Towards clinico-pathological application of Raman spectroscopy

Introduction
Detection of Meningioma in Dura Mater by Raman Spectroscopy
Meningiomas are the most common tumors of the meninges, composed of neoplastic
meningothelial (arachnoidal) cells. They account for about 20% of all brain tumors. 1 There
are many different histological subtypes of meningioma most of which are histologically
benign. 1 Meningiomas are usually broadly attached to dura and are slowly growing tumors
usually not infiltrating brain tissue. Despite their benign growth pattern these tumors are
responsible for serious morbidity. Complete resection is the treatment of choice for lesions
that are surgically accessible. 2 Although predominantly benign, meningiomas often recur,
even following apparently complete resection. 3 15-year recurrence rates of over 30% have
been observed after complete tumor resection. 4 A number of studies have addressed predictive
factors for recurrence of meningiomas. These include histological subtype, mitotic
index, age, gender, and also the extent of surgical excision. 4,5 In a classic paper by Simpson
this issue was addressed. 6 It was postulated that residual nests of meningioma within the
regional dura would play a major role, confirmed by later studies. 7,8 Surgical removal of
all dura infiltrated by tumor during resection is therefore important. Thusfar no objective
per-operative tools are available to verify whether all tumor tissue has been removed.
In the study reported here, we have investigated the possibility of using Raman spectroscopy
to distinguish between meningioma and dura to identify possibilities for the development
of an in vivo Raman method as the basis for real-time guidance during surgical resection of
meningioma. We used some of the most common subtypes of meningioma, e.g., syncytial
and transitional subtypes, and the less common microcystic subtype of meningioma. 1
Raman spectroscopy is a non-destructive vibrational spectroscopic technique, based on
inelastic scattering of light by the molecules in a sample. A Raman spectrum provides information
about the molecular composition, molecular structures and molecular interactions
in a tissue and can therefore be used to obtain specific biochemical information about a
given tissue or disease state. 9,10 In recent years, significant progress has been reported in
the application of Raman spectroscopy for in vitro characterization of tissues. A number of
studies reported on Raman spectra of various normal tissues and on spectral differences
between normal tissue and neoplastic tissue of the skin, colon, larynx, cervix and breast. 11-20
So far only few studies have reported on the use of Raman spectroscopy for brain tissue
characterization. Mizuno et al. analyzed Raman spectra of different anatomical and functional
structures of rat brain and they were the first to publish spectra of different brain
tumors. 21,22 Wolthuis et al. demonstrated that water concentration in brain tissue can be very
accurately determined by Raman spectroscopy. 23 Recently, we published the results of an in
vitro study on human glioblastoma tissue describing the potential of Raman spectroscopy
for brain biopsy guidance. In that study, a classification model, based on spectra obtained,
for discrimination between vital and necrotic glioblastoma tissue yielded 100% accuracy. 24
The fact that Raman spectroscopy is noninvasive and does not rely on extrinsic contrast
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