A Cerenkov fiber-optic dosimeter (CFOD) is fabricated using plastic optical fibers to measure Cerenkov radiation induced by a therapeutic photon beam. We measured the Cerenkov radiation generated in optical fibers in various irradiation conditions to evaluate the usability of Cerenkov radiation for a photon beam therapy dosimetry. As a results, the spectral peak of Cerenkov radiation was measured at a wavelength of 515 nm, and the intensity of Cerenkov radiation increased linearly with increasing irradiated length of the optical fiber. Also, the intensity peak of Cerenkov radiation was measured in the irradiation angle range of 30 to 40 deg. In the results of Monte Carlo N-particle transport code simulations, the relationship between fluxes of electrons over Cerenkov threshold energy and energy deposition of a 6 MV photon beam had a nearly linear trend. Finally, percentage depth doses for the 6 MV photon beam could be obtained using the CFOD and the results were compared with those of an ionization chamber. Here, the mean dose difference was about 0.6%. It is anticipated that the novel and simple CFOD can be effectively used for measuring depth doses in radiotherapy dosimetry.

During extracorporeal circulation (ECC), blood is periodically sampled and analyzed to maintain the blood-gas status of the patient within acceptable limits. This protocol has well-known drawbacks that may be overcome by continuous monitoring. We present the characterization of a new pH sensor for continuous monitoring in ECC. This monitoring device includes a disposable fluorescence-sensing element directly in contact with the blood, whose fluorescence intensity is strictly related to the pH of the blood. In vitro experiments show no significant difference between the blood gas analyzer values and the sensor readings; after proper calibration, it gives a correlation of R<0.9887 , and measuring errors were lower than the 3% of the pH range of interest (RoI) with respect to a commercial blood gas analyzer. This performance has been confirmed also by simulating a moderate ipothermia condition, i.e., blood temperature 32°C, frequently used in cardiac surgery. In ex vivo experiments, performed with animal models, the sensor is continuously operated in an extracorporeal undiluted blood stream for a maximum of 11 h. It gives a correlation of R<0.9431 , and a measuring error lower than the 3% of the pH RoI with respect to laboratory techniques.

The capabilities of micro-Raman spectroscopy for differentiating normal and malignant nasopharyngeal tissues were evaluated. Raman scattering signals were acquired from 22 normal and 52 malignant nasopharyngeal tissue samples. Distinctive spectral differences in Raman spectra between normal and malignant nasopharyngeal tissues were found, particularly in the spectral ranges of 853, 937, 1094, 1209, 1268, 1290 to 1340, 1579, and 1660  cm⁻¹ , which primarily contain signals related to proteins, DNA, and lipids. Compared to normal tissues, the band intensity located at 853, and 937  cm ⁻¹ were significantly lower for cancerous tissues (p<0.05 ), while the band intensity located at 1094, 1209, 1268, and 1579  cm ⁻¹ were significantly higher (p<0.05 ). The band intensity located at 1290 to 1340, and 1660  cm ⁻¹ were also higher for cancerous tissues; but the differences were not statistically significant (p<0.05 ). Principal component analysis (PCA) and linear discriminate analysis (LDA) were employed to generate diagnostic algorithms for classification of Raman spectra of the two nasopharyngeal tissue types. The PCA-LDA algorithms together with leave-one-out, cross-validation technique yielded diagnostic sensitivity of 92% and specificity of 82%. This work demonstrated that the Raman spectroscopy technique associated with PCA-LDA diagnostic algorithms has potential for improving the diagnosis of nasopharyngeal cancers.

Currently, photoplethysmography (PPG) is a frequently studied optical blood pulsation detection technique among biophotonic and biomedical researchers due to the fact that it shows high potential for estimating the arterial stiffness (AS). The extraction of diagnostically useful information requires standardized measurement procedure with good repeatability. However, the effects of a crucially important factor—the optimal contact pressure (CP) of the probe—are often ignored. Also, CP values are not reported to evaluate those effects. It is hypothesized that AS estimated from PPG pulse wave 2nd derivative parameter b/a is strongly inconsistent when recorded at nonoptimal probe CP. Our pilot study confirmed this during in vivo PPG recordings from conduit artery sites on five healthy subjects at variable probe CP (0 to 15 kPa) by using 880 nm reflectance type sensor, force transducer, and PPG alternating current (AC) signal pulse area derived optimal CP criterion. The b/a values, calculated from PPG with variable CP, showed variation <300  percent. In contrast, at the optimal CP, the b/a showed high repeatability (coefficient of variability <5  percent). The effect has been explained with exponential pulse pressure-volume relationship model which indicates the optimal CP range.

A noninvasive head probe that combines near-infrared spectroscopy (NIRS) and electroencephalography (EEG) for simultaneous measurement of neural dynamics and hemodynamics in the brain is presented. It is composed of a compliant expandable mechanism that accommodates a wide range of head size variation and an elastomeric web that maintains uniform sensor contact pressure on the scalp as the mechanism expands and contracts. The design is intended to help maximize optical and electrical coupling and to maintain stability during head movement. Positioning electrodes at the inion, nasion, central, and preauricular fiducial locations mechanically shapes the probe to place 64 NIRS optodes and 65 EEG electrodes following the 10–5 scalp coordinates. The placement accuracy, precision, and scalp pressure uniformity of the sensors are evaluated. A root-mean-squared (RMS) positional precision of 0.89±0.23  mm , percent arc subdivision RMS accuracy of 0.19±0.15% , and mean normal force on the scalp of 2.28±0.88  N at 5 mm displacement were found. Geometric measurements indicate that the probe will accommodate the full range of adult head sizes. The placement accuracy, precision, and uniformity of sensor contact pressure of the proposed head probe are important determinants of data quality in noninvasive brain monitoring with simultaneous NIRS-EEG.

Diffuse reflectance and fluorescence spectroscopy are used to detect histopathological abnormalities of an epileptic brain in a human subject study. Static diffuse reflectance and fluorescence spectra are acquired from normal and epileptic brain areas, defined by electrocorticography (ECoG), from pediatric patients undergoing epilepsy surgery. Biopsy specimens are taken from the investigated sites within an abnormal brain. Spectral analysis reveals significant differences in diffuse reflectance spectra and the ratio of fluorescence and diffuse reflectance spectra from normal and epileptic brain areas defined by ECoG and histology. Using these spectral differences, tissue classification models with accuracy above 80% are developed based on linear discriminant analysis. The differences between the diffuse reflectance spectra from the normal and epileptic brain areas observed in this study are attributed to alterations in the static hemodynamic characteristics of an epileptic brain, suggesting a unique association between the histopathological and the hemodynamic abnormalities in an epileptic brain.

Preterm infants are highly susceptible to ischemic brain injury; consequently, continuous bedside monitoring to detect ischemia before irreversible damage occurs would improve patient outcome. In addition to monitoring cerebral blood flow (CBF), assessing the cerebral metabolic rate of oxygen (CMRO₂ ) would be beneficial considering that metabolic thresholds can be used to evaluate tissue viability. The purpose of this study was to demonstrate that changes in absolute CMRO₂ could be measured by combining diffuse correlation spectroscopy (DCS) with time-resolved near-infrared spectroscopy (TR-NIRS). Absolute CBF was determined using bolus-tracking TR-NIRS to calibrate the DCS measurements. Cerebral venous blood oxygenation (SvO ₂ ) was determined by multiwavelength TR-NIRS measurements, the accuracy of which was assessed by directly measuring the oxygenation of sagittal sinus blood. In eight newborn piglets, CMRO₂ was manipulated by varying the anesthetics and by injecting sodium cyanide. No significant differences were found between the two sets of SvO₂ measurements obtained by TR-NIRS or sagittal sinus blood samples and the corresponding CMRO ₂ measurements. Bland–Altman analysis showed a mean CMRO 2 difference of 0.0268±0.8340  mL O ₂ /100  g/min between the two techniques over a range from 0.3 to 4 mL O ₂ /100  g/min .

The ability of combining serum surface-enhanced Raman spectroscopy (SERS) with support vector machine (SVM) for improving classification esophageal cancer patients from normal volunteers is investigated. Two groups of serum SERS spectra based on silver nanoparticles (AgNPs) are obtained: one group from patients with pathologically confirmed esophageal cancer (n=30 ) and the other group from healthy volunteers (n=31 ). Principal components analysis (PCA), conventional SVM (C-SVM) and conventional SVM combination with PCA (PCA-SVM) methods are implemented to classify the same spectral dataset. Results show that a diagnostic accuracy of 77.0% is acquired for PCA technique, while diagnostic accuracies of 83.6% and 85.2% are obtained for C-SVM and PCA-SVM methods based on radial basis functions (RBF) models. The results prove that RBF SVM models are superior to PCA algorithm in classification serum SERS spectra. The study demonstrates that serum SERS in combination with SVM technique has great potential to provide an effective and accurate diagnostic schema for noninvasive detection of esophageal cancer.

We present a novel way to recover intrinsic fluorescence in turbid media based on Monte Carlo generated look-up tables and making use of a diffuse reflectance measurement taken at the same location. The method has been validated on various phantoms with known intrinsic fluorescence and is benchmarked against photon-migration methods. This new method combines more flexibility in the probe design with fast reconstruction and showed similar reconstruction accuracy as found in other reconstruction methods.

Heparin is the most widely used anti-coagulant for the prevention of blood clots in patients undergoing certain types of surgeries including open heart surgeries and dialysis. The precise monitoring of heparin amount in patients’ blood is crucial for reducing the morbidity and mortality in surgical environments. Based upon these considerations, we have used Raman spectroscopy in conjunction with partial least squares (PLS) analysis to measure heparin concentration at clinical level which is less than 10 United States Pharmacopeia (USP) in serum. The PLS calibration model was constructed from the Raman spectra of different concentrations of heparin in serum. It showed a high coefficient of determination (R ² <0.91 ) between the spectral data and heparin level in serum along with a low root mean square error of prediction ∼4  USP/ml . It enabled the detection of extremely low concentrations of heparin in serum (∼8  USP/ml ) as desirable in clinical environment. The proposed optical method has the potential of being implemented as the point-of-care testing procedure during surgeries, where the interest is to rapidly monitor low concentrations of heparin in patient’s blood.

Results of the structural analysis of urinary sediments by means of infrared spectral microscopy are presented. The results are in good agreement with the results of standard optical microscopy in the case of single-component and crystalline urinary sediments. It is found that for noncrystalline or multicomponent sediments, the suggested spectroscopic method is superior to optical microscopy. The chemical structure of sediments of any molecular origin can be elucidated by this spectroscopic method. The method is sensitive enough to identify solid particles of drugs present in urine. Sulfamethoxazole and traces of other medicines are revealed in this study among the other sediments. We also show that a rather good correlation exists between the type of urinary sediments and the renal stones removed from the same patient. Spectroscopic studies of urinary stones and corresponding sediments from 76 patients suffering from renal stone disease reveal that in 73% of cases such correlation exists. This finding is a strong argument for the use of infrared spectral microscopy to prevent kidney stone disease because stones can be found in an early stage of formation by using the nonintrusive spectroscopic investigation of urinary sediments. Some medical recommendations concerning the overdosing of certain pharmaceuticals can also be derived from the spectroscopic studies of urinary sediments.

Several optical techniques and fiber-optic probe systems have been designed to measure the optical properties of tissue. While a wide range of options is often beneficial, it poses a problem to investigators selecting which method to use for their biomedical application of interest. We present a methodology to optimally select a probe that matches the application requirements. Our method is based both on matching a probe’s mean sampling depth with the optimal diagnostic depth of the clinical application and on choosing a probe whose interrogation depth and path length is the least sensitive to alterations in the target medium’s optical properties. Satisfying these requirements ensures that the selected probe consistently assesses the relevant tissue volume with minimum variability. To aid in probe selection, we have developed a publicly available graphical user interface that takes the desired sampling depth and optical properties of the medium as its inputs and automatically ranks different techniques in their ability to robustly target the desired depth. Techniques investigated include single fiber spectroscopy, differential path length spectroscopy, polarization-gating, elastic light scattering spectroscopy, and diffuse reflectance. The software has been applied to biological case studies.

Fiber-optic attraction of urinary stones during laser lithotripsy may be exploited to manipulate stone fragments inside the urinary tract without mechanical grasping tools, saving the urologist time and space in the ureteroscope working channel. We compare thulium fiber laser (TFL) high pulse rate/low pulse energy operation to conventional holmium:YAG low pulse rate/high pulse energy operation for fiber-optic suctioning of plaster-of-paris (PoP) stone phantoms. A TFL (wavelength of 1908 nm, pulse energy of 35 mJ, pulse duration of 500 μs, and pulse rate of 10 to 350 Hz) and a holmium laser (wavelength of 2120 nm, pulse energy of 35 to 360 mJ, pulse duration of 300 μs, and pulse rate of 20 Hz) were tested using 270-μm-core optical fibers. A peak drag speed of ∼2.5  mm/s was measured for both TFL (35 mJ and 150 to 250 Hz) and holmium laser (210 mJ and 20 Hz). Particle image velocimetry and thermal imaging were used to track water flow for all parameters. Fiber-optic suctioning of urinary stone phantoms is feasible. TFL operation at high pulse rates/low pulse energies is preferable to holmium operation at low pulse rates/high pulse energies for rapid and smooth stone pulling. With further development, this novel technique may be useful for manipulating stone fragments in the urinary tract.

This article [J. Biomed. Opt.. 18, , 026014 (2013)] was originally published online on 6 February 2013 with an error in the title: the word “studied” was added. The corrected title appears above. This article was corrected online on 13 February 2013. It appears correctly in print. The Authors

This article [J. Biomed. Opt.. 18, , 026022 (2013)] was originally published online on 14 February 2013 with an error in Fig. 7 caption. The word “corneum” has been replaced by “granulosum.” The corrected caption reads:Fig. 7 Maximum area-normalized fluorescence intensity corresponding to the lifetime τ 1 in stratum granulosum and stratum basale versus mean L ∗ value (Table 4) in (a) dorsal stratum granulosum; (b) dorsal stratum basale; (c) volar stratum granulosum; and (d) volar stratum basale. Data (mean±s:e:m: ) from the five volunteers.This article was corrected online on 20 February 2013. It appears correctly in print.The Authors

The second edition of Fundamentals of Light Microscopy and Electronic Imaging is a collaborative effort of Douglas B. Murphy and Michael W. Davidson. Murphy is known for his establishment of the School of Medicine Microscope Facility at the Johns Hopkins School of Medicine. He directed the facility until 2006 and has superb experience as a teacher of microscopy, optics, and image processing. He was the sole author of the first edition of this text and reference book. Davidson, who is at the National High Magnetic Field Laboratory, The Florida State University, is well known for his development of websites for online learning of microscopy; especially his development of dynamic Java and Flash tutorials to illustrate the principles and the applications. Davidson and his collaborators have produced very useful dynamic Java and Flash tutorials which are highly recommended. Nikon supports the site: CrossRef

XSLOpenURL/

. Olympus supports the Microscopy Resource Center at CrossRef

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. I have used both of these education sites, and I highly recommend them to the readers of the Journal of Biomedical Optics. The combined work of these two authors results in a recommended textbook and reference that is an excellent starting point for someone new to the field of microscopy. While there is much information contained within the covers, from theory to applications, to demonstrations that the reader can perform in the laboratory, to discussions of limitations, it must be stated that this book is directed to the novice in microscopy and is an entry-level exposition of the fundamentals of the subject, devoid of the mathematics that is usual for optics books. With that disclaimer, I think that this highly acclaimed book is well-suited to the person who is attempting to learn the fundamentals of microscopy and electronic imaging.