Integrating and optimizing tonabersat in standard glioblastoma therapy: A preclinical study.

Glioblastoma (GB), a highly aggressive primary brain tumor, presents a poor prognosis despite the current standard therapy, including radiotherapy and temozolomide (TMZ) chemotherapy. Tumor microtubes involving connexin 43 (Cx43) contribute to glioma progression and therapy resistance, suggesting Cx43 inhibition as a potential treatment strategy. This research aims to explore the adjuvant potential of tonabersat, a Cx43 gap junction modulator and blood-brain barrier-penetrating compound, in combination with the standard of care for GB.

An improved F98 glioblastoma rat model to evaluate novel treatment strategies incorporating the standard of care.

Glioblastoma (GB) is the most common and malignant primary brain tumor in adults with a median survival of 12-15 months. The F98 Fischer rat model is one of the most frequently used animal models for GB studies. However, suboptimal inoculation leads to extra-axial and extracranial tumor formations, affecting its translational value.

Assessment of the effect of therapy in a rat model of glioblastoma using [18F]FDG and [18F]FCho PET compared to contrast-enhanced MRI.

Objective: We investigated the potential of [18F]fluorodeoxyglucose ([18F]FDG) and [18F]Fluoromethylcholine ([18F]FCho) PET, compared to contrast-enhanced MRI, for the early detection of treatment response in F98 glioblastoma (GB) rats.

Methods: When GB was confirmed on T2- and contrast-enhanced T1-weighted MRI, animals were randomized into a treatment group (n = 5) receiving MRI-guided 3D conformal arc micro-irradiation (20 Gy) with concomitant temozolomide, and a sham group (n = 5). Effect of treatment was evaluated by MRI and [18F]FDG PET on day 2, 5, 9 and 12 post-treatment and [18F]FCho PET on day 1, 6, 8 and 13 post-treatment.

Automated MRI based pipeline for segmentation and prediction of grade, IDH mutation and 1p19q co-deletion in glioma.

In the WHO glioma classification guidelines grade (glioblastoma versus lower-grade glioma), IDH mutation and 1p/19q co-deletion status play a central role as they are important markers for prognosis and optimal therapy planning. Currently, diagnosis requires invasive surgical procedures. Therefore, we propose an automatic segmentation and classification pipeline based on routinely acquired pre-operative MRI (T1, T1 postcontrast, T2 and/or FLAIR).

In vivo selection of the MDA-MB-231br/eGFP cancer cell line to obtain a clinically relevant rat model for triple negative breast cancer brain metastasis.

Young triple negative breast cancer (TNBC) patients are at high risk for developing very aggressive brain metastases associated with a poor prognosis and a high mortality rate. Preclinical models that allow follow-up by magnetic resonance imaging (MRI) can contribute to the development of new therapeutic approaches for brain metastasis. To date, preclinical brain tumor research has almost exclusively relied on xenograft mouse models.

Network diffusion modeling predicts neurodegeneration in traumatic brain injury.

Objective: Traumatic brain injury (TBI) is a heterogeneous disease with multiple neurological deficits that evolve over time. It is also associated with an increased incidence of neurodegenerative diseases. Accordingly, clinicians need better tools to predict a patient's long-term prognosis.

Adjuvant therapeutic potential of tonabersat in the standard treatment of glioblastoma: A preclinical F98 glioblastoma rat model study.

Purpose: Even with an optimal treatment protocol, the median survival of glioblastoma (GB) patients is only 12-15 months. Hence, there is need for novel effective therapies that improve survival outcomes. Recent evidence suggests an important role for connexin (Cx) proteins (especially Cx43) in the microenvironment of malignant glioma.

Technical feasibility of [F]FET and [F]FAZA PET guided radiotherapy in a F98 glioblastoma rat model.

Background: Glioblastoma (GB) is the most common primary malignant brain tumor. Standard medical treatment consists of a maximal safe surgical resection, subsequently radiation therapy (RT) and chemotherapy with temozolomide (TMZ). An accurate definition of the tumor volume is of utmost importance for guiding RT.

Is diffuse axonal injury on susceptibility weighted imaging a biomarker for executive functioning in adolescents with traumatic brain injury?

Traumatic brain injury (TBI) is a heterogeneous disorder in which diffuse axonal injury (DAI) is an important component contributing to executive dysfunction. During adolescence, developing brain networks are especially vulnerable to acceleration-deceleration forces. We aimed to examine the correlation between DAI (number and localization) and executive functioning in adolescents with TBI.

Exploration of gray matter correlates of cognitive training benefit in adolescents with chronic traumatic brain injury.

Sustaining a traumatic brain injury (TBI) during adolescence has a profound effect on brain development and can result in persistent executive functioning deficits in daily life. Cognitive recovery from pediatric-TBI relies on the potential of neuroplasticity, which can be fostered by restorative training-programs. However the structural mechanisms underlying cognitive recovery in the immature brain are poorly understood.

New fluoroethyl phenylalanine analogues as potential LAT1-targeting PET tracers for glioblastoma.

The use of O-(2-[F]fluoroethyl)-L-tyrosine ([F]FET) as a positron emission tomography (PET) tracer for brain tumor imaging might have some limitations because of the relatively low affinity for the L-type amino acid transporter 1 (LAT1). To assess the stereospecificity and evaluate the influence of aromatic ring modification of phenylalanine LAT1 targeting tracers, six different fluoroalkylated phenylalanine analogues were synthesized. After in vitro K determination, the most promising compound, 2-[F]-2-fluoroethyl-L-phenylalanine (2-[F]FELP), was selected for further evaluation and in vitro comparison with [F]FET.

The Path Toward PET-Guided Radiation Therapy for Glioblastoma in Laboratory Animals: A Mini Review.

Glioblastoma is the most aggressive and malignant primary brain tumor in adults. Despite the current state-of-the-art treatment, which consists of maximal surgical resection followed by radiation therapy, concomitant, and adjuvant chemotherapy, progression remains rapid due to aggressive tumor characteristics. Several new therapeutic targets have been investigated using chemotherapeutics and targeted molecular drugs, however, the intrinsic resistance to induced cell death of brain cells impede the effectiveness of systemic therapies.

Cognitive training benefit depends on brain injury location in adolescents with traumatic brain injury: a pilot study.

Background: Executive dysfunction after pediatric traumatic brain injury (TBI) has been linked to poor outcomes in school performance, social functioning and employment. The credibility of training-induced cognitive enhancement in TBI is threatened by its limited proof of benefit in executive skills of daily living.

Aim: Our primary aim was to investigate if cognitive intervention for improving impairments in executive functions in the chronic stage of TBI is effective during adolescence.

Species-dependent extracranial manifestations of a brain seeking breast cancer cell line.

Purpose: Metastatic brain tumors pose a severe problem in the treatment of patients with breast carcinoma. Preclinical models have been shown to play an important role in unraveling the underlying mechanisms behind the metastatic process and evaluation of new therapeutic approaches. As the size of the rat brain allows improved in vivo imaging, we attempted to establish a rat model for breast cancer brain metastasis that allows follow-up by 7 tesla (7T) preclinical Magnetic Resonance Imaging (MRI).

Prefrontal and temporal cortical thickness in adolescents with traumatic brain injury.

Aim: To investigate the impact of traumatic injury on the developing prefrontal-temporal adolescent cortex, and correlated brain structural measures with neurocognitive functioning.

Method: Nineteen adolescents (12 males, 7 females, age range: 11-17y, mean 15y 8mo, standard deviation 1y 7mo, median 15y 11mo) with traumatic brain injury (TBI) were included. Cortical thickness of frontal and temporal lobes was assessed using magnetic resonance imaging.

In Vivo DCE-MRI for the Discrimination Between Glioblastoma and Radiation Necrosis in Rats.

Purpose: In this study, the potential of semiquantitative and quantitative analysis of dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) was investigated to differentiate glioblastoma (GB) from radiation necrosis (RN) in rats.

Procedures: F98 GB growth was seen on MRI 8-23 days post-inoculation (n = 15). RN lesions developed 6-8 months post-irradiation (n = 10).

"Unforgettable" - a pictorial essay on anatomy and pathology of the hippocampus.

Unlabelled: The hippocampus is a small but complex anatomical structure that plays an important role in spatial and episodic memory. The hippocampus can be affected by a wide range of congenital variants and degenerative, inflammatory, vascular, tumoral and toxic-metabolic pathologies. Magnetic resonance imaging is the preferred imaging technique for evaluating the hippocampus.

18F-FCho PET and MRI for the prediction of response in glioblastoma patients according to the RANO criteria.

Purpose: In this study, we investigated fluorine-18 fluoromethylcholine (F-FCho) PET and contrast-enhanced MRI for predicting therapy response in glioblastoma (GB) patients according to the Response Assessment in Neuro-Oncology criteria. Our second aim was to investigate which imaging modality enabled prediction of treatment response first.

Materials And Methods: Eleven GB patients who underwent no surgery or debulking only and received concomitant radiation therapy (RT) and temozolomide were included.

Correction: Kinetic Modeling and Graphical Analysis of 18F-Fluoromethylcholine (FCho), 18F-Fluoroethyltyrosine (FET) and 18F-Fluorodeoxyglucose (FDG) PET for the Fiscrimination between High-Grade Glioma and Radiation Necrosis in Rats.

[This corrects the article DOI: 10.1371/journal.pone.

Kinetic Modeling and Graphical Analysis of 18F-Fluoromethylcholine (FCho), 18F-Fluoroethyltyrosine (FET) and 18F-Fluorodeoxyglucose (FDG) PET for the Fiscrimination between High-Grade Glioma and Radiation Necrosis in Rats.

Background: Discrimination between glioblastoma (GB) and radiation necrosis (RN) post-irradiation remains challenging but has a large impact on further treatment and prognosis. In this study, the uptake mechanisms of 18F-fluorodeoxyglucose (18F-FDG), 18F-fluoroethyltyrosine (18F-FET) and 18F-fluoromethylcholine (18F-FCho) positron emission tomography (PET) tracers were investigated in a F98 GB and RN rat model applying kinetic modeling (KM) and graphical analysis (GA) to clarify our previous results.

Methods: Dynamic 18F-FDG (GB n = 6 and RN n = 5), 18F-FET (GB n = 5 and RN n = 5) and 18F-FCho PET (GB n = 5 and RN n = 5) were acquired with continuous arterial blood sampling.

Magnetic resonance imaging of third molars: developing a protocol suitable for forensic age estimation.

Background: Established dental age estimation methods in sub-adults study the development of third molar root apices on radiographs. In living individuals, however, avoiding ionising radiation is expedient. Studying dental development with magnetic resonance imaging complies with this requirement, adding the advantage of imaging in three dimensions.

Estimating blur at the brain gray-white matter boundary for FCD detection in MRI.

Focal cortical dysplasia (FCD) is a frequent cause of epilepsy and can be detected using brain magnetic resonance imaging (MRI). One important MRI feature of FCD lesions is the blurring of the gray-white matter boundary (GWB), previously modelled by the gradient strength. However, in the absence of additional FCD descriptors, current gradient-based methods may yield false positives.