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412
MR Imaging - Basic Concepts
pulses, coil to deliver the power to the organ being imaged in the subject and to pick up the
signal from the object, receiver to amplify the signal and computer console for controlling
and operating the MR system (figure 8). Typically superconducting magnets with a field
strength upto 3 Tesla (FDA approved) are used for human clinical imaging and upto 11 Tesla
for human MRI and MRS research.
Bioeffects and Safety
Since MRI does not use any form of ionizing radiation, it is considerably safer than
other imaging techniques. However, it is mandatory to monitor various transient effects that
are produced at the tissue level during the process of MRI. Results of studies, reported so
far, provide no conclusive evidence regarding any side effects, that could threaten the long
term well being of the exposed individual, at least at field strengths currently in clinical use.
While several reviews already exist for research carried out in this field, an overview of the
major areas of consideration for safety issues is provided below (18).
Bioeffects of Static Magnetic Field
Static magnetic fields of upto 3 Tesla do not produce any substantially harmful bioeffects
that include alterations in cell growth and morphology, DNA structure and gene expression,
pre- and post-natal reproduction and development, visual functions, nerve bioelectric activity,
animal behavior, visual response to photic stimulation, cardiovascular dynamics, hematological
indices, physiological regulation and circadian rhythms, or immune responsiveness. Currently,
there are many clinical research installations operating at field strengths of 4 and 7 Tesla
and one at 8 Tesla.
A serious effect of the static magnetic field is the response of ferromagnetic objects that
may be accelerated into the magnet in the form of a projectile. In research settings, this
would mean that most tools, accessories, connectors and other equipment to be used in the
vicinity of the field shouldn’t be ferromagnetic. Subjects have to be screened for objects
such as keys, pens, belts and other metal on clothing, as well as for the possibility of
surgical implants. MRI is normally contra-indicated for subjects with biomedical implants
and devices, because of the risk associated with the dislodgement of any such ferromagnetic
implant that might lead to disastrous consequences.
Bioeffects of magnetic field gradients
MR Imaging requires the use of numerous gradient magnetic fields applied at varying
frequencies for varying durations, with different peak gradient amplitudes. These lead to
power deposition and subsequent tissue heating and in some cases direct neuromuscular
stimulation or excitation caused by the induced currents or voltages. Though the thermal
effects associated with gradient switching are negligible and clinically insignificant,
the magnitude of induced currents might induce seizures, magnetophosphenes
MR Imaging - Basic Concepts
413
(electromagnetically-induced visual flashes of light), alterations in nerve conduction velocities,
peripheral nerve stimulation, skeletal muscular contractions, or even cardiac arrhythmias.
Direct peripheral muscle stimulation in the form of uncontrolled, involuntary skeletal muscle
contractions and/or twitching in human subjects, induced due to the application of echo
planar imaging sequences have been observed at or beyond 60 Tesla/s (19). However, normal
MR procedures do not generate induced current levels that exceed the threshold for various
forms of tissue stimulations.
An additional side effect of the use of rapidly switching magnetic field gradients is the
generation of acoustic noise. The Lorentzian forces induced when an electrical current is
applied to the gradient coils in the presence of an external magnetic field, introduces
mechanical oscillatory movement of the coils. This displacement is dependent upon the
strength of the static magnetic field, the amplitude of the voltage applied and the frequency
and waveform of switching. Gradient magnetic field-induced acoustic noise, despite being
an annoyance has been reported to be within recognized safety guidelines. For some ultrafast
sequences, earplugs or MR-compatible headphones that significantly muffle acoustic noise
alongwith active noise cancellation circuits that are coupled with the MR scanner can be
used to reduce gradient generated acoustic noise. It is mandatory for all MR manufacturers
to obtain FDA clearance for their “dB/dt” to be within the safe limits before marketing any
new gradient product.
The safety guidelines by FDA (20) with regards to exposure of subject to field gradients
are as follows,
i) Maximum dB/dT of the system is 6 Tesla/s or less
ii) For axial gradients:
dB/dt < 20 Tesla/s for t >120 ms or
dB/dt < 200 Tesla/s for t <12 ms
For transverse gradients: dB/dT is considered to be below the level of concern when
less than three times the above limits for axial gradients.
iii) Demonstrate with valid scientific evidence that the rate of change of magnetic field
for the system is not sufficient to cause peripheral nerve stimulation by an adequate
margin of safety.
Bioeffects of RF fields
The absorption of RF radiation is described by the dosimetric term known as the specific
absorption rate (SAR), defined as the mass normalized rate at which RF power is coupled to
biologic tissue (W/kg) and is given by,
SAR = E2 D / 2 (7)
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MR Imaging - Basic Concepts
where is the tissue conductivity, E/2 is the average induced electric field, D is the
duty cycle (ratio of pulse duration to TR) and is the tissue density (21,22). The relative
amount of RF radiation that an individual encounters during an MR procedure can be
characterized with respect to the whole-body averaged and peak SAR levels (the SAR
averaged in 1 gm of tissue).
RF power transmitted during imaging is converted into heat within the tissue following
ohmic losses. However, the increase in tissue temperature caused by exposure to RF energy
during MR procedure depends on various physiological, physical and environmental factors.
These range from the status of the patient’s thermoregulatory system to withstand a heat
load to the presence of any underlying health condition, the duration of exposure, the rate at
which energy is deposited and the ambient conditions existent within the MR system.
Furthermore, while most tissue has adequate blood flow to carry the heat away, some
anatomical regions such as the eye and testis do not. Heating due to RF radiation should not
result in core body temperature increase of over 1o centigrade. Corresponding physiologic
effects range from alterations in visual, auditory, endocrine, neural, cardiovascular, immune,
reproductive to developmental functions (20). Results of studies also indicate that an individual
with normal thermoregulatory function will be capable of physiologically tolerating MR
procedures performed with a SAR limit of 0.4 W/kg or less averaged over the body, and 8.0
W/kg or less for peak absorption in any 1 gm of tissue, and 3.2 W/kg or less averaged over
the head (20,23). It is also essential that there are no conductive items touching the subject’s
skin, since the heating of such objects by the RF radiation can cause serious burns. Most of
the present day MR systems have these safety aspects incorporated in the software and upon
any violation of the limits, the operator is notified to modify the sequence parameters.
Other Safety Considerations
Claustrophobia and other psychological problems can prevent a subject from entering
the scanner and cooperating for the study. It is therefore necessary that the subject be
completely informed regarding the nature of the experiment and the techniques to be used
during the course of the study.
Applications of MR in imaging and spectroscopy
MR imaging technique is non-invasive and does not involve any radioisotopes or ionizing
radiations, permitting its use for repeated measures. It also has multi-planar imaging
capabilities. The soft tissue contrast provided by this technique is far better than other
techniques, making it exquisitely suited for the study of structural, physiological and
developmental disease abnormalities.
Pathology Imaging
MR has high sensitivity and specificity for tumor detection, localization and extent of
involvement, and characterization of the nature of the lesion. It is also useful for staging of
MR Imaging - Basic Concepts
415
malignancy, distant spread, and post intervention follow-ups. Residual/recurrent lesions and
post radiotherapy changes can be assessed. Due to its multi-planar imaging capabilities and
high gray/white matter contrast, MRI is the preferred modality for detection and evaluation
of various congenital malformations. Contrast enhanced MR studies are especially useful
for detection, localization and assessing extent of spread of various infective and inflammatory
brain conditions. MR Angiography provides a non-invasive, non-contrast, high sensitivity
visualization of arterial and venous systems flow studies and is useful in CSF flow
quantification.
MR Spectroscopy
MR spectroscopy can detect pathological and functional metabolism at an early stage
and is an effective non-invasive diagnostic tool that can be used to monitor biochemical and
metabolic changes in serial disease processes that affect the brain. Isotopes that can be
detected by MRS include hydrogen (1H), lithium (7Li), carbon (13C), fluorine (19F), sodium
(23Na), and phosphorus (31P). This technique can access metabolites in bioenergetic pathways
such as membrane metabolites and metabolites of the tricarboxylic acid (TCA) cycle, as
well as some amino acids and neurotransmitters. Proton magnetic resonance spectroscopic
imaging permits in vivo ascertainment in a regionally specific manner of several cerebral
metabolites and neurotransmitters (e.g., glutamate and -aminobutyric acid [GABA]), as
well as determination of measures considered relevant to neuronal density/functional integrity
(N-acetylaspartate [NAA]) and cell membrane integrity (choline-containing compounds
[Cho)). 31P NMR is ideal for observing perturbations to cellular energetics since critical
metabolite concentrations, including phosphagens, ATP and inorganic phosphate (Pi), can be
measured non-invasively and in real time. Spectroscopic studies of psychotropic agents can
yield valuable data on the kinetics of these drugs as well as clues to their sites of action.
Morphometric assessments
MR Imaging can be used as a sensitive technique for quantifying lesion size, area,
volume, etc. It also helps in volumetric measurements for assessment of age related memory
impairment and dementias or in the gynaecological assessment in pre- or postnatal conditions.
Functional MRI: The umbrella term of functional MRI includes rapid imaging techniques
such as perfusion, diffusion and BOLD imaging.
Perfusion MR Imaging: Perfusion ideally represents a means of measuring blood delivery
to tissue at the capillary level. By combining simultaneous use of paramagnetic contrast
material and ultrafast imaging, it is possible to study the hemodynamics of normal and
diseased blood vessels and determine relative cerebral blood volume (rCBV) and blood flow
(rCBF). Major clinical applications of perfusion imaging include stroke and cerebrovascular
disease, tumors, white matter diseases, non-anatomic disorders (seizures, psychiatric disorders,
neuro-degenerative disorders), etc.
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MR Imaging - Basic Concepts
Diffusion Imaging: Diffusion imaging provides signal proportional to the molecular
diffusion of water molecules in tissues, which can be localized and provides clues about the
microenvironment in which the water molecules are dispersing. Disease may directly or
indirectly change the diffusion characteristics of the underlying tissue and can therefore be
detected using diffusion weighted imaging techniques. For example, the failure of the sodium
potassium ATP pump causes cytotoxic edema following acute brain infarction. This process
shifts extracellular fluid into the intracellular space in the affected area showing changes in
the signal intensities on MR images as compared to the unaffected brain tissue. Diffusion
tensor imaging (DTI) simultaneously provides four different types of parameters that help in
tissue characterization, i.e., mean diffusivity, anisotropy, orientation and T2 weighting.
Clinically, it has proven to be highly sensitive in detection of acute infarction and is reliable
in differentiating acute stroke from other diseases that clinically mimic stroke. It is also
useful in evaluation of other disease processes like neoplasm’s, infections and traumatic
brain injury. Figure 9 shows the fractional anisotrophy and fiber tracts in healthy and blind
subjects as an application of DTI in diseased conditions.
Figure 9.1: Fractional anisotropic images in a control subject showing normal diffusivity in the
three orthogonal planes using diffusion tensor imaging encoding in 12 directions (with two b
weightings)
Figure 9.2: Fiber tractography between retina and the occipital cortex in (A) Control (B) Early
Blind and (C)Late Blind subjects showing the different patterns of axonal connectivity with white
arrow denoting lateral geniculate nucleus. (DTI was acquired in 12 directions with 2 ‘b’
weightings).
MR Imaging - Basic Concepts
417
BOLD fMRI: BOLD fMRI shows regions of activation of the brain resulting from the
neural activity associated with various cognitive, sensory, and motor functions. Cognitive
neuroscience applications of fMRI include brain mapping for correlating structure to function
(functional localization), performing studies upon adaptation, priming and habituation,
possibility of evaluation of double dissociations of psychological processes, obtain
convergence of neuroimaging data and behavioural data in control subject databases and
patient databases. Invasive or recording studies on animals have raised important hypothesis
about the layout of various cognitive systems residing in the sensory, motor and association
cortices. Neuroimaging studies on humans allow researchers to test the validity of the
earlier hypotheses. The technique of event related (ER) fMRI has been used for carrying out
studies on mental chronometry (studying the activation profiles across an individual time
series, within a particular anatomical region). Functional MRI can aid in pre-operative
planning to determine the functionally eloquent cortex, so that regions in close proximity of
the lesion may be salvaged to the maximum extent possible. The technique can be used in a
number of brain disorders, such as drug abuse, alcoholism, schizophrenia, epilepsy, obsessivecompulsive disorders or neurodegeneration. BOLD fMRI provides an opportunity to monitor
the innate compensatory cerebral mechanisms that cope with compromised performance due
to disease. Figure 10 shows an example of application of fMRI in thyroid disorders.
(a) (b) (c)
Figure 10: The BOLD activation pattern in the brain represented pseudo color maps rendered on
orthogonal slices in Healthy (a), Hypothyroid (b) and Hyperthyroid (c) subjects.
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MR Imaging - Basic Concepts
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nuclear resonance position on chemical compound. Phys Rev
Part – IV
Quantification Techniques in Nuclear
Medicine
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Background Subtraction in
Nuclear Medicine
H. Rajabi
Nuclear medicine images are the display of radiopharmaceutical distribution in the organ
or the entire body of the patient. In conventional imaging an external detector collects the
photons emitted from radioisotopes and plots a two dimensional projection of a three
dimensional distribution. The counts in each element of a planar image are therefore
proportional to the total amount of activity in an imaginary narrow column perpendicular (or
oblique) to the image surface. Obviously a planar image cannot truly represent the amount
of activity within the organ under investigation as the activity in tissues above and below
also contributes. Such a contamination in the image is conventionally called background
activity. Though not very important for visual inspection, background is a big source of
error in many quantitation procedures (e.g. calculation of individual kidney glomerular
filtration rate).
From the compartmental analysis point of view background can be divided into the
intravascular and extravascular compartments. Intravascular background represents the
amount of activity in the blood vessels and extravascular activity represents the diffused
activity from the blood vessels into the extravascular space. A careful inspection of the issue
reveals that both types of background may also be identified in the target organs. For
example, kidney is highly vascularized and the activity in its vessels may have a great
contribution to the recorded counts over the kidney area. This activity is directly related to
the kidney blood perfusion but does not represent the excretory function of the kidney.
Therefore, while evaluating the kidney function, activity in blood vessels that acts as
background has to be corrected for otherwise it may cause overestimation of the kidney
function. Similarly when the blood perfusion of an organ is under investigation the diffused
activity from the blood vessels into the organ tissue, regarded as extravascular background,
has to be subtracted.
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