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Sergey Makarov · Marc Horner
Gregory Noetscher Editors
Brain and
Human Body
Modeling
Computational Human Modeling at
EMBC 2018
Brain and Human Body Modeling
Sergey Makarov • Marc Horner
Gregory Noetscher
Editors
Brain and Human Body

Modeling
Computational Human Modeling
at EMBC 2018
Editors
Sergey Makarov Marc Horner
Massachusetts General Hospital ANSYS, Inc.
Boston, MA, USA Evanston, IL, USA
Worcester Polytechnic Institute
Worcester, MA, USA
Gregory Noetscher
Worcester Polytechnic Institute
Worcester, MA, USA
This book is an open access publication.

ISBN 978-3-030-21292-6 ISBN 978-3-030-21293-3 (eBook)
https://doi.org/10.1007/978-3-030-21293-3
© The Editor(s) (if applicable) and The Author(s) 2019

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Preface to Computation Human Models and
Brain Modeling: EMBC 2018
Numerical modeling has become an essential enabling technology in a variety of

engineering fields, including mechanics, chemistry, fluid dynamics, electromagnet-
ics, and acoustics. Modeling accelerates the product development cycle, giving sci-
entists and engineers the opportunity to explore design iterations and scenarios in
virtual space, and allowing optimization over a host of external conditions that
would be time and cost prohibitive to experimentally characterize and quantify.
Furthermore, simulations permit the examination of resulting field values, such as
internal current distributions or energy absorption in tissues that would typically not
be available to an experimentalist due to safety or ethics concerns.
However, regardless of the physics under consideration or the method utilized,
every practitioner in the field of numerical modeling knows one fundamental rule:
the simulation is only as good as the underlying model being employed. This is a
more articulate or eloquent way of saying “garbage in equals garbage out,” but
regardless of how it is phrased, the message is the same. If there are fundamental
flaws or inaccuracies in the model that mask or modify the physics under examina-
tion, even if the simulation itself runs flawlessly, results might be erroneous and
predictions based on that simulation will not accurately embody the intended
aspects of the physical world. It is with this motivation in mind that developers of
phantoms characterizing the human body and its corresponding physiological pro-
cesses have continuously advanced the state of the art and pursued ever more accu-
rate representations of human anatomy at a variety of geometric scales.
Advancements in human phantoms are a product of many converging disciplines,
ranging from the basic sciences of chemistry, biology, and physics to more applied
areas such as electrical and computer engineering, material science, medical data
acquisition and segmentation, surface and volumetric mesh manipulation, and
large-scale data processing. The memory and computational processing limitations
encountered in previous model generations, where human bodies were represented
with basic, homogeneous geometric primitives or highly de-featured faceted mod-
els, no longer apply to modern simulation platforms. The rapid advance in comput-
ing hardware permits a new generation of ever more detailed models with
substantially enhanced levels of anatomical accuracy. Similarly, the incorporation
v
vi Preface to Computation Human Models and Brain Modeling: EMBC 2018
of sophisticated material properties to support coupled multi-physics simulations is

also now possible. Furthermore, advances in our understanding of the anatomy and
physiology of the human body continue to provide ever-growing insights into the
tissue properties and their detailed organization at the macro- and microscopic lev-
els, thus enabling models that increasingly capture the most relevant properties.
As human models have improved, the scope of applications examined via simu-
lation has also grown, providing researchers and engineers with powerful tools to
explore new and exciting hypotheses regarding human physiology, pathophysiol-
ogy, and biomedical engineering. The application of electromagnetic fields in bio-
medical engineering has produced promising diagnostic and therapeutic
methodologies and protocols that may now be competently and thoroughly studied
to generate detailed analyses on estimated efficacy and patient safety. Topics of
recent interest to the research and medical communities are broadly distributed
across the electromagnetic frequency spectrum and include: cancer ablation via
radio frequency (RF) heating; safety and efficacy assessments of patients with and
without implanted medical devices during procedures such as magnetic resonance
imaging (MRI); new and varied coil designs for optimal MRI protocols; treatment
of brain disorders, such as depression, via noninvasive brain stimulation techniques
like transcranial magnetic stimulation (TMS) and transcranial direct current stimu-
lation (tDCS); optimal design, configuration, and placement of single or multiple
coils or electrodes for focused and deep internal electromagnetic field generation;
pain management therapies that rely on noninvasive nerve stimulation rather than
potentially addictive pharmaceuticals; and many others. While seemingly disparate,
these applications are united in their need for high-quality computational human
phantoms and optimized simulation methods that enable fast and accurate approxi-
mations of the underlying physics that govern responses of the body to externally
applied electromagnetic stimuli. This is the motivation that drives the research con-
tained in this work and has provided inspiration to the researchers and engineers
laboring in this field.
This work is a collection of selected papers presented during the third Annual
Invited Session on Computational Human Models. The session was conducted from
July 17 to 21, 2018, in Honolulu, HI, as part of the 40th Annual International
Conference of the IEEE Engineering in Medicine and Biology Society (EMBS),
which provided a collaborative platform showcasing academic and commercial
research representing the current state of the art in computational human models
and applications for which they are employed. The various session tracks brought
together subject matter experts in diverse fields representing academia, government
institutions, and industry partners. A clear outcome of this effort was a comprehen-
sive, multidisciplinary review of each area, and the promotion of a rich dialogue on
promising future paths in human phantom development, numerical methods, and
simulation applications. The chapters presented here provide an overview of the
invited session and highlight a myriad of potential avenues of development and
exploration during future EMBS conferences.
The first section presents chapters devoted to models specifically tailored for
noninvasive stimulation. A collection of techniques that employ the physics of elec-
Preface to Computation Human Models and Brain Modeling: EMBC 2018 vii
tromagnetism to stimulate specific regions of human anatomy are reviewed. The

research is aimed at treating various pathologies, including neurological disorders
treated with noninvasive brain stimulation and chronic pain treated via peripheral
nerve stimulation. Several brain stimulation modalities are presented along with
custom models that have been generated to best represent the anatomic features
most affected by these treatments.
The second section is devoted to tumor-treating fields (TTFields), which is a new
and promising treatment for glioblastoma that was recently approved by the US
Food and Drug Administration. The simulations employed in these chapters include
human models that inform practitioners on the impact of electrode placements on
the surface of the body, leading to optimization of electrode configurations and
knowledge-based estimates of the resulting field strengths within the body. This
enables practitioners of TTFields protocols to optimally align the direction of the
fields produced by the electrodes, examine field penetration, and conduct studies
investigating the effects of numerous parameters (including field frequency and
intensity) on estimated tumor and glioblastoma treatment.
Section three is a collection of investigations into how computational human
models may be used to evaluate safety concerns for a variety of applications. These
investigations include patient-specific models generated from medical imaging data
to customize treatments as well as modified models adapted to integrate implanted
medical devices for assessing safety during MRI. The section also includes an
examination of bioelectricity at the cellular level and a study on techniques related
to microwave ablation. Industrial radiography accidents and models employed to
examine brain hemorrhage characteristics are also considered.
The final section details efforts related to customized human models tailored to
specific applications. These include incorporating a dynamic breathing sequence
into a normally static model to simulate human respiration, integration of highly
resolved and detailed ear canal structures for simulation of wearable devices, con-
version of voxel-based models to polygon surface models, and a new technique for
measuring material conductivity.
While the exciting work presented here is indeed impressive, there is much yet
to accomplish to enhance current modeling and simulation capabilities. Several ses-
sions at the upcoming 41st Annual International Conference of the IEEE Engineering
in Medicine and Biology Society to be held in Berlin, Germany, on July 23–27,
2019, will be devoted to model generation and related applications. These sessions
will offer both extensions to the results given in 2018 and new research that will
expand the field of computational human phantom generation.
Berenson-Allen Center for Noninvasive Alvaro Pascual-Leone

Brain Stimulation and Division for Cognitive
Neurology, Beth Israel Deaconess Medical Center,
and Harvard Medical School, Boston, MA, USA
Institut Guttman de Neurorehabilitación,
Universitat Autónoma de Barcelona, Barcelona, Spain
Contents
Part I Human Body Models for Non-invasive Stimulation

1 SimNIBS 2.1: A Comprehensive Pipeline for Individualized
Electric Field Modelling for Transcranial Brain Stimulation�� 3
Guilherme B. Saturnino, Oula Puonti, Jesper D. Nielsen,
Daria Antonenko, Kristoffer H. Madsen, and Axel Thielscher
2 Finite Element Modelling Framework for Electroconvulsive
Therapy and Other Transcranial Stimulations�� 27
Azam Ahmad Bakir, Siwei Bai, Nigel H. Lovell, Donel Martin,
Colleen Loo, and Socrates Dokos
3 Estimates of Peak Electric Fields Induced by Transcranial
Magnetic Stimulation in Pregnant Women as Patients or
Operators Using an FEM Full-Body Model�� 49
Janakinadh Yanamadala, Raunak Borwankar, Sergey Makarov,
and Alvaro Pascual-Leone
4 Electric Field Modeling for Transcranial Magnetic Stimulation
and Electroconvulsive Therapy�� 75
Zhi-De Deng, Conor Liston, Faith M. Gunning, Marc J. Dubin,
Egill Axfjörð Fridgeirsson, Joseph Lilien, Guido van Wingen,
and Jeroen van Waarde
5 Design and Analysis of a Whole-Body Noncontact
Electromagnetic Subthreshold Stimulation Device
with Field Modulation Targeting Nonspecific Neuropathic Pain�� 85
Sergey Makarov, Gene Bogdanov, Gregory Noetscher,
William Appleyard, Reinhold Ludwig, Juho Joutsa,
and Zhi-De Deng
ix
x Contents
Part II Tumor Treating Fields (TTFs)

6 Simulating the Effect of 200 kHz AC Electric Fields
on Tumour Cell Structures to Uncover the Mechanism
of a Cancer Therapy�� 127
Kristen W. Carlson, Jack A. Tuszynski, Socrates Dokos,
Nirmal Paudel, and Ze’ev Bomzon
7 Investigating the Connection Between Tumor-Treating Fields
Distribution in the Brain and Glioblastoma Patient Outcomes.
A Simulation-Based Study Utilizing a Novel Model
Creation Technique�� 139
Noa Urman, Shay Levy, Avital Frenkel, Doron Manzur, Hadas Sara
Hershkovich, Ariel Naveh, Ofir Yesharim, Cornelia Wenger,
Gitit Lavy-Shahaf, Eilon Kirson, and Ze’ev Bomzon
8 Insights from Computer Modeling: Analysis of Physical
Characteristics of Glioblastoma in Patients Treated
with Tumor-Treating Fields�� 155
Edwin Lok, Pyay San, and Eric T. Wong
9 Advanced Multiparametric Imaging for Response
Assessment to Tumor-Treating Fields in Patients
with Glioblastoma�� 163
Suyash Mohan, Sumei Wang, and Sanjeev Chawla
10 Estimation of TTFields Intensity and Anisotropy
with Singular Value Decomposition: A New and Comprehensive
Method for Dosimetry of TTFields�� 173
Anders Rosendal Korshoej
11 The Bioelectric Circuitry of the Cell�� 195
Jack A. Tuszynski
Part III Electromagnetic Safety

12 Brain Haemorrhage Detection Through SVM Classification
of Electrical Impedance Tomography Measurements�� 211
Barry McDermott, Eoghan Dunne, Martin O’Halloran, Emily Porter,
and Adam Santorelli
13 Patient-Specific RF Safety Assessment in MRI: Progress in
Creating Surface-Based Human Head and Shoulder Models �� 245
Mikhail Kozlov, Benjamin Kalloch, Marc Horner,
Pierre-Louis Bazin, Nikolaus Weiskopf, and Harald E. Möller
Contents xi
14 Calculation of MRI RF-Induced Voltages for Implanted

Medical Devices Using Computational Human Models �� 283
James E. Brown, Rui Qiang, Paul J. Stadnik, Larry J. Stotts,
and Jeffrey A. Von Arx
15 Dose Coefficients for Use in Rapid Dose Estimation
in Industrial Radiography Accidents �� 295
Haegin Han, Yeon Soo Yeom, Chansoo Choi, Hanjin Lee,
Bangho Shin, Xujia Zhang, Rui Qiu, Nina Petoussi-Henss, and
Chan Hyeong Kim
16 Effect of Non-parallel Applicator Insertion on 2.45 GHz
Microwave Ablation Zone Size and Shape�� 305
Austin W. White, Dwight D. Day, and Punit Prakash
Part IV Mesh Construction, Manipulation and Material Augmentation

17 A Robust Algorithm for Voxel-to-Polygon Mesh Phantom
Conversion�� 317
Justin L. Brown, Takuya Furuta, and Wesley E. Bolch
18 FEM Human Body Model with Embedded Respiratory
Cycles for Antenna and E&M Simulations�� 329
Anh Le Tran, Gregory Noetscher, Sara Louie, Alexander Prokop,
Ara Nazarian, and Sergey Makarov
19 Radio Frequency Propagation Close to the Human Ear
and Accurate Ear Canal Models�� 357
Louis Chen, Gerry Eaton, Sergey Makarov, and Gregory Noetscher
20 Water-Content Electrical Property Tomography (wEPT)
for Mapping Brain Tissue Conductivity in the 200–1000 kHz
Range: Results of an Animal Study�� 367
Cornelia Wenger, Hadas Sara Hershkovich,
Catherine Tempel-Brami, Moshe Giladi, and Ze’ev Bomzon
Index�� 395
Part I
Human Body Models for Non-invasive
Stimulation
Chapter 1
SimNIBS 2.1: A Comprehensive Pipeline
for Individualized Electric Field Modelling
for Transcranial Brain Stimulation
Guilherme B. Saturnino, Oula Puonti, Jesper D. Nielsen, Daria Antonenko,

Kristoffer H. Madsen, and Axel Thielscher
1.1 Introduction
Non-invasive brain stimulation (NIBS) aims at modulating brain activity by

inducing electric fields in the brain [1]. The electric fields are generated either by a
magnetic coil, in the case of transcranial magnetic stimulation (TMS), or by a cur-
rent source and electrodes placed directly on the scalp, in the case of transcranial
electric stimulation (TES). In both cases, the induced electric fields in the brain have
a complex and often counter-intuitive spatial distribution, which is dependent on the
individual anatomy of a target subject. In recent years, there has been a growing
interest in moving away from a one-size-fits-all stimulation approach in NIBS to
more individually informed protocols [2]. The driving force behind this shift is the
Guilherme B. Saturnino and Oula Puonti contributed equally to this chapter.
G. B. Saturnino · A. Thielscher (*)

Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic
Imaging and Research, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark
Department of Health Technology, Technical University of Denmark,
Kongens, Lyngby, Denmark
e-mail: axelt@drcmr.dk
O. Puonti
J. D. Nielsen · K. H. Madsen
Department of Applied Mathematics and Computer Science, Technical University of
Denmark, Kongens, Lyngby, Denmark
D. Antonenko
Department of Neurology, Universitätsmedizin Greifswald, Greifswald, Germany
© The Author(s) 2019 3

S. Makarov et al. (eds.), Brain and Human Body Modeling,
https://doi.org/10.1007/978-3-030-21293-3_1
4 G. B. Saturnino et al.
widely reported variation of NIBS effects within and between individuals [3], which
could be explained in part by the interplay of the individual anatomy and the electric
field propagation [4]. Although software tools have become available that generate
realistic anatomical models of the head based on magnetic resonance imaging
(MRI) scans and use those models to numerically estimate the electric field induced
in the brain, they are still not predominantly used in NIBS studies. This is likely due
to the lack of robustness and usability of the previous generation of tools, in turn
hampering the individualized application of NIBS in both mapping the human brain
function and as a rehabilitation tool in various neuropathologies [5, 6].
The aim of SimNIBS is to facilitate the use of individualized stimulation model-
ling by providing easy-to-use software tools for creating head models, setting up
electric field simulations, and visualizing and post-processing the results both at
individual and group levels. SimNIBS was first released in 2013 [7], had a major
update in 2015, with the release of version 2 [2], and more recently another major
update with the release of version 2.1, described in the current work. SimNIBS 2.1
is a free software, distributed under a GPL 3 license, and runs on all major operating
systems (Windows, Linux and MacOS). In this tutorial, we will concentrate on
what SimNIBS 2.1 can be used for and how the analyses are performed in practice
with step-by-step examples. The chapter is structured as follows: First, we give a
general overview of the simulation pipeline and of its building blocks. Next, we
provide a step-by-step example of how to run a simulation in a single subject, and
then we demonstrate a set of MATLAB tools developed for easy processing of mul-
tiple subjects. Finally, we conclude with an analysis of the accuracy of automated
electrode positioning approaches. More information, as well as detailed tutorials
and documentation can be found from the website www.simnibs.org.
1.2 Overview of the SimNIBS Workflow
Figure 1.1 shows an overview of the SimNIBS workflow for an individualized elec-
tric field simulation. The workflow starts with the subject’s anatomical MRI images,
and optionally diffusion-weighted MRI images. These images are segmented into
major head tissues (white and grey matter, cerebrospinal fluid, skull and scalp). From
the segmentations, a volume conductor model is created, and used for performing the
electric field simulations. The simulations can be set up in a graphical user interface
(GUI) or by scripting. Finally, the results can be mapped into standard spaces, such
as the Montreal Neurological Institute (MNI) space or FreeSurfer’s FsAverage.
1.2.1 Structural Magnetic Resonance Imaging Scans
The minimum requirement for running an individualized SimNIBS simulation is a

T1-weighted structural scan of a subject’s head anatomy. Although SimNIBS will
run on almost all types of T1-weighted scans, we have found that setting the readout
1 SimNIBS 2.1: A Comprehensive Pipeline for Individualized Electric Field… 5
Fig. 1.1 Overview of the SimNIBS workflow
bandwidth low to ensure a good signal-to-noise ratio in the brain region and using a
fat suppression method, such as selective water excitation, to minimize the signal
from spongy bone, typically ensure a high quality of the resulting head models. See
Fig. 1.2 for an example of good quality scans we found to work well with SimNIBS
and [8] for the details of the sequences.
Including a T2-weighted scan is optional, but highly recommended as it facili-
tates accurate segmentation of the border between skull and cerebrospinal fluid
(CSF). Both skull and CSF appear dark in T1-weighted scans, whereas in
T2-weighted scans the CSF lights up, thus guiding the separation between the tis-
sues. Skull has a low electric conductivity, while CSF is highly conducting, meaning
that any segmentation errors in these two compartments can have a large effect on
the resulting electric field distribution inside the head, especially when TES is
applied [8]. If you are interested in modelling the neck region in detail, we recom-
mend using neck coils if these are available at the imaging site.
Fig. 1.2 Example of high-quality T1- and T2-weighted scans likely to work well with
SimNIBS. Note that in the T1-weighted scan, the skull appears dark due to the fat suppression
Optionally, SimNIBS also supports modelling of anisotropic conductivities for

grey (GM) and white matter (WM), which requires a diffusion-weighted MRI scan
(dMRI). Only single shell data (i.e. with a single b-value in addition to some b = 0
images) with a single phase encoding direction for the echo planar imaging (EPI)
readout is supported.
1.2.2 Volume Conductor Modelling
The first step in the pipeline is the generation of a volume conductor model of the
head, which is needed for simulating the induced electric fields. In order to create
this finite element (FEM) mesh, we need to assign each voxel in the MRI scan(s) to
a specific tissue class, i.e. to segment the scan into the different head tissues.
Currently, SimNIBS offers two options for segmentation: mri2mesh [7] and head-
reco [8].
mri2mesh combines FSL [9] (version 5.0.5 or newer) and FreeSurfer [10] (ver-
sion 5.3.0 or newer) to segment the head tissues. FSL is used to segment the extra-
cerebral tissues, while FreeSurfer is used to segment the brain and to generate
accurate surface reconstructions of the grey matter sheet. Note that mri2mesh is
restricted only to the head and does not create models of the neck region.
headreco uses the SPM12 [11] toolbox for segmenting the MRI scan, and is now
the recommended option in SimNIBS. It has been shown to be more accurate in
segmenting the extra-cerebral structures, especially the skull, compared to
mri2mesh [8], while also providing accurate segmentations of the brain tissues.
The computational anatomy toolbox (CAT12, recommended) [12] provided with
SPM can be used to create surface reconstructions of the grey matter sheet which
are on par with the accuracy of those generated by FreeSurfer [12]. In addition,
headreco has an extended field of view, also modelling the neck region. For ease of
use, both SPM12 and CAT12 are distributed together with SimNIBS.
Once the segmentation by either method has finished successfully, the tissue
maps are cleaned by applying simple morphological operations, and used to create
surface reconstructions. As a final step, the FEM mesh is generated by filling in
tetrahedrons between the tissue surfaces using Gmsh [13].
Neither mri2mesh nor headreco have off-the-shelf support for pathologies such
as tumours or lesions. These can however be included into the head models by
manually editing the segmentation masks generated by the methods. When using
mri2mesh, please consult the FreeSurfer website (https://surfer.nmr.mgh.harvard.
edu/fswiki/FsTutorial/WhiteMatterEdits_freeview) on how to handle scans with
pathologies. Manual edits using headreco should be done on the output segmenta-
tion masks in the mask_prep folder located within the m2m_{subID} folder. Once
corrections have been made, the surface meshing step (“headreco surfacemesh
subID”) and volume meshing step (“headreco volumemesh subID”) should be
re-run to generate the edited head model. Note that when creating head models from
scans with pathologies, the CAT12 toolbox should not be used.
dwi2cond (optional) uses FSL (version 5.0.5 or newer) to prepare diffusion ten-
sors for GM and WM from dMRI data. The tensors are used by SimNIBS to esti-
mate anisotropic conductivities in WM and GM during the FEM calculations.
1.2.3 Simulation Setup
Simulations can be set up using the graphical user interface (GUI), which provides
an interactive view of the head model. This allows users to easily select parameters
such as coil positions, electrode positions and shapes, as well as more advanced set-
tings such as tissue conductivities and post-processing options.
It might also be of interest to do simulations of one or a few different setups
across a group of subjects. With this in mind, version 2.1.1 introduced a new inter-
face for setting up simulations using MATLAB or Python scripts.
The GUI as well as the scripts will be described in more detail in Sect. 1.3, as
well as on the website www.simnibs.org.
1.2.4 Finite Element Method Calculations
Transcranial direct current stimulation (tDCS) simulations begin by adding elec-

trodes to the head model. In this step, nodes in the skin surface are shifted to
form the shape of the electrode, while keeping good quality elements. Afterwards,
the body of the electrodes is constructed by filling in tetrahedra. As this step does
not require re-meshing the entire head, it can be done much more efficiently
compared to other methods that require re-meshing, especially when only a few
electrodes are used.
TMS simulations start by calculating the change in the magnetic vector potential
A, that is the dA field in the elements of the volume conductor mesh for the
dt
appropriate coil model, position and current. There are currently two types of coil
models:
.ccd files: Created from geometric models of the coil and represented as a set of
magnetic dipoles from which we can calculate the dA field using a simple
dt
formula [14].
.nii files: Created either from geometric models of the coils or direct measurement
of the magnetic field [15]. Here, the dA field is defined over a large volume,
dt
and the calculation of the dA at the mesh elements is done via interpolation.
dt
This allows for faster simulation setup at little to no cost in simulation
accuracy.
Both simulation problems are solved using the FEM with linear basis functions.
This consists of constructing and solving a linear system of the type Mu = b, where
M is a large (in SimNIBS typically ~106 × 106) but sparse matrix, called the “stiff-
ness matrix”, u are the electric potentials at the nodes and the right-hand side b
contains information about boundary conditions (such as potentials in electrode sur-
faces in tDCS simulations), and source terms (such as the dA field in TMS simu-
dt
lations). SimNIBS solves the linear system using an iterative preconditioned
conjugate gradient method [16]. SimNIBS 2.1 uses GetDP [17] to form the linear
system, which in turn calls PETSc [18] to solve it.
TDCS simulations can also be easily extended to simulations of transcranial
alternating current stimulation (tACS). In the frequency ranges used in tACS, a
quasi-static approximation holds [19]. In the quasi-static approximation, the rela-
tionship between input currents I(t) and the electric field at the positions x, E(x) is
linear:
E ( x,t ) = α ( x ) I ( t )
where α(x) is a proportionality constant, meaning that it does not vary during the
oscillation. This constant can be obtained simply by running a simulation where we
set the input current to unity. I(t) is the input current. For example, a sinusoidal cur-
rent input can be written as
(
I ( t ) = I o sin 2π t + φ
f )
where f is the stimulator frequency, ϕ the stimulator phase and Io the stimulator
amplitude, which corresponds to half of the peak-to-peak current. Usually, we
would visualize the electric field at the maximum or minimum of I(t), which
corresponds to ±Io. In case several stimulators are used at different frequencies of

phases, we have several pairs (αi(x)Ii(t)), one for each stimulator, and the total elec-
tric field at a given time point is given by the sum of their individual contributions
n
E ( x,t ) = ∑α i ( x ) I i ( t )
i =1
1.2.5 Mapping Fields
The result of the FEM calculation is the electric field at each tetrahedral element of
the subject’s head mesh. However, visualization is often easier using cortical sur-
faces or NifTI volumes. Therefore, SimNIBS 2.1 can transform fields from the
native mesh format to these formats via interpolation. Our interpolation algorithm is
based on the superconvergent patch recovery method [20], which ensures interpo-
lated electric field values that are consistent with tissue boundaries.
When performing simulations on multiple subjects, we often want to be able to
directly compare the electric field across subjects to, for example, correlate the elec-
tric field with behavioural or physiological data on the stimulation effects [21]. For
this purpose, SimNIBS can also transform simulation results to the MNI template,
using linear and non-linear co-registrations, as well as to the FreeSurfer’s FsAverage
surface.
1.3 Practical Examples and Use Cases
1.3.1 Hello SimNIBS: How to Process a Single Subject
Here we describe how to run a TMS and a tDCS simulation on a single example
subject. The example subject “Ernie” can be downloaded from the SimNIBS web-
site, and the steps below can be reproduced step by step to get familiar with
SimNIBS.
Generating the Volume Conductor Model
Open a terminal and go to the directory “ernie” to access the example data set. Copy
the content of the “org”-subfolder to another location in order to not overwrite the
files of the original example dataset. Next, go to the folder where you copied the
data, and call headreco to generate the volume conductor model:
headreco all --cat ernie ernie_T1.nii.gz ernie_T2.nii.gz

In the command, the first argument, “all”, tells headreco to run all reconstruction
steps including: segmentation, clean-up of tissue maps, surface meshing, and vol-
ume meshing. The second argument, “--cat” is a flag for using the CAT12 toolbox
for accurate reconstruction of the cortical surface. The third argument, “ernie”, is a
subject identifier (subID), which is used to name generated folders, e.g. m2m_ernie,
and output files, e.g. ernie.msh. The two final arguments are the paths to the T1- and
T2-weighted structural scans.
A few extra input options are useful to know:
-d no-conform Adding this option will prevent headreco from modifying, i.e. trans-
forming and resampling, the original MRI scan. This might be desirable when a
one-to-one correspondence between the head model coordinates and the neural
navigation system coordinates is required.
-v < density > This option allows you to set the resolution, or vertex density (nodes
per mm2), of the FEM mesh surfaces. By default, SimNIBS uses 0.5 nodes/mm2
as the <density > value.
In general, we recommend using the --cat option; however, the execution time
will be longer compared to omitting the option. In addition, if you want to process
scans with pathologies, you should not use CAT12, as the cortical reconstruction is
not designed to work with pathologies.
After headreco has finished, please check the quality of the head model by
calling:
headreco check ernie
If needed, open a new terminal for this operation and go into the folder in which
you started headreco the first time. For our example case, the subject identifier is
“ernie”, but please replace this one with whichever subID was used in the first call
to headreco. Note that we recommend that you have installed freeview (provided
by FreeSurfer, available on Linux and Mac OS X platforms) to visualize the results.
The check function displays two windows for inspecting the output. The first win-
dow shows the T1-weighted scan with the segmentation and structure borders over-
laid (Fig. 1.3, left). We recommend de-selecting the segmentation (ernie_final_contr.
nii) in freeview, and checking that the segmentation borders follow the intensity
gradients of different tissues (Fig. 1.3, middle). Fig. 1.4 shows the second freeview
window, which displays the T1-weighted scan co-registered to the MNI template.
We recommend checking if the T1-weighted scan overlaps well with the MNI tem-
plate by de-selecting the T1-weighted scan (T1fs_nu_nonlin_MNI.nii) in freeview
(Fig. 1.4, right). Figure 1.5 shows an example of a segmentation error where the
skull is erroneously labelled as skin. This can be seen in the front of the head, where
the skin label protrudes into the skull. This example emphasizes the need for fat-
suppressed data when only a T1-weighted scan is used. In the scan shown in Fig. 1.5,
spongy bone is bright with intensities comparable to those of scalp, causing the
segmentation method to mis-classify it as extra-cerebral soft tissue. Small segmen-
Fig. 1.3 Data displayed after calling the check option. Left: T1-weighted scan with the segmenta-
tion and structure borders overlaid. Middle: structure borders overlaid on the T1-weighted scan
after de-selecting the segmentation in freeview. Right: zoom-in of the cortex. Note that the seg-
mentation borders nicely follow the intensity borders between the tissues
Fig. 1.4 Data displayed after calling the check option. Left: T1-weighted scan co-registered to the
MNI template. Right: MNI template shown after de-selecting the T1-weighted scan in freeview.
Note that the scans seem to be well registered
tation errors like this can be corrected by manually re-labelling the segmentation
masks in the “mask_prep” folder located in the m2m_{subID} folder, and re-running
the surface and volume meshing steps. If you are not familiar with using freeview,
please refer to the tutorial on the SimNIBS website (http://www.simnibs.org/_media/
docu2.1.1/tutorial_2.1.pdf). If you do not have access to freeview, the visualizations
will be displayed using SPM. However, these are very primitive and are not recom-
mended for checking the output from headreco.
Fig. 1.5 Example of a segmentation error after headreco processing. The spongy bone is errone-
ously labelled as skin. This example emphasizes the need for fat-suppression when using only a
T1-weighted scan
Finally, you should inspect the volume conductor mesh for any obvious errors.
This can be done by calling:
gmsh ernie.msh
in the subject folder. This call opens a gmsh window displaying the generated
head model; please see the tutorial on the website if you are not familiar with
gmsh (http://www.simnibs.org/_media/docu2.1.1/tutorial_2.1.pdf).
The folder structure and most important files are shown in Table 1.1.
• eeg_positions/ Folder containing the 10-10 electrode positions for the subject
both as a “.csv”, used for acquiring electrode positions, and a “.geo” file, used for
visualization of the positions in Gmsh. If you have custom electrode positions,
they should be added here as a .csv file.
• mask_prep/ Folder containing the cleaned tissue maps along with the white mat-
ter and pial surface files if CAT12 was used. In case there are errors in the seg-
mentation, the masks can be manually corrected and a new head model can
subsequently be generated. Note that the CAT12 WM and GM surfaces can cur-
rently not be modified.
• headreco_log.html, a log-file with output from the headreco run. If something
goes wrong, the log-file helps with troubleshooting, and should be sent as an
attachment when contacting the SimNIBS support email list (support@simnibs.
org).
• ernie.msh, the FEM head model used for the simulations.
• ernie_T1fs_conform.nii.gz, the input scan in the conform space defined by the –d
option. This scan has the same millimetre space as the head model, and can be
used to annotate landmarks which can then be directly transformed onto the head
model.
Table 1.1 The folder

structure after headreco has
finished. In this table, only
the most important folders
and files are listed
Setting Up a Simulation
Once the head model is ready, we can set up tDCS and TMS simulations interac-
tively using the GUI. The GUI can be started on the command line by calling:
simnibs_gui
In the GUI, the user can:
• Visualize and interact with head models.
• Define electrode and coil positions by clicking in the model or selecting a posi-
tion from the EEG 10-10 system.
• Visually define electrode shapes and sizes.
• Select from the available coil models.
• Change tissue conductivity parameters and set up simulations with anisotropic
conductivity distributions.
• Run simulations.
In the GUI, there are two types of tabs, one for tDCS simulations, and another for
TMS simulations, shown respectively in the top and bottom of Fig. 1.6. The tDCS
tabs define a single tDCS field simulation with an arbitrary number of electrodes.
On the other hand, TMS tabs can define several TMS field simulations using the
same coil. For this example, we will set up a tDCS simulation with a 5 × 5 cm anode
placed over C3 and a 7 × 5 cm cathode placed over AF4, and a TMS simulation with
the coil placed over the motor cortex, pointing posteriorly. Details on how to use the
graphical interface can be found on the website (http://www.simnibs.org/_media/
docu2.1.1/tutorial_2.1.pdf).
After the simulation setup, click on the Run button to start the simulations.
Running both simulations takes 10–15 minutes, depending on the computer, and
uses around 6 GB of memory. As a note, before starting the simulations, you can set
additional options (in the menu Edit➔Simulation Options) to let SimNIBS write out
the results as surface data or NifTI volume data. This is not further covered in this
basic example, but the output files created in these cases are described in the next
example. The results of the simulation will be written in the output folder specified
in the GUI, in this case “simnibs_simulation/”. The folder has the files shown below
in Table 1.2.
Fig. 1.6 Set-up of a tDCS

(top) and a TMS (bottom)
simulation in the graphical
user interface
Table 1.2 The output folder of a simple tDCS and TMS simulation
• “ernie_TDCS_1_scalar.msh” is the output from the tDCS simulation, in Gmsh

“.msh” format. The first part of the file name, “ernie”, is the subID. The second
part, “TDCS”, informs us that this is a tDCS simulation. The third part, “1”,
denotes that this was the first simulation we have defined in the GUI, and finally,
“scalar” tells us have used scalar (as opposed to anisotropic) conductivities for
the simulations.
• “ernie_TMS_2-0001_Magstim_70mm_Fig8_nii_scalar.msh” is the output of the
second simulation, also in gmsh “.msh” format. As is the case for the tDCS out-
put, the first part of the file name is the subID, and the second is the number of
the simulation in the simulation list. We next see the number of the TMS posi-
tion, as it might happen that several TMS positions are defined in a single TMS
list. Following this, “Magstim_40mm_Fig8_nii” gives us the name of the coil
used for the simulation, and “scalar” the type of conductivity.
• “ernie_TMS_2-0001_Magstim_70mm_Fig8_nii_coil_pos.geo” is a Gmsh “.geo”
file which shows the coil position for the corresponding simulation.
• “simnibs_simulation_20180920-13041.log” is a text file with a detailed log of
the simulation steps. This file can be used for troubleshooting. Here, the second
part of the file is date and time information of when the simulation started.
• “simnibs_simulation_20180920-13041.mat” is a MATLAB data file with the
simulation setups. This file can be loaded into the GUI or MATLAB at a later time
to check the simulation parameters, or to change them and re-run the simulation.
Visualizing Fields
The electric field E is a vector field meaning that the electric field has both a norm
(i.e. vector length or magnitude) and a direction in space, as shown in Fig. 1.7. As
visualizations of the entire vector are challenging and often unclear, in SimNIBS we
Fig. 1.7 Decomposition of a vector E in relation to a surface. The norm corresponds to the length
of the vector. At each point, the surface defines a normal vector n̂ , and this vector is perpendicular
to the tangent plane to the surface at that point. Given the normal vector, we can decompose the
vector E into normal and tangent components. The normal component is the part of E in the same
line as the normal vector, and the tangent component is perpendicular to it. The normal component
also has a sign, indicating if the field is entering or leaving the surface. In SimNIBS, a positive
normal indicates that the field is entering the surface, and a negative normal indicate the field is
leaving the surface
usually visualize the norm (or strength) of the electric field instead. The norm of the
electric field corresponds to the size of the electric field vector, and therefore is
always positive and does not contain any information about the direction of the
electric field.
One way we can quickly visualize the simulation results is to use the mesh_
show_results MATLAB function. This function comes as a part of SimNIBS ver-
sion 2.1.2, and provides visualizations of the output fields using MATLAB plotting
tools, as well as some summary values for the field strength and focality. For exam-
ple, when running the function on the output tDCS mesh, we obtain the plot shown
in Fig. 1.8a, and the values below in Table 1.3.
The first lines in Table 1.3 show that the displayed data is the field “norm E”, that
is the norm or strength of the electric field, calculated in the region number 2, which
corresponds to the GM volume. Afterwards, we have information on the peak elec-
tric fields. We see that the value of 0.161 V/m corresponds to the 95th percentile of
the norm of the electric field, the value of 0.201 V/m to the 99th percentile and
0.249 to the 99.9th percentile. We also have information about the focality of the
Fig. 1.8 Visualization of (a) tDCS and (b) TMS electric field norms in MATLAB
Table 1.3 Output of

mesh_show_results for the
tDCS simulation
electric field. Here, focality is measured as the GM volume with an electric field
greater or equal to 50% or 75% of the peak value. To avoid the effect of outliers, the
peak value is defined as the 99.9th percentile.
Running the same function on the TMS result file, we obtain the plot shown in
Fig. 1.8b, as well as the peak fields and focality measures shown below in Table 1.4.
We can see that the peak fields for TMS are much higher than for tDCS, even
though we simulated with a current of 106 A/s, very low for TMS. In the focality
measures, we see that the TMS electric fields are much more focal than the tDCS
electric fields, with around five times less GM volume exceeding 75% of the peak
value than tDCS.
Additionally, the “.msh” files can be opened with the Gmsh viewer, producing
3D visualizations as shown in Fig. 1.9. Gmsh has a vast range of functionalities,
such as clipping planes, but can be harder to use than mesh_show_results.
Table 1.4 Output of

mesh_show_results for the
TMS simulation
Fig. 1.9 Visualization in Gmsh of (a) electric field vectors around central gyrus for the tDCS
simulation and (b) TMS electric field depth profile in the hotspot
1.3.2 Advanced Usage: Group Analysis
Now, we want to simulate one tDCS montage, with a 5 × 5 cm electrode over C3

and a 5 × 7 cm electrode over AF4 in five subjects, called “sub01”, “sub09”,
“sub10”, “sub12”, “sub15” and visualize the results in a common space, namely the
FsAverage surface. The subjects and example scripts can be downloaded from:
https://osf.io/ah5eu/
Head Meshing
For each subject, follow the steps in section “Generating the Volume Conductor
Model”.
Write a Python or MATLAB Script
We can set up the simulation of each subject using the GUI, as described in the first
example. However, when working with multiple subjects, it can be advantageous to
script the simulations for efficiency. SimNIBS provides both MATLAB and Python
interfaces to set up simulations. Script 1.1 shows how to set up and run a simulation
with a 5 × 5cm anode placed over C3 and a 7 × 5cm cathode placed over AF4 for all
subjects. The output of Script 1.1 for sub01 is shown in Table 1.5.
To define the rectangular electrodes, we need two coordinates. The “centre”
defines where the electrode will be centred, and “pos_ydir” how the electrode will
be rotated. More precisely, the electrode’s “y” axis is defined as a unit vector start-
ing at “centre” and pointing towards “pos_ydir”. Fig. 1.10 shows one of the cath-
odes (return electrode) defined using the script above, with the coordinate system
and EEG positions overlaid. We can see that the electrode is centred in AF4, and its
Y axis points towards F6. “pos_ydir” does not need to be set when the electrodes
are round.
When the map_to_fsavg option is set to true, SimNIBS computes the electric
fields in a surface located in the middle of the GM layer. This cortical surface, along
with the norm, normal and tangent components of the electric field at the cortical
surface and the angle between the electric field and the cortical surface can found in
the subject_overlays folder, for both the left hemisphere (lh) and for the right hemi-
sphere (rh) as shown in Table 1.5. Afterwards, these quantities are transformed into
the FsAverage space. The transformed quantities can be found in the fsavg_overlays
folder, as shown in Table 1.5. Additionally, we have the electric field and its norm in
MNI space in the mni_volumes folder.
Table 1.5 Output files and folders of Script 1 for sub01. The “.angle”, “.norm”,.. files are
FreeSurfer overlay files and the “.central” files are FreeSurfer surface files
Fig. 1.10 50 × 70 mm
electrode defined with a
“centre” in AF4 and a
“pos_ydir” in F6
path_to_headmodels = "/path/to/head/models/";
subjects = ["sub01", "sub09", "sub10", "sub12", "sub15"];
results_folder = "bipolar/fsavg_overlays";
normals = {};
for i = 1:length(subjects)
sub = subjects(i);
% Load normal field data
normal_surf = sprintf('lh.%s_TDCS_1_scalar.fsavg.E.normal', sub);
m = mesh_load_fsresults(char(...
fullfile(path_to_headmodels, sub, results_folder, normal_surf)));
% Add to cell
normals{i} = m.node_data{1}.data;
end
% Calculate average and standard deviation of the normal at each node
normals = cell2mat(normals);
avg_normal = mean(normals, 2);
std_normal = std(normals, 0, 2);
% Place the fields in the mesh structure
m.node_data{1}.data = avg_normal;
m.node_data{1}.name = 'E.normal.avg';
m.node_data{2}.data = std_normal;
m.node_data{2}.name = 'E.normal.std';
% Plot the fields
mesh_show_surface(m, 'field_idx', 'E.normal.avg')
mesh_show_surface(m, 'field_idx', 'E.normal.std')
Script 1.1 Script for running a tDCS simulations with an anode over C3 and a cathode over AF4 in
five subjects and transforming the results to FSAverage and MNI spaces.
path_to_headmodels = "/path/to/head/models/" ;
subjects = [ "sub01" , "sub09" , "sub10" , "sub12" , "sub15" ];
results_folder = "bipolar/fsavg_overlays" ;
normals = {};
for i = 1:length(subjects)
sub = subjects(i);
% Load normal field data
normal_surf = sprintf( 'lh.%s_TDCS_1_scalar.fsavg.E.normal' , sub);
m = mesh_load_fsresults(char( ...
fullfile( path_to_headmodels, sub, results_folder, normal_surf)));
% Add to cell
normals{i} = m.node_data{1}.data;
end
% Calculate average and standard deviation of the normal at each node
normals = cell2mat(normals);
avg_normal = mean(normals, 2);
std_normal = std(normals, 0, 2);
% Place the fields in the mesh structure
m.node_data{1}.data = avg_normal;
m.node_data{1}.name = 'E.normal.avg' ;
m.node_data{2}.data = std_normal;
m.node_data{2}.name = 'E.normal.std' ;
% Plot the fields
mesh_show_surface(m, 'field_idx' , 'E.normal.avg' )
mesh_show_surface(m, 'field_idx' , 'E.normal.std' )
Script 1.2 Analysis of simulation results in FSAverage space.

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“I am sorry you have asked me,” she replied in a low voice. “I can
only tell you what will pain you.”
“Tell me,” he said.
“I cannot answer for the truth of such a rumor. I do not see as
much of her as I used to do, but I am told there is every prospect of a
marriage between her and—and Kenelm Eyrle.”
Despite his self-control, Sir Ronald’s face grew deadly pale. He
was perfectly silent for some minutes, not daring to trust himself to
speak. Then he laughed, little guessing how hollow and bitter was
the sound of that laugh. Never would he lay bare this wound of his
heart. Men should never laugh at his madness, or women smile at
the weakness of his love. None should ever know this fair woman’s
hand had struck him.
“Did you think that would distress me?” he said. “Why, Miss
Severn, you told me almost as much two years ago.”
“I did not like to pain you,” she said, gently.
“Pain!” he said, mockingly. “Do we live in the old days of
constancy and truth, when a man loved but one woman and loved
her loyally until he died? How many loves have the children of this
generation in a lifetime? A man suffers pain nowadays when he
loses a limb or loses his fortune—not when he is unhappy in his
love.”
She looked at him and something like a sob rose to her lips; his
voice was so full of anguish, there was such unutterable woe in his
dark eyes.
“You must forgive me,” she said, still more gently. “I knew you
were unhappy about Lady Hermione in the time past, and I would
rather suffer all the pain there is in the world than that you should
have the least to bear.”
“Would you?” he asked. “Why are you so kind to me, Clarice?”
The only answer Clarice Severn gave was a long, deep-drawn
sigh. If he could not read why in her face, then should his question
never meet with a reply.
“Did you not tell me two years ago that there was something of
the kind between them?” he repeated.
“Yes; but I was not sure. Lady Hermione is so much admired, you
know, so beautiful, and has so many lovers.”
“True; and it is impossible to tell which she prefers. Who would be
one of a crowd? I would have the whole of a woman’s heart, or
none.”
“You deserve it,” she said, and again Sir Ronald looked at her,
wondering why she was so kind.
It did not occur to him just then, though afterward he thought of it.
“Shall I never grow sane?” he asked himself, as he rode slowly
home. “Is my madness to grow deeper as I grow older? I have been
away from all the places and scenes connected in my memory with
her. I have tried every resource that lay open—study, pleasure, and
yet now that I pause to think, I find I love her better than ever. Oh,
my God! can I do nothing to save myself from this lingering,
hungering fever of love?”
He hated himself for what he considered his cowardice. He
longed to be free from the chains that bound him, yet he could not
free himself. Two years had passed since he received the fatal letter
that had been a death warrant to him, and he loved her as deeply
and as dearly as on that day, when, full of hope, he had asked her to
be his wife.
He seldom met Mr. Eyrle. He never went near the Towers where
he had once spent so much of his time. When the two met, who had
been such dear friends, there was coldness and distance between
them that nothing could penetrate. Sir Ronald disliked and distrusted
Kenelm, because he believed Kenelm had willfully tried to take
Hermione’s love from him. Kenelm Eyrle almost hated Sir Ronald
because he honestly thought Sir Ronald had supplanted him, and
robbed him of all chance of winning Clarice. A few words of
explanation and the old love between them would have returned; it
may be that the tragedy of this story had never then happened.
But dislike and suspicion grew between them—the distance
increased, the coldness deepened, until at last Kenelm was told no
day passed without Sir Ronald going over to Mount Severn—after
hearing which, the next time he met the master of Aldenmere, Mr.
Eyrle gave him one stern look and passed by without speaking.
“The man has robbed me,” said Kenelm to himself, “a thousand
times more meanly than if he had stolen my purse. He has taken
from me the hope that made my manhood bright. I will never forgive
him.”
While Sir Ronald turned involuntarily to look after the man who
had been the dearest friend of his youth.
“It is Hermione who has told him to avoid me,” he said to himself.
“Perhaps she is afraid I shall quarrel with him and seek the
vengeance I know to be my due. Let her not fear; he is safe from
me.”
Yet his heart was heavy and sad within him, for Sir Ronald,
despite his pride—the family failing—was of an affectionate, loving,
warm-hearted disposition, and could ill brook coldness between
himself and those he loved.
People had begun to talk about him, to say how changed he was,
how miserable he was, to wonder what could have come over the
opening manhood that had at one time promised to be both brilliant
and good.
These rumors came to him when he was in a frame of mind most
fitted to bear them. He was no saint, this unhappy hero of mine. He
was quite human, full of faults, full of good qualities that might have
made his name famous, but they were wrongly used, and made it
what the name of no other Alden ever was.
At this time of which I write his mind was a chaos; angry love,
wounded pride, broken hopes, all raged together, and made him
unlike himself.
It was deeply wounding to his pride that people should speak of
him. He had hitherto deemed himself above the reach of gossip, and
it was not pleasant now to know that he was a continued subject of
conversation.
CHAPTER XVIII.
HOW THE LOVE STORY ENDED.
There is no limit to the suffering of a proud man. Every wondering

look, every word rankled in Sir Ronald’s mind.
“People wonder why you do not get married,” said his friend,
Captain Pierson, to him one day. “They tell a story about you here
that I, for one, do not believe.”
“What is it?” asked Ronald, with well-assumed indifference.
“Hardly worth repeating; some absurd story of a hopeless love.
They were discussing you at Leighton Grange last night, and one
bold spirit, bolder than the rest, declared that you had a profound
and hopeless attachment to—guess whom?”
“I would not trouble myself to guess,” he replied, with well-acted
indifference, although his changed face might have bade the
speaker beware of raising the Alden temper.
“Of course, I knew it was untrue,” said Captain Pierson. “I said
you were not the man to love in vain, and that Lady Hermione
Lorriston, beautiful and gifted as she is, could not look down upon Sir
Ronald Alden.”
Sir Ronald laughed, but the demon of angry pride was strong
within him.
“I pay so little heed to rumor,” he said, “and am well content to
know that when I am the victim of gossip, I save, perhaps, a better
man.”
But when his friend had told him all the conjectures, the wonder
expressed and all the annoying little words that are so much
wormwood to the soul of a proud man, Sir Ronald was indignant.
“I have not worn my heart upon my sleeve for daws to peck at,”
he said. “My secret has never passed my lips. Why should it be the
subject of woman’s laughter and man’s bets?”
“I will be a slave no longer,” he cried. “I will kill or cure myself
from this hour! I swear to tear all thought of her from my heart or take
my heart itself, and cast it from me.”
He would marry, no matter that he could not love; he would not
be laughed at and talked about because it was supposed he loved a
woman and loved her in vain. When he remembered Clarice a
hundred little incidents returned to him, how kind she always was to
him, how her beautiful face brightened at his coming, and her voice
sank to softest, sweetest music when she spoke to him.
Trifles all light as air, yet now they formed a strong chain. He was
proud, but not vain; he held women in highest reverence and
respect; yet he felt a silent, sure conviction that Clarice loved him.
How many lovers she dismissed! no one could imagine why; how
ready she had always been to devote her whole time and attention to
him. She had given up the most brilliant balls and parties to spend
the evening with him, when he had gone to Mount Severn in search
of comfort.
She was beautiful and gifted, and she loved him. Should he ask
her to be his wife? She would consent, he believed; but there came
to him a doubt as to whether it was fair. What had he to give in return
for her love and her life? Nothing but a broken heart and blighted by
another woman’s falsity. All that he had of love and devotion had
been offered at another shrine and had been rejected. Was it fair she
should give all to him—he nothing to her?
And then Sir Ronald raised his eyes to the clear, shining
heavens.
“If she will be my wife,” he said, “I swear to honor her and treat
her as though she had been my first love.”
He meant to keep his words; he intended to fling far from him all
remembrance of this woman whom to think of now would be sin; he
meant to cling with his whole heart to this one who had loved and
honored him while others had laughed at his distress.
He would go over to Mount Severn and ask her to be his wife. He
would, if God were willing, marry her, and from the ashes of the old
life construct a fair edifice; then when all barriers of love and honor
parted him from Lady Hermione, he should most certainly forget her.
He was not altogether blinded; he knew it was not so much love
for Clarice and the desire of taking up the broken threads of life that
actuated him as it was the wish to show the whole world, including
Lady Hermione, that he was not the victim of an unhappy love.
Is there any sadder story than the tale of a strong man’s love
when that love is wasted and vain? Had Sir Ronald been a man of
more commonplace character he would have done as commonplace
men do—recovered from the effects of his disappointment and
looked around him for a second object to love. Being what he was,
his life had now but one object—to hide from the world the pain that
was never to cease preying upon him.
One warm, beautiful September evening he went over to Mount
Severn. Although he did not love her, the scene will never leave his
memory until death takes all earthly pictures from him.
Warm and bright, with the lingering gold of summer in the sky,
and the breath of flowers in the air, the birds were singing in the
shade of the trees, the south wind whispered sweet and low. He
found Mrs. Severn alone and asked her where he could find her
daughter.
“Clarice is out in the grounds,” replied the lady. “I have been
scolding her, Sir Ronald, and she does not like it.”
“I cannot imagine the word ‘scolding’ as applicable from you to
her,” he replied.
“Well, I will modify it, and say that I have been finding fault with
her. She used to fill my home with sunshine and music, Sir Ronald;
now she does nothing but dream. I never saw so great a change in a
bright, high-spirited girl. I know as well as though I could see her she
is dreaming now, and I should like to know what fills her thoughts.”
“Shall I try to find out?” he said, laughingly. “Perhaps she is
writing a book or a poem, in which case you must allow her time to
dream.”
Mrs. Severn did not smile; she was not quite happy over her
beautiful daughter.
“Give me permission to find her and add my lecture to yours,” he
said, and Mrs. Severn told him she believed Clarice had gone toward
the lake.
“Do not let her stay out very long, Sir Ronald. Remember, it is
autumn, and the night dews are heavy.”
He promised, and went out of the long, open window into the
beautiful, picturesque grounds of Mount Severn. He walked quickly
toward the lake. One glance at the placid, dreamy water showed him
she was not there.
“Clarice,” he said, gently, and the wind from the trees alone
answered him.
Perhaps, had he found her there, Sir Ronald might have said
less. It is not for me to explain how the mere fact of not being able to
find anything the moment you require it enhances its value. Before
he had looked for Miss Severn twenty minutes Sir Ronald had begun
to believe it was necessary to his happiness that he should find her.
Far down in the shady depths of a long alley, he caught a glimpse
of her dress. He hastened forward, and then stood for a few minutes
to watch her, thinking to himself no poet or painter had ever dreamed
of a fairer picture.
She was leaning against the rugged trunk of an old tree; green
ivy clasped it round, and trailing scarlet creepers crept from bough to
bough. It was a poem in itself to see the white, rounded arm, the
beautiful face and golden head resting against the old tree. As he
came nearer to her, Sir Ronald saw that her passionate, lovely face
was wet with tears.
CHAPTER XIX.
AS A DROWNING MAN.
Sir Ronald went gently to her and called her by name. Whatever
her dream might be, it was so deep that she had not heard the
sound of his footsteps or the rustling of the boughs.
“Clarice,” he said, and when she raised her head and saw him,
the change that came over her face was so sudden and so great it
dazzled him.
“You, Sir Ronald!” she said, and then he knew that she had been
dreaming of him.
He went nearer to her, and they strode side by side under the
shade of the old tree.
“Clarice,” he repeated, “there are tears in your eyes and on your
lashes. You have been alone in this quiet place, weeping. What is
wrong?”
“Nothing,” she replied; “but my thoughts were very sad ones, and
tears are a luxury at times.”
“They should not be for you, for whom all things bright and
beautiful must have been made. Tell me what those sad thoughts
were.”
A mound of dead and dying leaves lay at her feet. Every vigorous
breath of wind brought fresh leaves down, yellow and red. She
pointed to them.
“Every autumn for the last four years I have watched the leaves
of this tree fall,” she said, “and the same thoughts have always
pursued me.”
“You will not tell me what they are?” he said.
“I cannot. Do you not know how impossible it is to put those
thoughts into words that we hardly understand ourselves?”
“Clarice,” he said, gently, “do you know what I have sought you
for?”
“No,” she replied, and he noticed something of dreaminess in her
voice and look.
“I came over to Mount Severn this evening especially to ask you
to be my wife.”
Something like a half-hysterical sob came from her lips.
“Your wife! But you say nothing of loving me.”
“Should I ask you to be my wife if I did not love you, Clarice?” he
asked, carried away, despite himself, by the passion of her words
and the love in her face. He never forgot her half-tearful joy.
“You love me, Ronald! Do not deceive me; do not tell me that
unless it is quite true.”
He could not have said what he intended to say had his life been
the forfeit. He had meant to own to her that his love lay in ashes; but
he could not hold those trembling hands in his, and look at those
quivering lips, yet speak such words as must stab that tender heart.
“I do love you, Clarice. Why, how many years is it since we were
children together, since we played at love and jealousy?”
“But,” she interrupted, “you have had another love since then.”
Yes, Heaven help him! he had; and as he stood there, holding
another woman’s hand in his, all the memory of that lost love came
over him, and, looking up at the green trees, he half wished they
might fall and crush him. Then he recovered himself with a violent
effort and turned to her.
“I do not attempt to deceive you, Clarice—I had another love. I
will tell you all the truth, and you must reject me or take me, as you
will. I loved Lady Hermione when we were children. She has been
the one love, the one passion, the one loadstar of my life. I had no
wish, no thought, that did not begin and end with her, and I believed
she loved me. God grant that I may not speak too harshly of her!
She deceived me with the most cruel words and looks; she drove me
half mad, for when I offered my love to her, she threw it back at me.
There were some false, scoffing words about being my friend for life
—my friend! when she knew she had slain all that was best in me.”
“Hush!” she said, with dignity; “you must not tell this to me.”
“But I must tell you, Clarice, if we are to understand each other.
Why are you so pale—why do you tremble—am I cruel to you?”
“No; speak on; it is better, perhaps, I should hear.”
“The letter she sent me, refusing me, slew in me all that was
honest and best. It made me a coward, it unfitted me to battle with
life, it destroyed every hope that makes manhood sweet and life
precious.”
“Was it so very hard to bear, Ronald?” she asked, pityingly; and
he could not be deaf to the pain in her voice.
“It was. I hide nothing from you. I do not know what madmen
suffer, but it seems to me, on looking back, that for many long
months afterward I was mad. There was nothing that I left undone to
drive even the memory of her fair face from me; I could not do it.
Clarice, a drowning man clings to a straw—I cling to you. Will you
save me from the total wreck of life, reason and happiness? Can you
be more generous than woman ever was before? Can you marry
me, knowing that another woman has had the best of my life? Can
you marry me, to save me and restore me to the world of men?”
She clasped her hands round his arm.
“You have said not one word of loving me, Ronald—not one
word.”
“But I will, God helping me. If you will trust your life and your
happiness to me, I will—I will make you happy.”
“Say you will love me, Ronald,” she whispered, raising her lovely
face to his. He would have been more than mortal not to have been
touched by the wistful sadness there.
“I will love you,” he cried. “Help me to love you, Clarice; help me
to forget this black, brooding shadow that darkens my life; help me to
be a braver, better, nobler man by becoming my wife.”
“I will, if you will love me. Ah, Ronald! why is she fairer to you
than I am? Why should you give her more than me? You say she
has been cruel to you. Listen! I have loved you as long as you have
loved her. I have never given one thought to any other than yourself.
You talk about love—oh, Ronald! could you count the leaves on the
trees you might, perhaps, be able to tell how dearly I love you.”
She clasped her white hands and laid them folded on his breast.
“Do you know that if at any time my life could have saved you, I
would have laid it down for you? Do not think I am speaking as
women should not speak. There is no pain you have suffered that
has not been doubled for me. I have asked but one boon from
Heaven, one grace, one blessing—and that was your love, Ronald.”
“Alas, that I have not more to give!”
“Never say that; I am content. You did not choose me first, but
perhaps in the years to come you may love me best. You have
chosen me as your comforter, and I would rather be that to you than
the worshiped queen of any man.”
Her golden head drooped on his breast, and her voice died away,
in a passionate murmur that was but a sigh.
“I do not deserve it,” he said, regretfully.
“Ah, yes, you do. Because she has slighted you, Ronald, it does
not follow that her estimate of you must be right. Oh, my love, my
king among men! I know how to honor you. I say among all living
men, you have not your peer. Because she has been cold and false,
I will love you doubly; because she has made you unhappy, I will
spend my whole life in trying to make you happy; and if she came to
us now, in all the fatal lure of her beauty, and tried to take you from
me, she should not. I would keep you by the force of my own mighty
love.”
It was very pleasant; even the sweet south wind seemed to listen
to the pleading, passionate voice.
“Why, Ronald, when you found me here,” she continued, “I was
weeping over you—weeping that my love was so unhappy—that the
bright young years of my life were passing in bitterest gloom; for I
came to the old tree last year, and watched the leaves fall, and,
Ronald, it seemed to me that, even as they fell one by one and died
so slowly, that thus my hopes faded, and every year saw you further
from loving me. That was why I wept. I shall never shed such tears
again.”
He could do nothing but bend down and kiss the beautiful face,
praying God in his heart that he might love her as she deserved, and
that he might make the life bright whose brightness depended so
entirely on him.
CHAPTER XX.
A LAST LOOK.
Sir Ronald never knew how the news of his engagement was
received by the “ladye he loved.” The Lorristons went away soon
afterward to pay a long-promised round of visits. He did not know
whether she were pleased, piqued, or surprised.
But he soon found out that, so far as the world was concerned,
he had done an excellent thing for himself. Congratulations poured in
on all sides; people laughed at the rumors they had been so ready to
believe. After all, it was very improbable that a man like Sir Ronald
should have been the dupe of any woman. It was Miss Severn he
had cared for; and, now they were going to be married, Sir Ronald
had urged a speedy marriage.
He began at once to make preparation; he ordered a magnificent
suite of rooms to be prepared for his wife. Perhaps it was significant
of his frame of mind that he never went once to see what progress
was made, contenting himself by giving orders that neither expense
nor trouble should be spared. He sent all the family jewels to London
to be reset, but he did not linger over them with a lover’s fondness,
choosing what would best suit her. He ordered the most lavish and
magnificent presents, but he never heeded the beautiful, blushing
smile with which they were received.
He never omitted any day going over to Mount Severn. He drilled
himself, he trained his thoughts, and would not let them wander from
her. When the memory of Lady Hermione and that evening among
the flowers came to him he crushed it back remorselessly.
Yet no one looking at him could have called him a happy man.
There were grave lines on his brow and round his lips that told of the
long, bitter struggle; his laugh had no music in it, his smile no light.
The ring of youth and happiness had died out of his voice. Even
when he tried to be most happy, the heart within him was cold and
heavy as lead.
One day, as he was riding home from Mount Severn, he met
Kenelm Eyrle. They had not spoken for some time, but on this
evening Kenelm walked up to him.
“One moment, Sir Ronald Alden,” he said. “I will not detain you;
answer me this one question.”
“I will answer a hundred,” replied Sir Ronald, “if you will ask them
as a friend, and not as an enemy.”
“There will be no more friendship between us,” was the calm
reply. “Have you honor and honesty enough to tell me whether it is
true that you are going to marry Miss Severn?”
“Although it can be no business of yours, I do not mind telling you
that in a few weeks from now Miss Severn will be my wife.”
“You have wooed her and won her—you confess it,” cried
Kenelm, fiercely.
“There is nothing to confess. I asked the lady to be my wife, and
she consented viola tout.”
“I shall never waste another word upon you,” said Mr. Eyrle,
indignantly, as he turned away; and Sir Ronald laughed.
“My lady has bidden him speak thus,” he thought. “Perhaps she
wished to see if I was marrying from pique or love. Ah, Clarice, no
one shall ever discover that.”
Kenelm Eyrle walked angrily to Mount Severn.
“I will hear it from her own lips,” he said; “I refuse to believe it
from his.”
He found Clarice where her lover had left her, leaning against the
stone balustrade of the balcony. He saw the softened tenderness of
that beautiful face, the love-light in the wondrous eyes, and from his
white lips came a muttered curse.
She looked up in surprise. While her whole heart and thoughts
were full of the man she loved, it was not pleasant to see the man
who for so long had hopelessly loved her.
“Clarice,” he said, reproachfully, “you are not pleased to see me.
Love is keen. Your face fell and your eyes lost half their light when
they fell upon me. I am not here to tease you; only to ask you a
simple question. Is it true you are going to marry Sir Ronald?”
Her face flushed. She would fain have spared him all the pain.
“I shall bear it more easily if you tell me, Clarice,” he pleaded.
“Yes; it is true,” she replied. “Why do you ask me, Kenelm?”
“I have been told so, and I would not believe it from any one else.
Nay, do not shrink from me, Clarice. I am not going to importune you.
I am too proud, dear, to try to rob another man of that which he has
won. Do you love him?”
Her face glowed unconsciously.
“Yes; I love him with all my heart.”
“I hope you will be happy. You see there is no bitterness in my
heart against you, Clarice. I pray God to bless you and make you
happy.”
“And you will be our friend?” she said.
“No; I could not. I do not blame you. I have tried hard to win your
love, but I could not succeed. You have given it to another. I have no
right to complain, but I shall not forgive him, the false friend, who
knew that every hope of my life rested in you, yet has stolen you
treacherously from me.”
“You are unjust,” she replied, hastily. “If I never belonged to you,
how could any one steal me away? It is of my own free will that I love
and marry Sir Ronald Alden.”
“We will not dispute about him,” he replied, sadly. “I will not
remain; I only wish to bid you farewell.”
“But we shall be neighbors—friends? we shall meet?”
“Never,” he replied. “Let me take one last, lingering look at your
face, the face that has been the star of my idolatry. I shall never see
it again, until, by God’s mercy, it shines among His angels in
heaven.”
Her tears fell fast at his words. He came nearer to her, and
looked for a few moments into that lovely face, as though he would
fain engrave every feature on his heart; then he turned abruptly
away.
When he saw her next she was lying dead, with white flowers on
her breast, and men were in hot pursuit of her murderer.
It was in November that Sir Ronald led his beautiful wife to the
altar. The wedding was one of the most magnificent spectacles ever
witnessed. Clarice would fain have had it quiet and without display,
but the master of Aldenmere insisted upon her receiving the honor
due to her.
To this day they tell of the brilliant crowd gathered in the old
church at Leeholme—of the noble men and beautiful women who
came from all parts of England to assist at what was the grandest
ceremony of the day. The only family of note in the country, absent,
was the Lorristons; but among the costly array of wedding presents
was a diamond necklace from Lord Lorriston, and a pearl bracelet
from Lady Hermione, accompanied by the kindest of letters.
Sir Ronald smiled bitterly when he saw them. His own presents to
his young wife were superb in their magnificence. Did he think by
lavish expenditure and great display to atone to her for the absence
of that which he could not give her—his heart’s best love?
CHAPTER XXI.
MARRIAGE.
The die was cast now. For weal or for woe, for better or worse,
Sir Ronald and Lady Clarice were to spend the remainder of their
lives together.
They went abroad! They made the usual Continental tour, and
then returned to Aldenmere. Lady Clarice was happy as the day was
long. No bird singing in the shade of summer trees was half so blithe
or gay.
On one occasion he was speaking of the grand ball they must
give on their return, and she said, half doubtingly:
“Shall you invite the Lorristons, Ronald?”
“Certainly. Why not? Lord Lorriston and I were always good
friends.”
“I fancied, perhaps, you would not like to meet his daughter.”
“She will, in all probability, be Lady Eyrle then, and what can
Kenelm Eyrle’s wife matter to me?”
“I hear nothing now of their engagement,” she said, thoughtfully.
He turned to her quickly.
“It was you who told me about it—surely you remember?”
“Oh, yes, perfectly; but I fancy it must be broken off, as I hear
nothing of it.”
He only said bitterly to himself that she had played with another
heart and broken it; but for the remainder of all that day no smile or
cheerful word came from him.
Yet she did not notice it. She knew the power of her own beauty,
and she would have deemed it simply impossible that the man upon
whom she lavished all her love could give one thought to another.
She was blind and deaf to the fierce contest going on in the heart
and soul of her husband—to the war that never ended, between right
and wrong.
He would go to her at times with a wearied look on his face that
never came from physical fatigue. He would lay his head down like a
tired child, and say:
“Clarice, sing to me.”
She never said to herself that she was needed to drive away the
demon of discontent; she only thought he preferred her singing to
any other, and was flattered accordingly.
Then the time came for them to return to Aldenmere, and great
were the preparations. The little town of Leeholme was in a perfect
fever of excitement. Triumphal arches were erected, flags were
flying, the beautiful bells of Leeholme church pealed merrily, the
tenants were all assembled to do honor to their lord.
“Welcome Home!” “Long Life to Lord and Lady Alden!” “A Bridal
Welcome!” and hundreds of other mottoes decorated the flags and
the arches. Through long lines of happy faces, through the music of
cheering voices, bride and bridegroom drove to their ancient home.
People might have wondered why the bridegroom’s face grew
sterner and paler as the thunder of a mighty welcome greeted him.
Lady Clarice looked at him with tears in her eyes.
“Oh, Ronald, how pleased they are to see us! What can we do for
them?”
“There will be plenty of home-brewed ale, and as many oxen
roasted as can be eaten,” he said, and the words jarred upon her.
She looked in the pale, impassive face, and would fain have seen
some lingering softness there.
He was thinking, Heaven help him! how different it would have
been had the face he loved been near him on this day, when he saw
how popular and well-loved he was. Then he took himself fiercely to
task for the thoughts.
“Let me remember I have a wife who loves me dearly,” he said to
himself, “and let me not forget the woman who ruined my life for her
own amusement will soon have, or perhaps has, a husband of her
own.”
So he went through the duties of the day with ease and dignity.
He made a most cordial and genial speech to his tenants, inviting
them all to partake of the lavish hospitality prepared for them. He
took his beautiful young wife by the hand, and spoke a few words in
her praise that caused cheers to rise to the very heavens. He spoke
of the work he hoped to do among them—of the life he hoped to
spend—of the brightness of his future, and in his heart he hated the
sun for shining to mock him, and the flowers for blooming so fair.
Had any one present said that that man’s heart was broken by an
unhappy love, who would have believed it? Did ever lot seem so
fair?
And as the well-satisfied tenants left they declared one and all
that Sir Ronald must be perfectly happy. Those who had troubles of
their own—the sorrowful and unhappy, whom many privations had
crushed—wondered that lots in life were so unequal, and envied this
man, young, rich, handsome, and beloved, while he would have
changed places with the poorest, lowliest there to have known only
for one hour such peace of mind as the happy enjoy.
There was but a few hours of respite, then the hall table was
covered with letters of welcome and cards. The same evening Mrs.
Severn drove over. It seemed to her years since she had parted with
her beloved child.
“You will not see Mr. Eyrle among your friends,” she said, as they
sat at dinner; “he went away three weeks ago.”
“Then he is not married?” said Sir Ronald, hastily.
“No,” she replied, with some little surprise, “I never heard even a
rumor of his marriage.”

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Brain and Human Body Modeling

Computational Human Modeling at

Brain and Human Body Modeling 2020: Computational Human

Dormancy in Aquatic Organisms Theory Human Use and

Advances in Simulation and Digital Human Modeling 1st

How It Works Inside the Human body 2018 Edition Edition

Computational Modeling in Bioengineering and

Enterprise and Organizational Modeling and Simulation

The concise human body book Steve Parker

Magnetic Resonance Brain Imaging Modeling and Data

Brain and Human Body

This book is an open access publication.

© The Editor(s) (if applicable) and The Author(s) 2019

Numerical modeling has become an essential enabling technology in a variety of

of sophisticated material properties to support coupled multi-physics simulations is

tromagnetism to stimulate specific regions of human anatomy are reviewed. The

Berenson-Allen Center for Noninvasive Alvaro Pascual-Leone

Part I Human Body Models for Non-invasive Stimulation

Part II Tumor Treating Fields (TTFs)

Part III Electromagnetic Safety

14 Calculation of MRI RF-Induced Voltages for Implanted

Part IV Mesh Construction, Manipulation and Material Augmentation

Guilherme B. Saturnino, Oula Puonti, Jesper D. Nielsen, Daria Antonenko,

Non-invasive brain stimulation (NIBS) aims at modulating brain activity by

Guilherme B. Saturnino and Oula Puonti contributed equally to this chapter.

G. B. Saturnino · A. Thielscher (*)

© The Author(s) 2019 3

1.2 Overview of the SimNIBS Workflow

1.2.1 Structural Magnetic Resonance Imaging Scans

The minimum requirement for running an individualized SimNIBS simulation is a

Fig. 1.1 Overview of the SimNIBS workflow

Optionally, SimNIBS also supports modelling of anisotropic conductivities for

1.2.2 Volume Conductor Modelling

1.2.3 Simulation Setup

1.2.4 Finite Element Method Calculations

Transcranial direct current stimulation (tDCS) simulations begin by adding elec-

corresponds to ±Io. In case several stimulators are used at different frequencies of

1.2.5 Mapping Fields

1.3 Practical Examples and Use Cases

1.3.1 Hello SimNIBS: How to Process a Single Subject

Generating the Volume Conductor Model

headreco all --cat ernie ernie_T1.nii.gz ernie_T2.nii.gz

Table 1.1 The folder

Fig. 1.6 Set-up of a tDCS

• “ernie_TDCS_1_scalar.msh” is the output from the tDCS simulation, in Gmsh

Table 1.3 Output of

Table 1.4 Output of

1.3.2 Advanced Usage: Group Analysis

Now, we want to simulate one tDCS montage, with a 5 × 5 cm electrode over C3

Write a Python or MATLAB Script

Script 1.2 Analysis of simulation results in FSAverage space.

There is no limit to the suffering of a proud man. Every wondering

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Part III Electromagnetic Safety

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Part IV Mesh Construction, Manipulation and Material Augmentation

1.2 Overview of the SimNIBS Workflow

1.2.1 Structural Magnetic Resonance Imaging Scans

1.2.2 Volume Conductor Modelling

1.2.3 Simulation Setup

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