In vivo identification of peripheral nerve bundles during surgery using optical spectroscopy techniques: a pilot study

Clinical problem:
Damage to nerve bundles caused by surgery can lead to temporary or long time
morbidity. In some cases, damage is inevitable because tumour invasion or
encasement requires sacrifice of the nerve. However, in many surgical
procedures nerve bundles can and should be spared. The identification of these
bundles can be challenging, especially in patients who underwent previous
surgery in the same area or in those who received radiotherapy prior to
surgery. The consequences of nerve damage have a significant impact on the
patients* quality of life.

Clinical examples:
In rectal surgery, damage of the hypogastric plexus results in bladder
dysfunction (e.g. urine retention, stress or urge incontinence, loss of bladder
sensitivity) and sexual disorders (e.g. erection and ejaculation disorders,
decreased vaginal lubrication). Bladder dysfunction occurs in 20-30%, and
sexual disorders in approximately 30% of patients after rectal surgery1;2.
Facial nerve paralysis is a devastating complication of oncologic procedures in
the head and neck such as in parotidectomy. Post-operative facial nerve
dysfunction involving some or all of the branches of the nerve is the most
frequent early complication of parotid gland surgery. Temporary facial nerve
paresis, involving all or just one or two branches of the facial nerve, and
permanent total paralysis have occurred, respectively, in 9.3% to 64.6% and in
0% to 8% of parotidectomies, reported in the literature3;4.

Optical spectroscopy:
In recent years promising advances in cancer treatment imaging have been made
with optical spectroscopy. By illuminating specific tissue with a selected
light spectrum and subsequent analysis of the characteristic scattering,
absorption and luminescence patterns, it is possible to obtain an *optical
fingerprint* of the tissue and to discriminate between benign and malignant
tissue5;6. In this way optical spectroscopy may be more sensitive in tissue
discrimination than conventional imaging techniques7.
Incorporation of optical spectroscopy technology into current diagnostic or
therapeutic tools, e.g. in biopsy needles, could improve significantly the
accuracy of the intended procedure and thus clinical outcome. Recently, we have
developed an optical spectroscopy system for in vivo measurement of tissue
characteristics. The concept has first been tested on excised human tissue. In
this ex-vivo study we evaluated the *optical fingerprint* of normal tissue and
malignant tissue of breast, lung and liver. We were able to differentiate
between normal tissue (including benign tumours) and malignant tissue with a
sensitivity and specificity of >94% within patient analysis. Comparison studies
in the literature have demonstrated maximum sensitivity and specificity
percentages to be 83%.

Spectroscopy of nerve tissue:
Several groups have studied the application of optical spectroscopy to identify
nerve tissue. Rathmell and Brynolf have investigated the use of optical
spectroscopy to identify the epidural space and the brachial plexus in an in
vivo model in swine8;9. They were able to reliably identify nerve tissue in
vivo using spectroscopic contrast for the optical absorption of lipids and
hemoglobin. In these studies, nerve tissue was distinguished from surrounding
tissue by means of their lipid and hemoglobin content. The transition of the
needle tip from skeletal muscle to the nerve target region was associated with
higher lipid parameter values and lower hemoglobin parameter values.
There is little known about the fluorescence of nerve tissue. Adhikary et al.
focused on bovine and mice models to detect bovine central nervous system (CNS)
tissue in meat products10. They show that spectral signatures of lipofuscin
enables the detection of CNS-tissue in meat products.

With this pilot study we aim to prove that our optical spectroscopy system can
provide accurate identification of nerve tissue during surgery.

The study is designed as a pilot study.

Patients eligible for inclusion into this study are patients admitted to The
Netherlands Cancer Institute (NKI-AvL) for elective surgery.

Suitable patients:
- inguinal or axillary lymph node dissection (femoral nerve and side braches,
thoracodorsal nerve)
- cervical lymph node dissection (great auricular nerve)
- parotidectomy (facial nerve)
- patients undergoing rectal resection for rectal carcinoma

Procedures
The surgeon responsible for the operation will identify the nerve bundle. The
blunt tip optical needle will be placed on the nerve bundle as well as on
surrounding tissue and measurements will be performed.

During the operation, during up to 10 minutes optical spectroscopic
measurements are performed.
There are no anticipated risks for patients by participating in this study.
Extensive research by and with the optical spectroscopy methods on human tissue
have shown no adverse events.