Introduction
Treatment of extensive thoracoabdominal aneurysm disease via any modality represents
a unique challenge. Despite various adjunctive neuroprotective strategies during and
after open and endovascular aortic repair, ischemic spinal cord injury (SCI) remains
a common and devastating complication with profound impact on individual long-term
outcome, subsequent health care costs, and quality of life.[1] Specifically, for Crawford type II aneurysm repair, the incidence of postoperative
neurologic deficits is reported at approximately 10 to 20%, based on clinical series
and meta-analyses.[2]
[3]
[4]
Since the first successful thoracoabdominal aortic operations in the early 1950s,[5] specialists in the field of aortic medicine have sought to overcome this problem.
Maintenance of adequate spinal cord tissue oxygenation is critical to prevent SCI
during periods of acutely impaired blood flow.
Reliable monitoring of spinal cord integrity is required to allow for rapid response
via hemodynamic, cardiopulmonary, and cerebrospinal fluid management.
Although some invasive tools for monitoring the spinal cord (e.g. motor-evoked potentials
[MEP] and somatosensory-evoked potentials [SSEP]) are widely accepted, to date no
validated method for noninvasive real-time monitoring has made its way into widespread
clinical practice. This article describes the systematic translational research approach
to a novel, noninvasive spinal cord monitoring modality using near-infrared spectroscopy.
Current Spinal Cord Perfusion Concept—The “Collateral Network”
Comprehensive translational research over the past two decades has led to a better
understanding of the dynamic arterial network ensuring the integrity of spinal cord
perfusion, progressively challenging the historic paradigm and suggesting new strategies
for spinal cord protection during and after thoracoabdominal aortic aneurysm (TAAA)
repair.[6] Referred to as the “collateral network” (CN), this dynamic arterial network is largely
localized in the paraspinal musculature and is fed by branches of the subclavian arteries,
hypogastric artery, and directly from aortic segmental arteries (SAs[1]
[3]
[7]
[8]; [Fig. 1]).
Fig. 1 The paraspinal collateral network (CN)—(A) schematic illustration of the CN (collateral network; image modified from von Aspern
et al[1]), (B) illustration of spinal cord blood supply from the dorsal segmental artery feeders
(image modified from Khachatryan et al[8]), (C) illustration of the paraspinal CN in relation to the upper thoracic and lower lumbar
inflow (image modified from Khachatryan et al[8]).
The CN is augmented by intraspinal—immediately available—circulatory circuits composed
of repetitive, “Willis-like” micronetworks.[1]
[9] Through changes in regional blood pressure—caused by inflow disruption (e.g., SA
occlusion)—the plasticity of the CN is capable of developing a robust alternative
blood supply by means of arteriogenesis of new, and caliber alterations of preformed,
arteries and arterioles.[1]
[10] This “priming” process is triggered after partial and complete aortic SA sacrifice,
similar to open surgical and endovascular TAAA repair,[1] with the consequence of enabling sufficient blood flow to the spinal cord tissue
during chronic or acute perfusion loss.[1]
[3]
[7]
Conventional Spinal Cord Monitoring
In order to circumvent imminent damage to the spinal cord tissue (intra- and postoperatively),
few monitoring modalities have been developed or become routinely used in clinical
practice. The most widely used invasive methods for intraoperative spinal cord monitoring
are MEP and SSEP measurements.[11] Although SSEP monitoring can be implemented during the postoperative period, MEP
monitoring on the awake, nonsedated patient is limited.[12]
[13] Usually, significant technical and human resources are required. These invasive
methods are oftentimes not readily applicable during the postoperative course, while
entailing various additional limitations (e.g., sedation and induced muscle relaxation).
Ideally, spinal cord monitoring should reflect perfusion and ultimately tissue oxygenation
in real time, so as to allow for rapid response in hemodynamic, cardiopulmonary (e.g.
atrial fibrillation, ventilation), and cerebrospinal fluid management.
Noninvasive Spinal Cord Monitoring: Collateral Network Near-Infrared Spectroscopy
Maintenance of adequate spinal cord oxygenation is critical to prevent SCI during
periods of acutely impaired blood flow. Although invasive tools for monitoring the
spinal cord (e.g. MEP and SSEP) are widely accepted,[14] for a long time no validated method for noninvasive real-time monitoring has made
its way into clinical routine. Near-infrared spectroscopy utilizes characteristic
adsorption spectra of oxygenated and deoxygenated hemoglobin at near-infrared wavelengths
(760–2,500 nm) to quantify the regional tissue oxygenation (StO2) and consecutively estimate local perfusion.[1]
[8]
Previous attempts to directly assess spinal cord tissue oxygenation using near-infrared
spectroscopy have not been successful. The unfavorable bone-to-tissue ratio when placing
the optodes directly above the spinous processes (axially in mid-line) limited direct
oxygenation measurements of the spinal cord tissue, and measurements were clinically
not useful.[1]
[4]
[15]
[16] Therefore, near-infrared spectroscopy of the collateral network (cnNIRS) has been
introduced for noninvasive (indirect) real-time monitoring of spinal cord perfusion
and oxygenation in TAAA repair[4]
[17]
[18] ([Fig. 2]).
Fig. 2 Near-infrared spectroscopy of the collateral network (cnNIRS). (Left) illustration of conventional bilateral optode placement pattern (thoracic and lumbar;
image modified from Etz et al[26]). (Asterisk) cerebrospinal fluid drainage; (Right) illustration of cnNIRS optodes with regard to the paraspinal collateral network
(image modified from von Aspern et al[21]). CN = collateral network.
The Translational Research Process
Method Conceptualization and Validation
Based on the CN concept, it was theorized that oxygenation and perfusion in the paraspinal
muscles—hence the CN—should reflect oxygenation and perfusion of the spinal cord tissue
([Fig. 3]). Therefore, two major assumptions needed to be confirmed.
Fig. 3 Image illustrating the rationale for noninvasive near-infrared spectroscopy monitoring
of the collateral network (cnNIRS). The assumption is that oxygenation in the paraspinal
collateral network compartment reflects spinal cord tissue oxygenation in real time.
(Image modified from Bischoff et al[27]).
-
Does oxygenation and perfusion in the paraspinal CN correlate with spinal cord tissue
oxygenation and perfusion?
-
Does lumbar cnNIRS correlate with spinal cord tissue oxygenation and perfusion in
real time?
To validate cnNIRS as a tool for monitoring CN-oxygenation and ultimately spinal cord
integrity, it needed to be compared with direct oxygenation measurements of the paraspinal
muscles and the spinal cord. For this purpose, an acute large animal model was designed
comparing laser Doppler flowmetry (LDF)—an already validated method for invasive direct
flow- and oxygenation measurements—and paraspinal cnNIRS during aortic blood flow
alterations.[18] The experiment was carried out on seven juvenile pigs (German landrace; weight 41–48 kg).
NIRS optodes for noninvasive CN monitoring were placed bilaterally at the thoracic
(T5–T6) and lumbar (L2–L3) levels. For invasive, direct oxygenation and perfusion
measurements, LDF probes were introduced (1) into the paravertebral muscles and (2)
intrathecally at thoracic (T5–T7) and lumbar (L2–L4) levels under vision after exposure
of the spinal column and the dura. A lateral thoracotomy via the seventh intercostal
space was performed in order to expose the thoracic aorta for ischemia and reperfusion
introduction. The experimental sequence was (1) baseline, (2) cross-clamping (ischemia),
and (3) release (reperfusion). This sequence was repeated four times in each animal.
This experiment gave insight into the physiology of spinal cord perfusion and confirmed
that the paraspinal CN vasculature has indeed a strong direct association with spinal
cord microcirculation. It was demonstrated that regional paraspinal muscle oxygenation
reflects spinal cord tissue oxygenation and that lumbar cnNIRS reproducibly depicts
tissue oxygenation of the paraspinal vasculature during distal aortic ischemia and
reperfusion (R = 0.51–0.52, p < 0.001). Within 30 seconds, lumbar cnNIRS significantly decreased, reaching its
nadir after 8 minutes of ischemia (69 ± 6 percent-of-baseline), returning to baseline
values within 40 seconds during reperfusion.[18]
Clinical Application of Noninvasive cnNIRS Monitoring in Aortic Repair
Based on the results of the large animal validation experiments, cnNIRS in theory
should provide valuable information on the oxygenation status of the CN and, thereby,
indirectly, of the spinal cord also in a clinical scenario. Since near-infrared spectroscopy
has already been implemented in clinical practice for other purposes, and because
of its noninvasive characteristics, two further key questions needed to be answered
in order to pave the way for clinical implementation as a new monitoring modality
in aortic repair.
-
Is lumbar cnNIRS clinically feasible?
-
Are reduced lumbar cnNIRS measurements associated with postoperative neurologic deficits
(paraplegia and paresis)?
In clinical practice, near-infrared spectroscopy has been used effectively only to
monitor cerebral oxygen saturation during CPB and selective cerebral perfusion.[4] Analogous to this, conventional near-infrared spectroscopy optodes were used to
monitor tissue oxygenation of the thoracic and lumbar paraspinal muscles—hence the
paraspinal CN—to provide real-time, noninvasive spinal cord monitoring, potentially
indicating pending spinal cord ischemia. This was the first clinical study on cnNIRS
prior to, during, and after extensive open, endovascular, and hybrid TAAA repair.[4]
The study included 20 patients (mean age: 66 ± 10 years). Fifteen patients had open
thoracoabdominal aortic repair (Crawford II and III), three had thoracic endovascular
aortic repair (TEVAR; Crawford I), and two had a hybrid repair (Crawford II). It was
demonstrated that noninvasive cnNIRS monitoring in extensive TAAA repair is feasible.
Lumbar cnNIRS directly responded to aortic cross-clamping, reaching minimum values
after 11 ± 4 minutes (74 ± 13 percent-of-baseline). Patients suffering from postoperative
paraplegia (N = 3) demonstrated significantly lower lumbar cnNIRS values compared with patients
who did not experience neurologic deficits (p = 0.041).[4] These findings were later also confirmed by other researchers, who were able to
further demonstrate a significant correlation between pathological MEP and low cnNIRS
measurements in a clinical setting. Patients who exhibited intraoperative MEP ratios
lower than 50% also had significantly lower cnNIRS values compared to patients with
nonpathological MEP measurements (p = 0.037).[17]
Also, in clinical multicentre collaboration, cnNIRS has been investigated during the
endovascular TAAA repair of 109 patients. In this study, Lewis and colleagues found
that, in comparison with MEP and SSEP, cnNIRS was less sensitive for detecting potential
SCI (33% NIRS; 100% MEP/SSEP); however, cnNIRS was more specific in that regard (99%
NIRS; 10% MEP; 12% SSEP).[19]
Translational Feedback Concept—Addressing Clinical Key Questions Experimentally
Although previous clinical and experimental studies have gradually shown that cnNIRS
was technically feasible and that lumbar measurements correlate with spinal cord perfusion
and oxygenation during and after aortic cross-clamping and reperfusion,[4]
[18] cnNIRS monitoring during consecutive SA occlusion has not been evaluated. Since
extensive open and endovascular aortic repair entails SA sacrifice and, in light of
the recent introduction of minimally invasive staged SA coil- and plug embolization
(MIS2ACE) for paraplegia prevention,[3]
[6]
[20] real-time spinal cord oxygenation monitoring became increasingly important. According
to the translational feedback concept of addressing clinical key questions using established
large animal models, subsequent acute and chronic experiments were needed to answer
two additional questions:
-
Does lumbar cnNIRS react to consecutive SA sacrifice in real time (comparable to the
effects of extensive open aortic replacement or endovascular stenting)?
-
Is lumbar cnNIRS significantly correlated with neurologic outcome in a controlled
experimental model (confirming previous clinical results)?
Through these experiments,[3]
[21] it was demonstrated for the first time in a controlled, chronic large animal experiment
that lumbar cnNIRS reacts to occlusion of SAs in real time and correlates with neurologic
outcome. These experiments included 12 juvenile pigs with SA occlusion via open surgery
and consecutive ligation and 18 juvenile pigs with SA occlusion via staged minimally
invasive coil embolization.[3]
[21] Subjects from the open surgery experiment were further subdivided into a total occlusion
(N = 7) and a subtotal occlusion group (mimicking reimplantation of crucial SAs with
patent T12/T13, N = 5). The minimally invasive occlusion experiment also differentiated between left-
and right-sided SA occlusion with regard to cnNIRS measurements. In both experiments,
pigs were monitored over 3 days after finalization. Clinical status and neurologic
evaluation were assessed regularly at 6-hour intervals. Neurologic outcome was evaluated
using a modified Tarlov scoring system.[3]
[21] In the open surgery experiment, all subjects from the subtotal occlusion group completely
recovered, whereas 57% of the total occlusion group were paraplegic (N = 4/7). In the minimally invasive coil embolization experiment, permanent paraplegia
occurred in two (11%) and any kind of neurological deficit—temporary or permanent—in
seven animals (39%).
After complete SA occlusion, cnNIRS decreased—analogous to the ischemia/reperfusion
experiments—from 90 ± 4% to 58 ± 9% (32% of baseline, p < 0.008) with significant correlation to neurologic outcome (R = 0.7, p < 0.001).[3] This preliminary data supported cnNIRS as a valuable noninvasive tool for detecting
imminent spinal cord ischemia during and after aortic procedures involving SA occlusion.
Implications of cnNIRS for Novel Spinal Cord Protection Methods
MIS2ACE has been introduced for paraplegia prevention prior to extensive aortic repair.
During this procedure, SAs are occluded via a coil or plug insertion into the proximal
portion of the vessel, inducing CN priming for subsequent definitive aortic repair.
Due to frequent technical difficulties in localizing certain SAs for coil insertion
in an aneurysmatic aorta and the potential risk for MIS2ACE-associated SCI, additional efforts to facilitate a safe and effective MIS2ACE procedure seemed warranted.[22] Exact knowledge of the SA position and angle is paramount in order to avoid repetitive
contrast application or aortic injury due to excessive catheter manipulation during
MIS2ACE. Correct occlusion assessment represents another issue, since incomplete SA occlusion
may render an MIS2ACE procedure ineffective, while excessive occlusion or distal embolization may result
in iatrogenic SCI.
In order to further simplify the MIS2ACE procedure, an additional acute as well as a chronic large animal experiment were
designed to answer the question:
-
Is cnNIRS capable of guiding the MIS2ACE procedure by reliably detecting occlusion of individual SAs, thereby potentially
minimizing the amount of contrast agent, radiation exposure, and overall duration
of an MIS2ACE procedure?
It was demonstrated for the first time that lumbar cnNIRS independently reacts to
unilateral SA occlusion ([Fig. 4]). The mean difference between left- and right-sided cnNIRS measurements was 7 ± 4%
as soon as 1 minute after SAs of one side (and level) were occluded and perfusion
via the contralateral side remained (p = 0.001).[21] Lumbar cnNIRS also corresponded with neurologic outcome after MIS2ACE.[21] Based on these results, it was concluded that cnNIRS-guided SA occlusion is feasible
and may provide a useful adjunct, facilitating adequate and complete vessel occlusion.
Fig. 4 Intraprocedural real-time lumbar near-infrared spectroscopy of the collateral network
(cnNIRS) measurements after occlusion of a left- (red lines) and right-sided (blue lines) lumbar segmental artery (SA), arrows indicate moment of separate SA coil embolization.
Expanding and Optimizing Noninvasive Spinal Cord Monitoring
Previous studies have demonstrated the correlation of lumbar cnNIRS with the degree
of spinal ischemia and neurologic outcome.[1]
[17] Furthermore, recent clinical and experimental studies have highlighted its efficacy
for measuring the lumbar portion of the paraspinous CN (L2-L4) and demonstrated that
high thoracic (T4-T6) cnNIRS measurements may be of limited clinical use (presumably
due to the extensive collateralization in that region).[18] At the time no experience with cnNIRS measurements of the remaining paraspinal portion—hence
the entire paraspinal CN—was available. Especially with regard to the plethora of
procedures focused on the thoracic portion of the aorta, potentially contributing
to a procedural-related SCI risk (such as aortic arch replacement with a frozen elephant
trunk, fET), cnNIRS for real-time CN mapping needed to be investigated. Two main questions
were addressed:
-
Does cnNIRS of the mid-thoracic region downwards (T7 to L5) react to distal aortic
ischemia and reperfusion?
-
Is an expanded noninvasive cnNIRS optode placement pattern (T7 to L5) potentially
a versatile monitoring method also for procedures limited to the proximal thoracic
aorta (e.g. fET)?
The rational of these subsequent experiments was to compare segmental cnNIRS measurements
to the corresponding direct CN and spinal cord regional perfusion (measured by microsphere
injection) and thereby identify optimal cnNIRS optode placement pattern. It was reliably
shown that cnNIRS is capable of detecting relevant changes during distal ischemia
and reperfusion from the midthoracic level (T7) downward.[1] Measurements at the midthoracic to low lumbar levels decreased rapidly to a nadir
at 10 minutes of distal ischemia (mean differences between 18 ± 11% and 44 ± 9% of
baseline; p < 0.001–0.045), with more pronounced changes in the caudal regions.[1] High thoracic cnNIRS (T3–T6) remained stable, analogous to previous clinical and
experimental studies. Measurements of cnNIRS, CN, and spinal cord regional perfusion
demonstrated comparable curve progressions starting from the midthoracic region (R = 0.5–0.7;
p < 0.001).[1] It was therefore concluded that for aortic procedures an expanded noninvasive cnNIRS
optode placement (T7-L5) seems useful and may serve as a versatile monitoring method
also for procedures limited to the proximal thoracic aorta.[1]
In a direct consequence, various groups used cnNIRS clinically during extensive arch
procedures utilizing the fET technique.[23]
[24]
[25] In these series, it was demonstrated that cnNIRS of the midthoracic region (starting
from thoracic level 7) measures a significant decrease during fET implantation.[23]
[24] Honkanen and colleagues demonstrated in their large animal experiments that cnNIRS
measurements at the mid- and lower thoracic region (T8–T10) significantly decrease
during simulated fET implantation with selective cerebral perfusion, reaching a nadir
within 35 minutes.[25] In a clinical series of 18 patients by Kinoshita et al, cnNIRS measurements at the thoracic level (T10) decreased markedly during circulatory
arrest and fET implantation, even after initiation of selective cerebral perfusion
(nadir at 30 percent-of-baseline after 20 minutes). Values increased and reached baseline
values within 30 minutes after resuming full body circulation.[24] However, these experiments, clinical series, and reports were underpowered to demonstrate
a clear correlation with neurologic outcome and remained speculative with regard to
the potential clinical implications of this new monitoring modality in the setting
of extended aortic arch procedures.
Conclusion and Perspective
Despite various contemporary adjuncts to mitigate treatment-associated SCI, the incidence
of paraplegia after open and endovascular TAAA repair remains high. Clinically established
methods for spinal cord monitoring are invasive and oftentimes not readily applicable
during the postoperative course. Ideally, spinal cord monitoring should be noninvasive
and easy to use and should reflect tissue perfusion/oxygenation in real time.
This presented translational research review, aims at systematically investigating
cnNIRS as a feasible monitoring method, from early conceptualization to clinical application
in aortic medicine.
The outlined translational research approach is dynamic and ongoing. Based on the
currently available data, however, lumbar cnNIRS reproducibly reflects spinal cord
tissue oxygenation and perfusion in real time and appears a feasible method for clinical
practice. cnNIRS reacts to open and endovascular SA sacrifice, functioning as a promising
new tool for guiding spinal cord protective procedures such as MIS2ACE. Both experimentally and clinically, it has been demonstrated that cnNIRS correlates
with postoperative neurologic outcome and other established monitoring modalities
such as MEP and SSEP with high specificity. The data at hand indicate that an expanded
optode placement pattern might be useful also for procedures limited to the proximal
thoracic aorta (e.g. fET); however, further studies are warranted to generate adequate
power for meaningful conclusions above and beyond current preliminary results.
As a consequence of a decade of systematic research, cnNIRS has since been introduced
as a method for spinal cord monitoring during and after aortic repair at many specialized
centers. Although additional clinical and experimental research is warranted (to further
investigate cnNIRS with regard to different patient- and procedural-related aspects
[e.g., hypothermia, SA reimplantation and sarcopenia], measurement thresholds indicative
of imminent SCI and prolonged monitoring periods beyond 48 hours to account for potential
delayed paraplegia), this noninvasive method has become a promising tool for spinal
cord monitoring during and after aortic procedures of any modality.
