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Der Schnittbilddiagnostik geht in der Behandlung onkologischer Erkrankungen des zentralen Nervensystems eine entscheidende Rolle zu. Ausreichende und im klinischen Alltag allgemein umsetzbare Standards für die Bildgebung existieren jedoch bisher nicht, was zu unzureichender Verwertbarkeit entstandener Untersuchungen führen kann. Diese Übersichtsarbeit trägt Empfehlungen zu Zeitpunkten und technischen Anforderungen an unterschiedliche bildgebende Verfahren in der Neuroonkologie zusammen. Typische klinische Situationen von der Erstvorstellung mit Differentialdiagnostik, über die präoperative Bildgebung, Bestrahlungsplanung und bis hin zum Response Assessment werden diskutiert.

The development of clinical trials has led to substantial improvements in the prevention and treatment of many diseases, including brain cancer. Advances in medicine, such as improved surgical techniques, the development of new drugs and devices, the use of statistical methods in research, and the development of codes of ethics, have considerably influenced the way clinical trials are conducted today. In addition, methods from the broad field of artificial intelligence, such as radiomics, have the potential to considerably affect clinical trials and clinical practice in the future. Radiomics is a method to extract undiscovered features from routinely acquired imaging data that can neither be captured by means of human perception nor conventional image analysis. In patients with brain cancer, radiomics has shown its potential for the non-invasive identification of prognostic biomarkers, automated response assessment, and differentiation between treatment-related changes from tumour progression. Despite promising results, radiomics is not yet established in routine clinical practice nor in clinical trials. In this Viewpoint, the European Organization for Research and Treatment of Cancer Brain Tumour Group summarises the current status of radiomics, discusses its potential and limitations, envisions its future role in clinical trials in neuro-oncology, and provides guidance on how to address the challenges in radiomics.

Purpose: Amino acid PET is a useful complement to MRI in a number of clinical settings for the evaluation of brain tumors. However, amino acid PET is rarely used repeatedly over the course of the disease. We reviewed the existing literature on the use of repeated amino acid PET imaging for monitoring primary or secondary brain tumors. Methods: A comprehensive literature search of articles describing the use of longitudinal amino acid PET imaging of brain tumors was performed on PubMed/MEDLINE using multiple search terms. Additional literature was retrieved from the reference lists of identified studies or based on the authors’ personal knowledge and experience. Results: With regard to primary tumors, two main clinical settings were identified in whom the performance of repeated amino acid PET imaging was most commonly assessed. These include the detection of malignant progression of patients with grade II or III glioma characterized according to older WHO classifications, and the early response assessment of various treatment options in glioma patients. For patients with brain metastases, only a few studies were identified using longitudinal amino acid PET for the diagnosis of post-treatment changes after stereotactic radiosurgery. The analyzed studies reported that longitudinal amino acid PET imaging frequently anticipate or even outperform the diagnostic performance provided by conventional MRI in these settings. Conclusions: The available literature suggests that conventional MRI should be accompanied by longitudinal amino acid PET monitoring in these clinical settings. Nevertheless, more reliable evidence derived from larger, prospective multicenter studies is warranted.

The large language model Generative Pretrained Transformer 4th-generation model (GPT-4; OpenAI) allows for the creation of summaries and graphic representations of the course of disease from the reports of various MRI examinations in patients with glioblastomas.

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A variety of neoplastic and nonneoplastic conditions involve the corpus callosum, which may result in a “butterfly” appearance on conventional MRI. Typically, that pattern shows a bilateral and heterogeneous contrast enhancement of the lesion, occasionally with central nonenhancing areas indicating intralesional necrosis. In contrast, anaplastic gliomas may show only minimal or even a lack of contrast enhancement on MRI. We here report neuroimaging findings in a 69-year-old man with a “butterfly” pattern on dynamic FET [O-(2-[18F]-fluoroethyl)-l-tyrosine] PET and the diagnosis of an anaplastic astrocytoma (WHO grade III; IDH-1/−2 wildtype, no 1p/19q co-deletion) but without typical MRI contrast enhancement.

Differentiating brain tumors from nonneoplastic lesions using conventional MRI may be challenging. Clinical symptoms often remain unspecific, and imaging findings from MRI may be inconclusive. We present the case of a 23-year-old woman in whom an MRI suggested a cerebral venous sinus thrombosis. On the other hand, additional atypical MRI findings raised doubts regarding the initial diagnosis. Given the need for a diagnostic procedure with higher sensitivity and specificity for neoplastic tissue, PET with the radiolabeled somatostatin receptor ligand DOTATATE (68Ga-DOTA-d-Phe1-Tyr3-octreotate) was performed. DOTATATE PET facilitated the diagnosis of a falcine meningioma consistent with its value for the differential diagnosis of meningioma.

There is an urgent need for more effective therapies for glioblastoma. Data from a previous unrandomised phase 2 trial suggested that lomustine-temozolomide plus radiotherapy might be superior to temozolomide chemoradiotherapy in newly diagnosed glioblastoma with methylation of the MGMTpromoter. In the CeTeG/NOA-09 trial, we aimed to further investigate the effect of lomustine-temozolomide therapy in the setting of a randomised phase 3 trial.

Despite the excellent capacity of the conventional MRI to image brain tumours, problems remain in answering a number of critical diagnostic questions. To overcome these diagnostic shortcomings, PET using radiolabeled amino acids and perfusion-weighted imaging (PWI) are currently under clinical evaluation. The role of amino acid PET and PWI in different diagnostic challenges in brain tumours is controversial. Based on the literature and experience of our centres in correlative imaging with PWI and PET using O-(2-[18F]fluoroethyl)-l-tyrosine or 3,4-dihydroxy-6-[18F]-fluoro-l-phenylalanine, the current role and shortcomings of amino acid PET and PWI in different diagnostic challenges in brain tumours are reviewed. Literature searches were performed on PubMed, and additional literature was retrieved from the reference lists of identified articles. In particular, all studies in which amino acid PET was directly compared with PWI were included. PWI is more readily available, but requires substantial expertise and is more sensitive to artifacts than amino acid PET. At initial diagnosis, PWI and amino acid PET can help to define a site for biopsy but amino acid PET appears to be more powerful to define the tumor extent. Both methods are helpful to differentiate progression or recurrence from unspecific posttherapeutic changes. Assessment of therapeutic efficacy can be achieved especially with amino acid PET, while the data with PWI are sparse. Both PWI and amino acid PET add valuable diagnostic information to the conventional MRI in the assessment of patients with brain tumours, but further studies are necessary to explore the complementary nature of these two methods.

Despite the fact that MRI has evolved to become the standard method for diagnosis and monitoring of patients with brain tumours, conventional MRI sequences have two key limitations: the inability to show the full extent of the tumour and the inability to differentiate neoplastic tissue from nonspecific, treatment-related changes after surgery, radiotherapy, chemotherapy or immunotherapy. In the past decade, PET involving the use of radiolabelled amino acids has developed into an important diagnostic tool to overcome some of the shortcomings of conventional MRI. The Response Assessment in Neuro-Oncology working group — an international effort to develop new standardized response criteria for clinical trials in brain tumours — has recommended the additional use of amino acid PET imaging for brain tumour management. Concurrently, a number of advanced MRI techniques such as magnetic resonance spectroscopic imaging and perfusion weighted imaging are under clinical evaluation to target the same diagnostic problems. This Review summarizes the clinical role of amino acid PET in relation to advanced MRI techniques for differential diagnosis of brain tumours; delineation of tumour extent for treatment planning and biopsy guidance; post-treatment differentiation between tumour progression or recurrence versus treatment-related changes; and monitoring response to therapy. An outlook for future developments in PET and MRI techniques is also presented.

A 56-year-old woman was initially diagnosed with optic neuritis. However, several “red flags” were present: older age at presentation, no multiple sclerosis suspicious findings on MRI, and negative oligoclonal bands. 68Ga-DOTATATE PET/CT confirmed the differential diagnosis of an optic sheath meningioma. Our case stresses the value of the somatostatin receptor ligand PET/CT in patients with suspected optic neuritis if the diagnostic workup does not support immune-mediated pathogenesis.

O-(2-18F-fluoroethyl)-L-tyrosine (18F-FET) is an established tracer for brain tumour imaging. 18F-FET kinetics in gliomas appear to have potential for tumour grading, but the mechanisms remain unclear. The aim of this study was to explore the relationship between regional cerebral blood flow (rCBF) as measured by arterial spin labelling MRI and the kinetic behaviour of 18F-FET PET in cerebral gliomas.

The aim is to explore the concept of photopenic defects in newly diagnosed glioma patients with the 2 widely used 11C-MET and 18F-FDOPA PET amino acid tracers. Thirty-two 11C-MET and 26 18F-FDOPA PET scans with amino acid PET-negative gliomas were selected in this European multicentric study. Of these gliomas, 16 11C-MET and 10 18F-FDOPA PET scans with photopenic defects were identified, exhibiting lower mean tumor-to-background ratio as compared with isometabolic gliomas (P< 0.001). Gliomas with photopenic defects had no different progression-free survival than isometabolic gliomas in the whole population (P= 0.40), but shorter progression-free survival in the subgroup of World Health Organization grade II IDH-mutant astrocytomas (35 vs 68 months; P= 0.047).

For the development of efficient and safe gene therapy protocols for clinical application it is desirable to determine the tissue dose of vector-mediated therapeutic gene expression noninvasively in vivo. The herpes simplex virus type 1 thymidine kinase gene (HSV-1-tk) has been shown to function as a marker gene for the direct noninvasive in vivo localization of thymidine kinase (TK) expression by positron emission tomography (PET). Using bicistronic or multicistronic gene-expressing cassettes with tk as the PET marker gene, the quantitative analysis of tk gene expression may indirectly indicate the distribution and the level of expression of linked and proportionally coexpressed genes. Here, we describe the construction and functional evaluation of HSV-1 amplicon vectors mediating proportional coexpression of HSV-1-tk as PET marker gene and the enhanced green fluorescent protein gene (gfp) as proof of principle and cell culture marker gene and the Escherichia coli cytosine deaminase (cd) as therapeutic gene. Several double-/triple-gene constructs expressing HSV-1-tk, gfp, and E. coli cd were engineered based on gene fusion or the use of an internal ribosome entry site (IRES). Functional analysis in cell culture (green fluorescent protein [GFP] fluorescence and sensitivity to the prodrugs ganciclovir [GCV] and 5-fluorocytosine [5-FC]) and Western blots were carried out after infection of proliferating rat 9L gliosarcoma and human Gli36 glioma cells with helper virus-free packaged HSV-1 amplicon vectors. To study the ability of PET to differentiate various levels of tk expression noninvasively in vivo, retrovirally transduced and selected populations of rat F98 and human Gli36dEGFR glioma cells with defined levels of proportionally coexpressed tk and gfp genes were grown as subcutaneous tumors in nude rats and nude mice, and tk imaging by PET was performed. To study HSV-1 amplicon vector-mediated gene coexpression in vivo, HSV-1 amplicon vectors bearing coexpression constructs were injected (4 × 107 to 1 × 108 transducing units) into subcutaneously growing Gli36dEGFR gliomas in nude animals, and tk imaging was performed 24 hr later. All vector constructs mediated GFP expression and sensitized 9L and Gli36 cells toward GCV- and 5-FC-mediated cell killing in a drug dose-dependent manner, respectively. The levels of gene expression varied depending on the location of the genes within the constructs indicating the influence of the IRES on the level of expression of the second gene. Moreover, functional proportional coexpression of the PET marker gene HSV-1-tk and the linked therapeutic E. coli cd gene was observed. In selected tumor cell populations, subtle IRES-dependent differences of tk gene expression could be noninvasively distinguished by PET with good correlation between quantitative assays for IRES-dependent attenuated GFP and TK expression in culture and in vivo. After infection of subcutaneously growing gliomas with HSV-1 amplicon vectors, various levels of TK expression were found ranging from 0.011-0.062 percentage injected dose per gram (%ID/g). These values were 4.0- to 5.7-fold lower than positive control tumor cells. TK expression could be imaged by PET in vivo even with the tk gene located at the weak position downstream from the IRES. In conclusion, these HSV-1 amplicon vectors carrying HSV-1-tk as PET marker gene and any linked therapeutic gene will serve an indirect noninvasive assessment of the distribution of therapeutic gene expression by PET. Monitoring the correlation between primary transduction and therapeutic efficiency of a given vector is highly desirable for the development of safe and efficient gene therapy and vector application protocols in clinical applications.

OBJECTIVE To describe a movement disorder characterized by ocular flutter, trunk ataxia, and mild generalized myoclonus associated with anti-GQ1b antibodies. DESIGN Case report. SETTING University hospital. PATIENT A 37-year-old woman presented with rapid, conjugated, and periodic oscillations of the eyes with a strict preponderance for the horizontal plane (ocular flutter); trunk ataxia; and occasional arrhythmic muscle jerks (myoclonus) most pronounced at the neck. RESULTS Brain magnetic resonance imaging results were normal. Cerebrospinal fluid examination revealed mild lymphocytic pleocytosis. Results of extensive serological tests on viral, bacterial, and fungal infections from blood and cerebrospinal fluid samples were unremarkable. Results of screening examinations for neoplasms and paraneoplastic antibodies, including whole-body fludeoxyglucose F18 positron emission tomography, were normal. Positive titers of IgG and IgM anti-GQ1b antibodies were found. CONCLUSIONS This is the first description of an association between the clinical syndrome of ocular flutter, mild stimulus sensitive myoclonus, and trunk ataxia and anti-GQ1b antibodies. The association with ganglioside antibodies lends further support to the notion of an autoimmune-associated pathology of the syndrome.Arch Neurol. 2008;65(5):659-661--

Primary central nervous system vasculitis is confined to the brain and spinal cord. While serological markers of inflammation are usually normal, conventional angiography may confirm the diagnosis. The diagnostic method of choice is central nervous system biopsy. A 57-year-old man suffered from a first generalized epileptic seizure. MRI revealed a contrast-enhancing lesion, and O-(2-[18F]fluoroethyl)-l-tyrosine amino acid PET displayed increased metabolic activity, both findings highly suggestive of a malignant glioma. Surprisingly, histology obtained following stereotactic biopsy revealed small-vessel vasculitis.

The incidence of wound botulism is increasing dramatically among intravenous drug users. Efficient intensive care and early treatment with antitoxin is essential to avoid lethal courses. The clinical picture of botulism is of descending, symmetric, flaccid paralysis. Early symptoms include cranial nerve palsies resulting in blurred vision and diplopia, difficulty in focusing, ptosis, facial weakness, dysphagia, dysphonia, and dysarthria. Because patients presenting with dysarthria and dysphagia will often be seen by an ear, nose and throat specialist initially, this rare but upcoming neurologic disease must be considered in the differential diagnoses.