Aad van den Boogaart - Academia.edu (original) (raw)

Papers by Aad van den Boogaart

Research paper thumbnail of Application of time-domain fitting in the quantification ofin vivo1H spectroscopic imaging data sets

NMR in Biomedicine, Jul 1, 1992

Time‐domain model function fitting techniques were applied to improve the reconstruction of metab... more Time‐domain model function fitting techniques were applied to improve the reconstruction of metabolite maps from the data sets obtained from in vivo 1H spectroscopic imaging (SI) experiments. First, residual water‐related signals were removed from the SI data sets by using SVD‐based linear time‐domain fitting based upon the HSVD (State Space) approach. Second, peak integrals of the metabolites of interest were obtained by quantifying the proton spin‐echoes of the voxels by means of non‐linear time‐domain fitting based upon the maximum likelihood principle. Third, in order to save computational time, interpolation of the metabolite images (from size 32 × 32 to 128 × 128) was performed in the image‐domain by applying one‐dimensional cubic splines. It was found that the residual water signals can be almost completely removed from the SI data sets by applying the linear HSVD fitting method. Furthermore, it was found that voxel dependency of certain NMR parameters (e.g., variations of the spin‐echo offset frequencies and/or phase factors) can be accounted for automatically by applying the non‐linear time‐domain fitting technique. For that purpose it appeared to be essential to employ prior knowledge of the NMR spectral parameters.

Research paper thumbnail of Time and frequency domain analysis of NMR data compared: An application to 1D1H spectra of lipoproteins

Magnetic Resonance in Medicine, Apr 1, 1994

A comparison between a time domain analysis algorithm (VARPRO) and a frequency domain analysis al... more A comparison between a time domain analysis algorithm (VARPRO) and a frequency domain analysis algorithm (FITPLA') for parameter estimation of magnetic resonance spectroscopy (MRS) data series is presented. VARPRO analyses the measured MRS signal (free induction decay; FID); FITPLA' analyses the discrete Fourier transform of the FID, the frequency domain magnetic resonance spectrum. A rapid time domain method, used to subtract the dominating water resonance from a 'H MRS FID, without affecting the metabolites of interest, is outlined and applied. Also a new "pseudofrequency selective" approach to time domain fitting is introduced. The possibilities of combining the most favorable features of time and frequency domain processing into one single MRS signal processing method are assessed. The 'H MRS signals of ultracentrifuged very low (VLDL), intermediate (IDL), and high (HDL) density lipoprotein fractions from human blood plasma were used for the comparisons. The results from both algorithms were in good agreement.

Research paper thumbnail of Multicentre quantitative data-analysis trial: the overlapping background problem

Research paper thumbnail of Fast and accurate parameter estimation of noisy complex exponentials with use of prior knowledge

European Signal Processing Conference, 1996

In this paper we address the problem of parameter estimation of magnetic resonance spectroscopy (... more In this paper we address the problem of parameter estimation of magnetic resonance spectroscopy (MRS) signals. MRS signals are modeled as complex exponentials in noise. Iterative methods based on an optimisation procedure can be used for the parameter estimation. We examine which functional we h a ve to minimise and which nonlinear least squares algorithms we h a ve t o u s e in order to attain maximum e ciency and robustness. The in uence of starting values and prior knowledge is examined.

Research paper thumbnail of MRUI Manual v 96.3. A user's guide to the Magnetic Resonance User Interface software package

Research paper thumbnail of Improved Fitting Method for Parameter Estimation of MRS Signals with Prior Knowledge

Research paper thumbnail of Quantitative data analysis ofin vivoMRS data sets

Magnetic Resonance in Chemistry, Dec 1, 1997

ABSTRACT The different characteristics between frequency domain and time domain analysis techniqu... more ABSTRACT The different characteristics between frequency domain and time domain analysis techniques are detailed for their application to in vivo MRS data sets. With the aim of quantitative analysis of MRS signals, i.e. estimation of parameters in the physical model function that describes the MRS experiment, it is considered desirable to avoid any preprocessing of the data, resulting in a preference for time domain parameter estimation techniques. A historical overview is provided for the time domain analysis methods presented in the literature, and a number of time domain methods are described in detail. Finally, the MRUI software package, providing an interactive graphical user interface for a variety of time domain methods, is summarized. © 1997 John Wiley & Sons, Ltd.

Research paper thumbnail of Absolute metabolite quantification by in vivo NMR spectroscopy: V. multicentre quantitative data analysis trial on the overlapping background problem

Magnetic Resonance Imaging, Nov 1, 1998

... The first one was an in vivo 1 H NMR echo signal, taken from the right parietal lobe of a hum... more ... The first one was an in vivo 1 H NMR echo signal, taken from the right parietal lobe of a human brain by using a 20 ms STEAM sequence (supplied by P. Gilligan, J. MacEnri and JT Ennis, The Institute of Radiological Sciences, Dublin). ...

Research paper thumbnail of New approach for quantitation of short echo timein vivo1H MR spectra of brain using AMARES

NMR in Biomedicine, Feb 1, 1998

Short echo time in vivo STEAM 1 H MR spectra (4.7 T, TE=16 ms) of normal rat brain were fitted in... more Short echo time in vivo STEAM 1 H MR spectra (4.7 T, TE=16 ms) of normal rat brain were fitted in the time domain using a VARPRO-like algorithm called AMARES which allows an inclusion of a large amount of prior knowledge. The prior knowledge was derived from phantom spectra of pure metabolite solutions measured under the same experimental conditions as the in vivo spectra. The prior knowledge for the in vivo spectra was constructed as follows: for each VARPRO-fitted phantom spectrum one peak (the most prominent one in the in vivo spectrum) was chosen and left unconstrained in the AMARES fitting while all the other peaks in the metabolite spectrum (i.e. their corresponding parameters-amplitudes, damping factors, frequencies and phases) were fixed to the parameter values of the unconstrained peak via amplitude and damping ratios and frequency and phase shifts. Including N-acetylaspartate, glutamate, total creatine, cholines, glucose and myo-inositol into the fits provided results which were in agreement with published data. An inclusion of glutamine into the set of fitted metabolites was also investigated.

Research paper thumbnail of Discrimination of Metabolite from Lipid and Macromolecule Resonances in Cerebral Infarction in Humans Using Short Echo Proton Spectroscopy

Journal of Magnetic Resonance Imaging, Nov 1, 1997

Short-echo proton spectroscopy allows the noninvasive study of metabolites, lipids, and macromole... more Short-echo proton spectroscopy allows the noninvasive study of metabolites, lipids, and macromolecules in stroke patients, but spectra are difficult to interpret and quantify because narrow metabolite peaks are added to a broad background of lipid and macromolecule peaks. "Metabolite nulling" was used to distinguish the lactate peak from underlying lipid and macromolecule peaks. Increases in the lipid and macromolecule peaks were initially observed within the region of infarction in all patients, and further increases in lipid peaks were seen in five of the six patients during the following 6 weeks. The initial high lactate concentration decreases during the first 2 weeks after stroke, whereas lipid and macromolecule signals show a persistent elevation during the same period. Differences in the time courses of the observed changes suggest that lipid, macromolecule, and lactate signals arise from more than one source.

Research paper thumbnail of Continuing Ischemic Damage After Acute Middle Cerebral Artery Infarction in Humans Demonstrated by Short-Echo Proton Spectroscopy

Stroke, Jun 1, 1995

Background and Purpose Proton MR spectroscopy is a noninvasive method of monitoring in vivo metab... more Background and Purpose Proton MR spectroscopy is a noninvasive method of monitoring in vivo metabolite concentration changes over time. The aim of this work was to study the ischemic penumbra in humans by measuring the metabolic changes that occur after a middle cerebral artery territory infarction. Methods Diagnostic MRI and short–echo time MR spectroscopy were performed on a 1.5-T system. Localized proton MR spectroscopy was performed within the area of cerebral infarction and in a homologous area of the contralateral hemisphere. The residual water resonance in the spectra was removed with the use of the Hankel Lanczos singular value decomposition method, after which peak area estimates were obtained by means of the variable projection time domain fitting analysis. The unsuppressed water signal was used as an internal concentration standard. Ten patients with acute middle cerebral artery infarction were studied within 28 hours of stroke onset and followed up for a period of up to 3 months. Results Significant changes were seen in the initial spectra from the infarct compared with the contralateral spectra. Lactate, a marker of anaerobic metabolism, was present within the infarct but not detected in the contralateral hemisphere. N -Acetyl aspartate, a neuronal marker, and total creatine were significantly reduced. The initial choline signal, arising from choline-containing compounds within the cell and cell membrane, remained unchanged in the infarct core compared with the contralateral hemisphere. Further reductions in N -acetyl aspartate and total creatine concentrations occurred within the first week. A fall in the lactate concentration was seen within the infarct core during the first 7 to 10 days. Similar reductions in the choline concentration were observed during this period. Conclusions The demonstration of the continuing loss of cerebral metabolites within an infarct region suggests that further cell loss occurs up to 10 days after infarction. The continuing loss of neurons may represent continued ischemic damage after middle cerebral artery infarction.

Research paper thumbnail of Aging of the adult human brain: In vivo quantitation of metabolite content with proton magnetic resonance spectroscopy

Journal of Magnetic Resonance Imaging, May 1, 1999

The purpose of this study was to examine the effect of aging on brain metabolite concentrations, ... more The purpose of this study was to examine the effect of aging on brain metabolite concentrations, including N-acetyl aspartate (NAA), the major marker of neurones, using short echo proton spectroscopy. Single-voxel proton spectra (TE 30 msec, TR 2 seconds) were obtained from white and gray matter using automated software (PROBE, G.E., Milwaukee, WI). Spectra were analyzed using the variable projection technique. Thirty healthy volunteers were studied within the age range 24-89 years. No significant trend in change of concentrations of NAA, total creatine, total choline or myo-inositol were seen with age. The total creatine concentration of parietal white matter in the over 60 age group (6.5 +/- 0.3 mmol/l) was significantly higher than the under 60 age group (6.0 +/- 0.4 mmol/l:; P < 0.05). No other significant difference between the two age groups was seen. The tissue concentration of the major neuronal marker, NAA, does not decline with age. No age-related changes in the concentrations of choline and myo-inositol and occipital gray matter total creatine were observed. These results provide a normal range of values for spectroscopically detectable metabolites within the regions studied, against which neurological diseases such as Alzheimer's disease can be compared in vivo.

Research paper thumbnail of 31P-Magnetic resonance spectroscopy studies of nucleated and non-nucleated erythrocytes; time domain data analysis (VARPRO) incorporating prior knowledge can give information on the binding of ADP

Biochimica Et Biophysica Acta - General Subjects, Oct 1, 1996

Human erythrocytes have no nucleus, mitochondria or endoplasmic reticulum, whereas chicken erythr... more Human erythrocytes have no nucleus, mitochondria or endoplasmic reticulum, whereas chicken erythrocytes have a nucleus and mitochondria and are closer in internal morphology, to cells such as the hepatocyte. Erythrocytes were used to test the hypothesis that alP-MRS invisibility of ADP is associated with the presence of intracellular organelles. Simple frequency domain spectral analysis methods showed that all the acid extractable ADP (and ATP) was MR-visible in human erythrocytes. However, such methods gave variable estimates for 31p-NMR spectra of fresh chicken erythrocytes from which no conclusions could be drawn about the MR-visibility of ADP. Only when the data were fitted by a method incorporating prior knowledge of the ATP and ADP peak structure, using the time domain VARPRO method, was it possible to conclude that in fresh chicken erythrocytes, similar to other nucleated cells (liver, muscle), all the acid extractable ADP appeared to be MRS invisible, indicating binding or sequestration by intracellular organelles.

Research paper thumbnail of SVD-based quantification of magnetic resonance signals

Journal of magnetic resonance, Mar 1, 1992

Abstract This study concerns the parametrization of NMR signals by state-space modeling (HSVD), w... more Abstract This study concerns the parametrization of NMR signals by state-space modeling (HSVD), which is based on singular value decomposition. It is shown that nonexponential decay can be parametrized by HSVD (and LPSVD). This property is applied to real-world ...

Research paper thumbnail of 31P-magnetic resonance spectroscopy and 2H-magnetic resonance imaging studies of a panel of early-generation transplanted murine tumour models

British Journal of Cancer, Jun 1, 1998

The objective of this study was first to determine whether three slowly growing early-generation ... more The objective of this study was first to determine whether three slowly growing early-generation murine transplantable tumours, the T40 fibrosarcoma, Ti 15 mammary carcinoma and T237 lung carcinoma, exhibit patterns of energetics and blood flow during growth that are different from those of the faster growing RIF-1 fibrosarcoma. Serial measurements were made with 31P-magnetic resonance spectroscopy (MRS), relating to nutritive blood flow and 2H-magnetic resonance imaging (MRI), which is sensitive to both nutritive and largevessel (non-nutritive) flow. All four tumour lines showed a decrease in fiNTP/Pi and pH with growth; however, each line showed a different pattern of blood flow that did not correlate with the decrease in energetics. Qualitative histological analysis strongly correlated with the 2H-MRI. Second, their response to 5 mg kg-' hydralazine i.v. was monitored by 31P-MRS. A marked decrease in f3NTP/Pi and pH was observed in both the RIF-1 fibrosarcoma and the third-generation T115 mammary carcinoma after hydralazine challenge. In contrast, the fourth generation T40 fibrosarcoma and T237 lung carcinoma showed no change in 31P-MRS parameters. However, a fifth-generation T237 cohort, which grew approximately three times faster than fourth-generation T237 cohorts, exhibited a significant deterioration in PNTP/Pi and pH in response to hydralazine. These data are consistent with a decoupling between large-vessel and nutritive blood flow and indicate that earlygeneration transplants that have a slow growth rate and vascular tone are more appropriate models of human tumour vasculature than more rapidly growing, repeatedly transplanted tumours.

Research paper thumbnail of A complete software package for MR signal processing

ABSTRACT Magnetic resonance spectroscopy (MRS) offers a wealth of information to the biochemist o... more ABSTRACT Magnetic resonance spectroscopy (MRS) offers a wealth of information to the biochemist or radiologist. Metabolite concentrations, J-couplings, pH, ion concentrations and gradients, temperature, etc., can all be obtained, in situ, from well-defined volumes in the human body, and in a totally non-invasive way. However, simple methods such as peak area integration or automatic line fitting in the FT MR spectrum are still relied on for routine MRS data analysis. The disadvantages of such methods are tolerated in order to keep processing fast and simple for the spectroscopist. The authors have developed a graphical user interface, in which advanced time domain signal processing methods are combined. They present a complete software package for routine MR data analysis, called MRUI, enabling the use of advanced parameter estimation algorithms with incorporation of prior knowledge via simple menus and spectral displays, in a fashion similar to the spectroscopist's spectrometer software

Research paper thumbnail of The use of continuous regularization in the automated analysis of MRS time-domain data

Journal of magnetic …, 1997

... 7. S. van Huffel, L. Aerts, J. Bervoets, J. Vandewalle, C. Decanniere and P. van Hecke. Signa... more ... 7. S. van Huffel, L. Aerts, J. Bervoets, J. Vandewalle, C. Decanniere and P. van Hecke. Signal Processing VI: Theories and Applications, Elsevier Science, Amsterdam (1992) p. 1721–1724 . 8. JA Cadzow. ... 12. A. Diop, W. Kölbel, D. Michel, A. Briguet and D. Graveron-Demilly. ...

Research paper thumbnail of Absolute metabolite quantification by in vivo NMR spectroscopy: I. introduction, objectives and activities of a concerted action in biomedical research

Magnetic Resonance Imaging, 1998

By utilizing achievements and results of two previous concerted research projects on magnetic res... more By utilizing achievements and results of two previous concerted research projects on magnetic resonance imaging and spectroscopy (MRS), the EU BIOMED 1 Concerted Action on "Cancer and brain disease characterization and therapy assessment by quantitative MRS" was specifically aimed at: 1) developing at a multicentre level harmonized methodologies and protocols for quantitative and reproducible MRS measurements, as a basis for validating these procedures in well controlled clinical and experimental conditions; and 2) providing multicentre critical reviews on the present understanding of the significance of MRS parameters as possible new markers of diagnosis, prognosis and response to therapy. The programme comprised the following main areas of collaborative research and multicentre evaluation: a) development of methods and protocols for quality assessment, calibration and absolute metabolite quantification in in vivo localized, volume-selective MRS; b) design and validation of a new method for assessing localization performance in spectroscopic imaging (MRSI); c) interlaboratory comparison of different methods of signal processing and data analysis, for improving signal quantification in vivo and in vitro MRS spectra; d) quality assessment of high resolution MRS analyses of biological fluids; e) protocol for assembling a pilot data base of MR spectra of tumour extracts for pattern recognition analysis; f) multicentre review on evaluation of the significance of MRS parameters in monitoring lipid metabolism and function in cancer; and g) multicentre review on evaluation of drug pharmacokinetics and metabolism using MRS. The main results and conclusions of four multi-centre trials on items (a), (b) and (c), which involved 24 teams, are reported in the accompanying papers of this series.

Research paper thumbnail of Quantitative data analysis ofin vivoMRS data sets

Magnetic Resonance in Chemistry, 1997

ABSTRACT The different characteristics between frequency domain and time domain analysis techniqu... more ABSTRACT The different characteristics between frequency domain and time domain analysis techniques are detailed for their application to in vivo MRS data sets. With the aim of quantitative analysis of MRS signals, i.e. estimation of parameters in the physical model function that describes the MRS experiment, it is considered desirable to avoid any preprocessing of the data, resulting in a preference for time domain parameter estimation techniques. A historical overview is provided for the time domain analysis methods presented in the literature, and a number of time domain methods are described in detail. Finally, the MRUI software package, providing an interactive graphical user interface for a variety of time domain methods, is summarized. © 1997 John Wiley & Sons, Ltd.

Research paper thumbnail of Quantification of metabolites from single-voxel in vivo NMR data of normal human brain by means of time-domain data analysis

Magn Reson Mater Phys Biol M, 1995

We present here a combination of time-domain signal analysis procedures for quantification of hum... more We present here a combination of time-domain signal analysis procedures for quantification of human brain in vivo 1H NMR spectroscopy (MRS) data. The method is based on a separate removal of a residual water resonance followed by a frequency-selective time-domain line-shape fitting analysis of metabolite signals. Calculation of absolute metabolite concentrations was based on the internal water concentration as a reference. The estimated average metabolite concentrations acquired from six regions of normal human brain with a single-voxel spin-echo technique for the N-acetylaspartate, creatine, and choline-containing compounds were 11.4 +/- 1.0, 6.5 +/- 0.5, and 1.7 +/- 0.2 mumol kg-1 wet weight, respectively. The time-domain analyses of in vivo 1H MRS data from different brain regions with their specific characteristics demonstrate a case in which the use of frequency-domain methods pose serious difficulties.

Research paper thumbnail of Application of time-domain fitting in the quantification ofin vivo1H spectroscopic imaging data sets

NMR in Biomedicine, Jul 1, 1992

Time‐domain model function fitting techniques were applied to improve the reconstruction of metab... more Time‐domain model function fitting techniques were applied to improve the reconstruction of metabolite maps from the data sets obtained from in vivo 1H spectroscopic imaging (SI) experiments. First, residual water‐related signals were removed from the SI data sets by using SVD‐based linear time‐domain fitting based upon the HSVD (State Space) approach. Second, peak integrals of the metabolites of interest were obtained by quantifying the proton spin‐echoes of the voxels by means of non‐linear time‐domain fitting based upon the maximum likelihood principle. Third, in order to save computational time, interpolation of the metabolite images (from size 32 × 32 to 128 × 128) was performed in the image‐domain by applying one‐dimensional cubic splines. It was found that the residual water signals can be almost completely removed from the SI data sets by applying the linear HSVD fitting method. Furthermore, it was found that voxel dependency of certain NMR parameters (e.g., variations of the spin‐echo offset frequencies and/or phase factors) can be accounted for automatically by applying the non‐linear time‐domain fitting technique. For that purpose it appeared to be essential to employ prior knowledge of the NMR spectral parameters.

Research paper thumbnail of Time and frequency domain analysis of NMR data compared: An application to 1D1H spectra of lipoproteins

Magnetic Resonance in Medicine, Apr 1, 1994

A comparison between a time domain analysis algorithm (VARPRO) and a frequency domain analysis al... more A comparison between a time domain analysis algorithm (VARPRO) and a frequency domain analysis algorithm (FITPLA') for parameter estimation of magnetic resonance spectroscopy (MRS) data series is presented. VARPRO analyses the measured MRS signal (free induction decay; FID); FITPLA' analyses the discrete Fourier transform of the FID, the frequency domain magnetic resonance spectrum. A rapid time domain method, used to subtract the dominating water resonance from a 'H MRS FID, without affecting the metabolites of interest, is outlined and applied. Also a new "pseudofrequency selective" approach to time domain fitting is introduced. The possibilities of combining the most favorable features of time and frequency domain processing into one single MRS signal processing method are assessed. The 'H MRS signals of ultracentrifuged very low (VLDL), intermediate (IDL), and high (HDL) density lipoprotein fractions from human blood plasma were used for the comparisons. The results from both algorithms were in good agreement.

Research paper thumbnail of Multicentre quantitative data-analysis trial: the overlapping background problem

Research paper thumbnail of Fast and accurate parameter estimation of noisy complex exponentials with use of prior knowledge

European Signal Processing Conference, 1996

In this paper we address the problem of parameter estimation of magnetic resonance spectroscopy (... more In this paper we address the problem of parameter estimation of magnetic resonance spectroscopy (MRS) signals. MRS signals are modeled as complex exponentials in noise. Iterative methods based on an optimisation procedure can be used for the parameter estimation. We examine which functional we h a ve to minimise and which nonlinear least squares algorithms we h a ve t o u s e in order to attain maximum e ciency and robustness. The in uence of starting values and prior knowledge is examined.

Research paper thumbnail of MRUI Manual v 96.3. A user's guide to the Magnetic Resonance User Interface software package

Research paper thumbnail of Improved Fitting Method for Parameter Estimation of MRS Signals with Prior Knowledge

Research paper thumbnail of Quantitative data analysis ofin vivoMRS data sets

Magnetic Resonance in Chemistry, Dec 1, 1997

ABSTRACT The different characteristics between frequency domain and time domain analysis techniqu... more ABSTRACT The different characteristics between frequency domain and time domain analysis techniques are detailed for their application to in vivo MRS data sets. With the aim of quantitative analysis of MRS signals, i.e. estimation of parameters in the physical model function that describes the MRS experiment, it is considered desirable to avoid any preprocessing of the data, resulting in a preference for time domain parameter estimation techniques. A historical overview is provided for the time domain analysis methods presented in the literature, and a number of time domain methods are described in detail. Finally, the MRUI software package, providing an interactive graphical user interface for a variety of time domain methods, is summarized. © 1997 John Wiley & Sons, Ltd.

Research paper thumbnail of Absolute metabolite quantification by in vivo NMR spectroscopy: V. multicentre quantitative data analysis trial on the overlapping background problem

Magnetic Resonance Imaging, Nov 1, 1998

... The first one was an in vivo 1 H NMR echo signal, taken from the right parietal lobe of a hum... more ... The first one was an in vivo 1 H NMR echo signal, taken from the right parietal lobe of a human brain by using a 20 ms STEAM sequence (supplied by P. Gilligan, J. MacEnri and JT Ennis, The Institute of Radiological Sciences, Dublin). ...

Research paper thumbnail of New approach for quantitation of short echo timein vivo1H MR spectra of brain using AMARES

NMR in Biomedicine, Feb 1, 1998

Short echo time in vivo STEAM 1 H MR spectra (4.7 T, TE=16 ms) of normal rat brain were fitted in... more Short echo time in vivo STEAM 1 H MR spectra (4.7 T, TE=16 ms) of normal rat brain were fitted in the time domain using a VARPRO-like algorithm called AMARES which allows an inclusion of a large amount of prior knowledge. The prior knowledge was derived from phantom spectra of pure metabolite solutions measured under the same experimental conditions as the in vivo spectra. The prior knowledge for the in vivo spectra was constructed as follows: for each VARPRO-fitted phantom spectrum one peak (the most prominent one in the in vivo spectrum) was chosen and left unconstrained in the AMARES fitting while all the other peaks in the metabolite spectrum (i.e. their corresponding parameters-amplitudes, damping factors, frequencies and phases) were fixed to the parameter values of the unconstrained peak via amplitude and damping ratios and frequency and phase shifts. Including N-acetylaspartate, glutamate, total creatine, cholines, glucose and myo-inositol into the fits provided results which were in agreement with published data. An inclusion of glutamine into the set of fitted metabolites was also investigated.

Research paper thumbnail of Discrimination of Metabolite from Lipid and Macromolecule Resonances in Cerebral Infarction in Humans Using Short Echo Proton Spectroscopy

Journal of Magnetic Resonance Imaging, Nov 1, 1997

Short-echo proton spectroscopy allows the noninvasive study of metabolites, lipids, and macromole... more Short-echo proton spectroscopy allows the noninvasive study of metabolites, lipids, and macromolecules in stroke patients, but spectra are difficult to interpret and quantify because narrow metabolite peaks are added to a broad background of lipid and macromolecule peaks. "Metabolite nulling" was used to distinguish the lactate peak from underlying lipid and macromolecule peaks. Increases in the lipid and macromolecule peaks were initially observed within the region of infarction in all patients, and further increases in lipid peaks were seen in five of the six patients during the following 6 weeks. The initial high lactate concentration decreases during the first 2 weeks after stroke, whereas lipid and macromolecule signals show a persistent elevation during the same period. Differences in the time courses of the observed changes suggest that lipid, macromolecule, and lactate signals arise from more than one source.

Research paper thumbnail of Continuing Ischemic Damage After Acute Middle Cerebral Artery Infarction in Humans Demonstrated by Short-Echo Proton Spectroscopy

Stroke, Jun 1, 1995

Background and Purpose Proton MR spectroscopy is a noninvasive method of monitoring in vivo metab... more Background and Purpose Proton MR spectroscopy is a noninvasive method of monitoring in vivo metabolite concentration changes over time. The aim of this work was to study the ischemic penumbra in humans by measuring the metabolic changes that occur after a middle cerebral artery territory infarction. Methods Diagnostic MRI and short–echo time MR spectroscopy were performed on a 1.5-T system. Localized proton MR spectroscopy was performed within the area of cerebral infarction and in a homologous area of the contralateral hemisphere. The residual water resonance in the spectra was removed with the use of the Hankel Lanczos singular value decomposition method, after which peak area estimates were obtained by means of the variable projection time domain fitting analysis. The unsuppressed water signal was used as an internal concentration standard. Ten patients with acute middle cerebral artery infarction were studied within 28 hours of stroke onset and followed up for a period of up to 3 months. Results Significant changes were seen in the initial spectra from the infarct compared with the contralateral spectra. Lactate, a marker of anaerobic metabolism, was present within the infarct but not detected in the contralateral hemisphere. N -Acetyl aspartate, a neuronal marker, and total creatine were significantly reduced. The initial choline signal, arising from choline-containing compounds within the cell and cell membrane, remained unchanged in the infarct core compared with the contralateral hemisphere. Further reductions in N -acetyl aspartate and total creatine concentrations occurred within the first week. A fall in the lactate concentration was seen within the infarct core during the first 7 to 10 days. Similar reductions in the choline concentration were observed during this period. Conclusions The demonstration of the continuing loss of cerebral metabolites within an infarct region suggests that further cell loss occurs up to 10 days after infarction. The continuing loss of neurons may represent continued ischemic damage after middle cerebral artery infarction.

Research paper thumbnail of Aging of the adult human brain: In vivo quantitation of metabolite content with proton magnetic resonance spectroscopy

Journal of Magnetic Resonance Imaging, May 1, 1999

The purpose of this study was to examine the effect of aging on brain metabolite concentrations, ... more The purpose of this study was to examine the effect of aging on brain metabolite concentrations, including N-acetyl aspartate (NAA), the major marker of neurones, using short echo proton spectroscopy. Single-voxel proton spectra (TE 30 msec, TR 2 seconds) were obtained from white and gray matter using automated software (PROBE, G.E., Milwaukee, WI). Spectra were analyzed using the variable projection technique. Thirty healthy volunteers were studied within the age range 24-89 years. No significant trend in change of concentrations of NAA, total creatine, total choline or myo-inositol were seen with age. The total creatine concentration of parietal white matter in the over 60 age group (6.5 +/- 0.3 mmol/l) was significantly higher than the under 60 age group (6.0 +/- 0.4 mmol/l:; P < 0.05). No other significant difference between the two age groups was seen. The tissue concentration of the major neuronal marker, NAA, does not decline with age. No age-related changes in the concentrations of choline and myo-inositol and occipital gray matter total creatine were observed. These results provide a normal range of values for spectroscopically detectable metabolites within the regions studied, against which neurological diseases such as Alzheimer's disease can be compared in vivo.

Research paper thumbnail of 31P-Magnetic resonance spectroscopy studies of nucleated and non-nucleated erythrocytes; time domain data analysis (VARPRO) incorporating prior knowledge can give information on the binding of ADP

Biochimica Et Biophysica Acta - General Subjects, Oct 1, 1996

Human erythrocytes have no nucleus, mitochondria or endoplasmic reticulum, whereas chicken erythr... more Human erythrocytes have no nucleus, mitochondria or endoplasmic reticulum, whereas chicken erythrocytes have a nucleus and mitochondria and are closer in internal morphology, to cells such as the hepatocyte. Erythrocytes were used to test the hypothesis that alP-MRS invisibility of ADP is associated with the presence of intracellular organelles. Simple frequency domain spectral analysis methods showed that all the acid extractable ADP (and ATP) was MR-visible in human erythrocytes. However, such methods gave variable estimates for 31p-NMR spectra of fresh chicken erythrocytes from which no conclusions could be drawn about the MR-visibility of ADP. Only when the data were fitted by a method incorporating prior knowledge of the ATP and ADP peak structure, using the time domain VARPRO method, was it possible to conclude that in fresh chicken erythrocytes, similar to other nucleated cells (liver, muscle), all the acid extractable ADP appeared to be MRS invisible, indicating binding or sequestration by intracellular organelles.

Research paper thumbnail of SVD-based quantification of magnetic resonance signals

Journal of magnetic resonance, Mar 1, 1992

Abstract This study concerns the parametrization of NMR signals by state-space modeling (HSVD), w... more Abstract This study concerns the parametrization of NMR signals by state-space modeling (HSVD), which is based on singular value decomposition. It is shown that nonexponential decay can be parametrized by HSVD (and LPSVD). This property is applied to real-world ...

Research paper thumbnail of 31P-magnetic resonance spectroscopy and 2H-magnetic resonance imaging studies of a panel of early-generation transplanted murine tumour models

British Journal of Cancer, Jun 1, 1998

The objective of this study was first to determine whether three slowly growing early-generation ... more The objective of this study was first to determine whether three slowly growing early-generation murine transplantable tumours, the T40 fibrosarcoma, Ti 15 mammary carcinoma and T237 lung carcinoma, exhibit patterns of energetics and blood flow during growth that are different from those of the faster growing RIF-1 fibrosarcoma. Serial measurements were made with 31P-magnetic resonance spectroscopy (MRS), relating to nutritive blood flow and 2H-magnetic resonance imaging (MRI), which is sensitive to both nutritive and largevessel (non-nutritive) flow. All four tumour lines showed a decrease in fiNTP/Pi and pH with growth; however, each line showed a different pattern of blood flow that did not correlate with the decrease in energetics. Qualitative histological analysis strongly correlated with the 2H-MRI. Second, their response to 5 mg kg-' hydralazine i.v. was monitored by 31P-MRS. A marked decrease in f3NTP/Pi and pH was observed in both the RIF-1 fibrosarcoma and the third-generation T115 mammary carcinoma after hydralazine challenge. In contrast, the fourth generation T40 fibrosarcoma and T237 lung carcinoma showed no change in 31P-MRS parameters. However, a fifth-generation T237 cohort, which grew approximately three times faster than fourth-generation T237 cohorts, exhibited a significant deterioration in PNTP/Pi and pH in response to hydralazine. These data are consistent with a decoupling between large-vessel and nutritive blood flow and indicate that earlygeneration transplants that have a slow growth rate and vascular tone are more appropriate models of human tumour vasculature than more rapidly growing, repeatedly transplanted tumours.

Research paper thumbnail of A complete software package for MR signal processing

ABSTRACT Magnetic resonance spectroscopy (MRS) offers a wealth of information to the biochemist o... more ABSTRACT Magnetic resonance spectroscopy (MRS) offers a wealth of information to the biochemist or radiologist. Metabolite concentrations, J-couplings, pH, ion concentrations and gradients, temperature, etc., can all be obtained, in situ, from well-defined volumes in the human body, and in a totally non-invasive way. However, simple methods such as peak area integration or automatic line fitting in the FT MR spectrum are still relied on for routine MRS data analysis. The disadvantages of such methods are tolerated in order to keep processing fast and simple for the spectroscopist. The authors have developed a graphical user interface, in which advanced time domain signal processing methods are combined. They present a complete software package for routine MR data analysis, called MRUI, enabling the use of advanced parameter estimation algorithms with incorporation of prior knowledge via simple menus and spectral displays, in a fashion similar to the spectroscopist's spectrometer software

Research paper thumbnail of The use of continuous regularization in the automated analysis of MRS time-domain data

Journal of magnetic …, 1997

... 7. S. van Huffel, L. Aerts, J. Bervoets, J. Vandewalle, C. Decanniere and P. van Hecke. Signa... more ... 7. S. van Huffel, L. Aerts, J. Bervoets, J. Vandewalle, C. Decanniere and P. van Hecke. Signal Processing VI: Theories and Applications, Elsevier Science, Amsterdam (1992) p. 1721–1724 . 8. JA Cadzow. ... 12. A. Diop, W. Kölbel, D. Michel, A. Briguet and D. Graveron-Demilly. ...

Research paper thumbnail of Absolute metabolite quantification by in vivo NMR spectroscopy: I. introduction, objectives and activities of a concerted action in biomedical research

Magnetic Resonance Imaging, 1998

By utilizing achievements and results of two previous concerted research projects on magnetic res... more By utilizing achievements and results of two previous concerted research projects on magnetic resonance imaging and spectroscopy (MRS), the EU BIOMED 1 Concerted Action on "Cancer and brain disease characterization and therapy assessment by quantitative MRS" was specifically aimed at: 1) developing at a multicentre level harmonized methodologies and protocols for quantitative and reproducible MRS measurements, as a basis for validating these procedures in well controlled clinical and experimental conditions; and 2) providing multicentre critical reviews on the present understanding of the significance of MRS parameters as possible new markers of diagnosis, prognosis and response to therapy. The programme comprised the following main areas of collaborative research and multicentre evaluation: a) development of methods and protocols for quality assessment, calibration and absolute metabolite quantification in in vivo localized, volume-selective MRS; b) design and validation of a new method for assessing localization performance in spectroscopic imaging (MRSI); c) interlaboratory comparison of different methods of signal processing and data analysis, for improving signal quantification in vivo and in vitro MRS spectra; d) quality assessment of high resolution MRS analyses of biological fluids; e) protocol for assembling a pilot data base of MR spectra of tumour extracts for pattern recognition analysis; f) multicentre review on evaluation of the significance of MRS parameters in monitoring lipid metabolism and function in cancer; and g) multicentre review on evaluation of drug pharmacokinetics and metabolism using MRS. The main results and conclusions of four multi-centre trials on items (a), (b) and (c), which involved 24 teams, are reported in the accompanying papers of this series.

Research paper thumbnail of Quantitative data analysis ofin vivoMRS data sets

Magnetic Resonance in Chemistry, 1997

ABSTRACT The different characteristics between frequency domain and time domain analysis techniqu... more ABSTRACT The different characteristics between frequency domain and time domain analysis techniques are detailed for their application to in vivo MRS data sets. With the aim of quantitative analysis of MRS signals, i.e. estimation of parameters in the physical model function that describes the MRS experiment, it is considered desirable to avoid any preprocessing of the data, resulting in a preference for time domain parameter estimation techniques. A historical overview is provided for the time domain analysis methods presented in the literature, and a number of time domain methods are described in detail. Finally, the MRUI software package, providing an interactive graphical user interface for a variety of time domain methods, is summarized. © 1997 John Wiley & Sons, Ltd.

Research paper thumbnail of Quantification of metabolites from single-voxel in vivo NMR data of normal human brain by means of time-domain data analysis

Magn Reson Mater Phys Biol M, 1995

We present here a combination of time-domain signal analysis procedures for quantification of hum... more We present here a combination of time-domain signal analysis procedures for quantification of human brain in vivo 1H NMR spectroscopy (MRS) data. The method is based on a separate removal of a residual water resonance followed by a frequency-selective time-domain line-shape fitting analysis of metabolite signals. Calculation of absolute metabolite concentrations was based on the internal water concentration as a reference. The estimated average metabolite concentrations acquired from six regions of normal human brain with a single-voxel spin-echo technique for the N-acetylaspartate, creatine, and choline-containing compounds were 11.4 +/- 1.0, 6.5 +/- 0.5, and 1.7 +/- 0.2 mumol kg-1 wet weight, respectively. The time-domain analyses of in vivo 1H MRS data from different brain regions with their specific characteristics demonstrate a case in which the use of frequency-domain methods pose serious difficulties.