Evaluation of a personalized functional near infra-red optical tomography workflow using maximum entropy on the mean.

In the present study, we proposed and evaluated a workflow of personalized near infra-red optical tomography (NIROT) using functional near-infrared spectroscopy (fNIRS) for spatiotemporal imaging of cortical hemodynamic fluctuations. The proposed workflow from fNIRS data acquisition to local 3D reconstruction consists of: (a) the personalized optimal montage maximizing fNIRS channel sensitivity to a predefined targeted brain region; (b) the optimized fNIRS data acquisition involving installation of optodes and digitalization of their positions using a neuronavigation system; and (c) the 3D local reconstruction using maximum entropy on the mean (MEM) to accurately estimate the location and spatial extent of fNIRS hemodynamic fluctuations along the cortical surface. The workflow was evaluated on finger-tapping fNIRS data acquired from 10 healthy subjects for whom we estimated the reconstructed NIROT spatiotemporal images and compared with functional magnetic resonance imaging (fMRI) results from the same individuals. Using the fMRI activation maps as our reference, we quantitatively compared the performance of two NIROT approaches, the MEM framework and the conventional minimum norm estimation (MNE) method. Quantitative comparisons were performed at both single subject and group-level. Overall, our results suggested that MEM provided better spatial accuracy than MNE, while both methods offered similar temporal accuracy when reconstructing oxygenated (HbO) and deoxygenated hemoglobin (HbR) concentration changes evoked by finger-tapping. Our proposed complete workflow was made available in the brainstorm fNIRS processing plugin-NIRSTORM, thus providing the opportunity for other researchers to further apply it to other tasks and on larger populations.

Effects of neoadjuvant chemotherapy on the contralateral non-tumor-bearing breast assessed by diffuse optical tomography.

BACKGROUND: The purpose of this study is to evaluate whether the changes in optically derived parameters acquired with a diffuse optical tomography breast imager system (DOTBIS) in the contralateral non-tumor-bearing breast in patients administered neoadjuvant chemotherapy (NAC) for breast cancer are associated with pathologic complete response (pCR). METHODS: In this retrospective evaluation of 105 patients with stage II-III breast cancer, oxy-hemoglobin (ctO2Hb) from the contralateral non-tumor-bearing breast was collected and analyzed at different time points during NAC. The earliest monitoring imaging time point was after 2-3 weeks receiving taxane. Longitudinal data were analyzed using linear mixed-effects modeling to evaluate the contralateral breast ctO2Hb changes across chemotherapy when corrected for pCR status, age, and BMI. RESULTS: Patients who achieved pCR to NAC had an overall decrease of 3.88 µM for ctO2Hb (95% CI, 1.39 to 6.37 µM), p = .004, after 2-3 weeks. On the other hand, non-pCR subjects had a non-significant mean reduction of 0.14 µM (95% CI, - 1.30 to 1.58 µM), p > .05. Mixed-effect model results indicated a statistically significant negative relationship of ctO2Hb levels with BMI and age. CONCLUSIONS: This study demonstrates that the contralateral normal breast tissue assessed by DOTBIS is modifiable after NAC, with changes associated with pCR after only 2-3 weeks of chemotherapy.

Global motion detection and censoring in high-density diffuse optical tomography.

Motion-induced artifacts can significantly corrupt optical neuroimaging, as in most neuroimaging modalities. For high-density diffuse optical tomography (HD-DOT) with hundreds to thousands of source-detector pair measurements, motion detection methods are underdeveloped relative to both functional magnetic resonance imaging (fMRI) and standard functional near-infrared spectroscopy (fNIRS). This limitation restricts the application of HD-DOT in many challenging imaging situations and subject populations (e.g., bedside monitoring and children). Here, we evaluated a new motion detection method for multi-channel optical imaging systems that leverages spatial patterns across measurement channels. Specifically, we introduced a global variance of temporal derivatives (GVTD) metric as a motion detection index. We showed that GVTD strongly correlates with external measures of motion and has high sensitivity and specificity to instructed motion-with an area under the receiver operator characteristic curve of 0.88, calculated based on five different types of instructed motion. Additionally, we showed that applying GVTD-based motion censoring on both hearing words task and resting state HD-DOT data with natural head motion results in an improved spatial similarity to fMRI mapping. We then compared the GVTD similarity scores with several commonly used motion correction methods described in the fNIRS literature, including correlation-based signal improvement (CBSI), temporal derivative distribution repair (TDDR), wavelet filtering, and targeted principal component analysis (tPCA). We find that GVTD motion censoring on HD-DOT data outperforms other methods and results in spatial maps more similar to those of matched fMRI data.

An Automated Preprocessing Method for Diffuse Optical Tomography to Improve Breast Cancer Diagnosis.

The ultrasound-guided diffuse optical tomography is a noninvasive imaging technique for breast cancer diagnosis and treatment monitoring. The technique uses a handheld probe capable of providing measurements of multiple wavelengths in a few seconds. These measurements are used to estimate optical absorptions of lesions and calculate the total hemoglobin concentration. Any measurement errors caused by low signal to noise ratio data and/or movements during data acquisition would reduce the accuracy of reconstructed total hemoglobin concentration. In this article, we introduce an automated preprocessing method that combines data collected from multiple sets of lesion measurements of 4 optical wavelengths to detect and correct outliers in the perturbation. Two new measures of correlation between each pair of wavelength measurements and a wavelength consistency index of all reconstructed absorption maps are introduced. For phantom and patients' data without evidence of measurement errors, the correlation coefficient between each pair of wavelength measurements was above 0.6. However, for patients with measurement errors, the correlation coefficient was much lower. After applying the correction method to 18 patients' data with measurement errors, the correlation has improved and the wavelength consistency index is in the same range as the cases without wavelength-dependent measurement errors. The results show an improvement in classification of malignant and benign lesions.

Optoacoustic micro-tomography at 100 volumes per second.

Optical microscopy remains a fundamental tool for modern biological discovery owing to its excellent spatial resolution and versatile contrast in visualizing cellular and sub-cellular structures. Yet, the time domain is paramount for the observation of biological dynamics in living systems. Commonly, acquisition of microscopy data involves scanning of a spherically- or cylindrically-focused light beam across the imaged volume, which significantly limits temporal resolution in 3D. Additional complications arise from intense light scattering of biological tissues, further restraining the effective penetration depth and field of view of optical microscopy techniques. To overcome these limitations, we devised a fast optoacoustic micro-tomography (OMT) approach based on simultaneous acquisition of 3D image data with a high-density hemispherical ultrasound array having effective detection bandwidth beyond 25 MHz. We demonstrate fast three-dimensional imaging of freely-swimming zebrafish larvae, achieving 3D imaging speed of 100 volumes per second with isotropic spatial resolution approaching the dimensions of large cells across a field of view exceeding 50mm3. As opposed to other microscopy techniques based on optical contrast, OMT resolves optical absorption acoustically using unfocused light excitation. Thus, no penetration barriers are imposed by light scattering in deep tissues, suggesting it as a powerful approach for multi-scale functional and molecular imaging applications.

Estimation of optoacoustic contrast agent concentration with self-calibration blind logarithmic unmixing.

Chromophore quantification in optoacoustic tomography is challenging due to signal contributions from strongly absorbing background tissue chromophores and the depth-dependent light attenuation. Herein we present a procedure capable of correcting for wavelength-dependent light fluence variations using a logarithmic representation of the images taken at different wavelengths assisted with a blind unmixing approach. It is shown that the serial expansion of the logarithm of an optoacoustic image contains a term representing the ratio between absorption of the probe of interest and other background components. Under assumptions of tissue-like background absorption variations, this term can be readily isolated with an unmixing algorithm, attaining quantitative maps of photo-absorbing agent distribution.

A generic, geometric cocalibration method for a combined system of fluorescence molecular tomography and microcomputed tomography with arbitrarily shaped objects.

PURPOSE: A combined system of fluorescence molecular tomography and microcomputed tomography (FMT&mCT) can provide molecular and anatomical information of small animals in a single study with intrinsically coregistered images. The anatomical information provided by the mCT subsystem is commonly used as a reference to locate the fluorophore distribution or as a priori structural information to improve the performance of FMT. Therefore, the transformation between the coordinate systems of the subsystem needs to be determined in advanced. METHODS: A cocalibration method for the combined system of FMT&mCT is proposed. First, linear models are adopted to describe the galvano mirrors and the charge-coupled device (CCD) camera in the FMT subsystem. Second, the position and orientation of the galvano mirrors are determined with the input voltages of the galvano mirrors and the markers, whose positions are predetermined. The position, orientation and normalized pixel size of the CCD camera are obtained by analysing the projections of a point-like marker at different positions. Finally, the orientation and position of sources and the corresponding relationship between the detectors and their projections on the image plane are predicted. Because the positions of the markers are acquired with mCT, the registration of the FMT and mCT could be realized by direct image fusion. RESULTS: The accuracy and consistency of this method in the presence of noise is evaluated by computer simulation. Next, a practical implementation for an experimental FMT&mCT system is carried out and validated. The maximum prediction error of the source positions on the surface of a cylindrical phantom is within 0.375 mm and that of the projections of a point-like marker is within 0.629 pixel. Finally, imaging experiments of the fluorophore distribution in a cylindrical phantom and a phantom with a complex shape demonstrate the feasibility of the proposed method. CONCLUSIONS: This method is universal in FMT&mCT, which could be performed with no restriction on the system geometry, calibration phantoms or imaging objects.

Performance of GDx and HRT in the Finnish Evidence-Based Guideline for Open-Angle Glaucoma.

AIM: To compare the performance of Heidelberg retina tomograph (HRT) and scanning laser polarimetry (GDx) with photographic evaluation of the optic nerve head (ONH) and retinal nerve fiber layer (RNFL) in the application of the Finnish Evidence-Based Guideline for Open-Angle Glaucoma. METHODS: A total of 41 control participants and 312 patients referred for glaucoma evaluation were included in the study. All the participants underwent ophthalmic evaluation, ONH stereophotography, monochromatic RNFL photography, HRT, optical coherence tomography, and GDx evaluation. Participants were classified on the basis of stereophotographic or imaging device results based by applying the Finnish Guideline. RESULTS: Agreement between the stereophotographic evaluation and that on the basis of the imaging devices was 52.9%. Classification of patients with similar management advice on the basis of these evaluations had 56.4% agreement. The specificity of the Finnish guideline for detecting normal patients was 78% (stereophotography) and 83% (imaging devices). Optic disc size interfered with the diagnosis in patients evaluated using the HRT3 glaucoma probability score. Structural changes were more frequently detected before functional changes. CONCLUSION: The Finnish Evidence-Based Guideline for Open-Angle Glaucoma is useful for classifying normal participants and patients with suspected glaucoma or glaucoma through either conventional stereophotographic evaluation of the neuroretinal structures or with the new imaging devices.

Standardized platform for coregistration of nonconcurrent diffuse optical and magnetic resonance breast images obtained in different geometries.

We present a novel methodology for combining breast image data obtained at different times, in different geometries, and by different techniques. We combine data based on diffuse optical tomography (DOT) and magnetic resonance imaging (MRI). The software platform integrates advanced multimodal registration and segmentation algorithms, requires minimal user experience, and employs computationally efficient techniques. The resulting superposed 3-D tomographs facilitate tissue analyses based on structural and functional data derived from both modalities, and readily permit enhancement of DOT data reconstruction using MRI-derived a-priori structural information. We demonstrate the multimodal registration method using a simulated phantom, and we present initial patient studies that confirm that tumorous regions in a patient breast found by both imaging modalities exhibit significantly higher total hemoglobin concentration (THC) than surrounding normal tissues. The average THC in the tumorous regions is one to three standard deviations larger than the overall breast average THC for all patients.

Glaucoma detection with the Heidelberg retina tomograph 3.

PURPOSE: To compare the ability of the Heidelberg retina tomograph version 3 (HRT 3) and HRT version 2 (HRT 2) to discriminate between healthy and glaucomatous eyes. DESIGN: Retrospective cross-sectional study. PARTICIPANTS: Seventy-one eyes of 71 healthy volunteers and 50 eyes of 50 glaucoma patients were studied. The average visual field mean deviation of the glaucoma group was -6.03+/-5.78 dB. INTERVENTION: All participants had comprehensive ocular examinations, perimetry, and HRT scanning within 6 months. HRT 2 data were analyzed using HRT 3 software without modifying the disc margin. MAIN OUTCOME MEASURES: Discrimination capabilities between healthy and glaucomatous eyes were determined by areas under the receiver operating characteristics (AROCs) curves. Comparisons between corresponding AROCs obtained by HRT 2 and HRT 3 analyses were performed using the nonparametric DeLong method. Agreement between classifications as defined by the different analysis methods was quantified by kappa analysis. RESULTS: The individual stereometric parameters with the best discrimination were linear cup/disc ratio (AROC = 0.897; 95% confidence interval [CI], 0.836-0.958) for standard HRT 3 analysis and horizontal retinal nerve fiber layer curvature (0.905) for HRT 3 glaucoma probability score (GPS) analysis. Areas under the receiver operating characteristics for discrimination between glaucomatous and healthy eyes of the overall classification by HRT 2 Moorfields regression analysis (MRA), HRT 3 MRA, and GPS were 0.927 (95% CI, 0.877-0.977), 0.934 (0.888-0.980), and 0.880 (0.812-0.948), respectively. The difference between the 3 AROCs was not significant (P = 0.44). The agreement between HRT 2 and HRT 3 overall MRA classification was good (kappa = 0.70; CI, 0.59-0.80) with HRT 3 tending to report more abnormalities than HRT 2 analysis. The agreement between overall HRT 3 MRA and overall GPS was kappa = 0.58 (CI, 0.45-0.70). CONCLUSIONS: The glaucoma discriminating ability of the new HRT 3 software is similar to that of the previous generation HRT 2. The GPS analysis showed promising results in differentiating between healthy and glaucomatous eyes without the need for subjective operator input.

Optic disc topography and peripapillary retinal nerve fiber layer thickness in nonarteritic ischemic optic neuropathy and open-angle glaucoma.

OBJECTIVE: To evaluate the results of scanning laser tomography and scanning laser polarimetry (SLP) and the correlations with visual field damage (VFD) in eyes with nonarteritic ischemic optic neuropathy (n-AION) compared with eyes with open-angle glaucoma (OAG). DESIGN: Cross-sectional study. PARTICIPANTS: Thirty-three eyes of 33 patients with n-AION and 33 eyes with OAG whose age and VFD evaluated with the Humphrey field analyzer were matched to those of the n-AION eyes. MAIN OUTCOME MEASURES: The parameters of optic disc topography obtained with the Heidelberg Retina Tomograph II (HRT II) and retinal nerve fiber layer (RNFL) thickness with GDx with variable corneal compensation and the correlation to VFD. RESULTS: The cup area, cup-to-disc area ratio, and mean cup depth were significantly smaller, and the cup shape measure more negative, in the n-AION eyes than in the OAG eyes (P<0.001), whereas rim area was significantly greater (P<0.001). Multivariate analyses showed that none of disc area, rim area, and mean cup depth in the n-AION eyes and only rim area (P = 0.029) in the OAG eyes was significantly associated with mean deviation (MD). Ellipse average of RNFL thickness significantly correlated with MD in the n-AION eyes (P = 0.045) and in the OAG eyes (P = 0.022). CONCLUSIONS: Disc topography of eyes with n-AION was quantitatively characterized by small and shallow cupping and a relatively large rim area compared to eyes with OAG matched for age and VFD. In eyes with n-AION, significant correlation with VFD was found only for the RNFL thickness evaluated with SLP but not for the HRT II parameters.

Diagnostic ability of different tools for detection of glaucoma with confocal scanning laser tomography (Heidelberg Retina Tomograph II).

We evaluated the diagnostic ability of various diagnostic tools to detect glaucomatous damage in 101 normal eyes and 102 glaucomatous eyes. Mikelberg's linear discriminant function (LDF) obtained the best sensitivity followed by our own four formulas. With respect to specificity, Burk's LDF showed better results than Mikelberg's LDF and our formulae. Several Heidelberg retina tomograph analysis tools are useful to discriminate healthy from patients with glaucoma. Alternative tools based on normative databases derived from different autochthon populations add evidence needed to support their global use.

The effectiveness of the Heidelberg Retina Tomograph and laser diagnostic glaucoma scanning system (GDx) in detecting and monitoring glaucoma.

OBJECTIVES: To determine the potential of optic nerve head tomography [Heidelberg Retina Tomograph (HRT)] and scanning laser polarimetry (GDx) for identifying patients with glaucomatous visual field loss. DESIGN: Examinations were performed with the HRT, GDx and Humphrey Field Analyzer (HFA). Glaucoma was defined by the presence of a field defect. Patients within the cross-sectional groups underwent a single examination, whereas patients in the longitudinal groups were examined 6 monthly, for an average of 3.5 years. SETTING: Manchester Royal Eye Hospital, UK. PARTICIPANTS: Patients with primary open angle glaucoma (POAG) or who were at risk of developing glaucoma. INTERVENTIONS: The diagnostic accuracies of the HRT and GDx were compared; specificity was set at 95%. The rate of change was determined by linear regression. To estimate the clinical application of the instruments, the proportion of an unselected group of patients on whom the examinations could be performed was calculated. Additionally, the time taken to perform and process each examination was measured. MAIN OUTCOME MEASURES: The ability of the techniques to identify cases showing deterioration. The level of agreement and applicability of the techniques. Time taken to perform and process each examination. RESULTS: From the cross-sectional group, the maximum sensitivities of the HRT and GDx were 59% and 45%, respectively (at 95% specificity). From the two longitudinal cohorts, the level of agreement between the three instruments for identification of the development and deterioration of POAG was low. The applicability of the techniques was 80% (HRT), 88% (GDx) and 98% (HFA). The length of time to perform a full examination with each instrument was 12.3, 11.8 and 28.3 minutes, respectively. Agreement of HRT and GDx parameters between and within observers was largely good. CONCLUSIONS: There is poor agreement for detection of glaucoma between the HFA, HRT and GDx. The techniques are amenable to use in the clinical environment, but no single examination has sufficient diagnostic precision to be used in isolation; also, the imaging techniques were not universally applicable. Neither the HRT nor GDx should be viewed as a replacement for visual field examination. Further research is needed into why most patients within the longitudinal arms of the study showed very little deterioration and into determining aspects of the structure versus function relationship in glaucoma that may explain why any one technique fails to detect a proportion of cases.

Towards a standard analysis for functional near-infrared imaging.

Functional near-infrared spectroscopy (fNIRS) allows the ability to monitor brain activation by measuring changes in the concentration of oxy- and deoxy-hemoglobin. Until now no standardized approach for fNIRS data analysis has been established, although this has to be regarded as a precondition for future application. Hence, we applied the well-established general linear model to optical imaging data. Further, fNIRS data were analyzed in the frequency domain. Two visual tasks were investigated with optical imaging: a checkerboard paradigm supposed to activate the primary and secondary visual cortex, and a paradigm consisting of moving colored stimuli (rotating 'L's) additionally involving the motion area V5. Analysis with the general linear model detected the activation focus in the primary and secondary visual cortex during the first paradigm. For the second paradigm, a second laterally localized activated brain region was found, most likely representing V5. Spatially resolved spectral analysis confirmed the results by showing maxima of power spectral density and coherence in the same respective brain regions. Moreover, it demonstrated a delay of the hemodynamic response in the motion area. In summary, the present study suggests that the general linear model and spatially resolved spectral analysis can be used as standard statistical approaches for optical imaging data, particularly because they are almost independent of the assumed differential path length factors.

Reflectance-based determination of optical properties in highly attenuating tissue.

Accurate data on in vivo tissue optical properties in the ultraviolet A (UVA) to visible (VIS) range are needed to elucidate light propagation effects and to aid in identifying safe exposure limits for biomedical optical spectroscopy. We have performed a preliminary study toward the development of a diffuse reflectance system with maximum fiber separation distance of less than 2.5 mm. The ultimate objective is to perform endoscopic measurement of optical properties in the UVA to VIS. Optical property sets with uniformly and randomly distributed values were developed within the range of interest: absorption coefficients from 1 to 25 cm(-1) and reduced scattering coefficients from 5 to 25 cm(-1). Reflectance datasets were generated by direct measurement of Intralipid-dye tissue phantoms at lambda=675 nm and Monte Carlo simulation of light propagation. Multivariate calibration models were generated using feed-forward artificial neural network or partial least squares algorithms. Models were calibrated and evaluated using simulated or measured reflectance datasets. The most accurate models developed-those based on a neural network and uniform optical property intervals-were able to determine absorption and reduced scattering coefficients with root mean square errors of +/-2 and +/-3 cm(-1), respectively. Measurements of ex vivo bovine liver at 543 and 633 nm were within 5 to 30% of values reported in the literature. While our technique for determination of optical properties appears feasible and moderately accurate, enhanced accuracy may be achieved through modification of the experimental system and processing algorithms.