Value of Trans-Impedance Matrix (TIM) measurement for detection of New Bone Formation (NBF) and influence on electrophysiology, residual hearing and performance.

Cochlear tissue formation around the electrode of a cochlear implant is well
known. Formation of scar tissue around the electrode of a cochlear implant can
be either iatrogenic or resulting from a natural process. Iatrogenic scar
tissue around the electrode can be induced by the *traumatic* insertion of the
electrode array during surgery. Natural scar tissue is related to the reaction
of the body to a foreign body by encapsulation of the object. It is believed
that a dense tissue sheath around the electrode is problematic. In its most
pronounced form, this tissue is ossified. This new bone formation (NBF) around
the electrode has been observed in several animal and histopathological
studies.1-4

In CI care, it is relevant to be able to detect the formation of a thick tissue
layer for several reasons. First, the stimulation current will have to pass
through this tissue layer, adding additional resistivity. Higher impedances
imply more power consumption and more out-of-compliance issues. This may impact
device fitting, e.g. higher C-levels, longer pulse widths or in general poorer
access to the neural tissue (in case of ossification). Second, the layer will
influence the current spread through the cochlea, possibly leading to more
channel interaction. Third, the NBF might influence long term loss of residual
hearing. In a recently conducted cross sectional study (unpublished results) it
was found that participants with presence of NBF (after an average follow-up
time of 45 months) had significantly more loss of long term residual hearing
compared to participants without NBF. Fourth and clinically most relevant,
overall performance outcomes may be impacted directly or indirectly due to
above factors.

In general, there is a desire to control and reduce the formation of a
substantial tissue sheath. However before we can control, we need to be able to
detect and monitor. The feasibility of detection has been demonstrated
(manuscript in preparation) in a recent cross-sectional study where NBF was
detected using an ultra high resolution computed tomography (UHRCT) scanner in
the Radboudumc. A certain degree of NBF was seen in 61% of the 125 participants
at an average follow-up of 3.8 years (SD 1.7; Range 1.2 - 7.7 years). A total
of 2750 electrode contacts were judged to be surrounded with NBF or not; 13% of
all contacts were found to have NBF around the electrode contact. In the same
patient group, at the same moment, transimpedance measures (TIM) were taken. A
first analysis showed that electrode contacts with NBF had higher values of
total impedance compared to electrode contacts without NBF. The mean total
impedance between contacts with / without NBF was respectively 7.468 (SD 2.022)
and 5.863 (SD 2.362). This finding indicated that TIM measurements might be
useful to detect and monitor NBF in CI patients. However, as indicated by the
standard deviation, the variability of total impedance between contacts with
and without NBF overlapped strongly; showing TIM measurements to depend on
individual factors and, thus, vary greatly between patients.

The difference in mean total impedance might be explained by an (stronger)
increase of TIM values in contacts with NBF compared to contacts without NBF.
The most important limitation of the cross sectional study is the absence of a
baseline TIM measurement (post implantation). To properly study the influence
of NBF a prospective study should be conducted. This prospective study should
include repetitive measurement of TIMs, to identify the increase of TIM values
and to test the hypothesis that a degree of TIM growth is associated with NBF
on long term imaging. With such a prospective study the hypothetical value of
TIM to identify and monitor NBF growth can be shown. In the future, TIM
measurements might be useful as a tool in NBF research and possibly as a
clinical diagnostic tool.

Primary Objective: Determine the value of trans-impedance measurement (TIM) for
detection of new bone formation (NBF).
Secondary Objective(s): Determine the influence of NBF on electrophysiological
parameters, residual hearing and speech perception development.

A prospective study in patients that will receive a CI system and are willing
to participate

Benefits of this study relay to an improved understanding and monitoring of
postoperative intra-cochlear changes and the effect of these changes on
residual hearing and performance, with possible implications for future
therapy. Moreover, if the hypothesis that TIM is able to detect and monitor NBF
is confirmed; in future studies, TIM can (partially) replace CT-scans and can
be used to monitor studies with interventions against NBF

In this study, two additional post-operative UHR CT-scans of the temporal bone
are required to monitor the NBF in participants. For those patients who for
some reason do not receive a pre-operative UHR CT-scan, this will be performed
as well. These UHR CT-scanners deliver a radiation load of 0.28 mSv per scan.
In comparison, according to the RIVM, a CT-scan of the human brain delivers an
average dose of 2.3 mSv, whilst a CT-scan of the abdomen delivers an average
dose of 10.3 mSv. The worldwide annual average background radiation dose is
approximately 2.6mSv.