Maria Sokół

Role of short TE 1H-MR spectroscopy in monitoring of post-operation irradiated patients

Post-surgical radiation therapy is a routine procedure in the treatment of primary malignant brain tumors. Along with modest therapeutic effects conventional fractionated radiotherapy, in spite of any modifications, produces damage to non-malignant brain tissues lying within the treatment volume, the extent of which depends on radiation dose. Serial 1H-MRS allows non-invasive investigation of tissue metabolic profiles. In the present study the ratios of resonance signals assigned to the major 1H-MRS-visible metabolites (N-acetylaspartate, choline, creatine, inositol, lactate and lipid methylene group) were evaluated before, during and after post-surgical fractionated radiotherapy in brain regions close to and more distant from the tumor bed, receiving different radiation exposures (60 and < 40 Gy, respectively). The study group consisted of ten patients (aged 28-51). A MRI/MRS system (Elscint 2T Prestige) operating at the field strength of 2 T and the proton resonance frequency of 81.3 MHz has been used and the 1H-MR spectra were acquired using single voxel double-spin-echo PRESS sequence with a short TE. The spectra were post-processed with automatic fitting in the frequency domain. It was found that although the metabolite profiles depend on the dose obtained, but other stress factors (like surgery) seem to contribute to the overall picture of the metabolic status of the brain as well. In studies of early irradiation injuries, an increase of choline related ratios may serve rather as cell proliferation indictors than as cell injury ones, whereas the mI/Cr ratio appears as one of the first indicators of local irradiation injury. In order to establish the prognostic marker for early radiation damage, however, it seems necessary to analyze all visible metabolites as well. None of the metabolites separately may serve as such an indicator due to the complexity of tissue metabolism. Interestingly, MRI reveals no changes during the therapy process, whereas the metabolite ratios are being affected in the course of time, thus supporting the presumption that the 1H-MRS is a valuable method of radiation therapy monitoring.

MR Spectroscopic Evaluation of Brain Tissue Damage After Treatment for Pediatric Brain Tumors

PURPOSE The aim of this study was to evaluate the metabolic profile of uninvolved brain tissue after treatment for pediatric brain tumors. MATERIAL A group of 24 patients aged 4-18 years was analyzed after combined treatment for brain tumors. In this group, there were nine medulloblastomas, seven low-grade gliomas, three high-grade gliomas, two ependymomas and three children with conservatively treated diffuse brainstem gliomas. METHODS Short echo-time (TE = 30 ms) point-resolved spectra were acquired using a 2 T clinical scanner (Elscint Prestige). The ratios of signal intensities for N-acetylaspartate (NAA), choline (Cho), myo-inositol (mI), lactate (Lac), and lipids (Lip) were calculated using the creatine (Cr) signal as an internal reference. The spectra were acquired both from the tumor bed and from contralateral uninvolved brain tissue; only control spectra were analyzed. The first examination was made between the third and sixth month after therapy (24 spectra), the second examination occurred 8-12 months after treatment (15 spectra available), and the third was performed approximately 18 months after completion of therapy (eight spectra available). The results were compared using the t-test for dependent samples. RESULTS At all time points, the metabolite ratios showed alterations indicating brain tissue damage. The most important were the decrease of NAA/Cr and increase of Lac/Cr and Lip/Cr ratios. The mean NAA/Cr values were 0.91, 0.91, and 0.86, respectively, for the three examinations, while the Lac/Cr and Lip/Cr values were 1.66, 2.11, 1.19 and 12.24, 12.05, 5.69, respectively. Interestingly, in children with supratentorial tumors, a significant increase in NAA/Cr value was observed (from 0.82 to 1.11 in the first and second examinations, respectively; p = 0.0487), which may be indicative of neuronal function recovery. CONCLUSIONS MRS examinations of uninvolved brain tissue indicate long-lasting metabolic disturbances. However, the NAA/Cr ratio increase may be a sign of at least partial recovery of metabolic function of the brain.

In vivo 1H MR spectra analysis by means of second derivative method.

Short echo time (TE) in vivo PRESS1H MR spectra (2 T. TE = 35 ms) of normal brain were fitted in the frequency domain using the second derivative method. In this approach, local maxima and hidden peaks are found as local minima of spectrum second derivative. The Lorentzian robust minimisation procedure (referred to as maximum likelihood or m-estimate fitting) using Levenburg -Marquardt non-linear fitting engine was applied. Spectral lines were approximated under the assumption of the mixed Lorentzian/Gaussian lineshapes. The same procedure was applied to 18 proton spectra. The number of peaks found within the range of 0.74/4.2 parts per million (ppm) was 52 ± 3 and their positions were almost the same. The fitted lines were assigned on the basis of the J-pattern recalculated for the field strength of 2 T and by comparing the chemical shifts with the shifts in the single compound spectra. The ratios of main metabolites, such as NAA/Cr, Cho/Cr, Cho/NAA and ml/Cr, are in accord with those obtained earlier using the software supplied with the MR imager and the absolute concentrations ofN-acetylaspartate (NAA). choline containing compounds (Cho),myo Inositol (ml), glucose (Gle) and glutamate (Glu) obtained from the fit agree with those reported in literature, which confirms the usefulness of the second derivative method in routine analyses of1H MR brain spectra.

Four-and-one-half years' experience in monitoring of reproducibility of an MR spectroscopy system — application of in vitro results to interpretation of in vivo data

The primary purpose of this work was to assess long‐term in vitro reproducibility of metabolite levels measured using 1H MRS (proton magnetic resonance spectroscopy). The secondary purpose was to use the in vitro results for interpretation of ‘H MRS in vivo spectra acquired from patients diagnosed with Canavan disease. 1H MRS measurements were performed in the period from April 2006 to September 2010. 118 short and 116 long echo spectra were acquired from a stable phantom during this period. Change‐point analysis of the in vitro N‐acetylaspartate levels was exploited in the computation of fT factor (ratio of the actual to the reference N‐acetylaspartate level normalized by the reciprocity principle). This coefficient was utilized in the interpretation of in vivo spectra analyzed using absolute reference technique. The monitored time period was divided into six time intervals based on short echo in vitro data (seven time intervals based on long echo in vitro data) characterized by fT coefficient ranging from 0.97 to 1.09 (based on short echo data) and from 1.0 to 1.11 (based on long echo data). Application of this coefficient to interpretation of in vivo spectra confirmed increased N‐acetylaspartate level in Canavan disease. Long‐term monitoring of an MRS system reproducibility, allowing for absolute referencing of metabolite levels, facilitates interpretation of metabolic changes in white matter disorders. PACS numbers: 87.19.lf, 87.61.Tg, 87.64.K‐, 87.64.kj

Melatonin in Epilepsy: A New Mathematical Model of Diurnal Secretion

Purpose. The main objective of the study was to create a mathematical model that describes the melatonin circadian secretion and, then the functionality of the model was tested by a comparison of the melatonin secretions in children with and without epilepsy. Material and Methods. The patients were divided into the epilepsy group (EG, n = 52) and the comparison group (CG, n = 30). The melatonin level was assessed by a radioimmunoassay method. The diurnal melatonin secretion was described using a nonlinear least squares method. Spearmans rank correlation coefficient was chosen to estimate the dependence of the acquired data. The model reproduces blood concentration profiles and its parameters were statistically analyzed using the Mann-Whitney-Wilcoxon test and logistic regression. Results. The correlation analysis performed for the EG and CG groups showed moderate correlations between age and the melatonin secretion model parameters. Patients with epilepsy are characterized by an increased phase shift of melatonin release.

Bridging the gap between metabolic profile determination and visualization in neurometabolic disorders: a multivariate analysis of proton magnetic resonance in vivo spectra

The purpose of this work was to check the degree of overlap between rare inborn errors of metabolism and other neurological disorders using principal component analysis of proton magnetic resonance spectroscopy (1H MRS) in vivo data. We examined 60 patients (median age of 22 months). Fourteen of them were diagnosed with neurometabolic disorders (three cases of metachromatic leukodystrophy, two cases of Canavan disease, two cases of megalencephalic leukoencephalopathy with subcortical cysts, three cases of mitochondrial cytopathy, one case of nonketotic hyperglycinemia, one case of globoid leukodystrophy, one case of congenital disorders of glycosylation, and one case of ethylmalonic encephalopathy). The remaining 46 patients were diagnosed with epilepsy, cerebral palsy, and developmental delay. Results obtained from principal component analysis of complete unresolved 1H MRS in vivo spectra were interpreted parallelly with LCModel‐derived metabolite levels. The main attention was paid to the following metabolites: N‐acetylaspartate, glutamate + glutamine, creatine, choline, myo‐inositol signal with an uncertain contribution of glycine, and glucose. 1H MRS in vivo coupled with multivariate analysis is an efficient tool in visualization of metabolic abnormalities in several inborn errors of metabolism (metachromatic leukodystrophy, globoid leukodystrophy, megalencephalic leukoencephalopathy with subcortical cysts, and Canavan disease). Copyright

Pattern recognition methods in (1)H MRS monitoring in vivo of normal appearing cerebellar tissue after treatment of posterior fossa tumors.

The objective of this study was to investigate the metabolic responses of normal appearing cerebellar tissue after posterior fossa tumor treatment, and to identify characteristics of the particular treatment method. Moreover, this work examined the metabolic alterations of normal appearing tissue induced by a particular tumor state including resection, stagnation, progression, and recurrence. The studied group consisted of 29 patients treated for posterior fossa tumors. All of them were irradiated with a total dose of 54 Gy at 1.8 Gy/fraction (median values). In addition, 13 underwent chemotherapy, 25 underwent total tumor resection, 18 were tumor-free in control examinations, 5 had a stable disease, and tumor progression or recurrence was observed in 2 and 4 cases, respectively. The 69 spectra, acquired using a MRI/MRS 2T system, were analyzed using Partial Least Squares Discriminant Analysis (PLS-DA) with orthogonal signal correction (OSC) spectral filtering. A significantly elevated spectral region (0.97-1.55 ppm) was observed in patients after total resection in comparison to non-operated subjects. Patients treated with chemotherapy showed an elevated band between 1.15-1.75 and 2.7-3.0 ppm and had decreases in the remaining parts of the spectra. Increases in lactate and decreases in the remaining metabolites were characteristic for the tumor progression/recurrence group. Pattern recognition methods coupled with MRS revealed significant treatment-dependent alterations in normal appearing cerebellar tissue, as well as metabolic changes induced by tumor progression/recurrence.

Reiteration of Hankel singular value decomposition for modeling of complex-valued signal

Modeling signal which forms complex values is a common scientific problem, which is present in many applications, i.e. in medical signals, computer graphics and vision. One of the possible solution is utilization of Hankel Singular Value Decomposition. In the first step complex-valued signal is arranged in a special form called Hankel matrix, which is in the next step decomposed in operation of Singular Value Decomposition. Obtained matrices can be then reformulated in order to get parameters describing system. Basic method can be applied for fitting whole signal but it fails in modeling each particular component of signal. Modification of basic HSVD method, which relies on reiteration and is used for main components, and application of prior knowledge solves presented problem.

Melatonin in Tuberous Sclerosis Complex Analysis Using Modern Mathematical Modeling Methods

Purpose. The aim of the study was to assess melatonin secretion pattern in children with TSC and to compare it with the secretion patterns in children with and without epilepsy. Material and Methods. Melatonin secretion was measured every three hours using the RIA method in four children with recognized TSC. The parameters of the melatonin secretion models were interpreted and compared with those obtained for the patients with epilepsy (n = 76) and the children from the control, nonepileptic group (n = 36). To describe the diurnal melatonin secretion, mathematical model was constructed and nonlinear least squares method with the Levenberg-Marquardt optimization algorithm was applied to approximate its parameters. The dim light melatonin onset (DLMO) parameters were also estimated from the model. Results and Conclusions. Statistically significant differences were found between the TSC melatonin secretion profiles and the nonepileptic control group. The profiles for the epileptic and TSC groups were found to be similar. For the TSC group, though a small one, the variations in the MLT release amplitudes seem to be independent of the total number of seizures; however, the MLT release shift appears to depend on the number of seizures.

Quality Control Procedure Based on Partitioning of NMR Time Series

The quality of the magnetic resonance spectroscopy (MRS) depends on the stability of magnetic resonance (MR) system performance and optimal hardware functioning, which ensure adequate levels of signal-to-noise ratios (SNR) as well as good spectral resolution and minimal artifacts in the spectral data. MRS quality control (QC) protocols and methodologies are based on phantom measurements that are repeated regularly. In this work, a signal partitioning algorithm based on a dynamic programming (DP) method for QC assessment of the spectral data is described. The proposed algorithm allows detection of the change points—the abrupt variations in the time series data. The proposed QC method was tested using the simulated and real phantom data. Simulated data were randomly generated time series distorted by white noise. The real data were taken from the phantom quality control studies of the MRS scanner collected for four and a half years and analyzed by LCModel software. Along with the proposed algorithm, performance of various literature methods was evaluated for the predefined number of change points based on the error values calculated by subtracting the mean values calculated for the periods between the change-points from the original data points. The time series were checked using external software, a set of external methods and the proposed tool, and the obtained results were comparable. The application of dynamic programming in the analysis of the phantom MRS data is a novel approach to QC. The obtained results confirm that the presented change-point-detection tool can be used either for independent analysis of MRS time series (or any other) or as a part of quality control.