Simulation of tumor density evolution upon chemotherapy alone or combined with a treatment to reduce lactate levels

In this study, we introduced a mathematical model mimicking as much as possible the evolutions and interactions between glioma and lactate in the brain, in order to test different therapies and administration protocols. We simulated both glioma cell density evolution and lactate concentration, and considered two therapies: chemotherapy and a treatment targeting lactate production. Three different protocols for administrating the therapies were tested. We compared the efficiency of the combined therapies, depending on the administration protocols and the dosage of the drugs, in order to evaluate the importance of controlling lactate production. Results show that the use of an agent to reduce lactate concentration permits one to significantly reduce the dose of the chemotherapeutic drug

Usefulness of Tc-99m Sestamibi studies for monitoring response to therapy in patients with high grade gliomas: a preliminary study

Congrès sous l’égide de la Société Française de Génie Biologique et Médical (SFGBM).National audienceEarly and late Sestamibi studies were acquired in addition to conventional MRI protocol in 14 patients with high-grade gliomas to monitor an antiangiogenic treatment. Global and local indices were deduced from these SPECT studies and were compared with progression free survival (PFS) and overall survival (OS). Variations of intensity in late studies were not correlated with PFS, but were related to OS. This suggests the possible role of Sestamibi for monitoring response to treatment

Thermodynamics in Gliomas: Interactions between the Canonical WNT/Beta-Catenin Pathway and PPAR Gamma

Gliomas cells are the site of numerous metabolic and thermodynamics abnormalities with an increasing entropy rate which is characteristic of irreversible processes driven by changes in Gibbs energy, heat production, intracellular acidity, membrane potential gradient, and ionic conductance. We focus our review on the opposing interactions observed in glioma between the canonical WNT/beta-catenin pathway and PPAR gamma and their metabolic and thermodynamic implications. In gliomas, WNT/beta-catenin pathway is upregulated while PPAR gamma is downregulated. Upregulation of WNT/beta-catenin signaling induces changes in key metabolic enzyme that modify their thermodynamics behavior. This leads to activation pyruvate dehydrogenase kinase 1(PDK-1) and monocarboxylate lactate transporter 1 (MCT-1). Consequently, phosphorylation of PDK-1 inhibits pyruvate dehydrogenase complex (PDH). Thus, a large part of pyruvate cannot be converted into acetyl-CoA in mitochondria and in TCA (tricarboxylic acid) cycle. This leads to aerobic glycolysis despite the availability of oxygen, named Warburg effect. Cytoplasmic pyruvate is, in major part, converted into lactate. The WNT/beta-catenin pathway induces also the transcription of genes involved in cell proliferation, cell invasiveness, nucleotide synthesis, tumor growth, and angiogenesis, such as c-Myc, cyclin D1, PDK. In addition, in gliomas cells, PPAR gamma is downregulated, leading to a decrease in insulin sensitivity and an increase in neuroinflammation. Moreover, PPAR gamma contributes to regulate some key circadian genes. Abnormalities in the regulation of circadian rhythms and dysregulation in circadian clock genes are observed in gliomas. Circadian rhythms are dissipative structures, which play a key role in far-from-equilibrium thermodynamics through their interactions with WNT/beta-catenin pathway and PPAR gamma. In gliomas, metabolism, thermodynamics, and circadian rhythms are tightly interrelated

Analyse comparative et prédictive des données des gliomes de bas grade issues de l'imagerie par résonance magnétique

Introduction Les gliomes de bas grade, de pronostic extrêmement variable, constituent une problématique non résolue de l'imagerie et de l'anatomopathologie. L'objectif de cette étude est d évaluer dans les gliomes de bas grade l articulation et la cohérence des paramètres IRM entre les différentes modalités (Diffusion, Tenseur de Diffusion, Perfusion et de Spectroscopie) et de déterminer des facteurs indépendants prédictifs de chacune des modalités MR à partir des autres modalités. Matériel et Méthodes. Etude prospective sur 7 mois, pour le recrutement de patients présentant un gliome de grade 2 confirmé histologiquement et n ayant reçu aucun traitement oncologique ou stéroïde. Les paramètres évalués sont : ADC (mm2/s), FAmean, CBVmean, CBVmax, rCBVmean, rCBVmax (mL), CBFmean, CBFmax (mL/s), Chol/Cr, Chol/NAA, Lact/Cr, Lip/Cr (mL), Mi. Une analyse statistique univariée puis multivraiée (modèles de régression multiples et logistiques) a été réalisée. Résultat. 31 patients d âge moyen 39,5 ans ont été inclus. L anabolisme membranaire cellulaire tumoral en rapport avec la souffrance neuronale (Chol/NAA) est d une part significativement corrélé avec 1-l hypercellularité ou densité tumorale (diminution du coefficient apparent de diffusion ADC), 2-la désorganisation micro architecturale tissulaire des fibres de la substance blanche (fraction d anisotropie FAmean) et 3-la perfusion capillaire tissulaire tumorale (volume sanguin régional maximal relatif, rCBV max), (P= 0,055 ; 0,001 et <0,001) et d autre part un facteur indépendant prédictif du volume sanguin rCBVmax et de la désorganisation micro architecturale tissulaire, FAmean, (P=0,0017 ; 0,002). L augmentation du métabolisme anaérobie (Lact/Cr), témoignant de la présence de processus ischémiques et de l invasion macrophagique, est significativement corrélée (P <0,001) et un facteur indépendant prédictif du volume sanguin rCBVmax, (P <0,001). La présence de lipides (Lip/Cr), facteur d agressivité tumorale, est significativement corrélée avec le débit sanguin maximal, CBFmax et le volume sanguin rCBVmax (P <0,0022 ; 0,057) et un facteur indépendant prédictif des volumes et débits de la perfusion capillaire tissulaire tumorale, (P <0,057 ; 0,001). Les différentes corrélations établies suivent une relation linéaire monotone positive. La fraction d anisotropie (FA, gradients de diffusion, 25 directions) apparaît comme un indicateur plus pertinent du métabolisme tumoral que l ADC (gradients de diffusion, 3 directions orthogonales et signal moyenné). Conclusion : Cette étude montre une articulation et une cohérence des paramètres entre les différentes modalités IMR utile pour la modélisation descriptive et prédictive des gliomes de bas gradeAMIENS-BU Santé (800212102) / SudocSudocFranceF

On a tumor growth model with brain lactate kinetics

Our aim in this paper is to study a mathematical model for high grade gliomas, taking into account lactates kinetics, as well as chemotherapy and antiangiogenic treatment. In particular, we prove the existence and uniqueness of biologically relevant solutions. We also perform numerical simulations based on di erent therapeutical situations which can be found in the literature. These simulations are consistent with what is expected in these situations

Spectral denoising for MR spectroscopy using noise level function

International audience1H-MRSI (proton Magnetic Resonance Spectroscopic Imaging) is now widely used to assist physicists to analyze and quantify brain metabolites in a noninvasive way. In case of glioma, the brain tissue metabolite composition is not widely different but metabolites concentration are varying depending on the grade of the tumor. In the higher stage of the tumor, new metabolites could be detected such as lactate or lipids in the long and short echo time. These variations appear owing to brain tissue modification generated by the tumoral process and help to classify the tumor in grades. 1H-MRS provides crucial data to feed models in order to estimate the best treatment (surgical, etc). Initially, the spectrum is the result of a large number of acquisitions. With a sufficiently long acquisition time, the resulting signal resulting from about 150 mean filter appears to be very low in noise. Nevertheless in this case acquisition time is too long to envisage the study of different parts of the brain. That is why we need to propose an efficient and robust spectrum denoising method

Une irm semi-générative par IA

International audienceL'Imagerie par Résonance Magnétique (IRM) permet de construire, de façon non-invasive, des représentations visuelles d'une précision inégalable pour différencier des tissus. Une séquence IRM, si précise soit elle, ne peut mettre en évidence la totalité des structures anatomiques et fonctionnelles connues. La production de différentes séquences T1, T2, FLAIR, diffusion, ou encore T2* est nécessaire mais très couteuse en temps machine. En outre, une injection de produit de contraste gadoliné peut être requise, affectant le principe d'une médicine non-invasive. Si la théorie de l'information nous apprend qu'une information robuste est une information redondante, elle nous révèle également qu'il existe des espaces latents de représentation des données éliminant toute redondance. Ce principe de compression, bien connu lors du stockage numérique des données, peut théoriquement être mis à profit dès leur acquisition. Nous proposons un dispositif d'Intelligence Artificielle (IA) permettant de limiter le coût d'examen et l'injection de produit de contraste en générant une partie des contenus IRM de façon synthétique à partir d'un ensemble réduit de séquences. Celui-ci part du principe que les séquences non-acquises présentent un caractère redondant, et se base sur un paradigme récent de synthèse d'images en IA : les réseaux adverses génératifs

Peripheral primitive neuroectodermal tumor of the cauda equina in an elderly patient. Case report.

International audiencePrimitive neuroectodermal tumors (PNETs) are aggressive neoplasms composed predominantly of undifferentiated cells that show evidence of neural differentiation. Although their classification remains disputed, PNETs are recognized as primary tumors in both the central and peripheral nervous systems. These rare tumors usually occur in children or young adults and are typically metastatic to the spinal cord. The authors report the case of a 70-year-old man with no significant medical history, in whom a peripheral PNET was demonstrated that, based on clinical and imaging findings, manifested as a nonspecific intrathecal tumoral process arising from the cauda equina. Although this lesion is rare in the elderly, the authors' case illustrates the importance of making this diagnosis as early as possible so that a treatment plan may be devised. The use of chemotherapy in association with radiotherapy in relation to the resection of the tumor should be reconsidered

3T MRI super-resolution using 3D cycle-consistent generative adversarial network

International audienceHigh-resolution magnetic resonance imaging (MRI) provides detailed anatomical information critical for clinical application diagnosis. However, current MRIs are acquired at clinical resolutions due to the limit of physical, technological, and economic considerations. On the other hand, existing approaches require paired MRI images as training data, which are difficult to obtain on existing datasets when the alignment between high and low-resolution images has to be implemented manually.Within the scope of project, we aim to provide an end-to-end system to solve the super-resolution method on 3D MRI. Our proposed method derives from recent neural network developments and does not require paired data for efficient training. By integrating different models with separated functions, our 3D super-resolution CycleGAN (SRCycleGAN) achieved compelling results on MRI volumes. The output is close with ground-truth, showing a low distortion on different scaling factors. Besides, we also compare our method against different GAN-based methods in this field to highlight the performance