Applied Precision Cancer Medicine in Neuro-Oncology.

Brain tumours that are refractory to treatment have a poor prognosis and constitute a major challenge in offering effective treatment strategies. By targeting molecular alterations, precision cancer medicine may be a viable option for the treatment of brain tumours. In this retrospective analysis of our PCM platform, we describe the molecular profiling of primary brain tumours from 50 patients. Tumour samples of the patients were examined by a 161-gene next-generation sequencing panel, immunohistochemistry, and fluorescence in situ hybridization (FISH). We identified 103 molecular aberrations in 36 (72%) of the 50 patients. The predominant mutations were TP53 (14.6%), IDH1 (9.7%) and PIK3CA (6.8%). No mutations were detected in 14 (28%) of the 50 patients. IHC demonstrated frequent overexpression of EGFR and mTOR, in 38 (76%) and 35 (70%) patients, respectively. Overexpression of PDGFRa and PDGFRb were less common and detected in 16 and four patients, respectively. For 35 patients a targeted therapy was recommended. In our database, the majority of patients displayed mutations, against which targeted therapy could be offered. Based on our observations, PCM may be a feasible novel treatment approach in neuro-oncology.

[Occipitocervical junction: Aanatomy, craniometry and pathology]. / Okzipitozervikaler Übergang: Anatomie, Kraniometrie und Pathologien.

The occipitocervical junction comprises of the occiput condyles, the atlas, and the axis. The radiological evaluation of this region is supported by craniometric measurement methods which are based on predefined anatomical landmarks. The main pathologies of the occipitocervical junction are traumatic injuries, congenital anomalies or normal variants, infections, arthropathies, and tumors. In this article, the anatomy of the occipitocervical junction as well as the most important craniometric measurement methods are explained. Moreover various pathologies and similar appearing normal variants are presented.

Non-invasive assessment of intratumoral vascularity using arterial spin labeling: A comparison to susceptibility-weighted imaging for the differentiation of primary cerebral lymphoma and glioblastoma.

Using conventional MRI methods, the differentiation of primary cerebral lymphomas (PCNSL) and other primary brain tumors, such as glioblastomas, is difficult due to overlapping imaging characteristics. This study was designed to discriminate tumor entities using normalized vascular intratumoral signal intensity values (nVITS) obtained from pulsed arterial spin labeling (PASL), combined with intratumoral susceptibility signals (ITSS) from susceptibility-weighted imaging (SWI). Thirty consecutive patients with glioblastoma (n=22) and PCNSL (n=8), histologically classified according to the WHO brain tumor classification, were included. MRIs were acquired on a 3T scanner, and included PASL and SWI sequences. nVITS was defined by the signal intensity ratio between the tumor and the contralateral normal brain tissue, as obtained by PASL images. ITSS was determined as intratumoral low signal intensity structures detected on SWI sequences and were divided into four different grades. Potential differences in the nVITS and ITSS between glioblastomas and PCNSLs were revealed using statistical testing. To determine sensitivity, specificity, and diagnostic accuracy, as well as an optimum cut-off value for the differentiation of PCNSL and glioblastoma, a receiver operating characteristic analysis was used. We found that nVITS (p=0.011) and ITSS (p=0.001) values were significantly higher in glioblastoma than in PCNSL. The optimal cut-off value for nVITS was 1.41 and 1.5 for ITSS, with a sensitivity, specificity, and accuracy of more than 95%. These findings indicate that nVITS values have a comparable diagnostic accuracy to ITSS values in differentiating glioblastoma and PCNSL, offering a completely non-invasive and fast assessment of tumoral vascularity in a clinical setting.

Arterial spin-labeling assessment of normalized vascular intratumoral signal intensity as a predictor of histologic grade of astrocytic neoplasms.

BACKGROUND AND PURPOSE: Pulsed arterial spin-labeling is a noninvasive MR imaging perfusion method performed with the use of water in the arterial blood as an endogenous contrast agent. The purpose of this study was to determine the inversion time with the largest difference in normalized intratumoral signal intensity between high-grade and low-grade astrocytomas. MATERIALS AND METHODS: Thirty-three patients with gliomas, histologically classified as low-grade (n = 7) or high-grade astrocytomas (n = 26) according to the World Health Organization brain tumor classification, were included. A 3T MR scanner was used to perform pulsed arterial spin-labeling measurements at 8 different inversion times (370 ms, 614 ms, 864 ms, 1114 ms, 1364 ms, 1614 ms, 1864 ms, and 2114 ms). Normalized intratumoral signal intensity was calculated, which was defined by the signal intensity ratio of the tumor and the contralateral normal brain tissue for all fixed inversion times. A 3-way mixed ANOVA was used to reveal potential differences in the normalized vascular intratumoral signal intensity between high-grade and low-grade astrocytomas. RESULTS: The difference in normalized vascular intratumoral signal intensity between high-grade and low-grade astrocytomas obtained the most statistically significant results at 370 ms (P = .003, other P values ranged from .012-.955). CONCLUSIONS: The inversion time by which to differentiate high-grade and low-grade astrocytomas by use of normalized vascular intratumoral signal intensity was 370 ms in our study. The normalized vascular intratumoral signal intensity values at this inversion time mainly reflect the labeled intra-arterial blood bolus and therefore could be referred to as normalized vascular intratumoral signal intensity. Our data indicate that the use of normalized vascular intratumoral signal intensity values allows differentiation between low-grade and high-grade astrocytomas and thus may serve as a new, noninvasive marker for astrocytoma grading.

[Fetal magnetic resonance imaging of thoracic and abdominal malformations]. / Fetale Magnetresonanztomographie thorakaler und abdomineller Malformationen.

CLINICAL/METHODICAL ISSUE: Diagnosis and differential diagnosis of fetal thoracic and abdominal malformations. STANDARD RADIOLOGICAL METHODS: Ultrasound and magnetic resonance imaging (MRI). METHODICAL INNOVATIONS: In cases of suspected pathologies based on fetal ultrasound MRI can be used for more detailed examinations and can be of assistance in the differential diagnostic process. PERFORMANCE: Improved imaging of anatomical structures and of the composition of different tissues by the use of different MRI sequences. ACHIEVEMENTS: Fetal MRI has become a part of clinical routine in thoracic and abdominal malformations and is the basis for scientific research in this field. PRACTICAL RECOMMENDATIONS: In cases of thoracic or abdominal malformations fetal MRI provides important information additional to ultrasound to improve diagnostic accuracy, prognostic evaluation and surgical planning.

[Indications and technique of fetal magnetic resonance imaging]. / Indikationen und Technik der fetalen Magnetresonanztomographie.

CLINICAL/METHODICAL ISSUE: Evaluation and confirmation of fetal pathologies previously suspected or diagnosed with ultrasound. STANDARD RADIOLOGICAL METHODS: Ultrasound and magnetic resonance imaging (MRI). METHODICAL INNOVATIONS: Technique for prenatal fetal examination. PERFORMANCE: Fetal MRI is an established supplementary technique to prenatal ultrasound. ACHIEVEMENTS: Fetal MRI should only be used as an additional method in prenatal diagnostics and not for routine screening. PRACTICAL RECOMMENDATIONS: Fetal MRI should only be performed in perinatal medicine centers after a previous level III ultrasound examination.

Mirror therapy in lower limb amputees--a look beyond primary motor cortex reorganization.

PURPOSE: Phantom pain in upper limb amputees is associated with the extent of reorganization in the primary sensorimotor cortex. Mirror visual feedback therapy has been shown to improve phantom pain. We investigated the extent of cortical reorganization in lower limb amputees and changes in neural activity induced by mirror therapy. MATERIALS AND METHODS: Eight lower limb amputees underwent 12 sessions of MVFT and functional magnetic resonance imaging (fMRI) of the brain before the first and after the last MVFT session. FMRI sessions consisted of two runs in which subjects were instructed to perform repetitive movement of the healthy and phantom ankle. RESULTS: Before MVFT, the mean phantom pain intensity was 4.6 ± 3.1 on a visual analog scale and decreased to 1.8 ± 1.7 (p = 0.04). We did not observe a consistent pattern of cortical activation in primary sensorimotor areas during phantom limb movements. Following MVFT, increased activity was obtained in the right orbitofrontal cortex during phantom ankle movements. Comparison of cortical activity during movements of the phantom ankle and the intact ankle showed significantly higher activity in the left inferior frontal cortex (pars triangularis). CONCLUSION: These results question the known association between phantom pain and primary sensorimotor reorganization and propose reorganizational changes involving multiple cortical areas in lower limb amputees. Finally, reduction of phantom pain after mirror visual feedback therapy was associated with increased prefrontal cortical activity during phantom ankle movements.

[Functional MRI in schizophrenia. Diagnostics and therapy monitoring of cognitive deficits of schizophrenic patients by functional MRI]. / Funktionelle MRT bei Schizophreniepatienten. Diagnostik und Therapiemonitoring kognitiver Defizite schizophrener Patienten mittels funktioneller MRT.

Cognitive impairments are core psychopathological components of the symptomatic of schizophrenic patients. These dysfunctions are generally related to attention, executive functions and memory. This report provides information on the importance of using functional magnetic resonance imaging (fMRI) for the diagnostics and therapy monitoring of the different subtypes of cognitive dysfunctions. Furthermore, it describes the typical differences in the activation of individual brain regions between schizophrenic patients and healthy control persons. This information should be helpful in identifying the deficit profile of each patient and create an individual therapy plan.