Intraoperative identification of functional brain areas with RGB imaging using statistical parametric mapping: Simulation and clinical studies.

Complementary technique to preoperative fMRI and electrical brain stimulation (EBS) for glioma resection could improve dramatically the surgical procedure and patient care. Intraoperative RGB optical imaging is a technique for localizing functional areas of the human cerebral cortex that can be used during neurosurgical procedures. However, it still lacks robustness to be used with neurosurgical microscopes as a clinical standard. In particular, a robust quantification of biomarkers of brain functionality is needed to assist neurosurgeons. We propose a methodology to evaluate and optimize intraoperative identification of brain functional areas by RGB imaging. This consist in a numerical 3D brain model based on Monte Carlo simulations to evaluate intraoperative optical setups for identifying functional brain areas. We also adapted fMRI Statistical Parametric Mapping technique to identify functional brain areas in RGB videos acquired for 12 patients. Simulation and experimental results were consistent and showed that the intraoperative identification of functional brain areas is possible with RGB imaging using deoxygenated hemoglobin contrast. Optical functional identifications were consistent with those provided by EBS and preoperative fMRI. We also demonstrated that a halogen lighting may be particularity adapted for functional optical imaging. We showed that an RGB camera combined with a quantitative modeling of brain hemodynamics biomarkers can evaluate in a robust way the functional areas during neurosurgery and serve as a tool of choice to complement EBS and fMRI.

Electro-optic probe for real-time assessments of RF electric field produced in an MRI scanner: Feasibility tests at 3 and 4.7 T.

During magnetic resonance imaging (MRI) examinations, the average specific absorption rate (SAR) of the whole body is calculated as an index of global energy deposition in biological tissue without taking into account the presence of metallic implants or conductive materials. However, this global SAR calculation is not sufficient to ensure patient safety and a local SAR measurement should be carried out. Several measurement techniques have already been used to evaluate the local SAR, in particular electric field (E-field) probes, but the accuracy of the measurements and the resolutions (spatial and temporal) depend strongly on the measurement method/probe. This work presents an MR-compatible, subcentimeter probe based on an electro-optic (EO) principle enabling a real-time measurement of the local E-field during MRI scans. The experiments using these probes were performed on two different MR systems (preclinical and clinical) having different static magnetic field strengths and with different volume coil geometries. The E-field was measured with unloaded (in air) and loaded volume coils in order to assess the sensing characteristics of the optical probe. The results show an excellent linearity between the measured E-field and the radiofrequency (RF) magnetic field in both experimental conditions. Moreover, the distribution of the E-field throughout the volume coil was experimentally determined and was in good agreement with numerical simulations. Finally, we demonstrate through our measurements that the E-field depends strongly on the dielectric properties of the medium.

In vivo MRS for the assessment of mouse colon using a dedicated endorectal coil: initial findings.

Inflammatory bowel disease is a common group of inflammation conditions that can affect the colon and the rectum. These pathologies require a careful follow-up of patients to prevent the development of colorectal cancer. Currently, conventional endoscopy is used to depict alterations of the intestinal walls, and biopsies are performed on suspicious lesions for further analysis (histology). MRS enables the in vivo analysis of biochemical content of tissues (i.e. without removing any samples). Combined with dedicated endorectal coils (ERCs), MRS provides new ways of characterizing alterations of tissues. An MRS in vivo protocol was specifically set up on healthy mice and on mice chemically treated to induce colitis. Acquisitions were performed on a 4.7 T system using a linear volume birdcage coil for the transmission of the B1 magnetic field, and a dedicated ERC was used for signal reception. Colon-wall complex, lumen and visceral fat were assessed on healthy and treated mice with voxel sizes ranging from 0.125 µL to 2 µL while keeping acquisition times below 3 min. The acquired spectra show various biochemical contents such as α- and ß-methylene but also glycerol backbone and diacyl. Choline was detected in tumoral regions. Visceral fat regions display a high lipid content with no water, whereas colon-wall complex exhibits both high lipid and high water contents. To the best of our knowledge, this is the first time that in vivo MRS using an ERC has been performed in the assessment of colon walls and surrounding structures. It provides keys for the in vivo characterization of small local suspicious lesions and offers complementary solutions to biopsies.

Endoluminal high-resolution MR imaging protocol for colon walls analysis in a mouse model of colitis.

OBJECTIVE: An endoluminal magnetic resonance (MR) imaging protocol including the design of an endoluminal coil (EC) was defined for high-spatial-resolution MR imaging of mice gastrointestinal walls at 4.7 T. MATERIALS AND METHODS: A receive-only radiofrequency single-loop coil was developed for mice colon wall imaging. Combined with a specific protocol, the prototype was first characterized in vitro on phantoms and on vegetables. Signal-to-noise ratio (SNR) profiles were compared with a quadrature volume birdcage coil (QVBC). Endoluminal MR imaging protocol combined with the EC was assessed in vivo on mice. RESULTS: The SNR measured close to the coil is significantly higher (10 times and up to 3 mm of the EC center) than the SNR measured with the QVBC. The gain in SNR can be used to reduce the in-plane pixel size up to 39 × 39 µm(2) (234 µm slice thickness) without time penalty. The different colon wall layers can only be distinguished on images acquired with the EC. CONCLUSION: Dedicated EC provides suitable images for the assessment of mice colon wall layers. This proof of concept provides gains in spatial resolution and leads to adequate protocols for the assessment of human colorectal cancer, and can now be used as a new imaging tool for a better understanding of the pathology.

A priori free spectral unmixing with periodic absorbance changes: application for auto-calibrated intraoperative functional brain mapping.

Spectral unmixing designates techniques that allow to decompose measured spectra into linear or non-linear combination of spectra of all targets (endmembers). This technique was initially developed for satellite applications, but it is now also widely used in biomedical applications. However, several drawbacks limit the use of these techniques with standard optical devices like RGB cameras. The devices need to be calibrated and a a priori on the observed scene is often necessary. We propose a new method for estimating endmembers and their proportion automatically and without calibration of the acquisition device based on near separable non-negative matrix factorization. This method estimates the endmembers on spectra of absorbance changes presenting periodic events. This is very common in in vivo biomedical and medical optical imaging where hemodynamics dominate the absorbance fluctuations. We applied the method for identifying functional brain areas during neurosurgery using four different RGB cameras (an industrial camera, a smartphone and two surgical microscopes). Results obtained with the auto-calibration method were consistent with the intraoperative gold standards. Endmembers estimated with the auto-calibration method were similar to the calibrated endmembers used in the modified Beer-Lambert law. The similarity was particularly strong when both cardiac and respiratory periodic events were considered. This work can allow a widespread use of spectral imaging in the industrial or medical field.

Optical Link as an Alternative for MRI Receive Coils: Toward a Passive Approach.

OBJECTIVE: The objective of this work was to propose an alternative solution to NMR signal transmission by replacing the coaxial cables of the receiver radiofrequency (RF) coil in the context of MRI so as to improve safety. Starting from the analysis of previous studies and reports on the topic, the difficulty of supplying power wirelessly to an RF coil was identified. To avoid this difficult task, the development of a passive analog optical link was studied. METHODS: In order to quantify the requirements for achieving an analog conversion, the performance of the link was evaluated based on the input NMR signal amplitude and the optical power and compared with that of a galvanic link. Acquisitions were performed on a 7-T preclinical MRI system with a doped saline solution as phantom. A passive and MRI-compatible polarization-state custom-made modulator was tested as well as a commercial Mach-Zehnder interferometer. RESULTS: The conversion was not sensitive enough to keep similar SNRs, but the main source of noise was identified along with parameters for improvement. Optical power emitted by the laser, insertion loss, and full-phase inversion voltage of the modulators were found to be crucial characteristics for the application. These data indicate that custom application devices are required since the frequency, bandwidth, and amplitude of NMR signals are quite different to usual telecommunication signals. CONCLUSION: An electro-optic modulation and a transmission channel were successfully conceived and tested. Images were reconstructed with some significant SNR drawbacks that are expected to be compensated with an appropriate modulator. SIGNIFICANCE: While technical challenges remain, our approach to a two-decades-long problem could solve a major issue of MRI safety by removing the need for supplying on-coil electrical current.

Intraoperative Resting-State Functional Connectivity Based on RGB Imaging.

RGB optical imaging is a marker-free, contactless, and non-invasive technique that is able to monitor hemodynamic brain response following neuronal activation using task-based and resting-state procedures. Magnetic resonance imaging (fMRI) and functional near infra-red spectroscopy (fNIRS) resting-state procedures cannot be used intraoperatively but RGB imaging provides an ideal solution to identify resting-state networks during a neurosurgical operation. We applied resting-state methodologies to intraoperative RGB imaging and evaluated their ability to identify resting-state networks. We adapted two resting-state methodologies from fMRI for the identification of resting-state networks using intraoperative RGB imaging. Measurements were performed in 3 patients who underwent resection of lesions adjacent to motor sites. The resting-state networks were compared to the identifications provided by RGB task-based imaging and electrical brain stimulation. Intraoperative RGB resting-state networks corresponded to RGB task-based imaging (DICE:0.55±0.29). Resting state procedures showed a strong correspondence between them (DICE:0.66±0.11) and with electrical brain stimulation. RGB imaging is a relevant technique for intraoperative resting-state networks identification. Intraoperative resting-state imaging has several advantages compared to functional task-based analyses: data acquisition is shorter, less complex, and less demanding for the patients, especially for those unable to perform the tasks.

Machine Learning-Based Classification of the Health State of Mice Colon in Cancer Study from Confocal Laser Endomicroscopy.

In this article, we address the problem of the classification of the health state of the colon's wall of mice, possibly injured by cancer with machine learning approaches. This problem is essential for translational research on cancer and is a priori challenging since the amount of data is usually limited in all preclinical studies for practical and ethical reasons. Three states considered including cancer, health, and inflammatory on tissues. Fully automated machine learning-based methods are proposed, including deep learning, transfer learning, and shallow learning with SVM. These methods addressed different training strategies corresponding to clinical questions such as the automatic clinical state prediction on unseen data using a pre-trained model, or in an alternative setting, real-time estimation of the clinical state of individual tissue samples during the examination. Experimental results show the best performance of 99.93% correct recognition rate obtained for the second strategy as well as the performance of 98.49% which were achieved for the more difficult first case.

Intraoperative quantitative functional brain mapping using an RGB camera.

Intraoperative optical imaging is a localization technique for the functional areas of the human brain cortex during neurosurgical procedures. However, it still lacks robustness to be used as a clinical standard. In particular, new biomarkers of brain functionality with improved sensitivity and specificity are needed. We present a method for the computation of hemodynamics-based functional brain maps using an RGB camera and a white light source. We measure the quantitative oxy and deoxyhemoglobin concentration changes in the human brain cortex with the modified Beer-Lambert law and Monte Carlo simulations. A functional model has been implemented to evaluate the functional brain areas following neuronal activation by physiological stimuli. The results show a good correlation between the computed quantitative functional maps and the brain areas localized by electrical brain stimulation (EBS). We demonstrate that an RGB camera combined with a quantitative modeling of brain hemodynamics biomarkers can evaluate in a robust way the functional areas during neurosurgery and serve as a tool of choice to complement EBS.

Analysis of simulated and experimental backscattered images of turbid media in linearly polarized light: estimation of the anisotropy factor.

Optical characterization of biological tissues is of real interest to improve medical diagnosis, in particular in the detection of precancerous tissues. We propose a new, noninvasive method allowing the estimation of the anisotropy factor. This method is based on the image analysis of the Q element of the Stokes vector backscattered from the turbid medium. These Q-element images show specific patterns depending on g. Therefore the use of Fourier descriptors (FDs) on simulated data to discriminate the specific geometrical features of the Q element enabled us to determine a linear relation between the anisotropy factor and six FDs. This method was applied on experimental data obtained with calibrated solutions. The anisotropy factor was estimated with a maximum relative error of 13%.

Measuring hemoglobin oxygen saturation during graded hypoxic hypoxia in rat striatum.

We evaluated in vivo reflectance spectroscopy of visible light as a method to assess brain tissue hemoglobin oxygen saturation in rat striatum (SstrO2). Seven anesthetized and mechanically ventilated rats were subjected to incremental reduction in the fraction of inspired oxygen (Fio2): 0.35, 0.25, 0.15, 0.12, and 0.10, followed by a reoxygenation period (Group 1). At each episode, local changes in SstrO2 and in cerebral blood flow (LCBF) were simultaneously determined in the two striatal regions, using reflectance spectroscopy and laser Doppler flowmetry, respectively. Another group of rats (Group 2, n = 6) was also studied to measure sagittal sinus blood hemoglobin saturation (SssO2) during graded hypoxic hypoxia. Corpus striatum exhibited a significant graded decrease in SstrO2, from 38% +/- 17% at Fio2 of 0.35 (control) to 16% +/- 10% at Fio2 of 0.12 and to 13% +/- 7% at Fio2 of 0.10 (P < 0.05), with no difference between the two hemispheres. These local changes in SstrO2 were associated with a significant graded increase in LCBF: 161% +/- 26% of control values and 197% +/- 34% during these 2 hypoxic episodes, respectively (P < 0.05). All local changes were fully reversed during the reoxygenation period. In Group 2, SssO2 decreased from 38% +/- 8% at Fio2 of 0.35 (control) to 10% +/- 3% at Fio2 of 0.10, closely related to SstrO2 decreasing in hypoxia. This study shows that reflectance spectroscopy of the visible light in rat striatum could be a possible measure of continuous changes in SstrO2. SssO2 and LCBF measurements during graded hypoxic hypoxia indicate that changes in SstrO2 reflect primarily those in brain venous oxygenation.

An optical fiber-based gating device for prospective mouse cardiac MRI.

Prospective synchronization of MRI acquisitions on living organisms involves the monitoring of respiratory and heart motions. The electrocardiogram (ECG) signal is conventionally used to measure the cardiac cycle. However, in some circumstances, obtaining an uncorrupted ECG signal recorded on small animals with radio frequency (RF) pulses and gradient switching is challenging. To monitor respiratory motion, an air cushion associated with a pressure sensor is commonly used but the system suffers from bulkiness. For many applications, the physiological gating information can also be derived from an MR navigated signal. However, a compact device that can simultaneously provide respiratory and cardiac information, for both prospective gating and physiological monitoring, is desirable. This is particularly valid since small volume coils or dedicated cardiac RF coil arrays placed directly against the chest wall are required to maximize measurement sensitivity. An optic-based device designed to synchronize MRI acquisitions on small animal's respiratory and heart motion was developed using a transmit-receive pair of optical fibers. The suitability of the developed device was assessed on mice ( n = 10) and was based on two sets of experiments with dual cardiac and respiratory synchronization. Images acquired with prospective triggering using the optical-based signal, ECG, and the pressure sensor during the same experiment were compared between themselves in the first set. The second set compared prospective technique using optical-based device and ECG to a retrospective technique. The optical signal that was correlated to both respiratory and heart motion was totally unaffected by radiofrequency pulses or currents induced by the magnetic field gradients used for imaging. Mice heart MR images depict low-visible motion artifacts with all sensors or techniques used. No significant SNR differences were found between each series of image. Full fiber-optic-based signal derived from heart and respiratory motion was suitable for prospective triggering of heart MR imaging. The fiber optic device performed similarly to the ECG and air pressure sensors, while providing an advantage for imaging with dedicated cardiac array coils by reducing bulk. It can be an attractive alternative for small animal MRI in difficult environments such as limited space and strong gradient switching.

Optical spectroscopy combined with high-resolution magnetic resonance imaging for digestive wall assessment: endoluminal bimodal probe conception and characterization in vitro, on organic sample and in vivo on a rabbit.

Colorectal cancer is a major health issue worldwide. Conventional white light endoscopy (WLE) coupled to histology is considered as the gold standard today and is the most widespread technique used for colorectal cancer diagnosis. However, during the early stages, colorectal cancer is very often characterized by flat adenomas which develop just underneath the mucosal surface. The use of WLE, which is heavily based on the detection of morphological changes, becomes quite delicate due to subtle or quasi-invisible morphological changes of the colonic lining. Several techniques are currently being investigated in the scope of providing new tools that would allow such a diagnostic or assist actual techniques in so doing. We hereby present a novel technique where high spatial resolution MRI is combined with autofluorescence and reflectance spectroscopy in a bimodal endoluminal probe to extract morphological data and biochemical information, respectively. The design and conception of the endoluminal probe are detailed and the promising preliminary results obtained in vitro (home-built phantom containing eosin and rhodamine B), on an organic sample (the kiwi fruit) and in vivo on a rabbit are presented and discussed.

Estimation of optical properties of turbid media: experimental comparison of spatially and temporally resolved reflectance methods.

We compare two methods for the optical characterization of turbid media. The estimates of the absorption and reduced scattering coefficients (mu(a) and mu(')(s)) by a spatially resolved method and a time-resolved method are performed on tissue-like phantoms. Aqueous suspension of microspheres and Intralipid are used as scattering media with the addition of ink as an absorber. mu(')(s) is first measured on weakly absorbing media. The robustness of these measurements is then tested with respect to a variation of mu(a). The spatially resolved method gave more accurate estimates for mu(')(s) whereas the time-resolved method gave better results for mu(a) estimates.

Differential optical spectroscopy for absorption characterization of scattering media.

Reflectance techniques are commonly used to characterize the optical properties of tissues. However, the precise determination of local chromophore concentrations in turbid media is usually difficult because of the nonlinear dependence of light intensity as a function of scattering and absorption coefficients. A technique is presented to easily determine absorbent compound concentration ratios in a turbid media from three optical reflectance spectra, in the visible range, measured for source-detector distances less than 1cm. The validity of the method is experimentally established, in cases of sets of diluted milk containing absorbent inks, over a relatively wide range of absorption (0.05-0.5 cm(-1)) and reduced scattering (10-20 cm(-1)) coefficients.

Differential optical spectroscopy for absorption characterization of mono & two-layered scattering media.

Diffuse reflectance techniques are commonly used to characterize the optical properties of various biological tissues in the visible and NIR spectral ranges. Nevertheless a sharp determination of local chromophores concentration in turbid media is usually difficult to obtain because of the nonlinear dependence of the reflected light intensity as a function of scattering and absorption coefficients. The proposed technique of this paper allows to determine absorbent compounds concentration ratios in a turbid medium from three reflectance spectra, measured for source-detector distances inferior to 1 cm. This method is validated in the visible range in case of typical biological absorption and reduced scattering coefficients. Two-layered scattering media are also investigated.

Backscattered stokes vectors of turbid media: anisotropy factor and reduced scattering coefficient estimation.

Optical characterization of biological tissues is of real interest to improve medical diagnosis and in particular in the detection of precancerous tissues. The reduced scattering coefficient micro's and the absorption coefficient microa are the most commonly retrieved coefficients. Some methods also allow to obtain the anisotropy factor g, but only few of them are non-invasive. We propose a new non-invasive method allowing the estimation of the anisotropy factor and the reduced scattering coefficient. This method is based on the image analysis of the Q-element of Stokes vector backscattered from the turbid medium. These Q-element images show specific patterns depending on g, and micro's is determined by the size of the patterns. Therefore the use of Fourier Descriptors (FD) on simulated and experimental data, to discriminate the specific geometrical features of the Q-element, enabled us to determine the anisotropy factor and the scattering coefficient.

Asymptotic behavior and inverse problem in layered scattering media.

The main challenge of noninvasive optical biopsy is to obtain an accurate value of the optical coefficients of an encapsulated organ (muscle, brain, etc.). The idea developed by us is that some interesting information could be deduced from the long-time behavior of the reflectance function. This asymptotic behavior is analyzed for layered media in the framework of the diffusion approximation. A new method is derived to obtain accurate values for the optical parameters of the deepest layers. This method is designed to work in a specific long-time regime that is still within the scope of standard time-of-flight experiments but far from being included in the mathematically defined asymptotic region. The limits of this method, linked to the cases where the asymptotic behavior is no longer governed by the deepest layer, are then discussed.