In vitro proton magnetic resonance spectroscopy at 14T for benign and malignant ovary: Part I, signal processing by the nonparametric fast Padé transform

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.

Metabolite Alternations in the Dopamine Circuit Associated with Methamphetamine-Related Psychotic Symptoms: A Proton Magnetic Resonance Spectroscopy Study

Objective: Chronic METH use results in neurodegenerative alternations in the human brain. The present study aimed to assess the long-term METH impact on brain metabolite concentrations in cases meeting the DSM-5 criteria regarding METH use. Method: We recruited 42 METH users meeting the DSM-5 criteria and 21 healthy controls. Psychotic signs were measured using the Positive and Negative Syndrome Scale (PANSS). Proton magnetic resonance spectroscopy (1HMRS) evaluating Myo-inositol (Ml), Choline (Cho), Glutamine plus Glutamate (Glx), N-acetyl aspartate (NAA), and Creatine (Cre) were obtained in the dopaminergic pathway (Frontal Cortex, Substantia nigra, Ventral Tegmental Area (VTA), Nucleus Accumbens (NAc), Hippocampus, Striatum,) the subjects. All participants collected urine specimens for 24 hours to measure presence of specific metabolites including METH metabolite level, 5-Hydroxy indoleacetic acid metabolite (for serotonin level monitoring), and metanephrine metabolite (for dopamine level monitoring). Results: Dopamine and Serotonin increased in the METH group (P < 0.001). METH caused an increase in the Cre (P < 0.001) and a decline in the Glx (P < 0.001), NAA (P = 0.008), and MI (P < 0.001) metabolite concentrations of dopamine circuits in METH users in comparison with healthy subjects. We found no change in Cho metabolite concentration. Psychological data and the neurometabolite concentrations in the studied area of the brain were significantly correlated. Conclusion: There is an association between METH use and active neurodegeneration in the dopamine circuit, and it causes serious mental illness. 1HMRS can detect patient’s deterioration and progression of disease as well as follow-up management in patients with METH use disorder.

Metabolic changes in the brain in children with cognitive epileptiform disintegration revealed by proton magnetic resonance spectroscopy

Introduction. Cognitive epileptiform disintegration is a complex of disorders of higher mental functions in a person with a pathological EEG pattern characteristic of epilepsy. In this case, the patient should not have epileptic seizures or a history of single seizures is allowed. The study of biomarkers of the pathological condition under consideration using proton magnetic resonance spectroscopy as indicators that can be objectively evaluated and measured determines the practical relevance of this work.The aim of the study was to determine the diagnostic significance of the metabolites of N-acetylaspartate, choline and creatine according to proton magnetic resonance spectroscopy in the brain of children with cognitive epileptiform disintegration. Material and methods. Using routine MRI and proton magnetic resonance spectroscopy, 6 children with a diagnosis of mental retardation, cognitive epileptiform disintegration at the age of 2 to 7 years (5 boys; 1 girl) were examined. The patients underwent EEG followed by identification of a typical QED pattern. All children had no history of seizures characteristic of epilepsy. Results. А decrease in the ratio of the concentration of NAA/Cr (p<0,05) in the temporal lobes on both sides and the hippocampus on the right was revealed, due to a decrease in the concentration of N-acetylaspartate. There is also an increase in the Cho/NAA concentration ratio (p<0,05) in the hippocampus on the right, and an increase in the Cho/Cr concentration ratio (p<0,05) in the prefrontal cortex, postcentral gyri on both sides, the temporal lobe on the right and the region of the inner capsule on the left, by increasing the concentration of choline. Conclusions. Тhe obtained data suggest that changes in neurometabolism in the cholinergic system in children with cognitive epileptiform disintegration are possibly caused by damage to neuronal connections, mainly in the hippocampus and temporal lobes.

Sex-specific maturation of muscle metabolites carnosine, creatine and carnitine over puberty: a longitudinal follow-up study

Due to the invasiveness of a muscle biopsy, there is fragmentary information on the existence and possible origin of a sexual dimorphism in the skeletal muscle concentrations of the energy delivery-related metabolites carnosine, creatine and carnitine. As these metabolites can be non-invasively monitored by proton magnetic resonance spectroscopy, this technique offers the possibility to investigate if sexual dimorphisms are present in an adult reference population and if these dimorphisms originated during puberty using a longitudinal design. Concentrations of carnosine, creatine and carnitine were examined using proton magnetic resonance spectroscopy in the soleus and gastrocnemius muscles of an adult reference population of female (n=50) and male adults (n=50). For the longitudinal follow-up over puberty, 29 boys and 28 girls were scanned pre-puberty. Six years later, 24 boys and 24 girls were rescanned post-puberty. A sexual dimorphism was present in carnosine and creatine, but not carnitine, in the adult reference population. Carnosine was 28.5% higher in the gastrocnemius (P<0.001) and carnosine and creatine were respectively 19.9% (P<0.001) and 18.2% (P<0.001) higher in the soleus of male, when compared to female adults. Through puberty, carnosine increased more in male subjects in comparison to female subjects, both in the gastrocnemius (+10.43 and -10.83%, respectively; interaction effect: P=0.002) and in the soleus (+24.30 and +5.49%, respectively; interaction effect: P=0.012). No significant effect of puberty was found in either creatine (interaction effect: P=0.307) or carnitine (interaction effect: P=0.066). A sexual dimorphism in the adult human muscle is present in carnosine and creatine, but not in carnitine.