Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT03032809 |
| Other study ID # |
2016P002505 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
September 2018 |
| Est. completion date |
July 2019 |
Study information
| Verified date |
September 2018 |
| Source |
Massachusetts General Hospital |
| Contact |
Javier Romero, MD |
| Phone |
6178402392 |
| Email |
jmromero[@]mgh.harvard.edu |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
The aims of this study are to optimize MR imaging and MR angiography sequences and image
reconstruction for 3T magnetic resonance imaging system scanners, which are already used in
the clinical environment on patients with or with suspected intracranial vasculopathies.
Improvements in these areas will have positive implications for medical diagnosis and
treatment.
Description:
Magnetic Resonance Imaging (MRI) is a non-invasive diagnostic techniques which allow
investigators to literally "see inside" the body without surgery or ionizing radiation (i.e.,
x-rays). The MRI scanner uses a magnetic field and radio waves to produce a picture of the
human anatomy. Magnetic resonance imaging techniques are constantly being developed and
optimized to increase the speed of acquisition and expand the information content of the
resulting images and spectra. Such developments are typically made possible by advances in
the machine hardware and computer software. Improved software options of the MR system
necessitate evaluation to determine how they can best be applied to research studies
employing the equipment. MR software are initially evaluated using inanimate test phantoms.
Trials involving human subjects are a necessary step in the development of new MR software
since test phantoms are often inadequate for simulating real life conditions. For example,
test phantoms cannot be used to visualize subtle changes in tissue contrast or evaluate the
effects of voluntary patient movement, breathing, or blood flow. Therefore, limited human
subject testing is necessary to evaluate and optimize the performance of the MR software.
This will entail varying the MR pulse sequence parameters and assessing specific image
quality measures such as tissue contrast, image artifact levels and signal to noise ratio.
Investigational software may include pulse sequences and reconstruction software. Pulse
sequences are software modules, which control the timing of current through the various coils
of the imager. After reception and digitization of the radiofrequency signal, reconstruction
software creates digital images, which are displayed on a video monitor. This software
adheres to the FDA's definition of non-significant risk.
The aims of this study are to optimize MR imaging and MR angiography sequences and image
reconstruction for the 3T magnetic resonance imaging system for subjects with or with
suspected CNS vasculitis.
Fifty (50) adult subjects with or with suspected intracranial vasculopathy will be enrolled.
These patients will be recruited by subspecialty physicians.
Eligibility will be determined by a screening interview. The treating physician will only
introduce the study to the potential subject, and will not try to obtain any consent from
them in order to avoid any possible coercion. The treating physician will also try to obtain
their approval for being contacted by phone to discuss the study in more detail.
A researcher will later call the potential subjects and explain what the study is about. An
IRB approved telephone script will be used in the case that a non-physician makes the
telephone call.
Most subjects are expected to be recruited from the clinics. And as described above, these
treating doctors from the clinics will only introduce the study and get the subjects approval
to be contacted by phone for more detailed discussion. No subjects will be called if prior
approval or interest was not obtained.
Since this is a study of the actual MRI images and spectra produced, and not of the
intracranial pathology of the subjects, it is sometimes optimal to scan the same subject more
than once for direct image comparison. This allows for the best comparison of the image, and
eliminates the variability between subjects. Therefore, the investigators will ask subjects
if they would like to return for one additional MRI session. They have no obligation to
return or be scanned a second time, but will be offered the choice. If the investigators scan
the same subject a second times, the investigators will obtain new consent for the second
scanning session. Although this study is considered low risk, adult subjects will be limited
two MRI scans in total for this study.
MR Imaging - MR images will be acquired using on the 3 Tesla scanners. Prior to scanning the
subjects will be asked to remove metal (including jewelry, etc.) from their clothing and
person. Subjects will wear earplugs as hearing protection during scanning. Subjects will lie
still in the scanner with their head positioned comfortably on a pillow for the duration of
the study. Subjects will be in communication with the investigators via two way intercom at
all times during the imaging study. Subjects will be encouraged to communicate any feelings
of discomfort to the investigator immediately. Periodically during the duration of the MRI
exam the investigators will confirm that the subject is comfortable and wishes to continue.
The entire imaging session will last 1-2 hours. Multiple anatomical or functional imaging
sequences will be run to assess specific image quality measures.
The same anatomical scans will be repeated varying a limited range of pulse sequence
parameters to assess their effect on the image contrast, image artifacts and signal to noise
ratio. Parameters that will be varied may include the repetition time of the MR acquisition
(TR), the echo time of the acquisition (TE), the presence of pre-acquisition inversion
pulses, the time interval between the pre-acquisition inversion pulse and the excitation
pulse, the spatial profile of the radiofrequency excitation pulse, the spectral profile of
the pre-excitation fat saturation pulse, the timing of when the spatial encoding occurs
within the repetition time of the sequence, the bandwidth of the signal digitizer, the
amplitude of the readout encoding gradient, The shape of the readout gradient waveform, the
duration and amplitude of diffusion weighting gradients, the spatial resolution of the MR
images, the number of spin-echoes acquired per excitation and the tip angle of the RF
excitation. The above parameters will also be evaluated in pulse sequences, which acquire
parameters used in the reconstruction of the MR images. The range of these parameters will be
maintained within the FDA's non-significant risk criteria as ensured by the software and
hardware interlocks that are put in place by the scanner manufacturer. Anatomical imaging
sequence may be repeated with different MR coil configurations to compare the performance of
these coils. These coils will include volume head coils, transmit and receive surface coil
and receive-only phased array coils.
Image Evaluation - Images will be evaluated to determine the effect of pulse sequence
parameters and/or hardware configuration on image contrast to noise ratio, signal to noise
ratio, and specific image artifacts such as the Nyquist ghost level. The images acquired with
different pulse sequence parameters or MR hardware configurations will be compared.
Comparison of the MR images entails comparing the result of specific image quality measures
such as Signal to Noise Ratio (SNR) and Contrast to Noise Ratio (CNR) as well as the level of
image artifacts such as Nyquist Ghost levels. The measurement of several of these quantities
has been standardized by the National Electronics Manufacturers Association (NEMA). The NEMA
standards have been adopted by FDA as standards for use during the evaluation of premarket
submissions for medical devices (see "FDA Modernization Act of 1997: Guidance for the
Recognition and Use of Consensus Standards; Availability", Federal Register Vol. 63 No. 37
page 9561). The investigators will use these standard measurements where appropriate.
In cases where a standard measurement is not available or appropriate, the investigators will
use standard methods in use in the field. For example, the measurement of Nyquist Ghost
levels will entail measuring the mean image intensity in a region of interest containing the
ghost artifact but not the image and expressing it as a percent of the mean object intensity
across a large Region of Interest (ROI) in the object.
The contrast-to-noise ratio measurement will compare the image intensity difference
determined from Regions of Interest drawn in the two types of tissue regions of interest
(gray matter and white matter for example) to the mean of the noise in the magnitude image
corrected for the magnitude nature of the image using the correction factor described in the
NEMA Signal-to-Noise Ratio measurement standard. While there is some subjectivity in this
measurements incurred when the researcher places the ROIs, it is not felt to be subjective
enough in the eyes of most MR scientists to require a blinded study. Therefore the results of
the measurements will be compared by the investigators of the study in an unblinded manner.
In this study, the investigators will vary an MR image acquisition parameter and plot the
value of an MR metric (such as SNR, CNR, and image artifact measures described above) as a
function of the MR image acquisition parameter value. The image quality metric will be
measured at four to ten values of the MR acquisition parameter. For studies such as RF coil
comparisons, only a single measurement is required for each RF coil and the comparison
requires only the comparison of the image quality metrics or image artifact metrics to
determine which coil is more desirable. In cases where a continuous parameter is to be
optimized, the range of over which the parameter to be varied will be first determined from
what is possible to perform on the scanner by hardware timing and/or amplitude limits and by
the safety limits as defined by the FDA's non significant risk criteria. These limits are
determined in phantom studies prior to the human studies. The range limits of the human
studies will also be narrowed using the information available from literature describing
similar studies and knowledge based on models in the literature and the investigators
previous studies and experience with the dependency of the MR signal on the sequence
parameter in question.
The graph of MR quality metric vs. parameter value will be reviewed by the investigators to
determine whether a subset of the parameter values merits a finer search. If the range of the
graph exceeds a factor of 5% times the number of points, a finer search will be performed in
an attempt to determine the maximum within the 5% accuracy criteria. A standard binary search
strategy will be used. If the highest two points are adjacent to one-another, the region
between them will be probed with an additional 3-10 measurements. The procedure will deemed
to have converged when the range of the data points is less than 5% times the number of data
points. If the graph shows evidence of multiple maxima (the highest points are not adjacent
to one another), the multiple regions will be explored with additional measurements.
Experience indicates that more than 2 maximum are unlikely when optimizing MR acquisition
parameters over a range determined with prior knowledge (such as phantom studies or
theoretical analysis). If the graph is monotonically increasing or decreasing, the limits
will be expanded in the appropriate direction if possible. When the limits can no longer be
expanded or a maximum is not revealed upon expansion, then the region near the range limit
will be explored in 3-10 additional measurements to verify that the boundary is at the
constraint and to determine the potential value of efforts to increase the available limit
through hardware development or other tradeoffs within the pulse sequence.
