Search citation statements
Paper Sections
Citation Types
Year Published
Publication Types
Relationship
Authors
Journals
Time signals are measured experimentally throughout sciences, technologies and industries. Of particular interest here is the focus on time signals encoded by means of magnetic resonance spectroscopy (MRS). The great majority of generic time signals are equivalent to auto-correlation functions from quantum physics. Therefore, a quantum-mechanical theory of measurements of encoded MRS time signals is achievable by performing quantum-mechanical spectral analysis. When time signals are measured, such an analysis becomes an inverse problem (harmonic inversion) with the task of reconstruction of the fundamental frequencies and the corresponding amplitudes. These complex-valued nodal parameters are the building blocks of the associated resonances in the frequency spectrum. Customarily, the MRS literature reports on fitting some ad hoc mathematical expressions to a set of resonances in a Fourier spectrum to extract their positions, widths and heights. Instead, an alternative would be to diagonalize the so-called data matrix with the signal points as its elements and to extract the resonance parameters without varying any adjusting, free constants as these would be absent altogether. Such a data matrix (the Hankel matrix) is from the category of the evolution matrix in the Schrödinger picture of quantum mechanics. Therefore, the spectrum of this matrix, i.e. the eigenvalues and the corresponding amplitudes, as the Cauchy residues (that are the squared projections of the full wave functions of the system onto the initial state) are equivalent to the sought resonance parameters, just mentioned. The lineshape profile of the frequency-dependent quantum-mechanical spectral envelope is given by the Heaviside partial fraction sum. Each term (i.e. every partial fraction) in this summation represents a component lineshape to be assigned to a given molecule (metabolite) in the tissue scanned by MRS. This is far reaching, since such a procedure allows reconstruction of the most basic quantum-mechanical entities, e.g. the total wave function of the investigated system and its ’Hamiltonian’ (a generator of the dynamics), directly from the encoded time signals. Since quantum mechanics operates with abstract objects, it can be applied to any system including living species. For example, time signals measured from the brain of a human being can be analyzed along these lines, as has actually been done e.g. by own our research. In this way, one can arrive at a quantum-mechanical description of the dynamics of vital organs of the patient by retrieving the interactions as the most important parts of various pathways of the tissue functions and metabolism. Of practical importance is that the outlined quantum-mechanical prediction of the frequency spectrum coincides with the Padé approximant, which is in signal processing alternatively called the fast Padé transform (FPT) for nonderivative estimations. Further, there is a novelty called the derivative fast Padé transform (dFPT). The FPT and dFPT passed the test of time with three fundamentally different time signals, synthesized (noise-free, noise-contaminated) as well as encoded from phantoms and from patients. Such systematics are necessary as they permit robust and reliable benchmarkings of the theory in a manner which can build confidence of the physician, while interpreting the patient’s data and making the appropriate diagnosis. In the present study, we pursue further this road paved earlier by applying the FPT and dFPT (both as shape and parameter estimators) to time signals encoded by in vivo proton MRS from an ovarian tumor. A clinical 3T scanner is used for encoding at a short echo time (30 ms) at which most resonances have not reached yet their decay mode and, as such, could be detected to assist with diagnostics. We have two goals, mathematical and clinical. First, we want to find out whether particularly the nonparametric dFPT, as a shape estimator, can accurately quantify. Secondly, we want to determine whether this processor can provide reliable information for evaluating an ovarian tumor. From the obtained results, it follows that both goals have met with success. The nonparametric dFPT, from its onset as a shape estimator, transformed itself into a parameter estimator. Its quantification capabilities are confirmed by reproducing the components reconstructed by the parametric dFPT. Thereby, fully quantified information is provided to such a precise extent that a large number of sharp resonances (more than 160) appear as being well isolated and, thus, assignable to the known metabolites with no ambiguities. Importantly, some of these metabolites are recognized cancer biomarkers (e.g. choline, phosphocholine, lactate). Also, broader resonances assigned to macromolecules are quantifiable by a sequential estimation (after subtracting the formerly quantified sharp resonances and processing the residual spectrum by the nonparametric dFPT). This is essential too as the presence of macromolecules in nonoderivative envelopes deceptively exaggerates the intensities of sharper resonances and, hence, can be misleading for diagnostics. The dFPT, as the quantification-equipped shape estimator, rules out such possibilities as wider resonances can be separately quantified. This, in turn, helps make adequate assessment of the true yield from sharp resonances assigned to metabolites of recognized diagnostic relevance.
Time signals are measured experimentally throughout sciences, technologies and industries. Of particular interest here is the focus on time signals encoded by means of magnetic resonance spectroscopy (MRS). The great majority of generic time signals are equivalent to auto-correlation functions from quantum physics. Therefore, a quantum-mechanical theory of measurements of encoded MRS time signals is achievable by performing quantum-mechanical spectral analysis. When time signals are measured, such an analysis becomes an inverse problem (harmonic inversion) with the task of reconstruction of the fundamental frequencies and the corresponding amplitudes. These complex-valued nodal parameters are the building blocks of the associated resonances in the frequency spectrum. Customarily, the MRS literature reports on fitting some ad hoc mathematical expressions to a set of resonances in a Fourier spectrum to extract their positions, widths and heights. Instead, an alternative would be to diagonalize the so-called data matrix with the signal points as its elements and to extract the resonance parameters without varying any adjusting, free constants as these would be absent altogether. Such a data matrix (the Hankel matrix) is from the category of the evolution matrix in the Schrödinger picture of quantum mechanics. Therefore, the spectrum of this matrix, i.e. the eigenvalues and the corresponding amplitudes, as the Cauchy residues (that are the squared projections of the full wave functions of the system onto the initial state) are equivalent to the sought resonance parameters, just mentioned. The lineshape profile of the frequency-dependent quantum-mechanical spectral envelope is given by the Heaviside partial fraction sum. Each term (i.e. every partial fraction) in this summation represents a component lineshape to be assigned to a given molecule (metabolite) in the tissue scanned by MRS. This is far reaching, since such a procedure allows reconstruction of the most basic quantum-mechanical entities, e.g. the total wave function of the investigated system and its ’Hamiltonian’ (a generator of the dynamics), directly from the encoded time signals. Since quantum mechanics operates with abstract objects, it can be applied to any system including living species. For example, time signals measured from the brain of a human being can be analyzed along these lines, as has actually been done e.g. by own our research. In this way, one can arrive at a quantum-mechanical description of the dynamics of vital organs of the patient by retrieving the interactions as the most important parts of various pathways of the tissue functions and metabolism. Of practical importance is that the outlined quantum-mechanical prediction of the frequency spectrum coincides with the Padé approximant, which is in signal processing alternatively called the fast Padé transform (FPT) for nonderivative estimations. Further, there is a novelty called the derivative fast Padé transform (dFPT). The FPT and dFPT passed the test of time with three fundamentally different time signals, synthesized (noise-free, noise-contaminated) as well as encoded from phantoms and from patients. Such systematics are necessary as they permit robust and reliable benchmarkings of the theory in a manner which can build confidence of the physician, while interpreting the patient’s data and making the appropriate diagnosis. In the present study, we pursue further this road paved earlier by applying the FPT and dFPT (both as shape and parameter estimators) to time signals encoded by in vivo proton MRS from an ovarian tumor. A clinical 3T scanner is used for encoding at a short echo time (30 ms) at which most resonances have not reached yet their decay mode and, as such, could be detected to assist with diagnostics. We have two goals, mathematical and clinical. First, we want to find out whether particularly the nonparametric dFPT, as a shape estimator, can accurately quantify. Secondly, we want to determine whether this processor can provide reliable information for evaluating an ovarian tumor. From the obtained results, it follows that both goals have met with success. The nonparametric dFPT, from its onset as a shape estimator, transformed itself into a parameter estimator. Its quantification capabilities are confirmed by reproducing the components reconstructed by the parametric dFPT. Thereby, fully quantified information is provided to such a precise extent that a large number of sharp resonances (more than 160) appear as being well isolated and, thus, assignable to the known metabolites with no ambiguities. Importantly, some of these metabolites are recognized cancer biomarkers (e.g. choline, phosphocholine, lactate). Also, broader resonances assigned to macromolecules are quantifiable by a sequential estimation (after subtracting the formerly quantified sharp resonances and processing the residual spectrum by the nonparametric dFPT). This is essential too as the presence of macromolecules in nonoderivative envelopes deceptively exaggerates the intensities of sharper resonances and, hence, can be misleading for diagnostics. The dFPT, as the quantification-equipped shape estimator, rules out such possibilities as wider resonances can be separately quantified. This, in turn, helps make adequate assessment of the true yield from sharp resonances assigned to metabolites of recognized diagnostic relevance.
The present study deals with two different kinds of time signals, encoded by in vitro proton magnetic resonance spectroscopy (MRS) with a high external static magnetic field, 14.1T (Bruker 600 MHz spectrometer). These time signals originate from the specific biofluid samples taken from two patients, one with benign and the other with malignant ovarian cysts. The latter two diagnoses have been made by histopathologic analyses of the samples. Histopathology is the diagnostic gold standard in medicine. The obtained results from signal processing by the nonparametric derivative fast Padé transform (dFPT) show that a number of resonances assignable to known metabolites are considerably more intense in the malignant than in the benign specimens. Such conclusions from the dFPT include the recognized cancer biomarkers, lactic acid and choline-containing compounds. For example, the peak height ratio for the malignant-to-benign samples is about 18 for lactate, Lac. This applies equally to doublet Lac(d) and quartet Lac(q) resonating near 1.41 and 4.36 ppm (parts per million), respectively. For the choline-containing conglomerate (3.19-3.23 ppm), the dFPT with already low-derivative orders (2nd, 3rd) succeeds in clearly separating the three singlet component resonances, free choline Cho(s), phosphocholine PC(s) and glycerophosphocholine GPC(s). These constituents of total choline, tCho, are of critical diagnostic relevance because the increased levels, particularly of PC(s) and GPC(s), are an indicator of a malignant transformation. It is gratifying that signal processing by the dFPT, as a shape estimator, coheres with the mentioned histopathology findings of the two samples. A very large number of resonances is identifiable and quantifiable by the nonparametric dFPT, including those associated with the diagnostically most important low molecular weight metabolites. This is expediently feasible by the automated sequential visualization and quantification that separate and isolate sharp resonances first and subsequently tackle broad macromolecular lineshape profiles. Such a stepwise workflow is not based on subtracting nor annulling any part of the spectrum, in sharp contrast to controversial customary practice in the MRS literature. Rather, sequential estimation exploits the chief derivative feature, which is a faster peak height increase of the thin than of the wide resonances. This is how the dFPT simultaneously improves resolution (linewidth narrowing) and reduces noise (background flattening). Such a twofold achievement makes the dFPT-based proton MRS a high throughput strategy in tumor diagnostics as hundreds of metabolites can be visualized/quantified to offer the opportunity for a possible expansion of the existing list of a handful of cancer biomarkers.
The topic of this study is in vitro proton magnetic resonance spectroscopy (MRS). The theme is on theoretical analysis of time signals encoded at a high magnetic field 14.1T, using a Bruker spectrometer, operating at a Larmor frequency of 600 MHz. The samples, dissolved in a D$${}_2$$ 2 O buffer, are from histopathologically analyzed ovarian cyst fluid from two patients. The benign and malignant diagnoses were serous cystadenoma and serous cystadenocarcinoma, respectively. It is of vital clinical importance to determine whether certain specific patterns, inferred from the analyzed/interpreted MRS data could be correlated with this and similar histopathologic findings for other patients. Encoded time signals contain the fingerprint of the examined sample, its metabolic content. Therefore, to detect the sought patterns from MRS data, the salient characteristics of a malignant tumor, implied by the diagnostically most relevant metabolites (including recognized cancer biomarkers, e.g. lactic acids, cholines, ...), need to be unambiguously identified by their significant departures from the associated control data of benign biomaterial, ovarian cyst fluid (serous cystadenoma) in the diagnostic problem under the present consideration. Such identifications are unfeasible by visualization in the domain of encoding (time domain). A direct inspection of the graphed waveforms of an encoded time signal would give no clue about its structure nor about the sample content. However, merely visualizing the plots of the equivalent, information-preserving spectral lineshape profiles in the frequency domain would make transparent at least some of clinically useful, discernible features of MRS data, a number of resonances assignable to the known and unknown metabolites. For instance, the size of each resonance (peak area) is proportional to the concentration of the given metabolite. This is a key quantitative measure, which could help differentiate a malignant from a benign specimen by reference to the normal standards. A number of metabolites (choline, alanine, lactate, threonine, $$\beta $$ β -hydroxybuturate, valine, isolecine, leucine, ...) have substantially different concentrations in the malignant compared with normal samples. Time signals can be processed by two substantially different categories of mathematical transforms, shape and parameter estimators. The former processors are alternatively called nonparametric estimators. They have been employed for envelopes in our recent study on this problem, which will presently be addressed with the prime focus on reconstructions of the corresponding components. Components and envelopes are partial and total shape spectra, respectively. The sum of all the component lineshapes (one per metabolite) yields the envelope nondegenerate spectrum representation of the entire sample. Presently, a deeper diagnostically valid insight is gained about the metabolic content of the scanned sample through the reported exact component spectra. The employed parameter estimators are the high-resolution, noise-suppressing nonderivative and derivative fast Padé transforms. Detailed are several critical achievements by the parametric Padé processing of direct clinical relevance. Importantly, all the accomplishments are shared by the nonparametric derivative Padé estimations. Three examples are highlighted here as follows. Confirmation of our recent nonparametric derivative detection of an unassigned metabolite (a singlet peak) co-resonating with free choline near chemical shift 3.19 ppm (parts per million). Therein, with the nonderivative envelope, only one compound peak usually appears and is conventionally assigned to a free choline singlet. However, such an oversight would yield about twice larger value of the true concentration of this key cancer biomarker. The concentration level of another cancer biomarker (lactate) is also overestimated by any nonparametric nonderivative envelope. In sharp contrast, the parametric nonderivative Padé estimation unequivocally detects six usually invisible resonances (assignable to other metabolites) beneath the lactate doublet, around chemical shift 1.41 ppm. At least two of the strongest among these invisible six resonances can be also identified in the nonparametric fourth derivative Padé envelope. Regularization of the spectral compound for the water residual (4.71 ppm), which deforms the neighboring resonance lineshapes and impacts adversely on the concentration assessments of other nearby metabolites. This is accomplished by the fourth derivative envelope (coincident with the components) whose narrowing of the widths, cutting off the long tails and the background flattening generate a quantifiable singlet of water. This can serve as a reliable calibration reference resonance. After such a localization, no distortion appears around water, so that even very near 4.71 ppm, several smaller resonances are detected (assignable to a multiplet of nitrogen acetyl asparate), totally invisible in the nonparametric nonderivative envelope.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.