Medical Biology - Research Publications

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    An artificial dielectric slab for ultra high-field MRI: Proof of concept.
    Vorobyev, V ; Shchelokova, A ; Zivkovic, I ; Slobozhanyuk, A ; Baena, JD ; Del Risco, JP ; Abdeddaim, R ; Webb, A ; Glybovski, S (Elsevier BV, 2020-11)
    High-permittivity dielectric pads, i.e., thin, flexible slabs, usually consisting of mixed ceramic powders and liquids, have been previously shown to increase the magnetic field at high and ultra high-fields in regions of low efficiency of transmit coils, thus improving the homogeneity of images. However, their material parameters can change with time, and some materials they contain are bio incompatible. This article presents an alternative approach replacing ceramic mixtures with a low-cost and stable artificial dielectric slab. The latter comprises a stack of capacitive grids realized using multiple printed-circuit boards. Results in this article show that the proposed artificial dielectric structure can obtain the same increase in the local transmit radiofrequency magnetic field distribution in a head phantom at 7 T as the conventional dielectric pad.
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    Gradient Coil Design and Realization for a Halbach-Based MRI System
    De Vos, B ; Fuchs, P ; O'Reilly, T ; Webb, A ; Remis, R (Institute of Electrical and Electronics Engineers (IEEE), 2020-03-01)
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    Applications of dielectric pads, novel materials and resonators in 1.5T and 3T MRI
    Slobozhanyuk, A ; Zivkovic, I ; Shchelokova, A ; Mikhailovskaya, A ; Sushkov, I ; Nenasheva, E ; Melchakova, I ; Belov, P ; Webb, A (IOP Publishing, 2020-04-23)
    Abstract In order to boost the performance of magnetic resonance imaging without increasing the static magnetic field, it is necessary to increase its intrinsic sensitivity. This allows a reduction in the scanning time, increased spatial resolution, and can enable low-field strength systems (which are much cheaper and can be used to scan patients with metallic implants) to have a higher signal-to-noise ratio (SNR) so that they are comparable to more expensive higher field strength systems. In this contribution, we demonstrate radiofrequency field enhancing and shaping devices based on novel materials, such as high permittivity dielectric structures and metamaterials. These materials can substantially enhance SNR, thus potentially increasing image resolution or allowing faster examinations.
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    Multi-parametric MR in Becker muscular dystrophy patients.
    Hooijmans, MT ; Froeling, M ; Koeks, Z ; Verschuuren, JJGM ; Webb, A ; Niks, EH ; Kan, HE (Wiley, 2020-11)
    Quantitative MRI and MRS of muscle are increasingly being used to measure individual pathophysiological processes in Becker muscular dystrophy (BMD). In particular, muscle fat fraction was shown to be highly associated with functional tests in BMD. However, the muscle strength per unit of contractile cross-sectional area is lower in patients with BMD compared with healthy controls. This suggests that the quality of the non-fat-replaced (NFR) muscle tissue is lower than in healthy controls. Consequently, a measure that reflects changes in muscle tissue itself is needed. Here, we explore the potential of water T2 relaxation times, diffusion parameters and phosphorus metabolic indices as early disease markers in patients with BMD. For this purpose, we examined these measures in fat-replaced (FR) and NFR lower leg muscles in patients with BMD and compared these values with those in healthy controls. Quantitative proton MRI (three-point Dixon, multi-spin-echo and diffusion-weighted spin-echo echo planar imaging) and 2D chemical shift imaging 31 P MRS data were acquired in 24 patients with BMD (age 18.8-66.2 years) and 13 healthy controls (age 21.3-63.6 years). Muscle fat fractions, phosphorus metabolic indices, and averages and standard deviations (SDs) of the water T2 relaxation times and diffusion tensor imaging (DTI) parameters were assessed in six individual leg muscles. Phosphodiester levels were increased in the NFR and FR tibialis anterior, FR peroneus and FR gastrocnemius lateralis muscles. No clear pattern was visible for the other metabolic indices. Increased T2 SD was found in the majority of FR muscles compared with NFR and healthy control muscles. No differences in average water T2 relaxation times or DTI indices were found between groups. Overall, our results indicate that primarily muscles that are further along in the disease process showed increases in T2 heterogeneity and changes in some metabolic indices. No clear differences were found for the DTI indices between groups.
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    Effects of Alzheimer's disease and formalin fixation on the different mineralised-iron forms in the human brain.
    van der Weerd, L ; Lefering, A ; Webb, A ; Egli, R ; Bossoni, L (Springer Science and Business Media LLC, 2020-10-05)
    Iron accumulation in the brain is a phenomenon common to many neurodegenerative diseases, perhaps most notably Alzheimer's disease (AD). We present here magnetic analyses of post-mortem brain tissue of patients who had severe Alzheimer's disease, and compare the results with those from healthy controls. Isothermal remanent magnetization experiments were performed to assess the extent to which different magnetic carriers are affected by AD pathology and formalin fixation. While Alzheimer's brain material did not show higher levels of magnetite/maghemite nanoparticles than corresponding controls, the ferrihydrite mineral, known to be found within the core of ferritin proteins and hemosiderin aggregates, almost doubled in concentration in patients with Alzheimer's pathology, strengthening the conclusions of our previous studies. As part of this study, we also investigated the effects of sample preparation, by performing experiments on frozen tissue as well as tissue which had been fixed in formalin for a period of 5 months. Our results showed that the two different preparations did not critically affect the concentration of magnetic carriers in brain tissue, as observable by SQUID magnetometry.
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    A flexible five-channel shielded-coaxial-cable (SCC) transceive neck coil for high-resolution carotid imaging at 7T.
    Ruytenberg, T ; Webb, A ; Zivkovic, I (Wiley, 2020-09)
    PURPOSE: Imaging the carotid arteries at 7T ideally requires a flexible multichannel array that allows B1-shimming and conforms to different neck sizes. The major challenge is to minimize coupling between closely spaced coils and to make the coupling relatively insensitive to loading conditions. METHODS: We have designed a five-channel flexible transceive array composed of shielded-coaxial-cable coils placed on the anterior part of the neck and conforming to the anatomy. In vivo imaging of the carotid arteries in three subjects has been performed. RESULTS: The measured noise correlation matrices show the decoupling level between the individual elements to be -12.5 dB and better. Anatomical localizer imaging of the carotids shows both carotids in every subject well visualized after B1-shimming. In vivo black-blood, carotid images were acquired with very high in-plane spatial resolution (0.25 × 0.25 mm2 ) with clear depiction of the vessel walls. CONCLUSIONS: The flexibility of the proposed coil has been demonstrated by imaging subjects with different neck circumferences. To the best of our knowledge, the in-plane resolution of 0.25 × 0.25 mm2 is the highest reported at 7T.
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    A smart switching system to enable automatic tuning and detuning of metamaterial resonators in MRI scans.
    Saha, S ; Pricci, R ; Koutsoupidou, M ; Cano-Garcia, H ; Katana, D ; Rana, S ; Kosmas, P ; Palikaras, G ; Webb, A ; Kallos, E (Springer Science and Business Media LLC, 2020-06-22)
    We present a radio-frequency-activated switching system that can automatically detune a metamaterial resonator to enhance magnetic resonance imaging (MRI) performance. Local sensitivity-enhancing metamaterials typically consist of resonant components, which means that the transmitted radio frequency field is spatially inhomogeneous. The switching system shows for the first time that a metamaterial resonator can be detuned during transmission and tuned during reception using a digital circuit. This allows a resonating system to maintain homogeneous transmit field while maintaining an increased receive sensitivity. As a result, sensitivity can be enhanced without changing the system-provided specific absorption rate (SAR) models. The developed digital circuit consists of inductors sensitive to the transmit radio-frequency pulses, along with diodes acting as switches to control the resonance frequency of the resonator. We first test the automatic resonator detuning on-the-bench, and subsequently evaluate it in a 1.5 T MRI scanner using tissue-mimicking phantoms. The scan results demonstrate that the switching mechanism automatically detunes the resonator in transmit mode, while retaining its sensitivity-enhancing properties (tuned to the Larmor frequency) in receive mode. Since it does not require any connection to the MRI console, the switching system can have broad applications and could be adapted for use with other types of MRI scanners and field-enhancing resonators.
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    Shielded-coaxial-cable coils as receive and transceive array elements for 7T human MRI.
    Ruytenberg, T ; Webb, A ; Zivkovic, I (Wiley, 2020-03)
    PURPOSE: To investigate the use of shielded-coaxial-cable (SCC) coils as elements for multi-channel receive-only and transceive arrays for 7T human MRI and to compare their performance with equivalently sized conventional loop coils. METHODS: The SCC coil element consists of a coaxial loop with interrupted central conductor at the feed-point side and an interrupted shield at the opposite point. Inter-element decoupling, transmit efficiency, and sample heating were compared with results from conventional capacitively segmented loop coils. Three multichannel arrays (a 4-channel receive-only array and 8- and 5-channel transceive arrays) were constructed. Their inter-element decoupling was characterized via measured noise correlation matrices and additionally under different flexing conditions of the coils. Thermal measurements were performed and in vivo images were acquired. RESULTS: The measured and simulated B1+ maps of both SCC and conventional loops were very similar. For all the arrays constructed, the inter-element decoupling was much greater for the SCC elements than the conventional ones. Even under high degrees of flexion, the coupling coefficients were lower than -10 dB, with a much smaller frequency shift than for the conventional coils. CONCLUSION: Arrays constructed from SCC elements are mechanically flexible and much less sensitive to changes of the coil shape from circular to elongated than arrays constructed from conventional loop coils, which makes them suitable for construction of size adjustable arrays.
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    How IGF-II Binds to the Human Type 1 Insulin-like Growth Factor Receptor
    Xu, Y ; Kirk, NS ; Venugopal, H ; Margetts, MB ; Croll, T ; Sandow, JJ ; Webb, A ; Delaine, CA ; Forbes, BE ; Lawrence, MC (CELL PRESS, 2020-07-07)
    Human type 1 insulin-like growth factor receptor (IGF-1R) signals chiefly in response to the binding of insulin-like growth factor I. Relatively little is known about the role of insulin-like growth factor II signaling via IGF-1R, despite the affinity of insulin-like growth factor II for IGF-1R being within an order of magnitude of that of insulin-like growth factor I. Here, we describe the cryoelectron microscopy structure of insulin-like growth factor II bound to a leucine-zipper-stabilized IGF-1R ectodomain, determined in two conformations to a maximum average resolution of 3.2 Å. The two conformations differ in the relative separation of their respective points of membrane entry, and comparison with the structure of insulin-like growth factor I bound to IGF-1R reveals long-suspected differences in the way in which the critical C domain of the respective growth factors interact with IGF-1R.
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    Cytotoxic T cells swarm by homotypic chemokine signalling
    Nino, JLG ; Pageon, S ; Tay, SS ; Colakoglu, F ; Kempe, D ; Hywood, J ; Mazalo, JK ; Cremasco, J ; Govendir, MA ; Dagley, LF ; Hsu, K ; Rizzetto, S ; Zieba, J ; Rice, G ; Prior, V ; O'Neill, GM ; Williams, RJ ; Nisbet, DR ; Kramer, B ; Webb, A ; Luciani, F ; Read, MN ; Biro, M (ELIFE SCIENCES PUBLICATIONS LTD, 2020-10-13)
    Cytotoxic T lymphocytes (CTLs) are thought to arrive at target sites either via random search or following signals by other leukocytes. Here, we reveal independent emergent behaviour in CTL populations attacking tumour masses. Primary murine CTLs coordinate their migration in a process reminiscent of the swarming observed in neutrophils. CTLs engaging cognate targets accelerate the recruitment of distant T cells through long-range homotypic signalling, in part mediated via the diffusion of chemokines CCL3 and CCL4. Newly arriving CTLs augment the chemotactic signal, further accelerating mass recruitment in a positive feedback loop. Activated effector human T cells and chimeric antigen receptor (CAR) T cells similarly employ intra-population signalling to drive rapid convergence. Thus, CTLs recognising a cognate target can induce a localised mass response by amplifying the direct recruitment of additional T cells independently of other leukocytes.