a motor speech disorder of planning and programming, is a tauopathy that has overlapping histological features with progressive supranuclear palsy. We aimed to compare, for the first time, atrophy patterns, as well as white matter tract degeneration, between these two syndromes.MethodsSixteen primary progressive apraxia of speech subjects were age‐ and gender‐matched to 16 progressive supranuclear palsy subjects and 20 controls. All subjects were prospectively recruited, underwent neurological and speech evaluations and 3.0‐Tesla magnetic resonance imaging. Grey and white matter atrophy was assessed using voxel‐based morphometry and atlas‐based parcellation, and white matter tract degeneration was assessed using diffusion tensor imaging.ResultsAll progressive supranuclear palsy subjects had typical oculomotor/gait impairments, but none had speech apraxia. Both syndromes showed grey matter loss in supplementary motor area, white matter loss in posterior frontal lobes and degeneration of the body of the corpus callosum. Whilst lateral grey matter loss was focal, involving superior premotor cortex, in primary progressive apraxia of speech, loss was less focal extending into prefrontal cortex in progressive supranuclear palsy. Caudate volume loss and tract degeneration of superior cerebellar peduncles were also observed in progressive supranuclear palsy. Interestingly, area of the midbrain was reduced in both syndromes compared to controls, although this was greater in progressive supranuclear palsy.ConclusionsAlthough neuroanatomical differences were identified between these distinctive clinical syndromes, substantial overlap was also observed, including midbrain atrophy, suggesting these two syndromes may have common pathophysiological underpinnings.

AbstractSTAT3 regulates cell growth by up-regulating downstream targets, such as Myc. The frequency of phosphorylated STAT3 (pSTAT3) and Myc expression and their prognostic relevance is unknown within diffuse large B-cell lymphoma (DLBCL) germinal center B-cell (GCB) and non-GCB subtypes. pSTAT3 and Myc were studied by immunohistochemistry (IHC) on tumors from 40 DLBCL patients uniformly treated on a clinical trial of epratuzumab/rituximab-CHOP. A total of 35% of cases were pSTAT3-positive, and pSTAT3 positivity was more frequent in the non-GCB (P = .06) type but did not correlate with event-free survival (EFS). Myc expression was observed in 50% of cases and was more frequent in non-GCB type (P = .07). Myc-positive cases had inferior EFS in all patients, including the GCB and pSTAT3-positive cases, were more likely to express Myc (P = .06). Myc translocations involving the major breakpoint regions were found in 10% (3 of 29) of cases, and all 3 cases were GCB and had an inferior EFS (P = .09). pSTAT3, but not Myc expression, was correlated with elevated pretreatment serum cytokines, such as IL-10 (P = .05), G-CSF (P = .03), and TNF-α (P = .04). pSTAT3 IHC in DLBCL tumors has the potential to identify patients for STAT3 pathway–directed therapy; Myc IHC is a potential marker for inferior EFS in GCB patients.

AbstractThe mechanisms of estrogen receptor (ER)-α activity can be categorized into those involving direct (classical) or indirect (nonclassical) DNA binding. Although various mouse models have demonstrated the importance of ERα in bone, the specific gene expression patterns affected by these modes of ERα action are unknown. In this report, the gene expression patterns of ERα-deficient (ERKO) mice and nonclassical ER knock-in (NERKI) mice, which can function only by nonclassical means, were analyzed. Three-month-old mice were ovariectomized and implanted with estrogen pellets for 1 month to normalize estrogen levels. Microarray analysis of flushed cortical bone revealed 28% (210 of 763) of the genes differentially expressed in ERKO mice were altered in NERKI mice, suggesting estrogen response element-dependent regulation of these genes in bone. Pathway analysis revealed alterations in genes involved in focal adhesion and extracellular matrix interactions. However, the majority of genes regulated in ERKO mice (72%) were unique (i.e. not altered in NERKI mice), suggesting these are regulated by nonclassical mechanisms. To further explore the pathways affected in ERKO mice, we performed focused quantitative PCR arrays for genes involved in various aspects of bone physiology. Genes involved in bone formation, senescence, apoptosis, and autophagy were significantly regulated. Overall, the majority of the genes regulated by ERα in bone are via nonclassical pathways. However, because NERKI mice display an osteoporotic phenotype, it can be deduced that the minority of the estrogen response element-dependent genes/pathways play critical roles in the regulation of bone physiology. These data demonstrate the importance of classical ERα signaling in regulating bone metabolism.

Many methods in the field of elasticity imaging use shear waves to investigate the material properties of various soft tissues. The accurate and robust measurement of the shear wave speed is necessary for reliable clinical measurements. We propose using the Radon transformation on the spatiotemporal shear wave data to estimate the shear wave speed. A similar algorithm called the Radon sum transformation was proposed by Rouze, et al (IEEE Trans. Ultrasonics Ferroelectr. Freq. Control. 2010. pp. 2662-70), but this algorithm requires different input parameters that can affect the results. The use of the full Radon transform allows for the differentiation of waves that are traveling in different directions, thus this method can be used as a directional filter. We will also demonstrate the connection between estimating shear wave speeds in the Radon transform domain and estimating shear wave speeds from Fourier transform k-space. Results from shear wave measurements using shear waves induced by ultrasound radiation force will be shown. We will examine the accuracy of measurements made in calibrated elasticity phantoms, and show examples of shear wave speed estimation in arteries and kidneys. [This research was supported in part by NIH grants EB002640 and DK082408.]

Acoustoelasticity is a technique that allows quantification of the elastic nonlinearity coefficients (the so-called third-order moduli) of a material by measuring the variation of the sound speed in different directions (and/or polarizations) versus the applied uniaxial static stress. When dealing with nominally isotropic solids, the variation of the shear wave speed in two orthogonal directions with the applied stress permits the computation of two out of three independent nonlinearity coefficients. To generate the shear wave in an experimental setting, the acoustic radiation force pulse was applied to uniaxially deformed phantoms with strains of up to 30%. The results demonstrate that the compressional-shear coefficient C, which governs the variation of the (linear) shear modulus with hydrostatic pressure was found to vary substantially from one phantom to another, with the highest value observed in an agarose-based phantom. The importance of this nonlinearity parameter resides in the fact that the magnitude of the acoustic radiation force (ARF) in soft solids is proportional to C-1. For consistency, the values of C obtained from the acoustoelasticity experiment are compared to those deduced from the shear wave amplitude via its relationship to the magnitude of the ARF used to generate the shear wave.

Elasticity imaging is a medical imaging modality that measures tissue elasticity to aid in diagnosis of certain diseases. Shear wave-based methods have been developed to perform elasticity measurements in soft tissue. Hybrid beamforming applies both the conventional spherical and axicon focusing to produce a beam for generating a shear wave with increased depth-of-field so that measurements can be made with a plane-like shear wave. We present our aperture design and beam optimization performed using Field II simulations. We varied the number of elements devoted to spherical and axicon focusing as well as the opening angle used for axicon focusing. We tested hybrid beamforming in three elastic phantoms and an excised kidney. We evaluated the shear wave speed measurements accuracy in the phantoms as well as the depth-of-field for each hybrid beam. We compared our results with those from using beams generated using spherical and axicon focusing. Our results show that hybrid beamforming is capable of producing a long narrow beam that performs well when among the 128 elements of transducer, 48 elements are allocated to each axicon portion and 32 elements for spherical aperture while the angle of the axicon aperture is set less than 20.