Volumetric quantification of choroid and Haller's sublayer using OCT scans: An accurate and unified approach based on stratified smoothing.

BACKGROUND AND OBJECTIVE: The choroid, a dense vascular structure in the posterior segment of the eye, maintains the health of the retina by supplying oxygen and nutrients, and assumes clinical significance in screening ocular diseases including age-related macular degeneration (AMD) and central serous chorioretinopathy (CSCR). As a technological assist, algorithmic estimation of choroidal biomarkers has been suggested based on sectional (B-scan) optical coherence tomography (OCT) images. However, most such 2D estimation techniques are compute-intensive, yet enjoy limited accuracy and have only been validated on OCT image datasets of healthy eyes. Not surprisingly, fine-scale analyses, including those involving Haller's sublayer, remain relatively rare and unsophisticated. Against this backdrop, we propose an efficient algorithm to quantify desired biomarkers with improved accuracy based on volume OCT scans. Specifically, we attempted an accurate, computationally light volumetric segmentation method involving stratified smoothing to detect choroid and Haller's sublayer. METHODS: For detecting the various boundaries of the choroid and the Haller's sublayer, we propose a common volumetric method that performs suitable exponential enhancement and maintains smooth spatial continuity across 2D B-scans. Further, we achieve suitable volumetric smoothing by primarily deploying light-duty linear regression, and sparingly using compute-intensive tensor voting, and hence significantly reduce overall complexity. The proposed methodology is tested on five health and five diseased OCT volumes considering various metrics including volumetric Dice coefficient and corresponding quotient measures to facilitate comparison vis-à-vis intra-observer repeatability. RESULTS: On five healthy and five diseased OCT volumes, respectively, the proposed method for choroid segmentation recorded volumetric Dice coefficients of 93.53 % and 93.30 %, which closely approximate the respective reference observer repeatability values of 95.60 % and 95.49 %. In terms of related quotient measures, our method achieved more than 50 % improvement over a recently reported method. In detecting Haller's sublayer as well, our algorithm records statistical performance closely matching that of reference manual method. CONCLUSION: Advancing the state-of-the-art, the proposed volumetric segmentation, tested on both healthy and diseased datasets, demonstrated close match with the manual reference. Our method assumes significance in accurate screening of chorioretinal diseases including AMD, CSCR and pachychoroid. Further, it enables generating accurate training data for developing deep learning models for improved detection of choroid and Haller's sublayer.

Preparation and characterization of water-soluble pH-sensitive nanocarriers for drug delivery.

pH-sensitive drug delivery systems can be engineered to release their contents or change their physicochemical properties in response to variations in the acidity of the surroundings. The present work describes the preparation and characterization of novel polymeric micelles (PM) composed of amphiphilic pH-responsive poly(N-isopropylacrylamide) (PNIPAM) or poly(alkyl(meth)acrylate) derivatives. On one hand, acidification of the PNIPAM copolymers induces a coil-to-globule transition that can be exploited to destabilize the intracellular vesicle membranes. In this work, PNIPAM-based PM were loaded with either doxorubicin or aluminium chloride phthalocyanine and their cytotoxicity was assessed in murine tumoral models. On the other hand, poly(alkyl(meth)acrylate) copolymers can be designed to interact with either hydrophobic drugs or polyions and release their cargo upon an increase in pH.

Azo-containing urethane analogues for colonic drug delivery: synthesis, characterization and in-vitro evaluation.

A urethane-based analogue containing an azo aromatic linkage in the backbone was synthesized for use in colon-specific delivery systems by reacting toluene-2,6-diisocyanate with a mixture of an aromatic azo diol, (bis-4-hydroxyphenyl)-4,4'-diazobiphenyl, poly(ethylene glycol) (Mn = 4000; number-average molecular weight) and 1,2-propanediol (propylene glycol). The resultant compounds (UR-1 and UR-2) were characterized by IR spectroscopy, 1H NMR spectroscopy, DSC studies, X-ray diffraction studies and molecular weight determination by gel permeation chromatography. The compounds exhibited low molecular weight, lacked film-forming properties and crystallinity in the structure. An in-vitro bacterial degradation test to demonstrate the susceptibility of azo bond to bacterial enzymes was performed using media inoculated with lactobacillus culture. The results indicated degradation of films by azoreductase. In-vitro permeation of 5-aminosalicylic acid was studied in control and lactobacilli-treated films. The permeability of the lactobacilli treated films was significantly increased suggesting the potential of these compounds for application in colonic targeting.

Ty1-copia retrotransposon-like elements in chickpea genome: their identification, distribution and use for diversity analysis.

Ty1-copia retrotransposon-like elements were amplified from Cicer species using primers derived from the conserved region of the reverse transcriptase gene. Two fragments, of size approximately 280bp and approximately 650 bp, were obtained, which on sequencing showed homology for the Ty1-copia reverse transcriptase region. Interestingly, the approximately 650 bp fragment showed two reverse transcriptase regions, one from Ty1-copia and the other from Tto1 element fused together. The copy number was high in the cultivated Cicer arietinum genome compared with the wild Cicer reticulatum. Genetic diversity among the Cicer species was investigated using the conserved primers which grouped the wild species and the cultivated C. arietinum separately.

Enhancement of anti-metastatic activity of pentoxifylline by encapsulation in conventional liposomes and sterically stabilized liposomes in murine experimental B16F10 melanoma model.

Pentoxifylline has been shown to exhibit anti-metastatic activity by inhibiting homing of B16F10 melanoma cells in the murine experimental metastasis model. In this study, the effect of encapsulation of pentoxifylline in conventional and sterically stabilized liposomes on its anti-metastatic activity in the murine experimental metastasis model was investigated. After a single intravenous dose (10, 20 or 40 mg kg(-1)), pentoxifylline solution, as well as conventional pentoxifylline liposomes, significantly reduced the number of pulmonary nodules compared with the untreated control group. Conventional pentoxifylline liposomes showed significantly higher inhibition (69%) of pulmonary tumour nodule formation at a dose of 20mg kg(-1) as compared with pentoxifylline solution (49%) at the same dose. Encapsulation of pentoxifylline in sterically stabilized liposomes prepared by incorporation of monomethoxypolyethyleneglycol (5000)-cholesteryl ester further enhanced the inhibition of pulmonary nodule formation (77%) at a dose of 20 mg kg(-1) as compared with conventional pentoxifylline liposomes. Overall, the results suggest that encapsulation of pentoxifylline in conventional liposomes enhanced its anti-metastatic activity. Steric stabilization of pentoxifylline liposomes also resulted in a two-fold increase in anti-metastatic activity (at dose of 10 mg kg(-1)) as compared with conventional liposomes.

Iontophoretic transdermal delivery of salbutamol: methyl-orange ion-pair.

The influence of pulsed current duty cycle, addition of electrically neutral species and pH on iontophoretic transdermal delivery of an organic ion-pair salbutamol:methyl orange through excised rabbit abdominal skin is described. It was compared with salbutamol sulphate and salbutamol:sulphate ion-pair. It was found that there exists an optimum duty cycle range (1:3-1:4) at which iontophoretic flux of the ion-pair was at a maximum because of partition-electric current synchronization. Addition of mannitol decreases the flux of the ion-pair showing the important role of electroosmosis in ion-pair transport. The extremes of pH decrease the flux rates.

Proliposome-based transdermal delivery of levonorgestrel.

Mesophasic proliposomal system for levonorgestrel was developed and evaluated both in vitro and in vivo. The vesicles were mostly unilamellar, however, few vesicles were multilamellar which budded off spontaneously upon hydration. The release of drug from this system adhered to zero order kinetics. The effect of alcohols and volatile oils on transdermal flux was investigated. The flux was found to be the highest for alcohol, and followed by that for lemon oil. The in vivo studies indicate the requirement for a loading dose, since, a significant lag phase was observed before the therapeutic levels were reached. This system was, however, superior to the PEG-based ointment system which was employed as the control formulation. The results demonstrate the potential of proliposomal system for efficacious transdermal delivery of hydrophobic drugs.