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Pioneers of Connectome Gradients Ralph Kimmlingen Siemens Healthineers, HC DI MR TR R&D-PL, Erlangen, Germany

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Pioneers of Connectome Gradients Ralph Kimmlingen Siemens Healthineers, HC DI MR TR R&D-PL, Erlangen, Germany 122 Technology MAGNETOM Flash (68) 2/2017 www.siemens.com/magnetom-world Pioneers of Connectome Gradients Ralph Kimmlingen Siemens Healthineers, HC DI MR TR R&D-PL, Erlangen, Germany anatomical and neural-tracing techniques, mammalian Abstract brains like that of mice or primates are still under investigation. These methods are capable of an in-plane A typical human brain contains 100 billion neurons resolution of 40 µm [6, 7]. which have about 10,000 individual connections with their neighbors. Being able to map structural and New non-invasive imaging methods which enable the functional connectivity of an individual brain could be study of brain connectivity of living humans have been a first step on a new way of understanding and developed since the beginning of this century. They are diagnosing mental illnesses. Continuous known as MR Imaging of anisotropic diffusion of water improvements on noninvasive magnetic resonance in the brain, and resting state fMRI [8–10]. The related imaging (MRI) methods like functional MRI, resting- advances in imaging technologies and data evaluation state MRI, and diffusion MRI enable this information are empowering us today to study the human brain as an (connectomics) to be obtained for the first time on a entire organ. large human databasis. A key parameter is the A group known as ‘Blueprint for Neuroscience Research’, available gradient field strength for diffusion-sensitive a collaboration among 15 National Institutes of Health MRI sequences [1–3]. Siemens MR has developed two (NIH) in Bethesda, Maryland, USA, decided in 2009 to fund powerful prototype gradient systems for this purpose, a five-year initiative for mapping the brain’s long-distance which have been employed at five different locations communications network. The goal of the so called Human in the US and Europe since 2011 (Fig. 1). Connectome Project (HCP) was set to construct a map of the structural and functional neural connections in vivo within and across individuals. The HCP was funded Up to today, the nervous system circuit diagram with $40 million and comprised two research efforts: (‘Connectome’) of few creatures is known. Back in the early the first, a five-year project at the Center for Magnetic 1980s the little roundworm called C. elegans was discovered Resonance Research (CMRR) in Minneapolis, Minnesota, to have a nervous system of roughly 300 neurons showing in collaboration with Washington University, St. Louis, a total of about 7,000 connections [4, 5]. Using invasive 1 CMRR, Minneaplis, USA MGH/MIT, Boston, USA CUBRIC, Cardiff, UK MPI, Leipzig, Germany 100 mT/m (2011) 300 mT/m (2011) 300 mT/m (2016) 300 mT/m (2016) CMRR, Minneaplis, USA 70 mT/m @7T (2014) WashU, St. Louis, USA 100 mT/m (2013) Figure 1: MAGNETOM Connectom scanners by Siemens Healthcare have been employed at five different locations since 2011. MAGNETOM Flash (68) 2/2017 Technology 123 www.siemens.com/magnetom-world 2 Modern Gradient Design Introduced by R. Turner et al. Single Layer Activly shielded (Asymmetric) head Dedicated systems: Large bore / Hi Gmax Gradient Coils gradients gradients, planar grds. Head/Whole-body System4) Shim Coils G ~3 mT/m G ~10 mT/m G ~20 mT/m G ~40 mT/m G 45–80 mT/m SR ~2 T/m/s SR ~10 T/m/s SR ~50 T/m/s SR ~200 T/m/s SR ~200 T/m/s 1976 1984 1986 1991 2000 2017 U < 600 V, I < 200 A U < 2.2 kV, I < 1 kA First whole-body MRI 20 mT/m SR 160 T/m/s 80 mT/m SR 700 T/m/s Aberdeen University, 1980 EPI enabling Headgradient3 J. Mallard et al add-ons1 40 mT/m SR 200 T/m/s Examples Cardiac/EPI Gradients2 Figure 2: Gradient history of MRI systems. 1 Cohen MS, Weisskoff RM. MRM. 1991; 2 Schmitt F, Eberlein E. et al. ISMRM, 1999; 3 Vom Endt A et al. ISMRM, 2006; 4 Equals an increase of gradient power (slewrate x amplitude) of three magnitudes over 20 years. Missouri, and the second a 3-year project at the Massa- (CUBRIC), equipped with a 300 mT/m MAGNETOM Connectom, chusetts General Hospital’s (MGH) Martinos Center in two 3T MAGNETOM Prisma and a MAGNETOM 7T system1, cooperation with the University of California, Los Angeles. was inaugurated by Queen Elizabeth II. At the end of 2016, A comprehensive description for the HCP can be found in the Max Planck Institute for Human Cognitive and Brain a 2012 Nature article [11]. Sciences, Leipzig, Germany, also installed a MAGNETOM Connectom 3T MRI system1. In order to map the human connectomics, the Washington University & the University of Minnesota (WashU-Minn) Gradient technology consortium, utilized resting state fMRI and high angular resolution diffusion imaging (HARDI) – a special diffusion Siemens Healthcare introduced the first MAGNETOM 0.35T imaging technique. However, Diffusion Spectrum Imaging whole-body scanner in 1983 and has continuously extended (DSI) – a general form of Diffusion Tensor Imaging that was the product portfolio with higher magnet and gradient field pioneered in 2005 at the Massachusetts General Hospital strengths. Starting with a peak amplitude (Gmax) of 3 milli- (MGH) – was the method of choice for the MGH/University Tesla per meter (mT/m) and a slew rate (SR) of 2 T/m/s in of California at Los Angeles (UCLA) consortium. To pursue the early 1980s, today’s (2017) clinical high-end 3T scanner this challenging task, both of these consortiums approached MAGNETOM Prisma achieves a Gmax of 80 mT/m and a SR of Siemens Healthineers to propose working together in 200 T/m/s (see Fig. 2). Gradient system performance depends hardware technology, more specifically in special gradient on many opposing factors including Gmax, SR, linearity volume systems, which will enable the demanding diffusion (LV) and available patient bore diameter. Highest performance imaging. demands are created by diffusion-weighted sequences which expect fast gradient switching for the readout pulses, highest More recently, two European research centers have joined peak amplitude / duty cycle for the diffusion pulses, and the exclusive club of Connectome gradient users. In 2016, excellent shielding of eddy fields. As a consequence, gradient the Cardiff University Brain Research Imaging Centre coils optimized for whole-body applications with a large linearity volume and inductance require high-voltage/-current 1 MAGNETOM Connectom and MAGNETOM 7T is ongoing research. power supplies. Starting with the first applications of the EPI All data shown are acquired using a non-commercial system under institutional imaging method in the early 1990s [12], especially gradient review board permission. Siemens does not intend to commercialize the system. 124 Technology MAGNETOM Flash (68) 2/2017 www.siemens.com/magnetom-world 3 U Increase of GPA current SR = Ƞ · max adjusted linearity and stray field LGC SR 100 T/m/s Umax SR 200 T/m/s Increase of GPA voltage SR = Ƞ · coil layer insulation G 25 mT/m G 40 mT/m max LGC max 1 Reduction of coil radius SR ~ patient bore / RF body coil r5 Figure 3: Improved gradient performance parameters (maximum gradient amplitude (Gmax) or slew rate (SR)) can be achieved by either increasing gradient amplifier (GPA) power (via maximum voltage Umax) and adjusting the coil design (via field efficiency (Ƞ) or inductance (LGC)) or by a reduction of the coil radius (r) and adjustments to the RF body coil and/or the patient bore diameter. 4 Biot Savart Methods Current Density methods2 Additional methods Maxwell / Golay design Target field / spherical harmonics Lorentz force / moment compensation analytical expressions active screening / min. inductance stray field forming / eddy current reduction building blocks (still used) stream function discretization heat & power minimization (analytical & matrix based) geometry-specific (e.g. split/oval) 1976 1984 1986 19911) 2000 2004 2017 Experiental MRI First whole-body MRIs EPI 3rd generation MRIs Discrete windings Distributed windings Wire wound on coil former PCBs Winding plates / Vacuum potting (punched, slotted, cut, glued) Analogue (audio-like) gradient amplifiers with high power losses Pulse width modulated High precision current regulation amplifiers with low losses (>18 Bit @ 1 kA) Figure 4: History of gradient coil design methods. 1 In 1991, PNS (peripheral nerve stimulation) proves to limit gradient performance (predicted by T. Budinger 1979); 2 R. Turner, Gradient Coil Design, A Review of Methods, MRM 11:903 (1993) slew rate became a challenge for gradient system design. or by reducing the inductance of the coil. Besides using more First attempts to reduce the rise time of EPI readout gradients than a single amplifier and coil-set [17], the third alternative involved additional resonant circuits, so-called ‘EPI boosters’ for higher SR is to reduce the inner radius of the coil system [13, 14]. (Fig. 3). The strong (5th order) dependence of the SR from the coil radius leads to about a factor of two increase when With conventional gradient design methods [15, 16], SR changing from 70 cm to 60 cm patient bore. Thus, this increase (at otherwise constant parameters) can be achieved parameter is a crucial part of the MR system concept by either increasing the voltage of the power amplifier (GPA) definition. It emphasizes the importance of efficient use MAGNETOM Flash (68) 2/2017 Technology 125 www.siemens.com/magnetom-world of radial space inside the magnet bore. The best gradient and acceptable nonlinearities of the linear gradient field performance is achieved by using only the necessary number tend to increase the required number of windings, making up of windings driven by the highest available current. In the challenge to the coil designer (Fig. 4). practice, the maximum current is mainly limited by power Cylindrical symmetry dominates today’s gradient coils.
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