The role of optical spectroscopy in epilepsy surgery in children

Sanjiv Bhatia Brain Institute, Miami Children's Hospital, Miami;
Department of Neurological Surgery, University of Miami Leonard M. Miller School of Medicine, Miami, Florida;

Search for other papers by Sanjiv Bhatia in
jns
Google Scholar
PubMed
Close
 M.D.
,
John Ragheb Brain Institute, Miami Children's Hospital, Miami;
Department of Neurological Surgery, University of Miami Leonard M. Miller School of Medicine, Miami, Florida;

Search for other papers by John Ragheb in
jns
Google Scholar
PubMed
Close
 M.D.
,
Mahlon Johnson Department of Pathology, Division of Neuropathology, University of Rochester Medical Center, Rochester, New York; and

Search for other papers by Mahlon Johnson in
jns
Google Scholar
PubMed
Close
 M.D., Ph.D.
,
Sanghoon Oh Brain Institute, Miami Children's Hospital, Miami;
Department of Biomedical Engineering, Florida International University, Miami, Florida

Search for other papers by Sanghoon Oh in
jns
Google Scholar
PubMed
Close
 Ph.D.
,
David I. Sandberg Brain Institute, Miami Children's Hospital, Miami;
Department of Neurological Surgery, University of Miami Leonard M. Miller School of Medicine, Miami, Florida;

Search for other papers by David I. Sandberg in
jns
Google Scholar
PubMed
Close
 M.D.
, and
Wei-Chiang Lin Brain Institute, Miami Children's Hospital, Miami;
Department of Biomedical Engineering, Florida International University, Miami, Florida

Search for other papers by Wei-Chiang Lin in
jns
Google Scholar
PubMed
Close
 Ph.D.
Full access

Object

Surgery is an important therapeutic modality for pediatric patients with intractable epilepsy. However, existing imaging and diagnostic technologies such as MR imaging and electrocochleography (ECoG) do not always effectively delineate the true resection margin of an epileptic cortical lesion because of limitations in their sensitivity. Optical spectroscopic techniques such as fluorescence and diffuse reflectance spectroscopy provide a nondestructive means of gauging the physiological features of the brain in vivo, including hemodynamics and metabolism. In this study, the authors investigate the feasibility of using combined fluorescence and diffuse reflectance spectroscopy to assist epilepsy surgery in children.

Methods

In vivo static fluorescence and diffuse reflectance spectra were acquired from the brain in children undergoing epilepsy surgery. Spectral measurements were obtained using a portable spectroscopic system in conjunction with a fiber optic probe. The optical investigations were conducted at the normal and abnormal cortex as defined by intraoperative ECoG and preoperative imaging studies. Biopsy samples were taken from the investigated sites located within the zone of resection. The optical spectra were classified into multiple subsets in accordance with the ECoG and histological study results. The authors used statistical comparisons between 2 given data subsets to identify unique spectral features. Empirical discrimination algorithms were developed using the identified spectral features to determine if the objective of the study was achieved.

Results

Fifteen pediatric patients were enrolled in this pilot study. Elevated diffuse reflectance signals between 500 and 600 nm and/or between 650 and 850 nm were observed commonly in the investigated sites with abnormal ECoG and/or histological features in 10 patients. The appearance of a fluorescent peak at 400 nm was observed in both normal and abnormal cortex of 5 patients. These spectral alterations were attributed to changes in morphological and/or biochemical characteristics of the epileptic cortex. The sensitivities and specificities of the empirical discrimination algorithms, which were constructed using the identified spectral features, were all > 90%.

Conclusions

The results of this study demonstrate the feasibility of using static fluorescence and diffuse reflectance spectroscopy to differentiate normal from abnormal cortex on the basis of intraoperative assessment of ECoG and histological features. It is therefore possible to use fluorescence and diffuse reflectance spectroscopy as an aid in epilepsy surgery.

Abbreviations used in this paper:

ECoG = electrocochleography; EEG = electroencephalography; PET = positron emission tomography; SPECT = single-photon emission CT.

Object

Surgery is an important therapeutic modality for pediatric patients with intractable epilepsy. However, existing imaging and diagnostic technologies such as MR imaging and electrocochleography (ECoG) do not always effectively delineate the true resection margin of an epileptic cortical lesion because of limitations in their sensitivity. Optical spectroscopic techniques such as fluorescence and diffuse reflectance spectroscopy provide a nondestructive means of gauging the physiological features of the brain in vivo, including hemodynamics and metabolism. In this study, the authors investigate the feasibility of using combined fluorescence and diffuse reflectance spectroscopy to assist epilepsy surgery in children.

Methods

In vivo static fluorescence and diffuse reflectance spectra were acquired from the brain in children undergoing epilepsy surgery. Spectral measurements were obtained using a portable spectroscopic system in conjunction with a fiber optic probe. The optical investigations were conducted at the normal and abnormal cortex as defined by intraoperative ECoG and preoperative imaging studies. Biopsy samples were taken from the investigated sites located within the zone of resection. The optical spectra were classified into multiple subsets in accordance with the ECoG and histological study results. The authors used statistical comparisons between 2 given data subsets to identify unique spectral features. Empirical discrimination algorithms were developed using the identified spectral features to determine if the objective of the study was achieved.

Results

Fifteen pediatric patients were enrolled in this pilot study. Elevated diffuse reflectance signals between 500 and 600 nm and/or between 650 and 850 nm were observed commonly in the investigated sites with abnormal ECoG and/or histological features in 10 patients. The appearance of a fluorescent peak at 400 nm was observed in both normal and abnormal cortex of 5 patients. These spectral alterations were attributed to changes in morphological and/or biochemical characteristics of the epileptic cortex. The sensitivities and specificities of the empirical discrimination algorithms, which were constructed using the identified spectral features, were all > 90%.

Conclusions

The results of this study demonstrate the feasibility of using static fluorescence and diffuse reflectance spectroscopy to differentiate normal from abnormal cortex on the basis of intraoperative assessment of ECoG and histological features. It is therefore possible to use fluorescence and diffuse reflectance spectroscopy as an aid in epilepsy surgery.

Surgery has become an acceptable form of management for intractable epilepsy in children. The management begins with a clear understanding of the semiology of habitual seizures. These symptoms help in understanding the possible site of onset of the seizure activity. The location of this site is then confirmed with surface and video EEG recordings, which may be performed on multiple occasions. Magnetic resonance imaging now is playing an increasingly prominent role in epilepsy surgery because it can be used to outline the structural abnormalities and demonstrate functional correlates.36,43 Both ictal SPECT and PET scans can outline the physiological abnormalities associated with the epileptic substrate46 and therefore assist in localizing the area of seizure onset and defining the target for more precise surgery. Often, these data must be supplemented by intraoperative or extraoperative electrocorticography32 and magnetoencephalography.29

Despite a number of attempts to localize seizure onset, results of resective surgery for pediatric intractable seizures are often less than optimal in certain situations. Difficulties in precise localization, the episodic nature of the seizure discharge, and colocalization with eloquent cortex make the entire exercise challenging. Residual tumors, cortical dysplasia, and structurally normal epileptic tissue can account for recurrent seizures. The challenges are increased significantly in children with nonlesional epilepsy.18 Improvements in technology to facilitate better recognition of epileptic neural tissue can help to improve the results of resection. These measures have included coregistration of ictal SPECT scans with MR anatomical images, intraoperative frameless neuronavigation to recognize areas of dysplasia in the depths of sulci and assist in the placement and depth of electrodes. Our group has investigated the use of optical spectroscopy to recognize the unique pathophysiological features associated with cortical abnormalities in pediatric epilepsy. In the present study, we elaborate on the basics of optical spectroscopy as applied to neural tissue and summarize our preliminary experience with this technology in epileptic tissue in the pediatric population.

Optical Spectroscopy

The propagation of light in biological tissue is governed by the morphological, biochemical, and physiological characteristics of the tissue; therefore, light provides a convenient, noninvasive means of characterizing tissue diseases and injuries.4,35,38,42,55 There are 3 optical spectroscopy types that are used frequently in biomedicine to monitor light-tissue interaction and therefore to perform in vivo tissue characterization: diffuse reflectance spectroscopy,6,7,9,12,13,19,20,25,30,34,39,48,50,54,56–58 fluorescence spectroscopy,26,27 and Raman spectroscopy.2,11,15,16,31,33 Each of these spectroscopy types targets a particular type of light-tissue interaction and a subset of biological molecules (Fig. 1).

Fig. 1.
Fig. 1.

Schematic diagram summarizing the potential uses for optical spectroscopic techniques for characterizing the brain in vivo. The intrinsic biological and morphological characteristics of the brain, their corresponding unique interactions with light, and the detection mechanisms are shown.

The primary neurosurgical utility of optical spectroscopy, explored thus far, is to demarcate a brain tumor intra-operatively. Several research groups have demonstrated the feasibility of using intrinsic fluorescence and optical characteristics to differentiate brain tumors from normal brain tissue in vivo over the past decade.1,5,10,21–24,47,51 In a recent clinical trial, the Vanderbilt group demonstrated high sensitivity with a combined optical spectroscopic method to detect the infiltrating brain tumor margins.47

The feasibility of using intraoperative optical spectroscopy to detect and demarcate epileptic lesions has been investigated on only very few occasions. In published studies to date, diffuse reflectance optical imaging has been used frequently to monitor the hemodynamics of an epileptic lesion in vivo in both animal models of epilepsy and humans.3,8,14,17,28,37,40,41,44,49,52,53 Although these results support the idea that the investigation of intrinsic physiological characteristics, especially hemodynamics, may be a viable alternative or addition to the current methods of epileptic lesion demarcation, the impact of such an approach on the outcome of epilepsy surgery has not yet been determined. Furthermore, the feasibility of using optical spectroscopy to delineate the margins of neocortical epileptic lesions in children has not yet been proven. We therefore performed a pilot clinical study to evaluate the feasibility of using static optical spectroscopic methods intraoperatively—specifically the combination of fluorescence and diffuse reflectance spectroscopy—to differentiate cortex with abnormal ECoG recordings and/or histological features from normal cortex during interictal periods in children.

Methods

We conducted our pilot in vivo patient study at Miami Children's Hospital to investigate the utility of optical spectroscopy as an aid in pediatric epilepsy surgery. We were specifically interested in ascertaining whether cortex with abnormal electrical and/or histological features could be differentiated from normal cortex on the basis of static optical spectroscopy methods. This study was approved by the Western Institutional Review Board. All eligible patients were recruited by one of the neurosurgeons involved in this study, and informed, written consent was obtained from the parents or guardians of each participant.

We used a portable fiberoptic spectroscopic system for static fluorescence and diffuse reflectance spectral acquisition (Fig. 2). The system contained 2 light sources: a pulsed nitrogen laser (337 nm, 20 Hz, VSL-337; Spectra-Physics) for fluorescence spectroscopy, and a portable halogen lamp (LS-1; Ocean Optics) for diffuse reflectance spectroscopy. The selection of 337-nm excitation for fluorescence spectroscopy enabled probing for biological fluorophores, including nicotinamide adenine dinucleotide phosphate, flavin adenine dinucleotide, collagen and tryptophan, serotonin and dopamine. Broadband emission from the tungsten halogen light source enabled investigation of the hemodynamic, structural, and other compositional characteristics of the cortex.

Fig. 2.
Fig. 2.

Intraoperative photograph of optical spectral acquisition. Upper left inset: Portable fiberoptic spectroscopic system. Bottom right inset: The configuration of the optical fibers in the optical probe. Red and white fibers are excitation fibers and the yellow fibers are collection fibers.

A fiberoptic probe (RoMack Inc.) was used in conjunction with the spectroscopic system, for remote in vivo spectral acquisition. The probe was composed of seven 300-μm core fibers arranged in a conventional 6-surrounding-1 design (Fig. 2). Two fibers were used to conduct the fluorescence and diffuse reflectance excitation lights separately. The arrangement of the optical fibers produced an investigated volume < 1 mm3. The collection fibers of the optical probe were coupled directly to a spectrometer (USB2000-FL Spectrometer; Ocean Optics) with a spectral range of 350–900 nm and a spectral resolution of ~ 5 nm. To filter out the reflected nitrogen laser light in the collected fluorescence and diffuse reflectance signals, two 385-nm long-pass filters were placed at the entrance port of the spectrometer. The spectrometer was controlled by a laptop computer via a universal serial bus interface. The integration time for each spectral acquisition was set at 1 second to ensure a sufficient signal-to-noise ratio in the acquired spectra.

Optical spectral acquisition was performed in both normal and abnormal cortex, as defined on preoperative MR images and intraoperative ECoG studies. In each patient, the surgeon selected at least 3 unique sites from the normal and abnormal cortical area. At each investigated site, the baseline, fluorescence, and diffuse reflectance spectra were acquired sequentially, and this process was repeated at least 3 times. The time to acquire optical spectra from a single investigated site was < 12 seconds. The locations of the optical investigation sites and their spatial correlations with the ECoG electrode grids were documented with digital photography. Biopsy samples were obtained from the investigated sites located within the resection zones, and processed using conventional histological methods (such as H & E staining). The histological features of these samples were evaluated by a neuropathologist (M.J.).

Prior to their analysis, the spectra were processed to eliminate any spectral alterations induced by the spectroscopy system itself. Specifically, background subtraction was performed, which removed the corresponding baseline spectra from all acquired fluorescence and diffuse reflectance spectra. Next, instrument-induced spectral alterations were removed using a set of calibration factors.23 The system's calibration factors were determined using a calibrated tungsten light source (LS-1-CAL, Ocean Optics Inc.).23 These spectral processing procedures allowed an accurate correlation between the optical spectral characteristics and the physiological/biochemical characteristics of the cortex.

The preprocessed spectral data were classified using either the corresponding histological or ECoG records. Specifically, spectral data were divided into 3 subsets: 1) normal cortex; 2) cortex with abnormal ECoG features but normal histological features; and 3) cortex with abnormal ECoG and histological features. Spectral comparisons were performed between the normal cortex and both types of abnormal cortex so that any spectral features unique to abnormal cortex, such as the spectral intensity at a given wavelength or the spectral profile, could be identified. In addition to the preprocessed fluorescence and diffuse reflectance spectra, normalized spectra were utilized in the spectral comparison and analysis procedures. The normalization methods incorporated here included normalization to the spectral intensity at an arbitrary wavelength, normalization to the mean spectrum of the subgroup, and normalization to an arbitrary point in the mean spectrum. The non-paired, 2-tailed Student t-test was used to identify statistically significant differences between the spectra obtained in normal and abnormal cortex. All statistically significant spectral alterations, in turn, were used to construct discrimination algorithms to evaluate the effectiveness of optical spectroscopy in separating normal from epileptic cortex.

Results

Fifteen patients were evaluated using the methods we have described in this pilot study. Patient demographic information and the gross histological diagnosis of their lesions are shown in Table 1. Note that the gross histological information presented in Table 1 was obtained from the general pathology report on the entire resected lesion.

The fluorescence and diffuse reflectance spectral data displayed in Fig. 3 are typical of our findings. In the fluorescence spectra acquired in both normal and abnormal cortex, 1 dominant peak was found at ~ 470 nm wavelength. In some fluorescence spectra obtained from the resected zone (ECoG abnormal cortex), a strong secondary peak was noticed at ~ 400 nm. In the diffuse reflectance spectra, 3 significant signal valleys were detected, these fell between 400 and 650 nm. Diffuse reflectance signals beyond 650 nm, in general, exhibited a steadily decreasing trend. We found that spectral intensity fluctuations in all investigated sites were more prominent than spectral profile alterations.

TABLE 1

Demographic, gross histopathological, and spectral data obtained in 15 patients who underwent resection for epilepsy*

Age (yrs), SexGross Histopathological CharacteristicsDR ElevationPeak at 400 nm
2, Mcortical tubersyesno
14, Mheterotopic neurons, Chaslin gliosisnoyes
4, Flocal cortical dyslaminationyesno
3, Msevere cortical dysplasia, Palmini Type IIbyesyes
4, Mmicrodysgenesisyesno
10, Mleft functional hemispherectomyyesyes
6, Mminimal cortical dysplasianono
2, Fgliosis, areas of Palmini Type IAyesno
14, Fmild multifocal Palmini Type IA cortical dysplasiayesyes
9, Fgliosis; no cortical dysplasianono
2, Mmultifocal cortical dysplasiayesyes
21, FChaslin gliosisyesno
20, Ftemporal lobe gliosisnono
17, Fneuronal disorganization & gliosisnono
5, Mlow-grade gliomayesno

* All resection sites showed abnormal ECoG patterns consistent with seizure discharge.

† Indicates diffuse reflectance (DR) intensity elevation at 500–600 nm and/or 650–850 nm.

‡ Indicates the presence of the secondary fluorescence peak at 400 nm.

Fig. 3.
Fig. 3.

Representative fluorescence (A), and diffuse reflectance spectra (B) obtained in a single patient. The presented spectra are the mean spectra obtained in 3 repeated measurements. Inset: The spectral region and its associated primary biological molecular features.

Comparisons of fluorescence and diffuse reflectance spectra, normalized to the arbitrary reference points in their corresponding subcategory mean spectra, identified many statistically significant spectral alterations between normal and abnormal cortex. We observed that the normalized diffuse reflectance intensities from normal cortex seemed to be higher than those from cortex with abnormal ECoG and/or histological features. Normalized fluorescence intensities from normal cortex were lower than those from cortex with abnormal histological features. However, this trend was reversed in the comparison between normal cortex and cortex with abnormal ECoG features. Using 1 fluorescence and 1 diffuse reflectance spectral feature, an empirically derived linear discrimination algorithm was constructed for each normal-abnormal cortex comparison (Fig. 4). The sensitivities and specificities of these empirical discrimination algorithms were all > 90%.

Fig. 4.
Fig. 4.

Graphs of empirical discrimination algorithms developed for normal cortex versus cortex with abnormal histological and ECoG features (left); and cortex with only abnormal ECoG features (right). The green line represents an arbitrary threshold for discrimination. Blue boxes indicate data obtained in normal cortex; red circles indicate data obtained in abnormal cortex.

Discussion

Our results demonstrate that combined fluorescence and diffuse reflectance spectroscopy can be used to separate epileptic cortex from normal cortex with a high degree of sensitivity and specificity. The fluorescence and diffuse reflectance spectral features depict unique, static, in vivo characteristics of the epileptic cortex during the interictal period, which should not be confused with the dynamic diffuse reflectance features reported by other groups.3,8,14,17,28,37,40,41,44,49,52,53 These observations warrant further studies to ascertain the clinical utility of optical spectroscopy in pediatric epilepsy surgery.

In the diffuse reflectance spectra from the cortex, hemoglobin absorption produces the predominant spectral features that can be observed between 400 and 650 nm (valleys at 400, 540, and 580 nm) due to its strong absorption of visible light. In fluorescence spectra from cortex, nicotinamide adenine dinucleotide phosphate is considered to be the primary contributor, because its peak emission location is very close to 460 nm. Although these spectral profile characteristics are observed consistently among all spectra acquired, the fluctuations in intensity are very prominent between investigated sites.

Cortex with definite pathological abnormalities often produces a stronger diffuse reflectance signal in both the visible and near-infrared wavelength regions than normal cortex does. In some cases, elevated diffuse reflectance signals also are observed from cortex with abnormal ECoG features, relative to normal cortex. It should be noted that this trend is reversed when the diffuse reflectance signal is normalized, as shown in Fig. 4. The increase in diffuse reflectance spectral intensity in a biological medium, especially between 650 and 900 nm, often indicates an increase in its scattering properties. This alteration in tissue-scattering properties may be attributed to the unique microscopic structural characteristics of epileptic brain lesions. It is known that several seizure-inducing brain lesions, including focal cortical dysplasia and cortical tubers, possess unique microscopic structural features. For example, the presence of focal cortical dysplasia and cortical tubers causes cortical laminar disorganization. Immature and dysmorphic neurons, giant cells, and balloon cells are hallmarks of cortical dysplasia. It has also been suspected that hyperactivity of the epileptic cortex could be caused by an increased number of mitochondria. These morphological alterations could in turn lead to an increase in the scattering properties of epileptic cortex. Further microscopic studies are needed to elucidate the true correlation between the morphological and biochemical characteristics of epileptic cortex and its scattering properties.

A unique feature was observed in some fluorescence spectra acquired from epileptic cortex: a secondary peak of wavelength ~ 400 nm (Fig. 5). There are several potential biological contributors to this particular emission peak, namely collagen, tryptophan, serotonin, and dopamine. Although it is possible that this peak is caused by the presence of a large blood vessel (collagen) in the area under investigation, it was not observed consistently in all patients. It is also possible that this spectral feature reflects abnormal concentrations of neurotransmitters in the region. Further studies must be conducted to identify the true origin of this peak.

Fig. 5.
Fig. 5.

Graph of fluorescence spectra obtained in abnormal cortex with a strong secondary emission peak at ~ 400 nm.

Although the results of the present study are promising, several obstacles must be overcome and improvements made before the true clinical utility of static fluorescence and diffuse reflectance spectroscopy in pediatric epilepsy surgery can be determined. A critical challenge to this in vivo study arises from the significant disparity in outcomes of ECoG and histological studies. Many biopsy samples obtained from cortex with abnormal ECoG readings were declared histologically normal by the study neuropathologist. There are several possible reasons for this discrepancy. First, the optical probe we used is limited to a depth of investigation ≤ 1 mm, and detection was performed solely on the cortical surface. It is possible that pathological abnormalities may actually be present in deeper layers of the cortex and hence not detected within the bioipsy samples taken from the cortical surface. To address this concern, a new optical probe with a greater separation between source and detector has been designed and built and will be used in a future study. Another possible reason for the disparity is that the underlying mechanisms for the abnormal ECoG features may not be detectable using conventional histological methods. Third, because of the rapidly spreading nature of cortical electrical activities, the abnormal ECoG features detected may not originate at the site of investigation. These concerns undermine the use of either ECoG or histological examination alone as the true gold standard for data analysis. To address these concerns we are investigating a change in the design of the probe so that it can be integrated with the subdural grid electrodes, enabling a real-time simultaneous acquisition and analysis of ECOG and spectroscopic data.

Inconsistencies in spectral measurements with hand-held probes are particularly evident when spectral measurements are repeated at a single site. In a previous study, we found that when the probe contact pressure exceeds a certain threshold, the hemodynamics of the target tissue and therefore its fluorescence and diffuse reflectance spectra can be influenced drastically.45 The hallmark spectral alterations that result from excessive probe contact pressure are alterations in the spectral profile between 500 and 600 nm, caused by to deoxygenation of hemoglobin and an increase in fluorescence emission. The possible presence of these artifacts in the acquired fluorescence and diffuse reflectance spectra may explain why absolute intensities of either signal type could not effectively differentiate normal from abnormal cortex. To obtain true fluorescence and diffuse reflectance spectra from brain in vivo, these types of motion and pressure effects must be minimized.

Establishing true baseline levels for the fluorescence and diffuse reflectance characteristics of normal cortex may be challenging in children, because their brains are continuously growing and developing. The size and weight of a child's brain continues to increase significantly for several years after birth because of brain cell division and growth. The biochemical processes involved in this development, including cholesterol synthesis and the formation of new mitochondria, further influence both the morphological and biochemical characteristics of the brain. We therefore expect that “normal” measurements will vary with patient age. A separate study currently is underway to investigate the effects of patient age and brain lesion location on optical and fluorescence spectra features.

The spectroscopic methods we used in this pilot study only explore the static nature of the cortex. In other words, they provide only a snapshot of the physiological characteristics of the cortex during a 1-second integration time. The dynamic nature of brain metabolism and hemodynam-ics3,8,14,17,28,37,40,41,44,49,52,53 is completely neglected in this statistical model. To address this potential shortcoming, we have designed and developed a new spectroscopic system that can be used to acquire broadband optical spectra (400–950 nm) from the brain at a rate of 33 Hz in a continuous manner. This new device should allow us to investigate both the static and dynamic natures of epileptic cortex, and to perform advanced analysis of tissue morphological characteristics, biochemistry, and composition. Currently, this system is being tested in a pilot study, the results of which will be reported in a future publication.

Conclusions

In the present study, we investigated the feasibility of using fluorescence and diffuse reflectance spectroscopy to aid in pediatric epilepsy surgery. Static fluorescence and diffuse reflectance spectra were acquired in cortex with normal and abnormal ECoG and histological features. Spectral features separating normal from epileptic cortex were identified and used to produce tissue discrimination algorithms with high sensitivities and specificities. The spectral alterations observed may be attributable to the unique compositional and/or structural characteristics of the epileptic cortex.

Disclosure

This work was supported by the Thrasher Research Fund and the Ware Foundation Research Endowment.

References

  • 1

    Andrews R, , Mah R, , Aghevli A, , Freitas K, , Galvagni A, & Guerrero M, et al.: Multimodality stereotactic brain tissue identification: the NASA smart probe project. Stereotact Funct Neurosurg 73:18, 1999

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 2

    Baena JR, & Lendl B: Raman spectroscopy in chemical bioanalysis. Curr Opin Chem Biol 8:534539, 2004

  • 3

    Bahar S, , Suh M, , Zhao M, & Schwartz TH: Intrinsic optical signal imaging of neocortical seizures: the ‘epileptic dip’. Neuroreport 17:499503, 2006

  • 4

    Bigio IJ, & Bown SG: Spectroscopic sensing of cancer and cancer therapy: current status of translational research. Cancer Biol Ther 3:259267, 2004

  • 5

    Bottiroli G, , Croce AC, , Locatelli D, , Nano R, , Giombelli E, & Messina A, et al.: Brain tissue autofluorescence: an aid for intraoperative delineation of tumor resection margins. Cancer Detect Prev 22:330339, 1998

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6

    Burger J, & Geladi P: Hyperspectral NIR imaging for calibration and prediction: a comparison between image and spectrometer data for studying organic and biological samples. Analyst 131:11521160, 2006

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7

    Cancio LC, , Batchinsky AI, , Mansfield JR, , Panasyuk S, , Hetz K, & Martini D, et al.: Hyperspectral imaging: a new approach to the diagnosis of hemorrhagic shock. J Trauma 60:10871095, 2006

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8

    Chen JW, , O'Farrell AM, & Toga AW: Optical intrinsic signal imaging in a rodent seizure model. Neurology 55:312315, 2000

  • 9

    Cooper CE, , Cope M, , Quaresima V, , Ferrari M, , Nemoto E, & Springett R, et al.: Measurement of cytochrome oxidase redox state by near infrared spectroscopy. Adv Exp Med Biol 413:6373, 1997

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10

    Croce AC, , Fiorani S, , Locatelli D, , Nano R, , Ceroni M, & Tancioni F, et al.: Diagnostic potential of autofluorescence for an assisted intraoperative delineation of glioblastoma resection margins. Photochem Photobiol 77:309318, 2003

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11

    Ellis DI, & Goodacre R: Metabolic fingerprinting in disease diagnosis: biomedical applications of infrared and Raman spectroscopy. Analyst 131:875885, 2006

  • 12

    Elwell CE, , Owen-Reece H, , Cope M, , Wyatt JS, , Edwards AD, & Delpy DT, et al.: Measurement of adult cerebral haemodynamics using near infrared spectroscopy. Acta Neurochir Suppl Wien 59:7480, 1993

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13

    Ferrari M, , Mottola L, & Quaresima V: Principles, techniques, and limitations of near infrared spectroscopy. Can J Appl Physiol 29:463487, 2004

  • 14

    Haglund MM, & Hochman DW: Optical imaging of epileptiform activity in human neocortex. Epilepsia 45:4 Suppl 4347, 2004

  • 15

    Haka AS, , Volynskaya Z, , Gardecki JA, , Nazemi J, , Lyons J, & Hicks D, et al.: In vivo margin assessment during partial mastectomy breast surgery using raman spectroscopy. Cancer Res 66:33173322, 2006

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16

    Hanlon EB, , Manoharan R, , Koo TW, , Shafer KE, , Motz JT, & Fitzmaurice M, et al.: Prospects for in vivo Raman spectroscopy. Phys Med Biol 45::R1R59, 2000

  • 17

    Holtkamp M, , Buchheim K, , Siegmund H, & Meierkord H: Optical imaging reveals reduced seizure spread and propagation velocities in aged rat brain in vitro. Neurobiol Aging 24:345353, 2003

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 18

    Jayakar P, , Dunoyer C, , Dean P, , Ragheb J, , Resnick T, & Morrison G, et al.: Epilepsy surgery in patients with normal or nonfocal MRI scans: Integrative strategies offer long-term seizure relief. Epilepsia 49:758764, 2008

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 19

    Koenig F, , Larne R, , Enquist H, , McGovern FJ, , Schomacker KT, & Kollias N, et al.: Spectroscopic measurement of diffuse reflectance for enhanced detection of bladder carcinoma. Urology 51:342345, 1998

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 20

    Kondepati VR, , Heise HM, & Backhaus J: Recent applications of near-infrared spectroscopy in cancer diagnosis and therapy. Anal Bioanal Chem 390:125139, 2008

  • 21

    Lin WC, , Toms SA, , Jansen ED, & Mahadevan-Jansen A: Intraoperative application of optical spectroscopy in the presence of blood. IEEE Journal of Special Topics in Quantum Electronics 7:9961003, 2001

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 22

    Lin WC, , Toms SA, , Johnson M, , Jansen ED, & Mahadevan-Jansen A: In vivo brain tumor demarcation using optical spectroscopy. Photochem Photobio 73:396402, 2001

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 23

    Lin WC, , Toms SA, , Motamedi M, , Jansen ED, & Mahadevan-Jansen A: Brain tumor demarcation using optical spectroscopy; an in vitro study. J Biomed Opt 5:214220, 2000

  • 24

    Marcu L, , Jo JA, , Butte PV, , Yong WH, , Pikul BK, & Black KL, et al.: Fluorescence lifetime spectroscopy of glioblastoma multiforme. Photochem Photobiol 80:98103, 2004

  • 25

    Marin NM, , Milbourne A, , Rhodes H, , Ehlen T, , Miller D, & Benedet L, et al.: Diffuse reflectance patterns in cervical spectroscopy. Gynecol Oncol 99:3 Suppl S116S120, 2005

  • 26

    Mayevsky A, & Chance B: Intracellular oxidation-reduction state measured in situ by a multichannel fiber-optic surface fluorometer. Science 217:537540, 1982

  • 27

    Mayevsky A, & Rogatsky G: Mitochondrial function in vivo evaluated by NADH fluorescence: from animal models to human studies. Am J Physiol Cell Physiol 292:C615C640, 2007

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 28

    Miyakawa N, , Yazawa I, , Sasaki S, , Momose-Sato Y, & Sato K: Optical analysis of acute spontaneous epileptiform discharges in the in vivo rat cerebral cortex. Neuroimage 18:622632, 2003

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 29

    Mohamed IS, , Otsubo H, , Donner E, , Ochi A, , Sharma R, & Drake J, et al.: Magnetoencephalography for surgical treatment of refractory status epilepticus. Acta Neurol Scand Suppl 115:2936, 2007

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 30

    Müller MG, , Valdez TA, , Georgakoudi I, , Backman V, , Fuentes C, & Kabani S, et al.: Spectroscopic detection and evaluation of morphologic and biochemical changes in early human oral carcinoma. Cancer 97:16811692, 2003

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 31

    Mulvaney SP, & Keating CD: Raman spectroscopy. Anal Chem 72:145R157R, 2000

  • 32

    Najm IM, , Bingaman WE, & Lüders HO: The use of subdural grids in the management of focal malformations due to abnormal cortical development. Neurosurg Clin N Am 13:8792, viiiix, 2002

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 33

    Owen CA, , Notingher I, , Hill R, , Stevens M, & Hench LL: Progress in Raman spectroscopy in the fields of tissue engineering, diagnostics and toxicological testing. J Mater Sci Mater Med 17:10191023, 2006

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 34

    Qin J, & Lu R: Measurement of the absorption and scattering properties of turbid liquid foods using hyperspectral imaging. Appl Spectrosc 61:388396, 2007

  • 35

    Ramanujam N: Fluorescence spectroscopy of neoplastic and non-neoplastic tissues. Neoplasia 2:89117, 2000

  • 36

    Raybaud C, , Shroff M, , Rutka JT, & Chuang SH: Imaging surgical epilepsy in children. Childs Nerv Syst 22:786809, 2006

  • 37

    Redecker C, , Hagemann G, , Köhling R, , Straub H, , Witte OW, & Speckmann EJ: Optical imaging of epileptiform activity in experimentally induced cortical malformations. Exp Neurol 192:288298, 2005

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 38

    Richards-Kortum R, & Sevick-Muraca E: Quantitative optical spectroscopy for tissue diagnosis. Annu Rev Phys Chem 47:555606, 1996

  • 39

    Rolfe P: In vivo near-infrared spectroscopy. Annu Rev Biomed Eng 2:715754, 2000

  • 40

    Saito S, , Yoshikawa D, , Nishihara F, , Morita T, , Kitani Y, & Amaya T, et al.: The cerebral hemodynamic response to electrically induced seizures in man. Brain Res 673:93100, 1995

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 41

    Schwartz TH, & Bonhoeffer T: In vivo optical mapping of epileptic foci and surround inhibition in ferret cerebral cortex. Nat Med 7:10631067, 2001

  • 42

    Sokolov K, , Follen M, & Richards-Kortum R: Optical spectroscopy for detection of neoplasia. Curr Opin Chem Biol 6:651658, 2002

  • 43

    Stief O'Shaughnessy E, , Berl M, , Moore E, & Gaillard WD: Pediatric functional magnetic resonance imaging (fMRI): issues and applications. J Child Neurol [epub ahead of print] 2008

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 44

    Szapiel SV: Optical imaging and its role in clinical neurology. Arch Neurol 58:10611065, 2001

  • 45

    Ti Y, & Lin WC: Effects of probe contact pressure on in vivo optical spectroscopy. Optics Express 16:42504262, 2008

  • 46

    Toczek MT, & Theodore WH: Cortical dysplasia and epilepsy: functional imaging using single photon emission computed tomography and positron emission tomography. Neurosurg Clin N Am 13:7186, viii, 2002

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 47

    Toms SA, , Lin WC, , Weil RJ, , Johnson MD, , Jansen ED, & Mahadevan-Jansen A: Intraoperative optical spectroscopy identifies infiltrating glioma margins with high sensitivity. Neurosurgery 57:4 Suppl 382391, 2005

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 48

    Tromberg BJ, , Cerussi A, , Shah N, , Compton M, , Durkin A, & Hsiang D, et al.: Imaging in breast cancer: diffuse optics in breast cancer: detecting tumors in pre-menopausal women and monitoring neoadjuvant chemotherapy. Breast Cancer Res 7:279285, 2005

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 49

    Tsau Y, , Guan L, & Wu JY: Epileptiform activity can be initiated in various neocortical layers: an optical imaging study. J Neurophysiol 82:19651973, 1999

  • 50

    Villringer A, & Chance B: Non-invasive optical spectroscopy and imaging of human brain function. Trends Neurosci 20:435442, 1997

  • 51

    Vo-Dinh T, , Stokes DL, , Wabuyele MB, , Martin ME, , Song JM, & Jagannathan R, et al.: A hyperspectral imaging system for in vivo optical diagnostics. Hyperspectral imaging basic principles, instrumental systems, and applications of biomedical interest. IEEE Eng Med Biol Mag 23:4049, 2004

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 52

    Watanabe E, , Nagahori Y, & Mayanagi Y: Focus diagnosis of epilepsy using near-infrared spectroscopy. Epilepsia 43:9 Suppl 5055, 2002

  • 53

    Weissinger F, , Buchheim K, , Siegmund H, , Heinemann U, & Meierkord H: Optical imaging reveals characteristic seizure onsets, spread patterns, and propagation velocities in hippocampalentorhinal cortex slices of juvenile rats. Neurobiol Dis 7:286298, 2000

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 54

    Wyatt JS: Noninvasive assessment of cerebral oxidative metabolism in the human newborn. J R Coll Physicians Lond 28:126132, 1994

  • 55

    Xu RX, & Povoski SP: Diffuse optical imaging and spectroscopy for cancer. Expert Rev Med Devices 4:8395, 2007

  • 56

    Zhang Q, , Ma H, , Nioka S, & Chance B: Study of near infrared technology for intracranial hematoma detection. J Biomed Opt 5:206213, 2000

  • 57

    Zhao J, , Ding HS, , Hou XL, , Zhou CL, & Chance B: In vivo determination of the optical properties of infant brain using frequency-domain near-infrared spectroscopy. J Biomed Opt 10:024028, 2005

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 58

    Zuzak KJ, , Naik SC, , Alexandrakis G, , Hawkins D, , Behbehani K, & Livingston E: Intraoperative bile duct visualization using near-infrared hyperspectral video imaging. Am J Surg 195:491497, 2008

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • Collapse
  • Expand
  • Schematic diagram summarizing the potential uses for optical spectroscopic techniques for characterizing the brain in vivo. The intrinsic biological and morphological characteristics of the brain, their corresponding unique interactions with light, and the detection mechanisms are shown.

  • Intraoperative photograph of optical spectral acquisition. Upper left inset: Portable fiberoptic spectroscopic system. Bottom right inset: The configuration of the optical fibers in the optical probe. Red and white fibers are excitation fibers and the yellow fibers are collection fibers.

  • Representative fluorescence (A), and diffuse reflectance spectra (B) obtained in a single patient. The presented spectra are the mean spectra obtained in 3 repeated measurements. Inset: The spectral region and its associated primary biological molecular features.

  • Graphs of empirical discrimination algorithms developed for normal cortex versus cortex with abnormal histological and ECoG features (left); and cortex with only abnormal ECoG features (right). The green line represents an arbitrary threshold for discrimination. Blue boxes indicate data obtained in normal cortex; red circles indicate data obtained in abnormal cortex.

  • Graph of fluorescence spectra obtained in abnormal cortex with a strong secondary emission peak at ~ 400 nm.

  • 1

    Andrews R, , Mah R, , Aghevli A, , Freitas K, , Galvagni A, & Guerrero M, et al.: Multimodality stereotactic brain tissue identification: the NASA smart probe project. Stereotact Funct Neurosurg 73:18, 1999

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 2

    Baena JR, & Lendl B: Raman spectroscopy in chemical bioanalysis. Curr Opin Chem Biol 8:534539, 2004

  • 3

    Bahar S, , Suh M, , Zhao M, & Schwartz TH: Intrinsic optical signal imaging of neocortical seizures: the ‘epileptic dip’. Neuroreport 17:499503, 2006

  • 4

    Bigio IJ, & Bown SG: Spectroscopic sensing of cancer and cancer therapy: current status of translational research. Cancer Biol Ther 3:259267, 2004

  • 5

    Bottiroli G, , Croce AC, , Locatelli D, , Nano R, , Giombelli E, & Messina A, et al.: Brain tissue autofluorescence: an aid for intraoperative delineation of tumor resection margins. Cancer Detect Prev 22:330339, 1998

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6

    Burger J, & Geladi P: Hyperspectral NIR imaging for calibration and prediction: a comparison between image and spectrometer data for studying organic and biological samples. Analyst 131:11521160, 2006

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7

    Cancio LC, , Batchinsky AI, , Mansfield JR, , Panasyuk S, , Hetz K, & Martini D, et al.: Hyperspectral imaging: a new approach to the diagnosis of hemorrhagic shock. J Trauma 60:10871095, 2006

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8

    Chen JW, , O'Farrell AM, & Toga AW: Optical intrinsic signal imaging in a rodent seizure model. Neurology 55:312315, 2000

  • 9

    Cooper CE, , Cope M, , Quaresima V, , Ferrari M, , Nemoto E, & Springett R, et al.: Measurement of cytochrome oxidase redox state by near infrared spectroscopy. Adv Exp Med Biol 413:6373, 1997

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10

    Croce AC, , Fiorani S, , Locatelli D, , Nano R, , Ceroni M, & Tancioni F, et al.: Diagnostic potential of autofluorescence for an assisted intraoperative delineation of glioblastoma resection margins. Photochem Photobiol 77:309318, 2003

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11

    Ellis DI, & Goodacre R: Metabolic fingerprinting in disease diagnosis: biomedical applications of infrared and Raman spectroscopy. Analyst 131:875885, 2006

  • 12

    Elwell CE, , Owen-Reece H, , Cope M, , Wyatt JS, , Edwards AD, & Delpy DT, et al.: Measurement of adult cerebral haemodynamics using near infrared spectroscopy. Acta Neurochir Suppl Wien 59:7480, 1993

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13

    Ferrari M, , Mottola L, & Quaresima V: Principles, techniques, and limitations of near infrared spectroscopy. Can J Appl Physiol 29:463487, 2004

  • 14

    Haglund MM, & Hochman DW: Optical imaging of epileptiform activity in human neocortex. Epilepsia 45:4 Suppl 4347, 2004

  • 15

    Haka AS, , Volynskaya Z, , Gardecki JA, , Nazemi J, , Lyons J, & Hicks D, et al.: In vivo margin assessment during partial mastectomy breast surgery using raman spectroscopy. Cancer Res 66:33173322, 2006

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16

    Hanlon EB, , Manoharan R, , Koo TW, , Shafer KE, , Motz JT, & Fitzmaurice M, et al.: Prospects for in vivo Raman spectroscopy. Phys Med Biol 45::R1R59, 2000

  • 17

    Holtkamp M, , Buchheim K, , Siegmund H, & Meierkord H: Optical imaging reveals reduced seizure spread and propagation velocities in aged rat brain in vitro. Neurobiol Aging 24:345353, 2003

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 18

    Jayakar P, , Dunoyer C, , Dean P, , Ragheb J, , Resnick T, & Morrison G, et al.: Epilepsy surgery in patients with normal or nonfocal MRI scans: Integrative strategies offer long-term seizure relief. Epilepsia 49:758764, 2008

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 19

    Koenig F, , Larne R, , Enquist H, , McGovern FJ, , Schomacker KT, & Kollias N, et al.: Spectroscopic measurement of diffuse reflectance for enhanced detection of bladder carcinoma. Urology 51:342345, 1998

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 20

    Kondepati VR, , Heise HM, & Backhaus J: Recent applications of near-infrared spectroscopy in cancer diagnosis and therapy. Anal Bioanal Chem 390:125139, 2008

  • 21

    Lin WC, , Toms SA, , Jansen ED, & Mahadevan-Jansen A: Intraoperative application of optical spectroscopy in the presence of blood. IEEE Journal of Special Topics in Quantum Electronics 7:9961003, 2001

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 22

    Lin WC, , Toms SA, , Johnson M, , Jansen ED, & Mahadevan-Jansen A: In vivo brain tumor demarcation using optical spectroscopy. Photochem Photobio 73:396402, 2001

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 23

    Lin WC, , Toms SA, , Motamedi M, , Jansen ED, & Mahadevan-Jansen A: Brain tumor demarcation using optical spectroscopy; an in vitro study. J Biomed Opt 5:214220, 2000

  • 24

    Marcu L, , Jo JA, , Butte PV, , Yong WH, , Pikul BK, & Black KL, et al.: Fluorescence lifetime spectroscopy of glioblastoma multiforme. Photochem Photobiol 80:98103, 2004

  • 25

    Marin NM, , Milbourne A, , Rhodes H, , Ehlen T, , Miller D, & Benedet L, et al.: Diffuse reflectance patterns in cervical spectroscopy. Gynecol Oncol 99:3 Suppl S116S120, 2005

  • 26

    Mayevsky A, & Chance B: Intracellular oxidation-reduction state measured in situ by a multichannel fiber-optic surface fluorometer. Science 217:537540, 1982

  • 27

    Mayevsky A, & Rogatsky G: Mitochondrial function in vivo evaluated by NADH fluorescence: from animal models to human studies. Am J Physiol Cell Physiol 292:C615C640, 2007

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 28

    Miyakawa N, , Yazawa I, , Sasaki S, , Momose-Sato Y, & Sato K: Optical analysis of acute spontaneous epileptiform discharges in the in vivo rat cerebral cortex. Neuroimage 18:622632, 2003

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 29

    Mohamed IS, , Otsubo H, , Donner E, , Ochi A, , Sharma R, & Drake J, et al.: Magnetoencephalography for surgical treatment of refractory status epilepticus. Acta Neurol Scand Suppl 115:2936, 2007

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 30

    Müller MG, , Valdez TA, , Georgakoudi I, , Backman V, , Fuentes C, & Kabani S, et al.: Spectroscopic detection and evaluation of morphologic and biochemical changes in early human oral carcinoma. Cancer 97:16811692, 2003

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 31

    Mulvaney SP, & Keating CD: Raman spectroscopy. Anal Chem 72:145R157R, 2000

  • 32

    Najm IM, , Bingaman WE, & Lüders HO: The use of subdural grids in the management of focal malformations due to abnormal cortical development. Neurosurg Clin N Am 13:8792, viiiix, 2002

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 33

    Owen CA, , Notingher I, , Hill R, , Stevens M, & Hench LL: Progress in Raman spectroscopy in the fields of tissue engineering, diagnostics and toxicological testing. J Mater Sci Mater Med 17:10191023, 2006

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 34

    Qin J, & Lu R: Measurement of the absorption and scattering properties of turbid liquid foods using hyperspectral imaging. Appl Spectrosc 61:388396, 2007

  • 35

    Ramanujam N: Fluorescence spectroscopy of neoplastic and non-neoplastic tissues. Neoplasia 2:89117, 2000

  • 36

    Raybaud C, , Shroff M, , Rutka JT, & Chuang SH: Imaging surgical epilepsy in children. Childs Nerv Syst 22:786809, 2006

  • 37

    Redecker C, , Hagemann G, , Köhling R, , Straub H, , Witte OW, & Speckmann EJ: Optical imaging of epileptiform activity in experimentally induced cortical malformations. Exp Neurol 192:288298, 2005

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 38

    Richards-Kortum R, & Sevick-Muraca E: Quantitative optical spectroscopy for tissue diagnosis. Annu Rev Phys Chem 47:555606, 1996

  • 39

    Rolfe P: In vivo near-infrared spectroscopy. Annu Rev Biomed Eng 2:715754, 2000

  • 40

    Saito S, , Yoshikawa D, , Nishihara F, , Morita T, , Kitani Y, & Amaya T, et al.: The cerebral hemodynamic response to electrically induced seizures in man. Brain Res 673:93100, 1995

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 41

    Schwartz TH, & Bonhoeffer T: In vivo optical mapping of epileptic foci and surround inhibition in ferret cerebral cortex. Nat Med 7:10631067, 2001

  • 42

    Sokolov K, , Follen M, & Richards-Kortum R: Optical spectroscopy for detection of neoplasia. Curr Opin Chem Biol 6:651658, 2002

  • 43

    Stief O'Shaughnessy E, , Berl M, , Moore E, & Gaillard WD: Pediatric functional magnetic resonance imaging (fMRI): issues and applications. J Child Neurol [epub ahead of print] 2008

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 44

    Szapiel SV: Optical imaging and its role in clinical neurology. Arch Neurol 58:10611065, 2001

  • 45

    Ti Y, & Lin WC: Effects of probe contact pressure on in vivo optical spectroscopy. Optics Express 16:42504262, 2008

  • 46

    Toczek MT, & Theodore WH: Cortical dysplasia and epilepsy: functional imaging using single photon emission computed tomography and positron emission tomography. Neurosurg Clin N Am 13:7186, viii, 2002

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 47

    Toms SA, , Lin WC, , Weil RJ, , Johnson MD, , Jansen ED, & Mahadevan-Jansen A: Intraoperative optical spectroscopy identifies infiltrating glioma margins with high sensitivity. Neurosurgery 57:4 Suppl 382391, 2005

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 48

    Tromberg BJ, , Cerussi A, , Shah N, , Compton M, , Durkin A, & Hsiang D, et al.: Imaging in breast cancer: diffuse optics in breast cancer: detecting tumors in pre-menopausal women and monitoring neoadjuvant chemotherapy. Breast Cancer Res 7:279285, 2005

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 49

    Tsau Y, , Guan L, & Wu JY: Epileptiform activity can be initiated in various neocortical layers: an optical imaging study. J Neurophysiol 82:19651973, 1999

  • 50

    Villringer A, & Chance B: Non-invasive optical spectroscopy and imaging of human brain function. Trends Neurosci 20:435442, 1997

  • 51

    Vo-Dinh T, , Stokes DL, , Wabuyele MB, , Martin ME, , Song JM, & Jagannathan R, et al.: A hyperspectral imaging system for in vivo optical diagnostics. Hyperspectral imaging basic principles, instrumental systems, and applications of biomedical interest. IEEE Eng Med Biol Mag 23:4049, 2004

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 52

    Watanabe E, , Nagahori Y, & Mayanagi Y: Focus diagnosis of epilepsy using near-infrared spectroscopy. Epilepsia 43:9 Suppl 5055, 2002

  • 53

    Weissinger F, , Buchheim K, , Siegmund H, , Heinemann U, & Meierkord H: Optical imaging reveals characteristic seizure onsets, spread patterns, and propagation velocities in hippocampalentorhinal cortex slices of juvenile rats. Neurobiol Dis 7:286298, 2000

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 54

    Wyatt JS: Noninvasive assessment of cerebral oxidative metabolism in the human newborn. J R Coll Physicians Lond 28:126132, 1994

  • 55

    Xu RX, & Povoski SP: Diffuse optical imaging and spectroscopy for cancer. Expert Rev Med Devices 4:8395, 2007

  • 56

    Zhang Q, , Ma H, , Nioka S, & Chance B: Study of near infrared technology for intracranial hematoma detection. J Biomed Opt 5:206213, 2000

  • 57

    Zhao J, , Ding HS, , Hou XL, , Zhou CL, & Chance B: In vivo determination of the optical properties of infant brain using frequency-domain near-infrared spectroscopy. J Biomed Opt 10:024028, 2005

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 58

    Zuzak KJ, , Naik SC, , Alexandrakis G, , Hawkins D, , Behbehani K, & Livingston E: Intraoperative bile duct visualization using near-infrared hyperspectral video imaging. Am J Surg 195:491497, 2008

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation

Metrics

All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 795 70 8
PDF Downloads 197 44 3
EPUB Downloads 0 0 0