Statistical Equivalence Test Protocol for RF Performance of AIMD Systems

Li-Yin Lee^{1}, Shiloh Sison^{2}, Shi Feng^{3}, Kishore Kondabatni^{4}, and Richard Williamson^{5}

Test methods for MRI
safety of AIMD systems has been defined through ISO/TS 10974^{1}. Specific to the assessments of RF lead
heating and RF unintended stimulation, the ISO/TS 10974 defines methods for
validating transfer functions (TFs) to within known uncertainty bounds. Since
there is uncertainty with any of the RF measurements, duplication of a
measurement or measurement set is unlikely.

AIMD systems are typical comprised of an electrical wire (lead) that terminates in one side in biologic tissue, and the other into a device with capacitive coupling to electronics. The leads of these devices should be expected to have the same RF characteristics (heating and voltage) when attached to variants of the devices (pacemaker, ICD or CRT-D) due to similar device input impedance and its corresponding linear scaling of RF voltage. A rigorous method to demonstrate equivalence of two systems in the presence of the uncertainty is yet to be defined. In absence of a rigorous criteria for determining equivalence, a complete retest of the new systems may be requested by regulators.

The Concordance
Correlation Coefficient^{2} (CCC) statistically determines data
reproducibility. CCC measures how far
observations deviate from the 45^{o} line between two sets of
measurements. It consists of a measurement of precisions through the
Pearson correlation coefficient (ρ)multiplied
by a measure of accuracy (C_{b})

The measurement of
precision, here the Pearson correlation coefficient , evaluates how far the observations deviate from the best-fit linear line.
The measure of accuracy (C_{b}), evaluates how far the best-fit line deviates from the concordance
line. C_{b }consists of the scale shift (the
ratio of two standard deviations) and location shift (the squared difference in
means relative to the product of the standard deviations). The equations for these are shown in figure 1.

Acceptance criteria
values to discriminate equivalence from non-equivalence for CCC, ρ , C_{b} were generated for over
uncertainty values that ranged from 1 to 50%.
These values are simulated across 2000 examples. CCC_{acceptance}, ρ_{acceptance} , C_{b, acceptance} was chosen that captured the 95% results of these 2000 simulated examples of CCC, ρ, C_{b.}

The flowchart in figure 1 is used to determine equivalence.

We evaluated if this method is an appropriate by evaluating 3 different paired datasets, and following the chart. The datatsets are one pair known to be equivalent, one pair known to be equivalent with scaling, and one pair known to be different.

Equivalence Pair - To demonstrate that the test can show
equivalence two versions of SJM Quartet™ leads (1456Q and 1458Q) that differ
only in electrode placement along the lead of the 4 electrodes (D1, M2, M3, P4)
were tested as the equivalent pair. Uncertainty was 19%. As the CCC_{comparison}
>CCC_{acceptance}, this pair confirm the method can
appropriately determine equivalence. Figure 2 shows the test criteria from the 2000 examples, and the results for this dataset

Equivalence with Scaling - To demonstrate the test can show scaling is required to show system equivalence, a single SJM Quartet™ lead was tested with a Quadra Allure™ CRT-P device and a Quadra Assura™ CRT-D device with a significant feedthrough capacitor difference. Uncertainty was 19%. Figure 3 contains a graph of the paired data from this test. Figure 4 shows the test criteria and results.

As ρ_{comparison}<ρ_{acceptance} but C_{b,comparison} > C_{b, acceptance}, Equivalence with scaling was determined. After scaling took place, CCC_{comparison} > C_{acceptance}.

Not Equivalent - To test a pair that does not correlate, an ICD lead was inserted into two different generations of ICD. The dataset from the same pathways were tested on the RV ring electrode and ICD, with the voltages from SVC electrode on ICD. As figure 5 shows, the data does is within uncertainty bounds but does not statistically correlate. The CCC and scaling criteria are not met, although most points are within the measurement uncertainty cone.

[1] ISO/TS10974 Assessment of the safety of magnetic resonance imaging for patients with an active implantable medical device

[2] Lin. L. I (1992), Assay validation using the concordance correlation coefficient. Biometrics 48:599-604

Figure 1 : Equations for Concordance Correlation Coefficient, Measure of Accuracy, and Pearson Correlation Coefficient, and how to apply to determine system equivalence

Figure 2 : Results showing Equivalence of Two Systems, as determined by CCC method. The CCCcomparison, derived through the paired measurements of the two systems, was greater than the CCCacceptance. Hence, equivalence is confirmed.

Figure 3 : Graphic showing plot of Paired Voltage measurements for Quadra Allure(TM) System with Quartet(TM)1458 leads and Quadra Assura System with Quartet(TM) 1458 leads. Pairs use the same Etan exposure. Figure visually confirms equivalence, but scaling is not unity.

Figure 4 : Results showing Comparison of Scalable systems. The above section of the table shows that the Cb (measure of accuracy) between the two systems is high (>0.98), but Pearson correlation Coefficient is low (<0.65). In lower section (scaled) both values are high and above the acceptance criteria.

Figure 5 : Results showing comparison of non equivalent systems. The results are from two electrodes (SVC,RV) of differing cable length. Although each paired measurement is within one uncertainty of a unity line, the CCC method does not meet the acceptance criteria. This confirms the method discriminates appropriately

Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)

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