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An intact and dynamic microtubule cytoskeleton is crucial for the development, differentiation, and maintenance of the mammalian cortex. Variants in a host of structural microtubulin-associated proteins have been identified to cause a wide spectrum of malformations of cortical development and alterations of microtubule dynamics have been recognized to cause or contribute to progressive neurodegenerative disorders. TBCD is one of the five tubulin-specific chaperones and is required for reversible assembly of the α-/β-tubulin heterodimer. Recently, variants in TBCD, and one other tubulin-specific chaperone, TBCE, have been identified in patients with distinct progressive encephalopathy with a seemingly broad clinical spectrum. Here, we report the clinical, neuroradiological, and neuropathological features in eight patients originating from the Faroe Islands, who presented with an early onset, progressive encephalopathy with features of primary neurodegeneration, and a homogenous clinical course. These patients were homozygous for a TBCD missense variant c.[3099C>G]; p.(Asn1033Lys), which we show has a high carrier frequency in the Faroese population (2.6%). The patients had similar age of onset as the previously reported patients (n = 24), but much shorter survival, which could be caused by either differences in supportive treatment, or alternatively, that shorter survival is intrinsic to the Faroese phenotype. We present a detailed description of the neuropathology and MR imaging characteristics of a subset of these patients, adding insight into the phenotype of TBCD-related encephalopathy. The finding of a Faroese founder variant will allow targeted genetic diagnostics in patients of Faroese descent as well as improved genetic counseling and testing of at-risk couples.

Bucket foundations, which are large cylindrical structures that are open at the base and closed at the top, recently have attracted much attention in offshore projects. To demonstrate the relationship between the vertical bearing capacity of a bucket foundation relative to the corresponding capacity of the circular plate, several loading tests on small-scale bucket and surface foundations were performed at Aalborg University. In the current research, the modified vertical bearing capacity of circular surface footings was investigated with the reduced friction angle. A linear relationship with reasonable accuracy was found between the relative density and the reduced friction angle.

AIM: Assessment of amino acid transport using PET tracers such as [18F]-fluor-ethyl-thyrosine (FET) is a valuable supplement to routine contrast enhanced structural MRI in the initial and follow up evaluations of patients with brain tumors. MRI blood volume (BV) imaging using dynamic susceptibility contrast (DSC) has also been shown to give important information about tumor angiogenesis. The aim of the study was to investigate the feasibility of simultaneous imaging of structural MRI, angiogenic activity (BV DSC), and metabolic activity (FET) in a short single session using an integrated PET/MRI scanner. METHODS AND MATERIALS: Twenty-five scans were obtained in 22 referred brain tumor patients. A 20 min static simultaneous PET/MRI (Siemens mMR) acquisition 20 min. p.i. of 200 MBq FET was performed. The MRI protocol included axial FLAIR and post-contrast T1 MPRAGE. For BV imaging the contrast agent (0.1-0.2 ml/kg, Gadovist 1 mmol/ml) was administered using a power injector and BV maps were calculated using dedicated software. Metabolically active tumor volume (FET-vol) was defined in tissue as activity > 1.6 x background activity (B), and metabolic activity, Tmax/B, as maximal tumor activity/B. A low-dose CT scan was obtained for attenuation correction. RESULTS: The PET/MRI scans were well-accepted by patients. Fourteen had high grade glioma (glioblastoma n = 9, oligodendroglioma III n = 4, astrocytoma III n = 1), 7 patients had low grade glioma (ganglioglioma =1, brain stem glioma n = 1, astrocytoma II n = 1, pontine glioma, oligodendroglioma n = 2, unspecified n = 1) and one patients has brain metastasis (malignant melanoma). Five patients had been exposed to anti-angiogenetic chemotherapy (Bevacizumab + irinotecan). Median tumor volume was 1.6 ml (range 0-138 ml). Areas with visually increased BV were observed in 15 of 18 scans with metabolically active tumor tissue. Scans with increased BV had significantly larger median FET-vol (4.1 ml vs 0 ml, p < 0.0005) and median Tmax/B (2.5 vs 1.4, p < 0.005) compared to those with without increased BV. Excluding scans without metabolically active tumor tissue, neither FET-vol nor Tmax/B was different. There was a high variability in the regional signals observed using FLAIR, FET PET, BV, and post-contrast T1, and poor spatial congruence between FET and BV. The fraction of scans with and without increased BV was not related to tumor grade or exposure to Bevacizumab. CONCLUSION: In the clinical management of brain tumors a simultaneous and comprehensive evaluation of structure, metabolism and blood volume is feasible in a short single session FET PET/MRI DSC scan yielding complementary high quality information. This modality may provide valuable insight into tumor biology and increase the overall diagnostic quality, decrease clinical decision time, and increase acceptance of PET imaging with patients and treating clinicians in clinical management and in trials.