Effect of Ultrasound Radiation Force on the Choroid

Purpose: While visualization of the retina and choroid has made great progress, functional imaging techniques have been lacking. Our aim was to utilize acoustic radiation force impulse (ARFI) response to probe functional properties of these tissues. Methods: A single element 18-MHz ultrasound transducer was focused upon the retina of the rabbit eye. The procedure was performed with the eye proptosed and with the eye seated normally in the orbit. The transducer was excited to emit ARFI over a 10-ms period with a 25% duty cycle. Phase resolved pulse/echo data were acquired before, during, and following ARFI. Results: In the proptosed eye, ARFI exposure produced tissue displacements ranging from 0 to 10 lm, and an immediate increase in choroidal echo amplitude to over 6 dB, decaying to baseline after about 1 second. In the normally seated eye, ultrasound phase shifts consistent with flow were observed in the choroid, but enhanced backscatter following ARFI rarely occurred. ARFI-induced displacements of about 10um were observed at the choroidal margins. Larger displacements occurred within the choroid and in orbital tissues. Conclusions: We hypothesize that elevated intraocular pressure occurring during proptosis induced choroidal ischemia and that acoustic radiation force produced a transient local decompression and reperfusion. With the eye normally seated, choroidal flow was observed and little alteration in backscatter resulted from exposure. Clinical application of this technique may provide new insights into diseases characterized by altered choroidal hemodynamics, including maculopathies, diabetic retinopathy, and glaucoma

High-speed, high-frequency ultrasound, \u3ci\u3ein utero\u3c/i\u3e vector-flow imaging of mouse embryos

Real-time imaging of the embryonic murine cardiovascular system is challenging due to the small size of the mouse embryo and rapid heart rate. High-frequency, linear-array ultrasound systems designed for small-animal imaging provide high-frame-rate and Doppler modes but are limited in regards to the field of view that can be imaged at fine-temporal and -spatial resolution. Here, a plane-wave imaging method was used to obtain high-speed image data from in utero mouse embryos and multi-angle, vector-flow algorithms were applied to the data to provide information on blood flow patterns in major organs. An 18-MHz linear array was used to acquire plane-wave data at absolute frame rates ≥10 kHz using a set of fixed transmission angles. After beamforming, vector-flow processing and image compounding, effective frame rates were on the order of 2 kHz. Data were acquired from the embryonic liver, heart and umbilical cord. Vector-flow results clearly revealed the complex nature of blood-flow patterns in the embryo with fine-temporal and -spatial resolution

Pulse-Encoded Ultrasound Imagine of the Vitreous With an Annular Array

The vitreous body is nearly transparent both optically and ultrasonically. Conventional 10- to 12-MHz diagnostic ultrasound can detect vitreous inhomogeneities at high gain settings, but has limited resolution and sensitivity, especially outside the fixed focal zone near the retina. To improve visualization of faint intravitreal fluid/gel interfaces, the authors fabricated a spherically curved 20-MHz five-element annular array ultrasound transducer, implemented a synthetic-focusing algorithm to extend the depth-of-field, and used a pulse-encoding strategy to increase sensitivity. The authors evaluated a human subject with a recent posterior vitreous detachment and compared the annular array with conventional 10-MHz ultrasound and spectral-domain optical coherence tomography. With synthetic focusing and chirp pulse-encoding, the array allowed visualization of the formed and fluid components of the vitreous with improved sensitivity and resolution compared with the conventional B-scan. Although optical coherence tomography allowed assessment of the posterior vitreoretinal interface, the ultrasound array allowed evaluation of the entire vitreous body

Age-related macular degeneration: choroidal ischaemia?

Aim: Our aim is to use ultrasound to non-invasively detect differences in choroidal microarchitecture possibly related to ischaemia among normal eyes and those with wet and dry age-related macular degeneration (AMD). Design Prospective case series of subjects with dry AMD, wet AMD and age-matched controls. Methods: Digitized 20 MHz B-scan radiofrequency ultrasound data of the region of the macula were segmented to extract the signal from the retina and choroid. This signal was processed by a wavelet transform, and statistical modelling was applied to the wavelet coefficients to examine differences among dry, wet and non-AMD eyes. Receiver operating characteristic (ROC) analysis was used to evaluate a multivariate classifier. Results: In the 69 eyes of 52 patients, 18 did not have AMD, 23 had dry AMD and 28 had wet AMD. Multivariate models showed statistically significant differences between groups. Multiclass ROC analysis of the best model showed an excellent volume-under-curve of 0.892±0.17. The classifier is consistent with ischaemia in dry AMD. Conclusions: Wavelet augmented ultrasound is sensitive to the organisational elements of choroidal microarchitecture relating to scatter and fluid tissue boundaries such as seen in ischaemia and inflammation, allowing statistically significant differentiation of dry, wet and non-AMD eyes. This study further supports the association of ischaemia with dry AMD and provides a rationale for treating dry AMD with pharmacological agents to increase choroidal perfusion

Measurement of choroidal perfusion and thickness following systemic sildenafil (Viagra)

Purpose: To demonstrate anatomic and physiologic changes in the human choroid following systemic sildenafil citrate (Viagra) using enhanced depth imaging spectral domain–optical coherence tomography (EDI-OCT) and swept-scan high-frequency digital ultrasound. Methods: Seven healthy male subjects (mean age 32.7 years) were evaluated at baseline and 2 hr after ingesting 50 mg of sildenafil. Swept-scan high-frequency digital ultrasound and EDI-OCT were utilized to measure choroidal perfusion and thickness, respectively. Results were read by masked observers. The Wilcoxon signed-rank test and t-test were used to analyse differences in choroidal flow and thickness at baseline and 2 hr after ingestion of sildenafil. Results: Two hours following sildenafil, increased choroidal perfusion was observed in 11 of 12 eyes measured by swept-scan high-frequency digital ultrasound. The mean increase was 3.46 (±2.00) times baseline with a range of 0.47–7.80 times baseline (p = 0.004). Increased choroidal thickness was observed in 12 of 12 eyes measured with EDI-OCT. The average choroidal thickness increased by 11.6% temporal to the fovea, 9.3% nasal to the fovea and 10.7% underneath the fovea (p < 0.001 for all values). Conclusions: Choroidal perfusion and thickness both increase in response to systemic sildenafil. These changes could secondarily affect retinal function, explain previously reported clinical symptoms and potentially be a useful adjunct for treatment of ocular diseases that would benefit from increased choroidal blood flow

Non-Planar Pad-Printed Think-Film Focused High-Frequency Ultrasonic Transducers for Imaging and Therapeutic Applications

Pad-printed thick-film transducers have been shown to be an interesting alternative to lapped bulk piezoceramics, because the film is deposited with the required thickness, size, and geometry, thus avoiding any subsequent machining to achieve geometrical focusing. Their electromechanical properties are close to those of bulk ceramics with similar composition despite having a higher porosity. In this paper, padprinted high-frequency transducers based on a low-loss piezoceramic composition are designed and fabricated. High-porosity ceramic cylinders with a spherical top surface are used as the backing substrate. The transducers are characterized in view of imaging applications and their imaging capabilities are evaluated with phantoms containing spherical inclusions and in different biological tissues. In addition, the transducers are evaluated for their capability to produce high-acoustic intensities at frequencies around 20 MHz. High-intensity measurements, obtained with a calibrated hydrophone, show that transducer performance is promising for applications that would require the same device to be used for imaging and for therapy. Nevertheless, the transducer design can be improved, and simulation studies are performed to find a better compromise between low-power and high-power performance. The size, geometry, and constitutive materials of optimized configurations are proposed and their feasibility is discussed

Phospholipid Scramblase 1 Potentiates The Antiviral Activity of Interferon

Phospholipid scramblase 1 (PLSCR1) is an interferon (IFN)- and growth factor-inducible, calcium-binding protein that either inserts into the plasma membrane or binds DNA in the nucleus depending on its state of palmyitoylation. In certain hematopoietic cells, PLSCR1 is required for normal maturation and terminal differentiation from progenitor cells as regulated by select growth factors, where it promotes recruitment and activation of Src kinases. PLSCR1 is a substrate of Src (and Abl) kinases, and transcription of the PLSCR1 gene is regulated by the same growth factor receptor pathways in which PLSCR1 potentiates afferent signaling. The marked transcriptional upregulation of PLSCR1 by IFNs led us to explore whether PLSCR1 plays an analogous role in cellular responses to IFN, with specific focus on antiviral activities. Accordingly, human cells in which PLSCR1 expression was decreased with short interfering RNA were rendered relatively insensitive to the antiviral activity of IFNs, resulting in higher titers of vesicular stomatitis virus (VSV) and encephalomyocarditis virus. Similarly, VSV replicated to higher titers in mouse PLSCR1−/− embryonic fibroblasts than in identical cells transduced to express PLSCR1. PLSCR1 inhibited accumulation of primary VSV transcripts, similar to the effects of IFN against VSV. The antiviral effect of PLSCR1 correlated with increased expression of a subset of IFN-stimulated genes (ISGs), including ISG15, ISG54, p56, and guanylate binding proteins. Our results suggest that PLSCR1, which is itself an ISG-encoded protein, provides a mechanism for amplifying and enhancing the IFN response through increased expression of a select subset of potent antiviral genes

Object Relations in the Museum: A Psychosocial Perspective

This article theorises museum engagement from a psychosocial perspective. With the aid of selected concepts from object relations theory, it explains how the museum visitor can establish a personal relation to museum objects, making use of them as an ‘aesthetic third’ to symbolise experience. Since such objects are at the same time cultural resources, interacting with them helps the individual to feel part of a shared culture. The article elaborates an example drawn from a research project that aimed to make museum collections available to people with physical and mental health problems. It draws on the work of the British psychoanalysts Donald Winnicott and Wilfred Bion to explain the salience of the concepts of object use, potential space, containment and reverie within a museum context. It also refers to the work of the contemporary psychoanalyst Christopher Bollas on how objects can become evocative for individuals both by virtue of their intrinsic qualities and by the way they are used to express personal idiom