Blood flow estimation via numerical integration of temporal autocorrelation function in diffuse correlation spectroscopy.

BACKGROUND AND OBJECTIVE: Diffuse correlation spectroscopy (DCS) is an optical technique widely used to monitor blood flow. Recently, efforts have been made to derive new signal processing methods to minimize the systems used and shorten the signal processing time. Herein, we propose alternative approaches to obtain blood flow information via DCS by numerically integrating the temporal autocorrelation curves. METHODS: We use the following methods: the inverse of K2 (IK2)-based on the framework of diffuse speckle contrast analysis-and the inverse of the numerical integration of squared g1 (INISg1) which, based on the normalized electric field autocorrelation curve, is more simplified than IK2. In addition, g1 thresholding is introduced to further reduce computational time and make the suggested methods comparable to the conventional nonlinear fitting approach. To validate the feasibility of the suggested methods, studies using simulation, liquid phantom, and in vivo settings were performed. In the meantime, the suggested methods were implemented and tested on three types of Arduino (Arduino Due, Arduino Nano 33 BLE Sense, and Portenta H7) to demonstrate the possibility of miniaturizing the DCS systems using microcotrollers for signal processing. RESULTS: The simulation and experimental results confirm that both IK2 and INISg1 are sufficiently relevant to capture the changes in blood flow information. More interestingly, when g1 thresholding was applied, our results showed that INISg1 outperformed IK2. It was further confirmed that INISg1 with g1 thresholding implemented on a PC and Portenta H7, an advanced Arduino board, performed faster than did the deep learning-based, state-of-the-art processing method. CONCLUSION: Our findings strongly indicate that INISg1 with g1 thresholding could be an alternative approach to derive relative blood flow information via DCS, which may contribute to the simplification of DCS methodologies.

Analysis of relation between skin elasticity and the entropy of skin image using near-infrared and visible light sources.

Skin elasticity has been regarded as one of the main indicators of skin condition. Current measurement devices for skin elasticity are mostly expensive for home-use and should contact the skin surface. As a first step to develop improved methods, we focus on the relation between skin elasticity and the entropy of skin images. Reduced skin elasticity causes wrinkles. It spreads frequency components and increases their randomness in the frequency domain. The randomness is quantified as entropy, which is a measure of the disorder of a system in physics. Therefore, skin elasticity is expected to have a negative relation with entropy. This tendency can be improved by applying penetration depth characteristics according to the wavelength of light. From cheeks and forehead of 12 Korean adults, skin images are acquired with three different light sources (470 nm, 870 nm and broadband light) and skin elasticity is measured. The root mean square error between the measured data and the fitted model is "0.27" (870 nm), "0.49" (broadband light) and "1.42" (470 nm). Furthermore, the results are analyzed by classifying by sex, age and measurement area. This study demonstrates the possibility of developing noncontact home-use devices to measure skin elasticity in the future.

Elastographic Tomosynthesis From X-Ray Strain Imaging of Breast Cancer.

Noncancerous breast tissue and cancerous breast tissue have different elastic properties. In particular, cancerous breast tumors are stiff when compared to the noncancerous surrounding tissue. This difference in elasticity can be used as a means for detection through the method of elastographic tomosynthesis by means of physical modulation. This paper deals with a method to visualize elasticity of soft tissues, particularly breast tissues, via x-ray tomosynthesis. X-ray tomosynthesis is now used to visualize breast tissues with better resolution than the conventional single-shot mammography. The advantage of X-ray tomosynthesis over X-ray CT is that fewer projections are needed than CT to perform the reconstruction, thus radiation exposure and cost are both reduced. Two phantoms were used for the testing of this method, a physical phantom and an in silico phantom. The standard root mean square error in the tomosynthesis for the physical phantom was 2.093 and the error in the in silico phantom was negligible. The elastographs were created through the use of displacement and strain graphing. A Gaussian Mixture Model with an expectation-maximization clustering algorithm was applied in three dimensions with an error of 16.667%. The results of this paper have been substantial when using phantom data. There are no equivalent comparisons yet in 3D x-ray elastographic tomosynthesis. Tomosynthesis with and without physical modulation in the 3D elastograph can identify feature groupings used for biopsy. The studies have potential to be applied to human test data used as a guide for biopsy to improve accuracy of diagnosis results. Further research on this topic could prove to yield new techniques for human patient diagnosis purposes.

Online registry for nationwide database of Helicobacter pylori eradication in Korea: Correlation of antibiotic use density with eradication success.

BACKGROUND: The Helicobacter pylori eradication rate has decreased with increasing antibiotic resistance. We conducted a prospective, nationwide, multicenter registry study to monitor the real status of H. pylori eradication therapy and to investigate the association between eradication success and antibiotic use density in Korea. MATERIALS AND METHODS: We enrolled 9318 patients undergoing H. pylori eradication therapy from 37 hospitals through "on-line database registry" from October 2010 to July 2015. Demographic data, detection methods, treatment indications, regimens, durations, compliance, adverse events, and eradication results were collected. The use of all commercially available eradication antibiotics was analyzed through the Korean National Health Insurance data of the Health Insurance Review and Assessment Service. The defined daily dose of antibiotics was used to standardize drug use comparisons. RESULTS: Finally, 6738 patients were analyzed. The overall eradication rate of first-line therapy was 71.8%. The eradication success rates were 71.7%, 86.9%, and 74.0% for standard triple therapy for 7 days, quadruple therapy, and concomitant therapy, respectively. The eradication success rate in naive patients was higher than that in those who previously underwent H. pylori eradication. Eradication success was significantly associated with younger age, female sex, and high compliance. Regional differences in eradication rates were observed. The yearly use density of clarithromycin increased statistically in seven regions across the country from 2010 to 2015. The yearly use density of amoxicillin in the Gyeongsang and Chungcheong areas was significantly increased (P < .01), whereas that of other macrolides was significantly lower in the Gyeonggi area than in other areas (P = .01). The overall use of eradication antibiotics has increased while the eradication rate steadily decreased for 5 years. However, there was no significant correlation between antibiotic use density and eradication. CONCLUSION: There was no relationship between the eradication rate and antibiotic use density in Korea.

Investigation of brain functional connectivity in patients with mild cognitive impairment: A functional near-infrared spectroscopy (fNIRS) study.

This study examines brain functional connectivity in both cognitively normal seniors and patients with mild cognitive impairment (MCI) to elucidate prospective markers of MCI. A homemade four-channel functional near-infrared spectroscopy (fNIRS) system was employed to measure hemodynamic responses in the subjects' prefrontal cortex during a resting state, an oddball task, a 1-back task, and a verbal fluency task. Brain functional connectivity was calculated as the Pearson correlation coefficients between fNIRS channels. The results show that during the verbal fluency task, while the healthy control (HC) group presents a significantly stronger inter-hemispheric connectivity compared to intra-hemispheric connectivity, there is no difference between the inter- and intra-hemispheric connectivity in the MCI group. In addition, a comparison between the MCI and HC connectivity reveals that the MCI group has a statistically higher right and inter-hemispheric connectivity during the resting state, but a significantly lower left and inter-hemispheric connectivity during the verbal fluency test. These findings demonstrate the potential of fNIRS to study brain functional connectivity in neurodegenerative diseases.

The hemodynamic changes during cupping therapy monitored by using an optical sensor embedded cup.

Cupping therapy is one form of alternative medicine that is used widely across the world. Although the applications of cupping therapy including pain relief have a 1000-year history, the therapeutic effect of cupping is still questionable due to a lack of scientific evidence. Therefore, in the present study, we embedded a near-infrared spectroscopic sensor into a suction cup to monitor the hemodynamic changes on the treated site while the hemodynamics at the surrounding tissue of the cup was also simultaneously monitored by another near-infrared spectroscopic sensor. The results from 10 healthy male subjects show a dramatic increase of the oxy-hemoglobin (OHb) and deoxy-hemoglobin (RHb) concentrations at the treatment site while the OHb and RHb levels were decreased at the surrounding tissue. Moreover, after the treatment, we observed that the OHb concentrations were maintained at a higher level than before treatment at both sites, which may demonstrate how cupping therapy works for treatment. In summary, the results showed that cupping therapy increases blood volume and tissue oxygenation at the treatment site while those were slightly decreased at the surrounding tissue. This study showed that the embedding of near-infrared spectroscopy in a cupping system could offer a better understanding of the mechanism of cupping therapy.

The changes of cerebral hemodynamics during ketamine induced anesthesia in a rat model.

Current electroencephalogram (EEG) based-consciousness monitoring technique is vulnerable to specific clinical conditions (eg, epilepsy and dementia). However, hemodynamics is the most fundamental and well-preserved parameter to evaluate, even under severe clinical situations. In this study, we applied near-infrared spectroscopy (NIRS) system to monitor hemodynamic change during ketamine-induced anesthesia to find its correlation with the level of consciousness. Oxy-hemoglobin (OHb) and deoxy-hemoglobin concentration levels were continuously acquired throughout the experiment, and the reflectance ratio between 730 and 850 nm was calculated to quantify the hemodynamic changes. The results showed double peaks of OHb concentration change during ketamine anesthesia, which seems to be closely related to the consciousness state of the rat. This finding suggests the possibility of NIRS based-hemodynamic monitoring as a supplementary parameter for consciousness monitoring, compensating drawbacks of EEG signal based monitoring.

Correction to: Concomitant, sequential, and 7-day triple therapy in first-line treatment of Helicobacter pylori infection in Korea: study protocol for a randomized controlled trial.

CORRECTION: In the original publication [1] was an error in the grant number in the funding section. The correct version can be found in this Erratum.

Concomitant, sequential, and 7-day triple therapy in first-line treatment of Helicobacter pylori infection in Korea: study protocol for a randomized controlled trial.

BACKGROUND: Most international guidelines recommend triple-therapy regimens consisting of a proton pump inhibitor, clarithromycin, and amoxicillin/metronidazole for at least 7 days for the eradication of Helicobacter pylori. However, the efficacy of 7-day clarithromycin-based standard triple therapy for H. pylori infection is currently unacceptable in Korea. In this study, we will compare the efficacy and safety of 7-day standard triple therapy, 10-day sequential therapy, and 10-day concomitant therapy for the first-line treatment of H. pylori infection in Korea. METHODS/DESIGN: In this multicenter, investigator-blinded, randomized trial we are recruiting adult patients with H. pylori infection from 15 hospitals in Korea to determine whether sequential or concomitant treatment is superior to standard triple therapy. Patients are randomly assigned to receive either standard triple therapy (lansoprazole, amoxicillin, and clarithromycin) for 7 days, or sequential treatment (lansoprazole and amoxicillin for the first 5 days, followed by lansoprazole, clarithromycin, and metronidazole for another 5 days) for 10 days, or concomitant therapy (lansoprazole, amoxicillin, clarithromycin, and metronidazole) for 10 days. The primary outcome is the rate of H. pylori eradication in the intention-to-treat population. DISCUSSION: The results of this study will be crucial for determining the optimal regimen for the primary treatment of H. pylori infection in Korea. This study will produce vital evidence that will lead to revisions to guidelines concerning first-line treatment regimens for H. pylori infection. TRIAL REGISTRATION: Clinical Research Information Service (CRIS), Republic of Korea, KCT0001980 . Registered on 25 July 2016.

Preoperative Body Mass Index May Determine the Prognosis of Advanced Gastric Cancer.

Radical gastrectomy followed by adjuvant chemotherapy for advanced gastric cancer causes serious nutritional impairment. Our study evaluated the clinical impact of body mass index (BMI) on the long-term outcomes of advanced gastric cancer (stage II and III). We analyzed 211 cases of stage II and III gastric cancer between January 2005 and December 2010 at Chung-Ang University Hospital, Seoul, Korea. Patients were divided into four groups according to BMI: underweight, normal, overweight, and obese. In addition, we divided patients into two groups: BMI-High (BMI ≥ 23 kg/m2) vs. BMI-Low (BMI < 23 kg/m2). We assessed age, sex, tumor location, lymph node (LN) involvement, operation method, initial cancer stage, recurrence, and survival between the two groups. There was significant difference in overall survival (OS) between the underweight group and the other groups (P = 0.005). The survival of the BMI-High group was better than that of the BMI-Low group. The rate of cancer-related death in the BMI-High group was significantly lower than that in the BMI-Low group (cancer-related death: BMI-Low 27% vs. BMI-High 12.6%, P = 0.022). Our findings suggest that preoperative BMI may have an influence on the long-term outcomes of advanced gastric cancer after radical surgery and chemotherapy.

Online Registry for Nationwide Database of Current Trend of Helicobacter pylori Eradication in Korea: Interim Analysis.

Eradication of Helicobacter pylori using first-line therapy is becoming less effective. Subjects who had been treated for H. pylori infection were prospectively enrolled through an on-line database registry from October 2010 to December 2012. Demographic data, detection methods, treatment indication, regimens, durations, compliance, adverse events, and eradication results for H. pylori infection were collected. Data of 3,700 patients from 34 hospitals were analyzed. The overall eradication rate of the first-line therapy was 73.0%. Eradication failure was significantly associated with old age, concomitant medication, and comorbidity. Regional differences in eradication rates were observed. The most common first-line therapy was proton pump inhibitor-based triple therapy (standard triple therapy, STT) for 7 days (86.8%). The eradication rates varied with regimens, being 73% in STT, 81.8% in bismuth-based quadruple therapy, 100% in sequential therapy, and 90.3% in concomitant therapy. The eradication rate in treatment-naïve patients was higher than that in patients previously treated for H. pylori infection (73.8% vs. 58.5%, P < 0.001). The overall eradication rate for second-line therapy was 84.3%. There was no statistical difference in eradication rates among various regimens. H. pylori eradication rate using STT is decreasing in Korea and has become sub-optimal, suggesting the need for alternative regimens to improve the efficacy of first-line therapy for H. pylori infection.

Exploring Neuro-Physiological Correlates of Drivers' Mental Fatigue Caused by Sleep Deprivation Using Simultaneous EEG, ECG, and fNIRS Data.

Investigations of the neuro-physiological correlates of mental loads, or states, have attracted significant attention recently, as it is particularly important to evaluate mental fatigue in drivers operating a motor vehicle. In this research, we collected multimodal EEG/ECG/EOG and fNIRS data simultaneously to develop algorithms to explore neuro-physiological correlates of drivers' mental states. Each subject performed simulated driving under two different conditions (well-rested and sleep-deprived) on different days. During the experiment, we used 68 electrodes for EEG/ECG/EOG and 8 channels for fNIRS recordings. We extracted the prominent features of each modality to distinguish between the well-rested and sleep-deprived conditions, and all multimodal features, except EOG, were combined to quantify mental fatigue during driving. Finally, a novel driving condition level (DCL) was proposed that distinguished clearly between the features of well-rested and sleep-deprived conditions. This proposed DCL measure may be applicable to real-time monitoring of the mental states of vehicle drivers. Further, the combination of methods based on each classifier yielded substantial improvements in the classification accuracy between these two conditions.

A discrepancy of penile hemodynamics during visual sexual stimulation observed by near-infrared spectroscopy.

BACKGROUND: In this paper, we observed a discrepancy of penile hemodynamics dependent on location by using near infrared spectroscopy (NIRS) sensor, and showcase NIRS as a potentially suitable sensor in supplementing the diagnosis and treatment of erectile dysfunction. METHODS: To observe the effect that location has on penile hemodynamics, the NIRS sensor was placed on the top and the side of genital organ, and oxy- (HbO), deoxy-(RHb), and total (HbT) hemoglobin concentration changes were acquired. Our results from 6 healthy subjects show that hemodynamic changes vary depending on where the probe was placed. To observe a statistical difference between the signals, a Wilcoxon signed-rank test was performed. RESULTS: The result shows a significant difference (p < 0.05) between concentration changes of RHb and HbT depending on the probes' location. Moreover, the sensor placed on the top of the organ shows a rise of HbO and HbT concentration while RHb concentration decreased. However, hemodynamics from the side of the organ showed that RHb concentration increased along with HbO. CONCLUSIONS: The outcomes demonstrates an ability of NIRS to be sensitive enough to detect the different hemodynamic changes in various locations of a healthy male genital organ during visual sexual stimulation. The results also show the importance of sensor location on the genital organ for the resulting hemodynamic changes. We can foresee our results as a way for clinicians to obtain more accurate hemodynamic measurements from the penis, and also show the likelihood for NIRS enhanced diagnosis tool of male erectile dysfunction over the current standards.

Second-look endoscopy with prophylactic hemostasis is still effective after endoscopic submucosal dissection for gastric neoplasm.

AIM: The clinical value of second-look endoscopy (SLE) after endoscopic submucosal dissection (ESD) has been doubted continuously. The aim of this study was to assess the effectiveness of SLE based on the risk of delayed bleeding after ESD. METHODS: A total of 310 lesions of gastric epithelial neoplasms treated by ESD were reviewed. The lesions were divided into two groups based on the risk of post-procedural bleeding estimated by Forrest classification. The high risk of rebleeding group (Forrest Ia, Ib and IIa) required endoscopic treatment, while the low risk of rebleeding group (Forrest IIb, IIc and III) did not. Delayed bleeding after ESD was investigated. RESULTS: Sixty-six lesions were included in the high risk of rebleeding group and 244 lesions in the low risk of rebleeding group. There were no significant differences in delayed bleeding between the high risk group (1/66) and the low risk group (1/244) (P = 0.38). The high risk of rebleeding group tended to be located more often in the mid-third and had higher appearance of flat or depressed shape than the low risk group (P = 0.004 and P = 0.006, respectively). CONCLUSION: SLE with pre-emptive prophylactic endoscopic treatment is still effective in preventing delayed bleeding after ESD.

Clinical practice guidelines for gastric cancer in Korea: an evidence-based approach.

Although gastric cancer is quite common in Korea, the treatment outcome is relatively favorable compared to those in western countries. However, there are currently no Korean multidisciplinary guidelines for gastric cancer. Experts from related societies developed guidelines de novo to meet Korean circumstances and requirements, including 23 recommendation statements for diagnosis (n=9) and treatment (n=14) based on relevant key questions. The quality of the evidence was rated according to the GRADE evidence evaluation framework: the evidence levels were based on a systematic review of the literature, and the recommendation grades were classified as either strong or weak. The applicability of the guidelines was considered to meet patients' view and preferences in the context of Korea. The topics of the guidelines cover diagnostic modalities (endoscopy, endoscopic ultrasound, and radiologic diagnosis), treatment modalities (surgery, therapeutic endoscopy, chemotherapy, and radiotherapy), and pathologic evaluation. An external review of the guidelines was conducted during the finalization phase.

Noninvasive optical cytochrome c oxidase redox state measurements using diffuse optical spectroscopy.

A major need exists for methods to assess organ oxidative metabolic states in vivo. By contrasting the responses to cyanide (CN) poisoning versus hemorrhage in animal models, we demonstrate that diffuse optical spectroscopy (DOS) can detect cytochrome c oxidase (CcO) redox states. Intermittent decreases in inspired O2 from 100% to 21% were applied before, during, and after CN poisoning, hemorrhage, and resuscitation in rabbits. Continuous DOS measurements of total hemoglobin, oxyhemoglobin, deoxyhemoglobin, and oxidized and reduced CcO from muscle were obtained. Rabbit hemorrhage was accomplished with stepwise removal of blood, followed by blood resuscitation. CN treated rabbits received 0.166 mg/min NaCN infusion. During hemorrhage, CcO redox state became reduced concurrently with decreases in oxyhemoglobin, resulting from reduced tissue oxygen delivery and hypoxia. In contrast, during CN infusion, CcO redox state decreased while oxyhemoglobin concentration increased due to CN binding and reduction of CcO with resultant inhibition of the electron transport chain. Spectral absorption similarities between hemoglobin and CcO make noninvasive spectroscopic distinction of CcO redox states difficult. By contrasting physiological perturbations of CN poisoning versus hemorrhage, we demonstrate that DOS measured CcO redox state changes are decoupled from hemoglobin concentration measurement changes.

[Synopsis on clinical practice guideline of gastric cancer in Korea: an evidence-based approach].

Although, gastric cancer is quite common in Korea, the treatment outcome is relatively favorable compared to that of Western countries. However, there is no Korean multidisciplinary guideline for gastric cancer and thus, a guideline adequate for domestic circumstances is required. Experts from related societies developed 22 recommendation statements for the diagnosis (n=9) and treatment (n=13) based on relevant key questions. Evidence levels based on systematic review of literatures were classified as five levels from A to E, and recommendation grades were classified as either strong or weak. The topics of this guideline cover diagnostic modalities (endoscopy, endoscopic ultrasound, radiologic diagnosis), treatment modalities (surgery, therapeutic endoscopy, chemotherapy, radiotherapy) and pathologic evaluation. External review of the guideline was conducted at the finalization phase.

X-ray strain tensor imaging: FEM simulation and experiments with a micro-CT.

In tissue elasticity imaging, measuring the strain tensor components is necessary to solve the inverse problem. However, it is impractical to measure all the tensor components in ultrasound or MRI elastography because of their anisotropic spatial resolution. The objective of this study is to compute 3D strain tensor maps from the 3D CT images of a tissue-mimicking phantom. We took 3D micro-CT images of the phantom twice with applying two different mechanical compressions to it. Applying the 3D image correlation technique to the CT images under different compression, we computed 3D displacement vectors and strain tensors at every pixel. To evaluate the accuracy of the strain tensor maps, we made a 3D FEM model of the phantom, and we computed strain tensor maps through FEM simulation. Experimentally obtained strain tensor maps showed similar patterns to the FEM-simulated ones in visual inspection. The correlation between the strain tensor maps obtained from the experiment and the FEM simulation ranges from 0.03 to 0.93. Even though the strain tensor maps suffer from high level noise, we expect the x-ray strain tensor imaging may find some biomedical applications such as malignant tissue characterization and stress analysis inside the tissues.

Substitutions in penicillin-binding protein 1 in amoxicillin-resistant Helicobacter pylori strains isolated from Korean patients.

BACKGROUND/AIMS: A worldwide increase in amoxicillin resistance in Helicobacter pylori is having an adverse effect on eradication therapy. In this study, we investigated the mechanism of the amoxicillin resistance of H. pylori in terms of amino acid substitutions in penicillin-binding protein 1 (PBP1). METHODS: In total, 150 H. pylori strains were isolated from 144 patients with chronic gastritis, peptic ulcers, or stomach cancer. The minimum inhibitory concentrations (MICs) of the strains were determined with a serial 2-fold agar dilution method. The resistance breakpoint for amoxicillin was defined as >0.5 µg/mL. RESULTS: Nine of 150 H. pylori strains showed amoxicillin resistance (6%). The MIC values of the resistant strains ranged from 1 to 4 µg/mL. A PBP1 sequence analysis of the resistant strains revealed multiple amino acid substitutions: Val16→Ile, Val45→Ile, Ser414→Arg, Asn562→Tyr, Thr593→Ala, Gly595→Ser, and Ala599→Thr. The natural transformation of these mutated genes into amoxicillin-sensitive strains was performed in two separate pbp1 gene segments. A moderate increase in the amoxicillin MIC was observed in the segment that contained the penicillin-binding motif of the C-terminal portion, the transpeptidase domain. CONCLUSIONS: pbp1 mutation affects the amoxicillin resistance of H. pylori through the transfer of the penicillin-binding motif.

Noninvasive monitoring of treatment response in a rabbit cyanide toxicity model reveals differences in brain and muscle metabolism.

Noninvasive near infrared spectroscopy measurements were performed to monitor cyanide (CN) poisoning and recovery in the brain region and in foreleg muscle simultaneously, and the effects of a novel CN antidote, sulfanegen sodium, on tissue hemoglobin oxygenation changes were compared using a sub-lethal rabbit model. The results demonstrated that the brain region is more susceptible to CN poisoning and slower in endogenous CN detoxification following exposure than peripheral muscles. However, sulfanegen sodium rapidly reversed CN toxicity, with brain region effects reversing more quickly than muscle. In vivo monitoring of multiple organs may provide important clinical information regarding the extent of CN toxicity and subsequent recovery, and facilitate antidote drug development.