Biomedical Spectroscopy and Imaging - Volume 6, issue 1-2

Authors: Chaudhuri, Arunima | Anand, Deepak

Article Type: Review Article

Abstract: The legacy of Micheal Chevruel’s discovery of “cholesterine” as a non-saponifiable lipid from gall stones has ignited the imagination and research of countless minds for over two centuries now. In this review, we have provided a brief chronicle of the early history of cholesterol research which paved the way to present day understanding of membrane biology. We have discussed the properties and functionality of various fluorescent analogs of cholesterol in view of the ultra-high sensitivity, rapid response and spatial resolution obtained using fluorescence spectroscopic, microscopic and flow cytometric techniques. The repertoire of fluorescent analogs discussed for cholesterol research include the …naturally occurring analogs (dehydroergosterol and cholestatrienol); polarity sensitive probes (NBD- and dansyl-cholesterol); bright and photostable probe (BODIPY-cholesterol); clickable alkyne cholesterol and cholesterol binding macromolecules (fluorescently labeled non-toxic subunits of perfringolysin O and filipin) in monitoring cholesterol content in live and fixed cells. We have elaborated on the applications of the fluorescent analogs of cholesterol in clinical research, taking atherosclerosis, Niemann–Pick C and Alzheimer’s disease as representative examples. The applicability of fluorescent probes of cholesterol has become more relevant with the advent of various super-resolution microscopic techniques today and holds the promise of shedding light into the molecular orchestra of lipid-protein interaction with nanometer-scale resolution. Show more

Keywords: Cholesterol, fluorescent probes, athersoclerosis, Niemann–Pick C disease, Alzheimer’s disease (AD)

DOI: 10.3233/BSI-170166

Citation: Biomedical Spectroscopy and Imaging, vol. 6, no. 1-2, pp. 1-24, 2017

Authors: Norton, Terence J.T. | Pereyra, Marcelo | Knight, Michael J. | McGarry, Bryony M. | Jokivarsi, Kimmo T. | Gröhn, Olli H.J. | Kauppinen, Risto A.

Article Type: Research Article

Abstract: Background: Objective timing of stroke in emergency departments is expected to improve patient stratification. Magnetic resonance imaging (MRI) relaxations times, T 2 and T 1 ρ , in abnormal diffusion delineated ischaemic tissue were used as proxies of stroke time in a rat model. Methods: Both ‘non-ischaemic reference’-dependent and -independent estimators were generated. Apparent diffusion coefficient (ADC), T 2 and T 1 ρ , were sequentially quantified for up to 6 hours of stroke in rats …(n = 8 ) at 4.7T. The ischaemic lesion was identified as a contiguous collection of voxels with low ADC. T 2 and T 1 ρ in the ischaemic lesion and in the contralateral non-ischaemic brain tissue were determined. Differences in mean MRI relaxation times between ischaemic and non-ischaemic volumes were used to create reference-dependent estimator. For the reference-independent procedure, only the parameters associated with log-logistic fits to the T 2 and T 1 ρ distributions within the ADC-delineated lesions were used for the onset time estimation. Result: The reference-independent estimators from T 2 and T 1 ρ data provided stroke onset time with precisions of ± 32 and ± 27 minutes, respectively. The reference-dependent estimators yielded respective precisions of ± 47 and ± 54 minutes. Conclusions: A ‘non-ischaemic anatomical reference’-independent estimator for stroke onset time from relaxometric MRI data is shown to yield greater timing precision than previously obtained through reference-dependent procedures. Show more

Keywords: Ischaemic stroke, magnetic resonance imaging, MRI relaxometry, stroke onset time, rat

DOI: 10.3233/BSI-160155

Citation: Biomedical Spectroscopy and Imaging, vol. 6, no. 1-2, pp. 25-35, 2017

Authors: Tadimalla, S. | Tourell, M.C. | Knott, R. | Momot, K.I.

Article Type: Research Article

Abstract: Collagen fibre architecture in articular cartilage is commonly described in terms of the predominant direction of fibre alignment. X-ray scattering has been used to study the distribution of fibre orientations in cartilage. In this paper, a new methodology for the analysis of small-angle X-ray scattering (SAXS) patterns of articular cartilage in order to quantitatively determine the distribution of collagen fibre orientations in the tissue is presented. A simple three-component model was used to fit intensity data from SAXS patterns to separate diffraction maxima from general diffuse scatter. Deconvolution of angular distributions of intensities of diffraction maxima obtained from SAXS patterns …of articular cartilage and ligament samples yielded fibre orientation distributions in the cartilage samples. The methodology developed in this study worked reliably on a large set of SAXS patterns collected from native, dehydrated and trypsin-treated articular cartilage samples. The methods can be extended to quantitative analysis of small or wide angle X-ray scattering patterns obtained from other collagenous materials. Show more

Keywords: X-ray scattering, SAXS, articular cartilage, collagen fibre orientation, fibre dispersion

DOI: 10.3233/BSI-170164

Citation: Biomedical Spectroscopy and Imaging, vol. 6, no. 1-2, pp. 37-57, 2017

Authors: Myatt, Daniel P.

Article Type: Research Article

Abstract: Previous clinical research has suggested high-affinity binding of flavopiridol (FLAP) to human blood serum proteins, specifically either human serum albumin (HSA) or human alpha-1-acid glycoprotein (hAGP), when compared to fetal bovine serum albumin (BSA) or bovine alpha-1-acid glycoprotein (bAGP) used in pre-clinical assays. This high-affinity binding was suggested as the reason for its poor human clinical trial performance as a treatment for chronic lymphocytic leukaemia (CLL). Using three biophysical techniques, specifically circular dichroism (CD), isothermal calorimetry (ITC) and fluorescence spectroscopy, I show that FLAP does not have an overly high-affinity for either fetal BSA, HSA, bAGP or hAGP. I therefore …suggest an alternate hypothesis that models the albumin and alpha-1-acid glycoprotein (AGP) binding sites at the different protein concentrations used in the fetal bovine pre-clinical assay and human physiological conditions. I use analytical ultracentrifugation (AUC) experiments to determine the validity of the theoretical models. The models can also be altered to account for the elevated AGP levels and reduced albumin levels seen in human cancer patients. Major differences in the concentrations of free available FLAP are observed between the fetal bovine pre-clinical model and human physiological conditions. A number of recommendations can therefore be made on how future pre-clinical assay studies should be conducted. Show more

Keywords: Cancer, drug binding, serum albumin, alpha-1-acid glycoprotein, flavopiridol

DOI: 10.3233/BSI-170165

Citation: Biomedical Spectroscopy and Imaging, vol. 6, no. 1-2, pp. 59-73, 2017

Authors: Ramírez-Elías, M.G. | Guevara, E. | Zamora-Pedraza, C. | Rogelio Aguirre R., J. | Juárez F., Bertha I. | Bárcenas P., Guadalupe M. | Ruiz, Facundo | González, Francisco J.

Article Type: Research Article

Abstract: Raman spectroscopy and multivariate analysis techniques are proposed as a method to evaluate the mezcal (Agave distillate) aging. Multivariate analysis was performed using Principal component analysis discriminant analysis (PCA-DA) and Partial least squares discriminant analysis (PLS-DA). The first principal component discriminates between aged and rested matured mezcal while the second principal component discriminates between non-matured and matured mezcal. PCA-DA and PLS-DA were chosen as supervised classifiers to predict the belonging of unlabeled spectra to one of the aging classes with accuracy of 93%. The results agree with previously published work and also demonstrated that using a reduced Raman spectral region …it is possible the discrimination mezcal with different aging time. A reduction on the spectral information allows development of a Raman instrumentation with reduced complexity and cost with specific application to alcoholic beverage quality assessment. Show more

Keywords: Raman spectroscopy, multivariate analysis, Mezcal, aging

DOI: 10.3233/BSI-170163

Citation: Biomedical Spectroscopy and Imaging, vol. 6, no. 1-2, pp. 75-81, 2017