Ultrasound modulated optical tomography: Young's modulus of the insonified region from measurement of natural frequency of vibration.

We demonstrate a method to recover the Young's modulus (E) of a tissue-mimicking phantom from measurements of ultrasound modulated optical tomography (UMOT). The object is insonified by a dual-beam, confocal ultrasound transducer (US) oscillating at frequencies f0 and f0 + Δf and the variation of modulation depth (M) in the autocorrelation of light traversed through the focal region of the US transducer against Δf is measured. From the dominant peaks observed in the above variation, the natural frequencies of the insonified region associated with the vibration along the US transducer axis are deduced. A consequence of the above resonance is that the speckle fluctuation at the resonance frequency has a higher signal-to-noise to ratio (SNR). From these natural frequencies and the associated eigenspectrum of the oscillating object, Young's modulus (E) of the material in the focal region is recovered. The working of this method is confirmed by recovering E in the case of three tissue-mimicking phantoms of different elastic modulus values.

Detection of optical and mechanical property inhomogeneities in tissue mimicking phantoms using an ultrasound assisted optical probe.

We discuss the issue of separating contributions from mechanical and optical properties of a moderately scattering tissue phantom to the modulation depth (M) of intensity autocorrelation measured in an ultrasound-assisted optical tomography system using axial and transverse illuminations. For axial illumination, M is affected by both the displacement and absorption coefficient, more prominently by displacement. But transverse illumination has very little contribution from displacement of scattering centers. Since displacement is related to the elastic property of the insonified region, we show that there is a possibility of separating the contributions from elastic and optical properties of the insonified region using axial and transverse illuminations. The main conclusions of our study using moderately scattering phantoms are: 1. axial illumination is the best for mapping storage modulus inhomogeneities, but M is also affected by optical absorption; 2. transverse illumination is the best for mapping absorption inhomogeneities; and 3. for the practically relevant case of an inclusion with larger storage modulus and absorption, both illuminations produced large contrast in M. When the scattering coefficient is high, the angle dependence of illumination is lost and the present method is shown to fail to separate these contributions based on direction of illumination.

Measurement of visco-elastic properties of breast-tissue mimicking materials using diffusing wave spectroscopy.

Diffusing wave spectroscopy (DWS), without the use of tracer particles, has been used to study the internal dynamics of polyvinyl alcohol (PVA) phantoms, which mimic the properties of normal and malignant breast tissues. From the measured intensity autocorrelations, the mean square displacement (MSD) of phantom meshing is estimated, leading to the storage and loss moduli of the medium covering frequencies up to 10 KHz. These are verified with independent measurements from a dynamic mechanical analyzer (DMA) at low frequencies. We thus prove the usefulness of DWS to extract visco-elastic properties of the phantom and its possible application in detecting malignancy in soft tissues.

Application of ultrasound-tagged photons for measurement of amplitude of vibration of tissue caused by ultrasound: theory, simulation, and experiments.

We investigate the modulation of an optical field caused by its interaction with an ultrasound beam in a tissue mimicking phantom. This modulation appears as a modulation in the intensity autocorrelation, which is measured by a photon counting correlator. The factors contributing to the modulation are: 1. amplitude of vibration of the particles of the tissue, 2. refractive index modulation, and 3. absorption coefficient in the region of the tissue intercepted by the ultrasound beam and light. We show in this work that a significant part of the contribution to this modulation comes from displacement of the tissue particles, which in turn is governed by the elastic properties of the tissue. We establish, both through simulations and experiments using an optical elastography phantom, the effects of the elasticity and absorption coefficient variations on the modulation of intensity autocorrelation. In the case where there is no absorption coefficient variation, we suggest that the depth of modulation can be calibrated to measure the displacement of tissue particles that, in turn, can be used to measure the tissue elasticity.

A double-blind, randomized study of azithromycin compared to chloroquine for the treatment of Plasmodium vivax malaria in India.

Azithromycin has demonstrated activity in a prevention of Plasmodium vivax infection, but no controlled treatment studies have been performed. We conducted a double-blinded trial in P. vivax malaria in which patients were randomized to either azithromycin 1,000 mg q.d. x 3 or chloroquine 600 mg q.d. x 2 then 300 mg on Day 3 followed by primaquine on Days 7 through 20. Eighty-five of 97 (88%) of those on azithromycin and 101 of 102 (99%) of those on chloroquine [difference 11%; 95% CI: -18, -4] were clinically cured at Day 7. The Day 28 results were similar [89% versus 99%, azithromycin versus chloroquine, respectively]. Parasitologic success was seen in 81 of 97 (84%) on azithromycin and 100 of 102 (98%) on chloroquine [difference 14%; 95% CI: -22, -6]. The median parasite clearance time was 55 hours on azithromycin and 20 hours on chloroquine (P < 0.001). Drug-related adverse events were seen in 13 of 98 (13%) on azithromycin and 24 of 102 (24%) on chloroquine (P = 0.062). Resolution of parasitemia was significantly faster with chloroquine compared with azithromycin, but azithromycin was better tolerated. These data provide support for further study of azithromycin to better define its role in the treatment of P. vivax malaria, either alone as second-line treatment or in combination with other active therapies.

Design, fabrication, and characterization of a tissue-equivalent phantom for optical elastography.

We suitably adapt the design of a tissue-equivalent phantom used for photoacoustic imaging to construct phantoms for optical elastography. The elastography phantom we consider should have optical properties such as scattering coefficient, scattering anisotropy factor, and refractive index; mechanical properties such as storage and loss modulus; and acoustic properties such as ultrasound velocity, attenuation coefficient, and acoustic impedance to match healthy and diseased tissues. The phantom is made of poly (vinyl alcohol) (PVA) and its mechanical, optical, and acoustic properties are tailored by physical cross-linking effected through subjecting a suitable mix of PVA stock and water to a number of freeze-thaw cycles and by varying the degree of hydrolysis in the PVA stock. The optical, mechanical, and acoustic properties of the samples prepared are measured by employing different techniques. The measured variations in the values of optical scattering coefficient, scattering anisotropy factor, and refractive index and storage modulus are found to be comparable to those in normal and diseased breast tissues. The acoustic properties such as sound speed, acoustic attenuation coefficient, and density are found to be close to the average values reported in the literature for normal breast tissue.

Anti-malarial activity of some xanthones isolated from the roots of Andrographis paniculata.

Four xanthones were isolated from the roots of Andrographis paniculata using a combination of column and thin-layer chromatographic methods. They were characterized as (i) 1,8-di-hydroxy-3,7-dimethoxy-xanthone, (ii) 4,8-dihydroxy-2,7-dimethoxy-xanthone, (iii) 1,2-dihydroxy-6,8-dimethoxy-xanthone and (iv) 3,7,8-trimethoxy-1-hydroxy xanthone by IR, MS and NMR spectroscopic methods. In vitro study revealed that compound 1,2-dihydroxy-6,8-dimethoxy-xanthone possessed substantial anti-plasmodial activity against Plasmodium falciparum with its IC(50) value of 4 microg ml(-1). Xanthones bearing hydroxyl group at 2 position demonstrated most potent activity while xanthones with hydroxyl group at 1,4 or 8 position possessed very low activity. In vivo anti-malarial sensitivity test of this compound on Swiss Albino mice with Plasmodium berghei infection using Peters' 4-day test gave substantial reduction (62%) in parasitaemia after treating the mice with 30 mg kg(-1) dose. In vitro cytotoxicity against mammalian cells revealed that 1,2-dihydroxy-6,8-dimethoxy-xanthone is non-cytotoxic with its IC(50) > 32 microg ml(-1).

Widespread occurrence of the Plasmodium falciparum chloroquine resistance transporter (Pfcrt) gene haplotype SVMNT in P. falciparum malaria in India.

The Plasmodium falciparum chloroquine resistance transporter (Pfcrt) K76T mutation and haplotype (amino acids 72-76) and the P. falciparum multidrug resistance 1 (Pfmdr1) mutation (N86Y) were analyzed as markers of chloroquine resistance in the DNAs of 73 blood samples from patients with P. falciparum malaria in India. Seventy of the 73 DNAs had the Pfcrt K76T mutation. Of these, 66 had the SVMNT haplotype and four had CVIET, the African/Southeast Asian haplotype. Only 20 of 69 DNAs had the Pfmdr1 N86Y mutation. It is surprising that the Pfcrt haplotype in India is predominantly SVMNT, rather than that seen in Southeast Asia. The widespread prevalence of the Pfcrt K76T mutation is a cause for concern.