Petra Hnilicová

Clinical correlations of proton magnetic resonance spectroscopy findings in acute phase after mild traumatic brain injury

Abstaract Introduction: Standard brain magnetic resonance imaging (MRI) is typically normal in most patients after mild traumatic brain injury (MTBI). Proton magnetic resonance spectroscopy (1H-MRS) is more sensitive to detect subtle post-traumatic changes. The aim of the study was to evaluate the clinical correlations of these changes in the acute phase (within 3 days) after MTBI. Methods: Twenty-one patients with MTBI and 22 controls were studied. Both groups underwent neuropsychological testing and single-voxel 1H-MRS examination of both frontal lobes and upper brainstem. Results: Significant decrease in NAA was found in both frontal lobes and in NAA/Cre ratio in the right frontal lobe (p < 0.05). Correlation analysis showed a correlation of NAA in the left frontal lobe with Backward Digit Span (p = 0.022) and Stroop test A (p = 0.0034) and a weak correlation with TMT B time (p = 0.046). The NAA/Cre in the right frontal lobe correlated with Stroop test A (p = 0.007) and with the total score of Digit Span (p = 0.016). Lower NAA was found in the upper brainstem (p = 0.0157) in the sub-group of patients with post-traumatic unconsciousness. Conclusions: This study found a correlation of 1H-MRS metabolite changes with cognitive decline and presence or absence of loss of consciousness in the acute phase after MTBI.

Hypothalamic damage in multiple sclerosis correlates with disease activity, disability, depression, and fatigue

Abstract Objectives: Disturbances in the hypothalamo-pituitary axis are supposed to modulate activity of multiple sclerosis (MS). We hypothesised that the extent of HYP damage may determine severity of MS and may be associated with the disease evolution. We suggested fatigue and depression may depend on the degree of damage of the area. Method: 33 MS patients with relapsing-remitting and secondary progressive disease, and 24 age and sex-related healthy individuals (CON) underwent 1H-MR spectroscopy (1H-MRS) of the hypothalamus. Concentrations of glutamate + glutamin (Glx), cholin (Cho), myoinositol (mIns), N-acetyl aspartate (NAA) expressed as ratio with creatine (Cr) and NAA were correlated with markers of disease activity (RIO score), Multiple Sclerosis Severity Scale (MSSS), Depressive-Severity Status Scale and Simple Numerical Fatigue Scale. Results: Cho/Cr and NAA/Cr ratios were decreased and Glx/NAA ratio increased in MS patients vs CON. Glx/NAA, Glx/Cr, and mIns/NAA were significantly higher in active (RIO 1–2) vs non-active MS patients (RIO 0). Glx/NAA and Glx/Cr correlated with MSSS and fatigue score, and Glx/Cr with depressive score of MS patients. In CON, relationships between Glx/Cr and age, and Glx/NAA and fatigue score were inverse. Conclusion: Our study provides the first evidence about significant hypothalamic alterations correlating with clinical outcomes of MS, using 1H-MRS. The combination of increased Glu or mIns with reduced NAA in HYP reflects whole-brain activity of MS. In addition, excess of Glu is linked to severe disease course, depressive mood and fatigue in MS patients, suggesting superiority of Glu over other metabolites in determining MS burden.

Spatial variability and reproducibility of GABA‐edited MEGA‐LASER 3D‐MRSI in the brain at 3 T

The reproducibility of gamma‐aminobutyric acid (GABA) quantification results, obtained with MRSI, was determined on a 3 T MR scanner in healthy adults. In this study, a spiral‐encoded, GABA‐edited, MEGA‐LASER MRSI sequence with real‐time motion–scanner‐instability corrections was applied for robust 3D mapping of neurotransmitters in the brain. In particular, the GABA+ (i.e. GABA plus macromolecule contamination) and Glx (i.e. glutamate plus glutamine contamination) signal was measured. This sequence enables 3D‐MRSI with about 3 cm3 nominal resolution in about 20 min. Since reliable quantification of GABA is challenging, the spatial distribution of the inter‐subject and intra‐subject variability of GABA+ and Glx levels was studied via test–retest assessment in 14 healthy volunteers (seven men–seven women).

Effect of whole-brain irradiation on the specific brain regions in a rat model: Metabolic and histopathological changes

HIGHLIGHTSFractionated whole‐brain irradiation led to metabolic and histopathological changes.Changes in neurotransmission and loss of neuronal viability were detected by MRI.Neurodegeneration and strong astrocytic response was seen 6 months after treatment. ABSTRACT Effect of ionizing radiation on the brain affects neuronal, glial, and endothelial cell population and lead to significant morphological, metabolic, and functional deficits. In the present study we investigated a dose‐ and time‐dependent correlation between radiation‐induced metabolic and histopathological changes. Adult male Wistar rats received a total dose of 35 Gy delivered in 7 fractions (dose 5 Gy per fraction) once per week in the same weekday during 7 consecutive weeks. Proton magnetic resonance spectroscopy (1H MRS), histochemistry, immunohistochemistry and confocal microscopy were used to determine whether radiation‐induced alteration of the brain metabolites correlates with appropriate histopathological changes of neurogenesis and glial cell response in 2 neurogenic regions: the hippocampal dentate gyrus (DG) and the subventricular zone‐olfactory bulb axis (SVZ‐OB axis). Evaluation of the brain metabolites 18–19 weeks after irradiation performed by 1H MRS revealed a significant decrease in the total N‐acetylaspartate to total creatine (tNAA/tCr) ratio in the striatum and OB. A significant decline of gamma‐aminobutyric acid to tCr (GABA/tCr) ratio was seen in the OB and hippocampus. MR revealed absence of gross inflammatory or necrotic lesions in these regions. Image analysis of the brain sections 18–21 weeks after the exposure showed a radiation‐induced increase of neurodegeneration, inhibition of neurogenesis and strong resemblance to the reactive astrogliosis. Results showed that fractionated whole‐brain irradiation led to the changes in neurotransmission and to the loss of neuronal viability in vivo. Metabolic changes were closely associated with histopathological findings, i.e. initiation of neuronal cell death, inhibition of neurogenesis and strong response of astrocytes indicated development of late radiation‐induced changes.

Quantitative evaluation of cerebral white matter in patients with multiple sclerosis using multicomponent T2 mapping

Objects: A standard magnetic resonance imaging (MRI) investigation of white matter (WM) areas with visible or expected pathology does not explain satisfactorily the relation between pathology and clinical outcome. Therefore, we focused on multicomponent T2 mapping of WM with the intention to characterize the WM, including normal-appearing white matter that has normal and prolonged T2 and lesions, including degenerated tissue. Materials and Methods: Twenty-nine patients with clinically diagnosed MS and 27 healthy controls underwent MRI examination. T2 mapping of the WM across the two whole MRI slices was carried out. The relative abundance of biologically relevant T2 regions was correlated with age and the expanded disability status scale (EDSS). Results: The relative abundance of the T2 values of water trapped in myelin increased with age in both healthy subjects (p < 0.05) and MS patients (p < 0.05). The relative abundance of intermediate T2 assigned to intra- and extracellular water decreased with age in both groups (p < 0.05) and with EDSS (p < 0.005) in the MS patients. The mixed water pools with a T2 above 110 ms were not related to age, but strongly increased with EDSS (p < 0.000005). Conclusion: Our results suggest that multicomponent T2 mapping of the WM can be a useful parameter for monitoring the progression of MS in patients.

Increased glutamate and deep brain atrophy can predict the severity of multiple sclerosis

OBJECTIVE In multiple sclerosis (MS), deep grey matter (DGM) atrophy has been recognised as a crucial component of the disease that presents early and it has been associated with disability. Although the precise mechanism underlying grey matter atrophy is unknown, several hypotheses have been postulated. Our previous research pointed to correlations of hypothalamic metabolic alterations with clinical outcomes of MS, therefore we decided to further test the relationship of these alterations with DGM atrophy. METHODS We used 1H-Magnetic Resonance spectroscopy (1H-MRS) of the hypothalamus to test its metabolites in 26 patients with RRMS and 22 healthy age-matched controls. DGM atrophy was evaluated by simple planimetry of third ventricular width on the hypothalamic level (3VW) in T1 weighted MRI pictures. Metabolite ratios of N-acetyl aspartate (NAA), choline (Cho), glutamate and glutamine (Glx), myo-inositol (mIns) and creatine (Cr) were correlated with Multiple Sclerosis Severity Scale (MSSS) and 3VW. RESULTS Metabolite concentrations were compared between patients and controls using multiple regression models allowing for age, 3VW and metabolites. It revealed that the only relevant predictors of MSSS were 3VW and Glx/NAA. At a significance level of P<0.05, a unit increase of 3VW was associated with a 0.35 increase of MSSS, for a typical value of Glx/NAA; P value 0.0039. A unit increase of Glx/NAA was associated with a 0.93 increase of MSSS, for a typical value of atrophy; P value 0.090. There were significant linear correlations between Glx/Cr and MSSS, Glx/NAA and MSSS, and between mIns/NAA and 3VW. CONCLUSIONS The results suggest that both NAA and Glx are associated with neurodegeneration of hypothalamic DGM and severe disease course. Glx related 1H-MRS parameters seem to be superior to other metabolites in determining disease burden, independently of otherwise powerful 3VW planimetry. Significantly increased mIns/NAA in MS patients compared to controls point to gliosis, which parallels the atrophy of hypothalamic DGM.

Proton MR spectroscopic imaging of human glioblastomas at 1.5 Tesla

In this study we evaluated clinical feasibility of proton magnetic resonance spectroscopy metabolite mapping (1H MRSI) by using 1.5 Tesla MR-scanner in 10 patients with high-grade glioblastoma. In vivo 1H MRSI performed with a relatively short scan time of 20 minutes enabled to obtain comprehensive information about metabolic changes in glioblastoma and adjacent tissues namely in the peritumoral edema, in the middle and solid part of the tumor, and in the normal-appearing brain tissue. Spectroscopically it was possible to identify initiation of neuronal cell death in the solid tumorous tissue via decreased N-acetyl-aspartate to creatine ratio (↓ tNAA/tCr) and expanding carcinogenesis reflected in elevated choline ratios (↑ tCho/tCr and tCho/tNAA). We showed also the central necrosis of glioblastoma accompanied by the tissue hypoxia, which were apparent as increased lactate and lipids ratios (↑ Lac/tCr and lip/Lac). Metabolic changes were noticeable also in the peritumoral area, showing the glioblastoma infiltration into the surrounding tissues. In intracranial tumors, 1H MRSI performed on 1.5 Tesla field strength was sufficient to provide information about the stage of carcinogenesis, tumor expansion or necrotization and thus it could be considered as a useful diagnostic tool in oncology.

Anaplastic astrocytoma mimicking progressive multifocal leucoencephalopathy: a case report and review of the overlapping syndromes

BackgroundCo-occurrence of multiple sclerosis (MS) and glial tumours (GT) is uncommon although occasionally reported in medical literature. Interpreting the overlapping radiologic and clinical characteristics of glial tumours, MS lesions, and progressive multifocal leukoencephalopathy (PML) can be a significant diagnostic challenge.Case presentationWe report a case of anaplastic astrocytoma mimicking PML in a 27-year-old patient with a 15-year history of MS. She was treated with interferon, natalizumab and finally fingolimod due to active MS. Follow-up MRI, blood and cerebrospinal fluid examinations, and biopsy were conducted, but only the latter was able to reveal the cause of progressive worsening of patient’s disease.ConclusionsAnaplastic astrocytoma misdiagnosed as PML has not yet been described. We suppose that the astrocytoma could have evolved from a low grade glioma to anaplastic astrocytoma over time, as the tumour developed adjacent to typical MS plaques. The role of the immunomodulatory treatment as well as other immunological factors in the malignant transformation can only be hypothesised. We discuss clinical, laboratory and diagnostic aspects of a malignant GT, MS lesions and PML. The diagnosis of malignant GT must be kept in mind when an atypical lesion develops in a patient with MS.

Nuclear Magnetic Resonance as a Diagnostic Tool in Breast Cancer

Nuclear Magnetic Resonance as a Diagnostic Tool in Breast Cancer The early detection and treatment of breast cancer is of direct benefit to patients. Magnetic resonance imaging (MRI) is a promising modality for detection, diagnosis, and staging of breast cancer. MRI enables two methods: the diffusion-weighted MRI (DW MRI) and the dynamic contrast enhanced MRI (DCE MRI). DW MRI reflects the diffusion of water molecules in the extracellular fluid space and allows the estimation of cellularity and tissue structure. The value of the diffusion of water in tissue is called the apparent diffusion coefficient (ADC). ADC values in malignant lesions are smaller than in benign tissue. DCE MRI yields appropriate pharmacokinetic data of physiological parameters that relate to tissue perfusion, microvascular vessel wall permeability and extracellular volume fraction. Gadolinium based contrast agent is usually used in breast DCE MRI diagnostics. Changes in the post-contrast signal intensity help to distinguish lesions according to characteristically enhanced accumulation of contrast agent. Malignant lesions are characterized by a faster and stronger signal enhancement than benign lesions which relate to their neoangiogenesis. Over the last few years, there has been appreciable interest in the use of magnetic resonance spectroscopy (MRS) for the non-invasive analysis of breast tisue metabolites. One of the spectroscopic hallmarks of the neoplastic process appears to be the presence of total choline signal in the in vivo spectrum. Despite the fact that MRI and MRS achieve excellent results, they are still not so frequently used in comparison to mammography and breast ultrasound.