Transcript The Medical Device Directorate and Quantitative Magnetic Resonance Paul Tofts

The Medical Device Directorate
and Quantitative Magnetic
Resonance
Paul Tofts (1) and Geoff Cusick (2)
Institute of Neurology, UCL
Department of Medical Physics, UCLH
(1)
(2)
IPEM November 12th 2004
• qMRI
(URL: qmri.org)
– Paradigm shift from happy
snappy MRI camera
– scientific instrument
measuring clinically
relevant quantities.
• MR pulse sequences
• MR image analysis
programs
• Work-in-progress
MR pulse sequence = program
• Three fields:
– magnetic field Bo - static
• Beware projectiles, implants
– magnetic field gradients – switched
• dB/dt – induces emf. Neural stimulation. Painful.
– Radiofrequency fields – pulsed
• Power deposition, heating, SAR
• Data collection, reconstruction
Why should MR physicists be
concerned with the MDD?
• Reduce personal liability of physicists
• Improve quality of the device
– better science
– fewer errors
(re)interpreting the MDD for qMR
• Many Essential Requirements (n=96?)
• Physicists hate ‘bureaucracy’
• Provide a friendly interface
☺
– only relevant ER’s visible (n=7)
MDD – 96 Essential Requirements (ER’s)
identify MR-relevant ER’s
Interface – response to each ER can be: N/A, SRm or GRn
Guidance
notes
Specific
Responses
(SR’s)
General
Responses
(GR’s)
questionnaire
Standard info
MR-relevant ER’s
1.
The device (whether sequence or program) must be shown to work
as intended [ER3, ER12.1] → SR1
2.
The device have an instruction manual [ER13.1] → SR2
3.
The device must give output with proper units [ER10.3] → SR3
4.
The accuracy of the device must be specified [ER10.1] → SR4
5.
The precision of the device must be specified [ER10.1] → SR5
6.
The limits of accuracy of the device must be specified [ER10.1] →
SR6
7.
A sequence device must have safe RF power deposition SAR [ER1,
ER9.2, ER11.1.1, ER12.1] → SR7
8.
A sequence device must operate with the lowest reasonable static
field, SAR and dB/dt. → GR8
Guidance notes - general
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developing good practice.
errors are valuable!
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analysed case studies and learn
modify procedures to at least prevent such known errors from
taking place again.
devices should have ‘test modes’, where the likely
errors can be anticipated
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an independent person should look at the device and
check its operation.
Guidance notes – general - 2
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qMR is a measuring instrument
– follow traditions of measurement
– specify accuracy and precision
– uncertainty and uncertainty budget
•
Human error is always present.
– recognition and acceptance
– design test procedures to detect it
1 The device (whether sequence or program)
must be shown to work as intended
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technical description: Name the device. What type of device is
it? describe the design of the device. Why was it developed?
What kind of output does it give? How does it work?
anticipate the most likely errors (up to three) that could occur
and how the chance of these happening can be minimised. Look
at the case studies where errors have occurred. Recognise that
human error is always present.
Provide test modes to anticipate problems (including those of
human error through inadequate training). For a sequence, this
could be to vary one or more of the user-set parameters (the
ones that the user is expected to alter as part of using the device)
and to monitor that the response is as expected. For programs,
provide test image data and ensure the user can replicate the
expected results (within given confidence limits).
1 The device (whether sequence or program)
must be shown to work as intended - continued
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Provide independent review of the device by an experienced
person or persons (one physicist and maybe one non-technical
user).
Monitor the device usage during a beta-test period. This could be
for one month, or 20 measurements, after the device has been
handed over to the user.
Through manufacturer upgrades (hardware or software) all these
validation procedures will have to be repeated.
Quality Assurance (QA) phantom results and normal control
values may be used to support the validity of the device
Accuracy and precision data (see elsewhere) also support
validity
2. The device have an instruction manual
•
write a (short) set of instructions for a non-technical
user. Make this inbuilt to the device if possible, so it
cannot get lost (for a pulse sequence ?? how can this
be done? Link to a website? Could get broken; for a
program, on-line usage and help). Test the manual
with at least 2 users.
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Anticipate potential problems and errors and include
these in the manual
3 the device must give output with proper units
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give the output in proper SI units where possible (for
example ms, percent units (pu), microseconds).
Stored integer values in calculated maps should be at
good enough resolution so as not to degrade the data,
whilst not coming near the 16-bit signed integer limit of
32767 ; this typically means values of between 100010,000.
Use the scaling factor facility in the display program
(dispim) and in the (UNC) file header so that real
floating point values can be used directly by the user,
without seeing the integer values.
4. The accuracy of the device must be specified
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show that the quantity being produced is close to the
truth, as far as possible.
For a pulse sequence, use a search coil to confirm
aspects of a new pulse that may be crucial,
particularly its amplitude.
For an analysis program, show that the quantity being
measured is true in phantoms, if possible. [Some
quantities, for example blood flow, may only
meaningfully exist in the brain, since accurate enough
phantoms do not (yet) exist. Others, such as volume,
can meaningfully be tested in phantoms (test objects)].
5. The precision of the device must be specified
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measure the reproducibility by repeated
measurements
use repeated scans if necessary
use paired measurements and the Bland
Altman analysis to estimate standard
deviation and 95% confidence limits
6. The limits of accuracy of the device must
be specified
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Presumably means the 95% CL for total
uncertainty (whether arising from systematic or
random sources).
can be calculated from the mean inaccuracy,
and the 95% confidence limit on repeated
measurements, by combining the two
quantities.
‘uncertainty budget’, type A and B errors
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See ‘QMRI of the brain’ page 68 for refs
7. A sequence device must have safe RF
power deposition SAR
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this is an ongoing tricky subject
see elsewhere (general response GR5)
General responses
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GR1. MR sequences are generally
developed and used in ‘research mode’,
and therefore do not, in general, have a
blanket coverage arising from the
manufacturer’s CE mark. Although the
static field cannot be altered in research
mode, the RF power, and possibly
gradient switching rate, can be and
therefore need to be considered in detail.
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GR2. There are general safety guidelines from various bodies. In the
UK, the relevant bodies are the National Radiation Protection Board
(NRPB) and Health and Safety Executive (HSE). In Europe there may
also be a body. In the USA, the FDA is relevant.
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These guidelines affect the static field, the rate at which the gradients can
be switched (dB/dt), and the Radiofrequency (RF) power deposition
(SAR).
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An additional issue is that the HSE seems to be recommending against
anything above 2.0T. This seems to be a problem affecting MR in the
whole UK, and has not been resolved.
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In general the risk associated with MRI is very low, and there is a
general move towards MRI and away from other (more risky) imaging
techniques such X-ray Computed Tomography and nuclear medicine,
both of which involve ionising radiation.
GR3 static field
• At Queen Square, including associated
Chalfont, there are clinical machines
operating with ethical approval at 1.5T,
3.0T and 4.7T
GR4 The gradient switching rate
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This determines the dB/dt (this increases with distance
from the magnet isocentre).
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In pulse sequences this is not usually increased above
the manufacturer’s value
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The consequences of a high dB/dt are stimulation of
some muscles, usually in the chest wall, and are
considered to be uncomfortable but not dangerous.
GR5 Radiofrequency (RF) Power deposition
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defined by the Specific Absorption Rate (SAR) watts/kg
potentially the most hazardous factor.
Small amounts can cause a feeling of being warm;
large amounts could in principle cause local heating in tissues
that do not have a blood supply, such as the vitreous humour or
lens in the eye, and as a worst case a cataract could result.
The GE scanner has a variety of SAR checks, in software and
hardware, some of which can be turned off in research mode. The
software checks are complex; they attempt to take into account
the mass of the subject, they make some assumptions about the
distribution of the deposited power, and also set rules about the
time course of the power deposition (i.e. controlling both
instantaneous and time-averaged power deposition).
This is an area about which we are currently investigating, and
where each scanner manufacturer will have a different Research
Mode environment. We are currently considering starting a project
to measure deposited power directly, in a phantom.
GR6 Acoustic noise
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can be annoying
for many sequences ear plugs are offered to
the subject.
The sound level is dependent primarily on the
gradient switching rate and the number of
gradient pulses per second
provided this is not increased (see above), the
sound level is not expected to increase above
that found in noisy sequences used in clinical
mode.
GR7 Other factors
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ferromagnetic projectiles, internal metal
structures, or quenches
no more risky than when conventional
sequence are used in clinical mode.
GR8. ALARA
• A sequence device must operate with the
lowest reasonable static field, SAR and
dB/dt.
• In general, the characteristics of the device
would be degraded by going to lower static field,
SAR and dB/dt.
• The signal-to-noise ratio and hence precision
would suffer.
• SAR could not be reduced without removing or
reducing RF pulses that are required for the
sequence to work.
• Reduced dB/dt would increase scanning time.
GR10 Image analysis programs
• take MR data from the scanner (in fact these can be in
the form of images or spectra).
• The data include header information (such as echo time,
patient ID). The accurate carrying through of header
information must be checked.
• Post 2004-upgrade scanner data are provided by GE in
DICOM format, and then translated to UNC format by an
in-house program (called Gedicom2unc ).
• Old (pre-2004 upgrade) will be available from GE in
DICOM format, although the exact DICOM
implementation may be subtly different.
GR11. programming environment
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is this in accordance with current good
practice?
Controlling binaries. Version control.
Authorship control. Keeping old ones
etc.
computer system, manager.
What is current good software engineering
practice?
Error case study 1 - B1 mapping sequence
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History:
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inexperienced scientist implemented a B1 mapping technique,
which worked correctly under their use. (B1 = RF field)
handed over to a non-technical user, with an instruction sheet.
sheet had an error in it.
sequence was used incorrectly for several months
Learning:
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experienced independent person should have oversight
before handing over the device.
Inbuilt test mode would have forced the users to find the
error (provided it was used!). For this device, reduce
transmitter output by known amount, and remeasure B1
Monitoring, by a technical person, of the device during its
first weeks of use would probably have detected the error.
The manual is part of the device, and need to be tested!
Silently watch how a naïve user uses the device.
Case study 2: qMT sequence
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History:
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A sequence to apply 3 different amplitudes of MT saturation
pulse amplitude was written.
The resulting data appeared to fit a model, and were
published in 3 places
An independent physicist, developing their own qMT
sequence, found they could not reproduce the original data.
Several experienced physicists became involved, and
suggested measuring the MT pulses directly.
The amplitude of one pulse was found to be wrong, and the
explanation found.
A retrospective correction of old data could be made; the
resulting corrected data were of higher quality, as judged by
fitting the model, and also agreeing with those from other
groups.
Magnetisation Transfer
Free water protons
RF
Bound protons
0
0
Unsaturated - Su
Magnetisation Transfer Ratio
0
Saturated - Ss
100.( Su  Ss )
MTR 
Su
Original qMT sequence
gaussian lineshape
qMT – corrected data
super-lorenzian lineshape
Case study 2: qMT sequence cont
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Learning:
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Do not assume a new sequence is doing what you think. Recognise
that pulse amplitudes may be wrong on a (GE) scanner.
Invent independent ways of testing the sequence
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progressively increase Bsat and observe the signal. Do this in a phantom,
and use Bsat values at least as high as in-vivo. Do this 20kHz offresonance (where the behaviour of the imaging pulse is monitored), and
signal should be constant, and 1khz off resonance, where a progressive
reduction should be seen.
observe MT and imaging pulses with search coil for progressive
experiment described above; measure amplitude (with confidence limits)
relative to first imaging pulse. Measure its width, and estimate its area
(and hence FA) relative to the imaging pulse.
We still need a way of testing the offset frequency, although errors in this
are less likely
Ask an independent person – do you believe this sequence is
doing what I have programmed it to do?
Error case study 3: MTR x10
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History:
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MTR values are in the range 10-40pu; they are stored in
computer files as integers (range 100-400) to obtain 0.1pu
precision.
The clinical researcher was dealing with the integer values in all
their analysis, including graphing
The integer values were passed to a statistician for complex
analysis
The statistician estimated wrong values of difference and slope
An independent person recognised the factor of 10 error.
Learning:
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Output all map values as floating point values, with proper units
No access for the user to the raw integer values.
Independent review works
conclusions
• MR Safety is in a state of flux
• More on good design practice
– Lessons from electrical instruments, software
• Acceptability to MR physicists?
• Science will improve
– “Every time I make a mistake I’m really pleased because I learnt something”