Correction: Blood brain barrier permeable gold nanocluster for targeted brain imaging and therapy: an in vitro and in vivo study.

Correction for 'Blood brain barrier permeable gold nanocluster for targeted brain imaging and therapy: an in vitro and in vivo study' by L. V. Nair et al., J. Mater. Chem. B, 2017, 5, 8314-8321, https://doi.org/10.1039/C7TB02247F.

Blood brain barrier permeable gold nanocluster for targeted brain imaging and therapy: an in vitro and in vivo study.

Blood brain barrier (BBB) is a dynamic interface, comprising polarized endothelial cells, that separates the brain from the circulatory system. The highly protective nature of this tight junction impairs diagnosis and treatment of brain disorders. In this study, we designed a sub atomic size, near infrared emitting, dual function glutathione gold cluster with high fluorescence yield to facilitate permeability of BBB, for imaging applications and drug delivery. The gold cluster was then modified with Levodopa (l-dopa), to utilize the large amino acid transporter 1 (LAT1) pathways to enhance brain entry. Uptake and permeability of the nanoprobes were demonstrated using an established model of BBB, comprising brain endothelial cells (bEnd.3). The uptake and the clearance of l-dopa modified cluster was faster than the glutathione cluster. l-Dopa modified cluster supports the slow and sustained delivery of a model drug, pilocarpine, to the brain. Results of in vivo imaging and drug release in normal mice hold promise for considering the probe for early diagnosis of brain diseases, when the barrier is not disrupted, and for subsequent drug treatment.

Synthesis of cubic ZnS microspheres exhibiting broad visible emission for bioimaging applications.

Biocompatible ZnS microspheres with an average diameter of 3.85 µm were grown by solvo-hydrothermal (S-H) method using water-acetonitrile-ethylenediamine (EDA) solution combination. ZnS microspheres were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), high-resolution transmission electron microscopy (HRTEM), Fourier transform (FT)-Raman spectroscopy and Fourier transform infrared spectroscopy (FTIR) techniques. The broad photoluminescence (PL) emissions from 380-580 nm that were seen from the ZnS microspheres attributed to the increase in carrier concentration, as understood from the observed intense Raman band at 257 cm(-1). Cytotoxicity and haemocompatibility investigations of these ZnS microspheres revealed its biocompatibility. ZnS microspheres, along with biological cell lines, were giving visible light emission and could be used for bioimaging applications.

Fractal analysis: fractal dimension and lacunarity from MR images for differentiating the grades of glioma.

Glioma, the heterogeneous tumors originating from glial cells, generally exhibit varied grades and are difficult to differentiate using conventional MR imaging techniques. When this differentiation is crucial in the disease prognosis and treatment, even the advanced MR imaging techniques fail to provide a higher discriminative power for the differentiation of malignant tumor from benign ones. A powerful image processing technique applied to the imaging techniques is expected to provide a better differentiation. The present study focuses on the fractal analysis of fluid attenuation inversion recovery MR images, for the differentiation of glioma. For this, we have considered the most important parameters of fractal analysis, fractal dimension and lacunarity. While fractal analysis assesses the malignancy and complexity of a fractal object, lacunarity gives an indication on the empty space and the degree of inhomogeneity in the fractal objects. Box counting method with the preprocessing steps namely binarization, dilation and outlining was used to obtain the fractal dimension and lacunarity in glioma. Statistical analysis such as one-way analysis of variance and receiver operating characteristic (ROC) curve analysis helped to compare the mean and to find discriminative sensitivity of the results. It was found that the lacunarity of low and high grade gliomas vary significantly. ROC curve analysis between low and high grade glioma for fractal dimension and lacunarity yielded 70.3% sensitivity and 66.7% specificity and 70.3% sensitivity and 88.9% specificity, respectively. The study observes that fractal dimension and lacunarity increases with an increase in the grade of glioma and lacunarity is helpful in identifying most malignant grades.

Rapid and simple method of photobleaching to reduce background autofluorescence in lung tissue sections.

Autofluorescence exhibited by tissues often interferes with immunofluorescence. Using imaging and spectral analysis, we observed remarkable reduction of autofluorescence of formalin fixed paraffin embedded tissues irradiated with light prior to incubation with immunofluorescent dyes. The technique of photobleaching offers significant improvement in the quality and specificity of immunofluorescence. This has the potential for better techniques for disease diagnosis.

Relative percentage signal intensity recovery of perfusion metrics­an efficient tool for differentiating grades of glioma.

OBJECTIVE: Glioma classification and characterization may be facilitated by a multiparametric approach of perfusion metrics, which could not be achieved by conventional MRI alone. Our aim is to explore the potential of relative percentage signal intensity recovery (rPSR) values, in addition to relative cerebral blood volume (rCBV) and relative cerebral blood flow (rCBF) of first-pass T2* dynamic susceptibility contrast (DSC) perfusion MRI, in differentiating high- and low-grade glioma. METHODS: This prospective study included 39 patients with low-grade and 25 patients with high-grade glioma. rPSR, rCBV and rCBF were calculated from the first-pass T2* DSC perfusion MRI. rPSR was calculated using standard software and validated with dedicated perfusion metrics analysis software. The statistical analysis was performed using analysis of variance and receiver operating characteristic (ROC) curves. RESULTS: Variation in rPSR, rCBV and rCBF values between low- and high-grade gliomas were statistically significant (p < 0.005). The ROC curve analysis for each of them yielded 96% sensitivity and 71.8% specificity; 88% sensitivity and 69.2% specificity; and 72% sensitivity and 66.7% specificity. The area under the curve (AUC) from the ROC curve analysis yielded 0.893, 0.852 and 0.702 for rPSR, rCBV and rCBF, respectively. The rPSR calculation with the validation software yielded 92.3% sensitivity and 72% specificity with an AUC of 0.864. CONCLUSION: rPSR inversely correlates while rCBV and rCBF values directly correlate with the tumour grade. Furthermore, the overall diagnostic performance of rPSR is better than rCBV and rCBF values. ADVANCES IN KNOWLEDGE: rPSR of T2* DSC perfusion is an indicator of blood-brain barrier status and lesion leakiness, which has not been explored yet compared with the usual haemodynamic parameters, rCBV and rCBF.

Autofluorescence spectroscopy augmented by multivariate analysis as a potential noninvasive tool for early diagnosis of oral cavity disorders.

OBJECTIVE: Oral leukoplakia is one of the common potentially malignant lesions encountered worldwide. We report the results of an in vivo clinical evaluation of autofluorescence (AF) spectroscopy for differential diagnosis of oral leukoplakia. Multivariate analysis of spectral data has been incorporated to improve the efficacy of the technique. The results of this noninvasive study are expected to provide potential for extending the technique to other disorders. MATERIALS AND METHODS: A total of 18 patients and 30 normal volunteers participated in this study. AF spectra were acquired from affected sites of patients and from right and left buccal mucosa of normal volunteers. Diagnostic performance was analyzed using spectral intensity ratio (SIR), and principal component analysis followed by linear discriminant analysis (PCA-LDA). RESULTS: AF spectra of leukoplakic patients showed characteristic emissions from flavin adenine dinucleotide (FAD) and porphyrin at 500 and 630 nm, respectively. But the emission from porphyrin is not very prominent in the case of healthy volunteers. Also, significant decrease in spectral intensity is observed for leukoplakia compared with normal volunteers in the unprocessed spectra. Method of SIR yielded 96% sensitivity and 100% specificity and an overall 100% for PCA-LDA respectively for efficient differentiation of the lesions. CONCLUSIONS: The result of this preliminary study shows that PCA-LDA or SIR applied to AF spectroscopy is a useful tool for the differential diagnosis of oral cavity disorders. This has been demonstrated in leukoplakia in a clinical setting, and it is expected that the technique can be extended to other oral cavity disorders as well.

Autofluorescence spectroscopy for the in vivo evaluation of oral submucous fibrosis.

OBJECTIVES: The goal of this study was to analyze the autofluorescence spectrum of oral submucous fibrosis (OSF); in order to find out whether the technique is effective for the in vivo detection of OSF and for the early detection of malignant changes in OSF. BACKGROUND: The feasibility of autofluorescence spectroscopy to detect subtle alterations in tissue architecture and biochemical composition induced by dysplasia and inflammation has been studied in the field of oral oncology. Because early detection and proper treatment of common oral precancerous conditions such as OSF and any malignant transformation are important, autofluorescence spectroscopy was applied to detect OSF in this study. METHODS: In vivo autofluorescence emission spectra were collected at excitation wavelength of 320 nm from buccal mucosa from patients grouped as normal, OSF, or OSF with malignancy. The emission spectra were recorded and analyzed for variations from normal spectra with respect to spectral profile and intensity. RESULTS: The emission spectrum of OSF had a significantly higher emission peak around 380 nm and 460 nm when compared with the normal mucosal spectrum. The carcinoma spectrum also had two peaks around 380 and 460 nm regions with reduced intensity. The spectrum of carcinoma in OSF was significantly different from spectrum of carcinoma arising from otherwise normal mucosa and also from the spectrum of normal mucosa. The difference in spectral intensities between normal, OSF, and carcinoma in OSF was found to be highly significant (p < 0.001). CONCLUSION: Autofluorescence spectroscopy has been proved to be a promising technique that can successfully differentiate precancerous and cancerous changes from normal mucosa. The spectra from each group studied (normal mucosa, OSF, and OSF with carcinoma) showed distinct features that made it possible to differentiate OSF from normal mucosa and also to detect malignant changes in OSF noninvasively and in real time.

Effect of 980-nm diode laser and 1064-nm Nd:YAG laser on the intervertebral disc--in vitro and in vivo studies.

OBJECTIVE: Our aim was to histologically evaluate the thermal changes in bovine intervertebral discs caused by 980-nm diode and 1064-nm Nd:YAG lasers. Further aims were to standardize the technique for in vivo animal research and to study its efficacy for clinical practice. BACKGROUND: When conservative methods fail, surgery has so far been the only measure for severe back pain due to disc prolapse and herniation. Recently, the minimally invasive technique of laser disc decompression has become more popular because it has advantages over open surgery in properly selected cases. METHODS: In vitro studies were done with Nd:YAG and diode lasers (1064 and 980 nm, respectively) on bovine intervertebral discs using a bare fiber tip or a focusing lens attached to a fiber tip. These studies were followed by in vivo studies in a canine model using a Nd:YAG laser with a bare fiber tip. Autopsies were done immediately and at 3, 6, 9, and 12 mo after ablation and the histopathology of excised discs was evaluated. RESULTS: Depending upon the depth of ablation and the intensity of charring and carbonization, a standardized energy density and pulse duration were identified. CONCLUSION: Nd:YAG laser with initial delivery of 40-W laser power and a reduced power of 10-15 W thereafter, delivering a total energy density of 1500-2000 J/cm(2) using a bare fiber tip, is recommended for clinical applications.

Optimum wavelength for the differentiation of brain tumor tissue using autofluorescence spectroscopy.

OBJECTIVE: The role of autofluorescence spectroscopy in the detection and staging of benign and malignant brain tumors is being investigated in this study, with an additional aim of determining an optimum excitation wavelength for the spectroscopic identification of brain tumors. MATERIALS AND METHODS: The present study involves in-vitro autofluorescence monitoring of different human brain tumor samples to assess their spectroscopic properties. The autofluorescence measurement at four different excitation wavelengths 320, 370, 410, and 470 nm, were carried out for five different brain tumor types: glioma, astrocytoma, meningioma, pituitary adenoma, and schwannoma. RESULTS: The fluorescence spectra of tumor tissues showed significant differences, both in intensity and in spectral profile, from those of adjacent normal brain tissues at all four excitation wavelengths. The data were then subjected to multivariate statistical analysis and the sensitivities and specificities were calculated for each group. Of the four excitation wavelengths being considered, 470 nm appeared to be the optimal wavelength for detecting tissue fluorescence of brain tumor tissues. CONCLUSIONS: In conclusion, the spectroscopic luminescence measurements carried out in this study revealed significant differences between tumor tissue and adjacent normal tissue of human brains for all the tumor types tested, except for pituitary adenoma. From the results of this study we conclude that excitation wavelengths ranging from 410-470 nm are most suitable for the detection of brain tumor tissue. Moreover, in this particular study, only excitation at 470 nm indicated that samples we considered to be normal tissue were not normal, and that these were indeed pituitary adenoma tissues. This distinction was not clear at other excitation wavelengths.

Three-year follow-up of oral leukoplakia after neodymium:yttrium aluminum garnet (Nd:YAG) laser surgery.

Oral leukoplakia is a relatively common lesion with a significant proportion of cases changing into cancer. Since most leukoplakias are asymptomatic, the primary objective of treatment must aim at the prevention of such malignant transformation. The main objectives of the study are to observe (1) the efficacy, safety and acceptability of the neodymium:yttrium aluminum garnet (Nd:YAG) laser in the management of oral leukoplakia; (2) the nature of postoperative complications, if any, associated with laser ablation, and (3) the 3-year prognosis of oral leukoplakia treated with laser. Twenty-eight patients with histologically proven leukoplakia were treated with Nd:YAG laser. From this study, we observed that the patients treated with Nd:YAG laser had only mild to moderate pain, swelling and restricted mouth opening, which peaked between 72 h and 1 week. In a majority of the patients the healing was prolonged, to a maximum of 5 weeks, and there was no clinical evidence of scarring in 26 out of 28 cases. In this study we achieved a cure rate of 92.86% in a 6-month period. Further follow-up after 3 years yielded almost the same result, except that one patient was not available for follow-up. We concluded that Nd:YAG laser is an effective device in the management of oral leukoplakia, which is one of the major pre-cancerous lesions in our country.

Spectroscopic and thermal analysis of a submandibular sialolith of Wharton's duct resected using Nd:YAG laser.

A sialolith observed in the Wharton's duct of a male patient was resected using an Nd:YAG laser. This is the first report on the resection of sialolith using laser. The resected sample was analyzed for structural details using Fourier transform infrared (FTIR), FT-Raman, and fluorescence spectroscopic techniques. Other techniques like energy dispersive X-ray analysis, scanning electron microscopy, and thermal analysis were also used for the analysis of structural details. The major peaks of the vibrational spectra are observed to be due to the vibrations of the phosphate and hydroxyl groups of the inorganic part of the sample and the proteinaceous component of the organic part. The major elements in the sample are identified as calcium and phosphorous in the ratio 7:3. The fluorescence spectra recorded at excitation wavelengths 280, 325, and 410 nm showed emission maxima corresponding to the endogenous fluorescence of structural proteins and amino acids. The inorganic part of the sialolith remained stable even at temperatures up to 1,673 K. The spectroscopic studies indicated that the structure of the sialolith is similar to that of the dentine part of the human teeth. In situ disintegration of the sialolith involves very high temperature. High calcium and phosphorous content in the food may be attributed to one of the reasons for the formation of sialoliths.

Percutaneous laser disc decompression: clinical experience at SCTIMST and long term follow up.

BACKGROUND: Low backache (LBA) is now increasing in younger population due to misdirected spinal kinetics secondary to improper posture, heavy load lifting and motorbike driving. Hence minimally invasive procedures are increasingly sought after. Among these, PLDD is currently popular and in use. We present our long term follow-up in the use of Nd:YAG laser for PLDD. AIM: To evaluate the efficacy of PLDD in treatment of contained herniation of lumbar discs & long term follow up results. MATERIALS AND METHODS: Forty patients with contained lumbar disc herniation on MRI and who did not respond to 6 weeks conservative treatment were subjected to PLDD. L4-5 disc was treated in 31, L5-S1 in 12 and L1-2 and L3-4 in one each. Nd:YAG laser at 1064 nm was used for the procedure. Total laser energy of 1500-2000 Joules was delivered at the disc space depending upon the size. RESULTS: There was immediate pain relief in 32/40 (80%). According to MacNab criteria good to fair response was seen in 37/40 (92%) and 3 patients (7.5%) responded poorly to this treatment. On follow up which ranged from 1 to 7 years, 34/40 (85%) had pain relief with no need for further treatment. COMPLICATIONS: Significant pain at local puncture site was experienced by 8 (20%), pain during lasing was experienced by one. One patient developed muscular spasm. CONCLUSION: Percutaneous laser disc decompression is a safe, relatively noninvasive and effective treatment modality for contained, nonsequestered, herniated lumbar disc disease in carefully selected patients.

Vibrational spectra of mono, di and trimethyl ammonium double sulphates of rare earths Pr, Nd, Ho and Eu.

Infrared and Raman spectra of four rare earth (Ho, Eu, Nd and Pr) double sulphates have been recorded and analysed based on the vibrations of methyl ammonium cations, sulphate anions and water molecules. Formation of hydrogen bonds of the type N-H...O and O-H...O are identified in all the compounds. Bifurcated hydrogen bonds are present in the compounds with dimethyl ammonium cations. The sulphate anions are distorted and occupy a lower site symmetry in the compounds. The bands obtained for (CH(3))(2)NH(2) and SO(4)(2-) ions indicate that the structural bonding of (CH(3))(2)NH(2)Eu(SO(4))(2).H(2)O and (CH(3))(2)NH(2)Ho(SO(4))(2).4H(2)O is identical. Electronic transition bands of Eu(3+) and Nd(3+) observed in the Raman spectra of these two compounds have been identified and discussed.

Temperature dependent polarized Raman spectra of nonaaqualanthanoid (Pr) single crystal.

Polarized Raman spectral changes with respect to temperature were investigated for Pr(BrO3)3.9H2O single crystals. FTIR spectra of hydrated and deuterated analogues were also recorded and analysed. Temperature dependent Raman spectral variation have been explained with the help of the thermograms recorded for the crystal. Factor group analysis could propose the appearance of BrO3 ions at sites corresponding to C3v (4) and D3h (2). Analysis of the vibrational bands at room temperature confirms a distorted C3v symmetry for the BrO3 ion in the crystal. From the vibrations of water molecules, hydrogen bonds of varying strengths have also been identified in the crystal. The appearance upsilon1 mode of BrO3- anion at lower wavenumber region is attributed to the attachment of hydrogen atoms to the BrO3- anion. At high temperatures, structural rearrangement is taking place for both H2O molecule and BrO3 ions leading to the loss of water molecules and structural reorientation of bromate ions causing phase transition of the crystal at the temperature of 447 K.

Regression of solid tumour using laser and 5-aminolevulinic acid in mice.

Solid tumour reducing effect in Swiss albino mice induced with Dalton's Lymphoma Ascites tumour cells (DLA) and Ehrlich Ascites tumour cells (EA) was determined with the application of He-Ne and Nd:YAG lasers along with the photosensitising agent 5-Aminolevulinic acid (ALA). The experiment was designed with six groups and each group consisted of six animals. Animals in Groups I-III were injected with DLA cell lines and Groups IV-VI were injected with EA cell lines (1 x 10(6) in 0.1ml saline) subcutaneously in the right hind limb of mice to induce solid tumours. The tumour was further treated with photosensitiser induced laser therapy. The hyperthermic effect of Nd:YAG laser on tumour reduction was also evaluated. The results of the study suggest that the combination of He-Ne laser and 1 W Nd:YAG laser along with the photosensitiser 5-Aminolevulinic acid is a very effective therapeutic method for the treatment of tumour of DLA and EA cell lines. It is clear from the results that this mode of therapy very well depends on the type of tumour that has to be treated.

The influence of photodynamic therapy on the wound healing process in rats.

In photodynamic therapy (PDT), photosensitisers (PS) are used along with lasers for the treatment of tumors. The combined effect of photosensitisers and lasers on the wound healing process is studied using delta-aminolevulinic acid (ALA) (5 mg/kg) and hematoporphyrin derivative (HPD) (5 mg/kg) as photosensitisers in the open excision wounds of rats. The lasers used were He-Ne laser (3 J/cm2) and Nd:YAG laser (30 J/cm2). This study is important for understanding the healing process involved after PDT. Open excision wounds treated with He-Ne lasers in animals that received ALA as photosensitiser showed complete wound closure at the earliest by 13 +/- 1 days, and with results obtained for HPD and the combination of lasers with complete closing by 14 +/- 1 days. However, the control group of animals that received ALS or HPD with no laser treatment showed wound healing on the twentieth and eighteenth days with a deviation of one day and two days, respectively. ALA with the combination of Nd:YAG and He-Ne lasers and HPD with He-Ne laser alone does not show quicker wound healing effects. Histopathological results also gave similar results. Tensile strength measurements do not vary significantly from control group to the test group. ALA along with He-Ne laser of HPD along with the combination of He-Ne and low power Nd-YAG lasers are found to be ideal methods for quickening the wound healing process in rat.

Development of artificial skin (Template) and influence of different types of sterilization procedures on wound healing pattern in rabbits and guinea pigs.

Different types of sterilization procedures have been applied onto artificial skin (Template) developed in our laboratory from polyether urethane, chitosan and polyvinyl alcohol, etc. Studies have been performed to investigate the differences in the wound healing pattern. It appears that quickened wound healing takes place in the rabbit model despite different types of samples and sterilization methods.