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Introduction
1.1 Imaging
Imaging is a representation of an objects form, especially (the formation of an
image).Imaging technology is the application of materials and methods to create, preserve, or
duplicate images.
The images show the parts of your body in different shades of black and white. This is
because different tissues absorb different amounts of radiation. Calcium in bones absorbs x-
rays the most, so bones look white. Fat and other soft tissues absorb less and look gray. Air
absorbs the least, so lungs look black. Since the discovery of X rays by Roentgen in 1895[1].
In X-ray diagnostics, radiation that is partly transmitted through and partly absorbed in the
irradiated object is utilized. An X-ray image shows the variations in transmission caused by
structures in the object of varying thickness, density or atomic composition.
After an introductory description of the nature of X-rays, the most important processes in the
X-ray source, the object (patient) and radiation detector for the generation of an X-ray image
will be described
The x-ray intensity is sufficient to image a human extremity at 14 kVp and 180 mAs.
Pulsed x-ray with a repetition rate greater than 100 kHz was readily achieved by
programming the gate voltage. The CNT-based cold-cathode x-ray technology can potentially
lead to portable and miniature x-ray sources for industrial and medical applications [3].
Ultrasound imaging is a medical technique that uses sound waves to produce images of inside
body organs. These images are formed by sending the sound waves into the body which
bounce off the different tissues and organs and then return to ultrasound machine. The
machine then converts these sound waves into images that can be seen on screen. The way
ultrasound images look depend on how sound waves interact with the tissues in the body .For
example, At some parts of body waves are more reflected by tissues so they appear brighter
on screen, other tissues absorb more waves so they appear darker on screen[2]
The physics of ultrasound imaging is particularly involves the propagation of sound waves
more than 20,000 Hz frequency and their interaction with the different tissues. These waves
are generated by transducer which converts electrical energy to sound waves. The sound
waves are then directed into the body of different tissues; whether they are either absorbed,
reflected or transmitted [3].
When an ultrasound encounters a boundary between two media, some energy is transmitted
and some energy is reflected back that reflected energy depends on acoustic impedance (Z)
between the two medium. If the difference in Z is large, then a significant amount of energy
will be reflected back, whereas if the difference is small, then most of the energy will be
transmitted through the boundary.
The formula for acoustic impedance (Z) is Z = ρc, where ρ is the density of the medium and c
is the velocity of sound in the medium. Therefore, if the density or velocity of sound changes
significantly across a boundary, then the acoustic impedance will also change, leading to a
greater reflection of ultrasound energy. This is why reflections and echoes are commonly
used in medical imaging like we can say strong reflection of ultrasound occurring at the air-
tissues, tissue-bones and chest wall- lung.
The Attenuation of the ultrasound by the medium also plays an important role in ultrasound
imaging. In real when energy is removed from the beam by absorption, scattering and
reflection then the remaining beam decreases exponentially and leads the depth penetration in
the medium, allowing attenuation in different media. As the attenuation co-efficient of
ultrasound is high for bone as compared to soft- tissue .so with the large reflection from bone
tissue ,it is difficult to get the image of structure laying under the bone. On the other hand
water, fat, blood and muscles are good transmitter of ultrasound.
Ultrasonic waves are generated as well as detected by ultrasonic probe and transducer. A
transducer is actually a device that changes one form of energy into another form. A
transducer converts electrical energy to ultrasonic energy this is done by piezoelectric
effect .The piezoelectric effect is the ability of certain material to generate electric field in
response to applied mechanical stress. This effect is applied by certain a crystal from which
electric field causes them to oscillate; as a result acoustic waves are generated. The
piezoelectric effect is exhibited by a number 0f naturally occurred crystals like zirconium.
As ultrasound wave reflected from different tissues received by transducer, voltage pulses are
produced and processed by CRT, usually in three modes A (amplitude) mode, B (brightness)
mode and the last one is M (motion) mode. A mode consist of displaying of signal
amplitude .B mode a single point is displayed by echo and viewer have an apparent cross
section through the patient .Such cross sectional images are called ultrasonic tomograms.in
the last mode that is M mode known to be as presentation, the ultrasound images shows the
motion of internal structure of patient’s anatomy .The most frequent application of m mode is
Echocardiograph[3]
1.3.3 Perfusion imaging
Perfusion imaging is a medical imaging techniques used to visualize the flow of blood
through the vessels and tissues of the body it is typically used to evaluate the function of
organs such as the brain, heart and kidneys to diagnose conditions such as stroke, heart attack
and tumors.
Numerous techniques have been proposed in the last 15 years to measure various perfusion-
related parameters in the brain. In particular, two approaches have proven extremely
successful: injection of paramagnetic contrast agents for measuring cerebral blood volumes
(CBV) and arterial spin labeling (ASL) for measuring cerebral blood flows (CBF).
Perfusion imaging provides the ability to detect regional and global alterations in organ blood
flow. The utility of hepatic perfusion characterization relies on the resolution of each
component of its dual blood supply—the portal vein and the hepatic artery— because
contributions from each are altered predictably in many diseases. As early as 1954, Breedis
and Young (1) first described relative increases in arterial supply in the setting of primary and
metastatic liver tumors, thus heralding the possibility of arterial phase imaging to detect
malignant tumors. Changes in relative arterial and portal venous blood flow also are known
to be associated with the evolution of cirrhosis (2, 3).
Because most pathologic entities of the liver affect blood flow regionally, globally, or both
(4), perfusion imaging of the liver has been invoked as a means of improving the sensitivity
and specificity of diagnostic liver imaging. Herein, we provide a context for liver perfusion
imaging and review its physiologic basis. After highlighting goals for its use and
development, we review existing methods and
discuss their role in the evaluation of cirrhosis, hepatocellular carcinoma (HCC), and
metastatic disease. We conclude with a consideration of future direction in emerging field.
Myocardial perfusion is an imaging test. It's also called a nuclear stress test. It is done to
show how well blood flows through the heart muscle. It also shows how well the heart
muscle is pumping. For example, after a heart attack, it may be done to find areas of damaged
heart muscle. This test may be done during rest and while you exercise.
A myocardial perfusion scan uses a tiny amount of a radioactive substance, called a
radioactive tracer. The tracer travels through the bloodstream and is absorbed by the healthy
heart muscle. On the scan, the areas where tracer has been absorbed look different from the
areas that do not absorb it. Areas that are damaged or don't have good blood flow do not
absorb the tracer. The damaged areas may be called “cold spots” or “defects.”
A stress myocardial perfusion scan assesses blood flow to the heart muscle when it is
stressed. The heart is usually “stressed” from exercise. But, if you are unable to exercise, the
heart can be stressed taking a certain medicine that increases your heart rate or dilate blood
vessels as would occur during exercise.
After the radioactive tracer is injected, a special type of camera is used that can detect the
radioactive energy from outside the body. The camera takes images of the heart during stress
and again later at rest. The two sets of images are compared.
Myocardial perfusion is an imaging test. It's also called a nuclear stress test. It is done to
show how well blood flows through the heart muscle. It also shows how well the heart
muscle is pumping. For example, after a heart attack, it may be done to find areas of damaged
heart muscle. This test may be done during rest and while you exercise.
A stress myocardial perfusion scan assesses blood flow to the heart muscle when it is
stressed. The heart is usually “stressed” from exercise. But, if you are unable to exercise, the
heart can be stressed by taking a certain medicine that increases your heart rate or dilate
blood vessels as would occur during exercise.
After the radioactive tracer is injected, a special type of camera is used that can detect the
radioactive energy from outside the body. The camera takes images of the heart during stress
and again later at rest[4].
1.3.4 CT scans imaging
A CT scans (computed tomography) also known as CAT (computerized axial tomography)
scan is a medical imaging procedure that uses X rays to create detailed cross sectional images
of the body. These images can be reconstructed in multiple plans including axial
(perpendicular to the body) coronal (parallel to the body but with the head at the top) and
sagittal (parallel to the body with the head at the side) plans Ct scans are useful for
diagnosing a wide range of conditions including injuries, infections, tumors and diseases of
the body diseases of blood vessels, liver, kidney and lungs. They are also used to guide
procedures such as biopsies and to monitor the progression of conditions over time.
Since the introduction of CT scanning about 40 years ago, there has been significant
advancement in both the hardware and software of CT scanners. One area of hardware
development has been in the improvement of scanner motion, which has allowed for faster
and more accurate scans.
Modern CT scanner that use a rotating X-ray tube and a large circular array of detectors,
known as multi-detector CT (MDCT) scanner. These scanners are capable of producing high-
resolution images in a very short amount of time, with scan times as fast as one second or
less[5]
In 1998, the first sample of PET system was used at the University of Pittsburgh. A similar an
atomic data merged with the PET scan have proved very convenient explanation of PET
images. The consequence of PET image fusion was so magnificent that hybrid PET scanner
was rapidly adapted by the industry[6].
The physics of PET involves positron-electron extermination into photons. For example, a
radiolabeled compound such as fluorodeoxyglucose (FDG) comprises 18F as the positron
emitting isotope. FDG is an analog of glucose that accumulates in metabolically active cells.
Because tumor cells are generally more active metabolically than the normal cells, an
increased absorption of FDG is positively correspond with the existence of tumor cells and
their metabolic activity.
When the positron is emitted by 18F, it annihilates a nearby electron, with the emission of
two 0.511-MeV photons in opposite directions. These photons are detected by ring detectors
placed in a circular gantry surrounding the patient. From the detection of these photons,
computer software (e.g., filtered back-projection algorithm) reconstructs the site of the
annihilation events the intervening anatomy. The site of increased FDG accumulates [8].
Magnetic resonance imaging is a versatile imaging modality that can be used to diagnose a
wide range of conditions and injuries including neurological disorders, musculoskeletal
injuries, cardiovascular diseases, and cancer. MRI’s ability to provide highly detailed images
of soft tissues, such as the brain, spinal cord, and internal organs has made it an essential tool
in medical diagnosis and treatment planning.
In recent years, new MRI techniques such as diffusion and perfusion MRI have improved the
diagnostic capabilities of the modality, especially in cancer imaging. These techniques allow
for the assessment of tissue microstructure and blood flow which can help identify cancerous
tumors and determine the most appropriate treatment approach.
Overall, MRI is a valuable tool in modern medicine, and its uses are likely to continue to
grow as new techniques and applications are developed[9]
1. Preparation: before the examination, the patient will be asked to remove all metal
objects from their body, including jewelry, watches, and clothing with metal zippers
and buttons. They will then be asked to change into hospital gowns and lie down on
the MRI table
2. Positioning: MRI technology will help the patient into the correct position for the
examination. Depending on which part of the body is being imaged, the patient may
be asked to lie on their back, stomach, or side
3. Radiofrequency pulse: A radiofrequency pulse is sent through the body which
causes the hydrogen atoms in the body’s tissues to align in a particular way
4. Magnetic field: the MRI machine generates a strong magnetic field which causes the
aligned hydrogen atoms to emit signals that can be detected by the machine
5. Image acquisition: the machine takes a series of images of the body from different
angles, which are then processed by a computer to create detailed 2D or 3D images.
6. Contrast injection: in some cases, a contrast agent may be inserted into the patient’s
bloodstream to enhance the images. The contrast agent is typically a solution
containing a metal, such as gadolinium.
7. Completion: once the exam is complete, the patient will be helped off the table and
can resume normal activities immediately.
8. The entire process usually takes between 30 and 60 minutes depending on the part of
the body being imaged and the complexity of the examination.
Protons in the body are forced to align with the magnetic field created by the strong magnets
used in MRI machines. The protons are activated and spin out of equilibrium when a
radiofrequency current is pulsed through the patient, which causes them to struggle against
the magnetic field. The energy produced as the protons realign with the magnetic field can be
detected by the MRI sensors when the radiofrequency field is switched off. The surroundings
and the chemical make-up of the molecules affect how long it takes for the protons to realign
with the magnetic field and how much energy is released[10]. Based on these magnetic
resonance images, doctors may differentiate between different types of tissues[11]
Figure 6: Proton like earth spin along its axis .In this respect it behaves like a small bar magnet. Under normal
circumstances, [10] these hydrogen proton “bar magnets” spin in the body with their axes randomly aligned [10]
To aid chemists who had produced weird chemicals they couldn't identify, NMR
spectroscopy was first devised. An unknown sample is placed in a static magnetic field,
momentarily activated with radio-frequency photons (light), and then permitted to re-emit
those photons according to the approach (much like in MRI).
Figure 7: leukoencephalopathy with multiple white matter lesions on an axial T2 image in a patient with vascular
Parkinsonism [11]
These methods supplement traditional MRI methods. Included in this are (i) the existence and
degree of diffuse damage in CNS tissue outside of lesions (tissue that seems normal); (ii) the
heterogeneity of damage and repair in focal lesions; and (iii) the particular damage to CNS
tissue components. This review summarizes current pathological validation of quantitative
MRI techniques, recent technical developments in the field, and emerging applications of
quantitative MRI to patients with multiple sclerosis in both research and clinical settings[13].
An established tool in clinical use and study of human neurological problems is magnetic
resonance imaging (MRI). With the proliferation of specialized small animal MRI equipment,
translational MRI research using rodent models of CNS illnesses is gaining popularity.
Projects using this technology typically fall into one of two categories: 1) true "pre-clinical"
studies using MRI as a noninvasive disease monitoring tool and as a biomarker for specific
aspects of the disease, or 2) studies examining the path mechanism of known human MRI
findings in CNS disease models. Most small animal MRI machines run at field strengths
between 4.7 and 11.7 Tesla[14]
More than 25% of adults worldwide are affected with nonalcoholic fatty liver disease
(NAFLD), a frequent cause of chronic liver disease. The term nonalcoholic steatohepatitis
(NASH) refers to a range of NAFLD conditions, including simple steatosis, in which fat
buildup in hepatocytes is the primary histological hallmark, and nonalcoholic steatohepatitis.
The current gold standard for distinguishing between steatohepatitis and hepatic steatosis is
liver biopsy. Noninvasive diagnostic techniques with high sensitivity and specificity are used
for the study of NAFLD because liver biopsy has a number of drawbacks.
The detection of post-infarction scars, aneurysms, pseudo aneurysms, septal defects, mural
thrombi, and valve regurgitations can all be done with the help of cardiac MRI, which has
been proven to be a useful tool. Due to the method's inherent benefits, it is particularly
valuable when these pathological conditions cannot be fully confirmed or ruled out with
echocardiography. The best imaging technique for measuring myocardial mass, systolic
myocardial thickening, chamber volumes, and thickness in MRI[16].
In the second section, we discuss how cutting-edge MRI methods can reveal dynamic or
functional blood artery anomalies that could be the subject of mechanistic study and early-
stage intervention studies. These methods include the measurement of blood-brain barrier
permeability using dynamic contrast enhanced MRI and the evaluation of cerebrovascular
reactivity using MRI techniques.
In the third section, we go through how imaging perforating arteries as well as flow velocity
and pulsatility within them is made possible by the enhanced spatial resolution offered by
ultrahigh field MRI at 7 T. The cutting-edge MRI methods we present enable enhanced
assessment of disease burden and progression while offering fresh pathophysiological
insights in cSVD. They are practical[17].
Figure 10: weighted scans [16]
MRI allows for the evaluation of both inflammatory changes within the bowel wall and
complications occurring outside the bowel in cases of Crohn's disease. The non-invasive
nature of MRI and its absence of ionizing radiation have motivated numerous research groups
to conduct comprehensive studies using this imaging technique to assess Crohn's disease[19].
Figure 12: Thicken bowl wall at terminal ileum mesenteric fat increases[18]
fMRI generates unique and useful information for applications in both basic and clinical
neuroscience by detecting minute changes in the signals used to create magnetic resonance
pictures that are connected to neuronal activity in the brain. fMRI has numerous potential
applications because it is secure, non-invasive, and repeatable in both adults and children.
This succinct summary will make an effort to explain the physical foundation of fMRI, how it
is carried out in practice, some of the limits of the method, and some of the applications that
have been used thus far[21].
Recent research has concentrated on how BOLD responses are produced, and includes
models of functional integration that explain local dynamics through interactions with distant
regions, as well as biophysical input-state-output models incorporating neuronal and
hemodynamic state equations. Both strategies are combined in forward models with brain
level parameters, such as dynamic causal modeling, which models the entire causal chain
from external stimuli via induced neuronal dynamics to observable BOLD responses.
By FMRI we can know specific relationships between BOLD signals and the underlying
metabolic and electrophysiological activity still need to be defined, their physical origins are
largely understood. In order to fulfill the greater demand for oxygen and other substrates, it is
well known that an increase in neuronal activity in a particular cortex region drives an
increase in the local blood flow. The blood flow shift is actually greater than what is required,
resulting in a net improvement in the ratio of oxygenated arterial blood to deoxygenated
venous blood at the capillary level. In essence, the higher metabolic demand is exceeded by
the change in tissue perfusion, resulting in a decrease in the concentration of
deoxyhemoglobin in tissues.
Figure 14: Schematic illustration of the origins of the BOLD effect in fMRI [22]
The main imaging method used in fMRI is echo-planar imaging (EPI), which is an ultrafast
imaging method that can capture complete cross-sectional images of the brain in less than a
second. While EPI images have poorer resolution and overall quality than the images used for
radiological diagnosis, they have the advantage of being able to record the entire brain in a
few seconds and can capture the hemodynamic response to transient events, making it
suitable for studying brain function.
Since the images in an fMRI sequence can differ due to signal variance and extraneous noise,
statistical analysis is used to compare sets of images acquired during different conditions.
Multiple recordings of the MRI signal increase the reliability of the results by allowing a
degree of signal averaging[23].
Overall, fMRI is a valuable tool for investigating brain function and connectivity in both
healthy and diseased populations, and it has the potential to contribute to the development of
novel diagnostic and treatment strategies for neurological and psychiatric disorders. The
resting state functional magnetic resonance imaging (rs-fMRI) technique has gained
advantages over other fMRI techniques due to its ease in signal acquisition and proficiency in
identifying functional areas in different patient populations.
Task-based fMRI has evolved as an advanced magnetic resonance technique to analyse and
evaluate the functional domains in the brain. Recent studies have observed that paediatric
patients, patients with disorders of consciousness, and patients with low intelligence quotient
are able to undergo RS-fMRI[24].
In the initial stages of drug research, FMRI may also be used to design new medications.
Researchers can swiftly screen a huge number of prospective therapeutic compounds to find
those that are most likely to be beneficial by utilizing fMRI to evaluate changes in brain
activity brought on by those molecules.
For guiding dose regimens in early-phase drug discovery, fMRI has a lot of untapped
promise. In theory, predictions about the anticipated brain reaction at greater or lower doses
might be made if there was a consistent link between dose and the BOLD response. There
are, however, not many examples of this form of pharmacometric fMRI modeling being used
in the literature.
2.2.5 FMRI in Alzheimer's disease
Both normal ageing and Alzheimer's disease (AD) result in significant modifications to the
structure and operation of the brain. Death of connections between brain systems and
extensive cortical neuronal death are two symptoms of AD in particular. The functional
coherence of brain activation is disturbed by the degradation of neuronal networks.
Functional network disturbances with recognizable characteristics have been found by recent
advances in brain imaging.
In healthy ageing, connection and network integrity appear to decline, but in AD, this decline
is accelerated and some systems, such the default mode network (DMN), are particularly
affected. Although functional connectivity is a relatively recent area of study, it has
considerable potential to shed light on how the dynamics of brain networks alter with age and
in disease[25]
The main clinical phenotypes of multiple sclerosis (MS) have been reliably shown to involve
functional cortical alterations in studies using functional MRI (fMRI) of the motor, visual,
and cognitive networks. These fMRI changes are distinguished from healthy participants by
altered recruitment of regions usually dedicated to performing a particular task, recruitment
of new regions, different resting state activity, and disturbed connectivity. Such anomalies
change over the course of the disease, not only after an acute relapse but even in patients who
are clinically stable, according to studies that used fMRI longitudinally. The abnormalities of
the MS brain's structural and functional MRIs are connected. The degree of damage to the
brain's normal-appearing white and grey matter and to the movement- and cognitive-
associated fMRI alterations was found to be correlated with movement[26].
The study of FMRI introduces a comprehensive approach for eliminating effects unrelated to
activation-induced blood oxygenation changes in fMRI brain activation maps. The method
employs hypercapnia stress normalization.
Firstly, the study demonstrates the significant impact of resting blood volume distribution
across voxels on activation-induced BOLD signal changes. Secondly, it presents evidence on
the effects of hypercapnia (increased carbon dioxide levels) and hypoxia (oxygen deficiency)
on both resting and activation-induced signal changes. These findings suggest that global
hemodynamic stresses may serve as a valuable tool for non-invasively mapping blood
volume[27].
Pre-operative fMRI mapping based on correlations in spontaneous brain activity has recently
been established, although it has its own drawbacks and is not currently used in many clinical
settings. Here, we demonstrate how task-based mapping and spontaneous mapping can both
be carried out simultaneously using the same pre-operative fMRI data. These two methods
offer complementary information pertinent to functional localization and may be used in
conjunction to more accurately identify eloquent motor cortex.
Our technique's accuracy, sensitivity, and specificity are evaluated by comparison with
mapping of electrical cortical stimulation in eight people with uncontrollable epilepsy.
Through prospective replication in a separate dataset of six patients from a different center,
we are able to show the broad applicability and repeatability of our method. We see a
considerable increase in signal to noise and mapping accuracy irrespective of threshold in
both cohorts as well as in each individual patient, as measured by receiver operating
characteristic curves.
Collectively, it show that altering fMRI data processing to include both task-based and
spontaneous activity greatly enhances functional localization in patients undergoing
preoperative procedures. This technique could be useful in many situations because it doesn't
need changing the standard pre-operative data collecting techniques or adding extra scan
time[28]
Image time MRI takes longer time as it fMRI takes less time to
involve detailed anatomical acquire image as FMRI scans
imaging[29]. focus only on brain activity,
so it allow on shorter
acquisition of time[30].
Temporal resolution MRI has nearly 20-25ms In case of fMRI temporal
temporal resolution which can resolution have some limits
be adjusted according to because of the hemodynamic
demand[29]. response as it imposes
fundamental limit on the time
precision measurement during
fMRI[27].
Sensitivity to motion As we know in MRI we get fMRI is more sensitive to
anatomical image of body by motion as record blood flow
passing magnetic fields so in brain and functioning,
patient remain in resting during movement the blood
position[31]. flow changes and results are
effected[32].
Spatial resolution MRI has comparatively low fMRI has spatial resolution of
spatial resolution then nearly 3-4mm with higher
fMRI[29]. magnetic field of 7T and
pixel size of 500 micron[33].
Functional In case of MRI the patient is While during fMRI
paradigms not required to perform any imaging ,participant had to
specific task during do some specific task
imaging[31]. according to the given
instructions[34].
Hemodynamics Magnetic resonance imaging Functional magnetic
response as used magnetic field to resonance imaging (fMRI),
visualize body organs and which monitors changes in
strange activity in body ,so we blood flow, volume, and
say that ,magnetic resonance oxygenation that take place
imaging does not measure concurrently with the activity
Hemodynamics response of neurons, is the most
directly. popular method for
noninvasively detecting
whole-brain activity in
people. The blood
oxygenation-level-dependent
(BOLD) signal, which is now
the most reliable and widely
utilized fMRI signal, is
created when these changes
are combined[35].
Sensitivity to small Magnetic Resonance Imaging FunctionalMagnetic
lesions technique (MRI) is more Resonance Imaging (FMRI)
sensitive to small lesions, such is not able to show these
as tumors or vascular small abnormalities as its just
abnormalities specific to brain functioning
3.2 Difference between diagnosed diseases
We can distinguish between MRI and FMRI based on the diseases that these two diagnostic
methods are used to treat, since we are aware that MRI uses a visual representation of the
body's organs like body interior structure[36].But in case of FMRI we discuss about the
functional images of any activity involve in our brain for example we can say metabolic
activity over time[23]So below going to discuss some of these disease to differentiate
between the main working of MRI and FMRI
Similarly MRI is also used in ligament injuries like in Peroneal tendon and ligament A
neglected cause of lateral hindfoot discomfort and dysfunction that can be challenging to
detect from lateral ankle ligament injuries is pathological abnormalities of the peroneal
tendons[39].
Above disease related to interior body structure, now some diseases are discussed further
which are related to brain functional activityand observed by using functional magnetic
resonance imaging technique.
3.4.1 Epilepsy
FMRI can help in identify the area that is affected by epilepsy and identify the potential
surgical treatment options. Epilepsy is disorder in brain which specified by repeated
seizures[42].
3.4.3 Depression
Although cortical connection networks may have a role in the choice of treatments for major
depressive illness, functional magnetic resonance imaging research has only limited
therapeutic usefulness. Electroencephalography (EEG), a technology more readily used in
clinical practice, has been used to uncover functional connectivity networks that resemble
those seen in functional magnetic resonance imaging[44].