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R Stoyanova

Publications and source records attributed to R Stoyanova.

At least 19 recordsLinked to original sources
PubMed2006

In vivo 31P MR spectral patterns and reproducibility in cancer patients studied in a multi-institutional trial.

The standardization and reproducibility of techniques required to acquire anatomically localized 31P MR spectra non-invasively while studying tumors in cancer patients in a multi-institutional group at 1.5 T are reported. This initial group of patients was studied from 1995 to 2000 to test the feasibility of acquiring in vivo localized 31P MRS in clinical MR spectrometers. The cancers tested were non-Hodgkin's lymphomas, sarcomas of soft tissue and bone, breast carcinomas and head and neck carcinomas. The best accrual and spectral quality were achieved with the non-Hodgkin's lymphomas. The initial analysis of the spectral values of the sum of phosphoethanolamine plus phosphocholine normalized by the content of nucleotide triphosphates in a homogeneous sample of 32 NHL patients studied by in vivo (31)P MRS showed good reproducibility among different institutions. No statistical differences were found between the institution with the largest number of cases accrued and the rest of the multi-institutional NHL data (2.28 +/- 0.64, mean +/- standard error; n = 17, vs 2.08 +/- 0.14, n = 15). The preliminary data reported demonstrate that the institutions involved in this trial are obtaining reproducible 31P MR spectroscopic data non-invasively from human tumors. This is a fundamental prerequisite for the international cooperative group to be able to demonstrate the clinical value of the normalized determination of phosphoethanolamine plus phosphocholine by 31P MRS as predictor for treatment response in cancer patients.

Biomarkers, Tumor↗
PubMed2002

NMR spectral quantitation by principal component analysis. III. A generalized procedure for determination of lineshape variations.

We present a general procedure for automatic quantitation of a series of spectral peaks based on principal component analysis (PCA). PCA has been previously used for spectral quantitation of a single resonant peak of constant shape but variable amplitude. Here we extend this procedure to estimate all of the peak parameters: amplitude, position (frequency), phase and linewidth. The procedure consists of a series of iterative steps in which the estimates of position and phase from one stage of iteration are used to correct the spectra prior to the next stage. The process is convergent to a stable result, typically in less than 5 iterations. If desired, remaining linewidth variations can then be corrected. Correction of (typically) unwanted variations of these types is important not only for direct peak quantitation, but also as a preprocessing step for spectral data prior to application of pattern recognition/classification techniques. The procedure is demonstrated on simulated data and on a set of 992 (31)P NMR in vivo spectra taken from a kinetic study of rat muscle energetics. The proposed procedure is robust, makes very limited assumptions about the lineshape, and performs well with data of low signal-to-noise ratio.

Algorithms↗
PubMed2001

NMR spectral quantitation by principal component analysis.

The use of principal component analysis (PCA) for simultaneous spectral quantitation of a single resonant peak across a series of spectra has gained popularity among the NMR community. The approach is fast, requires no assumptions regarding the peak lineshape and provides quantitation even for peaks with very low signal-to-noise ratio. PCA produces estimates of all peak parameters: area, frequency, phase and linewidth. If desired, these estimates can be used to correct the original data so that the peak in all spectra has the same lineshape. This ability makes PCA useful not only for direct peak quantitation, but also for processing spectral data prior to application of pattern recognition/classification techniques. This article briefly reviews the theoretical basis of PCA for spectral quantitation, addresses issues of data processing prior to PCA, describes suitable and unsuitable datasets for PCA applications and summarizes the developments and the limitations of the method.

Magnetic Resonance Spectroscopy↗
PubMed2001

Synthesis and antibacterial activity of 5-nitrofuryl and 3-methoxy-2-nitrophenyl derivatives of 6 beta-aminopenicillanic, 7 beta-aminocephalosporanic and 7 beta-aminodesacetoxy-cephalosporanic acids.

A number of 5-nitrofuryl and 3-methoxy-2-nitrophenyl derivatives of 6 beta-aminopenicillanic (6 beta-APA), 7 beta-aminocephalosporanic (7 beta-ACA) and 7 beta-aminodesacetoxycephalosporanic (7 beta-ADCA) acids were synthesized by the method of mixed anhydrides or via Schiff bases. The chemical structures of the new compounds were confirmed by IR-, 1H-NMR and mass spectral data, obtained by negative ion electrospray ionization. The in vitro testing results indicated that all penicillins and cephalosporins prepared exhibited antibacterial activity equal to or in many cases considerably higher than those of ampicillin (CAS 69-53-4) and cephalexin (CAS 23325-78-2) against the Gram-positive microorganisms, excluding B. subtilis L2, B. subtilis HB2 and S. aureus 1/45 "Oxford". Their activity towards the two strains of Proteus mirabilis was also good being greater than that of cephalexin contrary to the demonstrated lower activity towards all strains of E. coli tested. The most active compounds which simultaneously possessed the broadest spectrum of antibacterial activity proved to be compounds 1 and 8 both bearing as a substituent a 5-nitrofuran group.

Bacteria↗
PubMed2000

Synthesis and antibacterial activity of new arylamido derivatives of 6 beta-aminopenicillanic, 7 beta-aminocephalosporanic and 7 beta-aminodesacetoxycephalosporanic acids.

New semisynthetic penicillins and cephalosporins have been synthesized by acylation of 6 beta-aminopenicillanic, 7 beta-aminocephalosporanic and 7 beta-aminodesacetoxycephalosporanic acids with ortho-substituted aromatic acids, using the method of mixed anhydrides. The chemical structures of the compounds obtained were confirmed by elemental analysis and by IR- and 1H-NMR spectra. Antibacterial activities of the compounds were determined by the macrodilution susceptibility test in brain-heart infusion broth. Test organisms producing beta-lactamases: Bacillus subtilis L2, Bacillus subtilis HB2, Bacillus cereus 30, Bacillus subtilis 6633 ATCC, Bacillus mycoides 924; Staphylococcus aureus 1/45 "Oxford" as Gram-positive bacteria, and Escherichia coli 111, Escherichia coli K12/F-¿lac-/, Escherichia coli K12/F-¿lambda-/, Escherichia coli K12/F-¿lambda-¿lac+/ as Gram-negative bacteria. In general, the derivatives of 6 beta-aminopenicillanic acid were more active than 7 beta-aminocephalosporanic and 7 beta-aminodesacetoxycephalosporanic acid derivatives. Among all the compounds synthesized 6 beta-[4'-(dimethylamino)-azobenzene-2-amido]penicillanic acid and 6 beta-(N-phenylanthranilamido)penicillanic acid showed the best activity and were with the broadest spectrum of action.

Bacillus↗
PubMed1998

3D multivoxel proton spectroscopy of human brain using a hybrid of 8th-order Hadamard encoding with 2D chemical shift imaging.

Multivoxel 3D localized proton spectroscopy using a hybrid of 1D 8th-order transverse Hadamard spectroscopic imaging (HSI) with 2D chemical shift imaging (CSI) is demonstrated in human brain. The spatially selective HSI pulse incorporates naturally into the PRESS sequence (TE = 135 ms), which then both excites an 8 x 8 x 6 cm parallelepiped volume of interest (VOI) and subdivides it into eight slices. The planes of these slices are further partitioned into 16 x 16 voxel arrays using 2D CSI to yield 8 x 8 x 8 voxels within the VOI. Simultaneous 3D coverage yields good voxel signal-to-noise (8, 12, and 22 for choline, creatine, and N-acetylaspartate, respectively) from these 0.75-ml voxels, in approximately 45 min. The high spatial isolation allows localization to within less than 1 cm from the skull without fat contamination.

Adult↗
PubMed1998

Quantification of phosphorus metabolites from chemical shift imaging spectra with corrections for point spread effects and B1 inhomogeneity.

A method is described for quantifying phosphorus metabolites in tissue using spectra localized with surface coils and chemical shift imaging (CSI) and assuming that metabolites are uniformly distributed within a well-defined volume. An analytical expression is developed that yields a single numerical correction factor that takes into account the excitation and receiver profiles of the coil, T1 saturation, and point spread effects associated with Fourier transformation of CSI data. An external phosphorus standard is used to calibrate instrument gain and the B1 profile of the coil. For spherical samples, point spread effects can modulate the signal intensities of three-dimensional CSI spectra from -32% to +54%, depending on the voxel size. Measurements of phantoms of known concentrations showed systematic variations of +/- 10% and random errors of +/- 5%. We have used this method to measure the concentration of phosphocreatine in the thigh muscle of normal volunteers.

Algorithms↗
PubMed1997

In vivo phosphorus polarization transfer and decoupling from protons in three-dimensional localized nuclear magnetic resonance spectroscopy of human brain.

Refocused insensitive nucleus enhancement by polarization transfer (RINEPT) from protons (1H) to a J-coupled phosphorus (31P) has been incorporated into three-dimensional (3D) chemical-shift-imaging (CSI) sequence on a clinical imager. The technique is demonstrated on a phantom and in in vivo human brain. The polarization-transfer efficiency (approximately 1.2) is lower than the theoretical maximum of gamma1H/gamma31P approximately 2.4 resulting from 1H-1H homonuclear J couplings of similar magnitude competing with the 1H --> 31P transfer. Nevertheless, compared with direct 31P Ernst-angle excitation, signal gains of up to x1.8 were obtained mainly as a result of T1 differences between 31P and the 1H. Spectral interpretation is simplified by editing out all non-proton-coupled 31P signals. The duration, approximately 50 min, and power deposition, approximately 1 W x kg(-1), make the application suitable for human studies.

Brain↗
PubMed1996

Heteronuclear multivoxel spectroscopy of in vivo human brain: two-dimensional proton interleaved with three-dimensional 1H-decoupled phosphorus chemical shift imaging.

Multivoxel, heteronuclear interleaved two-dimensional proton and three-dimensional 1H-decoupled 31P CSI of human brain is demonstrated. This method offers efficient use of limited examination time as patient preparation, coil tuning, shimming and imaging are done only once and the CSI data sets from both nuclei are obtained concurrently. Effective interleaving of 31P and 1H is possible due to the shorter T1s of proton brain metabolites, allowing a 1H acquisition cycle to be inserted into each 31P TR. This way, the entire MRS time is available to both nuclei, increasing their SNR per-unit-time by approximately 12% for 31P and approximately 80% for 1H, compared with sequential detection of equal (45-50 min) length. The spectral resolution and SNR of 31P are further increased through bi-level 1H-decoupling and NOE.

Brain↗
PubMed1996

Quantitation of resonances in biological 31P NMR spectra via principal component analysis: potential and limitations.

This paper examines the potential and limitations of peak area quantitation of biological NMR spectra using principal component analysis (PCA), including its requirement for prior knowledge. The principles of the method are presented without in-depth mathematical treatment. PCA is illustrated for simulated data, 31P NMR spectra obtained consecutively over 1-2.5 days from perfused Rat-2 cells metabolizing the choline analogue phosphoniumcholine (Chop) and in vivo proton-decoupled, NOE-enhanced, three-dimensional CSI localized 31P NMR spectra of the liver of healthy volunteers. The results show that PCA can be used to quantitate strongly overlapping peaks without prior knowledge of the peak shapes or positions and to reconstruct spectra with significantly reduced noise variance. Two major limitations of PCA are presented: (1) PCA cannot separate peaks whose intensities are well correlated; (2) PCA is sensitive to differences in chemical shift and line-width of peaks between spectra. The discussion focuses on what knowledge of the biological and spectroscopic features of the samples and the principles of PCA is necessary for peak area quantitation via PCA.

Humans↗
PubMed1996

NMR spectral quantitation by principal-component analysis. II. Determination of frequency and phase shifts.

This paper extends the use of principal-component analysis in spectral quantification to the estimation of frequency and phase shifts in a single resonant peak across a series of spectra. The estimated parameters can be used to correct the spectra accordingly, resulting in more accurate peak-area estimation. Further, the removal of the variations in phase and frequency cause by instrumental and experimental fluctuations makes it possible to determine more accurately the remaining variations, which bear biological significance. The procedure is demonstrated on simulated data, a 3D chemical-shift-imaging dataset acquired from a cylinder of inorganic phosphate (Pi), and a set of 736 31P NMR in vivo spectra taken from a kinetic study of rate muscle energetics. In all cases, the procedure rapidly and automatically identifies the frequency and phase shifts present in the individual spectra. In the kinetic study, the procedure is used twice, first to adjust the phase and frequency of a reference peak (phosphocreatine) and then to determine the individual frequencies of the Pi peak in each of the spectra which further can be used for estimation of pH changes during the experiment.

Computer Simulation↗
PubMed1995

Metabolic characterization of human non-Hodgkin's lymphomas in vivo with the use of proton-decoupled phosphorus magnetic resonance spectroscopy.

Development of biological and clinical uses of in vivo 31P magnetic resonance spectroscopy has been hampered by poor anatomic localization of spectra and poor resolution of overlapping signals within phosphomonoester and phosphodiester regions of the spectrum. We applied 1H-decoupling and nuclear Overhauser enhancement to improve resolution of 31P magnetic resonance spectra accurately localized to 21 non-Hodgkin's lymphomas (NHL) by using three-dimensional chemical shift imaging. All 21 spectra had large phosphomonoester signals (26% of total phosphorus) that contained high amounts of phosphoethanolamine relative to phosphocholine. There were no signals from glycerophosphoethanolamine or glycerophosphocholine but only a broad signal from membrane phospholipids in the phosphodiester region (20% of phosphorus). Prominent nucleoside triphosphates (47% of phosphorus) and low inorganic phosphate (7% of phosphorus) indicate well-perfused tissue with viable cells. Mean intracellular pH was 7.23. These characteristics were similar in all grades and stages of NHL. By analogy with recently reported studies in cell lines in vitro, we hypothesize that the pattern of phospholipid metabolites observed in NHL in vivo is partly a manifestation of sustained activation of phospholipase C or D. The techniques we implemented permitted us to obtain more information about in vivo metabolism of NHL than has heretofore been available. This information is important for the establishment of appropriate experimental models and provides a basis from which to examine potential clinical uses of 31P magnetic resonance spectroscopy.

2,3-Diphosphoglycerate↗
PubMed1995

Hybrid three dimensional (1D-Hadamard, 2D-chemical shift imaging) phosphorus localized spectroscopy of phantom and human brain.

A hybrid of two localized spectroscopy techniques, chemical shift imaging (CSI) and Hadamard spectroscopic imaging (HSI), is used to obtain an array of 16 x 16 x 4 (3 x 3 x 3 cm3 voxels) proton-decoupled phosphorus (31P) spectra of human brain. For equal spatial resolution, this organ's oblate shape requires fewer axial than coronal or sagittal slices. These different spatial requirements are well suited to 1D, 4th order, transverse HSI in the axial direction, combined with 2D 16 x 16 CSI in the other two orientations. The reduced localization matrix (16 x 16 x 4 over just the brain versus a cubic-16 x 16 x 16 matrix of equal resolution, over the entire head) may proportionally shorten data acquisition if the voxel size is not signal-to-noise limited. In addition, the use of Hadamard encoding can improve the intervoxel spectral isolation.

Aged↗
PubMed1995

NOE enhancements and T1 relaxation times of phosphorylated metabolites in human calf muscle at 1.5 Tesla.

Nuclear Overhauser effect (NOE) enhancements and relaxation times of 31P metabolites in human calf were measured in 12 volunteers (4 men and 8 women) at 1.5 T using a dual tuned four-ring birdcage. The NOE enhancements of inorganic phosphate (Pi), phosphocreatine (PCr), gamma-, alpha-, and beta-nucleoside triphosphate (NTP) from 19 measurements were 0.51 +/- 0.10, 0.64 +/- 0.03, 0.53 +/- 0.03, 0.56 +/- 0.08, and 0.47 +/- 0.05, respectively. The relaxation times were independent of proton irradiation and from 23 measurements were 3.49 +/- 0.35, 4.97 +/- 0.58, 4.07 +/- 0.36, 2.90 +/- 0.25, and 3.61 +/- 0.25 s for Pi, PCr, gamma-, alpha-, and beta-NTP, respectively. No significant differences between gender and age were observed for either NOE enhancements or relaxation times. Also, among nine volunteers, we observed no significant differences in T1 between the coupled and decoupled cases.

Adolescent↗
PubMed1994

Dual interleaved 1H and proton-decoupled-31P in vivo chemical shift imaging of human brain.

A technique is demonstrated to obtain interleaved proton (1H) and 1H-decoupled phosphorus (31P) spectra of human brain using 2D CSI. A modified commercial full-body imager and a dual-tuned birdcage head-coil were employed. Because proton relaxation times are shorter than those of phosphorus, TR(1H) can be chosen to be shorter than TR(31P), thus permitting a 1H acquisition to be inserted in each 31P cycle. The scheme results in significant time savings as both CSI data sets are obtained concurrently with patient loading, coil tuning, shimming, and imaging needed to be done only once.

Adult↗
PubMed1994

Simultaneous and interleaved multinuclear chemical-shift imaging, a method for concurrent, localized spectroscopy.

A method is proposed for carrying out chemical-shift imaging simultaneously on several nuclei (1H and 31P in this example), using a commercial clinical NMR imager fitted with a second RF channel and a dual-tuned birdcage coil to fit the human head. Nuclei of different gamma are examined at the same field of view by exciting each nucleus successively at times proportional to gamma during the same phase-encoding gradient waveform. Thus, each higher-gamma nucleus is exposed to a smaller area of the gradient. Additionally, since in vivo protons typically have a shorter T1 and roughly an order of magnitude higher sensitivity than phosphorus, it is possible to interleave 1H-only acquisitions between the simultaneous 1H, 31P observations while the lower-gamma nucleus relaxes. Consequently, additional information is obtained with either higher spatial resolution or greater sensitivity (more signal averaging) without lengthening the duration of the examination.

Computer Simulation↗
PubMedDate not supplied

Proton-decoupled 31P chemical shift imaging of the human brain in normal volunteers.

Proton-decoupled, 31P three-dimensional (3-D) chemical shift imaging (CSI) spectra have been acquired from the entire human brain using a new dual tuned resonator. The resonator operates in quadrature mode to provide improved sensitivity, excellent B1 homogeneity and reduced power deposition at both frequencies. Proton-decoupled and fully NOE enhanced, 31P spectra were acquired from normal volunteers using Waltz-4 proton decoupling with continuous wave bi-level excitation applied through a second radio frequency channel. Well resolved peaks in the phosphomonoester (PME) and phosphodiester regions were obtained from nonlocalized FIDs and spectra localized with 3-D CSI without processing for resolution enhancement. pH measurements made over large regions of the brain using the P(i) resonance show no significant variations (6.9 +/- 0.02) for a single individual. The improved spectral resolution and sensitivity of the PME resonances results in more well defined metabolite images of the PME peak region.

Brain↗