In vivo imaging of blood flow in the mouse Achilles tendon using high-frequency ultrasound

Objective

Achilles tendinitis is a common clinical problem with many treatment modalities, including physical therapy, exercise and therapeutic ultrasound. However, evaluating the effects of current therapeutic modalities and studying the therapeutic mechanism(s) in vivo remains problematic. In this study, we attempted to observe the morphology and microcirculation changes in mouse Achilles tendons between pre- and post-treatment using high-frequency (25 MHz) ultrasound imaging. A secondary aim was to assess the potential of high-frequency ultrasound in exploring therapeutic mechanisms in small-animal models in vivo.

Methods

A collagenase-induced mouse model of Achilles tendinitis was adopted, and 5 min treatment of continuous-mode low-frequency (45 kHz) ultrasound with 47 mW/cm² maximum intensity and 16.3 cm² effective beam radiating area was applied. The B-mode images showed no focal hypoechoic regions in normal Achilles tendons either pre- or post-treatment. The Doppler power energy and blood flow rate were measured within the peritendinous space of the Achilles tendon.

Conclusion

An increase in the microcirculation was observed soon after the low-frequency ultrasound treatment, which was due to immediate induction of vascular dilatation. The results suggest that applying high-frequency Doppler imaging to small-animal models will be an invaluable aid in explorations of the therapeutic mechanism(s). Our future work includes using imaging to assess microcirculation changes in tendinitis between before and after treatment over a long time period, which is expected to yield useful physiological data for future human studies.     

Effect of dual-frequency clutter suppression in harmonic Doppler detection

Background

High-frequency Doppler imaging is highly potential for detection of blood flow in microcirculation. In a swept-scan system, however, the spectral broadening of tissue clutter limits the detectability of low-velocity flow signal. Conventionally, the scanning speed of transducer has to be reduced to alleviate the clutter interference but at the cost of imaging frame rate. For example, the blood velocity of 0.5 mm/s becomes detectable only with a scanning speed lower than 1 mm/s. In this study, an alternative method is examined by suppressing the clutter magnitude to reduce the interference to flow signal without sacrificing scanning speed.

Methods

The method of third harmonic (3f₀) transmit phasing can suppress the tissue harmonic clutter by transmitting at the fundamental and the additional 3f₀ frequencies to achieve mutual cancellation between the frequency-sum and the frequency-difference components of the second harmonic signal. With 3f₀ transmit phasing, the cut-off frequency of wall filtering can be reduced to preserve low-velocity flow without compromising the frame rate.

Results

Our results indicate that the 3f₀ transmit phasing effectively reduces the harmonic clutter magnitude and thus improves the flow signal-to-clutter ratio. Compared to the conventional counterpart, the clutter-suppressed color flow and power Doppler images show fewer clutter artifacts and is capable of detecting more low-velocity flow of microbubbles. The resultant color-pixel-density also improves with clutter suppression.

Conclusion

For the swept-scan high-frequency (>20 MHz) system, 3f₀ transmit phasing is capable of providing effective clutter suppression. With the same achievable scanning speed, the resultant Doppler image has higher sensitivity for low-velocity flow and is less susceptible to clutter artifacts.     

Power estimation predicts specific function action of acupuncture: an fMRI study

Purpose

The purpose was to investigate the distinct pattern of brain response induced by electroacupuncture stimulation (EAS) related to sustained acupuncture effects.

Material and Methods

Twenty-eight healthy volunteers were enrolled and randomized into two groups. According to grouping, volunteers were separately treated by EAS at GB37 (Guangming) or KI8 (Jiaoxin) during functional magnetic resonance imaging. Differences in acupuncture effects between the groups were tested by the power estimation approach.

Results

Spatial patterns of the whole brain power were different in the periaqueductal gray, occipital cortex (OC) and temporal cortex when induced by EAS at GB37 and KI8. Moreover, the differences in the sustained effects between these two acupoints were also identified and associated with the OC, dorsolateral prefrontal cortex, medial prefrontal cortex, anterior cingulate cortex and insula.

Conclusion

Electroacupuncture stimulation induced different power fluctuation patterns related to GB37 and KI8. We suggest that these findings might be attributed to the specific function action of these acupoints.     

Gas challenge-blood oxygen level-dependent (GC-BOLD) MRI in the rat Novikoff hepatoma model

Purpose

The purpose of the study was to investigate the relationship between gas challenge-blood oxygen level-dependent (GC-BOLD) response angiogenesis and tumor size in rat Novikoff hepatoma model.

Materials and Methods

Twenty adult male Sprague-Dawley rats (weighting 301-325 g) were used for our Animal Care and Use Committee-approved experiments. N1-S1 Novikoff hepatomas were grown in 14 rats with sizes ranging from 0.42 to 2.81 cm. All experiments were performed at 3.0 T using a custom-built rodent receiver coil. A multiple gradient-echo sequence was used for R2^? measurements, first during room air (78% N₂/20% O₂) breathing and then after 10 min of carbogen (95% O₂/5% CO₂) breathing. After image acquisition, rats were euthanized, and the tumors were harvested for histological evaluation.

Results

The R2^? change between air and carbogen breathing for small hepatomas was positive; R2^? changes changed to negative values for larger hepatomas. We found a significant positive correlation between tumor R2^? change and tumor microvessel density (MVD) (r=0.798, P=.001) and a significant inverse correlation between tumor R2^? change and tumor size (r=−0.840, P<.0001).

Conclusions

GC-BOLD magnetic resonance imaging measurements are well correlated to MVD levels and tumor size in the N1-S1 Novikoff hepatoma model; GC-BOLD measurements may serve as noninvasive biomarkers for evaluating angiogenesis and disease progression and/or therapy response.     

Three-dimensional susceptibility-weighted imaging at 3 T using various image analysis methods in the estimation of grading intracranial gliomas

Object

Although three-dimensional (3D), high-spatial resolution susceptibility-weighted imaging (SWI) appears to be valuable in the evaluation of central nervous system gliomas, several evaluation methods are proposed in the literature. The purpose of this study was to evaluate the use of 3D SWI for grading intracranial gliomas with various analysis methods.

Materials and Methods

Twenty-three patients suspected of having gliomas participated in this study. SWI was performed in addition to conventional MR sequences. In 15 cases, post-gadolinium enhanced SWI was also obtained. Imaging evaluation criteria were conventional grade, hypointensity ratio in the tumor-dominant structure of hypointensity on SWI (hemorrhage or vascular structure) and presence of abnormal enhancement surrounding the tumor.

Results

Mean grading scores of conventional grade showed no statistically significant difference among WHO grades. Mean grading scores of hypointensity ratios in the tumor were higher for WHO Grades 3 and 4 than for lower grade tumors (P=.05, Mann–Whitney U test). Hemorrhagic foci were more frequently seen in the higher grade tumor. Post-contrast susceptibility-weighted images of five of 11 WHO Grade 3 and 4 cases showed bright enhancement surrounding the tumor, suggesting a breakdown of the blood–brain barrier.

Conclusions

SWI at 3 T may be a useful method to analyze the structural characteristics of gliomas and to evaluate pathology in vivo. Assessment of hypointensity ratios in the glioma was the most preferable method in grading glioma. However, more studies, specifically concerning a suitable method for image analysis, are needed to establish SWI at 3 T as a useful tool in clinical routine.     

Absorbing phase transition in energy exchange models

We study energy exchange models with dissipation (λ) and noise (of amplitude σ) and show that in presence of a threshold these models undergo an absorbing phase transition when either dissipation or noise strength or both are varied. Using Monte Carlo simulations we find that the behaviour along the critical line, which separates the active phase from the absorbing one, belongs to directed percolation (DP) universality class. We claim that the conserved version with λ = 1 and σ = 0 also shows a DP transition; the apparent non-DP behaviour observed earlier is an artifact of undershooting in the decay of activity density starting from a random initial condition.     

Relationship between central and peripheral corneal astigmatism in elderly patients

Purpose

We investigated the relationship between central and peripheral corneal astigmatism in elderly patients.

Methods

Seventy-six eyes of 76 elderly subjects (mean age?=?72.6?±?3.0 years) were included in the study. Corneal shape was evaluated using the Pentacam HR (Oculus, Wetzlark, Germany), which is comprised of a rotating Scheimpflug camera and a short-wavelength slit light. The power distribution map was selected and corneal astigmatism was calculated using front K-Readings in zones centered on the pupil. Analyzed zones were 2.0–6.0 mm in diameter.

Results

Corneal astigmatism decreased as diameter increased, similar to what was observed in eyes with with-the-rule astigmatism and against-the-rule astigmatism (ANOVA, p?<?0.01). This effect was more pronounced in eyes with a large central corneal astigmatism (Spearman’s rank-correlation coefficient test, r?=?0.51, p?<?0.01). There was no change as to axis of corneal astigmatism (ANOVA, p?=?0.98).

Conclusion

These results suggest that the relationship between central and peripheral corneal astigmatism should be taken into consideration to optimize vision when astigmatic correction is needed.

     

Determining uterine blood flow in pregnancy with magnetic resonance imaging

Objective

The purpose of this study is to determine the feasibility of measuring total uterine blood flow in pregnancy using magnetic resonance imaging (MRI) technique.

Methods

Uterine blood flow was determined in pregnant women in whom MRI was being carried out to assess a fetal anomaly. A two-dimensional time-of-flight magnetic resonance (MR) angiogram sequence was performed. Scout images and a peripherally gated phase contrast MR sequence were planned to study simultaneous blood flow in the uterine and ovarian arteries.

Results

The MR pelvic angiogram sequence was completed in 13 women. The uterine arteries were visualized and their cross-sectional area determined. The complexity of the pelvic blood supply prevented the calculation of blood flow velocity and, thus, total uterine blood flow.

Conclusion

The measurement of total uterine blood flow during pregnancy was not possible using our MR technique. The ovarian vessels were not consistently visualized. Doppler ultrasonography remains the best modality by which to estimate total uterine blood flow in pregnancy.     

Shape of the Doppler absorption profile in measurements by magnetic scanning

In measurements of the absorption of single-frequency laser radiation at the 3s ₂?2p ₄ transition in neon performed by magnetic scanning, a noticeable asymmetry of the Doppler profile was revealed. This asymmetry was observed when the laser frequency was detuned from the line center. The sign of the asymmetric contribution to the shape of the Doppler profile is related to the sign of the detuning.     

Effect of visual target blurring on accommodation under distance viewing

Purpose

To examine the effect of visual target blurring on accommodation.

Methods

We evaluated the objective refraction values when the visual target (asterisk; 8°) was changed from the state without Gaussian blur (15 s) to the state with Gaussian blur adapted [0(without blur)?→?10, 0?→?50, 0?→?100: 15 s each].

Results

In Gaussian blur 10, when blurring of the target occurred, refraction value did not change significantly. In Gaussian blur 50 and 100, when blurring of the target occurred, the refraction value became significantly myopic.

Conclusion

Blurring of the distant visual target results in intervention of accommodation.

     

Studies of pathology and VEGF expression in rabbit cerebrospinal fluid metastasis: application of dynamic contrast-enhanced MRI

Objective

The objective was to analyze the correlation of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) with vascular endothelial growth factor (VEGF) protein expression and to assess the potential application of DCE-MRI to the rabbit cerebrospinal fluid (CSF) metastasis model.

Methods

Thirty New Zealand rabbits were divided into experimental and control groups. In the experimental group, VX2 tumor cells were injected into the subarachnoid space at the plane of cisterna magna in 24 rabbits. In the control group, physiological saline was injected into the subarachnoid space at the plane of cisterna magna in six rabbits. DCE-MRI was performed at multiple time points, and several pharmacokinetic parameters, including K^trans, K_ep and V_e, were calculated. Also, VEGF levels in plasma and CSF were evaluated by enzyme-linked immunosorbent assay prior to DCE-MRI examination. After DCE-MRI examination, the rabbits were sacrificed, and the corresponding tumor specimens were harvested. Hematoxylin–eosin staining and VEGF immunohistochemical staining were carried out, and VEGF expression in the specimens was evaluated by the immunohistochemical scoring system.

Results

Vascular endothelial growth factor positive staining was localized in the cytoplasm and cell membranes of tumor cells, as well as in a subset of epithelial cells. Both VEGF immunohistochemical scores and VEGF expression in CSF and plasma exhibited positive correlations with K^trans and K_ep values as demonstrated by rank correlation statistical analysis.

Conclusions

Vascular endothelial growth factor expression in plasma and CSF in the CSF metastasis model was higher than in normal tissues. Therefore, DCE-MRI reliably indicated VEGF expression in the rabbit CSF metastasis model.     

Quantum dynamics in strong fluctuating fields

A large number of multifaceted quantum transport processes in molecular systems and physical nanosystems, such as e.g. nonadiabatic electron transfer in proteins, can be treated in terms of quantum relaxation processes which couple to one or several fluctuating environments. A thermal equilibrium environment can conveniently be modelled by a thermal bath of harmonic oscillators. An archetype situation provides a two-state dissipative quantum dynamics, commonly known under the label of a spin-boson dynamics. An interesting and nontrivial physical situation emerges, however, when the quantum dynamics evolves far away from thermal equilibrium. This occurs, for example, when a charge transferring medium possesses nonequilibrium degrees of freedom, or when a strong time-dependent control field is applied externally. Accordingly, certain parameters of underlying quantum subsystem acquire stochastic character. This may occur, for example, for the tunnelling coupling between the donor and acceptor states of the transferring electron, or for the corresponding energy difference between electronic states which assume via the coupling to the fluctuating environment an explicit stochastic or deterministic time-dependence. Here, we review the general theoretical framework which is based on the method of projector operators, yielding the quantum master equations for systems that are exposed to strong external fields. This allows one to investigate on a common basis, the influence of nonequilibrium fluctuations and periodic electrical fields on those already mentioned dynamics and related quantum transport processes. Most importantly, such strong fluctuating fields induce a whole variety of nonlinear and nonequilibrium phenomena. A characteristic feature of such dynamics is the absence of thermal (quantum) detailed balance.

Quantum dynamics in strong fluctuating fields

All authors

Igor Goychuk &; Peter Hänggi

https://doi.org/10.1080/00018730500429701

Published online:

19 February 2007

Table     

Enhancement of blood-tumor barrier permeability by Sar-[D-Phe8]des-Arg9BK,a metabolically resistant bradykinin B1 agonist,in a rat C6 glioma model

Background

While it is well known that bradykinin B2 agonists increase plasma protein extravasation (PPE) in brain tumors, the bradykinin B1 agonists tested thus far are unable to produce this effect. Here we examine the effect of the selective B1 agonist bradykinin (BK) Sar-[D-Phe8]des-Arg9BK (SAR), a compound resistant to enzymatic degradation with prolonged activity on PPE in the blood circulation in the C6 rat glioma model.

Results

SAR administration significantly enhanced PPE in C6 rat brain glioma compared to saline or BK (p < 0.01). Pre-administration of the bradykinin B1 antagonist [Leu8]-des-Arg (100 nmol/Kg) blocked the SAR-induced PPE in the tumor area.

Conclusions

Our data suggest that the B1 receptor modulates PPE in the blood tumor barrier of C6 glioma. A possible role for the use of SAR in the chemotherapy of gliomas deserves further study.

     

Electron interaction effects on the thermoelectric power of a quantum dot at T &gt; T<Subscript>K</Subscript>

In the absence of phonon thermal conductivity, we theoretically investigate the output power of an interacting quantum dot thermoelectric setup that is moderately coupled to two electronic reservoirs in the regime T ? T _K . In the noninteracting case, the output power is maximized when the energy level of the dot is around a critical value ε _c . We find that when the energy level of the dot is lower than ε _c , Coulomb interaction can enhance the maximum thermoelectric power that can be achieved by tuning the bias and a wider operating region is also observed. However, when the energy level of the dot is higher than ε _c , Coulomb interaction suppresses the maximum power. Finally when the dot level is around ε _c , Coulomb interaction has minimal effects on the maximum power.     

Positive contrast visualization for cellular magnetic resonance imaging using susceptibility-weighted echo-time encoding

Objective

The objective of this study was to investigate a method to generate positive contrast, selective to superparamagnetic iron oxide (SPIO) labeled cells, using the susceptibility-weighted echo-time encoding technique (SWEET).

Materials and Methods

SPIO-labeled human epidermal carcinoma (KB) cells were placed in a gel phantom. Positive contrast from the labeled cells was created by subtraction between conventional spin-echo images and echo-time shifted susceptibility-weighted images. SPIO-labeled cells were injected into the left dorsal flank and hind limb of nude mice, and unlabeled cells were placed on the right side as controls. Tumor growth was monitored using the proposed method, and a histological analysis was used to confirm the presence of the labeled cells.

Results

Based on in vitro testing, we could detect 5000 labeled cells at minimum and the number of pixels with positive contrast increased proportionally to the number of labeled cells. Animal experiments also revealed the presence of tumor growth from SPIO-loaded cells.

Conclusions

We demonstrated that the proposed method, based on the simple principle of echo-time shift, could be readily implemented in a clinical scanner to visualize the magnetic susceptibility effects of SPIO-loaded cells through a positive-contrast mechanism.     

Efficient saturation of an ion in free space

We report on the demonstration of a light-matter interface coupling light to a single \(^{174}\hbox {Yb}^+\) ion in free space. The interface is realized through a parabolic mirror partially surrounding the ion. It transforms a Laguerre–Gaussian beam into a linear dipole wave converging at the mirror’s focus. By measuring the non-linear response of the atomic transition, we deduce the power required for reaching an upper-level population of \(1/4\) to be \(692\pm 20\,\hbox {pW}\) at half linewidth detuning from the atomic resonance. Performing this measurement while scanning the ion through the focus provides a map of the focal intensity distribution. From the measured power, we infer a coupling efficiency of \(7.2\pm 0.2\,\%\) on the linear dipole transition when illuminating from half solid angle, being among the best coupling efficiencies reported for a single atom in free space.     

Phase contrast and time-of-flight magnetic resonance angiography of the intracerebral arteries at 1.5, 3 and 7 T

Purpose

Time-of-flight (ToF) and phase contrast (PC) magnetic resonance angiographies (MRAs) are noninvasive applications to depict the cerebral arteries. Both approaches can image the cerebral vasculature without the administration of intravenous contrast. Therefore, it is used in routine clinical evaluation of cerebrovascular diseases, e.g., aneurysm and arteriovenous malformations. However, subtle microvascular disease usually cannot be resolved with standard, clinical-field-strength MRA. The purpose of this study was to compare the ability of ToF and PC MRA to visualize the cerebral arteries at increasing field strengths.

Materials and Methods

The Institutional Review Board-approved study included eight healthy volunteers (age: 36±10 years; three female, five male). All subjects provided written informed consent. ToF and PC MRAs were obtained at 1.5, 3 and 7 T. Signal intensities of the large, primary vessels of the Circle of Willis were measured, and signal-to-noise ratios were calculated. Visualization of smaller first- and second-order branch arteries of the Circle of Willis was also evaluated.

Results

The results show that both ToF and PC MRAs allow the depiction of the large primary vessels of the Circle of Willis at all field strengths. Ultrahigh field (7 T) provides only small increases in the signal-to-noise ratio in these primary vessels due to the smaller voxel size acquired. However, ultrahigh-field MRA provides better visualization of the first- and second-order branch arteries with both ToF and PC approaches. Therefore, ultrahigh-field MRA may become an important tool in future neuroradiology research and clinical care.     

Comprehensive Bayesian analysis of rare (semi)leptonic and radiative \varvec{B} decays

The available data on \(|\Delta B| = |\Delta S| = 1\) decays are in good agreement with the Standard Model when permitting subleading power corrections of about \(15\,\%\) at large hadronic recoil. Constraining new-physics effects in \(\mathcal {C}_{7}^{\mathrm {}}\) , \(\mathcal {C}_{9}^{\mathrm {}}\) , \(\mathcal {C}_{10}^{\mathrm {}}\) , the data still demand the same size of power corrections as in the Standard Model. In the presence of chirality-flipped operators, all but one of the power corrections reduce substantially. The Bayes factors are in favor of the Standard Model. Using new lattice inputs for \(B\rightarrow K^*\) form factors and under our minimal prior assumption for the power corrections, the favor shifts toward models with chirality-flipped operators. We use the data to further constrain the hadronic form factors in \(B\rightarrow K\) and \(B\rightarrow K^*\) transitions.     

Augmentation of the Porcine Vocal Fold Using Autologous Composite Cervical Fascia and Fat Graft. Comparison Between the Transmuscular and Submuscular Approaches

Objectives

To assess the integration of an autologous composite fascia and fat graft implanted into the lamina propria of a porcine vocal fold using two different approaches.

Study Design

An experimental prospective study on the porcine larynx was conducted at a tertiary research institution.

Methods

An external cervical approach was used to expose the thyroid cartilage of 24 healthy minipigs under general anesthesia. The composite fascia/fat graft was implanted through two distinct approaches, transmuscular and submuscular. Animals were sacrificed at 7, 30, 90, and 180 days for macroscopic and histological study of the larynx. Graft integration and local inflammatory response were studied.

Results

The survival rate of the experimental model was 100% and all animals had local inflammatory response to the surgical procedure. Only 41.7% of the grafts placed inside the thyroarytenoid (TA) muscle fibers were identified postmortem, whereas 83.3% of the submuscular grafts remained intact.

Conclusions

Graft incorporation was better and there was less inflammation when the architecture of the TA muscle fibers was preserved. Graft extrusion was observed in the most of the cases where it was placed inside the muscle.     

On the matching of top-down knowledge with sensory input in the perception of ambiguous speech

Background

How does the brain repair obliterated speech and cope with acoustically ambivalent situations? A widely discussed possibility is to use top-down information for solving the ambiguity problem. In the case of speech, this may lead to a match of bottom-up sensory input with lexical expectations resulting in resonant states which are reflected in the induced gamma-band activity (GBA).

Methods

In the present EEG study, we compared the subject's pre-attentive GBA responses to obliterated speech segments presented after a series of correct words. The words were a minimal pair in German and differed with respect to the degree of specificity of segmental phonological information.

Results

The induced GBA was larger when the expected lexical information was phonologically fully specified compared to the underspecified condition. Thus, the degree of specificity of phonological information in the mental lexicon correlates with the intensity of the matching process of bottom-up sensory input with lexical information.

Conclusions

These results together with those of a behavioural control experiment support the notion of multi-level mechanisms involved in the repair of deficient speech. The delineated alignment of pre-existing knowledge with sensory input is in accordance with recent ideas about the role of internal forward models in speech perception.