Publications by authors named "Michael O Breckwoldt"

Article Synopsis
  • Glioblastomas are aggressive brain tumors that resist treatment and utilize neuron-tumor connections to promote their growth, with cholinergic neurons playing a key role in this invasion.
  • The study utilized rabies viruses for retrograde tracing to reveal how glioblastomas integrate into brain circuits, showing that radiotherapy can enhance neuron-tumor connectivity, complicating treatment efforts.
  • By disrupting neuron-tumor connections, researchers discovered a potential therapeutic approach that could halt glioblastoma progression, emphasizing the need to target these synapses for better treatment outcomes.
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Objectives: Recurrent glioma is highly treatment resistant due to its metabolic, cellular, and molecular heterogeneity and invasiveness. Tumor monitoring by conventional MRI has shortcomings to assess these key glioma characteristics. Recent studies introduced chemical exchange saturation transfer for metabolic imaging in oncology and assessed its diagnostic value for newly diagnosed glioma.

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Introduction: Mechanical thrombectomy is a highly effective treatment for acute ischemic stroke (AIS) caused by large vessel occlusions (LVO). However, our understanding of the pathophysiology of AIS is still limited, particularly regarding the ischemic microenvironment distal to the occlusion.

Aim: To investigate the relationship between the intracerebral blood pressure (BP) distal to an LVO and clinical and imaging parameters.

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Aim: Peripheral nerve scarring is a severe yet common complication following nerve injury or surgery that can lead to impaired nerve function, including chronic pain and sensory or motor deficits. In this study, we aimed to establish high-resolution magnetic resonance neurography (MRN) to accurately visualize and monitor de novo-formed epineural fibrotic adhesions (EFAs) of the sciatic nerve in a rat nerve injury model.

Methods: Employing an established model to induce overshooting EFA, the study included 3 experimental groups of animals (n = 6 each): a positive control group (PC), an intervention group (IG), and a sham group.

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Article Synopsis
  • Intravital 2P-microscopy facilitates the study of brain tumor behavior in mouse cortex, previously limited by imaging challenges in deep brain areas.
  • The new Deep3P imaging workflow combines microscopy with artificial intelligence, allowing researchers to visualize glioblastoma infiltrating up to 1.2 mm into the brain.
  • The study reveals that glioblastoma primarily invades through blood vessels in the white matter, and identifies potential imaging biomarkers associated with early tumor colonization.
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Background: Gliomas are highly invasive brain neoplasms. MRI is the most important tool to diagnose and monitor glioma but has shortcomings. In particular, the assessment of tumor cell invasion is insufficient.

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Unlabelled: Type I interferons (IFN) are immune-stimulatory cytokines involved in antiviral and antitumor immune responses. They enhance the efficacy of immunogenic anticancer therapies such as radiotherapy by activating both innate and adaptive immune cells. Macrophages are one of the most abundant innate immune cells in the immune microenvironment of melanoma brain metastases (MBM) and can exert potent immune-suppressive functions.

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Article Synopsis
  • Glioblastoma is a really serious brain tumor that's hard to treat, but new methods using the immune system are being tested.
  • Doctors often use MRI scans to see how the tumor is doing, but sometimes it's tough because the treatment can change the brain tissue.
  • A new method called magnetic resonance elastography (MRE) might help by checking how soft the tumor is after treatment, which could show whether the therapy is working better than just looking at the tumor size.
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Background: Concurrent malignant brain tumors in patients with multiple sclerosis (MS) constitute a rare but paradigmatic phenomenon for studying neuroimmunological mechanisms from both molecular and clinical perspectives.

Methods: A multicenter cohort of 26 patients diagnosed with both primary brain tumors and multiple sclerosis was studied for disease localization, tumor treatment-related MS activity, and molecular characteristics specific for diffuse glioma in MS patients.

Results: MS neither predisposes nor protects from the development of gliomas.

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Cerebral organoids recapitulate the structure and function of the developing human brain in vitro, offering a large potential for personalized therapeutic strategies. The enormous growth of this research area over the past decade with its capability for clinical translation makes a non-invasive, automated analysis pipeline of organoids highly desirable. This work presents a novel non-invasive approach to monitor and analyze cerebral organoids over time using high-field magnetic resonance imaging and state-of-the-art tools for automated image analysis.

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Intrinsic brain tumors, such as gliomas are largely resistant to immunotherapies including immune checkpoint blockade. Adoptive cell therapies (ACT) including chimeric antigen receptor (CAR) or T cell receptor (TCR)-transgenic T cell therapy targeting glioma-associated antigens are an emerging field in glioma immunotherapy. However, imaging techniques for non-invasive monitoring of adoptively transferred T cells homing to the glioma microenvironment are currently lacking.

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Substitution of lysine 27 to methionine in histone H3 (H3K27M) defines an aggressive subtype of diffuse glioma. Previous studies have shown that a H3K27M-specific long peptide vaccine (H3K27M-vac) induces mutation-specific immune responses that control H3K27M tumors in major histocompatibility complex-humanized mice. Here we describe a first-in-human treatment with H3K27M-vac of eight adult patients with progressive H3K27M diffuse midline glioma on a compassionate use basis.

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Background: Mechanical thrombectomy (MT) is the standard of care for patients with a stroke and large vessel occlusion. Clot composition is not routinely assessed in clinical practice as no specific diagnostic value is attributed to it, and MT is performed in a standardized 'non-personalized' approach. Whether different clot compositions are associated with intrinsic likelihoods of recanalization success or treatment outcome is unknown.

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Article Synopsis
  • * Research shows that neuroinflammatory lesions in mouse spinal cords lead to significant energy deficits in axons, impacting mitochondrial performance and enzyme levels in the tricarboxylic acid (TCA) cycle.
  • * Enhancing the expression of specific TCA cycle enzymes can help restore energy balance in affected neurons, indicating a potential therapeutic target for treating energy deficiencies in MS.
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Glioblastoma is the most common malignant primary brain tumor with poor overall survival. Magnetic resonance imaging (MRI) is the main imaging modality for glioblastoma but has inherent shortcomings. The molecular and cellular basis of MR signals is incompletely understood.

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Background: Radiological neuro-interventions, especially endovascular stroke treatment (EST), are increasing in case numbers worldwide with increasing occupational radiation exposure. Aim of this study was to define the radiation exposure of neurointerventionalists (NI) during EST and to compare the accumulated dose reaching the left arm with the left temple.

Methods: This is a prospective observational study in a tertiary stroke center conducted between 11/2021 and 07/2022.

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Glioblastoma, the most common and aggressive primary brain tumor type, is considered an immunologically "cold" tumor with sparse infiltration by adaptive immune cells. Immunosuppressive tumor-associated myeloid cells are drivers of tumor progression. Therefore, targeting and reprogramming intratumoral myeloid cells is an appealing therapeutic strategy.

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Objectives: This study aims to evaluate the utility of simultaneous multislice (SMS) acceleration for routine magnetic resonance neurography (MRN) at 3 T.

Materials And Methods: Patients with multiple sclerosis underwent MRN of the sciatic nerve consisting of a standard fat-saturated T2-weighted turbo spin echo (TSE) sequence using integrated parallel acquisition technique (PAT2) acceleration and 2 T2 TSE sequences using a combination of PAT-SMS acceleration (1) to reduce scan time (PAT2-SMS2; SMS-TSE FAST ) and (2) for time neutral increase of in-plane resolution (PAT1-SMS2; SMS-TSE HR ). Acquisition times were 5:29 minutes for the standard T2 TSE, 3:12 minutes for the SMS-TSE FAST , and 5:24 minutes for the SMS-TSE HR .

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Diffuse gliomas, particularly glioblastomas, are incurable brain tumours. They are characterized by networks of interconnected brain tumour cells that communicate via Ca transients. However, the networks' architecture and communication strategy and how these influence tumour biology remain unknown.

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Mitochondria are complex organelles with multifaceted roles in cell biology, acting as signaling hubs that implicate them in cellular physiology and pathology. Mitochondria are both the target and the origin of multiple signaling events, including redox processes and calcium signaling which are important for organellar function and homeostasis. One way to interrogate mitochondrial function is by live cell imaging.

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Background: Magnetic resonance imaging is essential for monitoring people with multiple sclerosis, but the diagnostic value of gadolinium contrast administration in spine magnetic resonance imaging is unclear.

Objective: To assess the diagnostic value of gadolinium contrast administration in spine magnetic resonance imaging follow-up examinations and identify imaging markers correlating with lesion enhancement.

Methods: A total of 65 multiple sclerosis patients with at least 2 spinal magnetic resonance imaging follow-up examinations were included.

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Purpose: Gliomas are intrinsic brain tumors with a high degree of constitutive and acquired resistance to standard therapeutic modalities such as radiotherapy and alkylating chemotherapy. Glioma subtypes are recognized by characteristic mutations. Some of these characteristic mutations have shown to generate immunogenic neoepitopes suitable for targeted immunotherapy.

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Background: Glioblastomas, the most common primary malignant brain tumors, are considered immunologically cold malignancies due to growth in an immune sanctuary site. While peptide vaccines have shown to generate intra-tumoral antigen-specific T cells, the identification of these tumor-specific T cells is challenging and requires detailed analyses of tumor tissue. Several studies have shown that CNS antigens may be transported via lymphatic drainage to cervical lymph nodes, where antigen-specific T-cell responses can be generated.

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Background: Medulloblastomas with chromothripsis developing in children with Li-Fraumeni Syndrome (germline TP53 mutations) are highly aggressive brain tumors with dismal prognosis. Conventional photon radiotherapy and DNA-damaging chemotherapy are not successful for these patients and raise the risk of secondary malignancies. We hypothesized that the pronounced homologous recombination deficiency in these tumors might offer vulnerabilities that can be therapeutically utilized in combination with high linear energy transfer carbon ion radiotherapy.

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