Revisiting Transcranial Light Stimulation as a Stroke Therapeutic-Hurdles and Opportunities.

Near-infrared laser therapy, a special form of transcranial light therapy, has been tested as an acute stroke therapy in three large clinical trials. While the NEST trials failed to show the efficacy of light therapy in human stroke patients, there are many lingering questions and lessons that can be learned. In this review, we summarize the putative mechanism of light stimulation in the setting of stroke, highlight barriers, and challenges during the translational process, and evaluate light stimulation parameters, dosages and safety issues, choice of outcomes, effect size, and patient selection criteria. In the end, we propose potential future opportunities with transcranial light stimulation as a cerebroprotective or restorative tool for future stroke treatment.

Alterted Adipogenesis of Human Mesenchymal Stem Cells by Photobiomodulation Using 1064 nm Laser Light.

BACKGROUND AND OBJECTIVES: Photobiomodulation (PBM) describes the influence of light irradiation on biological tissues. Laser light in the near-infrared (NIR) spectrum has been shown to mitigate pain, reduce inflammation, and promote wound healing. The cellular mechanism that mediates PBM's effects is generally accepted to be at the site of the mitochondria, leading to an increased flux through the electron transport chain and adenosine triphosphate (ATP) production. Moreover, PBM has been demonstrated to reduce oxidative stress through an increased production of reactive oxygen species (ROS)-sequestering enzymes. The aim of the study is to determine whether these PBM-induced effects expedite or interfere with the intended stem cell differentiation to the adipogenic lineage. STUDY DESIGN/MATERIALS AND METHODS: To determine the effects of 1064 nm laser irradiation (fluence of 8.8-26.4 J/cm2 ) on human mesenchymal stem cells (hMSCs) undergoing adipogenic differentiation, the ATP and ROS levels, and adipogenic markers were quantitatively measured. RESULTS: At a low fluence (8.8 J/cm2 ) the ATP increase was essentially negligible, whereas a higher fluence induced a significant increase. In the laser-stimulated cells, PBM over time decreased the ROS level compared with the non-treated control group and significantly reduced the extent of adipogenesis. A reduction in the ROS level was correlated with a diminished lipid accumulation, reduced production of adipose-specific genetic markers, and delayed the chemically intended adipogenesis. CONCLUSION: We characterized the use of NIR light exposure to modulate adipogenesis. Both the ATP and ROS levels in hMSCs responded to different energy densities. The current study is expected to contribute significantly to the growing field of PBM as well as stem cell tissue engineering by demonstrating the wavelength-dependent responses of hMSC differentiation. Lasers Surg. Med. © 2020 Wiley Periodicals LLC.

Transcranial Photobiomodulation (tPBM) With 1,064-nm Laser to Improve Cerebral Metabolism of the Human Brain In Vivo.

BACKGROUND AND OBJECTIVES: In our previous proof-of-principle study, transcranial photobiomodulation (tPBM) with 1,064-nm laser was reported to significantly increase concentration changes of oxygenated hemoglobin (∆[HbO]) and oxidized-state cytochrome c oxidase (∆[oxi-CCO]) in the human brain. This paper further investigated (i) its validity in two different subsets of young human subjects at two study sites over a period of 3 years and (ii) age-related effects of tPBM by comparing sham-controlled increases of ∆[HbO] and ∆[oxi-CCO] between young and older adults. STUDY DESIGN/MATERIALS AND METHODS: We measured sham-controlled ∆[HbO] and ∆[oxi-CCO] using broadband near-infrared spectroscopy (bb-NIRS) in 15 young (26.7 ± 2.7 years of age) and 5 older (68.2 ± 4.8 years of age) healthy normal subjects before, during, and after right-forehead tPBM/sham stimulation with 1,064-nm laser. Student t tests were used to test statistical differences in tPBM-induced ∆[HbO] and ∆[oxi-CCO] (i) between the 15 young subjects and those of 11 reported previously and (ii) between the two age groups measured in this study. RESULTS: Statistical analysis showed that no significant difference existed in ∆[HbO] and ∆[oxi-CCO] during and post tPBM between the two subsets of young subjects at two study sites over a period of 3 years. Furthermore, the two age groups showed statistically identical net increases in sham-controlled ∆[HbO] and ∆[oxi-CCO]. CONCLUSIONS: This study provided strong evidence to validate/confirm our previous findings that tPBM with 1,064-nm laser enables to increase cerebral ∆[HbO] and ∆[oxi-CCO] in the human brain, as measured by bb-NIRS. Overall, it demonstrated the robust reproducibility of tPBM being able to improve cerebral hemodynamics and metabolism of the human brain in vivo in both young and older adults. Lasers Surg. Med. © 2020 The Authors. Lasers in Surgery and Medicine published by Wiley Periodicals, Inc.

Characterization of the functional near-infrared spectroscopy response to nociception in a pediatric population.

BACKGROUND: Near-infrared spectroscopy can interrogate functional optical signal changes in regional brain oxygenation and blood volume to nociception analogous to functional magnetic resonance imaging. AIMS: This exploratory study aimed to characterize the near-infrared spectroscopy signals for oxy-, deoxy-, and total hemoglobin from the brain in response to nociceptive stimulation of varying intensity and duration, and after analgesic and neuromuscular paralytic in a pediatric population. METHODS: We enrolled children 6 months-21 years during propofol sedation before surgery. The near-infrared spectroscopy sensor was placed on the forehead and nociception was produced from an electrical current applied to the wrist. We determined the near-infrared spectroscopy signal response to increasing current intensity and duration, and after fentanyl, sevoflurane, and neuromuscular paralytic. Heart rate and arm movement during electrical stimulation was also recorded. The near-infrared spectroscopy signals for oxy-, deoxy-, and total hemoglobin were calculated as optical density*time (area under curve). RESULTS: During electrical stimulation, nociception was evident: tachycardia and arm withdrawal was observed that disappeared after fentanyl and sevoflurane, whereas after paralytic, tachycardia persisted while arm withdrawal disappeared. The near-infrared spectroscopy signals for oxy-, deoxy-, and total hemoglobin increased during stimulation and decreased after stimulation; the areas under the curves were greater for stimulations 30 mA vs 15 mA (13.9 [5.6-22.2], P = .0021; 5.6 [0.8-10.5], P = .0254, and 19.8 [10.5-29.1], P = .0002 for HbO2 , Hb, and HbT , respectively), 50 Hz vs 1 Hz (17.2 [5.8-28.6], P = .0046; 7.5 [0.7-14.3], P = .0314, and 21.9 [4.2-39.6], P = .0177 for HbO2 , Hb, and HbT , respectively) and 45 seconds vs 15 seconds (16.3 [3.4-29.2], P = .0188 and 22.0 [7.5-36.5], P = .0075 for HbO2 and HbT , respectively); the areas under the curves were attenuated by analgesics but not by paralytic. CONCLUSION: Near-infrared spectroscopy detected functional activation to nociception in a broad pediatric population. The near-infrared spectroscopy response appears to represent nociceptive processing because the signals increased with noxious stimulus intensity and duration, and were blocked by analgesics but not paralytics.

Elevated cranial ultrasound resistive indices are associated with improved neurodevelopmental outcomes one year after pediatric cardiac surgery: A single center pilot study.

OBJECTIVE: To determine if a non-invasive, repeatable test can be used to predict neurodevelopmental outcomes in patients with congenital heart disease. METHODS: This was a prospective study of pediatric patients less than two months of age undergoing congenital heart surgery at the Children's Health Children's Medical Center at Dallas. Multichannel near-infrared spectroscopy (NIRS) was utilized during the surgery, and ultrasound (US) resistive indices (RI) of the major cranial vessels were obtained prior to surgery, immediately post-operatively, and prior to discharge. Pearson's correlation, Fischer exact t test, and Fischer r to z transformation were used where appropriate. RESULTS: A total of 16 patients were enrolled. All had US data. Of the sixteen patients, two died prior to the neurodevelopmental testing, six did not return for the neurodevelopmental testing, and eight patients completed the neurodevelopmental testing. There were no significant correlations between the prior to surgery and prior to discharge US RI and neurodevelopmental outcomes. The immediate post-operative US RI demonstrated a strong positive correlation with standardized neurodevelopmental outcome measures. We were able to demonstrate qualitative differences using multichannel NIRS during surgery, but experienced significant technical difficulties implementing consistent monitoring. CONCLUSIONS: A higher resistive index in the major cerebral blood vessels following cardiac surgery in the neonatal period is associated with improved neurological outcomes one year after surgery. Obtaining an ultrasound with resistive indices of the major cerebral vessels prior to and after surgery may yield information that is predictive of neurodevelopmental outcomes.

Simultaneous multi-slice (SMS) acquisition enhances the sensitivity of hemodynamic mapping using gas challenges.

Hemodynamic mapping using gas inhalation has received increasing interest in recent years. Cerebrovascular reactivity (CVR), which reflects the ability of the brain vasculature to dilate in response to a vasoactive stimulus, can be measured by CO2 inhalation with continuous acquisition of blood oxygen level-dependent (BOLD) magnetic resonance images. Cerebral blood volume (CBV) can be measured by O2 inhalation. These hemodynamic mapping methods are appealing because of their absence of gadolinium contrast agent, their ability to assess both baseline perfusion and vascular reserve, and their utility in calibrating the functional magnetic resonance imaging (fMRI) signal. However, like other functional and physiological indices, a major drawback of these measurements is their poor sensitivity and reliability. Simultaneous multi-slice echo planar imaging (SMS EPI) is a fast imaging technology that allows the excitation and acquisition of multiple two-dimensional slices simultaneously, and has been shown to enhance the sensitivity of several MRI applications. To our knowledge, the benefit of SMS in gas inhalation imaging has not been investigated. In this work, we compared the sensitivity of CO2 and O2 inhalation data collected using SMS factor 2 (SMS2) and SMS factor 3 (SMS3) with those collected using conventional EPI (SMS1). We showed that the sensitivity of SMS scans was significantly (p = 0.01) higher than that of conventional EPI, although no difference was found between SMS2 and SMS3 (p = 0.3). On a voxel-wise level, approximately 20-30% of voxels in the brain showed a significant enhancement in sensitivity when using SMS compared with conventional EPI, with other voxels showing an increase, but not reaching statistical significance. When using SMS, the scan duration can be reduced by half, whilst maintaining the sensitivity of conventional EPI. The availability of a sensitive acquisition technique can further enhance the potential of gas inhalation MRI in clinical applications.

Detecting positive surgical margins: utilisation of light-reflectance spectroscopy on ex vivo prostate specimens.

OBJECTIVE: To assess the efficacy of light-reflectance spectroscopy (LRS) to detect positive surgical margins (PSMs) on ex vivo radical prostatectomy (RP) specimens. MATERIALS AND METHODS: A prospective evaluation of ex vivo RP specimens using LRS was performed at a single institution from June 2013 to September 2014. LRS measurements were performed on selected sites on the prostate capsule, marked with ink, and correlated with pathological analysis. Significant features on LRS curves differentiating malignant tissue from benign tissue were determined using a forward sequential selection algorithm. A logistic regression model was built and randomised cross-validation was performed. The sensitivity, specificity, accuracy, negative predictive value (NPV), positive predictive value (PPV), and area under the receiver operating characteristic curve (AUC) for LRS predicting PSM were calculated. RESULTS: In all, 50 RP specimens were evaluated using LRS. The LRS sensitivity for Gleason score ≥7 PSMs was 91.3%, specificity 92.8%, accuracy 92.5%, PPV 73.2%, NPV 99.4%, and the AUC was 0.960. The LRS sensitivity for Gleason score ≥6 PSMs was 65.5%, specificity 88.1%, accuracy 83.3%, PPV 66.2%, NPV 90.7%, and the AUC was 0.858. CONCLUSIONS: LRS can reliably detect PSMs for Gleason score ≥7 prostate cancer in ex vivo RP specimens.

Dimensionality Reduction Based Optimization Algorithm for Sparse 3-D Image Reconstruction in Diffuse Optical Tomography.

Diffuse optical tomography (DOT) is a relatively low cost and portable imaging modality for reconstruction of optical properties in a highly scattering medium, such as human tissue. The inverse problem in DOT is highly ill-posed, making reconstruction of high-quality image a critical challenge. Because of the nature of sparsity in DOT, sparsity regularization has been utilized to achieve high-quality DOT reconstruction. However, conventional approaches using sparse optimization are computationally expensive and have no selection criteria to optimize the regularization parameter. In this paper, a novel algorithm, Dimensionality Reduction based Optimization for DOT (DRO-DOT), is proposed. It reduces the dimensionality of the inverse DOT problem by reducing the number of unknowns in two steps and thereby makes the overall process fast. First, it constructs a low resolution voxel basis based on the sensing-matrix properties to find an image support. Second, it reconstructs the sparse image inside this support. To compensate for the reduced sensitivity with increasing depth, depth compensation is incorporated in DRO-DOT. An efficient method to optimally select the regularization parameter is proposed for obtaining a high-quality DOT image. DRO-DOT is also able to reconstruct high-resolution images even with a limited number of optodes in a spatially limited imaging set-up.

Transcranial laser stimulation improves human cerebral oxygenation.

BACKGROUND AND OBJECTIVE: Transcranial laser stimulation of the brain with near-infrared light is a novel form of non-invasive photobiomodulation or low-level laser therapy (LLLT) that has shown therapeutic potential in a variety of neurological and psychological conditions. Understanding of its neurophysiological effects is essential for mechanistic study and treatment evaluation. This study investigated how transcranial laser stimulation influences cerebral hemodynamics and oxygenation in the human brain in vivo using functional near-infrared spectroscopy (fNIRS). MATERIALS AND METHODS: Two separate experiments were conducted in which 1,064-nm laser stimulation was administered at (1) the center and (2) the right side of the forehead, respectively. The laser emitted at a power of 3.4 W and in an area of 13.6 cm2, corresponding to 0.25 W/cm2 irradiance. Stimulation duration was 10 minutes. Nine healthy male and female human participants of any ethnic background, in an age range of 18-40 years old were included in each experiment. RESULTS: In both experiments, transcranial laser stimulation induced an increase of oxygenated hemoglobin concentration (Δ[HbO2 ]) and a decrease of deoxygenated hemoglobin concentration (Δ[Hb]) in both cerebral hemispheres. Improvements in cerebral oxygenation were indicated by a significant increase of differential hemoglobin concentration (Δ[HbD] = Δ[HbO2 ] - Δ[Hb]). These effects increased in a dose-dependent manner over time during laser stimulation (10 minutes) and persisted after laser stimulation (6 minutes). The total hemoglobin concentration (Δ[HbT] = Δ[HbO2] + Δ[Hb]) remained nearly unchanged in most cases. CONCLUSION: Near-infrared laser stimulation applied to the forehead can transcranially improve cerebral oxygenation in healthy humans.

Light Reflectance Spectroscopy to Detect Positive Surgical Margins on Prostate Cancer Specimens.

PURPOSE: Intraoperative frozen section analysis is not routinely performed to determine positive surgical margins at radical prostatectomy due to time requirements and unproven clinical usefulness. Light reflectance spectroscopy, which measures light intensity reflected or backscattered from tissues, can be applied to differentiate malignant from benign tissue. We used a novel light reflectance spectroscopy probe to evaluate positive surgical margins on ex vivo radical prostatectomy specimens and correlate its findings with pathological examination. MATERIALS AND METHODS: Patients with intermediate to high risk disease undergoing radical prostatectomy were enrolled. Light reflectance spectroscopy was performed on suspected malignant and benign prostate capsule immediately following organ extraction. Each light reflectance spectroscopy at 530 to 830 nm was analyzed and correlated with pathological results. A regression model and forward sequential selection algorithm were developed for optimal feature selection. Eighty percent of light reflectance spectroscopy data were selected to train a logistic regression model, which was evaluated by the remaining 20% data. This was repeated 5 times to calculate averaged sensitivity, specificity and accuracy. RESULTS: Light reflectance spectroscopy analysis was performed on 17 ex vivo prostate specimens, on which a total of 11 histologically positive and 22 negative surgical margins were measured. Two select features from 700 to 830 nm were identified as unique to malignant tissue. Cross-validation when performing the predictive model showed that the optical probe predicted positive surgical margins with 85% sensitivity, 86% specificity, 86% accuracy and an AUC of 0.95. CONCLUSIONS: Light reflectance spectroscopy can identify positive surgical margins accurately in fresh ex vivo radical prostatectomy specimens. Further study is required to determine whether such analysis may be used in real time to improve surgical decision making and decrease positive surgical margin rates.

Prostate cancer detection using combined auto-fluorescence and light reflectance spectroscopy: ex vivo study of human prostates.

This study was conducted to evaluate the capability of detecting prostate cancer (PCa) using auto-fluorescence lifetime spectroscopy (AFLS) and light reflectance spectroscopy (LRS). AFLS used excitation at 447 nm with four emission wavelengths (532, 562, 632, and 684 nm), where their lifetimes and weights were analyzed using a double exponent model. LRS was measured between 500 and 840 nm and analyzed by a quantitative model to determine hemoglobin concentrations and light scattering. Both AFLS and LRS were taken on n = 724 distinct locations from both prostate capsular (nc = 185) and parenchymal (np = 539) tissues, including PCa tissue, benign peripheral zone tissue and benign prostatic hyperplasia (BPH), of fresh ex vivo radical prostatectomy specimens from 37 patients with high volume, intermediate-to-high-grade PCa (Gleason score, GS ≥7). AFLS and LRS parameters from parenchymal tissues were analyzed for statistical testing and classification. A feature selection algorithm based on multinomial logistic regression was implemented to identify critical parameters in order to classify high-grade PCa tissue. The regression model was in turn used to classify PCa tissue at the individual aggressive level of GS = 7,8,9. Receiver operating characteristic curves were generated and used to determine classification accuracy for each tissue type. We show that our dual-modal technique resulted in accuracies of 87.9%, 90.1%, and 85.1% for PCa classification at GS = 7, 8, 9 within parenchymal tissues, and up to 91.1%, 91.9%, and 94.3% if capsular tissues were included for detection. Possible biochemical and physiological mechanisms causing signal differences in AFLS and LRS between PCa and benign tissues were also discussed.

Hierarchical clustering method to improve transrectal ultrasound-guided diffuse optical tomography for prostate cancer imaging.

The inclusion of anatomical prior information in reconstruction algorithms can improve the quality of reconstructed images in near-infrared diffuse optical tomography (DOT). Prior literature on possible locations of human prostate cancer from transrectal ultrasound (TRUS), however, is limited and has led to biased reconstructed DOT images. In this work, we propose a hierarchical clustering method (HCM) to improve the accuracy of image reconstruction with limited prior information. HCM reconstructs DOT images in three steps: 1) to reconstruct the human prostate, 2) to divide the prostate region into geometric clusters to search for anomalies in finer clusters, 3) to continue the geometric clustering within anomalies for improved reconstruction. We demonstrated this hierarchical clustering method using computer simulations and laboratory phantom experiments. Computer simulations were performed using combined TRUS/DOT probe geometry with a multilayered model; experimental demonstration was performed with a single-layer tissue simulating phantom. In computer simulations, two hidden absorbers without prior location information were reconstructed with a recovery rate of 100% in their locations and 95% in their optical properties. In experiments, a hidden absorber without prior location information was reconstructed with a recovery rate of 100% in its location and 83% in its optical property.

Occurrence and environmental risk assessment of PAEs in Weihe River near Xi'an City, China.

The occurrence and distribution of phthalate acid esters (PAEs) in surface water of the Weihe River basin (eight mainstream sampling points and 15 tributary sampling points) in the Shaanxi section were investigated during the dry season, level period (spring), wet season and level period (autumn). The PAEs tested for were diethyl phthalate (DEP), di-n-butyl phthalate (DBP), dicyclohexyl phthalate (DCHP) and di-(2-ethylhexyl) phthalate (DEHP). The testing proceeded by millipore filtration, then solid phase extraction and then gas chromatography-mass spectrometry determination for all examined PAEs. The monitoring results indicated that, in terms of seasonal changes, concentration of the PAEs in the mainstream is: Dry season > Level period (spring) > Wet season ≈ Level period (autumn). An environmental risk assessment was then performed on PAE pollution levels of the Weihe River basin. This paper employed a risk assessment methodology to evaluate the potential adverse health effects of the individual PAE compounds according to their carcinogenicities. For DEP, DBP and DEHP, a low Risk Index (all of them were lower than the specified level of 1.0) reveals that small non-carcinogenic risks exist resulting from the presence of trace concentrations in the surface water of the Weihe River basin.

Auto-fluorescence lifetime and light reflectance spectroscopy for breast cancer diagnosis: potential tools for intraoperative margin detection.

This study investigates the use of two spectroscopic techniques, auto-fluorescence lifetime measurement (AFLM) and light reflectance spectroscopy (LRS), for detecting invasive ductal carcinoma (IDC) in human ex vivo breast specimens. AFLM used excitation at 447 nm with multiple emission wavelengths (532, 562, 632, and 644 nm), at which auto-fluorescence lifetimes and their weight factors were analyzed using a double exponent model. LRS measured reflectance spectra in the range of 500-840 nm and analyzed the spectral slopes empirically at several distinct spectral regions. Our preliminary results based on 93 measured locations (i.e., 34 IDC, 31 benign fibrous, 28 adipose) from 6 specimens show significant differences in 5 AFLM-derived parameters and 9 LRS-based spectral slopes between benign and malignant breast samples. Multinomial logistic regression with a 10-fold cross validation approach was implemented with selected features to classify IDC from benign fibrous and adipose tissues for the two techniques independently as well as for the combined dual-modality approach. The accuracy for classifying IDC was found to be 96.4 ± 0.8%, 92.3 ± 0.8% and 96 ± 1.3% for LRS, AFLM, and dual-modality, respectively.

Multifunctionality of indocyanine green-loaded biodegradable nanoparticles for enhanced optical imaging and hyperthermia intervention of cancer.

The aim of this study was to develop and characterize multifunctional biodegradable and biocompatible poly lactic-co-glycolic acid (PLGA) nanoparticles loaded with indocyanine green (ICG) as an optical-imaging contrast agent for cancer imaging and as a photothermal therapy agent for cancer treatment. PLGA-ICG nanoparticles (PIN) were synthesized with a particle diameter of 246±11 nm, a polydispersity index of 0.10±0.03, and ICG loading efficiency of 48.75±5.48%. PIN were optically characterized with peak excitation and emission at 765 and 810±5 nm, a fluorescence lifetime of 0.30±0.01 ns, and peak absorbance at 780 nm. The cytocompatibility study of PIN showed 85% cell viability till 1-mg/ml concentration of PIN. Successful cellular uptake of ligand conjugated PIN by prostate cancer cells (PC3) was also obtained. Both phantom-based and in vitro cell culture results demonstrated that PIN (1) have the great potential to induce local hyperthermia (i.e., temperature increase of 8 to 10°C) in tissue within 5 mm both in radius and in depth; (2) result in improved optical stability, excellent biocompatibility with healthy cells, and a great targeting capability; (3) have the ability to serve as an image contrast agent for deep-tissue imaging in diffuse optical tomography.

In vivo near-infrared spectroscopy and magnetic resonance imaging monitoring of tumor response to combretastatin A-4-phosphate correlated with therapeutic outcome.

PURPOSE: To develop a combination treatment consisting of combretastatin A-4-phosphate (CA4P) with radiation based on tumor oxygenation status. METHODS AND MATERIALS: In vivo near-infrared spectroscopy (NIRS) and diffusion-weighted (DW) magnetic resonance imaging (MRI) were applied to noninvasively monitor changes in tumor blood oxygenation and necrosis induced by CA4P (30 mg/kg) in rat mammary 13762NF adenocarcinoma, and the evidence was used to optimize combinations of CA4P and radiation treatment (a single dose of 5 Gy). RESULTS: NIRS showed decreasing concentrations of tumor vascular oxyhemoglobin and total hemoglobin during the first 2 h after CA4P treatment, indicating significant reductions in tumor blood oxygenation and perfusion levels (p < 0.001). Twenty-four hours later, in response to oxygen inhalation, significant recovery was observed in tumor vascular and tissue oxygenation according to NIRS and pimonidazole staining results, respectively (p < 0.05). DW MRI revealed significantly increased water diffusion in tumors measured by apparent diffusion coefficient at 24 h (p < 0.05), suggesting that CA4P-induced central necrosis. In concordance with the observed tumor oxygen dynamics, we found that treatment efficacy depended on the timing of the combined therapy. The most significant delay in tumor growth was seen in the group of tumors treated with radiation while the rats breathed oxygen 24 h after CA4P administration. CONCLUSIONS: Noninvasive evaluation of tumor oxygen dynamics allowed us to rationally enhance the response of syngeneic rat breast tumors to combined treatment of CA4P with radiation.

Optical reflectance spectroscopy for detection of human prostate cancer.

We present the method and application of optical reflectance spectroscopy to differentiate prostate cancer from normal tissue using a needle like, bifurcated, fiber-optic probe. An analytical expression to model light reflectance recently published by Zonios et. al. was used to derive optical properties of tissue. A total of 23 cases of human prostate specimens were investigated to analyze statistical differences between the respective cancerous tissues versus normal tissues. The results demonstrate that the derived hemodynamic parameters and optical properties can serve as good bio-markers to differentiate tumor tissue from normal tissue in human prostate.

Globally accelerated reconstruction algorithm for diffusion tomography with continuous-wave source in an arbitrary convex shape domain.

A new numerical imaging algorithm is presented for reconstruction of optical absorption coefficients from near-infrared light data with a continuous-wave source. As a continuation of our earlier efforts in developing a series of methods called "globally convergent reconstruction methods" [J. Opt. Soc. Am. A23, 2388 (2006)], this numerical algorithm solves the inverse problem through solution of a boundary-value problem for a Volterra-type integral partial differential equation. We deal here with the particular issues in solving the inverse problems in an arbitrary convex shape domain. It is demonstrated in numerical studies that this reconstruction technique is highly efficient and stable with respect to the complex distribution of actual unknown absorption coefficients. The method is particularly useful for reconstruction from a large data set obtained from a tissue or organ of particular shape, such as the prostate. Numerical reconstructions of a simulated prostate-shaped phantom with three different settings of absorption-inclusions are presented.

Optical reflectance spectroscopy to differentiate benign from malignant renal tumors at surgery.

OBJECTIVES: Optical reflectance spectrophotometry (ORS) is part of a group of novel techniques that have demonstrated promise for the assessment and differentiation of various solid tumors. In this study, we evaluated the ability of ORS to differentiate malignant from benign kidney tumors at surgery. METHODS: From January to April 2007, we completed optical spectroscopy measurements (OSM) at several standardized tumoral and normal parenchymal locations immediately after specimen removal during radical or partial nephrectomy. The depth of tissue penetration with our specific probe was 1 mm. We compared the slopes of the optical reflectance curves between 630- and 900-nm wavelengths and assessed the correlation between benign and malignant tumors. RESULTS: There were 8 partial and 13 radical nephrectomies for 6 benign (oncocytomas) and 15 malignant (14 clear cell and 1 papillary) tumors. Overall, benign and malignant OSM slopes were significantly different (P = .005). In the near-infrared region, there was excellent correlation among benign (r = .99) and malignant OSM (r = .97). On the contrary, there was a poor correlation coefficient when we compared benign and malignant tumors (r = .49). CONCLUSIONS: Optical reflectance spectrophotometry may be a novel real-time method to distinguish malignant from benign tumors in vivo. However, we performed these pilot study measurements immediately after specimen removal, and therefore expansion to in situ assessments is necessary.

Optical reflectance spectroscopy to differentiate renal tumor from normal parenchyma.

PURPOSE: Optical spectroscopy has been evaluated as an innovative technique for the ex vivo study of renal and prostate tumors. In this pilot study we assessed the ability of optical reflectance spectroscopy to reliably differentiate tumor and normal tissue in renal specimens. MATERIALS AND METHODS: From January to April 2007 we completed optical reflectance spectroscopy measurements at several standardized tumor and normal parenchymal locations immediately after kidney tumor removal. The slopes of the optical reflectance spectroscopy curves were compared, and the correlation between tumor and normal parenchyma reflectance was assessed. RESULTS: Reliable measurements were obtained from 13 radical and 8 partial nephrectomy specimens. Histology was malignant in 15 cases (clear cell in 14 and papillary in 1) and benign in 6 cases of oncocytoma. Overall we found a significant difference between the average optical reflectance spectroscopy slopes of tumor and normal parenchyma (p = 0.03). In individual radical nephrectomy specimens optical reflectance spectroscopy measurements at different locations in the tumor showed an excellent correlation (r = 0.968). Normal parenchymal measurements also correlated well (r = 0.88), although there was poor correlation between tumor and nontumor tissue in the specimen (r = 0.07). In the partial nephrectomy subset we also found a close correlation among measurements made on the normal parenchymal margin of the tumor (r = 0.94) except in 1 case of a positive margin (oncocytoma), in which the measurement from the positive margin site did not correlate with that of the adjacent parenchymal margin (r = 0.48). CONCLUSIONS: Optical reflectance spectroscopy can help distinguish tumor from normal renal tissue in specimens immediately removed at surgery. Optical reflectance spectroscopy may allow real-time assessment of positive margins during partial nephrectomy.