Purpose: To evaluate the usefulness of MRI detection of hypointensity areas (iron deposits) in the brain using a dedicated MRI technique in patients with ALS in establishing this sign as a potential surrogate biomarker that correlates with the severity of disease.Materials and Methods: Forty‐six ALS patients and 26 age‐matched controls were examined by MRI. The ALS Functional Rating Scale (ALSFRS) score was determined before the first MRI examination. The sub‐set of 25 ALS patients was re‐examined around 6 months after the first MRI examination. The MRI examination consisted of routine T1W, T2W, and FLAIR sequences with the addition of a thin slice heavily T2* weighted sequence to accentuate magnetic susceptibility artifacts.Results: T2*W sequence is superior to any other MRI sequence in detecting hypointensities in the brain of ALS patients. Hypointensities were found only in the precentral gyruses gray matter (PGGM) and were detected in 42 patients. The extent of hypointensities was measured and scored (0–3) and correlated with ALSFRS (r = −0.545). Twenty‐five patients were re‐examined 6 months later, and the majority of them showed the shift toward higher MRI scores. No control subjects had hypointensities in PGGM.Conclusion: The detection of hypointensities in PGGM appears to be a very promising surrogate MRI biomarker for ALS due to its simplicity, high sensitivity and specificity, suitability for longitudinal studies, and relationship with the pathogenesis of the disease. J. Magn. Reson. Imaging 2013;38:1472–1479.

Summary: The partial alpha emitting lanthanide isotope ¹⁴⁹Tb seems to have a great potential in systemic radioimmuno therapy (RIT), especially when single cells in transit or circulation are targeted. The isotope ¹⁴⁹Tb has a half life of 4.118 h and decays by alpha emission (3.97 MeV, 17%) EC-process (76%) and β⁺-emission (7%). In this paper, we analyze the possible production routes: light- and heavy ion induced nuclear reactions and p-induced spallation. The excitation functions for light- and heavy ion induced reactions have been calculated using the ALICE91 code. The direct nuclear reaction ¹⁵²Gd (p, 4n) ¹⁴⁹Tb was found to be the most promising production path. Alternatively, the indirect reaction ¹⁴²Nd (¹²C, 5n) ¹⁴⁹Dy → ¹⁴⁹Tb seems to be much more suitable compared to the reaction on the mono-isotopic target element ¹⁴¹Pr ¹²C, 4n) ¹⁴⁹Tb. In this case, both, the production yield of ¹⁴⁹Tb and the radionuclidic purity are considerably lower, compared to the (p, 4n)-reaction. In preliminary experiments we produced ¹⁴⁹Tb via the indirect reaction Nd (¹²C, 5n) ¹⁴⁹Dy → ¹⁴⁹Tb (108 MeV ¹²C⁺⁶ ions and 1 particle-µA) at the U-200 heavy ion cyclotron at the FLNR of the JINR Dubna. From a 1.25 h irradiation of a 12 mg/cm^{2 nat}Nd₂O₃ target, we obtained 2.7 MBq of ¹⁴⁹Tb (70 µCi) at 20 min EOB. This allows the conclusion, that a dedicated cyclotron equipped with a modern ECR-ion source, providing high ion currents would allow the continuous production of batches of the order of 10–20 GBq of ¹⁴⁹Tb for routine RI-therapy. The lower cross section of the spallation process can be compensated by using very thick targets. On-line mass separation technique provides high purity isotopically clean ¹⁴⁹Tb preparations, independently on the production route chosen. At the ISOLDE facility at CERN, we prepared batches of up to 500 MBq ¹⁴⁹Tb by combining on-line mass separation process followed by a cation exchange chromatography process using α-HIBA as eluent. The obtained ¹⁴⁹Tb preparations showed excellent behavior in labeling of chelated monoclonal antibodies.

Introduction: Migraine with aura (MwA) is a neurological condition manifested in moderate to severe headaches associated with transient visual and somatosensory symptoms, as well as higher cortical dysfunctions. Considering that about 5% of the world’s population suffers from this condition and manifestation could be abundant and characterized by various symptoms, it is of great importance to focus on finding new and advanced techniques for the detection of different phenotypes, which in turn, can allow better diagnosis, classification, and biomarker validation, resulting in tailored treatments of MwA patients.Methods: This research aimed to test different machine learning techniques to distinguish healthy people from those suffering from MwA, as well as people with simple MwA and those experiencing complex MwA. Magnetic resonance imaging (MRI) post-processed data (cortical thickness, cortical surface area, cortical volume, cortical mean Gaussian curvature, and cortical folding index) was collected from 78 subjects [46 MwA patients (22 simple MwA and 24 complex MwA) and 32 healthy controls] with 340 different features used for the algorithm training.Results: The results show that an algorithm based on post-processed MRI data yields a high classification accuracy (97%) of MwA patients and precise distinction between simple MwA and complex MwA with an accuracy of 98%. Additionally, the sets of features relevant to the classification were identified. The feature importance ranking indicates the thickness of the left temporal pole, right lingual gyrus, and left pars opercularis as the most prominent markers for MwA classification, while the thickness of left pericalcarine gyrus and left pars opercularis are proposed as the two most important features for the simple and complex MwA classification.Discussion: This method shows significant potential in the validation of MwA diagnosis and subtype classification, which can tackle and challenge the current treatments of MwA.

Petrusic I, et al. Korean J Radiol. 2018 Jul-Aug;19(4):767-776. https://doi.org/10.3348/kjr.2018.19.4.767