Development of MRI technology for improved visualization and quantification of tissue and organs in healthy volunteers

Magnetic Resonance Imaging (MRI) is a technique which allows the visualization
of the human body with a strong magnetic field. After positioning of a
volunteer or patient in the MRI scanner radio frequent waves are submitted and
absorbed by the body. These RF waves are released and detected by coils in the
MRI scanner. This technique is non-invasive, without radiation exposure,
without side-effects and it can easily be repeated.
Normally, multiple scans are performed during one MRI examination. Each MRI
scan, which is called MRI sequence has its own parameter setting. Each sequence
has its own characteristics and image contrast. For example, in one sequence,
fluid is depicted as a dark structure, while in another sequence fluid is
depicted as a white structure. The length of the sequence is the main
determinant of the signal to noise in the image. An increased signal to noise
can be used to improve the resolution of the image. The more sequences are
performed during one MRI exam, the more information is gathered. For optimal
MRI exams, the patient has to cooperate by lying quiet in the scanner without
motion.
Most patients or healthy volunteers can only undergo an MRI exam for a
restricted amount of time for logistical reasons due to the need for an
efficient use of the scanner time, claustrophobia and/or the restricted
duration that a patient or volunteer can be quiet without motion. Most patients
cannot exceed the 45 minutes, while volunteers can undergo a MRI scan for more
than 90 minutes.
For these reasons, each MRI exam is a compromise between number of sequences,
scan time, image resolution and signal to noise ratio.

MRI technology (scanner, sequences en analysis software) is improved constantly
due to an increase in scientific knowledge, technical improvements and the
needs of the clinical and scientific users. After the first steps in the
development of new technology, it enters a phase of optimization, testing and
evaluation in a clinical and scientific environment to assess the real
potential of the technology, before large scale application of a commercial
product can be promoted.
Optimization, testing and evaluation of new or modified sequences/technology is
first performed on phantoms. Thereafter, optimization, testing and evaluation
has to be performed in healthy volunteers. The MRI sequences/technologies are
not yet approved for diagnostic use, but the MRI company has received a CE mark
for investigational use only (Appendix 1).
The MRI sequences involved are developed for imaging of all body organs,
including but not limited to head, neck, chest, heart, abdomen, extremities.

At that moment the relevant questions are:
* What is the optimal parameter setting of a specific new or modified MRI
sequence. In other words, Which parameter setting provides the best image
quality/ information. verkregen. Parameter setting of a sequence is optimal as
it provides the available information in a restricted scan time with high
resolution?
* Is the sequences performing properly in humans. In other words, are images
which good quality obtained in healthy volunteers?
* How good performs the MRI sequence/technology in comparison to existing
sequences?
* Are new applications foreseen with the new or modified MRI
sequences/technology. In other words can structures be detected or
physiological parameters be measured which could not be detected or measured
with previously developed sequences/technologies.

Optimization, testing and evaluation of MRI sequences/technologies in humans is
first performed in healthy volunteers as they are able to undergo a lenghty MRI
exam. Some sequences are optimized for the depiction of vessels, perfusion of
organs or the enhancement after contrast injection. Therefore optimization,
testing and evaluation of some MRI sequences/technologies requires the
injection of contrast agents.
The proposed studies will demonstrate what the additional value is of new or
modified MRI sequences/technology in the visualization and/or quantification of
tissues and organs. The studies will make clear whether the next phase,
evaluation in patients, is warranted.

1) Optimize new or modified MRI sequences/technology for the visualization and
quantification of tissue structure and physiological processes.
2) Test the optimized MRI sequences/technology against commercially-available,
clinical MRI sequences in terms of image quality, signal-to-noise ratio (SNR),
contrast-to-noise ratio (CNR), speed, and accuracy/reproducibility of extracted
quantitative parameters.
3) Evaluate technical capability such as: availability of parallel imaging,
coil availability, acquisition time, flexibility in scan direction, flexibility
in choice of resolution, and field of view (FoV). Compare technical
capabilities to best MR practices.
4) Evaluate the possibilities to improve MRI sequences through modification of
its source code. Explore options to improve diagnostic performance through
independent image reconstruction of raw data generated by the sequence.
5) Assess the utility of the optimized MRI sequences/technology in the
evaluation of normal and abnormal tissue structure and physiological
processes.
6) Evaluate the optimized MRI sequences/technology for new indications and
applications.

One evaluation study will be performed per sequence/technology. This studies
will be single center observational diagnostic studies. We expect to analyze 10
MRI sequences/ technologies in 4 years. The maximum number of volunteers per
study will be 50. A maximum of 500 volunteers will be included.

Burden: MRI examination for maximum 90 minutes. Exposure to acoustic noise.
Contrast media injection. Blood withdrawal (can be collected from intravenous
access for contrast media injection). Risks: incidental findings. Allergy or
shock due to contrast media injection.