Mathematical Analysis of Membrane Transporters Dynamics: A Calcium Fluxes Case Study.

A tight control of intracellular [Ca[Formula: see text]] is essential for the survival and normal function of cells. In this study we investigate key mechanistic steps by which calcium is regulated and calcium oscillations could occur using in silico modeling of membrane transporters. To do so we give a deterministic description of intracellular Ca[Formula: see text] dynamics using nonlinear dynamics in order to understand Ca[Formula: see text] signaling. We first present the ordinary differential equations (ODEs) system for cell calcium kinetics and make a preliminary work on Sobol indices. We then describe and analyze complex transporters action. Besides, we analyze the whole system. We finally perform numerical simulations and compare our results to real data.

Using mathematics in MRI data management for glioma assesment.

Our aim is to review the mathematical tools usefulness in MR data management for glioma diagnosis and treatment optimization. MRI does not give access to organs variations in hours or days. However a lot of multiparametric data are generated. Mathematics could help to override this paradox, the aim of this article is to show how. We first make a review on mathematical modelling using equations. Afterwards we present statistical analysis. We provide detailed examples in both sections. We finally conclude, giving some clues on in silico models.

Analysis of a Mathematical Model for the Glutamate/Glutamine Cycle in the Brain.

Our aim in this article is to study the well-posedness and properties of a system with delay which is related with brain glutamate and glutamine kinetics. In particular, we prove the existence and uniqueness of nonnegative solutions. We also give numerical simulations and compare their order of magnitude with experimental data.

Revisiting the spectrum of lower motor neuron diseases with snake eyes appearance on magnetic resonance imaging.

BACKGROUND AND PURPOSE: The 'snake eyes' sign refers to bilateral hyperintensities of the anterior horns on axial spinal cord imaging. Based on sporadic reports, it has been associated with a range of lower motor neuron (LMN) syndromes, such as spondylotic amyotrophy and Hirayama disease, as well as spinal cord infarction. The objective of our study was to comprehensively characterize the full diagnostic spectrum of LMN syndromes with this radiological clue and discuss potential aetiological factors. METHODS: A large patient cohort with snake eyes sign and upper limb LMN degeneration was recruited from three French neuromuscular units. Patients underwent detailed electrophysiological, radiological, clinical and anamnestic profiling. RESULTS: Twenty-nine patients were ascertained and followed up for 9.5 ± 8.6 years. The majority of the patients were male (86.2%) with a mean age of 37.3 ± 14.4 years. Symptoms were bilateral in most cases (86.2%). Patients with predominantly proximal and distal deficits were equally represented (44.8% and 55.2%, respectively). A history of preceding trauma or intense physical activity was confirmed in 58.6% of the cases; 27.6% of the patients were given an initial clinical diagnosis of amyotrophic lateral sclerosis (ALS), and 51.7% were originally suspected to have multifocal motor neuropathy. None of the patients developed ALS on longitudinal follow-up. CONCLUSION: The snake eyes sign on magnetic resonance imaging is associated with a wide spectrum of neurological conditions and is more common in young men with a history of strenuous activity or antecedent trauma. The recognition of this syndrome is crucial as many of these patients are initially misdiagnosed with ALS.

Mathematical modeling of metabolism and hemodynamics.

We provide a mathematical study of a model of energy metabolism and hemodynamics of glioma allowing a better understanding of metabolic modifications leading to anaplastic transformation from low grade glioma. This mathematical analysis allows ultimately to unveil the solution to a viability problem which seems quite pertinent for applications to medecine.

Predicting the outcome of grade II glioma treated with temozolomide using proton magnetic resonance spectroscopy.

BACKGROUND: This study was designed to evaluate proton magnetic resonance spectroscopy ((1)H-MRS) for monitoring the WHO grade II glioma (low-grade glioma (LGG)) treated with temozolomide (TMZ). METHODS: This prospective study included adult patients with progressive LGG that was confirmed by magnetic resonance imaging (MRI). Temozolomide was administered at every 28 days. Response to TMZ was evaluated by monthly MRI examinations that included MRI with volumetric calculations and (1)H-MRS for assessing Cho/Cr and Cho/NAA ratios. Univariate, multivariate and receiver-operating characteristic statistical analyses were performed on the results. RESULTS: A total of 21 LGGs from 31 patients were included in the study, and followed for at least n=14 months during treatment. A total of 18 (86%) patients experienced a decrease in tumour volume with a greater decrease of metabolic ratios. Subsequently, five (28%) of these tumours resumed growth despite the continuation of TMZ administration with an earlier increase of metabolic ratios of 2 months. Three (14%) patients did not show any volume or metabolic change. The evolutions of the metabolic ratios, mean(Cho/Cr)(n) and mean(Cho/NAA)(n), were significantly correlated over time (Spearman ρ=+0.95) and followed a logarithmic regression (P>0.001). The evolutions over time of metabolic ratios, mean(Cho/Cr)(n) and mean(Cho/NAA)(n), were significantly correlated with the evolution of the mean relative decrease of tumour volume, mean(ΔV(n)/V(o)), according to a linear regression (P<0.001) in the 'response/no relapse' patient group, and with the evolution of the mean tumour volume (meanV(n)), according to an exponential regression (P<0.001) in the 'response/relapse' patient group. The mean relative decrease of metabolic ratio, mean(Δ(Cho/Cr)(n)/(Cho/Cr)(o)), at n=3 months was predictive of tumour response over the 14 months of follow-up. The mean relative change between metabolic ratios, mean((Cho/NAA)(n)-(Cho/Cr)(n))/(Cho/NAA)(n), at n=4 months was predictive of tumour relapse with a significant cutoff of 0.046, a sensitivity of 60% and a specificity of 100% (P=0.004). CONCLUSIONS: The (1)H-MRS profile changes more widely and rapidly than tumour volume during the response and relapse phases, and represents an early predictive factor of outcome over 14 months of follow-up. Thus, (1)H-MRS may be a promising, non-invasive tool for predicting and monitoring the clinical response to TMZ.

[Multimodal magnetic resonance imaging of brain tumors]. / Imagerie multimodale par résonance magnétique des tumeurs cérébrales.

Magnetic resonance imaging arose as a reference for diagnosis, pre-therapeutic and follow-up of brain tumors. Among parameters obtained from standard MRI (of low specificity), only volumetric growth allows prognostic information. The multiple "advanced" sequences have leaded to increase both sensitivity and specificity of brain MRI. Yet, perfusion-weighted imaging and spectroscopy provide metabolic information, and diffusion tensor imaging and cortical activation provide functional information. Characterization, grading, therapeutic management and follow-up have improved, with prognostic information.

[Medulloblastomas: review]. / Les médulloblastomes: revue générale.

INTRODUCTION: The term of "medulloblastoma" refers to cerebellar tumors belonging to the family of primitive neuro-ectodermic tumors (PNET). Medulloblastomas represent 40% of cerebellar tumors, 15 to 20% of brain tumors and the first cause of malignant brain tumors in childhood. Seventy to 80% of cases are diagnosed in children versus 20 to 30% in adults. UPDATED KNOWLEDGE: Diagnosis is based on clinical and radiological exams, and proved on pathological analysis in association with molecular biology. Treatment comprises surgery, craniospinal radiotherapy except for children under five years of age and chemotherapy according to age and high-risk criteria. Medulloblastoma is a rare case of a central nervous system tumor which is radio- and chemo-sensitive. Treatment goals are, on one hand, to improve the survival rates and, on the other hand, to avoid late neurocognitive, neuroendocrine and orthopedic side effects related to radiation therapy, notably in children. The prognosis is relatively good, with a five year survival rate over 75% after complete resection of a localized tumor although sequelae may still compromise outcome. PERSPECTIVES AND CONCLUSION: Management of patients with medulloblastoma implies a multidisciplinary approach combining the contributions of neurosurgery, neuroradiology, pediatric oncology, neuro-oncology and radiotherapy teams.

[Bing-Neel syndrome revealing Waldenström's macroglobulinemia]. / Syndrome de Bing-Neel révélateur d'une maladie de Waldenström : étude d'un cas et revue de la littérature.

INTRODUCTION: The most frequent neurological complication of Waldenström's macroglobulinemia is IgM-mediated polyneuropathy. Direct tumor cell infiltration of the nervous system is very rare and better known as the "Bing and Neel syndrome". This syndrome relates usually to a meningeal or meningo-myelo-cerebral tumor infiltration. OBSERVATION: A 54-year-old man developed a terminal cauda equina syndrome over several years. MRI disclosed lumbar roots infiltration and lumbar puncture the presence of lymphocytic meningitis with intrathecal synthesis of monoclonal IgM identical to that found in the blood. The bone biopsy revealed a lymphoplasmocytic infiltration consistent with the diagnosis of Waldenström's macroglobulinemia. The final diagnosis was meningeal and lumbar roots infiltration revealing Waldenström's macroglobulinemia. Partial remission was obtained after polychemotherapy with CHOP, rituximab and methotrexate. At the end of the treatment, the patient improved his bladder's control and was able to walk with a stick. DISCUSSION: We reviewed the 35 cases of "Bing and Neel syndrome" we have identified by a PubMed research. The present case report is original by the initial neurological presentation of the disease three years before diagnosis and the successful use of rituximab in the polychemotherapy regimen.

[Phosphorus magnetic resonance spectroscopy: Brain pathologies applications]. / Spectroscopie du phosphore 31 par résonance magnétique : applications en pathologies cérébrales.

Until recent years, brain applications of (31)P magnetic resonance spectroscopy were poor. Arising of clinical high field strength magnets (three Tesla) as well as dedicated brain coils (eg: bird cage), using specific and useful sequences providing appropriate spatial localisation and signal to noise ratio brought highlights on multinuclear spectroscopy. Better understanding of brain metabolism emphasizes the role of phosphoenergetic compounds and its potential issues in tumoral, metabolic and degenerative diseases. In the present paper, we report 1 year of experience and preliminary results for 40 patients as well as review of the literature. By successive in vivo determination and quantitation of numerous metabolites it allows, multinuclear spectroscopy may provide additional information to biomathematical models of brain metabolism.

[Imaging of gliomas]. / Imagerie des gliomes.

The imaging of gliomas, as well as diffuse infiltrative gliomas or as more recently individualized entities, has been profoundly modified these last years. Correlated with the classic morphological MRI, numerous new sequences have appeared that allowed a more metabolic approach of the tumors, such as diffusion, perfusion--related to angiogenesis--and spectroscopy--reflecting metabolic data. Their development in daily practice allows to precise the diagnostic, to definite the more active areas (correlated with the hyperperfused or more metabolic active areas in relation with the Ki67 index) and so optimize the biopsy and/or evaluate the evolution of the lesion. When associated, they allow also and perhaps especially to precise the diagnostic, particularly with other tumoral masses such as lymphomas or metastases that can present misleading patterns, but also with other more benign lesions such as abcesses. Always critically analysed, and reevaluated along the time if necessary, they can sometimes help the histological diagnosis, but never can be used in place of it.

[Clinical interest of fMRI and functional exploration methods of brain activity and interactivity: physical and neurophysiological considerations]. / Intérêt clinique de l'IRMf et des méthodes d'exploration fonctionnelle de l'activité et de l'interactivité cérébrales : considérations physiques et neurophysiologiques.

After having provided a brief reminder of the principle of the blood oxygen level-dependent (BOLD) contrast effect, the physiological bases of brain activity and the concepts of functional integration and effective connectivity, we describe the most recent approaches, which permit to explore brain activity and putative networks of interconnected active areas in order to examine the normal brain physiology and its dysfunctions. We present various methods and studies of brain activity analysis clinically applicable, and we detail the concepts of functional and effective connectivity, which allow to study the cerebral plasticity which occurs at the child's during the maturation (e.g., dyslexia), at the adult during the ageing (e.g., Alzheimer disease), or still in schizophrenia or Parkinson disease. The study of specific circuits in networks has to allow defining in a more realistic way the dynamic of the central nervous system, which underlies various cerebral functions, both in physiological and pathological conditions. This connectivity approach should improve the diagnostic and facilitate the development of new therapeutic strategies.

[Biochemical exploration of energetic metabolism and oxidative stress in low grade gliomas: central and peripheral tumor tissue analysis]. / Exploration biochimique du métabolisme énergétique et du stress oxydant des gliomes de bas grade: analyse du tissu tumoral central et périphérique.

Gliomas represent 50% of primary brain tumors, and their prognosis remains poor despite the advances in diagnosis and therapeutic strategies. Low grade gliomas (LGG) are infiltrative tumors and they constantly undergo malignant transformation. Metabolic exploration of human gliomas in vivo, in animals and by using cell culture models showed important differences between tumor tissues and normal brain tissues, which can provide new markers for diagnosis, prognosis and therapeutic targets. In this study, energetic and oxidant metabolisms were explored in biopsy extracts of LGG obtained from the centre and the periphery of tumors. Metabolic pattern of these tumors was explored and the differences between the centre and the periphery pointed. Our study showed a metabolic heterogeneity between tumors, with hypermetabolic and hypometabolic profiles. Lactate to pyruvate ratio was>1, suggesting that the energy metabolism in LGG is glycolytic in nature, particularly in the centre of the tumors. Peripheral samples of tumors showed increased glucose consumption and cytochrome c oxidase activity. Lipid peroxidation and catalase activity were also increased in the periphery compared to the centre of tumors. A relationship between the main antioxidant and energy metabolism enzymes activities was observed, suggesting that periphery of tumors is more active metabolically and more resistant to free radical injury.

Added Value of Spectroscopy to Perfusion MRI in the Differential Diagnostic Performance of Common Malignant Brain Tumors.

BACKGROUND AND PURPOSE: Perfusion and spectroscopic MR imaging provide noninvasive physiologic and metabolic characterization of tissues, which can help in differentiating brain tumors. We investigated the diagnostic role of perfusion and spectroscopic MR imaging using individual and combined classifiers of these modalities and assessed the added performance value that spectroscopy can provide to perfusion using optimal combined classifiers that have the highest differential diagnostic performance to discriminate lymphomas, glioblastomas, and metastases. MATERIALS AND METHODS: From January 2013 to January 2016, fifty-five consecutive patients with histopathologically proved lymphomas, glioblastomas, and metastases were included after undergoing MR imaging. The perfusion parameters (maximum relative CBV, maximum percentage of signal intensity recovery) and spectroscopic concentration ratios (lactate/Cr, Cho/NAA, Cho/Cr, and lipids/Cr) were analyzed individually and in optimal combinations. Differences among tumor groups, differential diagnostic performance, and differences in discriminatory performance of models with quantification of the added performance value of spectroscopy to perfusion were tested using 1-way ANOVA models, receiver operating characteristic analysis, and comparisons between receiver operating characteristic analysis curves using a bivariate χ2, respectively. RESULTS: The highest differential diagnostic performance was obtained with the following combined classifiers: maximum percentage of signal intensity recovery-Cho/NAA to discriminate lymphomas from glioblastomas and metastases, significantly increasing the sensitivity from 82.1% to 95.7%; relative CBV-Cho/NAA to discriminate glioblastomas from lymphomas and metastases, significantly increasing the specificity from 92.7% to 100%; and maximum percentage of signal intensity recovery-lactate/Cr and maximum percentage of signal intensity recovery-Cho/Cr to discriminate metastases from lymphomas and glioblastomas, significantly increasing the specificity from 83.3% to 97.0% and 100%, respectively. CONCLUSIONS: Spectroscopy yielded an added performance value to perfusion using optimal combined classifiers of these modalities, significantly increasing the differential diagnostic performances for these common brain tumors.

Spine metastasis imaging: review of the literature.

Any malignant neoplasm possesses the capacity to metastasize to the musculoskeletal system. Because the spine is the most frequent site of bone metastasis, imaging must be discussed in cases of cancer. Bone marrow is the main interest in imaging the metastatic process by magnetic resonance, while X-rays allow the study of cortical involvement. This article presents our experience, and a review of the literature, in an overview of the different imaging techniques-X-rays and magnetic resonance-with emphasis on the many difficulties that can be encountered in the diagnosis and monitoring of spinal metastases, allowing a management strategy for diagnosis and follow-up.

[Contribution of proton magnetic resonance spectroscopy to the diagnosis of Balo's concentric sclerosis]. / Intérêt de la spectroscopie par résonance magnétique dans la sclérose concentrique de Balo.

INTRODUCTION: Balo's concentric sclerosis is a neuropathological type of multiple sclerosis characterized by alternating rings of spared myelin and demyelination. Diagnosis is based on MRI, but very few data are available concerning the lesion features using serial proton magnetic resonance spectroscopy (1H-MRS). METHODS: We report 1H-MRS initial findings and disease course in one case of Balo's concentric sclerosis. RESULTS: The first 1H-MRS study of 2 concentric ring-enhanced lesions showed a decreased N-acetyl-aspartate (NAA) peak, an increased choline peak, 2 broad lactate peaks and the presence of a lipid peak at 0.9 ppm. Six months later, 1H-MRS showed a decrease of choline peak, whereas the lactate peak had disappeared. The NAA peak was still at a low level. CONCLUSION: These findings are similar to those reported in demyelinating disorders, such as multiple sclerosis. Thus, in Balo's concentric sclerosis, 1H-MRS may provide neurochemical arguments for inflammation and demyelination, and indicate the severity of axonal damage and recovery.

Merkel cell tumor: report of two cases and review of the literature.

The "Merkel cell carcinoma" is a rare tumor usually occuring in the sun-exposed skin. Its poor prognosis is explained by a high rate of metastasis (one third of the patients at the initial presentation) and a high post-operative recurrence rate. Descriptions of the imaging features of this type of tumor are rare. We present two cases of Merkel cell carcinoma localized to the head region. In the first patient, the lesion involved the soft tissues of the scalp with secondary invasion of the skull and meninges. The second patient had a metastasis to the parietal lobe.

[The sphenoid: tumoral pathology]. / Pathologie tumorale du sphénoïde.

The interest and difficulty of sphenoid tumor imaging relate mainly to its great diversity. Detection may be difficult due to variable tumor size and often misleading clinical data. Because the sphenoid is located at the center of the skull base, tumor extension may be quite variable and difficult to assess, requiring sufficient knowledge of anatomy and imaging features to detect tumor spread, especially retrograde perineural spread, since this has a negative impact on prognosis.

Low-grade gliomas: the challenges of imaging.

WHO grade II gliomas are a major challenge for magnetic resonance imaging (MRI) due to their delayed anaplastic transformation. Today it is possible to individually characterize tumor progression from diagnosis to anaplastic transformation based on the many parameters identified in studies in the literature and the possibility of integrating these data into mathematical models. Early identification of negative morphological and metabolic factors, as well as treatment follow-up, help identify predictive factors of tumor progression, as well as determine treatment response to adapt management of this disease.